Peeds Infection Lectures

Table of Contents
I. KSMU lectures ................................................................................................ 1. Acute viral hepatitis ........................................................................... 3 2. Acute intestinal infections ............................................................... 11 3. Scarlet fever and measles. ............................................................... 20 4. Meningococcemia ............................................................................ 29 5. Diphtheria ........................................................................................ 37 II. Notes ............................................................................................................. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Introduction to infectious diseases.................................................. 44 Virus (Epidemic) Hepatitis A and B .................................................. 51 Whooping-Cough (Pertussis) .......................................................... 59 Scarlet Fever (Scarlatina) I ............................................................... 68 Scarlet Fever (Scarlatina) II .............................................................. 73 Mumps (Epidemic Parotitis) ............................................................ 79 Meningococcal Infection.................................................................. 84 Measles (Morbilli) ........................................................................... 91 German Measles (Rubella) (Rubeola Morbillosa) ........................... 97 Chickenpox (Varicella) ..................................................................... 98 Infectious Erythema (Fifth Disease) .............................................. 104 Sixth Disease (Exanthema Subitum Seu Criticum) ........................ 104 EPSTEIN-BARR VIRUS ..................................................................... 105 Diphtheria ...................................................................................... 112 Dysentery ....................................................................................... 122 Influenza......................................................................................... 131 III. MCQ ............................................................................................................. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Viral hepatitis ................................................................................. 148 Shigellosis ....................................................................................... 152 Whooping cough (Pertussis) ......................................................... 155 Scarlet fever ................................................................................... 157 Salmonellosis ................................................................................. 161 Pseudotuberculosis ........................................................................ 164 Mumps. ......................................................................................... 166 Measles .......................................................................................... 169 Meningococcal infection ................................................................ 171 Influenza......................................................................................... 176 Infectious mononucleosis .............................................................. 179 Chickenpox ..................................................................................... 181 Diphtheria. .................................................................................... 182 German measles ............................................................................ 185 Escherichiosis ................................................................................. 186 Acute respiratory viral infections................................................... 187
*Viral Hepatitis* *Lec 1*
Viral hepatitis these are acute infectious diseases infecting hepatocytes and characterized by cyclic course, enlargement of liver, disturbance of it functions, appears of jaundice and intoxication symptoms. There are allot of causative agents: hepatitis A, B, C, D, E are all are RNA continuing except hepatitis B which is DNA containing; herpes simplex, CMV, Epstein bar virus, rubella adenovirus, anterovirus, Rota virus, and HIV (it can cause hepatitis but only one component of multisystem diseases).
*Hepatitis A*
Mechanism of transmission:
Fecal oral, direct contact through foods and water it may be contagious.
Pathology:
The initial injury in hepatitis A Cytopathic to hepatocyte: damage permeability of hepatocellar membrane and increase activity of ALT. Chloestatic component: increase serum alkaline phosphotase, gamma glummatyl transpeptidase and bilirubinogen which all can injure the billiary system. - In cholestasis there is decrease of intestinal content of bile acid which decreases the absorption of fat and vitamins. - Abnormal protein synthesis by hepatocytes are reflected by increase in PT (it is very sensitive indicator for liver damage). - Hepatocytes injury also leads to changes in the metabolism of carbohydrates and ammonia. - There is damage of disintoxication functions of the liver.
Clinical manifestations:
The course has a cyclic character (3 stages): 1. Pre-ictric. 2. Ictric. 3. Convalescence.
Pre-ictric period:
Most constant symptoms are:
Pediatrics Infection 1. Nausea. 2. Abdominal pain. 3. Diarrhea. There are 5 variants: 1. 2. 3. 4. 5. Dyspeptic (Hepatitis A). Catarrhal (Rhinitis, cough, headache). Rheumatoid pain (more common in adults). Asthenovegatative (Hepatitis B). Mixed. Slight hepatosplenomegally, there is increase of liver enzymes. The onset of jaundice is marked by decrease of dieresis, appearance of bile pigments in urine and it color is changed to dark yellow and stool become pale.
Ictric period:
There is fall of temperature and the patient general condition is improved. The liver is enlarged, hard and tender. Spleen enlarged by 1/5 or 1/3 (it more commonly enlarged in Heaptitis B). Disorders of liver functions, decrease of total proteins, dysproteinemia (due to increase of Gamma globulin content). Decrease of coagulation factors.
Ictric period is divided into: 1. Progressive. 2. Maximum development. 3. Ictric. Jaundice is present for 10 days; the recovery may take months due to post-hepatic asthenodyspeptic syndrome with functional disorder, enlarged liver with jaundice.
Classification:
According to clinincal variant: 1. Acute (mild, moderate, severe, and grave). 2. Chronic. Grave variant: toxic dystrophy of the liver, it starts as common hepatitis but later it transforms to malignant form within 7 days. o Adynamia, anorexia, vomiting, specific smell, billirubinemia (indirect), increase residual nitrogen and acidosis). o Very great toxemia with neuropsychic symptoms. o Contraction of the liver due to massive necrosis. o Hemorrhagic tendencies, tachycardia. 4
Pediatrics Infection According to the type: 1. Typical (Jaundice). 2. Atypical (no jaundice) [Hepatitis A].
Peculiarities of hepatitis for patients under 1 year:

1. 2. 3. 4. 5. 6. They can be associated with Hepatitis B infection. The course is more severe than in older children. Toxic dystrophy is more frequent. Pre-ictric period is short or absent. Jaundice is longer (marked enlargement of spleen, liver, and bilirubinemia). Secondary bacterial infection.
Parameters of severity:
Hepatomegaly Spleenomgaly Intoxication Common bilirubin Free bilirubin Level of prothrombin index Mild 3 cm Slight enlarged in 1015% of cases Slightly pronounced Up to 85 mmol/L 25 mmol/L 80-60% Moderate 3-5 or 6 cm Enlarged in 25-40% of cases More pronounced 85-170 mmol/L 25-50 mmol/L 60-40% Severe More than 5 cm Enlarged in 75% of cases Considerably pronounced 170-200 mmol/L More than 50 mmol/L Less than 40%
Diagnosis:
1. Epidemiological anamnesis: - Contact with patients. - Intoxication symptoms. - Color of urine and feces. - Hepatomegaly. - Dyspeptic syndrome. 2. Blood examination for bilirubin. 3. Determination of activities of ALT. 4. Proteins sediment test (Tymol and Sublimate). 5. Ultrasound. 6. Serology.
Differential diagnosis:
Pre-ictric period: 1. Infectious diseases of alimentary tract. 5
Pediatrics Infection 2. Acute respiratory tract infections. Ictric: 1. 2. 3. 4. 5. Physiological jaundice, sepsis. Infectious diseases (malaria, leprosy, toxoplasmosis, TB). Hemolytic and obstructive jaundice. Hemolytic uremic syndrome. Collagen vascular diseases.
Treatment:
o o o Bed rest. Hospitalization. Diet: - Milk, cheese, vegetables, fruits, sugar, and honey. - Minimum amount of fat and salt. - No spices and chocolate. - Adequate amount of liquids. - Vitamins E, A, and ascorbic acid. - In grave course a special diet is recommended: fruits, sugar, abundant fluids for 1-2 days. Siphon enema (to remove toxic products). Glucose IV infusion, isotonic saline solution with ascorbic acid. Plasma transfusion with albumin. Vitamin B12 IV. Predinsolone 2mg/kg/day for 7-10 days. Physiotherapy: in the presence of secondary infection; therapeutic drainage by Dymanos. Antibiotics: ampicillin, chlorophenicol. Hepatoprotectors: hepabena, Liv 52, essentiale. Spasmolytics. Sanitary treatment.
Children should be kept under observation for 6-12 months; they should follow a specific diet and limitation of physical activities.
o o o o o o o o o o
Prophylaxis:
1. Immunoprophylaxis: Active: - Safe formalin killed vaccine. - Young children are vaccinated in the endemic areas. - Hepatitis A gives lifelong immunity after infection. Passive: - Standard immunoglobulins are affective in half of infections. 2. Common measures: Patients with hepatitis should be hospitalized in special departments; convalescences should be discharged after complete recovery not earlier than 3 weeks or 30 days after the onset of jaundice. 6
Pediatrics Infection Children with relapse are readmitted 10 days after discharge. The child should be under observation for 50 days after last day of doctor visit. ALT test is recommended for early diagnosis. Test blood before transfusion for hepatitis B.
*Hepatitis B*
Index of severity of infection is the same in hepatitis A.
3 genuses of hepatitis B antigens:

1. Surface antigen (HBsAg). 2. Core antigen (HBcoreAg). 3. E antigen (HBeAg). Replication of hepatitis B is mainly take place in the liver, and sometimes in the intestine. The greatest risk of infection is mother to child when the mother is HBeAg positive. HbeAg is present in blood, serous exudate (high content); saliva, semen and vaginal secretions (moderately).
Blood. Mother to child. Sexual transmission.
Pathogensis:
It is non-psychopathic virus that hepatocyte injury is mediated by immune response. The first stage of infection of hepatocyte results in appearance of viral antigens on the surface of the hepatocytes. The most important are nucleocaspid antigens HBcoreAg and HbeAg these two antigens react with C1 complex which makes the hepatocytes the target for cytotoxic T cell lysis.
Clinical features:
1. 2. 3. 4. 5. Asymptomatic. Usual acute symptomatic episodes are similar to other infections and involve the joints and skin. It usually proceeds as a serum sickness like prodrome (arthalgia, skin lesions, urticaria and popular rashes). Popular acrodermatitis (Geroti Crosty syndrome). Extrahepatic manifestations: a. Polyarthritis. b. Glomerulonephritis. c. Aplastic anemia. 7
Pediatrics Infection d. Chronic hepatitis (it may lead to cirrhosis of carcinoma). Chronic hepatitis is more characterized for hepatitis B.
Diagnosis:
Serology: HAV IgM antiHAV Ag HBsAg HBeAg HBV AB IgM anti HBcoreAg IgM anti HBeAg HCV IgM antiHCV HDV IgM antiHDV HEV IgM antiHEV
IgM anti HBcoreAg: persists for few months then replaced by IgG anti HBcoreAg. IgG anti HBcoreAg: persist for lifelong. HBcoreAg: it is the most valuable marker for acute hepatitis, but it is not present in prenatal period. HBsAg is present in immunized people. HBcoreAg is absent in blood and can be detected only by liver biopsy.
Complications:
1. Fulminate hepatitis (co-infection with hepatitis D). 2. Chronic hepatitis that may lead to carcinoma and cirrhosis.
Prevention:
1. Immunoprophylaxis: 3 steps for vaccination: - First days of life. - On the first month of life. - On the 6th month of life. If the mother if HBsAg positive: - During the first 12 hrs of life. - After 1st month. - After 6 months. - After 12 months. 2. Prophylactic measures: Examination of blood donors for HBsAg. Dont transfuse blood from Hepatitis B patient.
*Hepatitis C*
8
Pediatrics Infection
HCV is a simple strand RNA virus.
Parantral. Sexual contact.
Pathogensis:
Cytopathic injury to hepatocytes (cytopathic is mild and less severe than over forms of hepatitis). Immune mediated.
Clinical picture:
2/3 or post transfusion and 1/3 sporadic cases will become chronic. Chronic form may progress to cirrhosis only in of infected patients. Carcinoma develops in patient with cirrhosis. The carcinoma associated with HCV is result of inflammation and necrosis rather than oncogenic affect of the virus.
Complications:
1. Chronic hepatitis. 2. Fulminate hepatitis (not often).
Prophylaxis:
No vaccination.
*Hepatitis D*
HDV it is smallest non animal virus and it is consider defective because it cant produce infection with HBV. In contrast with HBV, HDV causes injury directly by cytopathic mechanism. In co-infection acute hepatitis is much more severe than Hepatitis B alone, but with low risk of development of chronic hepatitis. In supra infection acute illness is rare, but the risk of fulminate hepatitis is high. Incubation period: 40 days.
Diagnosis:
No circulating antigens are identified.
Pediatrics Infection Diagnosis is confirmed by detecting antibodies against HDV which appears 2-4 weeks after co-infection and 10 weeks after supra-infection.
Prevention:
No vaccination. Consider elimination of HBV infection.
*Hepatitis E*
Fecal oral.
Epidemiology:
India, asia, middle east.
Pathogensis:
Cytopathic.
Clinical manifestations:
Are similar to hepatitis A, but more severe. It produce only acute disease and never cause chronic disease. Hepatitis E affects all the patients thats way it is severe. High fatality rates are during pregnancy, or between 16-35 years.
Prevention:
No vaccination.
Diagnosis:
Detection of IgM anti HEV
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*Acute intestinal diseases* *Lec 2*

Types of diarrhea:
1. Secretory: Viruses (Ritavirus, adenovirus, astravirus, cornavirus). Bacteria (V.cholera, salmonella, campylobacter, enterotoxocgenic, enteropathogenic, enteraggravating, E.coli). Protozoa (cryptosporidium, mycosporidum, balantiduim). 2. Invasive: Bacteria (Shigella, salmonella, yersinia, enterocolotica, E.hemorrhagica, E.coli, campylobacter, clostridia).
Mechanism of diarrhea:
Through the action of toxins. Direct invasion of intestinal mucosa.
*Shigellosis*
Shigella, salmonella, E.coli, belongs to the family enterobacteriocae.
4 species of shigella:
1. 2. 3. 4. S. Dysenteriae (Serogroup A-12 serotype). S.Flexineri (Serogroup B-6 serotype and 13 subserotype). S. Boydii (serogroup C-18 serotype). S.sonni (serogroup D-1 serotype).
Pathophysiology:
The shigella invades the colonic epithelium cells by synthesis of a group of S.dysenteriae serotype I produce plasmid coded antigen (shigatoxins, exotoxin) inhibit synthesis of proteins LPS.
Pathology:
The colon is target organ for shigella. The changes are most intense in the distal colon although pancolitis may occur. The form of intestinal affection: o Catarrhal. 11
Pediatrics Infection o o o Follicular. Croupous. Diphtheria
Epidemiology:
Contaminated food and water. Person to person transmission.
Criteria for severity:

LOCAL PHENOMENA Bloody stool. Constant abdominal pain. Defection more than 25-30 times/day. Sphincter paresis or paralysis (gaping of anus). GENERAL PHENOMENA Cardiovascular weakness. Neurological disorders. Electrolytes disorders (due to vomiting and diarrhea).
Raltipin classification:
I. Typical: Mild (defection 3-8 times). Moderate (defection 9-20 times). Severe form. Atypical: Abortive form. Subclinical form. Toxic form (general toxicity). There is acute and chronic dysentery. For children it is not typical.
II.
Symptoms:
I. Generalized (acute onset): 1. High fever. 2. Emesis. 3. Anorexia. 4. Seizures. 5. Meningism. Colitic symptoms: 1. Abdominal pain (spasmodic in character). 2. Tenesums (apastic contraction of sigmoid). 3. Urgency. 4. Painful defection (defection brings relief from pain). 5. Scanty stool (loss of their fecal character): - Thick. - Almost transparent mucus. 12
II.
Pediatrics Infection III. Odorless. Later mucus with blood.
Physical examination: 1. Abdominal distension. 2. Abdominal tenderness. 3. Spastic condition of the sigmoid colon. 4. Hyperactive bowel sounds. 5. Tenderness in rectal examination.
Shigellosis in infants:
1) 2) 3) 4) Stool (dyspeptic): liquid, greenish in color, with mucus, rarely blood flakes. No tenesmus, redness of the face during defecation. Anal responsiveness. Dehydration.
Complications:
1) 2) 3) 4) 5) Dehydration with renal failure and death. Sepsis. DIC. Dysbacteriosis. Intercurrent disease.
*Salmonella*
3 species:
1) S.typhi. 2) S. choleraesuis. 3) S. enteritidis (more than 1800 distinct serotypes). They are motile non-sporing, non-encapsulated, gram negative rods, and resistance to many physical agents.
Antigenic structure:
Somatic antigen OAg: heat stable LPS component of cell wall. Flagler antigen HAg: heat liable proteins. Virulence antigen Vi: capsular PS (S.typhi and rare S.paratyphi).
Non-typhoidal salmonellosis:
Epidemiology: Infected animals (chicken). Poultry and its products. Person to person (fecal oral). 13
Pediatrics Infection Nasocomial infections (contaminated medical instruments, pharmacological preparations).
Pathology: Salmonella is capable of penetrating the intestinal mucus involving lamina properia. Hyperplasia of reticulo-endothelial system such symptoms like hepatosplenomegally occurs 2 weeks of the disease. Heat liable, cholera like enterotoxin and the prostaglandins that are produced locally, increase of cAMP levels within intestinal crypts, causing a net efflux of electrolytes and water into intestinal lumen.
Clinical manifestations: I. Typical: Gastrointestinal. Typhoid (in immune compromised child). Septic (in immune compromised child). About 90% - gastrointestinal disease, gastroenteritis, enterocolitis. Atypical: Absorptive. Subclinical form.
II.
Acute gastroenteritis: Abrupt onset. General toxiemia (fever, headache, dizziness, drowsiness, confusion, meningism, seizures). Nausea. Vomiting. Abdominal pain in the peri-umbilical area and right lower quadrant. Mild to moderate watery greenish diarrhea (sometimes dysenteric diarrhea: with mucus and rarely blood). Heptosplenomegally.
*E. Coli*
Enterotoxogenic E.coli (ETEC) due to colonize factor antigens adhere to intestinal epithelium and produce a heat
liable enterotoxin (LT) and a heat stable enterotoxin (ST), stimulation of adenylase cyclase which increases cAMP (cholera like illness).
Enteroinvasive E.coli (EIEC) - invade gut epithelium, posses a large virulence plasmid closely related to the shigella
plasmid (Dysentery like).
14
Enteropathogenic (EPEC) - adhere to intestinal mucosa (loss of microvilli), attach results is increase Ca concentration
hence polymerization action at the site of attachement (infantile gastroenteritis).
Enterohemorrhagic (EHEC) - produces one or more toxins that kill mammalian cells. Shigatoxin- inhibits exotoxin of shigella serotype I. Enteroaggregating (EAgEC)- adhere to HEP-2 cells in tissues culture.
Epidemiology:
Person to person contact. Contaminated water and food.
Clinical picture:
ETEC: 1. 2. 3. 4. 5. 6. EIEC: 1. 2. 3. 4. 5. 6. EPEC: 1. 2. 3. 4. EHEC: 1. Abdominal pain with diarrhea. 2. Diarrhea within few days becomes grossly bloody. 3. Fever. 15 Infants and children in first few years of life. Non bloody diarrhea with mucus, stool yellow-orange in color. Repeated vomiting. Fever (protracted prolong course). Indistinguishable form of classic bacillary dysentery. Fever. Systemic toxicity. Abdominal cramps. Tenesumus. Urgency with watery or bloody diarrhea. Dehydration. Infantile diarrhea (explosive watery diarrhea). Abdominal pain. Nausea. Vomiting. Fever.
Pediatrics Infection EAgEC: 1. Signs of fluid loss with dehydration. 2. Infrequent vomiting and grossly bloody stools. 3. Prolong diarrhea.
Diagnosis:
1) 2) 3) 4) 5) Epidemiological data. Bacteriology (stool, and rectal swab). Serology (indirect hemoagglutination test [titer of antibodies 4 times more]). Copragram (mucus, WBC, RBC [colitic syndrome]). Blood culture.
Treatment:
1) Diet: Early feeding with breast milk or formula. 10-15ml X10times/day. 60-80ml X8times/day. 90-120ml X7times/day. 130-160X6times/day.
2) Oral rehydration: Boiled water, salt solution, tea [2 teaspoons every 5-10 minutes]. 2 stages of dehydration: 1. To control the weight loss due to dehydration (6 hrs): o Calculation formula: volume = weight of child X deficit of weight X10. o Stage I: dehydration (mild): 30-50ml/kg. o Stage II: moderate: 80-100ml/kg. 2. Supportive therapy (18 hrs): o 50-100ml/kg. o This is to support physiological requirement.
Clinical signs of dehydration:

SYMPTOMS Body weight loss (%) General condition and appearance Radial pulse Respiration Anterior fontanell Systolic BP Eyes MILD 3-5 % Thirsty, alert, restless Normal Normal Normal Normal Normal MODERATE 6-9% Thirsty, restless, lethargy, irritability Rapid and weak Deep and rapid Sunken Normal or orthostatic hypotension Sunken SEVERE 10% or more Drowsiness, cold limbs, sweating, cyanosis, pt may be comatose Rapid and febrile Deep and rapid Every sunken Decreased Grossly sunken
16
Tears Mucus membrane Urine flow Capillary refill Estimated fluid deficit Present Moist Normal Normal 30-50 Absent to reduced Dry Decreased and dark +/- 2 sec 60-90 Absent Very dry and hyperemic Oligouria to anouria More than 3 sec 100 or more
Dehydration and serum Na concentration:

TYPE Hypotonic or hyponatremic Isotonic or isonatremic Hypertonic or normonatremic ELECTROLYES Na < 130 mEq/L Na < 130-150 mEq/L Na > 150 mEq/L
Fluid therapy consists of 3 categories: 1. Maintenance. 2. Deficit replacement. 3. Supplement replacement of ongoing losses. Method of calculation of caloric expenditure from weight:
BODY WEIGHT (KG) Up to 10 10-20 More than 20 CALORIC EXPENDITURE/DAY 100 Kcal/Kg 1000 Kcal +50 Kcal/Kg for each Kg above 10 1500 Kcal +20 Kcal/Kg for each Kg above 20
Maintenance of fluids and electrolytes loss: 100ml water (35ml insensible water loss, 65ml of urinary H20 loss). 2-4 mEq of Na and K for every 100 calories expended.
Replacement of ongoing losses: 10ml/Kg daily on each degree over 37.5 c. 20ml/Kg at vomiting. 20-40ml/Kg for daily flatulence. 25-75ml/Kg daily at diarrhea. 30ml/Kg daily at perspiration.
Principles of treatment of dehydration: o o o Mild: treatment should be orally. Moderate: 1/3 IV ; 2/3 orally. Severe: 1/3 orally ; 2/3 IV.
Initial therapy: In initial phase 20-30 ml/Kg of body weight of isotonic solution should be given by bolus and repeated second time. 17
Pediatrics Infection This procedure should be repeated 3rd time if the patient general condition is not normalized (repeat until normalization of hemodynamics to prevent shock). Type of solution depend on the dehydration: o If isotonic dehydration: - 5% glucose + physiological solution. - In a ratio of 1:2 (1 isotonic; 2 physiological solution). o If hypotonic dehydration: - Isotonic solution + glucose solution 5%. - In a ratio of 2:1 o If hypertonic dehydration: - Glucose solution 5% + Physiological solution. - In a ratio of 2:1
3) Antibiotics therapy (etiopathogenic therapy):

ANTIBIOTIC Ciprofloxacin Cefixime Ceftriaxone Nalidixic acid Sulfanilamide (biseptol) DOSE 15mg/kg in 2 doses orally 8mg/kg/24 hrs in 2 doses 100mg/kg/24 hrs 55mg/kg/24 hrs
Indications for antibiotics therapy: 1. 2. 3. 4. Age more than 1 year. Bloody diarrhea. Depressed immunity. Inter-coherent diseases.
4) Bacteriophage (specific therapy). 5) Biological preparations: Bifidum bacteria, Bifilact, Inex. These preparations for prevention and treatment of dysbacteriosis.
6) Enzymes therapy. 7) Enterosorpent: It is used at the start of the disease and not used in case of bloody diarrhea.
8) Symptomatic therapy: Hyperthermia: 50% analgin 0.1ml/yr. Vomiting: metaclopromide 0.1-0.2 mg/kg. Convulsions: diazepam 0.2mg/kg. 18
Prevention:
1. Breast feeding. 2. Hand washing. 3. Chlorinated H2O, proper sanitary system and adequate food hygiene.
19
*Scarlet fever & Measles* *Lec3*

*Scarlet fever*
Causative agent hemolytic streptococci group A.
Toxins of hemolytic streptococci:

1. Local action toxin. 2. Diffuse action toxin: o Thermoliable (toxin of rash or Dicks toxin). o Thermostable (typical streptococcus allergen).
Incubation period:
1-7 days.
Pathogenesis:
Sources of infection: Patient carrier: the infected patient expels the causative agent in saliva from the first hour of the disease.
Way of transmission: Air drop. Direct contact. Disinfection is needed after scarlet fever. Susceptibility: Children between 2-7 years are affected more commonly. Babies have an absolute immunity against scarlet fever. Caused by Streptococcus itself with it toxins of local action. (tonsillitis) Dicks erythrogenic exotoxin Term 1st day Clinics -Tonsilitis -Regional lymphadenitis -Intoxication -Short type specific immunity -Rashes appear on the 1st day -Hyperemic skin -Changes in oral cavity -Antitoxic immunity
Mechanism of pathogenesis Septic
Toxic
1st day
20
Pediatrics Infection (immunity to toxins only, but no to streptococcus) -Fever -Allergic rash - Poly lymph adenitis -Sensibilization infection allergic disease
Allergic
Thermostable exotoxin erthrogenic exotoxin, -Typical allergen: 1) streptococcus. 2) products of breakdown of tissue. (joints heart and kidneys are the most damaged organs)
Only on the 7th-10th day of the disease
The disease is characterized by an acute onset, and all symptoms appears simultaneously. The disease start with fever, vomiting, headache, intoxication, pharyngitis, tonsillitis, and chills within 12-20 hrs the typical rash appears and temperature usually increases. The tonsils: are hyperemic and covered with grey film. Pharynx: is inflamed and covered with membrane. The tongue: o In the first day the tongue is coated. o Edematous and reddened, during early stages the dorsum of the tongue has a white coat through which the red edematous papulas project (white Roseberry tongue). o After several days the white coat desquamates and the red tongue started to appear with permanent papules (red tongue red strawberry tongue). The palate: may be reddened, edematous and covered with pitichia. Characteristic changes in the mouth: o Changes in the tongue. o Tonsillitis. o Pharngitis. o Soft plate involvement (reddened, edematous, and rashes [enanthema]). Punctuate lesions are present on all over the body including the face, forehead, and cheeks, but the area around the mouth is pale. The rash is most intense in the axilla, groin, and on the pressure sites. o The rashes appear due to increase of vascular permeability. o The rashes are accompanied by itching and sorties it may be hemorrhagic rashes. o No rashes around nasolabial fold. o Rashes disappear with desquamation but without pigmentation. o No stages for appearance of the rashes. o The patient skin looks red. o The skin and mucus membrane are dry (due to affection of vegetative nervous system). We should pay attention to the inner surface of the upper and lower extremities. Desquamation begins in the face as fine flakes on the end of the first week and spread to the trunk, hands, and feet. White skin demography (more on the 2nd to 3rd week).
3 main signs:
1. Exanthema. 2. Tonsillitis. 21
Pediatrics Infection 3. Fever.
Classification:
I. Typical: 1) Mild (80-90%). 2) Moderate (10-20%). Parameters of severity (mild & moderate): - Pronounce intoxication. - Severity of tonsilitis (catarrhal & purulent). 3) Severe (0.5-1%): - Toxic. - Septic. - Toxicoseptic. Atypical: 1) Frustes. 2) Milde form: - Abortive. - Extra-pharyngeal. 3) Very severe (aggravated form): - Hemorrhagic.
II.
Mild form (80-90%): Mild malaise, febrile temperature, with disturbances of general condition. The tonsillitis has a catarrhal in character. Rashes are typical and sometimes are pale. The skin is goose and dry.
Moderate (10-20%): Acute onset. Marked toxemia, temperature 40 c, headache, malaise, and delirium (at night). Frequent vomiting during the first day and may occur later. Tachycardia 140 beats/minutes; there is no depression of the cardiac activities. Tonsilitis has purulent character. Rashes are bright and abundant.
Severe (Toxic form): Onset is violent. Repeated vomiting which continues to the 2nd and even 3rd day. Diarrhea. Fever is high almost 40-41 c. Strong depression, the consciousness is clouded, and delirium. 22
Pediatrics Infection Convulsions and meningeal symptoms may be present. Rashes appear, dry and bright lips, and the sclera is injected. - Allergic rash. - Slight fever. - Moist mucus membrane. - Itching with maculopapular rash. - Activation of sympathetic system (bradycardia and red demographism).
Severe (Septic form): Slight toxemia. Severe necrotic tonsilitis . Very frequent septic complications.
Severe (Septico-toxic form): Frustes: Repeating intoxication symptoms. Comatose state. Patient dies from the first day. Combination of symptoms of toxic and septic forms. It usually begins as toxic and on the 2nd or 3rd day signs of septic form appear.
Complications:
I. Early: Appears on the initial period as a result of toxemia (first week) these complications have a septic origin. 1. Necrotic tonsilitis. 2. Purulent lympho-adenopathy. 3. Otitis. 4. Mastoditis. 5. Sinusitis. 6. Adenophlegmon. Toxic origin toxic shock. Late: Appears on the 3rd or 4th week, these complications have an allergic origin. 1. Hepatitis. 2. Nephritis. 3. Rheumatoid arthritis. 4. Endocarditis. 5. Polyarthritis. 6. Rheumatism.
II.
Criteria of severity:
1. Hemorrhagic rash. 23
Pediatrics Infection 2. 3. 4. 5. Necrotic tonsillitis. Shock. Hyperthermia. Numerous rash elements.
Diagnosis:
1. Blood test: Leucocytosis. Neutrophilosis. Positive bacteriological test. 2. Level of streptolysine. 3. Urine. 4. Culture. 5. ECG.
1. 2. 3. 4. 5. Measles. German measles (Rubella). Meningococcemia. Toxicoderma. Pseudo-TB.
To differentiate scarlet fever with measles:

In measles catarrhal period is present and characterized by: o Conjunctivitis. o Soft palate is not reddened. Pathognomonic sign (Polsky spots): o The rash of measles appears late mainly on the 3rd or 4th day of the disease and have stages for it appearance. o They change to muculopapular rashes which have the tendency to merge together, the skin around it is unaffected and without changes in it color. o After fading of the rashes pigmentation appears (no pigmentation is scarlet fever). o In blood analysis: Leucopenia (in scarlet fever - leucocytosis). Eisonophilia.
To differentiate scarlet fever with German measles (Rubella):

Low fever. Maculopapular rashes which characterized by poylmorphology (maculas, papules, vesicles, crusts). The causative agent have the property of tropism to fetus embryonic tissues, if a pregnant women falls ill with rubella in early pregnancy the embryo develops chronic congenital rubella (microcephalia, hydrocephalus, loss of hearing, and retinopathy); when the women is infected in late stages of pregnancy the fetus will have (anemia, thrombocytopenia, hepatitis, affection of lungs, and bones). Affection of all lymphoid tissues (lymphoadenopathy) especially occipital and posterior cervical. 24
Pediatrics Infection Rashes in germen measles are: o Maculopapular rash which are small 3-4 mm in diameter and have no tendency to confluence. o They appear on the external part of the limbs (extensor surface of the buttocks, extremities, and on the back). o No changes in the tongue and no tonsilitis .
To differentiate scarlet fever with Pseudotuberculosis:

It is caused by Yesinia pseudotuberculosis (it has the ability to grow in very low temperature). o Route of transmission: fecal oral, more common in winter and spring seasons. No tonsilitis and slight catarrhal phenomena of the oral cavity. It involved different joints. Rashes are around the joint or distal part of the upper and lower extremities (symptom of Socks and gloves). Fever persists for longer time for not less than one week. Longer course. The rashes end with desquamation. White skin demography. Roseberry tongue is present. Complain: o Pain in the joints or lumbar region. o GIT disorders are frequent (diarrhea). o The disease mostly affects adults. o Signs of appendicitis. o Heptosplenomegaly and enlargement of mesenteric lymph nodes. Types of rashes: o Pinpoint or maculopapular rash. Investigations: o CBC, urine, stool, bacteriology, corpalogical, serolog, and ultrasound [serology is positive at the end of the first week]. Treatment: o Cephalosporins (ceftriaxone 100mg/kg). o Chlormphenicol 30mgkg o Distintoxication therapy IV or oral. o Glucocorticoids in severe cases. o Sorbents. o For 7-14 days.
Treatment of scarlet fever:

1. Diet: - During the feverish period we should give the patient fluids or semi fluid food with adequate amount of vitamins especially vitamin C. 2. Antistreptococcal therapy: - Penicillin 100mg/kg X4/day IV or IM. - Macrolides. 25
Pediatrics Infection - Cephalosporins. - Local antiseptics. 3. Pathogenic therapy: - Disintoxication therapy (PO or IV is severe cases [extrose, glucose, saline]). - Desensitizing therapy (loratidine). Treatment for not less than 10 days, if complications are present prolongs the treatment. One week in hospital and 2 weeks in home. The patient should be under observation to prevent the complications (One week in hospital and 2 weeks in home).
*Measles*
Stages:
1. Incubation (8-17 days, in who had serum prophylaxis it can be 21 days): no manifestations. 2. Prodromal stage: symptom complex. o Enanthema: slight to moderate fever, conjunctivitis, coryza, slight increase of cough. o Laryngitis and conjunctivitis: catarrhal phenomena. 3. Eruptive stage. o Catarrhal: - Persist and has tendencies to increase. - Maculopapular rash on the face, arm, legs, and accompanied high fever.
Etiology:
Eruptive stage is characterized appearance of rash increase of catarrhal phenomena with very high fever (due to intoxication). Causative agent is RNA virus (RNA viridae) the measles virus is unstable and destroyed outside the human body. Source of infection: sick person; no carriers. Susceptibility is very high, stable lifelong immunity is confirmed by one attack of measles.
Pathogenesis:
Mucus membrane, upper respiratory tract and conjunctiva lesion. Altered reactivity is expressed in development of [Measles energy]: positive tuberculin test disappears, titer of Immune body decrease, complement titer decreased, immunization capacity of organism is decrease. Can persist for longtime in brain and causes chronic infection, subacute sclerosing pan-encephalitis .
Clinical picture:
Onset: symptoms of catarrhal period which usually last for 3-5 days and characterized by fever, barking cough, coryza, pharyngitis, laryngitis, and conjunctivitis. Enathema usually on the hard and soft palate. 26
Pediatrics Infection Pathogonomic sign (Belsky-Filotov-Koplik spots): o Mucus membrane of the cheeks opposite to the molar teeth. o Each element looks like whitish papule of poppy seeds surrounded by narrow bed of hyperemia and then hemorrhage. Then the patient begins sneezing, dry barking cough, and sensation of irritation in respiratory tract (pharyngitis). Catarrhal phenomena: conjunctivitis, rhinitis, laryngitis, pharyngitis. o Rhinitis: difficult nasal breathing, and serous discharge. o Laryngitis: dry barking cough. o Conjunctivitis: hyperemia of conjunctiva (water in the eye), photophobia (eyes close spontaneously). General appearance of the patient: o Swelling of the face, eyelids are hyperemic, and edematous, water in the eyes, photophobia, and serous discharge from the nose.
Eruptive stage: General malaise, symptom of functional disturbances of CNS, adynamia, increase of weakness, decrease of appetite, and disturbances of sleep. Catarrhal phenomena, conjunctiva, enlargement of mesenteric lymph nodes which may cause abdominal pain. It may causes obliteration of the lumen of appendix causing appendicitis. Rashes: o Macula in the upper lateral part of the neck, centre of the face, behind the ears, along the hair line, and posterior part of the neck (within 24 hrs it covers the face, neck and upper chest). o The appearance of rash is accompanied by increase in temperature. o On the 2nd day: exanthema spread over the trunk and proximal part of the extremities. o On the 3rd day: the rashes appear on the limbs. - The rashes first appears as a pink papules, then each papule is surrounded by bright erythema and then they merges together to form a bigger rash with irregular borders which have the tendency to merges further. - Often the affected skin is not changed. - From the 4th day the rash fades in order of it appearance. - On the face the rashes are brightened, on the 5th day each element leave spots of light brown pigmentation (fro 1-2 weeks). - Fine brawny desquamation on the face and trunk following the eruption last for 5-7 days. In the hemorrhagic type (black measles) bleeding may occur from mouth, bowel. In incubation period mild leucocytosis and neutrophilosis; in early eruptive stage leucopenia; in eruptive stage: neutrophilosis; in convalescence: leucopenia. The indices of general immune reactivity are decreased.
Clinical forms:
1. Mild. 2. Moderate. 3. Severe (marked toxemia, affection of CNS, adynamia). Atypical forms: 27
Pediatrics Infection 1. Toxic. 2. Abortive (in immunized patient).
Complications:
I. Early: a. Etiology: 1. Caused by the virus itself. 2. Caused by secondary flora. b. Term of development: 1. Early prodromal or eruptive. 2. Late pigmentation. c. Involved system: 1. Respiratory system: pneumonia, bronchitis, pleurisy, laryngotrochitis, and exciting TB process (due to measles energy). 2. GIT: stomatitis, enteritis, colitis. 3. CNS: encephalitis, meningitis, subacute sclerosing pan-encephalitis. 4. UT: cystitis, pyelonephritis, glomerulonephritis. 5. Ears: conjunctivitis, blepharitis. 6. Eyes: otitis, mastoditis. 7. Skin: adenophlegmon, hard phlegmon. Late.
II.
Differential diagnosis (catarrhal stage):

Clinical manifestation Intoxication Coryza, nasopharyngitis Nasopharyngitis & intoxication Laryngitis & laryngotrochitis Koplik spots Differential diagnosis Influenza Adenoviral infection Rhinovirus Parainfluenza Stomatitis
28
*Meningococcal infection* *Lec 4*

Causative agent
It is Weichselbauns meningococcus (Nisseria meningitis). Gram negative, diplococcus, grows in moist environment in temperature of 37 c0. It is localized inside the neutrophilis.
Pathogenic factors:
1. Capsular polysaccharide: It is protect bacteria against phagocytosis. 13 serotypes A, B, C, W, and Y. A serotype appears only in epidemic. 2. Lipoligosaccharide: Endotoxin appears in the blood due to decompression of microbes. This endotoxin leads to DIC (the main cause of rash). 3. Pilli: It is responsible for adherence. 4. IgA protease: Damage of secretary IgA.
Epidemiology:
Sources of infection: 1. Sick person (catarrhal phenomena is present). 2. Carriers (asymptomatic [catarrhal phenomena is absent]). Ways of transmission: - Aerial droplet (distance 0.5-1 meter). Season: - More common in winter and early spring. The disease is more typical for children who are younger than 10 years.
Pathogenesis:
The bacteria colonize in the mucus membrane of naso-pharynx (95% leads to carrier stage). Bacteria enters non-ciliated epithelial cells by a parasitic direct endocytic process. Bacteremia (0,5-1%). Phagocytosis is incomplete and naso-pharynx mucus get through hemolytic encephalitic barrier and lead to development of meningitis (because neutrophilis cant produce myloperoxidase).
29
Pediatrics Infection Activation of fibrinolytic system which increase the chance of development of DIC, multiple organs failure (due to appearance of endotoxin) and septic shock. When concentration of toxin is 800micrograms or more it leads to lethal outcome. Coetaneous hemorrhage ranging from petechia to purpura (due to acute vasculitis with fibrin deposition in arterioles and capillaries). Thrombus contains bacteria so we can take swab from the rash for laboratory investigations.
Clinical classification by Pokrusky:

I. Local forms: 1) Naso-pharyngitis. 2) Healthy carrier. Generalized forms: 1) Meningitis. 2) Meningococcemia. 3) Meningoencephalitis. 4) Mix meningitis meningococcemia. Rare forms: 1) Arthritis. 2) Iridocyditis. 3) Chorioditis. 4) Pneumonia.
II.
III.
Incubation period:
3-10 days
Healthy carriers:
It is difficult to diagnose. We should take a bacterial swab from nasopharynx for all people in contact.
Nasopharyngitis:
Symptoms: 1. Fever. 2. Headache. 3. Nausea. 4. Vomiting. 5. Respiratory nasopharyngitis. 6. Meningohypoplasia of lymphoid tissues. 7. Scanty discharge from the nose. Changes in blood: 1. Leucocytosis. 2. Shift to left. 3. Increase of ESR. 30
Pediatrics Infection 4. Aneisonophilia.
Meningitis:
Symptoms: 1. Very severe headache. 2. Repeated vomiting and dont bring relief to patient. 3. High fever. - All symptoms appears at once the patients general condition is very severe. - Vomiting is no related to food intake and no nausea before it. - Headache occurs due to increase of intracranial pressure and accompanied by dizziness, hyperesthesia and hyperalgia. Meningeal sings: 1. Neck rigidity. 2. Brusinski sign (upper, middle, and lower). 3. Kerning sign. These signs are always positive in child under 1 year (normal physiology). Patients position: - Lying on the side, legs are flexed, and head is towered downward. The pressure in the spinal cord is increased. Meningococcal infection can lead to activation of all viral infections especially herpes simplex mainly after 2-3 days. In adults (constipation and flat abdomen), in children (diarrhea and tensmus).
Peculiarities for children: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. The child refuse to suck. Persistent vomiting with high fever. Marked hyperesthesia. Loss of weight. Loud screaming. Dyspeptic syndrome. Meningeal signs. Fontanel are protruded and tensed. Red demographism. Convulsions, tremors, and hypertonia. Hypertension. Irritability and drowsiness. Lesarge symptom: rise the patient and the child will move , in meningitis the child will flex his legs and hands.
Meningococcal encephalitis:
Symptoms: 31
Pediatrics Infection 1. Hallucinations. 2. Mental disorders. 3. Loss of consciousness. Laboratory investigations: 1. Lumbar puncture: - Increase of pressure 300-500. - Turbid and purulent. - Pliocytosis. - Increase neutrophils. - Increase proteins. - Decrease glucose. - Cells proteins dissociation increase (cells are more than proteins). 2. Bacteriological test: - Nasopharynx swabs. - Blood culture. - CSF. - Rash. 3. CBC. 4. Serology: - PCR. - Agglutination test. - PRHA.
Meningococcemia:
Acute onset of the disease. Toxicity. High fever. Hemorrhagic rash. o From the lower extremities, buttocks. o In severe cases the rash are large with central necrosis, very hard n palpation and never disappear when we press it. o Rash can be present on trunk, upper extremities and face. Vomiting. Myalgia. Arthralgia.
Prognostic factors: 1. 2. 3. 4. 5. 6. If petechia appears in 2-20 hrs. Quick spreading of the rash. Seizures and signs of shock. Hypothermia (<36o)or hyperthermia (>41o). Hypotension SBP <50 mmHg. Leucopenia < 4.109/l. 32
Pediatrics Infection 7. Thrombocytopenia < 100.109 [prothrombin index < 40%; high level of endotoxin > 8000 micrograms and increase of tumor necrosis factor (TNF)]. 8. Absences of meningitis. 9. Frederickson water-house syndrome (hemorrhage in adrenals): 1) Hyper-pyrexia. 2) Myalgia. 3) Arthralgia. 4) Vomiting (with blood). 5) Bloody diarrhea. 6) DIC. 7) Loss of consciousness. 8) Decrease of BP. 9) Appearance of rash. 10) Hypoxemia. 11) Multiple organs failure that lead to shock and death (usually patient dies within 24 hrs).
Chronic form of meningococcemia:

Last for 2-3 years. Increase of temperature (but not as much as acute form). Rash like meals. Irritability. Self limited disorder. Bacterioscopy is positive after 11-12 hrs.
Meningo-encephalitis:
Cortical disorders.
Arthritis:
Edema, disturbances of functions of joint (usually small one).
Iridocyditis:
Changes in the color of the eye (dust color).
1. Meningism is any other diseases: - Signs (very severe headache, vomiting, fever). - If we control the toxemia the temperature and signs of meningism will disappear. - Dissociation of meningeal signs (e.g only neck rigidity, or only lower brusinski). - No changes in CSF. 2. Serous meningitis (viral infections, mumps): Toxemia is not so pronounced. 33
Pediatrics Infection Signs of meningitis are no so pronounced. CSF: o Transparent. o Lymphocytosis. o Poliocytosis. o Normal glucose. o No cellular protein dissociation. TB meningitis: - The disease start gradually. - Moderate pyrexia. - Paraesthesia on the 10th -12th day of the disease. - Tuberculin test is positive. - X-ray of lungs shows milliary TB. - CSF: o Web like pedicles of fibrin on the surface. o MBT. o Lymphocytes. Meningeal form of poliomyelitis: - CSF: o Transparent. o Cellular proteins dissociation on the 10th day. - Disappearance of tendon reflex. - Paralysis. Hemophilic influenzal meningitis: - Common in age of 3 months to 1 year. - Convulsions. - Subdural effusion. - Auditory defect. Subarachnoid hemorrhage: - Sudden headache. - Fever. - Meningeal irritation are marked. - Changes in CT and MRI. Thrombocytic purpura: - The disease begin with no fever, but with petechia of the skin. - Nasal, intestinal bleeding, abdominal pain. - The general condition is not so disturbed. - CBC: thrombocytopenia. Hemorrhagic vasculitis: - Affects joints. - Abdominal pain, fever is absent. - General condition is not so disturbed.
3.
4.
5.
6.
7.
8.
Treatment:
Local form: 34
Pediatrics Infection Isolation. Rifampicin 10-20mg/kg for 5-10days. Antiseptic sol (nasal and gaggling in throat). Perform laboratory investigations again to find if the patient is a carrier.
Germanized meningitis: - Hospitalization. - IV infusion 50-100 ml/kg/day (to prevent edema of the brain give colloids and salts, in severe cases albumin and rheopolyglucins). - Ceftriaxone 100mg/24 hrs. - Cefaxime 200mg/24hrs. - Hormones therapy 2-3mg/day. - Diuretics (manitol): 20% - 0.5g/kg + potassium. - Seduxen to control convulsions. - 4% of sodium bicarbonate in case of acidosis. - Dopamine 1-7microg/kg/min in BP is decreased. - Vitamin B complex. - Nortropic drugs. All drugs should be given IV or IM. If the patient is allergic to penicillin we give cephalosporins. When to stop antibiotics treatment: 1. No fever for 5 days. 2. CSF proteins and sugar are normal. 3. CSF cellular count is less than 70/mm3, and 70% of all cells are lymphocytes. Meningococcemia: - IV infusion to control shock. - Chloromphenicol 50-100 mg X4/day. - Ceftriaxone 100mg/kg/day. - Hormone therapy 2-3mg/kg: o Shock stage 1: 5mg/kg. o Shock stage 2: 5-10mg/kg. o Shock stage 3: 15-20mg/kg. - Inotropic drugs dopamine 17 micrograms/kg/min Supportive therapy: Nasopharynx swab. Vitamin B complex. Noortropic drugs.
Prophylaxis:
1. Isolation and treatment of patients. 35
Pediatrics Infection 2. 2 days after the antibiotics course repeat bacteriological test. 3. Repeat bacteriological test after 7 days of isolation of patient and he can go to school. 4. Vaccination (capsular polysaccharide of meningococcal group A, C, Y W135), it is not used for children under 2 years.
36
*Diphtheria* *Lec 5*
Etiology:
It is caused by Corny bacterium diphtheria. It produce exotoxin during it growth. There are 3 biological types: o Gravis. o Intermediates. o Mites.
Epidemiology:
Source of infection: Carriers. Patients.
Ways of transmission: Areal droplet.
Portal of entry: Upper respiratory tract. Conjunctiva. Mucus membrane of genital. Damaged skin.
The disease is developed when the individuals are susceptible. The patient is contagious from the last day of incubation period until the full clinical recovery.
Pathological signs:
Fibrinous inflammation that occurs as coagulative necrosis of epithelium with dilation and congestion of the blood vessels and mucus membrane. Fluid exudates contains fibrinogen (due to increase of porosity of vascular wall), fibrin form a clots which comes in contact with necrotic tissues which will form a fibrinous membrane.
Types of inflammation:
Croups inflammation: o Formed in mucus lined with simple columnar epithelium. Diaphtheric inflammation: o Formed in mucus membrane that is lined with stratified squamous epithelium and connective tissues. o The regional lymph nodes are involved. 37
Pediatrics Infection Toxin effects: CNS. Adrenals. CVS. Kidneys. The most important defensive mechanism against diphtheria is production of antitoxin. Incubation period: o 2-10 days (4-6 days in average).
Variants of diphtheria according to localization and severity of the disease:

1. Diphtheria of the face, nose, larynx, bronchi, eyes, and skin. 2. Combined forms: face and nose, face and larynx. 3. Rare forms: 1) Nasal. 2) Conjunctival. 3) Diphtheria of genitals. 4) Diphtheria of skin and wounds. The most common type is face diphtheria (85-90%).
Face diphtheria:
1. Localized form: o Membranous film covers the tonsils only. o Variants: 1) Insular. 2) Catarrhal. 3) Tonsilar. 2. Diffused: o The membrane is extended beyond the tonsils to palatine arch, uvula, and throat. 3. Toxic: o Extensive lesions on the face. o Marked reaction of regional lymph nodes. o Toxic edema of the neck. o Generalized marked toxemia. Degrees of toxic diphtheria depending on the extent of the edema: First degree (to middle of the neck): o Generalized malaise, loss of appetite, headache and moderate rise of temperature. o Slight pain in swallowing (pain in scarlet fever is more). o Mild to moderate hyperemia and slight pain in tonsils (one the 1st day and rarely on 2nd).
38
Pediatrics Infection o Tonsils are enlarged and are covered with typical film which has the appearance of smooth wavy surface with well define edges. The membrane may be yellowish white or greenish white in color it adheres closely to the tissues and cant be separated by swab. Regional lymph nodes are moderately enlarged, hard on palpation, with well defined borders and slight redness on the periphery. It cant be diagnosed with bacterial examination.
o o
Second degree (to clavicle): o It is accompanied by vomiting. o The membrane covers the tonsils and the structures around them. o More produced malaise. o Anorexia, headache, disturbances of sleep. o Rise of temperature up to 38-39 Co or even more. Third degree (below the clavicle): o It begins suddenly with rapid rise of temperature (39 and more). o The patient is pale. o Headache, malaise, sleeplessness, anorexia, vomiting, abdominal pain, apathy, and adynamia (sometimes excitation). o The consciousness is clouded and the patient is delirious. o The mucus membrane of the tonsils, pharynx, and soft palate is edematous wth slight hyperemia. o Tonsils are covered with thick membrane, dirty white or brownish in color which is extended to the soft palate and even the tongue. o The face is pale, tongue is coated, lips are patched and unpleasant odor is smelled from the mouth. o Painful infiltrate of dense consistency which is outlines by area of cervical lymph nodes and the skin over the lymph nodes is unchanged. Palpation of this area is painless, percussion we can feel like jelly like mass. o Edema of the soft tissues and lymhpo-adenopathy leads to Bulls neck appearance. o Malignant course. Edema of the neck depends on the degree of toxemia.
Hypertoxic diphtheria:
Grave toxemia. Progressive fall of CVS activities.
Hemorrhagic diphtheria:
In 2nd or 3rd degree of toxic diphtheria. Pale or gray skin. Rapid fall of CVS activities. Hemorrhagic diathesis, and frequent bleeding. Increase blood coagulation time. Thrombocytopenia. Very high death rate. 39
Subtoxic diphtheria:
Transit form between toxic and diffused from. Less pronounced edema. Lymph nodes affection is unilateral. Malignant course.
Laryngeal diphtheria (upper respiratory tract):

It is encountered in young children 1-4 years old.
Stages of croups diphtheria: Initial stage: o Last for 24 hrs 2 days. o Dysphonia. o Increase temperature and generalized weakness. o Dry and hard cough (barking) appears simultaneously, when dysphonia develop then hoarseness. Second stage (stenosis Ist, IInd, IIIrd degrees): o Stenosis of the respiratory tract. o Retraction of part of chest during inspiration. o Tension in auxiliary respiratory muscles. o Disturbances of gases exchange. o Laryngoscopy: membrane (true and false)on the larynx and is also visible on the subglotic area. Third degree (stensosi IVth degree): o The child is fretfulness. o Skin is clammy with sweat. o Lips, limb and face are cyanotic. o Paradoxical pulse. o It distinguished as rapidly or slow progressing croup.
Types of croup: True (diphtheric): typical membrane. False (viruses [parainfluenza]): stenosis, edema, hypersecretion.
Complications:
1. 2. 3. 4. 5. Complications arise due to toxemia. CVS (Myocarditis). Neuritis (III, VII, IX, X, XII pairs of cranial nerves). Toxic nephritis. Polyneuritis. Pneumonia (common in diphtheric croup). Complications can be early and late: 40
Pediatrics Infection o o Myocarditis: Unfavorable course for early myocarditis. Gallop rhythm. Abdominal pain. Vomiting. Typical symptoms of myocarditis. Early: develop within the 1st week. Late: develop within the 2nd week.
Complications affecting nervous system: Paralysis of the soft palate, accommodation, facial expression. Speech become nasal. Fluid leakage from the mouth. The soft palate is flaccid and immobile. Asymmetrical paralysis of soft palate with deviation of the uvula.
Diagnosis:
1. Clinical examination. 2. Case history. 3. Bacteriological examination. If we diagnosed tonsillitis we should suspect diphtheria and ask for bacteriological examination.
1. Infectious mononucleosis: o Lymph nodes enlargement not only cervical, but other lymph nodes as posterior cervical, auxiliary. o Hepatomegaly and spleenomegaly. o Blood changes: atypical mononucleous and lymphocytosis. 2. Tonsillitis with blood diseases. 3. Follicular tonsillitis (purulent ): o White purulent coat, and pain in swallowing. o Hyperemia. o Lymph nodes enlargement. 4. Lacunar tonsillitis: o Purulent coat, enlarged tonsils with pain in swallowing. o Pronounced wide spread hyperemia and tenderness over regional lymph nodes. o More for tonsillitis caused by streptococcus and staphylococcus. In diphtheria pain during swallowing is absent or mild because the diphtheric toxin has an anesthetic effect.
Treatment:
1. Diet: 41
Pediatrics Infection o Fluids and semi solid food. o Only for the first day. Infusion therapy (rheopolyglucin). Glucocorticoids. Vitamin (nicotinic acid, B6, B12). Antibiotics for treatment of healthy carriers. Antitoxic serum: o It should be given by Bezredka method. o Test the skin by hoarse serum dilute 1:100. And check patients reaction every 20 minutes (0.1 ml is injected subcutaneously, and then 0.2 ml after 30 minutes and the ). o Inject the remaining dose in 60 minutes. First dose 10,000-30,000 30,000-40,000 40,000-50,000 60,000-70,000 60,000-80,000 100,000-120,000 100,000-120,000 10,000-15,000 15,000-20,000 20,000-30,000 Average dose 10,000-40,000 50,000-60,000 60,000-80,000 150,000-200,000 160,000-200,000 250,000-450,000 250,000-450,000 20,000-30,000 30,000 40,000-60,000
2. 3. 4. 5. 6.
Form of diphtheria Local form Diffused Subtoxic Toxic 1st stage Toxic 2nd stage Toxic 3rd stage Hypertoxic Nasal Laryngeal Descending (diffused) croup
Effects of treatment: The antitoxic serum effects appears after 8-12 hrs. 24-26 hrs the membrane shrinks and disappear. In toxic for the membrane takes longer time to diappear.
Treatment of diphtheric croup: Absolute rest. Thermal procedures have a sedative effect and decrease spasm of laryngeal muscles. Steam inhalation with sodium bicarbonate to relief the cough. Cold fresh air. Oxygen therapy. Glucocorticoids to relief the stenosis and decrease the need of surgery.
Surgery (in diphtheric stenosis): 1. Intubation. 2. Tracheostomy.
Prophylaxis:
1. Control of healthy carriers. 2. General preventive measures. 42
Pediatrics Infection 3. Active immunization: o APDT: absorbed pertusis diphtheritic tetanus. o ADT: absorbed diphtheritic toxin. - Primary immunization: o In age of 3 months: o 3 doses 0.5ml with intervals of 30-40 days. o APDT - Second immunization: o In age of 18 months. o Same dose. o APDT. - Third immunization: o With ADT. o First at age of 6 months, then 11-18 years, and in adulthood.
43
*Introduction to infectious diseases*

Infection or infectious process is the interaction of a pathogenic microorganism and a macroorganism under the influence of environment.1 If, as a result, the equilibrium of the organism's interaction with its environment is disturbed an infectious disease ensues manifested by clinical symptoms. An infectious disease is a form of infectious process. The specific feature of an infectious (epidemic) disease is its contagiosity, i.e. transmissibility from one body to another. The General Character of an Infectious Disease A characteristic of acute infectious diseases is their cyclic course, which is distinctly divided into the following individual stages: the incubation period, or stage of latency, the prodromal stage (premonitory symptoms), the stage of development, the stage of subsidence, and the period of convalescence. The incubation period begins from the moment of infection and ends with the appearance of the first signs of the disease. Every disease has an incubation period of definite length. During incubation the causative agent multiplies producing toxic products in the process. In addition a reconstruction of the organism takes place as it reacts to the action of the extreme irritant. A prodromal or premonitory period is not observed in all infectious diseases. It is characterized by the appearance of the first indefinite signs of illness (mild chill, low fever, malaise, headache, etc.). It does not usually last long (one to three days). The stage of development of a disease has its own complex of symptoms appearing and developing in a definite sequence, and then gradually declining in the stage of subsidence. The general symptoms of all the acute infectious diseases are fever, the development of inflammatory processes, and a more or less pronounced toxaemia. Bacteraemia and virusaemia are very important in the pathogene-sis and development of clinical signs of some infectious diseases. An important sign of an infectious disease is a more or less marked intoxication. Toxicoses caused by endotoxins, the products of decomposition of bacteria, tissues, products of disordered metabolism, are not specific.
44
Pediatrics Infection Many infectious diseases are attended by neurotoxicosis which is characterized by affections of the central nervous system. Hyperther-mic, meningeal, and convulsive syndromes, oedema of the brain, during which the danger of brain protrusion into the great foramen arises, are very important. The Waterhouse-Friderichsen syndrome, which is characterized by a violent onset, hyperthermia, marked adynamia, loss of consciousness, frequent vomiting, fall of arterial pressure to a circulatory collapse, is especially dangerous. Acute intestinal infections, and sometimes other infectious processes in children to 2 years of age, may be attended by toxicosis with dehydration due to loss of the body water caused by frequent stools and vomiting. Metabolic acidosis develops due to the loss of the electrolyte (as a result of the upset water-ionic balance, haemo-dynamics, and the disordered acid-base equilibrium). The degree and character of dehydration may be different. Isoton-ic, water-deficit and salt-deficit dehydrations are differentiated. With convalescence there is more or less rapid elimination of all symptoms of the disease, but complete restoration of the organism's normal functional condition is often a lengthy process. Adynamia, rapid mental fatiguability, and lability of the cardiovascular system are common. Not infrequently exacerbation is observed in the stage of subsidence of the clinical manifestations of an infectious disease, and relapse or recurrence of almost the whole symptom complex in the period of recovery. Superinfection there is a new infection, mostly by another type of the same causative agent (dysentery, scarlet fever). Mixed infections, in which the infectious process is complicated by involvement of two and more causative agents, occur frequently. Various associations of causative "gents are possible: mixed bacterial, bacterial-fungal, viral-bacterial, and viral infections are differentiated. Clinical Forms and Complications Infectious diseases have a great variety of clinical forms. The-manifestations and severity of a disease depend both on the properties (virulence) of the causative agent and on individual peculiarities of the organism's reactivity, which are determined by age, type of higher nervous activity, physical state, previous illnesses, etc. Hypertoxic forms of infectious disease (diphtheria, scarlet fever,. dysentery, etc.) are apparently associated with previous sensitization of the child's organism. Atypical forms are of great practical interest, and are often difficult to diagnose. They include so-called formes frustes with rudimentary symptoms (viz. angina scarlatinosa, whooping-cough without paroxysms, the catarrhal form of diphtheria, etc.) 45
Pediatrics Infection which are especially common when carrier state is encountered. They therefore play a great role in the epidemiology of infectious diseases. Complications are pathological processes closely linked genetically with the main disease and developing during the course of the latter or during convalescence. Their incidence depends on the severity of the disease (its clinical form), peculiarities of the organism's reactivity (particularly of age reactivity), the conditions of the patient's environment, and on nursing and treatment. FEATURES OF INFECTION AND IMMUNITY IN CHILDREN Physiological immaturity is the cause of imperfect protective reaction of the newborns. Atypical inflammatory processes, inability to form the cell barrier round the infection focus, i.e. to localize it and to preclude its propagation, are found in infants. The non-specific mechanism of protection against viruses, interferonogenesis, also depends on maturity of the body and its age. Production of interferon is minimal in infants under one year of age, or they are interferon-negative. This is encourage to develop deferent viruses diseases. The source or the natural reservoir of an infection is an infected human animal (the sick and carriers). Not only patients with clinically manifest forms of the disease are dangerous as regards infection but also those suffering from atypical forms frustes. The mechanism of infection is specific for each infectious disease and depends on localization of the causative agent in the human (of animal) organism, i.e. or the source of infection. This localization determines the route of discharge of the microbe into the environment. In diseases in which the causative agents are discharged from the organism mainly in the secretions of the mucous membranes of the nose, throat, pharynx, and upper respiratory tract infection is direct, by the aerial-droplet route (
respiratory infections measles, german measles, influenza, whooping-cough, diphtheria, scarlet fever, chickenpox, mumps). The causative agent can also be spread by direct contact of a healthy person with a source of infection. The transmission of infection via infected objects, i.e. by indirect contact (through dishes, toys, towels, handkerchiefs, patient,s clothes. The alimentary method of transmission of infection (by food) is characteristic of intestinal infections. Foodstuffs can become infected by a sick person or a carrier during transportation, sale, or cooking. Water-borne infection can occur through drinking infected water, accompanying extensive epidemics with an explosive onset and course. 46
Pediatrics Infection Transmission of the causative agents by living vectors (the transmissive route) is characteristic of many infection diseases (flies, blood-sucking arthropod parasites, mosquitoes, ticks). The problem of congenital infectious diseases is transplacental transmission of the causative agent from a sick mother to the foetus. A most important factor in the epidemic process is the susceptibility of a population. This is usually defined by the socalled index of contagion, of more correctly, the index of susceptibility.
When a case of nosocomial infection is discovered, the patient should be immediately isolated, and the ward ventilated, and when the infection is caused by a stable agent, disinfected. With aerial-droplet infections (except German measles) the whole department or an individual ward is quarantined, depending on the infection, the type of patients, and the conditions in the ward. Children who have not had the infection previously are no longer admitted, and the discharge of contacts is delayed. The question of what group of patients to quarantine, and on the need for this measure in such infections as chickenpox, mumps, whooping-cough, and influenza, is decided individually in each case, depending on the specific conditions; but it is desirable to consult an epidemiologist. An important item in control of nosocomial measles infection is properly organized serum prophylaxis among unimmunized contacts, thanks to which this very dangerous nosocomial infection is now relatively harmless in well-organized hospitals, and mortality has been reduced to zero. Each individual case of nosocomial infection needs to be analysed and recorded in a special journal of hospital infections. To avoid the danger of spread of infection from a hospital, or to reduce it to the minimum, it is necessary to observe strictly the rules for dismissal of infectious patients. Officially recommended terms for isolation of contagious patients should be strictly adhered to. Before discharge convalescents are given a bath or shower, and dressed in disinfected clothes. When a convalescing child is dismissed from the hospital, the parents are given an epicrisis where contacts (or absence of contacts) with infectious patients are indicated. The rules for caring for convalescents, and the prophylactic measures needed at home, are explained to the relatives taking a child away from hospital. Sanitary, prophylactic, and anti-epidemic measures need to be skillfully combined with the treatment and the therapeutic regimen. It is of great importance in combating nosocomial infections to maintain the moral of patients and the general nonspecific resistance of their organisms at a high level.
Diagnosis 47
Pediatrics Infection Precise and early diagnosis of acute infections in children is of great practical significance not only because it largely determines the efficacy of the treatment, but also because it is indispensable for the most important anti-epidemic measure early isolation of the source of infection. The various laboratory tests and other auxiliary methods of examination are of vital importance. The most reliable are methods of detecting the infective agent in the patient's organism. Serological reactions are employed for certain bacterial infections. Repeated agglutination reactions showing a gradual rise in titre have great diagnostic value.
Treatment Treatment of infectious patients aims on the one hand at eradicating or rendering harmless the causative agent and its toxic products that are giving rise to the infectious process, and on the other hand at raising both specific and non-specific resistance. Treatment of patients suffering from an infectious disease should be aetio-pathogenic, complex, systemic, individualized, and as early as possible. REGIMEN, NURSING, AND DIET The most important element in the treatment of infectious patients is correct organization of the regimen. Children are especially sensitive patients. The growing body with its characteristic reactivity requires special care on the part of the medical personnel during performance by them of medical, diagnostic, and prophylactic measures. Psychic perception of the child is quite different from that of an adult. Much attention should be paid to giving an adequate amount of fluid; this is particularly important in toxaemia and exsiccosis. Children should be fed at definite intervals, depending on their age, and meal times should be strictly observed. CAUSAL TREATMENT (THERAPEUTIC MEASURES DIRECTED AGAINST THE CAUSATIVE AGENT AND ITS TOXINS) Various methods are employed in order to eliminate or render harmless the organism causing or maintaining the infectious process, and to detoxicate bacterial toxins (chemotherapy, immunotherapy, phagotherapy). 1. Chemotherapy (anti-malarial drugs, derivatives of arsenic and antimony, sulphonamides, antibiotics, etc.) is the treatment of an infectious disease by chemical agents acting on the causative agent. 48
Pediatrics Infection 2.Immunotherapy is divided on 2 groups -active (vaccinotherapy, anatoxynotherapy) and passive (serotherapy, immunoglobulin). no little importance in 3. Phagotherapy is another method of acting on the causative agent of a disease. Bacteriophages are strictly specific, acting only on definite species of microbe, causing complete lysis. Specific bacteriophages are indicated in dysentery and salmonellosis. 4. Therapy with biological preparations is close to the latter two methods. The preparations are obtained from microbes of normal intestinal microflora that are antagonists to some pathogenic microbes. These preparations are bifidumbacterin, bificol, lactobacteria, etc.; giving these preparations to treat dysbacteriosis caused by various diseases favours the restoration of normal biocenosis. NON-SPECIFIC PATHOGENETIC THERAPY Apart from aetiological therapy, of great importance in infectious diseases is pathogenetic therapy, i.e. action on the mechanisms determining the development of pathological processes, and developing the organism's protective, compensatory, and restorative reactions. The methods of pathogenetic therapy include many elements with aetiotropic action. Strict separation of aetiologic and pathogenetic therapy is impossible. The various methods of pathogenetic therapy employed in infectious diseases may provisionally be grouped as follows, according to their principal action: (a) non-specific methods of eliminating toxaemia (blood and plasma transfusion (polyglucin), intravenous injection of hypertensive glucose solution, increased fluid intake, use of cortico-steroids, saturation with vitamins); (b) action on the pathologically changed reactivity of the organism through stimulation, desensitization (hormone therapy, use of anti-histamine drugs, general ultra-violet irradiation, etc.); (c) restoration of disturbed physiological functions and their regulation (normalization of metabolism, for example, of water-mineral metabolism in toxic dysentery; restoration of disturbed cardiovascular activity, restoration of normal lung ventilation, etc.); (d) depression of excessive and pathologically altered reactions (inflammation, hyperthermia, cough in croup and whooping-cough, intestinal spasm in dysentery, etc.); (e) replacement therapy (blood transfusion in anaemia, enzyme therapy in dysentery, vitamins in hypovitaminoses, corticosteroids in disturbed funct'on of suprarenals, etc.). 49
Pediatrics Infection PROPHYLAXIS General prophylactic measures are of the utmost importance, but to be continuous (even during periods that are favourable epidemicwise). Preventive measures desirable in an epidemic focus are as follows. 1. Early isolation of the source of infection. 2. To send the urgent massage to sanepidemic station 3. Quarantine of contact children. 4. Immunization of contact children (active of passive). 5. Disinfections (concurrent and terminal).
6. Follow-up of the epidemic focus. When a case of nosocomial infection is discovered, the patient should be immediately isolated, and the ward ventilated, and when the infection is caused by a stable agent, disinfected. With aerial-droplet infections (except German measles) the whole department or an individual ward is quarantined, depending on the infection, the type of patients, and the conditions in the ward. Children who have not had the infection previously are no longer admitted, and the discharge of contacts is delayed. The question of what group of patients to quarantine, and on the need for this measure in such infections as chickenpox, mumps, whooping-cough, and influenza, is decided individually in each case, depending on the specific conditions; but it is desirable to consult an epidemiologist. An important item in control of nosocomial measles infection is properly organized serum prophylaxis among unimmunized contacts, thanks to which this very dangerous nosocomial infection is now relatively harmless in well-organized hospitals, and mortality has been reduced to zero. Each individual case of nosocomial infection needs to be analysed and recorded in a special journal of hospital infections. To avoid the danger of spread of infection from a hospital, or to reduce it to the minimum, it is necessary to observe strictly the rules for dismissal of infectious patients. Officially recommended terms for isolation of contagious patients should be strictly adhered to. Before discharge convalescents are given a bath or shower, and dressed in disinfected clothes. When a convalescing child is dismissed from the hospital, the parents are given an epicrisis where contacts (or absence of contacts) with infectious patients are indicated. The rules for caring for convalescents, and the prophylactic measures needed at home, are explained to the relatives taking a child away from hospital. Sanitary, prophylactic, and anti-epidemic measures need to be skillfully combined with the treatment and the therapeutic regimen. It is of great importance in combating nosocomial infections to maintain the moral of patients and the general nonspecific resistance of their organisms at a high level.
50
*Virus (Epidemic) Hepatitis A and B*

Virus Hepatitis are the acute viral diseases affecting hepatic cells, are characterized by cyclical course, enlargement of hepatic and disturbance of its function, jaundice. S. P. Botkin regarded epidemic virus hepatitis as an independent infection. The discovery in the late '30s and early '40s of the 'serai' or 'inoculation' hepatitis, and of the so-called Australian antigen in patients with serai hepatitis (Blumberg, 1962-1964) have become important events in the study of the disease. An important contribution to the study of clinical picture and pathogenesis of virus hepatitis, and improvement of the therapeutic tactics was made by the scientists: E. Tareev, A. Bluger, N. Nisevich, E. Ter-Grigorova, "and others. Causative agents. At the present time it has been established that virus hepatitis is caused by different viruses designated as viruses of hepatitis A,B,C,D,E,F et ctr. (There are at about 9). The viruses of hepatitis are stable to the environmental factors (temperature in particular). EPIDEMIOLOGY The source of infection with hepatitis A and B is a diseased man who becomes contagious during the preicteric period. Patients with non-icteric, inapparent and chronic hepatitis are-also important as the source of infection. Carriers of virus B are quite frequent. The pathogenic agents causing hepatitis A and B are transmitted by different mechanisms. Hepatitis A is transmitted by the faecal-oral route. The patient liberates the causative agent with faeces and urine. Infection is transmitted by direct contact with the patient, through food, and possibly water. The virus is found in the blood of patients with hepatitis B during the incubation period (i.e. 25-45 days before the persons become actually affected by the disease). The virus is found in the blood for months and even years after the disease has been cured. A 0.01 ml portion of infected blood or serum is sufficient for parenteral ingress of the infection. A person may be infected with hepatitis B during various medical manipulations: during transfusion of blood or plasma, during injections with inadequately sterilized needles or other pointed or sharp tools upon which minutest amounts of the infected blood may remain. There is evidence that the infection may be transmitted during tattooing, injection of narcotics, sexy-borne of transmission etc. The virus of hepatitis B may be transmitted from the mother to the foetus through the placenta. It has been established that the HBs antigen may be contained in various discharges of patients and carriers, such as faeces, urine, saliva, milk, etc. The infection may be transmitted by routes other than parenteral, e.g. by the faecal-oral mechanism. But the role of this route of transmission of the causative agent of hepatitis B is probably insignificant. 51
Pediatrics Infection Children under 15 are affected by hepatitis A. They are 60 per cent of the overall morbidity; children from 3 to 7-9 are mostly affected. Seasonal variations are noted: the maximum rise is noted to occur during the cold season. Persons of all ages may be affected by virus hepatitis B. Only this form of the disease occurs in infants under 1. No seasonal variations of the incidence are noted. PATHOLOGICAL ANATOMY AND PATHOGENESIS The principal pathological changes in epidemic hepatitis occur in the liver. adults. The pathogenesis of epidemic hepatitis is still unclear. The portal of entry of infection is usually the alimentary tract, and for virus B the site of injection of the blood or serum, in which the causative agent is introduced directly into the circulation, muscle, or tissues. By whatever route it enters the organism the virus multiplies in the blood and selectively a'ftects the liver. Lesions in this organ lead to disturbances of hepatic function, which, in turn, causes metabolic changes. The greater the hepatic involvement, the more pronounced are the metabolic shifts. The affection of hepatocytes and deranged permeability of cell membranes account for the increased activity in the blood of the enzyme aminotransferase, etc. Protein, fat, carbohydrate, pigment, and water-salt metabolism are affected. There is hypoproteinaemia, accumulation of metabolites, and a considerable increase in blood bilirubin content. The liver loses its capacity to produce and store glycogen. There is a deficiency of vitamins A, B1, and B2; disturbance of vitamin K assimilation leads to reduction of prothrombin level and as a result to haemorrhagic phenomena. At the height of the disease water and chlorides are retained in the organism. The detoxifying function of the liver is also much affected. An allergic factor plays a definite role in the development and course of epidemic hepatitis. The remittent course and exacerbations during abatement of clinical phenomena (i.e. from the 15th or the 20th day) would seem to be the symptoms of allergy. There are grounds for supposing that processes of auto-sensitization and auto-aggression. CLINICAL PICTURE The incubation period of epidemic hepatitis A is between 15 and 50 days; in serum (post-injectional) hepatitis B it is longer, from 60 to 180 days and more. The course of epidemic hepatitis has a cyclic character and consists of three stages, the pre-icteric, icteric, and convalescent.
52
Pediatrics Infection The pre-icteric stage, lasting from three to ten days, is met in most patients. Its most constant symptoms are dyspeptic, namely: anorexia, nausea, vomiting, abdominal pain, and sometimes diarrhea or, on the contrary, constipation (dyspeptic variant). There is prostration, moderate or slight elevation of temperature, and headache, but the temperature often remains normal. Catarrh of the respiratory tract, i.e. rhinitis, cough, pain all over the body, and headache are met less often (catarrhal variant). In some cases the leading symptom is rheumatoid pain in the joints and neuralgia, more common in adults than in children (rheumatoid variant). A certain enlargement and slight tenderness of the liver are already noted at the preicteric stage, and sometimes (mostly in nursing babies) there is also enlargement of the spleen. Blood bilirubin content rises by the end of this period; there is also increased activity of the enzymes aldolase and transaminase. Bile pigments appear in the urine, often rendering it dark yellow; the stool becomes pale. The ESR is usually normal or decreased. Mixed variants occur more often. There is asteno-vegetatic variant, especially for hepatitis B. Although the icteric stage is sometimes accompanied with a fall of temperature and improvement in the patient's condition, the general toxaemia of the pre-icteric stage is apt, on the contrary, to become more pronounced. Jaundice develops gradually; initially the sclera and the soft palate are involved, and then the skin. The severity of the jaundice does not always conform to that of the disease. Hepatitis with a mild form of jaundice, or even without it, may sometimes end in cirrhosis, or change to toxic dystrophy of the liver. The jaundice is sometimes accompanied with slight pruritus of the skin, and epistaxis and a haemorrhagic rash are occasionally displayed, but, as a rule. When the hepatitis runs a benign course the neuropsychic phenomena are usually mild, only adynamia, listlessness, and sometimes sleepiness and irritability, being noted. Cardiovascular findings are bradycardia and enfeebled and impure cardiac sounds; but bradycardia is not met, as a rule, in nursing babies. The dyspeptic symptoms noted during the preicteric stage often become intensified: there is sharp loss of appetite, belching, nausea, vomiting, and epigastric pain either develop or become more pronouncedt Some patients have diarrhoea, and others constipation. The stool is usually pale (achylous). The liver is enlarged, hard, and moderately tender. Spontaneously arising pain in the hepatic region is common. The spleen is enlarged in one-fifth to one-third of patients. The affection of the liver is accompanied with its disturbed function detectable by examination of the blood and urine and by special functional tests. There is a marked increase in blood bilirubin content - mostly from 1.6 to 12 mg per cent (van den Bergh, Jendrassik) (27.4-205.2 u.mole/litre), mainly due to bound (anfree, direct). Bilirubinaemia increases significantly in severe cases (mainly due to free (indirect) bilirubin). The onset of jaundice is marked by decreased diuresis. 53
Pediatrics Infection The urine becomes dark yellow or brownish-yellow in colour. Bilirubin and sometimes a little protein and individual erythrocytes are found in it. The deranged liver function (which corresponds to the gravity of the disease) involves (in addition to the pigment disorders) a decrease in the total protein content of the blood serum, dysproteinaemia, which develops mainly due to the increased gamma-globulin content. Dysproteinaemia is also confirmed by positive sedimentation tests (thymol and sublimate tests) characterizing the stability and dispersion of the serai proteins. The coagulating factors (prothrombin and proconvertin) are decreased. The activity of the blood serum enzymes aldolase and aminotransferase increases. The increased activity of sorbit-dehydrogenase and fructosomonophosphate aldolase is especially important. These enzymes are regarded as organospecific of the liver. Fat and carbohydrate metabolism is also upset. Blood findings. Erythrocyte count and haemoglobin content are often found to be reduced, particularly when the process is protracted. In the initial period leucocyte count usually remains within the range normal for the given age, but in the icteric stage slight leuco-penia and relative lymphocytosis are often noted. The ESR remains normal or decreases. The icteric stage is divided into phases of progress, maximum development and abatement of icterus. Jaundice persists for ten to twenty days, on the average, but is sometimes as short as seven, or as long as 40 and more. As a rule, subsidence is slower than progress. As blood bilirubin falls and the other symptoms of the disease disappear, there is increased diuresis and improvement of the patient's general condition. A gradual restoration of hepatic function and decrease in the size of the liver proceed during the convalescent stage which is sometimes protracted. There may be exacerbations and relapses. They may be due to superinfection (acute respiratory, staphylococcal, and other intercurrent infections). The residual phenomena (enlargement of the liver and mild icterus) may last for several months. The younger a child, however, the more rapid is convalescence. This description of the clinic of virus hepatitis equally holds for its inoculation variant (hepatitis B). The latter only has the following special characteristics: shorter duration of the pre-icteric period and more frequent absence of this period; more pronounced intoxication; gradual intensification of jaundice, its longer duration and more pronounced bilirubinaemia; relatively low indices of the thymol test and relatively low increase in IgM; more frequent enlargement of the spleen and a more severe course in general. Compared with hepatitis A, hepatitis B is more characterized by its protractedness and chronic forms. But it should be noted that this, to a certain extent, may be due to the special reactivity of infants under 1 year of age in whom the inoculation hepatitis mostly occurs. Epidemic hepatitis has various clinical forms. Acute, protracted, and chronic hepatitis are distinguished. Hepatitis is considered acute if it lasts to 3 months, protracted if it lasts for over three months, and chronic if it continues over six months. The latter term is however only conventional and chronic hepatitis may (especially in severe cases) develop at earlier terms. At the same time, the process of recovery may continue for a few months which may be due to the so-called post-hepatic astheno-dyspeptic syndrome with functional disorders. Acute hepatitis is divided by severity into mild, 54
Pediatrics Infection moderately severe, severe, and grave; the last-named follows the course of toxic dystrophy of the liver. Hepatitis without clinical jaundice is distinguished as an atypical form; this form presents considerable diagnostic difficulties. The form without clinical jaundice is much more common, but is not always recognized. Hepatitis occurring without jaundice and bilirubinaemia (as established at the laboratory) is regarded by many clinicists as the non-icteric hepatitis. It has the symptoms of the pre-icteric stage of hepatitis. Of-particular importance for diagnosis are pain in the hepatic region, swelling or slight tenderness of the liver, increased activity of aldolase and transaminase, positive thymol turbidity test, and increase of urobilin content in the urine. Although this form is mild, it sometimes leads to toxic dystrophy of the liver or to cirrhosis. The grave form (toxic dystrophy of the liver) may begin as common hepatitis. The change to malignancy usually occurs during the first seven or ten days of the icteric stage. Adynamia progresses rapidly; anorexia, persistent vomiting, and specific mouth smell are noted. Bilirubinaemia increases significantly at the expense of indirect bilirubin; residual nitrogen increases, and the alkali reserve of the blood decreases sharply (acidosis). There is a picture of very grave toxaemia with fulminant neuropsychic symptoms (including maniac excitation, motor agitation, and delirium followed by a lapse into a comatose state). Most patients display a rapidly progressive contraction of the liver, a haemorrhagic tendency, arterial hypotension, and tachycardia. The disease is often fatal, but active treatment may bring recovery. Epidemic hepatitis may become chronic (this being particularly facilitatedby repeated exacerbations and relapses), and last for months or even years. The outcome is either recovery, usually with residual phenomena, or cirrhosis of the liver. Virus hepatitis is often aggravated by affection of the bile ducts (mostly their dyskinesia). The late periods of the disease may be marked by cholecystitis and cholangitis which develop as a result of secondary bacterial infection. Virus hepatitis in infants under 1 year of age has special characteristics. They can probably be partially associated with the fact that the disease in infants is mostly evoked by virus B. The course of virus hepatitis in infants under 1 is more severe than in older children; toxic dystrophy of the liver occurs more frequently in them. The pre-icteric period in infants is short and is often overlooked. Jaundice, on the contrary, is longer (30-40 days) and is attended by pronounced hyperbilirubinaemia and a marked enlargement of the liver. Secondary bacterial (staphylococcal) infection often supervenes in these infants to account for the intermittent course of the disease (A. Kuz-micheva and I. Sharlai). DIAGNOSIS Great difficulties are encountered in recognizing the disease during the pre-icteric stage or in cases without clinical jaundice. Examination of the blood for bilirubin, activity of enzymes, and the epidemiological anamnesis, are of diagnostic value in these cases. For early diagnosis of hepatitis, particularly of the form without apparent jaundice, of great aid is the determination of the activity of the following enzymes: aldolase (normal value 0,4-0,8 units), which increases in hepatitis over 1-1,5 units and 55
Pediatrics Infection higher, aspartate amino-transferase and alanin aminotransferase. The content of the latter two substances increases several times in virus hepatitis. Protein sedimentation tests (with thymol and sublimate) are also used. Data of epidemiological anamnesis may be useful for establishment of the diagnosis. Formerly carried out medical parenteral procedures (that fall within the term of the incubation period) cannot be considered as a reliable criterion for establishment of the diagnosis of hepatitis B. This diagnosis can only be confirmed by determining HBs, HBe antigen and antibodies to them (IgM). Acute respiratory infections and other diseases characterized by fever during their initial period should be excluded in differential diagnosis. Enlarged liver, dark colour of the urine and colourless faeces, and especially increased activity of aminotransferase are very important for correct diagnosis. Haemolytic and obstructive jaundice may also interfere with correct diagnosis in the icteric period. Haemolytic jaundice is characterized by the absence of bilirubin in the urine, the faeces are not colourless but on the contrary are coloured more intensely. Free bilirubin content of blood increases. Obstructive jaundice, which is caused by obstruction of the bile ducts by stones, parasites, etc., is characterized by the absence of biochemical indices of liver affection; the indices of aminotransferase activity are normal. It is necessary to deferent with such infection as leptospirosis, toxoplasmosis, infectious mononucleosis, pseudotuberculosis and other. PROGNOSIS The overwhelming majority of patients recover. There may be a transition to a chronic form (in 5 per cent of cases on average) with subsequent cirrhosis of the liver. It is more common in hepatitis B. TREATMENT Hepatitis patients must be hospitalized. Physical and mental quiet are of utmost importance. Bed rest is prescribed for the whole course of epidemic hepatitis. Clinical experience is that breach of bed rest aggravates a patient's condition, retards the process of recovery, and often leads to exacerbations. In the mild form patients can be allowed up after main symptoms have disappeared; in the moderate form bed rest should be enjoined for a longer period (depending on the condition of the patient); the patient is only allowed to leave his bed during the recovery period. Close attention has to be given to diet, which must be planned with due consideration of the disturbed function of the liver, the extent of the toxaemia, and the patient's appetite. It should be mainly carbohydrates with adequate amount of animal protein. Limited intake of proteins and even complete eradication of proteins from the diet is only indicated in grave intoxication when a precom-atose state develops (E. Tareev). The menu should include milk products (cottage cheese, sour milk, yoghourt), vegetables, fruit, stewed fruit, sweet jellies, sugar, jam, honey. A minimum of fat and salt, and no extracts, hot spices, cocoa, or chocolate should be given. Adequate fluid (tea, fruit juices, alkaline mineral water, etc.) must be ensured. The patient's food should be enriched with vitamins. In addition it should be supplemented by vitamin extracts and synthetic vitamin preparations, like ascorbic acid (100 to 300 mg daily), nicotinic acid (30 to 50 mg), and vitamins E1 and 56
Pediatrics Infection A. Vitamin K (vikasol) is indicated for three to five days (0.005 to 0.01 g, depending on age, three times a day) when there are haemorrhagic symptoms. In mild hepatitis bed rest and diet supplemented by these vitamins suffice for the majority. When the course of hepatitis is grave special measures are sometimes required to control the toxaemia. To this end a special diet, consisting only of fruit, sugar, jam, yoghourt, and abundant fluids, is recommended for one or two days. Cleansing or syphon enemas are prescribed to rid the bowel of accumulated toxic products. Intravenous drip infusions of 5 per cent glucose solution or isotonic solution with ascorbic acid are recommended. Transfusion of plasma substitutes and albumin solution is employed for detoxication, stimulation of hepatic function, and desensitization. Vitamin B12 is prescribed intramuscularly (1 to 2 ml, daily or every other day) as well as glutamic acid. Steroid hormones (prednisolone, 2 mg/kg daily for seven to ten days) which possess an antiphlogistic, detoxifying, and desensitizing effect, are valuable, and are included in the general therapeutic complex in severe forms of hepatitis. Definite indications for their prescription in increased doses (up to 5 ml/kg intramuscularly or intravenously) are a precomatose condition, and subacute or acute dystrophy of the liver. Plasma transfusion and hormone therapy are also employed when the disease has a protracted course. Physiotherapy (UHF, paraffin and ozokerite therapy) is also prescribed in these cases. In the presence of secondary infection of the bile tracts (or when it is suspected) therapeutic drainage by Demyanov's method is recommended. Antibiotic therapy (ampicillin, chloramphenicol, etc.) is prescribed. Children who have had an attack of epidemic hepatitis should be kept under medical observation for six months and longer (up to 2 years) after discharge from hospital. They should be forbidden excessive physical strain and put on a light, digestible diet. Sanatorium treatment is recommended for children with long-term residual phenomena. PROPHYLAXIS Prophylaxis of epidemic hepatitis is based on the same principles as control of intestinal infections. Patients are hospitalized in special departments; observation wards are advisable for patients with an uncertain diagnosis. Convalescents should only be discharged after complete clinical recovery, and not earlier than three weeks after the onset of jaundice or 30 days from the beginning of the disease. Children are re-admitted to children's institutions not earlier than ten days after discharge from the hospital. Contacts need to be kept under medical observation for 45 days from the last day of contact. Aminotransferase activity tests are recommended for early recognition of the disease. Concurrent disinfection is carried out before a patient is hospitalized, and terminal disinfection afterward. Flies should be exterminated before disinfection. 57
Pediatrics Infection In children's institutions the group in which a case of epidemic hepatitis is revealed is quarantined: no new children are admitted to the group and no children transferred from it to another group for a period of 45 days from the date of the patient's isolation. All children should be given a thorough clinical examination and kept under observation throughout quarantine period. Gamma-globulin should be given intramuscularly to children that were in contact with hepatitis A patients. The dose for children under 3 is 0.5 ml and from 4 to 7, 1 ml. This method is widely used at children's institutions. Early prophylactic use of gamma-globulin decreases significantly morbidity at foci (the incidence is 3-5 and even 7 times lower). This method is used at preschool children's institutions and at school (during the first four years). Gamma-globulin does not protect from infection with virus hepatitis B. Another prophylactic measure against hepatitis B is a thorough examination of donor blood. Donors should be examined for carrying' HBs antigens. Persons who had virus hepatitis in the past may not be regarded as potential donors of blood. Blood transfusions should preferably be given for special indications only. Needles and other tools used for parenteral procedures should be sterilized thoroughly (for 30 minutes at a temperature of 100C). Immunoprophylacxys. Active immunization against hepatitis is now compulsory for all children. Immunization composes of 3 vaccinations. The 1 on first day of life, the 2- on the 1 month, the 3 on the 6 month of life. If the mother of baby is carrier of HbsAg, is applied other scheme: the 1 vaccination on the first 12 hours of life, 2 1 month, 3- 6 month, 4- 12 month.
58
*Whooping-Cough (Pertussis)*
The causative agent of whooping-cough is the Bordet-Gengou bacillus Haemophilus (Bordetelld) pertussis, discovered in 1906, a small, ovoid, non-motile rod 0.5 to 2.0 urn long, gram-negative, strictly aerobic, and haemoglobinophilic. It grows best on a potato-glycerol blood agar (Bordet-Gengou culture medium). Other nutrients, however, particularly caseincarbon agar medium, are now widely used. When cultured, the bacillus forms small, round, lustrous colonies resembling drops of mercury. Its resistance is very low, and it succumbs rapidly to the effect of high temperature, direct sunlight, desiccation, and various disinfectants. Its antigenic apparatus is complicated and not yet quite clear. The most closely studied factors of the microbial cell evoking a response in the organism are agglu-tinogen (allergen), toxin, and haemagglutinin. When cultured for a long time on an artificial nutrient medium H. pertussis passes through four phases. The freshly isolated bacillus (first phase) alone possesses maximum antigenic properties and virulence. In experimental conditions H. pertussis is pathogenic to monkeys, kittens, and white mice, but does not produce in them, however, the clinical picture typical in man. EPIDEMIOLOGY The source of infection in whooping-cough is a sick person. The disease is particularly infective in the initial stage, but gradually becomes less contagious. Patients continue to discharge H. pertussis up to the 28-30th day, and very rarely a little longer. Treatment with antibiotics shortens the period of infectivity. Patients with abortive forms can also be sources of infection; these forms are very common according to literature (from 55 to 70 per cent of all cases). Immune carriers of H. pertussis have been found, and also patients with asymptomatic forms of whooping-cough (actually carriers), but their epidemiological role is still obscure. It must be supposed that the absence of cough in carriers sharply reduces their infectivity. Infection is transmitted by the aerial-droplet route, but is possible only by direct, more or less lengthy, contact with a patient. Isolation of patient in separate wards or semicubicles, therefore, prevents dissemination of infection. Transmission via objects or intermediaries occurs only in exceptional cases owing to low viability of the causative agent. Susceptibility to whooping-cough is high, but not as high as to measles (in nonimmune group the index of susceptibility is 0.7). Its heaviest incidence is in children between one and five, but unlike other infections it very often affects very young children not sparing babies of a few months or even a few days old. Because of mass-scale immunization, the proportion of incidence of pertussis among older children (schoolchildren) has increased in the past decades. Only separate cases of pertussis occur among adults. A life-lasting immunity develops in persons after pertussis; relapses are very rare. The high susceptibility of children and unfavourable housing and living conditions (overcrowding, for example) are conducive to epidemic spread of the infection. Regular and constant seasonal variations in its incidence are not characteristic, but either a spring-summer or a winter peak in the epidemic wave may occur depending on conditions. The mass-scale immunization of population in the Soviet Union, which was begun in 1959-1960; has had an appreciable effect on the epidemic process: the morbidity decreased dozens of times everywhere throughout the country, periodic
59
Pediatrics Infection variations of the disease (formerly in 2-3 years) smoothed down, abortive forms of the disease occur more frequently, and the age structure of the incidence changed. Mortality from pertussis has dropped to an unrivalled level. PATHOLOGICAL ANATOMY The commonest lesions are in the respiratory organs. Laryngoscopy reveals catarrh of the larynx and trachea during the catarrhal stage. This picture of common catarrh of the larynx, trachea, and bronchi is a postmortem finding in patients dying during the paroxysmal stage, and only in rare, particularly severe, and complicated cases is there superficial epithelial necrosis in the respiratory tract. The mucous lining of the small bronchi has a festoon pattern, indicating the spastic condition of the bronchial muscles. Peribronchitis and peribronchiolitis often develop, and changes in the receptor apparatus of the larynx have also been observed. Atelectases and microfocal and confluent bronchopneumonia are apt to occur, but the pulmonary lesions have no features of any kind specific to whooping-cough. There is marked derangement of the blood and lymph circulation (lymphostasis and haemostasis). Patients dying at the height of the paroxysmal stage are often found on autopsy to have acute emphysema of the lungs. When dilated alveoli rupture, interstitial emphysema develops with penetration of air into the mediastinum and the subcutaneous tissues of the neck (subcutaneous emphysema). A. Strukov found pronounced changes in the argyrophilic ground substance in the pulmonary tissue (thickened argyrophilic fibres); this would seem to be the consequence of hypoxaemia and hypoxia. Congestion of the pulmonary circulation, dystrophic changes of the myocardium, and dilatation of the right ventricle of the heart with hypertrophy of its walls are not uncommon. Haemorrhages are occasionally found in the internal organs. A constant postmortem finding is lesions of the nervous system: the disturbance of circulation expressed mainly in marked dilatation of cerebral capillaries and oedema of the brain; haemorrhages into the brain matter are not uncommon. Dystrophic and necrobio-tic lesions of the nerve cells in the cortex of the great hemispheres, reticular formation and medulla oblongata are found in histological examinations of the brain, and are very intense in complicated cases of whooping-cough. PATHOGENESIS The portal of entry of infection in whooping-cough is the upper respiratory tract. H. pertussis settles in the mucous membrane of the larynx, bronchi, and bronchioles, and also in the pulmonary alveoli, but no bacteriaemia or penetration of the causative agent into the organs and tissues occurs. The principal pathogenic factor is the toxin produced by H. pertussis, which brings the cough reflex into play by its intense irritation of the nervous receptors of the respiratory mucosa. Toxin absorbed into the blood, on the other hand, has a general effect (chiefly on the nervous system), expressed in a marked tendency to generalized vascular spasm (arterial hypertension), spasm of the small bronchi and vocal cords, and in spasmodic twitching or even attacks of clonicotonic convulsions of the skeletal muscles. Stimulation of the nerve centres (respiratory, vasomotor, etc.) is apparently responsible for these phenomena. The mechanism of one of the chief symptoms of whooping-cough the paroxysmal bouts of coughingis most fully and convincingly explained by the conception advanced by A. Dobrokhotova, I. Ar-shavsky, and V. Soboleva. It's essence is as follows. The continuous flow of impulses coming from receptors in the mucosa of the respiratory tract leads to the development of a stable focus of excitation in the central nervous system, characterized by signs of dominance in A. Ukhtomsky's definition of the term. Formation of this focus is apparently aided by the effect of pertussis toxin upon the 60
Pediatrics Infection central nervous system already mentioned. Paroxysms of coughing result, therefore, not only from impulses arriving from the respiratory tract, but also in response to stimulation of receptor regions not connected with the cough reflex; a fit can be provoked, for example, by examination of the throat, injections, or a loud noise, etc. Owing to the inert character of the dominant focus, paroxysms can persist for a long time after recovery from the infection. The dominant focus becomes inhibited when other, stronger centres of excitation arise. This mechanism is probably responsible for the absence of fits of coughing during absorbing, interesting games. The cough, being an unconditioned reflex action, can become established as a conditioned reflex action as the disease develops. A paroxysm may be provoked, for example when the doctor visits the ward or by the sight of a spatula, etc. As a result of the frequent and prolonged paroxysms of coughing, and of the circulatory disturbances in the lungs, pulmonary ventilation becomes disturbed leading to hypoxaemia and hypoxia. When the latter develops, a major role is probably played by the lesions to the capillary wall (disturbance of its permeability) caused by the pertussis endotoxin. Such symptoms of the nervous system as convulsions are apparently associated with disturbed cerebral circulation and with the hypoxaemia resulting from reduced pulmonary ventilation; but a direct effect of the pertussis toxin on the central nervous system may also be responsible for their development. Inadequate supply of oxygen to the tissues, and disruption of oxidation processes, leads to the development of acidosis, while hypoxia and acidosis in turn aggravate the disturbed function of the nervous system. In whooping-cough, particularly in infants, there is a fall in the non-specific resistance of the organism, nutritional disturbances, and hypovitaminosis. As a result, it may provoke exacerbation and generalization of tuberculous infection, as many authoritative clinicians have affirmed. Secondary flora (pneumococcus, streptococcus, etc.) plays a major role in the development of complications, which are particularly frequent when whooping-cough is combined with other infections, e.g. influenza, catarrh of the upper respiratory tract, measles or dysentery. CLINICAL PICTURE The incubation period of whooping-cough is 3 to 15 days and averages 5 to 8 days.1 The course of the disease can be divided into three stages: catarrhal, paroxysmal, and convalescent. The first, catarrhal stage is attended with a moderate rise in temperature, but the latter may sometimes be subfebrile, or even normal. Significant fever (above 39C) is rare. A dry cough with no specific features develops in the first days. This symptom intensifies gradually, becoming the leading one in the clinical picture of the disease. By the end of the catarrhal period the cough takes on the character of more or less prolonged paroxysmal bouts, occurring mostly at night. Cold in the nose is also often noted during the catarrhal stage, but the patient's general state is not much disturbed, if at all. .Appetite is normal. The catarrhal stage lasts for three to fourteen days, but may sometimes be shorter, especially in nursing babies; in other cases, on the contrary, it may be protracted. The transition to the second, paroxysmal stage is gradual. Fits of spasmodic or convulsive coughing develop. At the height of the disease paroxysms are unmistakable; they begin suddenly, or after a brief precursor (aura)a feeling of irritation in the throat, pressure in the chest, and uneasiness. The fit consists of a series of short coughs following one another in rapid succession without a break. Then the child makes an inspiration which, owing to laryngeal spasm, is accompanied with a crowing sound (whoop). The paroxysm is then repeated in the form of the same successive spells with a subsequent whoop. There may be several whoops during a bout. The more severe the whooping-cough, the more prolonged are the paroxysms and the greater the number of whoops. A bout often ends in expectoration of a pellet of viscid, transparent mucus and sometimes vomiting. In severe fits the mucus may be blood-stained. Vomiting, however, is 61
Pediatrics Infection not an absolutely constant sign, but the more severe the whooping-cough, the more often it occurs. In mild forms there may be only occasional or no vomiting. The outward appearance of the patient during a fit is characteristic: the face becomes red or even takes on a cyanotic hue; the cervical veins become engorged; the eyes are injected and filled with tears; the tongue is forcibly protruded to the limit, and its tip curves upward; and in severe bouts urine and faeces may be involuntarily passed. Various external stimuli (examination of the throat, dressing and undressing, feeding, a loud noise, the crying of children, etc.) can provoke a fit. Many clinicians have noted that bouts occur mostly at night, which may be associated with poor ventilation of the room where the child is sleeping. One should, however, remember N. Filatov's remark that the greater frequency of paroxysms during the night is only apparent, because 'a cough is more disturbing to everyone at night'. According to A. Dobrokhotova, infants cough more during the day. For diagnostic purposes a fit of coughing can be provoked by pressing against the larynx and the jugular fossa, or, still better, by pressing the root of the tongue with a spatula. As a result of frequent paroxysms accompanied with disturbed circulation and congestion, the patient's face and eyelids become swollen, and haemorrhages sometimes appear in the skin and conjunc tiva (Plate VIII). In severe cases the oedema also involves the whole body, particularly the lower limbs. When the oral cavity is examined a shallow ulcer on the frenulum of the tongue is found, which soon becomes covered by a white protruding film. The ulcer results from mechanical rubbing of the frenulum against the sharp edges of the lower incisors. As bouts subside it gradually becomes smaller and heals. In uncomplicated whooping-cough general condition is not disturbed in most patients, even when bouts are frequent, so that children lead their normal life playing between attacks; their appetite is not impaired. Temperature, which rises moderately in the catarrhal stage, usually falls to normal in most patients by the time coughing fits begin; only slight subfebrile elevations occasionally occur. Marked pyrexia during the paroxysmal stage is usually indicative of a complication; in uncomplicated whooping-cough the temperature remains high for a long time only in individual cases. Signs of emphysema are often found during examination of the lungs (a tympanitic or bandbox quality in percussion sound). Auscultation reveals dry and dull moist rales. Heightened transradiancy of lung tissue, low position and flatness of the diaphragm (signs of emphysema), increased shadow of both hili, intensified pulmonary pattern, and reticulations or linear bands are revealed by X-ray examination. Sometimes, mostly in older children, a shadow is distinguished in the form of a triangle, with its base on the diaphragm and the apex in the region of the hilus ('a basal triangle'). In the cardiovascular system an acceleration of pulse is noted during paroxysms, and an elevation of arterial and venous pressure. Capillary resistance is reduced, which encourages haemorrhages into the skin and mucous membranes. In severe cases complicated by pneumonia there is often a dilatation of the heart (more to the right) with signs of disturbed activity. Signs of the nervous system involvement are irritability, in severe cases inertness, adynamia, disturbed sleep, convulsive twitching of the facial muscles, and sometimes dimmed consciousness. In the overwhelming majority of patients blood counts reveal marked leucocytosis and lymphocytosis. The number of leucocytes may reach 20109/1-70109/1 (20 000-70 000) and over. The leucocytosis to some extent depends on the severity of the disease: as a rule, the more serious the case, the higher the leucocyte count. The ESR is either lowered or normal. These haematological shifts are already met in the catarrhal stage, and disappear as the infectious process is overcome. Changes in the cell composition of the blood are less frequent in patients who were earlier vaccinated against pertussis; 62
Pediatrics Infection these changes, if any, are less marked. The paroxysmal stage lasts from two to eight weeks. The frequency and severity of attacks gradually diminish as the disease passes into the third stage. During convalescence the cough is no longer paroxysmal and bouts gradually become less frequent. The sputum becomes mucopurulent. All symptoms of the disease subside gradually. This stage lasts from two to four weeks, so that the overall duration of the disease varies between five and twelve weeks, and even more protracted cases have been observed. The typical paroxysmal bouts of coughing that are sometimes seen during convalescence, or even after complete disappearance of all symptoms of whooping-cough, are false relapses. They occur after complete elimination of H. pertussis from the organism, and are not accompanied with the blood reaction typical of whooping-cough. These 'relapses' develop in convalescents by a mechanism of trace reactions when certain diseases like influenza, catarrh of the upper respiratory tract, or measles, supervene. Clinical forms. Three principal forms of whoop'ng-cough are distinguished: mild, moderate, and severe. In the mild form the frequency of coughing fits is between five and fifteen a aay; they are typical, but short, and only rarely end in vomiting. The patient's condition is undisturbed. In the moderate form the number of fits varies between 15 and 24; they are protracted, with several whoops, and often end in vomiting. The patient feels unwell, but is not seriously ill. In the severe form, there are numerous bouts of coughing (25 to 30, or more, a day). Paroxysms are severe and last up to 15 minutes, with ten whoops, and almost always terminate in vomiting. Disturbed sleep, loss of appetite, loss of weight, adynamia and often a long febrile state are noted. This differentiation of the severity of whooping-cough by the number of paroxysms (suggested by N. Filatov) is conditional, of course, since it cannot be applied equally to nursing babies and older children. In young children, even with a moderate frequency and short duration of fits, whooping-cough can take a very serious course. An abortive form of pertussis, characterized by the absence of typical attacks with coughing relapses, and by a shortened course, often occurs in recent years in addition to the three main forms of the disease. Tracheitis or tracheobronchitis is often misdiagnosed in such cases. These forms occur mostly in vaccinated children. Asymp-tomatic pertussis also occurs. The clinical signs of the disease are absent but cyclic immunological and sometimes haematological shifts occur in the patient. Changes in the blood supply of the lungs, in the capillary circulation, and other roentgenographically revealed changes were reported. The course of whooping-cough in vaccinated children is usually mild or abortive, if compared to the unimmunized; complications are less common, haematological shifts are less pronounced, and the outcome is more favourable. DIAGNOSIS The most important condition for effective control of whooping-cough is its recognition at the initial (catarrhal) stage, when it is most infective. But diagnosis at that stage presents considerable difficulties. It is also sometimes difficult to establish the diagnosis when the disease runs an atypical course, especially in babies a few months old. In diagnosis of whooping-cough the distinctive features of its clinical course must be considered (its cyclic character, paroxysmal bouts of coughing with whoops, ending with expectoration of viscid mucus and vomiting, typical appearance of the patient, ulcer on the frenulum of the tongue, etc.), and also typical haematological shifts; the results of X-ray examination of the chest andanalysis of the epidemiological situation are also of value. Bacteriological tests can also be of great diagnostic aid, particularly during the early stage of whooping-cough. Testing for H. pertussis is usually done by means of 'cough plates': an open Petri dish of nutrient medium is held five to eight 63
Pediatrics Infection centimetres from the patient's mouth during a paroxysm. Small droplets of the mucus expelled precipitate on the surface of the medium. The technique is inconvenient in certain respects; its efficacy is low in infants and it is applicable only when there is cough. A sterile cotton tampon is now used to take the material from the nasopharynx for examination for the pertussis bacillus. The tampon end is bent to facilitate obtaining the material from under the uvula and the pharynx walls. Microbiological studies are very valuable for diagnosis of pertussis. It should be noted that when pertussis is treated with antibiotics cultivation of the pertussis bacillus for diagnostic purpose is effective only in rare cases. To accelerate diagnosis, an immunofluorescence method is now recommended by which the pertussis microbe can be detected directly in the mucus taken from the nasopharynx. Agglutination and complement-fixation reactions have also been suggested. They are particularly convincing when repeated tests show increasing immunological shifts. But these reactions only become positive from the second week of the paroxysmal stage; they are often negative in nursing babies. The reactions are thus mainly employed for retrospective diagnosis and to detect formes frustes. Passive haemagglutination test is recommended, but its advantages over the agglutination test are doubted The catarrhal stage of whooping-cough has to be differentiated from influenza, viral catarrhs of the upper respiratory tract, and measles. It is distinguished by less pronounced nasal and conjunctival catarrh and by more frequent nocturnal fits of coughing; another distinctive sign is marked by leucocytosis. It diners from measles, in addition, in the absence of enanthema, of Belsky-Filatov-Koplik spots, and of marked pyrexia. The paroxysmal stage of whooping-cough is mistaken at times (a) for tracheobronchitis, which is accompanied with persistent cough, sometimes followed by vomiting; (b) for tuberculous bron-choadenitis, which causes compression of the vagus nerve and of the inferior laryngeal nerves; and (c) for a foreign body in the upper respiratory tract, which can occasionally be responsible for attacks of suffocating cough. In contrast to whooping-cough, however, there is no progressive increase in the strength of paroxysms, no whoops, no ulcer on the frenulum of the tongue, and none of the haematological shifts characteristic of whooping-cough. PROGNOSIS Mortality from whooping-cough has fallen considerably in recent years (in some of the large cities of the USSR it is almost nil, but in a number of republics and towns the drop is less pronounced among babies). The overwhelming majority of deaths occur among children under one year of age. The cause of death is pneumonia and, less frequently, convulsive fits. The outcome of whooping-cough is aggravated by concomitant diseases (tuberculosis, rickets, or dystrophy), and by other acute supervening infections (influenza, measles, dysentery, etc.). Bronchiectasis and chronic pneumonia can be sequelae of whooping-cough complicated by atelectasis and pneumonia. Children who have had severe whooping-cough with marked hypoxaemia, respiratory arrest, and convulsive fits, are later found to have a tendency to various neuropsychic disturbances; they are absent-minded, backward at school, and even very retarded mentally. TREATMENT Properly organized regimen and nursing are very important in the treatment of whooping-cough. Bed rest is called for only when there is fever and severe complications. Cold fresh air has a wonderful effect on patients. Continuous open air treatment improves pulmonary ventilation and oxygen exchange, and apparently also has a powerful reflex effect on the central nervous system. Paroxysms become fewer and weaker. In summer children should be outdoors for most of the day, and in winter for several hours each day. Tn winter walks can be made in places protected from the wind, but only if nasal respiration is free. Patients are allowed outdoors at temperatures not lower than minus 10C. Individual tolerance of fresh
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Pediatrics Infection air and low temperatures naturally has to be considered, and care must be taken to avoid chilling. It is also necessary to ensure that the sick-room is freely ventilated. Much attention should be given to educational work among older children; their leisure should be organized, with various lessons and occupations, games, reading of stories, and so on. Coughing is less frequent in children absorbed in games. The fact that paroxysms usually cause vomiting, which greatly interferes with the assimilation of food, must be taken into account in feeding the patients. Calorie-rich digestible, concentrated food, with plenty of vitamins, is prescribed. Patients should be fed small portions shortly after a paroxysm; care must be taken to protect children after feeding from external stimuli that can provoke a paroxysm, such as various diagnostic and therapeutic manipulations, examination of the throat, etc. When vomiting does occur soon after a meal, feeding should be repeated. Antibiotics are successfully used today as a specific (aetiotropic) therapy of whooping-cough. Antibiotics are indicated in grave and medium-grave forms of the disease, in the presence of complications, and in infants in whom the complications are especially grave. Erythromycin, ampicillin, tetracyclines given in the catarrhal or early spasmodic period decrease the number and gravity of fits, lessen the course of the disease, and its gravity. Erythromycin is given per os, 5 000-10 000 U/kg, 3-4 times a day. Ampicillin is given per os or intramuscularly, 25-50 mg/kg, four times a day. The therapy should continue for 8-10 days. Tetracyclines are given 25 000-30 000 U/kg a day, for 10-12 days. They produce a favourable effect on the course of the disease. If the symptoms recur after suspension of the therapy, it should be repeated. Combined therapy with two antibiotics is recommended in complications: the mentioned antibiotics should be given together with penicillin or semisyn-thetic penicillins. Specific antipertussis gamma-globulin, prepared from placental sera with a high antibody titre, or specific donor gammaglobulin (intramuscular injection, 3 ml, three days running), has been successfully employed in the early stage of the disease. This method is recommended in combination with antibiotic therapy. Nowadays the production of the preparation is temporarily suspended. In order to attenuate the pertussis attacks, neuroplegics are recommended: aminazine, propazine. The ampouled solution of aminazine is given intramuscularly, 1-3 mg/kg; propazine is given per os, 2-4 mg/kg a day. The daily dose is given for three intakes; the course continues for 10-12 days. The frequency and gravity of attacks of coughing decrease; vomiting stops or becomes less frequent; the spastic condition of the vessels decreases. Many phy-siotherapeutic procedures are recommended, such as U-V rays, calcium ionophoresis, diathermia, inhalation of negative aerosols with proteolytic enzymes, etc. Oxygen therapy (oxygen tent) is especially valuable in pertussis, in particular in infants and neonates with marked signs of hypoxia. Symptomatic therapy and the treatment of complications are on general lines. Intramuscular injections of a 25 per cent solution of magnesium sulphate, and intravenous injections of hypertonic glucose solution (producing dehydration) are prescribed, in addition to oxygen therapy, for convulsions. Pneumonia is widely treated with antibiotics (penicillin and its derivatives, antibiotics of tetracycline series, erythromycin, gara-mycin, etc.) and oxygen. Hormonal preparations (prednisolone) with an anti-inflammatory, desensitizing effect are also recommended in severe pneumonia. Respiratory arrest calls for prolonged artificial respiration.
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Pediatrics Infection Stimulating therapy (gamma-globulin injections, vitamins, etc.) is prescribed when the course of whooping-cough tends to be sluggish and protracted. It is advisable to send children convalescing from a severe attack to a sanatorium for two to three weeks after they cease to be infectious. PROPHYLAXIS Measures to be taken in an epidemic focus. The earliest possible isolation of the patient is imperative. In practice diagnosis of whooping-cough is often established only when whoops appear, so that isolation is delayed, reducing its epidemiological value. Early diagnosis is therefore essential for the success of the anti-epidemic measures. The patient is usually left at home, and put in a separate room or behind a screen. Hospitalization is indicated in severe and complicated forms of whooping-cough, particularly in children under two years of age, children from families living in poor conditions, and from families where there are babies under six months of age that have not had the disease. Patients are isolated for 30 days from the onset of the disease. The organization of the hospital regimen requires special attention. Patients must be carefully protected against secondary hospital infection, which is often the cause of exacerbations and complications. The quarantine period for unimmunized contacts under seven years of age who have not had whooping-cough is 14 days from the time of isolation of the patient. If the latter has not been isolated, and contact with him continued during the whole period of the disease, quarantine is imposed until the patient ceases to be infective. There is no need in complete terminal disinfection of the premises after isolation of a patient, because the causative agent is not viable and perishes rapidly; but thorough ventilation of the premises and disinfection of handkerchiefs, towels, and dishes are necessary. Favourable results have been obtained through prophylactic use of gamma-globulin, particularly of specific antipertussis gamma-globulin with a high antibody content (3 to 6 ml twice, at an interval of 48 hours). A vaccine, which is a suspension of the first phase of H. pertussis detoxified by formalin or merthiolate, is used for active immunization. At present this preparation is used in combination with diphtheria and tetanus toxoid (pertussis-diphtheriatetanus vaccine or APDT vaccine). For instructions on its use see page 92. Planned mass active immunization against whooping-cough, which is conducted in combination with other prophylactic and anti-epidemic measures, can influence the epidemic process and bring about further decrease in the incidence of this infection in the coming future.
Parapertussis In 1937 Eldering and Kendrick isolated and described HaemophiJus (Bordetella) parapertussis, the causative agent of a disease similar to whooping-cough, which has since been found in the USA, England, Denmark, France, Czechoslovakia, and the USSR. The causative agent of parapertussis is similar to the pertussis bacillus by its morphological and cultural properties. It is however less toxic and less virulent. Epidemiology of parapertussis is the same as of pertussis. The source of infection is the patient, and possibly, the carrier. The infection is transmitted by the aerial-droplet way. A person who had pertussis or was vaccinated by the APDT vaccine, develops certain resistance to parapertussis (partial cross-immunity). The susceptibility is determined by the index 0.3-0.42. Children mainly from 2 to 10 years of age develop the disease.
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Pediatrics Infection Both sporadic cases and epidemic outbursts occur in children's institutions. The parapertussis infection is widely spread among children. CLINICAL PICTURE The incubation period varies from seven to fifteen days, but is mostly ten or eleven days. There is usually no fever. The onset is marked by mild catarrhal symptoms. The cough is not very severe at first, but may later become paroxysmal.
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*Scarlet Fever (Scarlatina)*

The causative agent of scarlet fever is, according to most researchers, beta-hemolytic streptococcus of the group A. The sources of infection in scarlet fever are patients and carriers. The patient is infective from the first hours of the disease. The causative agent is expelled into the environment with the secretion of the mucousomembrane of the fauces and
nasopharynx yit may also be contained in the discharge of various open purulent fociotitis. sinusitis, purulent lymphademtis etc. The patient is contagtoTO^ if) during the wnoIe^enoa'oTHie diseaseTwhich is connected with streptococcus discharge. The most important forms in the epidemiology of scarlet fever are the so-called formes frustes, healthy carriers. These forms often escape diagnosis; the patients are not isolated and therefore serve as sources of infection. The main way of transmission is aerial-droplet. Infection can also occur through infected articles, or through an intermediary. The last depends on the known stability of the causative agent, i.e. on its ability to removable for some time. Susceptibility. The portal of entry of scarlet-fever infection is i the mucous^membranes of the fauces and pharynx, and the primary |focus of infection develops there; but the causative agent can some-times penetrate the organism through damaged is kin or the mucous / membrane of the genital organs (the extrabuccal or extrapharyngeal form). Susceptibility to scarlet fever varies considerably with age. Children between two and six or seven years of age are mostly affected; the disease is rare among adolescents over 15 and in adults. The well known, almost absolute immunity of babies under three months to scarlet fever cannot be explained by specific immunity acquired through mother's placenta. Even being in a constant and close contact with the nursing mother with scarlatina, infants of this age do not develop scarlet fever, thus showing complete insusceptibility to this disease, which is probably the result of the specific reactivity of the neonates.
PATHOGENESIS According to A. Koltypin, three principal components can be schematically distinguished in the pathogenesis of scarlet fever: toxic, infectious (septic), and allergic. They are closely interrelated, their distinction is, of course, rather artificial, and they are manifested in a different degree. In some cases toxic phenomena, and in others septic, predominate; in some cases there may be allergic waves and in others none. The toxaemia caused by the scarlatinal toxin is expressed by a complex of characteristic symptoms (central and vegetative disorders, hyperthermia, exanthema, and cardiovascular disturbances). 68
Pediatrics Infection The action of the streptococcus itself is thought to condition the development of the infectious (septic) component of scarlet fever, which is expressed in an inflammatory-necrotic process at the portal of entry, a septic condition, and complications of a septic order (purulent lymphadenitis, purulent otitis, sinusitis, septic metastases, etc.). Given preliminary sensitization of the organism, signs of allergy begin to develop from the very onset of the disease. Moreover, sensitization during the first stage resulting from the action of various allergens (streptococci and their breakdown products) creates favourable conditions for the development of late complications if there is re-infection.
Clinical Forms The clinical picture of scarlet fever varies considerably in severity and in the character of its symptoms. Along with very mild rudimentary cases, hypertoxic forms with a fulminant course are encountered. But apart from these extreme forms, there are many-clinical variants. A number of Soviet authors (V. Molchanov, A. Koltypin, M. Danilevich) distinguish the following forms of scarlet fever, according to the severity of its course: mild, moderately severe, and severe. Depending on the predominance of toxic or septic phenomena, the severe form is distinguished as toxic or septic. If both components are present, the scarlet fever is defined as mixed or toxicoseptic. In addition to the principal forms, there are also atypical ones: hypertoxic, abortive, and extrapharyngeal (extrabuccal). In mild scarlet fever the toxaemia is weak. The temperature is within the range of 38-38.5C. The patients' general condition is little disturbed. There may sometimes be no vomiting at the onset. The angina has a catarrhal character. Rash is typical, but sometimes pale and sparse. Fever and all acute manifestations disappear toward the fourth or fifth day. This is the commonest form of scarlet fever, which lately occurs in 80 or even 90 per cent of cases revealed. Complications are rare, but are possible, mainly during the second period (lymphadenitis, otitis, nephritis). Moderately severe scarlet fever has an acute onset, with a complete set of symptoms. Toxaemia is marked; the temperature rises to 39C, and even to 40C on individual days. There are headache, lassitude, malaise, and sometimes delirium at night. Vomiting is frequent during the first days and may recur. Tachycardia: pulse rate is up to 140-160 per min. There is no depression of cardiac activity. Angina is catarrhal and there are sometimes films on lacunae and slight necroses. The rash is bright and abundant. The onset of the severe toxic form is violent. It is characterized by repeated vomiting, which may continue during the second and third day. Diarrhoea is not infrequent. Fever is high, up to 40-41C. The patient is in a state of strong excitation or, on the contrary, of depression. Consciousness is clouded, and there is delirium; there may be convulsions and meningeal symptoms. Rash is abundant and bright. The lips are dry, the sclera of the eyes injected, and the pupils contracted.
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Pediatrics Infection In the severe septic form toxaemia is not of primary importance. The disease is chiefly characterized by severe lesions in the fauces (necrotic angina), an exceptionally marked inflammatory reaction in the regional lymph nodes and extremely frequent septic complications. Severe toxicoseptic scarlet fever has a combination of the symptoms of the two forms described above. It usually begins as a toxic form, but on the third to fifth day signs of a septic character aggravate it. In the hypertoxic or fulminant form the symptoms of severe toxaemia described above progress with extreme rapidity; the patient lapses into a comatose state and dies in the first days, sometimes even during the first 24 hours. A rare variety of toxic formhaemorrhagic scarlet feverlias been described, in which severe nervous and cardiovascular phenomena are accompanied with extensive haemorrhages into the skin and mucous membranes. This form is usually fatal. The rudimentary form is the mildest form of scarlet fever and lias very weakly expressed symptoms. In extrabuccal or extrapharyngeal forms of scarlet fever the portal of entry of infection is not the fauces, but damaged skin or mucosa in various regions. The following variants can be distinguished according to the portal of entry and the mechanism of infection: (a) burn (in burns of the 2nd and 3rd degree); (b) wound, or traumatic; (c) surgical; (d) puerperal; (e) complicating various exposed purulent foci on the skin.
COMPLICATIONS Complications are very frequent and varied in scarlet fever, and are distinguished as early and late according to when they occur. Early complications develop in the initial period of the disease, and are the result of the toxemia in streptococcal infection (otitis, Cervical lymphadenitis, mastoiditis, sinusitis, Adenophlegmon or hard phlegmon, pneumonia). Late complications are generally encountered during the third or fourth week, and are apparently allergic in origin; streptococci play an important role in most of them (nephritis, myocarditis, and synovitis, rheumatism rheumatic polyarthritis, endocarditis). DIAGNOSIS Recognition of scarlet fever should be based mainly on thorough clinical examination and observation of the patient, bacteriological test.
70
Pediatrics Infection Differential Diagnosis As a result of its deviations from the classic symptom complex, the clinical picture of scarlet fever can resemble other diseases accompanied with rash: viz. rubeola scarlatinosa, measles, German measles, the prodromal rash of chickenpox and smallpox, miliaria, drug and toxic eruptions (toxicodermia), Far-East scarlatina-like fever, etc. Measles differs from scarlet fever in the presence of an initial catarrhal period with fever, catarrhal phenomena, enanthema, and Belsky-Filatov spots on the oral mucous membrane. The rash, which appears in stages, usually breaks out on the fourth day. Its elements are small at first, but later change to large maculopapules of irregular shape with a marked tendency to confluence. The skin between the individual elements remains unaffected. After fading of the rash a spotty pigmentation is apparent, followed by fine, branny desquamation. Leucopenia, neutropenia, eosinopenia, or aneosinophilia are revealed in the blood. German measles (rubeola morbillosa) are characterized by low fever in the absence of constitutional disturbances. Rash elements are small and pink, with only a slight tendency to fuse, and are localized chiefly on the trunk and the extensor surfaces of the limbs; the area around the mouth and nose is also affected. There are no petechial haemorrhages on the skin or subsequent desquamation. There is a swelling of the lymph nodes (micropolyadenitis), particularly of the occipital and posteriorly located cervical nodes. Blood findings are leucocytosis, neutropenia, and the presence of plasma cells. Far-East scarlatina-like fever. This is anthropozoonotic disease classified as yersiniasis caused by the pseudotuberculous microbe Yersinia pseudotuberculosis (V. Znamensky et all). Like scarlatina, it is characterized by an acute onset of the disease, elevated temperature (sometimes to 39-40C) that persists for 3-5 days, fine (scarlatina-like) rash with subsequent peeling of the skin on the hands and soles. Vomiting occurs as well. Changes in the blood are the same: leucocytosis, neutrophilosis, insignificant eosinophilia. As distinct from scarlatina, true angina is absent, and only hyperaemia of the faucial mucosa occurs; the tonsils are unaffected. Almost all patients complain of pain in the joints and muscles of the extremities and in the lumbar region; gastrointestinal disorders are frequent, and some patients complain of acute pain in the iliac region (mesenteric adenitis). The disease affects mostly adults. The diagnosis is verified by the agglutination test with the pseudotuberculosis bacillus; other laboratory tests, such as immunofluorescence and indirect haemagglutition tests are also recommended for differential diagnosis. TREATMENT Diet. During the initial feverish period, when there are difficulty in swallowing, disturbance of metabolism, and reduced secretory function of the digestive glands, food should be fluid or semifluid, mainly carbohydrates with an adequate vitamin content, vitamin C in particular.
71
Pediatrics Infection Antibacterial (antistreptococcal) therapy. Antibiotics markedly accelerate the removal of the streptococcus from the fauces, preclude complications. The penicillin dose depends on the age of the patient and gravity of the disease; it varies from 50 000 to 100 000 U/kg a day (for 2-4 intakes). The treatment should continue for 5-7 days. Intoxication should be controlled by intravenous administration of the Ringer solution, and a glucose solution. Antiallergenic therapy are used. Corticosteroids (in combination with antibiotics) are recommended to treat grave toxic and toxicoseptic forms of scarlatina. Prednisolone should be given in a dose of 1-1.2 mg/kg daily; the dose should be gradually decreased in 2-3 days. The treatment should continue for 5-7 days. Disintoxication therapy is also necessary: intravenous infusion of colloidal solutions (polyglucin, neocompensan), glucose solution with strophanthin and vitamins, and other measures. These methods should be used in various combinations depending on each particular case.
PROPHYLAXIS The isolation continues for at least ten days from the day of the onset of the disease, provided all signs of the acute period subside. Recovering children and adults who attend preschool children's institutions (and schoolchildren of the first two years) may be admitted to these institutions in 12 days after suspension of the isolation. Treatment of contacts. When a patient is found to have scarlet fever all close contacts (members of the family and fellowtenants) are given a thorough medical examination for abortive forms of the disease. A quarantine of seven days from the moment of isolation of the patient is imposed on contacts who attend children's institutions or are in the first two years at school. Regular concurrent disinfection should be carried out in premises where a patient has been home-treated.
72
*Scarlet fever 2*
process may spread to the nasopharynx, the nasal cavity, the para nasal sinuses, and the mucous membrane of the oesophagus. Inflammatory changes in the cervical lymph nodes are a constant occurrence; particularly severe cases are accompanied with inflammatory infiltration of the tissue surrounding the nodes, and of the skin and muscles. Circulation is disturbed in the affected tissues owing to thrombosis of the small blood vessels, and necrosis without any tendency to purulent liquefaction (adenophlegmon) ensues. Septic interstitial nephritis is found in the kidneys during the first or second week. Glomerulonephritis is characteristic of the second stage of scarlet fever. In addition there are nearly always more or less pronounced dystrophic changes of the tubular epithelium. Myocarditis is not uncommon in severe (especially septic) forms of scarlet fever. Lesions of an allergic (hyperergic) character are found in the blood vessels when death occurs late (after three or four weeks). The vessels, particularly the small arteries, of various organs (kidneys, myocardium, brain, liver, etc.) are affected. There is a preponderance sometimes of infiltrative-proliferative changes, and at other times of lesions in the form of fibrinoid necrosis of the vascular wall. Various elements of the nervous system are, as a rule, found to be altered. The Soviet pathologists A. Abrikosov, B. Mogilnitsky, and M. Skvortsov have made finds indicating considerable lesions in the vegetative nervous system, revealing changes in the sympathetic and parasympathetic ganglia. The adrenal glands are quite often affected in severe form of the disease; marked oedema, diffuse cellular infiltrates, hyperaemia, haemorrhages, and often focal necroses are found. The pathological changes outlined above vary in intensity and occur in different combinations, reflecting the form of the illness and its duration. CLINICAL PICTURE The incubation period of scarlet fever averages from two to seven days. It may be curtailed to a day or even a few hours (for example, in the extrabuccal form), or may be protracted to twelve days. Its onset is acute, almost sudden, and is manifested in a rapid rise of temperature attended with malaise, weakness, and tachycardia. The child becomes fretful, asks to be put to bed, and complains of headache. Pain in swallowing is either concomitant with the rise in temperature or appears a few hours later. Examination of the fauces reveals angina, a vivid hyperaemia of the mucous membrane of the tonsils and soft palate, and sometimes films in the crypts or on the surface of the tonsils. The superior cervical lymph nodes swell and become tender. A frequent initial symptom is vomiting, one of the signs of toxaemia; when the latter is severe, the vomiting may be repeated and is often accompanied with diarrhoea. Within 24 hours of the beginning of the disease, or more rarely on the second day or even later, a bright pink or red, finely punctate rash appears. Thus, the full symptoms are usually manifest on the second day, or even as early as the end of the first. 73
Pediatrics Infection The patient's condition becomes progressively aggravated at the height of the disease (between the second and fifth days). Symptoms of affection of the central nervous system (excitation, delirium, clouded consciousness) may develop. The initial symptoms (angina, lympha-denitis, rash, etc.) become more pronounced. The tongue, at first furred, clears by the fourth or fifth day and takes on a characteristic appearance ("raspberry tongue'). Symptoms begin to subside from the third to sixth day depending on the severity of the disease; the temperature falls gradually by irregular lysis, the rash fades, the fauces clear, and the patient's general condition improves. The temperature normalizes by the 5-lOth day, the initial symptoms subside completely or partially, and the condition of the patient is restored. Desquamation begins by the end of the first week or the beginning of the second, and the first, initial, period of scarlet fever ends. Various early complications may arise during this period. Symptoms of the second allergic stage of the disease sometimes make their appearance at the end of the second week, but mostly during the third. They are expressed by fever and polyadenitis, and at times by a rapidly, disappearing blotchy or urticarial rash and secondary angina. Late complications (lymphadenitis, otitis, affections of the joint, nephritis, etc.) may also develop. Symptomatology General symptoms of toxaemia. In mild cases of scarlet fever toxaemia is expressed only as a temperature reaction, with a certain disturbance of the patient's general condition and loss of appetite; sometimes there may be vomiting and increased tonus of the sympathetic nervous system. In severe cases these symptoms become more pronounced and may be accompanied with marked involvement of the central nervous system and severe cardiovasculardisturbances. Height of the fever reaction is an index of the degree of toxaemia: The rise of -temperature is usually abrupt, and may become high (39-40C) within the first few hours. Onset is also sometimes signaled by chilliness, and occasionally by shivering. The temperature has a tendency at first to rise, then fluctuates irregularly between the third and sixth days, and gradually falls to normal by the fifth to tenth day. But given complications high temperature may persist for a long time. A subfebrile rise in the temperature is sometimes seen in the evenings after the end of the first stage; a new elevation of temperature during the second stage may be due to supervening complications, and its intensity and duration depend on their character. Vomiting is a frequent symptom of scarlet-fever toxaemia; it is the result of the action of toxin on the emetic centre. Repeated persistent vomiting is characteristic of severe toxaemia; diarrhoea is also not uncommon. Lesions of the central nervous system are characteristic, and are always present in severe toxic cases of scarlet fever. According to N. Krasnogorsky, persons with different types of the nervous system display a different reaction to the scarlatinal toxin: in some children the symptoms are mainly irritation, excitation, insomnia, delirium, and convulsions; other patients are adynamic, apathetic, and sleepy to the point of stupor. There are quite regular symptoms of affection of the vegetative nervous system, which have been studied in great detail by A. Kol-typin and his school. The following signs are seen during the first five days of the disease: increased tonus of the sympathetic nervous system (sympathicus phase), tachycardia (a pulse rate of 120 to 140 perminute), elevation of arterial pressure (110140'mm Hg), negative Aschner's phenomenon, white dermographism with a prolonged latent period (9-10 seconds) and a short apparent one (l-lVa minutes). In severe toxaemia there may be a syndrome of paresis or paralysis of the sympathetic 74
Pediatrics Infection nervous system, with adynamia, marked pallor, cyanosis, an abseace of white dermographism, a very sluggish vasomotor reaction, low arterial pressure, thready pulse, and a weak or no reaction of the pupil to light. The sequelae on the fourth or fifth day are decreased tone of the sympathetic and increased tone of the parasympathetic nervous systems (vagus phase), expressed in bradycardia, reduction of arterial pressure, prolonged and marked positive Aschner's sign, pronounced white dermographism with a shortened latent period (5 to 7 seconds) and a prolonged apparent one (5 to 8 minutes). The dynamic equilibrium of the vegatative nervous system is restored at the phase of convalescence. Skin phenomena. The rash is a most distinctive symptom of scarlet fever. Appearing first on the skin of the neck and the upper part of the body, it spreads rapidly over the whole body, face, and limbs. At first glance it seems that the whole skin is erythematous, but on closer examination the rash proves to consist of a dense mass of small points, bright pink or red in colour, more intense in the centre than on the periphery. The elements of the rash are distributed on a hyperaemic background (Plates V, VI). In some places (the lower part of the abdomen, groins, buttocks, and internal aspect of the extremities) they are particularly numerous, and in fusing create a picture of complete erythema. Digital pressure produces a transient, rapidly disappearing, blanching. This vivid vascular reaction of the skin is a favourable prognostic sign; in severe attacks of scarlet fever it is sluggish; hyperaemia is restored very slowly due to reduced tonus of the cutaneous vessels. The skin feels dry, and in some cases smooth, since the rash is not elevated above the surface of the skin; but at the height of the disease it usually feels rough as the elements become maculopapular. Sometimes the papular character of the rash is so pronounced as to be visible to the naked eye; this is mainly noted on the extensor aspects of the limbs, where the elements may look like tiny hard nodules. The appearance of the patient's face is characteristic: the forehead and temples are covered with a minutely punctate pink rash; the cheeks are flushed, but the skin of the nose, lips, and chin is pale. This pallor around the mouth and nose (described by N. Filatov), distinctly delimited by the nasolabial folds, is a typical sign of scarlet fever. In the flexures of joints, where rash is especially abundant, the folds of the skin are distinguished by a dark red, sometimes even slightly cyanotic, colour, which later takes on a brownish tinge. Thorough examination of the skin here (at the elbow and knee, in the armpits, and the anterior and posterior axillary folds) reveals minute petechiae, which are sometimes, especially when the rash is bright, quite profuse. When the rash is pale and its elements sparse, only individual petechiae are noted. Although of no prognostic significance, this sign is of some diagnostic value. Petechiae can be induced artificially in various ways (Konchalov-sky's symptom, for example, in which petechiae are produced by pinching the skin moderately). These symptoms are also observed in other diseases (louse-borne typhus, measles, sepsis, haemorrhagic diathesis, etc.), and their diagnostic significance is therefore relative. As already pointed out, white dermographism is usually distinct in scarlet fever: nine or ten seconds after drawing a line on the surface of the skin a conspicuous white line appears on the background of the rash. The symptom is often so pronounced that it is possible to write on the patient's skin. The rash is almost always accompanied with itching, especially when it is abundant, and fresh scratches are therefore often seen on the patient's skin. Not uncommonly the rash displays peculiarities. It may not appear until the third or fourth day, or be even missing ('scarlet fever without rash'). Sometimes the exanthema assumes the character of a miliary rash; with profuse eruption, mainly on the skin of the chest, abdomen, neck, and the internal aspect of the thighs, numerous minute vesicles filled with transparent, sometimes turbid, fluid appear; they are most distinct when light falls at a tangent to the skin. 75
Pediatrics Infection Another (but relatively rare) variety of the rash is scarlatina variegata; along with a typical micropunctate rash on the skin of th& extremities (mainly on their extensor aspect) there are also blotchy elements of irregular shape and different size (up to that of a large pea and larger) which are of the same, or rather more intense, colour as the principal rash. Sometimes they elevate above the surface of the skin, assuming a maculopapular character. Very rare cases of haemorrhagic rash have been described, characterized by numerous and extensive haemorrhages into the skin and mucous membranes. They are a sign of a very grave form of the disease. In mild attacks the rash fades in the course of two to four days, but persists in severe cases for six to eight days. In very mild cases-it may disappear in a day, and even in a few ours. The rash fades gradually, losing its brightness and taking on a brownish tinge; after its disappearance the skin remains slightly pigmented, as if dirty. Prgmented striae also persist in the flexures of joints for several days. Desquamation usually begins after, but sometimes before, the rash subsides. Scarlatinal desquamation is the result of a condition known as parakeratosisimperfect formation of horn cells of the epidermis impregnated with an exudate. It begins at the end of the first week, or the beginning of the second, and the brighter the rash, the greater the desquamation. Following a pale, sparse rash, desquamation is usually delayed and not pronounced; and not infrequently it does not occur at all (especially in children under two years of age). The peeling begins first on the neck, chest, ears, and pubis^and then spreads over the whole trunk and to the limbs. On the wrists and feet peeling begins from the back and sides or from the fingertips, where separation begins as a fissure parallel to the free edge of the nail (Fig. 8). The face and neck shed a fine powder; larger flakes peel from the trunk. The most typical form of desquamation is on the limbs, which occurs later; here the skin peels in large strips, the epidermis separating in large layers, especially coming on the palms and soles. The period of desquamation averages between two and three weeks, but can last as long as five or six weeks, depending on its intensity. Angina is a constant symptom of scarlet fever, absent only in the extrapharyngeal form. Typical is angina with an intense bright redness of the whole fauces and the soft palate, which is quite sharply delineated along the margin of the hard palate. During the first days a punctate enanthema, or punctate haemorrhages, may be seen on the mucous membrane of the soft palate rather than overall redness. The tonsils are enlarged and loose, and may be covered with films, which are usually of the same character as in common lacunar angina. In the lacunae there are easily detachable yellowish-white' greyish-white films that disappear quite quickly toward the end of the initial period. Very typical of scarlet fever is the necrosis that develops usually on the third or fourth day. Necrotic angina is a typical constant symptom of the septic form of scarlet fever. It is characterized by the appearance on the tonsils, without association with the lacunae, of dirty-white patches of necrosis that tend to spread over their whole surface and, in severe cases, to the palatine arches, uvula, soft palate, and walls of the pharynx. At first the patches are crumbly and irregular, elevating a little above the surface of the mucous membrane. Soon, however, as a result of suppurative liquefaction, they seem to be lying in a depression, and their surface becomes smooth, resembling semimelted lard. The underlying and surrounding mucous membrane is somewhat oedematous and brightly hyperaemic (Plate VII). A foetid odour from the mouth is characteristic of extensive necrosis; the tongue is furred and dry. 76
Pediatrics Infection When the process spreads to the nasopharynx there are symptoms of necrotic nasopharyngitis: nasal breathing is- obstructed; an abundant fluid mucopurulent discharge trickles from the nose; the skin around the nostrils becomes excoriated and cracked. At first necrotic angina is accompanied with marked pain on swallowing; later, even when necrosis persists for a long time, the pain eases considerably. Clearance of the fauces from necrosis proceeds slowly, and the more extensive and deeper the lesions, the slower is the process. The condition can last as long as two or three weeks; in connection with that fever of an irregular type usually persists for a long time. The incidence of necrotic angina varies depending on the severity of the scarlet fever and the incidence of its septic form. A considerable, progressive reduction in its incidence has occurred in the last decades. Angina is usually accompanied in scarlet fever with another quite constant symptom; that of cervical lymphadenitis. The superior cervical lymph glands, which enlarge from the very first day, become hard and tender on palpation. Lymphadenitis with marked inflammatory phenomena is classed as a complication. The tongue coated with white fur at the onset of the disease begins to clear on the second or third day; towards the fourth or fifth day it clears completely and takes on a characteristic appearance known as 'raspberry tongue'; the tongue is bright red in colour with a crimson tinge, with swollen papillae protruding through the white fur and resembling raspberry. This symptom is the result of des-quamative catarrh of the mucosa, and persists up to the ninth or tenth day, after which the tongue resumes its normal appearance. In mild attacks the picture of 'raspberry tongue' is sometimes not very distinct or entirely absent. In the severe septic form, with extensive necrosis, it remains coated for a long time. The lips, which are swollen and cherry-red, or crimson in colour, become ulcerated and cracked from the fourth or fifth day. The intensity of the changes corresponds to the severity of the disease, and may be quite absent in mild cases. Internal organs. Apart from the vomiting, diarrhoea, angina, and changes in the tongue, there are no other significant symptoms or lesions in the digestive organs. The appetite, which is lost or reduced in the initial febrile period, is later recovered. In moderately severe or severe attacks the liver is usually enlarged and rather tender. Enlargement begins from the fifth or sixth day and coincides with functional cardiac disturbances. The lesions in the liver would also seem to be associated with toxic affection of the hepatic parenchyma itself. In some cases a mild jaundice is noted; the bilirubin level in the blood is a little elevated in the initial stage. The disturbances of pigment metabolism are sometimes caused by intensive destruction of erythrocytes. The activity of the 'liver-specific' enzymes (arginase and histidase) increases in the blood serum; some other liver functions change as well (N. Gordeev). Uro-bilinuria is usually marked between the second and fourth day, but subsides rapidly on the sixth or seventh. The spleen is usually enlarged in grave septic and toxicoseptic forms. Blood changes have certain characteristic features. Leucocytosis up to 1010!>/l-3010f'/l (from 10 000 to 30 000) and above, depending on the form, is found in the very first days. Neutrophil count rises to 60-70 per cent, and in severe cases even to 90 per cent; neutrophils display a nuclear shift to the left, to young forms and even to my-elocytes. The degree of leucocytosis and neutrophilosis, and the extent of the nuclear shift, are in direct proportion to the severity of the disease, and are highest in severe septic forms. Eosinophil count, which begins to increase from the third day, sometimes rises to 15 or 20 per cent. It reaches a maximum at the end of the first week. An increase in neutrophil and subsequently eosinophil counts is typical of scarlet fever and aids diagnosis; but in very mild cases eosinophilia is quite rare, and in grave septic and toxicoseptic fbrms the number of eosinophils may fall or they may completely disappear. 77
Pediatrics Infection Haemoglobin and the erythrocyte count are below normal, and the more severe the disease, the more pronounced is developing anaemia; in mild cases there may be none. The ESR is accelerated (20-50 mm an hour by Panchenkov's method), and the acceleration is especially marked in septic forms and when there are complications. The blood symptoms described alter in the course of the disease. Leucocytosis diminishes by the end of the first week and the beginning of the second in the majority of patients. During the allergic wave the leucocyte and lymphocyte counts fall. Eosinophilia decreases from the beginning of the second week, but a small or moderate rise of eosinophil count is found during the convalescence. The ESR increases in cases aggravated with complications, especially by purulent processes. Clinical Forms The clinical picture of scarlet fever varies considerably in severity and in the character of its symptoms. Along with very mild rudimentary cases, hypertoxic forms with a fulminant course are encountered. But apart from these extreme forms, there are many-clinical variants. A number of Soviet authors (V. Molchanov, A. Kol-typin, M. Danilevich) distinguish the following forms of scarlet fever, according to the severity of its course: mild, moderately severe, and severe. Depending on the predominance of toxic or septic phenomena, the severe form is distinguished as toxic or septic. If both components are present, the scarlet fever is defined as mixed or toxicoseptic. As it is very convenient in practice, this subdivision can also be employed in moderately severe forms. In addition to the principal forms, there are also atypical ones: hypertoxic, abortive, and extrapharyngeal (extrabuccal). In mild scarlet fever the toxaemia is weak. The temperature is within the range of 38-38.5C. The patients' general condition is little disturbed. There may sometimes be no vomiting at the onset. The angina has a catarrhal character. Rash is typical, but sometimes pale and sparse. Fever and all acute manifestations disappear toward the fourth or fifth day. This is the commonest form of scarlet fever, which lately occurs in 80 or even 90 per cent of cases revealed. Com-
78
*Mumps (Epidemic Parotitis)*
The causative agent in mumps is a filterable RNA-virus from the group of myxoviruses (Paramyxovirus parotitidis) that varies in size, averaging 100-200 nm. The virus is of low stability and is rapidly inactivated by high temperatures, ultraviolet rays, weak formalin solutions, lyzol, and alcohol. It is grown on developing chick embryos. The mumps virus is pathogenic for monkeys, in which it produces a characteristic inflammation of the parotid glands.
EPIDEMIOLOGY The source of infection is a patient. The research of recent years has shown that the virus is discharged only during the last days of incubation and the first days after onset of the illness. Patients cease to be contagious by the ninth day. Patients with an abortive (rudimentary) form of mumps are of epidemiological value. A latent form has been demonstrated in contacts by virological methods, but its epidemiological role remains obscure. Infection is transmitted mainly by the aerial-droplet route, but is also apparently communicated by various objects contaminated by the patient's saliva (such as dishes, toys, etc.) if they are passed to a healthy child within a short time and he puts them into his mouth. Susceptibility to mumps is lower than to other infections spread by an aerial-droplet route (like measles and chickenpox), and is the greatest between the ages of five and fifteen. The index of susceptibility is 0.5-0.7. Its incidence is relatively low in small children, and babies under 12 months. The disease is not uncommon in adults, particularly under the age of 25, and there are many reports of epidemic outbreaks in military units. A stable immunity develops after the disease. The disease shows a seasonal prevalence, with the greatest incidence in winter and spring. PATHOGENESIS It is a general infection in which the virus develops not only in the salivary glands, but also in the blood and other organs. The possibility of primary infection in the meninges or testes has been established. The portal of entry is apparently the mucous membrane of the mouth, nose, and pharynx from which the virus penetrates into the blood and is carried secondarily to the salivary glands and other organs where it predominantly affects the interstitial tissue. The parotid gland is apparently the site of accumulation of the virus from which it is discharged into the environment with saliva. The antibodies, whose titre attains its maximum in 2-4 weeks, appear during the first days of the disease. CLINICAL PICTURE 79
Pediatrics Infection The incubation period of mumps lasts on average for 18 to 20 days, but extremes of 11 and 23 days occur. Its onset is characterized by elevation of temperature (up to 38 or 39C) and swelling of the parotid gland (usually on one side, but sometimes on both). The swelling obliterates the fossa retromaxil laris and may spread downwards anteriorly and posteriorly to the neck. When the swelling is considerable the auricle is lifted upward. The centre of the swelling is elastic-solid on palpation and painful when pressed; the thickness and the tenderness of the swelling fall off toward the periphery. A painless or slightly tender inflammatory oedema is seen on the periphery. At times it spreads to the face and far to the neck. The skin over the inflamed gland is tense and lustrous, but remains usually of normal colour. Swelling of the parotid gland is accompanied with pain irradiating to the ear or neck, that becomes more intense during chewing or swallowing. In one or two days the parotid gland on the opposite side may become involved; and in about half the cases the submaxillary, and sometimes the sublingual, glands are affected. In submaxillitis palpation directly inward from the margin of the lower jaw displays a swollen, solid, and painful submaxillary gland, oval or round in shape). Submaxillitis is sometimes accompanied with extensive oedema of the cervical cellular tissue; cases of isolated inflammation of the submaxillary gland and of its primary affection with subsequent supervention of parotitis have been observed. The swelling of the affected gland increases for the first three to five days, then begins to regress and subsides by the eighth to tenth day. Resolution of the inflammatory infiltrate may be prolonged to several weeks, but as a rule the glands do not suppurate. Simultaneously with subsidence of inflammation the temperature falls, the pain declines, and the patient's general condition improves. If several glands are affected one after the other the disease may last for two and more weeks. Mumps is sometimes attended, with bradycardia and enlargement of the spleen. Leucopenia or normocytosis, a relative lymphocytosis, and frequently monocytosis, are chief blood findings. The ESR usually falls or deviates a little from the normal. A variety of mumps that must be mentioned is the abortive forms expressed in mild swelling of the parotid gland with little or no rise of temperature. Pathological involvement of the nervous system and of various glandular organs is a typical feature of mumps. The lesions of these organs are more correctly considered a symptom rather than a complication of the disease, whose causative agent has a definite tropism. Orchitis, which occurs in 10 to 30 per cent of young men and boys at puberty, usually develops on the sixth to eighth day of the disease. Rise of temperature, often accompanied with chill, malaise, and adynamia, and sometimes with delirium, excitation, and symptoms of circulatory failure are noted. More or less strong pain developing in one of 80
Pediatrics Infection the testes irradiates to the inguinal and lumbar regions. The testis enlarges, becomes tender and painful; the scrotum is oedematous and its skin is ofteq tense and red. A bilateral process is rare. The symptoms begin to subside in two or three days, and usually disappear completely by the end of the first week or the beginning of the second. Primary orchitis without previous affection of the salivary glands has been reported. Oophoritis, mastitis and bartholinitis are rare manifestations of mumps in older girls and normal or slightly increased, the cytosis is increased at the expense of lymphocytes young women. Mumps dacryocystitis and pancreatitis have been described. Pancreatitis normally manifests by strong epigastric pains and pains in the region of the left hypochondrium. Girdle pain occurs sometimes. Palpation is markedly painful. Nausea, anorexia, sometimes vomiting and diarrhoea occur. The diastase of the blood and urine increases highly. The pancreas may be affected in the presence of only part of these symptoms, or the symptoms may be nonmanifest. Acute serous meningitis is not infrequent in mumps, and mostly arises when the affection of the salivary glands is mild or moderate. It usually develops at the height of the disease, and is characterized by symptoms of meningeal irritation (headache, frequent vomiting, rigidity of the occipital muscles, Kernig's and Brudzinsky's signs). The transparent or opalescent cerebrospinal fluid flowing in lumbar puncture is at normal or elevated pressure. Its protein content is normal, there are 30-700 cells per mm3. The sugar and chloride content is normal. The mumps virus is often discovered in the cerebrospinal fluid. All these symptoms persist for 5-10 days and then subside gradually leaving no traces. Residual phenomena remain however in some patients' for long periods of time. Primary serous meningitis with or without subsequent affection of salivary glands has been encountered. The true nature of such meningitis is proved by the presence of characteristic epidemiological links, and by serological tests. Severe, but very rare complications of mumps are acute encephalitis and meningo-encephalitis, which are characterized by disturbed consciousness, delirium, and focal symptoms (paralysis, paresis, aphasia, etc.), and by affection of the inner ear with rapid development of stable deafness. Atrophy of the optic nerve is encountered even more rarely. DIAGNOSIS AND PROGNOSIS Difficulties in diagnosing mumps occur in mild and abortive forms, and when only submaxillary glands are affected, or the meningitis or orchitis is its first manifestation. Diagnosis is established from the features of the clinical course described above and the epidemiological data. The secondary parotitis developing in the course of severe acute infections (typhoid fever and typhus, sepsis, pneumonia, etc.) is usually unilateral and, as a rule, suppurative. 81
Pediatrics Infection Toxic parotitis is met mainly in adults suffering from acute or chronic mercury, lead, or iodine poisoning; it develops slowly, does not run a cyclic course, and is often accompanied with changes in the buccal mucous membrane. Cervical lymphadenitis is differentiated from mumps by an inflammatory focus in the fauces with localization of the swelling in the region of superior cervical lymph nodes. In mumps the swelling first obliterates the sulcus between the mandible and the mastoid process (directly under the auricle). Determination of diastase in the urine may be useful in diagnostication of pancreatitis. Primary meningitis of mumps aetiology can be confused with tuberculous meningitis. The latter develops slowly and gradually, the pressure of the cerebrospinal fluid is increased and its sugar content lowered; it may contain Mycobacterium tuberculosis. It is more difficult to differentiate primary meningitis of mumps etiology from acute serous meningitis caused, for instance, by an enteroviris. Diagnosis is established either on the basis of subsequent inflammation of the salivary glands, or when there is a history of exposure to mumps. An accurate diagnosis is made with the help of virological and serological methods. The complement-fixation and haemagglutination inhibition tests (isolation of the causative agent in the culture of cells) have been suggested as auxiliary methods for early diagnosis of mumps. Both reactions can be made with a standard antigen, a diagnostic culture, consisting of the virus grown on the membranes of a developing chick embryo. Both these tests should be made twice, once during the first week, and again at the end of the second week or during the third. Thus, elevation of antibody titre, which has special diagnostic value, is revealed. Prognosis is favourable. Mortality of mumps is remarkably low. Affection of the internal ear may lead to permanent deafness. Atrophy of the testes with subsequent aspermia can follow bilateral orchitis. TREATMENT Treatment is symptomatic. Diet is restricted to fluids or semi-fluids to spare the affected glands. Heat is applied to the glands by means of cotton or wool bandages, Sollux lamp, etc. Ultra-high frequency therapy and ultra-violet irradiation are also recommended. The mouth should be rinsed with weak disinfecting solutions. In severe mumps some investigators recommend gamma-globulin (3-6 ml). Strict confinement to bed is called for in orchitis; the testis should be supported and cold applied; gamma-globulin is given intra-muscularly. Corticosteroid preparations produce considerable alleviation of pain and subjective improvement. To relieve the severe headache and other meningeal symptoms in concomitant meningitis lumbar puncture. Dehydration therapy is carried out. PROPHYLAXIS
82
Pediatrics Infection The patient is isolated at home. Hospitalization is indicated only in individual cases when the course of the disease is severe or there are epidemic indications. Considering that the patients are infective for a relatively short time the period of isolation has been reduced to nine days. Contacts who have not previously had the disease should be segregated on the 21st day from the beginning of the disease. When the time of their contact is definitely known, they are allowed to attend the children's institution during the first ten days of incubation, and are only isolated from the ll-th to the 21st day from the time of contact. Serum prophylaxis is recommended. Exposed children are given gamma-globulin in a dose of 1.5 to 3 ml. A method of active immunization against mumps has been developed. A. Smorodintsev have suggested a living, antimumps vaccine of high efficacy and low reactogenicity. The vaccine is preserved in dry form. Children of 12- months are immunized subcutaneously (0.5 ml) or intradermally (0.1 ml).
83
*Meningococcal Infection*
The causative agent of epidemic meningitis is Weichselbaum's meningococcus (Neisseria meningitidis). This microorganism has the form of a diplococcus 0.6-0.8 ,u,m in size, which stains well with aniline dyes, and is gram-negative. The existence of several serotypes of meningo-cocci (A, B, C, D, Z, X, and Y) has been established. Types A and B prevail in this country. Epidemic outbreaks of the disease are associated with the type A. EPIDEMIOLOGY The sources of infection are sick persons and carriers who expel the causative agent with the secretions of the nasopharynx and upper respiratory passages. Since there are a great many more carriers than patients, the epidemiological role of the former is very great. Infection is transmitted by the aerial-droplet route. Children are mostly susceptible to the disease: about 70 per cent of incidence are infants under 5. The proportion of adults increases in epidemics. Those who suffer from meningitis or meningococcal carrier state, develop immunity, and recurrent epidemic meningitis is rarity. The meningococcal infection is characterized by periodic rises of the incidence at 10-15 or longer year intervals. Seasonal variations in the incidence are also observed; it increases in winter and early spring months. The incidence depends on the specific immunity of the population. High density of population, the absence of proper hygiene, and improper sanitation favour the spreading of the disease. PATHOGENESIS AND PATHOLOGICAL ANATOMY The portal of the infection entry is the nasopharyngeal mucosa. The carrier state develops frequently, while nasopharyngitis occurs significantly less frequently. The generalized form of infection occurs only in 0.5-1 per cent of cases: the causative agent is carried by bood to various organs (soft cerebral meninges, joints, eye membralnes, etc.). Meningococcal bacteraemia, or meningococcaemia manifests sometimes as sepsis. The important role in meningococcaemia belongs to marked intoxication with the endotoxin released during decomposition of the microbial bodies. Various organs are affected, in the first instance fine vessels. Microcirculation is thus affected to provoke thrombosis and extravasates. Typical haemorrhagic eruption appears on the skin. Purulent meningitis develops due to the ingress of the meningococcus into the soft meninges of the brain and the spinal cord. Purulent exudate is particularly abundant in the base, and also on the surface of the frontal and parietal lobes of the brain (a 'purulent cap') (Plate XVI). When the process implicates the ependyma of the cerebral ventricles (in untreated or inadequately treated patients), the latter become dilated by the accumulating purulent fluid (ependymatitis). Clinical classification by V.Pokrovsky.
84
Pediatrics Infection 1. Local forms - nasopharyngitis - healthy carrier 2. Generalized forms -meningitis 3. R forms - arthritis iridocyclitis chorioiditis phnumonia meningococcemia meningoencephalitis
The last form occures with meningococcemia CLINICAL PICTURE The incubation period lasts for 3-5 days on average (maximum 10 days). The most frequent form of the manifest meningococcal infection is nasopharyngitis. Its symptoms are headache, painful swallowing, subfebrile temperature in some patients, hyperaemia of the nasopharyngeal mucosa and hyperplasia of lymphoid follicles, rhinitis with scanty discharge, and difficult nasal breathing. The clinical signs persist for 5-7 days. Meningitis. The onset of the disease is usually violent, and a considerable elevation of temperature accompanied by chill is noted; severe headache, vertigo, and vomiting also occur. Catarrh of the nasopharynx is common. Characteristic is hyperaesthesia of the skin and increased sensitivity to light and sound. Disturbances of consciousness are also frequent (a state of stunning, delirium, etc.). In young children clonic and tonic convulsions are not infrequent. Rigidity of the occipital muscles develops very early (usually during the first 24 or 48 hours), and Kernig's and Brudzinsky's signs become positive. The abdomen is retracted. Anisocoria, strabismus, and paresis of the facial nerve are occasional. The patient's posture is usually typical: he is lying on his side with head tossed back and legs flexed to the abdomen. Red dermographism is very common and herpes often occurs on the lips. The pulse is initially rapid, but slows down later. Respiration is usually accelerated. Constipation is common in older children, but diarrhoea is often seen in infants. The blood shows marked leucorytosis (up to 20-40-109/l), neutrophilosis with a shift to the left, aneosinophilia; the ESR is considerably increased. In lumbar puncture spinal fluid flows under increased pressure (300-500 mm H2O). During the first day of illness it may be transparent or slightly opalescent, but later becomes turbid and purulent. It displays marked neutrophilosis (from 85
Pediatrics Infection several hundreds to several thousands of cells per mm3) and a considerable protein content (up to 1-2 g/1, or 1-2 per cent); sugar content is lowered. The gravity and course of meningococcal infection differ in various patients. The clinical manifestations are also quite varied. Especially grave are encephalitic, septic (meningococcaemia) and hyper-toxic forms. The meningococcaemia (septic form) occurs in patients of all ages. The relative incidence of the disease has increased in th& '70s. Signs of meningococcaemia may be observed in the presence (less frequently in the absence) of a pronounced symptom complex of meningitis. The onset is acute and violent, with intermittent fever. This infection is usually attended by skin rash, which is the most frequent symptom. The rash is haemorrhagic, often with macular (measles-like) lesions. The haemorrhagic lesions are stellar formations varying in size; they are hard to palpation and are often elevated over the skin level. They are usually localized on the buttocks and lower extremities, less frequently on the arms, the trunk, and the face. Me-ningococci are found in blood smears taken from the periphery of the lesions. Significant haemorrhage into the skin is often followed by necrosis of the tissues with subsequent rejection of the necrotized tissue; scars remain on the skin. Arthritides in meningococ-caemia are less frequent (according to V. Pokrovsky, in 5 per cent of cases). Several joints would be usually affected, with a purulent or a seropurulent exudate in the joint capsule. Inflammation of the chorioidea (iridocyclochorioiditis) is a less common, but very typical, complication of meningococcaemia; its first sign is a change in the colour of the ins, which becomes sort of rusty. The hypertoxic (fulminating) form of meningococcal infection has a sudden turbulent onset and is characterized by grave toxaemia (uncontrollable vomiting, convulsions, clouded consciousness, cardiovascular weakness). The patient soon becomes comatose. Meningeal symptoms are sharply pronounced or, on the contrary, rudimentary. Death usually ensues within 12 to 24 hours after the onset. Swelling of the brain and protrusion of the cerebellar tonsils into the great foramen is one of the frequent causes of death. The fulminating form may develop as the Waterhouse-Friderichsen syndrom, which is the sign of an acute renal insufficiency. Multiple petechiae and haemorrhage into the skin (resembling livors) are characteristic. The arterial pressure falls progressively, the pulse is rapid and hardly palpable. Cyanosis, vomiting (often with blood) and convulsions are other signs. The patient is prostrated and loses his consciousness. The patient dies in 16-30 hours after the onset of the disease unless an urgent and effective therapy is given. Along with these malignant forms, there also occur clinical variants of meningococcal infection characterized by very mild course. Next form is the meningoencephalitic form is seen mainly in infants and has a prevalence of cortical symptoms, namely disturbances of consciousness, convulsions, focal phenomena paresis, paralysis). The meningeal symptoms may be trivial. 86
Pediatrics Infection In the rudimentary (abortive) form all the symptoms are weakly expressed, including the meningeal. The changes in the cerebrospinal fluid may be insignificant and transitory. Features peculiar to meningitis in nursing babies. Onset of the disease is accompanied with high temperature, general restlessness, vomiting, and refusal to suckle. There is marked hyperaesthesia of the integuments and frequent dyspeptic disturbances. Infants scream loudly. Meningeal symptoms and red dermographism are often mild or absent. Tension and protrusion of the unossified anterior fontanelle are apparent at the beginning of the disease. In the newly born the course of meningitis as a rule is atypical. High temperature, convulsions or tremor, and general muscular hypertension develop. Meningeal symptoms are absent or become apparent only with further progress of the disease. Even with modern methods of treatment mortality remains high among the newly born and babies under three months old. COMPLICATIONS Modern early treatment markedly decreases the incidence and gravity of complications, as well as of residual symptoms. Some patients develop complications associated with the bacterial superin-fection. Pneumonia develops mainly in grave meningococcaemia with disordered consciousness: the patient runs a risk of aspiration of his vomit, and mucus from the pharynx and the upper airways. Pneumonias are usually of staphylococcal aetiology; meningococcus is actively involved in their development in some cases. Chronic hydrocephalus, motor disorders (paralyses, pareses), retardation of mental growth are now rare. Asthenia, headache, and various functional disorders are observed. DIAGNOSIS Diagnosis of epidemic meningitis is established from the distinctive features of the clinical symptomatology and course (acute onset and rapid development of meningeal symptoms). The most important diagnostic aid is lumbar puncture and examination of the cerebrospi-nal fluid. The diagnosis is indisputable when meningococcus is detected by bacterioscopy or is found in a cerebrospinal fluid culture. Examination of cerebrospinal fluid is particularly important in atypical forms and in meningitis in nursing babies. Errors in recognizing epidemic meningitis in children are not infrequent: epidemic meningitis can be confused with other forms of meningitis, with various diseases accompanied with meningism syndrome. Meningeal symptoms are usually mild in meningism and the cerebrospinal fluid unchanged. Tuberculous meningitis starts gradually and is accompanied with a moderate pyrexia; it is recognized from the anamnesis and the results of tuberculin tests. Miliary tuberculosis often shows up on X-ray pictures of the lungs. Cerebrospinal fluid is transparent or slightly opalescent; cell count is moderately increased through an increase in the number of lymphocytes. When cerebrospinal fluid is allowed to stand a delicate web-like pellicle of fibrin forms on its surface. Mycobacterium tuberculosis is often found in the cerebrospinal fluid. 87
Pediatrics Infection Acute serous meningitis diners in the cerebrospinal fluid findings {complete transparency; moderately increased cell count through a higher number of lymphocytes; normal sugar content). In the meningeal form of poliomyelitis the cerebrospinal fluid is transparent. A slight or moderately increased cell count and normal or slightly increased protein content (cellular-protein dissociation) is noted during the first five days; later the cell count drops, and a protein-cellular dissociation is observed from the tenth day. Lymphocytes predominate among the cells. Diagnosis is facilitated if tendon reflexes disappear, and even more so if flaccid paralysis or paresis develops. In contrast to primary meningococcus meningitis, purulent meningitis caused by staphylococcus, pneumococcus, Afanasyev-Pfeiffer bacillus, and streptococcus usually develops secondarily to purulent otitis, pneumonia, sepsis, etc. Gram-positive cocci and diplococci are found in the cerebrospinal fluid, which is purulent. Difficulties in differential diagnosis of meningococcaemia arise in cases where it has no symptoms of meningitis, and may be mistaken for septicaemia of other aetiology, thrombopenic purpura, and hae-morrhagic vasculitis. It should be remembered that meningococcaemia is characterized by high temperature, pronounced intoxication, marked changes in the blood (hyperleucocytosis with the shift to the left); a stellar pattern of haemorrhagic eruption is typical. Accurate diagnosis is established bacteriologically. Meningococcus can be detected not only in the blood but also in the skin lesions. PROGNOSIS Given early and proper treatment with modern methods mortality is now very low. The worst outcome in meningitis is prognosed in cases with the Waterhouse-Friderichsen syndrome and he hypertoxic clinical form. At a meningococcal infection prognosticaly unfavorable are the following signs : plenty of petechias on a skin, specially necrotic, distribution of rash upwards from extremities to the trunk and face; Low arterial pression; Hypothermia or considerable hyperthermia; Leukopenia in a blood, high leukocytic indexis of intoxication; Considerable thrombocytopenia, low prothrombin test Low pleocytosis in CSF at the extremely grave condition of patient or considerable protein- celllike dissociation.
TREATMENT Children are given a daily dose of 300000 - 400000 units per kilogram of body weight at intervals of three to four hours (infants under 3 months of age are given 400 000 - 500 000 U/kg). Treatment lasts for 5-8 days without reducing the dose.
88
Pediatrics Infection If the patient is hypersensitive to penicillin, laevomycetin sodium succinate can be given (50-100 mg/kg for 6-8 days), ampicillin (150-200 mg/kg a day),. The antibiotics can be given together with sulpha drugs. Older children can be given preparations of prolonged action, e.g. sulphamonomethoxin: 40 mg/kg two times during the first day, and then 20 mg/kg a day. The treatment should be continued for 7-10 days. A marked therapeutic effect can already be seen during the first two days. Children with meningococcemia can be given antibiotics of bacteriostatic action - laevomycetin sodium succinate during first day of disease, simultaneously witm big dozes of hormones. In addition to aetiotropic preparations, pathogenetic and symptomatic therapies are also important. Toxicosis can be controlled by administration of large amounts of liquids (ample drinking, intravenous infusion of physiological solution of glucose, plasma substitutes, and plasma); electrolyte balance and osmotic pressure should be taken into consideration. Dehydration techniques are also used. Dehydration therapy should be especially intensive in the presence of brain swelling (respiratory arrhythmia, convulsions, cyanosis, arterial hypertension). Corticosteroids should be given simultaneously. Seduxen, aminazine, phenobarbital, sodium oxybutyrate are given in the presence of convulsions. Vitamins should also be given. To correct metabolic acidosis, a 4 per cent sodium bicarbonate solution should be given to the patient; hypokalaemia can be corrected by potassium preparations (potassium chloride, panangin). To improve the cardiovascular function ATP, and cocarboxylase are indicated. The patient needs adequate care and supervision, and good nutrition. Grave forms of meningococcal infection require urgent aid and should be treated at resuscitation and intensive therapy departments. PROPHYLAXIS The following measures are carried out in an epidemic focus. The patient is hospitalized and isolated; he is discharged after the clinical manifestations of the disease subside and on condition that the results of two bacteriological studies of the pharyngeal mucus are negative. Child contacts and exposed adults are quarantined (isolated at home). Only after a negative bacteriological report (examination of nasopharyngeal discharge), or, if there are no laboratory facilities, after 7 days of separation from the patient, are they admitted to children's institutions. It is advisable that contacts and virus carriers should be treated with sulphonamides or antibiotics for 5 days as a prophylactic measure, the standard dose being given three times a day. Polysaccharide meningococcal vaccines have been recently developed in some countries. But many practical problems of their use are not still solved.
89
At a meningococcal infection prognosticaly unfavorable are the following signs : plenty of petechias on a skin, specially necrotic, distribution of rash upwards from extremities to the trunk and face; Low arterial pression; Hypothermia or considerable hyperthermia; Leukopenia in a blood, high leukocytic indexis of intoxication; Considerable thrombocytopenia, low prothrombin test Low pleocytosis in CSF at the extremely grave condition of patient or considerable protein- celllike dissociation.
90
*Measles (Morbilli)*
The pathogenic agent causing measles is the virus which belongs to the group of myxovirusesi Anderson and Goldberger (1911) established filterability of this virus. The measles virus is very unstable and is soon destroyed outside the human body. EPIDEMIOLOGY The source of infection in measles is a sick person. Infectivity is greatest in the initial catarrhal stage and during the first days after the appearance of the rash; it falls abruptly from the third day of the rash, and after the fourth day the patient is no longer a source of danger. There are no carriers. Infection is usually conveyed by the aerial-droplet route. The virus is expelled from the organism in the secretion of the mucous membranes of the nose, nasopharynx, and upper respiratory tract, particularly during coughing and sneezing. The susceptibility of humans to measles is very high (susceptibility index 0.96). Persons of all ages who have not had measles almost invariably contract the disease when exposed even briefly to infection. Stable lifelong immunity is invariably conferred by one attack of measles. Second attacks are very rare (0.5 to 1.0 per cent of cases). Infants under three months of age are absolutely immune to measles, and, those between three and six or eight months are relatively immune. This is attributed to immunity transplacentally transmitted from a mother who had previously had the disease. Features of the epidemic process. In the absence of rational control measures, measles has a tendency to spread with great rapidity. PATHOGENESIS The portal of entry of measles is the mucous membrane of the upper respiratory tract, and possibly the conjunctiva. The altered reactivity of the child's organism during measles is expressed in the state known as measles anergy; positive tuberculin reaction disappears, the titre of immune bodies falls, the complement titre decreases, the immunization capacity of the organism diminishes. Complications are caused both b measles virus itself and by secondary bacterial flora. It was established recently that the measles virus can persist for a long time in the brain tissue of man and cause chronic infection. Subacute sclerosing panencephalitis develops. This is a rare and a very grave demyelinizing disease of the central nervous system with a lethal outcome. Its incidence is, on an average, 1 per million persons who had measles in their childhood. 91
Pediatrics Infection PATHOLOGICAL ANATOMY The principal pathological changes attending measles are inflammatory processes in the nasopharynx, respiratory organs, and skin. Histologically measles rash is a non-specific focal inflammation in the upper layers of the dermis; foci of inflammation are localized at a more or less considerable distance from each other. Later, intensified and irregular cornification of the epithelial cells in the affected areas results in fine branny desquamation. The Belsky-Fyatov-Koplik spots scattered over the mucous membrane of the mouth in the initial stage are the result of an inflammatory process. CLINICAL PICTURE The incubation period of measles is usually from 8 to 17 days. In children who have had serum prophylaxis, or been treated with blood or plasma transfusion, the incubation period may even be as long as 21 days. The onset of the disease is characterized by symptoms of the initial catarrhal period 1, viz. a rise in temperature up to 38-39G, headache, rhinitis, and cough. There is general malaise, adynamia, poor appetite, and insomnia; the child is listless and fretful. The temperature usually falls on the second or third day, sometimes to a subfebrile level. But the symptoms of affection of the mucous membrane increase. The cold in the nose gets worse; the patient begins sneezing an5 there is a more or less copious serous discharge. A perturbing dry hacking cough develops, and there is a sensation of irritation in the respiratory tract. Hoarseness is sometimes noted, and with it a change in the cough, which becomes hard and harsh. Conjunctivitis expresses itself in hyperaemia of the conjunctiva, watering of the eyes, and photophobia, which may be so strong that the eyelids close spasmodically and involuntary (blepharospasm). The look of the patient is characteristic: the face is swollen, the eyelids slightly hyperaemic and oedematous, the eyes water, photophobia is apparent, and there is a serous discharge from the nose. Very typical alterations of the mucous membranes of the mouth and soft palate occur. One or two days before the outbreak of rash on the skin red irregular spots varying in size from the head of a pin to a lentil can be seen on the mucosa of the soft, and in part of the hard, palate. This eruption, known as enanthema, is an important early diagnostic sign of measles. Fusing in one or two days, these spots become indistinguishable against the general background of hyperaemic mucosa. Almost simultaneously with the spotty enanthema, and sometimes before it, the typical initial symptom of measlesBelsky-Filatov-Koplik spotsappears. Belsky-Filatov-Koplik spots mostly break out on the mucous membranes of the cheeks opposite the line of opposition of the molar teeth, and less commonly on the inner surfaces of the lips and gums, and occasionally on the conjunctiva. Each element looks like a whitish papule, the size of a poppy-seed, surrounded by a narrow band of hyperaemia, or areola. The eruptive stage begins with a new rise of temperature which reaches its maximum on the second or third day, and falls to the normal in a short irregular lysis towards the fifth to seventh day of eruption. 92
Pediatrics Infection The appearance of the rash coincides with the rise of temperature. Its first elements are found behind the ears and in the centre of the face. Within 24 hours it spreads rapidly over the whole face, neck, and upper part of the chest; it also covers the skin of the circumoral region (Plate IX). On the second day the exanthema rapidly spreads over the trunk and the proximal parts of the extremities, and on the third day covers the limbs. This order of succession in the spread of the eruption is typical of measles. Outbreak of the rash may, however, sometimes be accelerated or retarded, or may appear first on the trunk. At first the elements of the rash look like pink papules of a soft consistency, the size of a grain of millet or buckwheat. Within a few hours each papule becomes surrounded by a zone of bright erythema. Soon adjacent maculopapules become confluent, forming large blotches of irregular outline, with the initial papules in the centre. Large maculopapular elements have a tendency to fuse further. The unaffected pale areas of the skin show up distinctly against the background of the bright rash. Elements of the rash 'effloresce' for three days; from the fourth day they begin to fade in order of their appearance. Quite often the rash on the face .loses its brightness on the third day when it appears on the extremities. The subsiding rash becomes less prominent and assumes a cyanotic tinge; its elements, gradually fading, leave spots of a light-brown pigmentation which persists for one or two weeks. Fine branny desquamation (on the face and trunk) sometimes following the subsidence of eruption lasts around five to seven days. The general malaise and symptoms of functional disturbance of the central nervous system first seen-during the catarrhal stage progress during the eruptive stage. General inhibition and adynamia are observed; headache becomes worse; there is loss of appetite. Sleep is disturbed and the child is sometimes restless and delirious during the night. The catarrh of the mucosa of the respiratory passages and conjunctiva (running nose, cough, suffused eyes, and intolerance of light) becomes more pronounced. At the end of the incubation period the blood picture shows mild leucocytosis and netrophilosis, at the end of the catarrhal stage leucopenia and neutropenia, .and at the eruptive stage leucopenia, often with a relative neutropnilosis, eosinopenia and thrombopenia. During convalescence, even when all clinical manifestations of the disease have already subsided, the restorative process is far from completed. The indices of general immunological reactivity have fallen sharply. Clinical Forms Mild, moderately severe, and severe forms of measles are distinguished, according to its severity. Atypical forms (measles with a toxic, abortive, or rudimentary course) are also encountered. The severe form has marked symptoms of toxaemia (hyperthermia, affection of the nervous system with disturbances of consciousness, adynamia, and acute cardiovascular failure). 93
Pediatrics Infection An abortive or rudimentary form of measles is encountered quite rarely among the unimmunized. Measles sometimes runs an atypical (but not mitigated) course in children treated with antibiotics. In children subjected to serum prophylactic|immunization mitigated (attenuated) measles is observed, in which the incubation period is protracted to a maximum of 21 days, but the initial and eruptive periods are shortened. Catarrhal symptoms in the mucous membrane are usually mild or absent; and the enanthema and Belsky-Filatov-Koplik spots may also not appear. Rash is usually sparse or even represented by a few elements. Temperature is sometimes only subfebrile and lasts for two or three days. The patient's general condition is usually not disturbed, or only slightly affected. COMPLICATIONS The younger the patient, the greater the frequency of complications; it is particularly high in children under two. The complications of respiratory ones (laryngitis, measles croup, bronchitis, pneumonia, etc.) Complications of the alimentary tract (stomatitis, dyspepsia) are quite frequent in measles. Catarrhal otitis, blepharitis and keratitis occupies a leading place among the other complications in measles. Nervous complications of measles are seldom encountered, but may occur in the form of serous meningitis, encephalopathy and encephalitis. DIAGNOSIS Diagnosis is based on the clinical symptoms, with due account of the epidemiological anamnesis. In the catarrhal stage diagnosis of measles must rest on the presence of the typical complex of catarrhal symptoms. An important early diagnostic symptom is spotty enanthema on the palatal mucosa. The finding of Belsky-Filatov-Koplik spots is indisputable evidence of measles. The catarrhal stage of measles can simulate influenza and other respiratory viral infections. When measles is suspected the patient should be isolated and observed for a day or two until diagnosis is clarified by the appearance of typical symptoms. During the eruptive stage there are usually no difficulties in recognizing measles, and errors can only occur when its course is atypical. Measles is sometimes confused with German measles; but in the latter there are no Belsky-Filatov-Koplik spots, and catarrhal phenomena are either absent or trivial. In German measles the rash invades the whole body almost simultaneously, is micromacular in character, has no tendency to confluence, and leaves no pigmentation; the patient's
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Pediatrics Infection general condition is almost undisturbed, and the temperature reaction is mild. Almost constant symptom of German measles is swelling of the occipital and posterior lymph nodes. Scarlet fever differs from measles in the absence of catarrh of the respiratory tract, of spotty enanthema, and of BelskyFilatov-Koplik spots. A constant symptom of scarlet fever is angina; the disease is often heralded by vomiting, and the tongue presents typical changes. The rash in scarlet fever does not break out in stages as in measles, but covers the whole body almost at once and is minutely punctate. The circumoral region remains free of rash. There is no leucopenia or aneosinophilia typical of measles, but neutrophilosis, eosinophilia and leucocytosis are found. Serum rash often has a morbilliform character, but there are usually indications in the anamnesis of serum therapy having been employed seven to twelve days before the sickness. Serum sickness does not have a cyclic course, eruption begins from the site of the injection, follows no order, and is accompanied with itching. Together with the spotty rash, at least individual urticarial elements are found. There are no marked catarrhal phenomena. Drug rash appears in any order, never covers the whole body, and is polymorphous; other measles symptoms are also absent. TREATMENT Properly organized hygienic conditions for the patient, careful nursing, and protection from secondary infections are of immense significance for the treatment of measles and the prevention of complications. Since most cases are not hospitalized, it is necessary to ensure that proper conditions and routine are created for them at home. Measles cases are hospitalized when (a) they are grave and complicated; (b) home conditions are unsatisfactory, or it is impossible to arrange correct nursing; (c) when indicated by epidemiological signs. The skin of the patient should be given a proper care. The face and the hands should be washed frequently; at later terms the patient should be allowed to take a bath. The visible mucosa should be systematically cleansed: the eyes should be washed, the nose freed from mucus and crusts, the lips should be coated with fat. Frequent drinking will help the infant keep its mouth clean. Older children should rinse their mouths regularly. The diet should be nourishing, easily digestible, and leave a minimum of residue; liquids and semiliquids are to be preferred. If measles is not aggravated by any complications, symptomatic means are taken if necessary. Antibiotics are given in the presence of complications, which are usually of the bacterial nature, or in the presence of conditions that may favour the development of the bacteria. The symptomatic and hypoallergenic therapy are administered.
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Pediatrics Infection PROPHYLAXIS The live vaccine 'Leningrad-16' is given subcutaneously in a single 0.5ml dose at the 12th month. Revaccination in 6 year. Gamma-globulin is only used for prophylactic purposes in children, who were in contact with the measles patients. Gamma-globulin is given not later than in 6 days from the day of contact. The preparation is given in a dose of 1.5 ml (3 ml to infants who already develop the disease). The disease is not prevented by this procedure but it develops in a mitigated form, leaving a stable immunity against measles. Measures to be carried out in an epidemic focus. The most important conditions for the success of counter-measures in a focus of infection are early diagnosis and prompt isolation. All unimmunized children who have been in contact with a case of measles and have not had measles in the past should be carefully followed up. They should urgently be vaccinated against measles and isolated for 17 days. The quarantine for children, who had contacts with measles patients and who were given gamma-globulin, should last for 21 days. Children subject to segregation are excluded from children's institutions with unvaccinated children (creches, kindergartens, and the first years of school) from the eighth day of exposure to the end of the quarantine period.
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*German Measles (Rubella) (Rubeola Morbillosa)*

This infection has recently drawn attention of many investigators (especially in foreign countries) because it was established that rubella is responsible for the development of congenital growth defects. The agent that causes rubella is a micro virus sizing from 100 to 300 nm; the virus is polymorphous, it contains RNA, and is sensitive to chemical agents and temperature. EPIDEMIOLOGY The source of infection is a sick person. The infection is probably transmitted mainly by the aerial-droplet route. Pregnant women with manifest or symptomless rubella may become the source of intrauterine infection of the foetus. Susceptibility of children to rubella is high. Most develop the disease at the age between 1 and 7. CLINICAL PICTURE The incubation period lasts 15-21 days, sometimes up to 24 days. Typical symptom is swelling of the posteriorlylocated cervical, occipital, and other lymph nodes which develops one to three days before the eruption and disappears several days after its defervescence. The swollen glands are usually about the size of a large pea, hard, and slightly tender on palpation. The rash invades the face and neck, and covers the whole body within a few hours. It is localized mainly on the extensor aspects of the limbs, back and buttocks, and is sparse on the abdomen and chest, and particularly on the face. Its elements are pale red, round or oval spots, sometimes slightly elevated above the surface of the skin, with no tendency to confluence. They vary in size from a pin-head to a lentil. Small elements predominate in some cases, and large in others. The rash lasts two or three days and disappears rapidly without leaving any pigmentation. Subsequent desquamation is not observed. Eruption is accompanied with a slight rise of temperature, usually up to 38C, but temperature often remains normal throughout the whole course of the disease. The catarrhal phenomena of prodromal stage do not become more intense. The patient's condition is not disturbed, as a rule. Complications (arthropathy, otitis, pneumonia, nephritis, polyneuritis) are exceptionally rare. Encephalitis and encephalomyelitis were reported; they often terminated lethally (in 15-20 per cent of cases). Clinic of congenital rubella. If a pregnant woman falls ill at her early pregnancy (1-3 months), the embryo and foetus often (from 10 to 50 per cent) develops chronic rubella with grave affections of various organs: microoephalic, hydrocephalus, hearing loss, cataract, retinopathy, glaucoma. When pregnant women become infected with rubella after the organogenesis has been completed, foetopathies develop as a result of the viral affection of the foetus (anaemia, thrombopenic purpura, hepatitis, affections of the lungs, bones, etc.). Infants born from such mothers become persistent carriers. The antibody titre at birth is high in them. TREATMENT AND PROPHYLAXIS No treatment is required. Contacts are not segregated. Prophylactic immunization with live vaccines is given at 12th month. Revaccination - at 6 and 15 years for girls.
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*Chickenpox (Varicella)*
The causative agent of chickenpox is a filterable virus Aragao's elementary bodies that is found in matter from the vesicles by staining by Morozov's technique with silver. The morphological and biological properties of the virus were later studied virologically. The virus of chickenpox is oval, polyhedral or spherical in shape; it sizes 150-200 nm, and contains DNA. Chickenpox and herpes zoster (shingles) were proved to be caused by the same virus, which was thus given the name of varicella-herpes zoster virus (V-Z virus, for short). EPIDEMIOLOGY Patients are a source of infection from the last (1-2) days of the incubation period up to the ninth day from appearance of the elements of the rash. The patient is not infective at the stage of formation and separation of crusts. Many clinicians (Bokay and others) believe that chickenpox can be contracted in individual cases from herpes zoster patients. Infection is transmitted by air-droplet route, and can be conveyed over quite considerable distances (along passages to neighbouring rooms and apartments). But owing to its low stability, the virus is not transmitted via articles or third persons. Susceptibility to chickenpox is very high, practically universal, but a lower rate has been noted in nursing babies under six months old. Chickenpox is very rare in children after ten years of age or in adults. This being probably the result of a disease in early child hood. Stable lifelong immunity follows one attack; second attacks are extremely rare. The incidence of chickenpox is very high. It is endemic in cities, where epidemics occur from time to time. All or nearly all children who have not previously had chickenpox are usually affected when infection is accidentally introduced from outside into a children's institution for infants in which prophylactic measures have not been taken in time. Epidemics occur mainly in the autumn, winter, and spring (Fig. 31). The regularity shown in Fig. 31 remains the same nowadays. PATHOGENESIS AND PATHOLOGICAL ANATOMY The pathogenesis and pathological anatomy of chickenpox are still not very clear. The portal of entry is the mucous membrane of the upper respiratory tract. After an incubation period, the virus circulating in the blood localizes by preference in the skin owing to its dermotropicity. Vacuole degeneration of cells of the Malpighian layer with the formation of giant multinuclear cells at the periphery is distinctive of the pathological process in the skin; intranuclear eosinophilic inclusions are characteristic of the altered cells of the epidermis. Vacuolization leads to the formation of small cavities that are divided at first by the residue of the cell walls but soon fuse into a unilocular vesicle. Leucocytes 98
Pediatrics Infection (mostly lymphocytes) and multi-nuclear giant cells are found in the contents of fresh vesicles. The Guarnieri bodies are not found in the cells. In very rare cases the lungs, liver, spleen, kidneys, pancreas, and other internal organs may be affected by the virus. The lesions have small circular foci of necrosis surrounded by a haemorrhagic band and petechial haemorrhages (Fig. 32). Many investigators think it possible that the chickenpox virus may persist in the body of man for a long period of time. It may probably be retained in the cells of the intervertebral ganglia after the human recovers from chickenpox. The latent infection may persist for years and revive when the conditions favour (various diseases, injuries, intoxications, etc.). The virus then becomes activated in older children or in adults to show clinically as herpes zoster. CLINICAL PICTURE The incubation period averages 14 days, but is sometimes as short as 11 days or as long as 21. Prodromal signs are usually absent or mild (subfebrile temperature, and a certain general discomfort for 12 to 24 hours). Sometimes there is a so-called prodromal rash (in 4 to 6 per cent of cases), usually scarlatiniform, less often morbilliform, which ordinarily soon disappears: but more commonly it appears after the outbreak of the typical elements of chickenpox. The outbreak of rash coincides with a rise of temperature or follows a few hours later; but the first vesicles often appear at normal temperature. There is no definite order of appearance of the rash; it may develop on the face, scalp, trunk, or limbs. Unlike smallpox chickenpox rash 'has no predilection for the face and does not avoid the abdomen' (N. Filatov). Only occasionally, when it is very profuse, are individual elements seen on the palms and soles. At first maculopapular, the elements are very quickly converted (within a few hours) into vesicles, but some papules dry up without vesiculation. Vesicles are round or oval, differ in size from a pinpoint to a large pea, and are seated superficially on an unindurated base; their wall is tense, and they are lustrous and filled with a clear fluid; umbilication is seen in only individual lesions. A narrow erythem-atous corona surrounds the vesicle. Because the vesicles are uniloc-ular they collapse when pricked. Vesicles dry up in one or two days, forming flat brown crusts that are shed in one to three weeks, leaving no scars. Since chickenpox eruption does not develop at once, but comes out in crops at intervals of 24 to 48 hours, it is polymorphous, i.e. the lesions are in different stages of development (papules, vesicles, crusts) at any time on a given area of the skin. The itch is disturbing. In some patients eruption is often seen on the mucous membranes of the mouth, naso pharynx, larynx, genital organs, etc., and may even precede the outbreak on the skin. The vesicles are rapidly converted into superficial erosions with a yellowish-grey floor, which are rather tender but heal in a few days. In contrast to smallpox, this rash on the mucous membranes is usually sparse. 99
Pediatrics Infection The rise of temperature in chickenpox usually coincides with appearance of the rash. It usually goes up to 38C, and may become high (39C or 40C). The temperature curve is irregular, ea h peak reflecting the dynamics of the eruption. The elevation of temperature is accompanied with aggravation of the child's general condition: sleep is disturbed; appetite is lost; and the patient becomes irritable and capricious. All these symptoms are more marked with a profuse rash. On the third to fifth day the temperature falls simultaneously with drying up of the rash, and improvement of the patient's general condition. But in some cases, when the rash continues, the fever may drag on for six to eight days. The chief blood findings in the eruptive stage are slight leucopenia, neutropenia, and a relative lym-phocytosis.
Clinical Forms of Chickenpox The profusion of the rash and the severity of the general symptoms vary widely in chickenpox. In some patients only solitary vesicles are revealed with no fever (rudimentary form), while in others the eruption is very profuse and is accompanied with hyperthermia and marked symptoms of general toxaemia. In abortive cases the papular rash dries up without reaching the stage of vesiculation. When the contents of vesicles become purulent pustules are formed, and the disease is said to enter the stage of pustulation. Scars may then be left when the crusts are shed. This form occurs in around 10 per cent of all cases. In the bullous form of chickenpox (varicella bullosa) large flabby bullae develop (up to two or three centimetres in diameter, with turbid contents) in addition to the typical vesicular rash. The bullae may burst leaving an extensive moist surface. The outcome in the overwhelming majority of cases is favourable. This form, the same as the pustular, is probably related to concomitant secondary coc-cal infection. In the gangrenous form (varicella gangrenosa) solitary vesicles assume a haemorrhagic character and are surrounded by inflamed zone. Later these vesicles dry up into necrotic scabs that leave deep ulcers with a dirty necrotic floor and steep or undermined edges after separation. As a consequence of progressive gangrenous destruction the ulcers may grow and become quite large. The course is prolonged, and pyoseptic complications are common. A fatal outcome is possible. This rare form of chickenpox in the main affects enfeebled sickly children, particularly when poor care creates favourable conditions for secondary infection. A haemorrhagic form (varicella haemorrhagica) is encountered very occasionally in feeble children with symptoms of haemorrhagic diathesis. 100
Pediatrics Infection Generalized or visceral form of chickenpox with affections of the internal viscera is usually found on posthumous section. Pneumonia is only diagnosed during lifetime in adults because of the specific roentgenological signs. This complication of chickenpox is grave as a rule. Marked dyspnoea, cyanesis, blood in the sputum (containing also cells with specific intranuclear inclusions) attend this complication. Multiple small dark foci are found roentgenologically in adults, while in children the picture of the lung roots and emphysema are only intensified. It is supposed that pneumonia developing in children with chickenpox during the period of eruption and ending by recovery, is in some cases of specific aetiology (V. Vertzner). COMPLICATIONS Complications are rare in chickenpox. Keratitis is possible when a vesicle appears on the cornea. A picture of laryngitis, sometimes with stenosis of the respiratory tract (chickenpox croup), can develop with vesicular eruption on the mucous membrane of the larynx. Abscesses, phlegmons, erysipelas, stomatitis, otitis, lymphadenitis and bronchopneumonia can result from supervening secondary infection. Cases of serous synovitis and nephritis have been described as very rare complications, and individual cases of encephalitis and serous meningitis. DIAGNOSIS Difficulties only occur in diagnosis when the course of chickenpox is atypical and can be mistaken for some other similar diseases. The most important differentiation to be made is that between chickenpox and smallpox. The following distinctive signs should be taken as guides in distinguishing the two. The initial period in smallpox is accompanied with a considerable rise in temperature and marked backache, and lasts for approximately three days. In chickenpox there is either no fever preceding the eruption, or pyrexia lasts for not more than 24 hours; as a rule, patients do not complain of pain in the back. In smallpox eruption is accompanied with a fall, and in chickenpox with an elevation of temperature. In smallpox the spread of the rash follows a definite order appearing first on the face and then the hands, trunk, and extremities. In chickenpox the rash breaks out without any special order, and in crops. In smallpox the eruption is particularly profuse on the face and hands, and is almost always present on the palms and soles; in chickenpox it is thickest on the trunk, but almost always avoids the palms and soles. In smallpox the elements of the rash are usually shotty on palpation and are localized in the depth of the skin on an indurated base; being multilocular, they do not collapse when pricked by a needle, and they are umbilicated. In chickenpox the elements of the rash are seated superficially, their bases are not indurated, and they collapse when pierced by a needle because of their unilocular structure. The pocks are seldom umbilicated. In smallpox a given 101
Pediatrics Infection area of the skin displays lesions all at the same stage of development (monomorphism); in chickenpox, because the rash appears in successive crops, the elements do not develop all at the same time and exhibit polymorphism. A more or less profuse rash is always seen on the mucous membranes of smallpox patients; lesions of this localization are usually sparse in chickenpox or quite absent. The laboratory techniques described in the chapter on smallpox can be used for differential diagnosis; epidemiological anamnesis is also of great value. The bullous form of chickenpox can resemble pemphigus. In ad dition to the large bullae, varicella bullosa is distinguished by the presence of typical chickenpox vesicles, which are often found on the scalp. Impetigo diners from chickenpox by predilective localization on the face and hands, Qabbiness and rapid rupture of the bullae with subsequent formation of purulent crusts. In strophulus vesicles may sometimes form on the summits of papules. But, in contrast to chickenpox, the rash elements are hard, and invade mainly the lumbar region, buttocks, and rear aspect of the legs; the rash is accompanied with strong itching. Temperature is normal. The course of the disease is protracted. Vacciniform pustulosis (Kaposi's varicelliform eruption) is very much like chickenpox. It usually occurs in infants (during their first year of life) to supervene upon an existing eczema or dermatitis. It manifests by eruption of vesicles, which resemble the chickenpox rash. The vesicles are mainly located on the eczema-affected skin and soon become umbilicated. As distinct from chickenpox, this disease is usually grave, with high fever that persists for ten days. Chickenpox can be confused with scarlet fever when there is an outbreak of prodromal scarlatiniform rash. Double infection is usually suspected (simultaneous development of both diseases), but scarlet fever can be excluded by the absence of angina, of the typical changes in the tongue, or of the circumoral pallor. Diagnosis is sometimes cleared up by further observation. Laboratory methods (the same as in smallpox) can be used when necessary in the differential diagnosis of chickenpox. PROGNOSIS As a rule, chickenpox ends in complete recovery. A fatal outcome is exceedingly rare and occurs only when there are severe complications, and in gangrenous or haemorrhagic forms. The younger the child, the more severe the course of the disease is. Severe forms of chickenpox and various complications are usually encountered in enfeebled children and those suffering from acute or chronic infections. Chickenpox aggravates the course of many infectious diseases (whoopingcough, measles, scarlet fever, influenza, etc.), promoting the development of complications; and it can light up chronic infections (tuberculosis, dysentery). The literature is full of reports indicating that chickenpox runs a very grave course, with
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Pediatrics Infection a haemorrhagic syndrome (sometimes with a fatal outcome) in children treated with adrenocortical hormonal preparations before contraction of the disease or at the beginning of the incubation period; but this danger should not be exaggerated. TREATMENT The basic treatment of chickenpox is hygienic measures aimed to prevent secondary infection. Baths with a weak solution of potassium permanganate are recommended, taking care to avoid maceration and injury to the vesicles. The patient's hands should be kept clean and the nails cut short. Vesicles are painted with a 1 to 2 per cent solution of potassium permanganate, or a 1 to 2 per cent aqueous or alcoholic solution of brilliant green, or are treated with indifferent ointments. The mouth should be rinsed with a suitable weak disinfecting solution. Antibiotics (penicillin, erythromycin, tetracycline, etc.) are indicated for purulent complications. The gangrenous form (varicella gangrenosa) and protracted sluggish repair call for stimulating therapy, including pen toxyl, gamma-globulin, etc., in combination with antibiotics. PROPHYLAXIS The basic means of prophylaxis are sanitary measures. The patients are isolated (usually at home) for nine days from the beginning of the disease. When chickenpox is discovered in a hospital, or in a residential children's institution, the patient should be isolated in a cubicle of the Meltzer type. Experience has shown that early isolation (with the appearance of the first vesicles) serves to prevent new cases. Infected premises are well ventilated after the patient has been isolated. Disinfection is not required because the virus is very unstable. Children under three years of age who have previously had no chickenpox and who have been exposed to it should be quarantined for a period between eleven and twenty-one days counting from the time of contact. Intramuscular injections of 3-6 ml of gamma-globulin are recommended as serovaccination for prophylactic purpose. According to some clinicists, this method reduces the incidence of the disease in the vaccinated and if a person develops the disease, it is mitigated. Attempts of active immunization were reported. Live attenuated vaccines, that ensure good effect, have been developed. But vaccination on a wide scale cannot be considered reasonable or substantiated.
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*Infectious Erythema (Erythema Infectiosum or Fifth Disease)*

The causative agent is unknown. Viral aetiology is suspected. The disease is characterized by low contagiousness. Children from 5 to 12 mostly fall ill. In rare cases the disease also occurs in adults. Persons with infectious erythema probably develop a stable immunity; no relapses were reported so far. The average incubation period is between seven and fourteen days. There is either no prodromal period at all or it is expressed by a slight elevation of temperature just before the eruption. The disease begins with an outbreak of eruption that first appears on the cheeks. The elements of the rash are small pink maculopapules with a tendency to enlarge rapidly and fuse. The skin on the top of the nose and the lips remains pale. The redness of the cheeks and bridge of the nose makes a characteristic 'butterfly1 picture. On the second day, and less commonly on the first, the rash makes its appearance on the limbs, mainly on their extensor aspects. It is sparse on the trunk, except the buttocks. The rash first develops as small red or pink macula-like lesions, which rapidly grow in size and fuse to form large erythematous patches of irregular shape. Deflorescence is characteristic, the rash elements begin to fade from the centre, gradually becoming cyanotic, violet, and greyish. The margins of the patches retain their bright colour, and become annular or garland-like in appearance. Fresh elements are found along with old ones. The rash persists for six to ten days, and then disappears leaving an indistinct 'marbled' pattern on the skin. There is no desquamation. The eruption is accompanied with a slight rise in temperature; but the latter sometimes remains normal throughout the disease. Mild hyperaemia of the fauces is occasionally seen. There are no marked constitutional symptoms. Blood findings are eosinophilia, normal leucocyte count, and sometimes leucopenia.
*Sixth Disease (Exanthema Subitum Seu Criticum)*

Exanthema subitum is characterized by a sudden rise of temperature up to 39-40C (which falls critically on the fourth day), followed immediately, or in a few hours, by an outbreak of micromacular pale pink rash, which first invades the trunk, most often the back, and later spreads to the abdomen, chest and extremities; it is very sparse or absent on the face. After two or three days the rash fades leaving no pigmentation. Symptoms of meningoencephalitis and serous meningitis with a benign course are sometimes observed in a febrile period, in severe cases, but the general condition of most patients is undisturbed. Blood findings are leucopenia, marked relative lytnphocytosis, and a 'stab' shift of neutrophils to the left.
104
*EPSTEIN-BARR VIRUS*
Infectious mononucleosis is the best-known clinical syndrome caused by Epstein-Barr virus (EBV). It is characterized by systemic somatic complaints consisting primarily of fatigue, malaise, fever, sore throat, and generalized lymphadenopathy. Originally described as glandular fever, it derives its name from the mononuclear lymphocytosis with atypical-appearing lymphocytes that accompany the illness. Other less common infections may cause infectious mononucleosislike illnesses. ETIOLOGY. EBV, a member of the Herpesviridae, causes more than 90% of infectious mononucleosis cases. Approximately 510% of infectious mononucleosislike illnesses are caused by primary infection with cytomegalovirus, Toxoplasma gondii, adenovirus, viral hepatitis, human immunodeficiency virus (HIV), and possibly rubella virus. In the majority of EBVnegative infectious mononucleosislike illnesses, the exact cause remains unknown. EPIDEMIOLOGY The epidemiology of infectious mononucleosis is related to the epidemiology and age of acquisition of EBV infection. EBV infects up to 95% of the world's population. It is transmitted in oral secretions by close contact such as kissing or exchange of saliva from child to child, such as occurs between children in out-of-home child care. Nonintimate contact, environmental sources, or fomites do not contribute to spread of EBV. EBV is shed in oral secretions for 6 mo or longer after acute infection and then intermittently for life. Healthy individuals with serologic evidence of past EBV infection excrete virus 1020% of the time. Immunosuppression may permit reactivation of latent EBV; approximately 60% of seropositive, immunosuppressed patients shed the virus. EBV is also found in the genital tract of women and may possibly be spread by sexual contact. Infection with EBV in developing countries and among socioeconomically disadvantaged populations of developed countries usually occurs during infancy and early childhood. In central Africa, almost all children are infected by 3 yr of age. Primary infection with EBV during childhood is usually inapparent or indistinguishable from other childhood infections; the clinical syndrome of infectious mononucleosis is practically unknown in undeveloped regions of the world. Among more affluent populations in industrialized countries, infection during childhood is still most common, but approximately one third of cases occur during adolescence and young adulthood. Primary EBV infection in adolescents and adults is manifest in 50% or more of cases by the classic triad of fatigue, pharyngitis, and generalized lymphadenopathy, which constitute the major clinical manifestations of infectious mononucleosis. This syndrome may be seen at all ages but is rarely apparent in children younger than 4 yr, when most EBV infections are asymptomatic, or in adults older than 40 yr, when most individuals have already been infected by EBV. The true incidence of the syndrome of infectious mononucleosis is unknown but is estimated to occur in 2070 of 100,000 persons per year; in young adults the incidence rises to about 1 in 1,000 persons per year. The prevalence of serologic evidence of past EBV infection increases with age; almost all adults in the United States are seropositive. PATHOGENESIS After acquisition in the oral cavity, EBV initially infects oral epithelial cells; this may contribute to the symptoms of pharyngitis. After intracellular viral replication and cell lysis with release of new virions, virus spreads to contiguous 105
Pediatrics Infection structures such as the salivary glands with eventual viremia and infection of B lymphocytes in the peripheral blood and the entire lymphoreticular system including the liver and spleen. The atypical lymphocytes that are characteristic of infectious mononucleosis are CD8+ T lymphocytes, which exhibit both suppressor and cytotoxic functions that develop in response to the infected B lymphocytes. This relative as well as absolute increase in CD8+ lymphocytes results in a transient reversal of the normal 2:1 CD4+/CD8+ (helper-suppressor) T-lymphocyte ratio. Many of the clinical manifestations of infectious mononucleosis may result, at least in part, from the host immune response, which is effective in reducing the number of EBV-infected B lymphocytes to less than one per 106 of circulating B lymphocytes. Epithelial cells of the uterine cervix may become infected by sexual transmission of the virus, although neither local symptoms nor infectious mononucleosis have been described following sexual transmission. EBV, like the other herpesviruses, establishes lifelong latent infection after the primary illness. The latent virus is carried in oropharyngeal epithelial cells and systemic B lymphocytes as multiple episomes in the nucleus. The viral episomes replicate with cell division and are distributed to both daughter cells. Viral integration into the cell genome is not typical. Only a few viral proteins, including the EBV-determined nuclear antigens (EBNA), are produced during latency. These proteins are important in maintaining the viral episome during the latent state. Progression to viral replication begins with production of EBV early antigens (EA), proceeds to viral DNA replication, followed by production of viral capsid antigen (VCA), and culminates in cell death and release of mature virions. Reactivation with viral replication occurs at a low rate in populations of latently infected cells and is responsible for intermittent viral shedding in oropharyngeal secretions of infected individuals. Reactivation is apparently asymptomatic and not recognized to be accompanied by distinctive clinical symptoms. Oncogenesis. EBV was the first human virus to be associated with malignancy and, therefore, was the first virus to be identified as a human tumor virus. EBV infection may result in a spectrum of proliferative disorders ranging from selflimited, usually benign disease such as infectious mononucleosis to aggressive, nonmalignant proliferations such as the virus-associated hemophagocytic syndrome to lymphoid and epithelial cell malignancies. Benign EBV-associated proliferations include oral, hairy leukoplakia, primarily in adults with the acquired immunodeficiency syndrome (AIDS), and lymphoid interstitial pneumonitis, primarily in children with AIDS. Malignant EBV-associated proliferations include nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin disease, and lymphoproliferative disorders and leiomyosarcoma in immunodeficient states including AIDS. Nasopharyngeal carcinoma occurs worldwide but is 10 times more common in persons in southern China, where it is the most common malignant tumor among adult men. It is also common among whites in North Africa and Inuits in North America. All malignant cells of undifferentiated nasopharyngeal carcinoma contain a high copy number of EBV episomes. Undifferentiated and partially differentiated, nonkeratinizing nasopharyngeal carcinomas have diagnostic and prognostic antibodies to EBV antigens. High levels of immunoglobulin (Ig) A antibody to EA and VCA may be detected in asymptomatic individuals and can be used to follow response to tumor therapy. Cells of well-differentiated, keratinizing nasopharyngeal carcinoma contain a low or zero copy number of EBV genomes and have EBV serologic patterns similar to those of the general population. Endemic (African) Burkitt lymphoma, often found in the jaw, is the most common childhood cancer in equatorial East Africa and New Guinea. The median age of onset is 5 yr. These regions are holoendemic for Plasmodium falciparum malaria and have a high rate of EBV infection early in life. The constant malarial exposure acts as a B-lymphocyte mitogen that contributes to the polyclonal B-lymphocyte proliferation with EBV infection. It also impairs the Tlymphocyte control of EBV-infected B lymphocytes. Approximately 98% of cases of endemic Burkitt lymphoma contain 106
Pediatrics Infection the EBV genome compared with only 20% of nonendemic (sporadic or American) Burkitt lymphoma cases. Individuals with Burkitt lymphoma have unusually and characteristically high levels of antibody to VCA and EA that correlate with the risk of developing tumor. All cases of Burkitt lymphoma, including those that are EBV negative, are monoclonal and demonstrate chromosomal translocation of the c-myc proto-oncogene to the constant region of the immunoglobulin heavy-chain locus, t(8;14), to the kappa constant light-chain locus, t(2;8), or to the lambda constant light-chain locus, t(8;22). This results in the deregulation and constitutive transcription of the c-myc gene with overproduction of a normal c-myc product that autosuppresses c-myc production on the untranslocated chromosome. The incidence of Hodgkin disease peaks in childhood in developing countries and in young adulthood in developed countries. Levels of EBV antibodies are consistently elevated preceding development of Hodgkin disease; only a small minority of patients are seronegative for EBV. Infection with EBV appears to increase the risk of Hodgkin disease by a factor of two to four. EBV is associated with more than one half of cases of mixed-cellularity Hodgkin disease and approximately one quarter of cases of the nodular sclerosing subtype and is rarely associated with lymphocytepredominant Hodgkin disease. Immunohistochemical studies have localized EBV to the Reed-Sternberg cells and their variants, the pathognomonic malignant cells of Hodgkin disease. Failure to control EBV infection may result from host immunologic deficits. The prototype is the X-linked lymphoproliferative syndrome (Duncan syndrome), an X chromosomelinked recessive disorder of the immune system associated with severe, persistent, and sometimes fatal EBV infection. Approximately two thirds of these male patients die of disseminated and fulminating lymphoproliferation involving multiple organs at the time of primary EBV infection. Surviving patients acquire hypogammaglobulinemia, B-cell lymphoma, or both. Most patients die by 10 yr. A number of other congenital and acquired immunodeficiency syndromes are associated with an increased incidence of EBV-associated B-lymphocyte lymphoma, particularly central nervous system lymphoma. The incidence of lymphoproliferative syndromes parallels the degree of immunosuppression. A decline in T-cell function evidently permits EBV to escape from immune surveillance. Congenital immunodeficiencies predisposing to EBV-associated lymphoproliferations include the X-linked lymphoproliferative syndrome, common-variable immunodeficiency, ataxiatelangiectasia, Wiskott-Aldrich syndrome, and Chdiak-Higashi syndrome. Individuals with acquired immunodeficiencies resulting from anticancer chemotherapy, immunosuppression after solid organ or bone marrow transplantation, or HIV infection have a significantly increased risk of EBV-associated lymphoproliferations. The lymphomas may be focal or diffuse, and they are usually histologically polyclonal but may become monoclonal. Their growth is not reversed on cessation of immunosuppression. EBV has been linked with a multitude of other tumors; the strongest association of EBV is to primary central nervous system lymphoma and carcinoma of the salivary glands. Other tumors include T-lymphocyte lymphoma, lethal midline granuloma (a T-cell lymphoma), angioimmunoblastic lymphadenopathylike lymphoma, thymomas and thymic carcinomas derived from thymic epithelial cells, supraglottic laryngeal carcinomas, lymphoepithelial tumors of the respiratory tract and gastrointestinal tract, leiomyosarcoma, and gastric adenocarcinoma. The precise contribution of EBV to these various malignancies is not well defined. CLINICAL MANIFESTATIONS.
107
Pediatrics Infection The incubation period of infectious mononucleosis in adolescents is 3050 days. In children it may be shorter. The majority of cases of primary EBV infection in infants and young children are clinically silent. In older patients, the onset of illness is usually insidious and vague. Patients may complain of malaise, fatigue, fever, headache, sore throat, nausea, abdominal pain, and myalgia. This prodromal period may last 12 wk. The complaints of sore throat and fever gradually increase until patients seek medical care. Splenic enlargement may be rapid enough to cause left upper quadrant abdominal discomfort and tenderness, which may be the presenting complaint. The physical examination is characterized by generalized lymphadenopathy (90% of cases), splenomegaly (50% of cases), and hepatomegaly (10% of cases). Lymphadenopathy occurs most commonly in the anterior and posterior cervical nodes, and submandibular lymph nodes and less commonly in the axillary and inguinal lymph nodes. Epitrochlear lymphadenopathy is particularly suggestive of infectious mononucleosis. Symptomatic hepatitis or jaundice is uncommon. Splenomegaly to 23 cm below the costal margin is typical; massive enlargement is uncommon. The sore throat is often accompanied by moderate to severe pharyngitis with marked tonsillar enlargement, occasionally with exudates. Petechiae at the junction of the hard and soft palate are frequently seen. The pharyngitis resembles that caused by streptococcal infection. Other clinical findings may include rashes and edema of the eyelids. Rashes are usually maculopapular and have been reported in 315% of patients. Eighty per cent of patients with infectious mononucleosis will experience a rash if treated with ampicillin or amoxicillin; the reason for this phenomenon is unknown. COMPLICATIONS Very few patients with infectious mononucleosis experience complications. The most feared complication is splenic rupture, which occurs most frequently during the 2nd week of the disease. A 0.2% rate has been reported in adults; the rate in children is unknown but is probably much lower. Rupture is commonly related to trauma, which often may be mild. Swelling of the tonsils and oropharyngeal lymphoid tissue may be substantial and cause airway impairment manifest by stridor and interference with breathing. Airway impairment may be treated by administration of corticosteroids; respiratory distress with incipient or actual airway occlusion should be managed by maintaining the airway with intubation in an intensive care setting. Many uncommon and unusual conditions have been reported to be associated with EBV infectious mononucleosis. Neurologic involvement may be serious with ataxia and seizures. Perceptual distortions of space and size, referred to as the Alice in Wonderland syndrome, may be a presenting symptom. There may be meningitis with nuchal rigidity and mononuclear cells in the cerebrospinal fluid, facial nerve palsy, transverse myelitis, and encephalitis. Guillain-Barr syndrome or Reye syndrome may follow acute illness. Hemolytic anemia, often with a positive Coombs test and with cold agglutinins specific for red cell antigen i, may occur late in the illness. Aplastic anemia is a rare complication that usually presents 1 mo after the onset of illness. The prognosis for eventual recovery is good, although substantial supportive treatment is necessary during the acute stages. Myocarditis or interstitial pneumonia may occur, both resolving in 34 wk. Other rare complications include pancreatitis, parotitis, and orchitis. DIAGNOSIS The diagnosis of infectious mononucleosis implies primary EBV infection. A presumptive diagnosis may be made by the presence of typical clinical symptoms with atypical lymphocytosis in the peripheral blood. The diagnosis is confirmed by serologic testing. 108
Pediatrics Infection Differential Diagnosis. Infectious mononucleosislike illnesses may be caused by primary infection with cytomegalovirus, T. gondii, adenovirus, viral hepatitis, HIV, or possibly rubella virus. Cytomegalovirus infection is a particularly common cause in adults. Streptococcal pharyngitis may cause sore throat and cervical lymphadenopathy indistinguishable from that of infectious mononucleosis but is not associated with hepatosplenomegaly. Approximately 5% of cases of EBVassociated infectious mononucleosis have positive throat cultures for group A b{beta}-hemolytic streptococci; this represents pharyngeal streptococcal carriage. Failure of a patient with streptococcal pharyngitis to improve within 48 72 hr should evoke suspicion of infectious mononucleosis. The most serious problem in the diagnosis of acute illness arises in the occasional patients with low white cell counts, moderate thrombocytopenia, and even hemolytic anemia. In these patients, bone marrow examination and hematologic consultation are warranted to exclude the possibility of leukemia. Routine Laboratory Tests. In more than 90% of cases, there is leukocytosis of 10,00020,000 cells/mm3, of which at least two thirds are lymphocytes; atypical lymphocytes usually account for 2040% of the total number. The atypical cells are mature T lymphocytes that have been antigenically activated. Compared with regular lymphocytes microscopically, atypical lymphocytes are larger overall, with larger, eccentrically placed indented and folded nuclei with a lower nuclearcytoplasm ratio. Although atypical lymphocytosis may be seen with many of the infections usually causing lymphocytosis, the highest degree of atypical lymphocytes is classically seen with EBV infection. Other syndromes associated with atypical lymphocytosis include acquired cytomegalovirus infection (as contrasted to congenital cytomegalovirus infection), toxoplasmosis, viral hepatitis, rubella, roseola, mumps, tuberculosis, typhoid, mycoplasma infection, malaria, as well as some drug reactions. Mild thrombocytopenia to 50,000200,000 platelets/mm3 occurs in more than 50% of patients, but only rarely are values low enough to cause purpura. Mild elevation of hepatic transaminases occurs in approximately 50% of uncomplicated cases but is usually asymptomatic without jaundice. Heterophile Antibody Test. Heterophile antibodies agglutinate cells from species different from those in the source serum. The transient heterophile antibodies seen in infectious mononucleosis, also known as Paul-Bunnell antibodies, are IgM antibodies detected by the Paul-BunnellDavidsohn test for sheep red cell agglutination. The heterophile antibodies of infectious mononucleosis agglutinate sheep or, for greater sensitivity, horse red cells but not guinea pig kidney cells. This adsorption property differentiates this response from the heterophile response found in patients with serum sickness, rheumatic diseases, and some normal individuals. Titers greater than 1:28 or 1:40 (depending on the dilution system used) after absorption with guinea pig cells are considered positive. The sheep red cell agglutination test is likely to be positive for several months after infectious mononucleosis; the horse red cell agglutination test may be positive for as long as 2 yr. The most widely used method is the qualitative, rapid slide test using horse erythrocytes. It detects heterophile antibody in 90% of cases of EBV-associated infectious mononucleosis in older children and adults but in only up to 50% of cases in children younger than 4 yr because they typically develop a lower titer. Approximately 510% of cases of infectious mononucleosis are not caused by EBV and are not uniformly associated with a heterophile antibody response. The false-positive rate is less than 10%, usually resulting from erroneous interpretation. If the heterophile test is negative and an EBV infection is suspected, EBVspecific antibody testing is indicated. Specific EBV Antibodies. EBV-specific antibody testing is useful to confirm acute EBV infection, especially in heterophilenegative cases, or to confirm past infection and determine susceptibility to future infection. Several distinct EBV antigen systems have been characterized for diagnostic purposes. summarizes serologic responses that are expected in various situations. The EBNA, EA, and VCA antigen systems are most useful for diagnostic purposes. The acute phase of 109
Pediatrics Infection infectious mononucleosis is characterized by rapid IgM and IgG antibody responses to VCA in all cases and an IgG response to EA in most cases. The IgM response to VCA is transient but can be detected for at least 4 wk and occasionally up to 3 mo. The laboratory must take steps to remove rheumatoid factor, which may cause a false-positive IgM VCA result. The IgG response to VCA usually peaks late in the acute phase, declines slightly over the next several weeks to months, and then persists at a relatively stable level for life. Anti-EA antibodies are usually detectable for several months but may persist or be detected intermittently at low levels for many years. Antibodies to the diffuse-staining component of EA, EA-D, are found transiently in 80% of patients during the acute phase of infectious mononucleosis and reach high titers in patients with nasopharyngeal carcinoma. Antibodies to the cytoplasmic-restricted component of EA, EA-R, emerge transiently in the convalescence from infectious mononucleosis and often attain high titers in patients with EBV-associated Burkitt lymphoma, which in the terminal stage of the disease may be exceeded by antibodies to EA-D. High levels of antibodies to EA-D or EA-R may be found also in immunocompromised patients with persistent EBV infections and active EBV replication. Anti-EBNA antibodies are the last to develop in infectious mononucleosis and gradually appear 34 mo after the onset of illness and remain at low levels for life. Absence of anti-EBNA when other antibodies are present implies recent infection, while the presence of anti-EBNA implies infection occurring more than 34 mo previously. The wide range of individual antibody responses and the various laboratory methods used can occasionally make interpretation of an antibody profile difficult. The detection of IgM antibody to VCA is the most valuable and specific serologic test for the diagnosis of acute EBV infection and is generally sufficient to confirm the diagnosis. TREATMENT. There is no specific treatment for infectious mononucleosis. Therapy with high doses of intravenous acyclovir decreases viral replication and oropharyngeal shedding during the period of administration but does not affect the severity of symptoms or the eventual clinical course. Rest and symptomatic therapy are the mainstays of management. Bed rest is necessary only when the patient has debilitating fatigue. As soon as there is definite symptomatic improvement, the patient should be allowed to begin resuming normal activities. Because blunt abdominal trauma may predispose patients to splenic rupture, it is customary and prudent to advise withdrawal from contact sports and strenuous athletic activities during the first 23 wk of illness or while splenomegaly is present. Short courses of corticosteroids (less than 2 wk) may be helpful for complications of infectious mononucleosis, but their use has not been evaluated critically. Some appropriate indications include incipient airway obstruction, thrombocytopenia with hemorrhaging, autoimmune hemolytic anemia, and seizures and meningitis. A recommended dosage is prednisone 1 mg/kg/24 hr (maximum 60 mg/24 hr) or equivalent for 7 days and tapered over another 7 days. There are no controlled data to show efficacy of corticosteroids in any of these conditions. In view of the potential and unknown hazards of immunosuppression for a virus infection with oncogenic complications, corticosteroids should not be used in usual cases of infectious mononucleosis. PROGNOSIS. The prognosis for complete recovery is excellent if no complications ensue during the acute illness. The major symptoms typically last 24 wk followed by gradual recovery. Second attacks of infectious mononucleosis caused by EBV have not been documented. Fatigue, malaise, and some disability that may wax and wane for several weeks to a few months are common complaints even in otherwise unremarkable cases. Occasional persistence of fatigue for a few years after 110
Pediatrics Infection infectious mononucleosis is well recognized. At present, there is no specific evidence linking EBV infection to chronic fatigue syndrome.
111
*Diphtheria*
The causative agent of diphtheria is Corynebacterium diphtheriae discovered in 1883-4 by Klebs and Loeffler The bacillus produces an exotoxin during growth that is the principal factor in its virulence. The toxin is accumulated by inoculation of liquid nutrient media with the diphtheria microbe The disease is caused only by toxigenic strains of diphtheria bacillus. Avirulent strains are non-pathogenic. Three biological types of diphtheria bacilli (gravis, mitis, and intermedius) are distinguished according to the character of their growth on slanted agar media with potassium tellurite, and according to certain biochemical features EPIDEMIOLOGY Diphtheria incidence has drastically decreased (hundreds of times) during the past three decades due to active immunization of children on a mass scale. The occurrence of the diseaseis now actually sporadic. Hence the changes in its epidemiology. The source of infection in diphtheria is a patient or a carrier of virulent strains of Corynebacterium diphtheriae. A patient may prove to be contagious from the last days of the incubation period, and remains so throughout the whole course of the disease, even after the-disappearance of all its clinical manifestations. Of great epidemic danger are patients with atypical forms and healthy carriers. The principal mechanism of infection is aerial-droplet. The mucous membranes of the fauces, nose, and upper respiratory passages are the portal of entry of diphtheria. Less frequent is invasion through the eye conjunctiva, the mucous membranes of the external genitalia, or damaged skin. But the disease develops only when the infected subject is susceptible. Unsusceptibility depends on the presence of diphtheria antitoxin in the organism and on the state of nonspecific protective mechanisms. PATHOLOGICAL ANATOMY Diphtheria bacilli invading the human organism settle in the portal of entry (on the mucous membranes of the fauces, nose, or respiratory passages), where they find favourable conditions for multiplication and production of toxin. The most harmful factor in the interaction between the Klebs-Loeffler bacillus and the macro-organism is diphtheria toxin. A pathomorphological sign of the interaction between the macro-and the micro-organism is fibrinous inflammation in the portal of entry, which occurs as coagulated necrosis of the epithelium and also dilatation and congestion of the blood vessels 112
Pediatrics Infection of the mucous membranes. Fluid exudate containing fibrinogen is extravasated as a result of the increased porosity of the vascular wall; and the fibrinogen, under the effect of thrombokinase released through necrosis of the cells, forms a clot on coming into contact with the necrotic tissue, and is transformed into a fibrin network. In that way a fibrinous membrane is formed. When the pathological process develops in a mucous membrane lined with single-layer columnar epithelium forms croupous inflammation. When the pathological process develops in a mucous membrane lined stratified squamous epithelium, not only the epithelium, but also the connective tissue (tunica propria mucosae) forms diphtheritic inflammation. The regional lymph nodes are usually also involved. The diphtheria toxin affects the nervous and cardiovascular systems and the adrenal glands and kidneys. The most important protective reaction of the organism in response to diphtheria toxin is the production of antitoxin. This immune reaction, taken with other protective mechanisms, ensures elimination of toxemia and the development of postinfectious specific immunity. CLINICAL PICTURE The incubation period of diphtheria is from two to ten days. Depending on the localization of the pathological process and its severity, there is a great variety of clinical forms of the disease: diphtheria of the fauces, nose, larynx, trachea and bronchi, eyes, external genitalia, skin, etc., is distinguished according to its localization. Each of its clinical forms can be divided according to the severity of its course. Simultaneous affection of the fauces and nose, or of the fauces and larynx, is not infrequent. These forms are known as combined. Faucial Diphtheria Diphtheria of the fauces is the most common form of the disease; it used to occur in 40 to 70 per cent of cases but now accounts for 85 to 90 per cent. Three principal forms are distinguished: a) localized faucial diphtheria with membranous films coating the tonsils only; b) a diffuse form1 with the membrane spreading beyond the tonsils to the palatine arches, uvula, and throat; and c) a toxic form characterized by extensive lesions in the fauces, a marked reaction in the regional lymph nodes with toxic oedema of the tissues of the neck, and marked general toxaemia. Each clinical form can be divided into several subtypes according to their severity; one of these, of a localized nature, is known as insular because the diphtheritic membrane on the tonsils resembles separate islands, dots, or bands. Many authors distinguish a catarrhal form (without membrane). Subtoxic diphtheria is a subtype that is a kind of transition between the 113
Pediatrics Infection diffuse and toxic forms. Variants of toxic diphtheria with a particularly malignant coursehypertoxic and haemorrhagic should be distinguished. The localized form of faucial diphtheria is the most common. Its onset is characterized by general malaise, loss of appetite, headache and a moderate rise in temperature. Slight pain on swallowing is usually noted. These phenomena are often mild, and there may be no pain in the throat at all. On examination of the fauces a mild or moderate hyperaemia of the mucous membrane of the tonsils, palatine arches, and uvula is usually seen on the first day, more rarely on the second. The tonsils are enlarged and covered with a typical film, which has the appearance of a superimposition with smooth or wavy surface, with well-defined edges, as if it were creeping over the adjacent mucosa. The membrane may be white, yellowish-white, or greyish-white in colour; it adheres closely to the underlying tissues, and cannot be separated with a swab. At the same time the regional lymph nodes enlarge moderately; on palpation they are hard, with well-defined borders, and slightly or moderately tender. The insular form is characterized by the appearance on the tonsils (and sometimes on the mucous membrane of the palatine arches and uvula) of closely adherent films looking like white or greyish-white patches or spots. The catarrhal form shows only as a moderate enlargement of the tonsils, moderate or mild hyperaemia of the fauces, and slightly elevated temperature. It can only be diagnosed by bacteriological examination. The diffuse form of faucial diphtheria, which is sometimes heralded by vomiting, is characterized the characteristic membrane covers not only the swollen tonsils but also, to a greater or less extent, the mucous membrane of the palatine arches, the uvula, and sometimes the whole of the soft palate and the walls of the throat, more pronounced general malaise, lassitude, weakness, anorexia, headache, and disturbed sleep. The temperature rises to 38-39C. The toxic form of faucial diphtheria usually begins suddenly, the temperature rapidly rises to 39-40C, tlie patient turns pale sharply, and there are headache, general malaise, marked lassitude, sleep-lessness, anorexia and, at times, vomiting and abdominal pain. Excitation, but more commonly, marked apathy and adynamia develop. The mucous membrane of the soft palate and pharynx is ocdematous and slightly liyperaemic. Tlie tonsils are covered witli a thick uneven membrane of a dirty white or brownisli-groy colour that extends to soft palate and even to I lie hard (Plato II). Tlie patirul'a face is pale, the tonsue is coaled, while or brownish. The lips are parched. An unplca.sant odour is smelt w-lien examining tin'fauces, described as foetid-sweetish or sweet ishpulrid. The process often spreads to lilt' nasopliarynx and nasal cavity. Quite characteristic changes appear in the superior cervical lymph nodes and the soft tissues around them. A painful infiltrate of a dense consistency and blurred outline is found in the area of the lympli nodes, wliile there is inore or less extensive oedema of the soft, tissues above and around, the al'tected nodes (sub-cnlaneous cellular tissue). The skin over the oedumatous tissue remains of a normal colour. Pressure on the area is painless and does not leave pits and when the tissue is 114
Pediatrics Infection percussed with the linger it shakes like a jelly. The oedema is usually bilateral occupying the whole submaxillary area; it can spread upward over the edge of the lower jaw to the cheeks, and backward and downward to the clavicle or lower, to the nipples, and even to the xyphoid process. Its intensity in the subcutaneous tissue depends on the degree of toxaemia, and it is therefore taken as the basis for the following classification of toxic diphtheria into three degrees: Degree Extent of oedema I to the middle of the neck II III to the clavicles below the clavicles
The subtoxic form of faucial diphtheria is manifested by less marked characteristic signs of toxic diphtheria: the oedema of the faucial mucosa is less pronounced and the false membrane less extensive, oedema of the tissues of the neck is usually seen only in the direct vicinity of the affected regional lymph nodes, and as a rule is unilateral. The other varieties of toxic faucial diphtheria are distinguished by a particularly malignant course. In the hypertoxic form, apart from the rapidly developing local process characteristic of toxic diphtheria, there is grave toxaemia with a catastrophically progressing fall in cardiovascular activity. The patient usually dies within the first five days of the disease. The haemorrhagic form has a symptom complex of second or third degree toxic diphtheria combined with haemorrhagic diathesis. The affected mucosa tends to bleed, and copious bleeding from th& nose and haemorrhages into the skin are frequent. There is marked thrombopenia and increased blood coagulation time. The skin is pale or greyish and there is a rapidly progressing cardiovascular failure. This form has a very high death rate. Laryngeal Diphtheria or Diphtheritic Croup It is still often encountered in young children (between a year and three or four years of age. Laryngeal diphtheria begins with a rise in temperature and general malaise. Hoarseness quickly develops and is followed by complete aphonia. Cough appears simultaneously, at first dry, hard and 'barking', but as dysphonia develops it loses its resonant quality and becomes hoarse. The initial stage of the disease, characterized by these symptoms, is called dysphonic or catarrhal. It lasts on average about 24 hours, but is sometimes as short as a few hours or may be prolonged to two, or even three or four, days. When stenosis of the upper respiratory passages supervenes, the disease passes into its second or stenotic stage. The first and earliest symptom of stenosis is a characteristic stenotic respiratory stridor, The second symptom of stenosis is retraction during inspiration of the yielding parts of the chest The third symptom of stenosis is tension in the auxiliary respiratory muscles. 115
Pediatrics Infection At this stage there are already brief attacks of progressive respiratory obstruction, accompanied witli marked restlessness in Hie child. The fits of coughing and emotional strain aggravate the stenosis. Laryngoscopic examination sliows the presence of a membrane on tlie mucosa of the larynge.il vestibule, and the false and true cords, and in the area of arytenoid cartilages. Membrane is also sometimes visible in the subglottic space. Gaseous excliange is disturbed, owing to the progressing difficulty in breathing and fatigue. Development of the third, asphyxial stage of croup is marked above all by child's fretfulness. He is restless, tosses about, sits up and then lies down again, asks to be picked up, or to be potted. His skin is clammy with sweat, and his lips, face, and limbs become cyanotic. The pulse becomes paradoxical at the beginning of this stage. We distinguish rapidly progressing and slowly progressing croup according to the rate of development and succession of stages. Descending (diffuse) diphtheritic croup takes a particularly grave course. The rapid rise of disturbances of gaseous exchange is usually expressed not in cyanosis, but in marked pallor of the skin (white asphyxia). In the majority of cases death occurs in the second or third day. Rare Clinical Forms of Diphtheria are Nasal Diphtheria, Conjunctival diphtheria, Diphtheria of the external genitalia, Diphtheria of the skin and wounds. Nasal diphtheria occurs with faucial diphtheria (mixed form). These forms can be typical (membranous) and atypical (catarrhal).
COMPLICATIONS Complications associated with specific toxaemia are distinctive of diphtheria, viz. cardiovascular disturbances, neuritis and polyneuritis, and nephrosis. Their incidence directly depends on the clinical form of the disease, but they mainly occur in toxic diphtheria, particularly of the second and third degree. The number of toxic complications also depends directly on the time the treatment, particularly antitoxin therapy, is begun; the earlier it is started, the less the incidence of complications. Complications in the cardiovascular system. Early and late cardiovascular disturbances are distinguished. Early circulatory disturbances develop during the first days of the disease. Late cardiovascular disturbances arise at the end of the first or during the second or third week, in association with development of the myocarditis that often complicates severe toxic diphtheria and that is always present in the haemorrhagic form. There are unfavorable sings of diphtheritic myocarditis by Molchanov gallop rhythm, abdominal pains and vomiting. 116
Pediatrics Infection Complications affecting the nervous system. A typical complication of diphtheria is peripheral paralysis, a manifestation of toxic lesions of the peripheral nerves (mononeuritis, polyneuritis, polyradiculoneuritis). Early and late diphtheritic paralyses are distinguished. Early paralysis (paralysis of the soft palate, paralysis of accommodation, facial paralysis), which occurs almost exclusively in the toxic form, begins from the second week of the disease, and most often has a course like mononeuritis, usually affecting the third, sixth, seventh, ninth, and tenth cranial nerves. Speech becomes nasal, and fluids tend to flow out through the nose. The soft palate is flaccid and immobile during phonation; in unilateral paralysis it is asymmetric with deviation of the uvula to-one side. Paralysis of the soft palate lasts on average from two to four weeks, but may go on for six weeks. The forms presenting the greatest danger are paralysis and paresis of the laryngeal muscles, respiratory intercostal muscles, the diaphragm, and those resulting from lesions to the innervation mechanism of the heart (n. vagus). Renal complications - toxic nephrosis (Proteinuria and a slight cylindruria).
Pneumonia is a common complication of diphtheritic croup. DIAGNOSIS Thorough clinical examination, case history, bacteriological tests are most important for early diagnosis. The morphological properties of the isolated microbe are determined in 24 hours and the laboratory can give a tentative conclusion. The final result of the investigation can be obtained in 48-72 hours after isolation of the pure microbe culture and determination of its cultural, biochemical, toxicogenic, and serological properties. The agglutination test with the patient's serum has been suggested as an aid to diagnosis. This method can be used for retrospective diagnosis. Protective titre is 1:80 and higher (0,03 AU). Differential Diagnosis Faucial diphtheria can be mistaken for follicular, lacunar, or phlegmonous angina, fusospirillar angina (SimonovskyVincent), infectious mononucleosis, angina accompanying diseases of the blood (agranulocytosis, leukaemia), etc. Follicular angina is distinguished by greyish-white or yellowish-white round, purulent follicles, translucent through the mucous membrane of the tonsils, while lacunar angina is characterized by marked, crumbly, quite easily removed films in the lacunae of enlarged and loose tonsils. Both forms have a marked temperature reaction, much pain on swallowing, bright widespread hyperaemia of the fauces, and a considerable tenderness of the regional lymph nodes. They can be mistaken for the atypical form of insular faucial diphtheria particularly common in the immunized. But in the latter form of diphtheria the patient's general condition does not suffer much, the temperature reaction is mild, there is little or no pain on swallowing, the submaxillary lymph nodes are less painful or even painless, and faucial inflammation is not marked; the diphtheritic 117
Pediatrics Infection membrane is not only localized in the follicles and lacunae, but also outside them, is rather dense and can only be removed with difficulty. Phlegmonous paratonsillitis (phlegmonous angina) is sometimes confused with toxic faucial diphtheria.. Fusospirillar angina (angina caused by 'bacilli and spirillae with tapering ends) was described by Simonovsky -Vincent. It differs from diphtheria in the unilateral affection of the tonsils and the presence of a deep ulcer with an uneven, dirty-grey or yellow necrotic floor. Bacterioscopy revealing a fusospirillar flora clears up the diagnosis. Infectious mononucleosis or mononuclear angina (Filatov's glandular fever) can easily be mistaken for faucial diphtheria. Characteristic of the first is a considerable enlargement of the posterior cervical lymph nodes, enlargement of the liver and spleen, and blood changes (mononucleosis). Differential diagnosis of diphtheritic croup. Diphtheritic croup is often confused with the laryngitis developing in young children during para-influenza, measles and other acute viral respiratory infections. These are often accompanied with rhinitis and a hard dry cough, but the voice is almost unaffected. There is a stenotic stridor and some recession of the yielding parts of the chest wall. In some cases the stenosis progresses and may become marked. Laryngoscopy reveals catarrh and sometimes oedema of the laryngeal mucous membrane, its spasm and hypersecretion. The case history often points to a foreign body in the larynx or trachea (the child was playing with some small object or eating nuts, choked, etc.). Sudden obstruction of the respiratory passages is accompanied with an attack of choking and coughing; the voice may remain loud. Laryngotra-cheobronchoscopy is of considerable assistance in diagnosis; metal is readily detected by X-rays. OUTCOME AND PROGNOSIS The outcome of diphtheria depends on the patient's age and physical condition, timely administration of-antitoxin therapy, the soundness of the treatment given, and, finally, on the severity (clinical form) of the disease. The main cause of death is myocarditis that develops in toxic forms of the disease. Lethal outcomes in diphtheric croup are quite rare nowadays. TREATMENT Regimen, Nursing Care, and Diet The main role in the treatment of diphtheria, especially in grave forms and complicated cases, is played by a proper regimen and careful nursing. Protective regimen is essential in the initial stage, especially in severe cases; maximum quiet must be ensured.. But in toxic diphtheria, even when there are no complications, patients are kept in hospital and strictly confined to bed for the following minimum periods: in subtoxic and toxic diphtheria of the first degree for 21 to 28 days; in toxic diphtheria of the second degree for 40 days; and in toxic diphtheria of the third degree for 50 days from the beginning of the disease. The complications of diphtheria like myocarditis and polyneuritis also call for prolonged absolute bed rest. 118
Pediatrics Infection A special diet is not necessary in diphtheria; only during the first days are fluids and semi-fluids prescribed, when there are marked lesions in the fauces. Control of Toxaemia 1. Treatment of diphtheria with antitoxic serum. As soon as the physician diagnoses diphtheria, be must immediately administer the serum to the child. In doubtful cases the physician can choose the expectant tactics only on the condition that the localized form of the disease can be suspected. The most important rule, therefore, is to inject antitoxin as soon as possible. The dose of antitoxin depends on the severity (clinical form) of the disease and the time lapse from its onset; the more severe the forms, and the later treatment is started, the greater the dose should be. Age is only of relative significance in determining the required dose. Serum should be given by the modified Bezredka method- 0,1 ml is first given subcutaneously. Followed by 0,2ml dose in 30 minutes, and finally the remaining dose in 60 minutes. Preliminary skin test with horse serum (deluted 1-100) are used to reveal possible hypersensitivity of the patietn. The reaction is checked in 20 minutes. TABLE 1 Average Doses of Antitoxin (in AU) in Various Forms of Diphtheria Form of diphtheria Localized faucial Diffuse faucial Subtoxic faucial Toxic faucial, 1st degree Toxic faucial, 2nd degree First single dose 10000-30000 30 000-40 000 40 000-50 000 50000-70000 60 000-80 000 Average dose (over course ot treatment) 10000- 40000 50000- 60000 60000- 80000 100 000-120 000 160000-200000 250 000-350 000 20000- 25000 3000040000- 60000
Toxic faucial, 3rd degree and hypertoxic 100 000-120000 Nasal (except for toxic) Laryngeal Descending (diffuse) croup 10000-15000 15 000-20 000 20000-30000
40000 The effect of antitoxin treatment begins to show within eight to twelve hours, or in 24 hours. In 24 to 36 hours the diphtheritic membrane begins to shrink, and disappears in most cases toward the third or fourth day. In the toxic form it takes longer, from five to seven days, and even more. 2. Infusion of rheopolyglucin and other salt solutions in combination with a 10% solution of glucose (1:1) is prescribed in toxic diphtheria. This treatment favours disintoxication. 119
Pediatrics Infection 3. Some clinicians have had success in treating toxic diphtheria with glucocorticoids (hydrocortisone, prednisolone). The course of treatment takes from seven to twelve days. The effect of countering the toxaemia is more rapid and there is reduction of the incidence of grave complications. 4.Vitamin therapy is widely employed in diphtheria, especially in its toxic forms. Nicotinic acid (Ac. nicotinicum) is widely used to treat toxic diphtheria as it improves metabolism in the tissues. Bed rest, strychnine, vitamin B6, nicotinic acid, cyanocobalamine (vitamin B12), glutamic acid, dibazol and proserine are indicated if diphtheritic paralysis supervenes. Antibacterial Therapy Antibacterial therapy is of particular value in treating the carrier; in addition, it also combats secondary cocci-flora (streptococcus, pneumococcus, etc.). Measures to Improve the Tone of the Nervous and Cardiovascular Systems Strychnine is used for toxic diphtheria. This preparation increases the tone of the nervous system and the resistance to pathogenic agents. A 1 per cent solution of adenosine triphosphoric acid (0.3-1 ml) and cocarboxylase (25-50 mg) are also recommended for 10-12 days. Treatment of Diphtheritic Croup Absolute rest must be provided; everything that can excite a child has to be avoided, and he should be entertained by toys, fairy tales, etc. to divert his attention. Thermal procedures have a sedative effect, and can diminish spasm of the laryngeal muscles reflexly. Steam inhalations (with sodium bicarbonate solution) sometimes relieve the cough and aid expectoration. Cold fresh air is effective and is widely used for treatment. The cold fresh air tranquillizes children, they usually fall asleep, and the symptoms of stenosis subside. Thermal procedures must not precede fresh air treatment. Oxygen therapy is also recommended. Hypnotics and sedatives (phenobarbital, bromural, chloralhydrate, chlorpromazine, etc.) are prescribed in the usual doses. A favourable therapeutic effect is noted with glucocorticoids; laryngeal stenosis is relieved, and the need for surgical intervention is often reduced. In croup a favourable effect is produced by aspiration of mucus and false membrane from the respiratory passages by means of a strong electric pump under control of direct laryngoscopy. The method deserves wider use, particularly in descending croup. Two surgical methods are used in diphtheritic stenosis, intubation and tracheostomy.. Tracheostomy is indicated in the presence of oedema and bleeding membrane in the fauces, laryngeal deformity, or concurrent whooping-cough with severe bouts of coughing. 120
Pediatrics Infection PROPHYLAXIS The general preventive measures in diphtheria are the same as in other children's infectious diseases. Active immunization plays the principal role. Active immunization. Immunization against diphtheria is now compulsory for all children. Adsorbed pertussis-diphtheriatetanus vaccine (APDT) and diphtheria-tetanus toxoids (ADT) are used for immunization. Three doses (of 0.5 ml) are given at intervals of 30 to 40 days in the primary immunization of babies (at three months). Children are reimmunized with the same dose (0.5 ml) 18 months. A third reimmunization is given with adsorbed diphtheria-tetanus toxoid at the age of six, than eleven, 18 and adult. Control of diphtheria carriers is the second most important antiepidemic measure. The measures to be taken in an epidemic focus are as follows. (1) As soon as diphtheria is recognized, the patient should be promptly hospitalized. Patients are discharged after recovery when two consecutive bacteriological checks, made with an interval of two days, are negative; but before they are re-admitted to a children's institution two negative supplementary checks for carrier state are required. Carriers of nonvirulent bacilli are allowed to attend children's institutions, but carriers of virulent diphtheria bacilli are not given permission to attend children's institutions where all children are immunized until 30 days after detection of their carrier state. It is decided by a commission, the epidemiologist including. (2) All children and adults who were in contact with a patient should be examined for forme fruste of diphtheria and given laboratory tests for carrier state. Children, and adults working in children's institutions, can be re-admitted to these institutions only after a negative bacteriological report and disinfection of the focus. (3) Terminal disinfection is carried out in the patient's home. (4) An epidemic focus should be placed under medical supervision for seven or eight days after the patient's isolation. Further reduction of diphtheria incidence is an important problem, which is successfully solved in many republics, regions, and large cities of the Soviet Union. Morbidity is actually reduced to sporadic cases, or it is not reported for reasons of extreme rarity.
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*Dysentery*
The causative agents are dysentery bacilli (Shigellae), small, gram-negative, non-motile rods (1 to 3 ^m in diameter) with curved ends, that grow on the usual culture media. The aetiological role of the various dysentery bacilli has not always been the same in different geographical conditions and in various historical periods. Sonne dysentery prevails in the European part of the USSR as well as in most countries of Europe during recent years, while Flexner's shigellae still prevail in Ukraine and Republics of Central Asia. Toxic properties are most pronounced in Grigoryev-Shiga bacillus, which produces an exotoxin, unlike other representatives of the dysentery group which elaborate an endotoxin. At the present time the dysentery bacteria are resistant to many antibiotics; polyresistant strains are widely spread. Their resistance to direct sunlight, desiccation, high temperatures, and disinfectants is low, but in favourable conditions (darkness, moderate temperature, humidity, etc.) they can remain viable for quite long periods: viz. in soil up to three months; on damp bedding, bedpans, and eating utensils for weeks, and even months; on items of food for many days; and in water for five to nine days. Sonne bacteria are relatively highly stable to the environmental factors and this accounts for their transmission with foods. The prevalence of Sonne shigellae can probably be explained by this fact. EPIDEMIOLOGY The source of infection is the dysentery patient or carrier. The patient becomes contagious from the very first day of illness, excreting the causative agent in the faeces in enormous amounts. Clinical recovery is not always accompanied with complete release from the bacillus, so that the patient often becomes a carrier. Patients suffering from a chronic
form of dysentery who harbour the bacillus for long periods are very dangerous epidemiologically. No less dangerous are formes frustes and atypical forms. The mechanism of transmission of infection is complicated. The cardinal role is played by the hands of the patient (or carrier) and of the healthy person to whom the infection is conveyed. Dysentery has therefore been called 'the disease of dirty hands'. Water-borne infection is less common than in other intestinal infections (like cholera and typhoid fever). Dysentery, especially Sonne dysentery, is transmitted with food (milk, dairy products, cold dishes, etc.). Outbreaks of the diseases resembling toxicoinfections can arise. Susceptibility to dysentery is very high, particularly in infants. Children under six months of age are affected relatively seldom. 122
Pediatrics Infection The role of the natural factor is expressed in a marked seasonal prevalence of dysentery; its incidence is highest during the summer and autumn months. PATHOLOGICAL ANATOMY The most characteristic pathological changes in dysentery are in the large intestine, chiefly in its distal portion. The inflammatory process in the intestinal mucosa is due to the action of both the dysentery bacteria themselves and their endotoxins. The following forms of intestinal affection are distinguished in dysentery: catarrhal, follicular, croupous, and diphtheritic. In the catarrhal form the mucous membrane of the intestine is swollen and brightly hyperaemic in places, with areas of microhaemorrhages. In the follicular form the picture is that of the catarrhal form with inflammatory hyperplasia of the follicles followed by central necrosis and the formation of small ulcers. Fibrinous inflammation with the formation of membranes consisting of necrotic tissue and fibrin is rarely encountered now, particularly in infants. PATHOGENESIS The portal of entry of infection is the alimentary tract. Dysentery bacilli reside on the mucous membrane of the large intestine. The endotoxin is the principal factor in the pathogenically of dysentery bacilli. An organism sensitized at the beginning of the disease by the breakdown products of microbes and tissues may respond to their repeated action or concomitant superinfection by an hyperergic reaction (in the form of inflammation of the dysenteric process). The reactivity of the organism, which depends on the functional state of the central nervous system, determines the strength of its protective reactions and the severity of the course of infection. The disease may be aggravated by supervention of secondary infection and intestinal dysbacteriosis which is often the result of a prolonged and irrational treatment with antibiotics of wide spectrum. Functional changes in the vegetative nervous system as a result of toxaemia are pronounced. Circulatory disturbances are expressed in initial elevation of arterial pressure, replaced by hypotension as the toxaemia progresses. In infants the features of dysentery are a mild, local inflammatory reaction, slight primary toxaemia, and a tendency to rapid development of metabolic disturbances. CLINICAL PICTURE The character and the severity of the symptoms are much less dependent on the species of the causative agent. Thus, it is well known that severe toxic forms of the disease are more commonly caused by the Grigo-ryev-Shiga bacillus than by 123
Pediatrics Infection other representatives of the dysentery group; but they may also be caused by Flexner and Sonne bacilli. The severity and the character of the disease are chiefly determined by features peculiar to the reactivity of the patient's organism, and particularly by his age. The most convenient and widespread classification of the clinical forms of dysentery is Kaltupin classification. There are typical and atypical forms of dysentery. Typical dysentery is divided into mild, moderately severe, and severe forms, the last-named may show a prevalence either of local or of general phenomena (toxic form). Acute and chronic dysentery are distinguished. Abortive forms (atypical form), which are quite common, should be considered a variety of mild dysentery. The incubation period of dysentery is between one and seven days (mostly two or three days). The clinical picture may display symptoms in the intestinethe so-called colitie syndrome or phenomena of general toxaemia. The degree of severity and the predominance of one of these syndromes determine the form of the disease. Although there is usually a certain relative conformity between the severity of these syndromes and the other, it is not always constant. In some patients the onset of the disease is attended with symptoms of general malaise: namely, elevation of temperature, lassitude, weakness, headache, and sometimes vomiting; intestinal phenomena supervene later. But in most cases dysentery begins with the intestinal symptoms that are the leading ones in its symptom complex. Abdominal pain and frequent liquid motions are characteristic; the stool is faecal in character at first, but later much mucus and flecks of blood appear. In mild cases the frequency of defaecation is three to eight times a day; the stool remains faecal in character, but assumes a greenish hue; pathological admixtures are not copious. In abortive forms the stool is often dyspeptic in character, and is frequently without pathological admixtures. In more severe cases bowel movements are very frequent (15 to 20 times a day, and even as high as 30, 40, and more times). The stools are scanty, lose their faecal character, consist almost entirely of thick, tenacious, almost transparent, mucus, and are practically odourless. Later the mucus becomes opaque, with pus visible to the naked eye. The blood is usually either embedded in the mucus, or is irregularly mixed with it, staining it a dirty red. A leading place in the clinical picture of dysentery is taken by symptoms reflecting a spastic condition in the large intestine, namely, abdominal pain, tenesmus, spastic contraction of the sigmoid colon, etc. Abdominal pain is spasmodic in character and precedes and accompanies each bowel movement. Older children are sometimes able to localize the pain more or less precisely along the whole of the large intestine, or, more frequently, only in the left iliac region.
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Pediatrics Infection Defaecation is accompanied with painful straining tenesmus. This symptom is a manifestation of spasm in the lower part of the large intestine and anal sphincter. As severe dysentery progresses, spasm of the sphincter is replaced by paresis or paralysis, with resultant gaping of the anus. The abdomen is retracted, and its lower part is tender, particularly on the left. A painful spastic sigmoid colon is often palpable in older children. The entire colon can be indurate and painful to palpation in severe dysentery. In the mild form of dysentery the symptoms of general toxemia are slight or absent; there is a moderate fever, headache, general malaise, and loss of appetite. These symptoms are more constant and more pronounced in moderately severe dysentery. In the grave toxic form there is a characteristic picture of marked toxemia. The patient is depressed and adynamic. His face is pinched and distorted by suffering. The eyes are sunken and dull. Consciousness is usually dimmed. Sometimes there are convulsions. Temperature, high from the onset, later falls, but is sometimes subfebrile, normal, or even subnormal throughout the whole course of the illness. Tissue turgor is diminished, the skin wrinkles readily and remains so for some time. The tongue becomes dry and coated; appetite is lost; nausea and vomiting appear. Cardiovascular weakness develops, expressed in a small and frequent pulse, fall of the maximum and minimum arterial pressure, cyanosis, coldness of the limbs, and diminished cardiac sounds. Respiration is accelerated and deep ('toxaemic'). Blood findings in dysenteric toxaemia are hyperleucocytosis and neutrophilia. The great loss of fluid causes concentration of the blood expressed in elevated haemoglobin content and increased erythrocyte count. Toxaemia may be enhanced as a result of poisoning by the products of the much disturbed metabolism. The symptoms of dysentery in infants have special features. The colitic syndrome is relatively mild at this age, and is usually not fully expressed. The stool often retains its faecal character but becomes liquid and greenish in colour. Mucus is almost always present, but blood flecks occur much less frequently. In some babies there are few or no pathological admixtures in the stool, and it is dyspeptic in character. In most cases there is no tenesmus, but the baby shrieks and becomes red in the face during defaecation. Gaping of the anus is quite rare; much more frequently anal responsive-ness is observed, i.e. the anus opens as a result of paresis of the sphincter when the buttocks are parted. The abdomen is inflated. General toxaemia is especially common in infants, but corresponds in severity with the intensity of the intestinal symptoms less often than in older children._Infants are particularly prone to sharp disturbances of metabolism as a result of which poisoning by products of deranged metabolism occurs. Dysenteric toxicosis with exsiccosis symptoms develops mostly in hot climate and its course would usually be more grave. 125
Pediatrics Infection Dysentery with a protracted course (lasting longer than three months) with no distinct tendency to recovery is classed as a chronic form. It is rare now. Two varieties of chronic dysentery are distinguished; (a) continuous and (b) relapsing.
COMPLICATIONS The complications associated with the dysenteric process itself (encephalitis, neuritis, prolapse of the rectum) are seldom seen, and occur chiefly in severe forms. Complications caused by secondary infection are common in dysentery, particularly in infants (disbacteriosis, bronchopneumonia, stomatitis, gingivitis, thrush, otitis, pyodermitis, furunculosis, pyuria, nephritis, dystrophy, avitaminosis and anaemia DIAGNOSIS Positive bacteriological study of the faeces is of decisive importance. The best bacteriological results are obtained when the culture medium is inoculated with fresh faeces directly at the patient's bedside. Faecal samples containing pathological admixtures, such as mucus or pus, should be selected. Seeding is more effective when material is taken in the early stages of the disease (and before the beginning of treatment with antibiotics and sulphonamides), and when tests are repeated several times. Indirect haemagglutination test, which is carried out with the blood serum of the patient, deserves special attention. The reaction becomes positive during the first week of the disease and it is highly sensitive. Coprology, i.e. microscopic study of faeces for pathological admixtures (mucus, leucocytes, erythrocytes), is widely employed as an auxiliary method. Differential diagnosis. In its symptomatology and course dysentery closely resembles many other intestinal diseases. The differentiation is often difficult in mixed infections (concurrence with coli-infection or salmonellosis). Mild dysentery in infants under 1 should be differentiated from simple dyspepsia. It develops from overfeeding or from other negligence; its course is marked by apyrexia; stools are liquid, green, with insignificant admixtures of mucus (4-6 defaecations a day). Adherence to normal feeding rules will normally give a rapid positive effect. Intestinal infection caused by pathogenic serological types of group I escherichiae is characterized by the absence of the colitic syndrome, by scanty pathological admixtures in the faeces (or their absence), and by persistent fever with a wavelike course. Diseases caused by group II escherichiae serotypes (0.124, 'Krym') are almost indistinguishable from dysentery by its clinical picture (see 'Intestinal Coli-Infection'). 126
Pediatrics Infection Salmonellosis occurring in the enterocolitic form is also difficult to differentiate from dysentery. Stool In salmonellosis is of normal faecal character, tenesmus is either weak or absent, elevated temperature persists for a long period, but it does not correspond to the pronounced intestinal symptoms. Staphylococcal enterocolitis occurring mostly in infants under 6 months is also difficult to diagnosticate. Amoebiasis is now a very rare disease in this country. It occurs sporadically in our country and republics of Central Asia. It can be mistaken for acute and chronic bacterial dysentery. The disease is characterized by a protracted feverless course, symptoms of dextralateral colitis, and specific stools (crimson-coloured jelly). Ulcers with overhanging margins are revealed by rectosig-moidoscopy. Eosinophilia is often detected in the blood. Microscopy of the faeces can reveal the presence of the causative agent, Enta moeba histolytica. An erroneous diagnosis of dysentery in infants with intestinal invagination can lead to grave results. Invagination begins abruptly at a normal temperature, and the baby becomes very restless. There is tenesmus; stool consists of mucus and blood alone without faecal matter; no gases are evacuated. Usually the abdomen is soft, and a sausage-like tumour is palpable. Invagination can sometimes be revealed by digital examination of the rectum. Scout roentgeno-graphy of the abdominal cavity can help diagnosis. TREATMENT Nursing and diet. The most important conditions for successful treatment of dysentery patients are a properly organized regimen, careful nursing, and suitable diet. Patients with doubted diagnosis are placed in diagnostic department provided with cubicles. Patients with acute symptoms of the disease and those recovering from the disease should be kept in separate rooms according to the type of the causative agent. In mild forms when the child's appetite is good and the colitic syndrome not very pronounced the normal diet for the child's age is prescribed. The best food for a baby under a year old is mother's milk, either from the breast or expressed; when that is not possible, acidophilus milk (yoghourt) should be prescribed. In toxic dysentery nursing babies are given only boiled water, salt solutions, tea. Patients suffering from hypotrophy are not to be kept on water alone for a long time. An adequate amount of fluid, namely 150 ml per kg of body weight, should be given. When vomiting is frequent, fluid must be given in small portions by spoon (one to two teaspoonfuls every five or ten minutes) or dripped from a pipette. Water diet is followed by fractional feeding with expressed breast milk (10-50 ml ten times per 24 hours, with fluid added up to the volume required for the given age. Antibiotics are important antibacterial preparations used to treat dysentery. They are most efficacious in early treatment. Laevomycetin (50 mg/kg), ampicillin trihydrate (100 mg/kg), norfloxacin, rifampicin, cefalosporins 3-4 levels
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Pediatrics Infection should be given. If the given causative agent is known to be resistant to antibiotics, the corresponding preparations should be selected. Sulpha drugs and nitrofurane (furazolidon 8-10 mg/kg a day) preparation may be given together with antibiotics. Treatment with a dysentery bacteriophage in tablets coated with an acid-proof material is indicated. Complex of urgent measures should be taken to control intoxication. The appropriate treatment should be given in the presence of neurotoxicosis and the corresponding syndromes (hyperthermic, convulsive, etc.). In the presence of exsiccosis, measures should be taken to control it with due consideration of the degree and character of dehydration. Severe toxicosis is recommended to be treated with antibiotics and hormones: short (5-7 day) courses of hydrocortisone (the initial dose, 5 mg/kg) and prednisolone (1-1.3 mg/kg per os). The hormones should be injected intramuscularly or into the vein in very grave cases. The protracted course of the disease may often be due to intestinal dysbacteriosis which in turn depends on the use of antibacterial preparations. Biological preparations such as coli-bacterin, bifidumbacterin, lactobacterin, bifilact, linex and other preparations should be used to prevent and to treat dysbacteriosis. Symptomatic therapy is essential in dysentery.
PROPHYLAXIS As with other intestinal infections, general sanitary and prophylactic measures are decisive in the control of dysentery. They consist primarily in the provision of adequate amenities in inhabited localities, namel; combating flies, proper provision of sanitary conditions and medical supervision of children in children's institutions is of paramount importance, especially in summer camps and cottages for children. The early detection and isolation of sources of infection are most important in controlling dysentery. Children treated for dysentery should not be dismissed from hospital sooner than in three days after all clinical symptoms of the disease have disappeared and after bacteriological examination of the faeces (negative result). The faeces for the analysis should be taken in two days after the suspension of the specific therapy. The dismissed persons should be followed up by the physician for three months after chronic dysentery, and for one month after acute dysentery. Disinfection is essential in combating dysentery. Prophylactic disinfection is systematically carried out in children's institutions, theatres, public toilets, etc.
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Pediatrics Infection Intestinal Coli-Infection (Colienteritis)1 The causative agent of intestinal coli-infection, or escherichiosis, are pathogenic serological types of the intestinal bacillus Escherichia coli (B. coli). Eleven groups are now differentiated by the 0 antigen, and each is, in turn, subdivided by H antigen into serological types. Each serotype is designated by the appropriate letter and given an ordinal number of the antigen. All enteropathogenic esche-richiae are divided conventionally into three groups. The first group includes the main agents causing colienteritis. Serotypes 0.111, 0.55, 0.26. The second group (enteroinvasive) includes ten serotypes, of which 0.124 and 0.151 ('Krym') occur in this country. The former has a common antigen with some shigellae, while the latter has the antigen similar to salmonellae. Serotypes of the second group cause dysentery-like escherichiosis. The proportion of these serotypes was noted to increase in the '70s. The third group (enterotoxicogenic) includes escherichiae that are not yet sufficiently well studied (serotypes 0.6, 0.15, 0.75, 0.148, etc.). These can produce a toxin similar to that produced in cholera. These escherichiae attack mostly infants under 2 to cause a cholera-like disease attended by the dehydration syndrome. Epidemiology. Children suffering from coli-infection, who excrete the bacilli in enormous numbers, not infrequently in pure culture, are the source of infection. Patients with a mild or abortive form of the infection are a major danger. Infection can also be communicated by healthy carriers and convalescents (mostly children). A baby can become infected during birth by a mother-carrier. Coliform intestinal infections are predominantly met among infants a few months old, who are most susceptible to it. Colienteritis is the prevailing form of intestinal infections in/nfants under 1 year of age. Newly born, premature, and enfeebled babies are particularly susceptible. Clinical picture. The incubation period lasts from one to twenty-two days, but mostly from three to six. The disease starts acutely, with increase of temperature, and disturbance of general condition: diarrhoea and vomiting appear. Loose, sometimes fluid, stools are passed from five to thirty times a day and over; the stool is golden yellow, orange, or greenish in colour, and occasionally has mucus. Vomiting occurs only two or three times a day, but persists for many days. Meteorism is an almost constant symptom. The colitic syndrome is absent. In grave cases, as a result of the gradually intensifying toxicosis, frequent defaecation and persistent vomiting, much water and salts are lost from the body of the patient. Pronounced exsiccosis(mostly salt-deficit type) develops (see 'Introductory Part', page 12). There is a rapid loss of weight. Constitutional symptoms progress rapidly and adynamia and sleep disorders develop. Disturbed water, mineral, and protein metabolism lead to hypoproteinaemia, and acidosis; vitamin metabolism is also markedly disturbed. Pronounced cardiovascular disturbances are not uncommon. All these symptoms are quite persistent. The temperature remains elevated for a long time and is irregular. 129
Pediatrics Infection The course of the disease and its gravity depend mostly on the age of the child, the premorbid condition, and the presence of debilitating factors. The type of the causative agent is however also important. The disease is most severe (with frequent toxicosis) if it is caused by E. coli 0.111. The agent 0.124, which is similar to the Large-Sachs dysentery bacterium, and also serotype 0.151 ('Krym') affect also older children and adults. The diseases caused by these pathogenic agents resemble dysentery by its clinical symptoms. Diagnosis. Coliform bacterial intestinal infection is very similar to other intestinal diseases in infants. Certain features of the clinical symptomatology (persistence of pyrexia, vomiting and gradually aggravated toxicosis, irregular course, me-teorism, copious, often watery stool with little or no admixture of leucocytes and mucus in it) are suggestive of coliform bacterial infection even before a bacteriological report is received, but the latter, of course, is of decisive significance. Faecal cultures are positive in the first days of the disease. Samples for culture are obtained as for dysentery. A serological agglutination test with autostrains of the causative agent, or with laboratory cultures, is also used. Treatment is based on the general principles used in the complex therapy of other acute intestinal infections in infants.
130
*Influenza*
The causative agent is a filterable virus from the group of myxo-viruses (Myxovirus influenzae), first isolated in 1933. Electron photomicrography has shown the virus to consist of particles of spherical shape, 80 to 120 nm in diameter (Fig. 40). It contains ribonucleic acid (RNA). The influenza virus perishes rapidly outside the human organism and is very sensitive to the action of disinfectants, heating, ultra-violet rays, and desiccation. In glycerol and when vacuum dried at low temperatures it is preserved for a long time. The virus is cultivated on tissue cultures and chick embryos. Three different types of the virus are known (A, B and C) differing in a number of biological and antigenic properties. Each type has several serological varieties. The virus has marked variability. It is especially characteristic of influenza A virus and shows itself in variation of its surface antigens: haemagglutinin (H) and neuraminidase (N). When both antigens change, new subtypes (Ai and A,;) are formed which cause pandemics. Since the time of discovery of the influenza A virus only one surface antigen changed several times. New variants of the virus (A2/Hong Kong, A2/Victoria, A2/Port Chalmers, etc.) appeared which became the cause of vast epidemics. The set of antigens of the influenza virus and the number of its possible variants are limited, and 'new' variants are actually the revived formerly circulating strains (Enders). The virus of influenza in experimental conditions proves to be pathogenic for polecats, mice, rats, and hamsters. The existence of influenza viruses in animals (hogs, horses, poultry, etc.) has been established. These viruses are similar to but not identical with those of humans by their biological properties. EPIDEMIOLOGY The source of infection is the patient, who is particularly infective It the height of the disease, during pyrexia. The contagious period lasts for four to seven days. Ambulant patients with mild and abortive forms of influenza play a very great epidemiological role as they Jean actively spread infection. The existence of an asymptomatic form |has been confirmed, but its epidemiological significance is debatable. j Infection is chiefly conveyed by the aerial-droplet route at relatively close distances from the patient. Infection by fomites (dishes, handkerchiefs, etc.) plays no marked role because of low viability if the virus. The susceptibility of man to influenza is very high, practically miversal. Very brief contact with a patient suffices for infection. Only children in the first months after birth are relatively resistant to influenza because of passive immunity acquired transplacentally from mothers immune to the variety concerned. Children are very pusceptible to influenza from six months of age. Immunity against influenza A is effective in man for about two years, and against influenza B, three years. The post-infection immunity is characterized by specific features: it only protects from the corresponding antigenic variant of the virus. Development of an epidemic is favoured by overcrowding, migration, and unsatisfactory hygienic conditions in public places. The seasonal factor is of relative significance: epidemics may occur at By time of the year, though mostly in the cold months of winter and spring. If the epidemic is linked with the subtype of virus common in the given locality and responsible for sporadic cases between epidemics, the epidemic curve climbs slowly, the incidence of influenza nly exceeding the usual level by a factor of two to four. Epidemics of this type usually occur from October to December. Children and adolescents are affected first, and then gradually the adult population. If the epidemic is caused by the virus (type or subtype) from which a given area was free for a long time, the infection spreads violenly and morbidity is high. Both children and adults are affected. All age groups are affected; the epidemic reaches a very high level. 131
Pediatrics Infection Influenza spreads for great distances along lines of communication and in a few weeks can be widely spread and involve many regions of a country, with a sharp rise in the epidemic curve. From 20 to 30 percent, and in particularly severe epidemics from 50 to 70 per cent (in some places even 100 per cent) of the population become affected within a short time. Rapid subsidence of the epidemic follows. Epidemics caused by the type A virus are repeated every one or years, and by the type B virus every three to six years. In certain conditions, the interval between separate epidemics may be quite long. Severe pandemics of influenza occur from time to time, at more or less lengthy intervals, when there is a change of both superficial antigens. Thus, between 30 and 50 per cent of the world population was affected by the pandemic of 1890. During the Spanish influenza pandemic of 1918-19 a total of 500 million persons was affected with around 20 million deaths. Between 1920 and 1954 eighteen epidemics were recorded in various countries or continents. In the spring of 1957 a new pandemic, which came to be called 'Asiatic influenza' occurred, caused by a new serological type of the virus designated as A2. Between 20 and 60 per cent of the total population was affected in various countries. Unlike the 'Spanish' pandemic, mortality was not high, varying between 0.001 and 0.008 per cent. The development of influenza pandemics is explained ' by variability of the antigenic properties of the virus and the appearance of new varieties resistant to the protective factors of the human organism. Many investigators think that new variants of the influenza A virus may appear through recombination of the human and animal virus. This is only a hypothesis but it should not be disregarded. PATHOLOGICAL ANATOMY Reproduction of the influenza virus in the epithelium cells of the respiratory mucosa (i.e. the locus of its primary implantation) is attended by the formation of specific intraplasmatic inclusions containing RNA. The affected cells would normally degenerate and be rejected. At the same time, proliferation and metaplasia of the cylindrical epithelium occur. Paralytic dilation of the vessels in the mucosa, small haemorrhages, oedema, and intensified secretion of the mucous glands are observed. The development of marked inflammation is normally associated with secondary supervention of the bacterial infection. Catarrhal-desquamative tracheitis and bronchitis develop. The pulmonary tissue is readily involved in the inflammatory | process and segmental oedema, focal and segmental (sometimes confluent) pneumonia with involvement of the interstitial tissue develop. Influenza pneumonia in children is often desquamative, and giant cells of alveolar epithelium are commonly found in the exudate. Early affections of the lungs are probably of purely viral aetiology. Further progress of the pathological inflammation involves secondary bacterial flora to cause virobacterial or bacterial pneumonia. Their aetiology is connected with staphylococcal infection now. Influenza is attended by pronounced circulatory disorders in various organs, the lungs and the brain included: markedly excessive blood supply, vascular stasis, small haemorrhages. Dystrophic changes occur in the cells of the parenchymatous organs. Grave affections of the nervous system, such as encephalitis, meningoencephalitis, usually develop in the presence of mixed viral infections; the allergic mechanisms are very important in their development. PATHOGENESIS The pathogenicity of the influenza virus is mainly expressed in its epitheliotropicity and toxicity. It interacts with the organism primarily within the epithelial cells of the respiratory tract, where the most delicate processes of viral multiplication occur. Intracellular inclusions, degeneration, death and desquamation of epithelial cells are external
132
Pediatrics Infection manifestations of this process. Subjacent tissue and the vascular network are also involved (catarrh of the respiratory tract in which concomitant bacterial flora of endogenous origin plays a considerable role). Toxaemia is a typical clinical feature of influenza, and is much more common in this disease than in other similar viral respiratory infections. The toxic effect of the influenza virus has been confirmed and substantiated by the experiments of a number of investigators. L. Zakstelskaya has convincingly demonstrated on animals that influenza virus possesses toxic properties inseparable from its active particles. Toxaemia is, probably, a manifestation of virusaemia occurring in influenza. The places most affected by the toxic action of the virus are the nervous system (central and vegetative) and blood vessels. It seems to affect certain other organs and systems and gives rise to disturbances of hypophyseo-adrenal regulation. A central place in the pathogenesis of influenza is taken by circulatory disturbances associated with lesions of the vegetative in-nervation and vascular system, disturbances that play a cardinal role in causing functional derangement of the nervous system and pulmonary complications. Immunity is brought about by a number of factors; that most studied is the formation of specific antibodies. Secondary bacterial flora invading the primary viral lesions can aggravate and prolong the course of the primary viral disease, and can be the principal aetiological factor in secondary catarrhs, pneumonia, and other pathological processes. The activation of bacteria in influenza is due to disruption of the barrier functions of the respiratory tract, disturbance of the neurohumoral regulation of physiological processes, and the reduction of non-specific resistance. Both the influenza virus itself and the accompanying bacteria and breakdown products forming in the foci of affection can sensitize the organism, with subsequent development of allergic and auto-allergic reactions. It must be supposed that sensitization of the organism prior to the development of influenza plays an important role in its pathogenesis. CLINICAL PICTURE The incubation period of influenza is one or two days, but may sometimes be as short as a few hours. The onset of the disease is acute, with elevation of temperature and chill. The febrile reaction may vary according to the severity of the disease; the temperature may be high (39-40C and over), but may remain subfebrile when the course of the disease is mild. Nursing babies stop gaining weight before the onset of influenza; it often begins insidiously with them, and runs a course with normal or subfebrile temperatures. General toxaemia is characteristic, and is mainly expressed in symptoms of involvement of the central nervous system, namely strong headache, vertigo, hyperaesthesia, adynamia, and sleepiness or, on the contrary, excitation. High fever is often accompanied with dimmed consciousness, delirium, and hallucinations. Muscular and neuralgic pain is frequent. Vomiting, convulsions and loss of consciousness (cerebral syndrome), and a syndrome of meningism are not uncommon in young children. Influenza toxaemia also produces marked changes in the cardiovascular system. A brief period of hypertension is followed by a fall of arterial pressure, tachycardia or bradycardia, arrhythmia, diminished heart sounds, and sometimes by cyanosis. Collapse occurs in severe cases. There may be haemorrhage into the conjunctiva and mucous membranes owing to involvement of capillaries. Epistaxis is not uncommon. Catarrhs of the upper respiratory tract are not constant in influenza, they are absent in 20 to 30 per cent of the cases. But in the majority of patients, they (along with toxaemia) are the leading and appear from the first day. In others they develop 133
Pediatrics Infection on the second or third day. Signs of catarrh of the upper respiratory tract are the following: cold, dryness and irritation in the fauces, a dry cough, and not infrequently hoarseness and dyspnoea. Blood-stained mucopurulent sputum is seen in some older children. The nasopharyngitis arising in nursing babies disturbs respiration considerably, and inhibits sucking; their appetite is poor, they sleep badly and lose weight. Laryngitis is sometimes encountered, most frequently in children under two years of age. In some cases influenza laryngitis is accompanied with stenosis. Croup in influenza patients develops mostly in infancy as a result of oedema of the laryngeal mucosa and the spasm of the laryngeal muscles. Its signs and course differ from those of diphtheric croup. In most cases its onset is sudden. Voice is normal or only slightly hoarse, coughing is loud, coarse and barking. Signs characteristic of laryngeal stenosis develop: noisy respiration (especially during the inspiration), depressions in the yielding parts of the chest, tension of the auxiliary respiratory muscles. In contrast to diphtheric croup, the croup attending influenza and also other respiratory viral infections is characterized by mild signs of laryngeal stenosis. Because of the absence of cyclic character, stages of laryngeal stenosis, rather than stages of croup, like in diphtheritis, are differentiated: I and II degrees are characterized by moderate or weak signs and the absence of respiratory insufficiency; III degree is characterized by permanent intense signs of marked stenosis and symptoms of respiratory insufficiency (cyanosis, drop of pulse at the height of the inspiration, restlessness of the patient); IV degree is characterized by a grave respiratory insufficiency, general cyanosis, and cardiovascular insufficiency. In some children influenza provokes an obstructive bronchitis (bronchiolitis) and an asthmatic syndrome expressed in marked expiratory dyspnoea, copious whistling and moist non-resonant rales, and emphysema; not infrequently there are also marked symptoms of disturbed gaseous exchange. Loss of appetite, a coated and often dry tongue, nausea, and sometimes vomiting and constipation are characteristic digestive disturbances. In young children, the stool is often liquid, dyspeptic. Sick children lose weight rapidly. An abdominal syndrome with pain in the stomach, vomiting and frequent stool, but no signs of peritoneal irritation, sometimes develops on the first or second day, so that an erroneous diagnosis of appendicitis is sometimes made. But the syndrome, which is apparently caused by toxic affection of the vegetative nervous system, disappears in one or two days, often before the temperature has fallen. The skin of patient is moist owing to the heavy sweating. A rapidly fading skin rash of various kinds (scarlatiniform, macular, or urti-carial) is occasionally met; its nature has to be judged with caution since it could be a sign of some other infection (scarlet fever, measles, etc.). Herpes may develop in some patients. The fauces are often hyperaemic. The granular character of the mucous membrane of the soft palate, which according to N. Moroz-kin is very characteristic of influenza in adults, is far from a constant sign in children; moreover, it is also met in other infections. Blood findings at the beginning of the disease are a transitory leucocytosis followed by moderate leucopenia, lymphocytosis, mono-cytosis, eosinopenia or aneosinophilia, and toxic granularity of neu-trophils; the ESR is within the normal range or a little higher. The temperature is at a high level with irregular remissions; as soon as it falls the patient's condition improves considerably. Diphasic fever (that is, a new rise of temperature in the absence of complications of any kind after a short remission of one to three days) is considered typical of influenza, but it is met in a minority of patients. In the absence of complications the total duration of the illness varies between three and seven or eight days. After the temperature comes down the children's strength is restored very slowly, and they often feel quite weak for some time; they suffer from sleepless-ness and irritability, and display a lowered resistance to various environmental influences. 134
Pediatrics Infection We distinguish three main forms of influenza according to the principal clinical syndromes reflecting the clinicopathogenic nature of the disease. They are as follows: (a) toxic (and a subtoxic variant), (b) catarrhal, and (c) toxicocatarrhal. Additional syndromes may supplement the characteristic features of each of these forms (with syndromes of encephalopathy, croup, asthma, haemorrhage, etc.). Influenza may also be distinguished as mild, moderately severe, and severe according to the gravity of its course. A variety of mild influenza is the abortive form; patients are ambulant, and it is therefore of great epidemiological significance. COMPLICATIONS The incidence of complications is in direct relationship to the age of patients and the state of resistance of their organism. Complications are particularly frequent and are especially severe in children under a year old, and in persons suffering from hypotrophy and enfeebled by other diseases. Respiratory complications are the most common. Infection can spread from the nasal cavity to the accessory sinuses causing catarrhal and purulent sinusitis (highmoritis, ethmoiditis, sphenoiditis). Pneumonia is a common and dangerous complication that develops either during the first days of the disease or later, when it is the result of mixed viral-bacterial infection. Microfocal, segmentary, or confluent pneumonia with involvement of interstitial tissue are encountered. Peculiar pulmonary 'segmentary affections', occurring in influenza in adults and children, have been described, and are characterized by inconformity of the clinical and X-ray findings, namely, in the presence of very few physical symptoms or their complete absence, roentgenographs show homogeneous shadows corresponding in localization to a pulmonary segment or a whole pulmonary lobe. These changes are seen in the first days of the disease; they usually disappear in a few days, and are apparently due to marked circulatory disturbances in a single segment or lobe (V. Soboleva). Pleura may become implicated with resultant fibrinous or purulent pleurisy caused by secondary bacterial flora (mostly staphylococcus). Abscesses of the lungs are sometimes the outcome of pneumonia. Various complications involving the nervous system, such as neuralgia, neuritis, or radiculitis, may occur. Clinical syndromes of encephalitis, meningo-encephalitis, and purulent meningitis (the latter due to secondary infection) are occasionally met. Catarrhal otitis is not uncommon in children. Other complications (stomatitis, purulent otitis, pyelitis, cystitis, nephritis, keratitis, phlebitis, etc.) may also occur. Influenza may exacerbate chronic diseases (dysentery, rheumatism, chronic tonsillitis, etc.); complications, mainly linked with lesions of the respiratory organs, are particularly frequent. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS Clinical recognition of influenza is not easy because it has a certain similarity with the initial symptoms of many acute febrile diseases. The greatest difficulties arise in differentiating it from other acute viral respiratory infections, and differentiation is only possible when the clinical picture is typical. Typical signs of influenza are its acute onset, marked toxaemia, frequent catarrhs of the respiratory tract, and leucopenia following a transitory initial leucocytosis. Intoxication in para-influenza and respiratory syncytial and adenoviral infections is less pronounced, whereas the catarrh of the airways is more marked. Adenoviral infection is also characterized by a gradual onset, the presence of symptoms of 135
Pediatrics Infection pharyngitis, conjunctivitis and swelling of the cervical and submandibular lymph nodes. The lower respiratory ducts are often involved in the respiratory syncy-tial infection (bronchitis, bronchiolitis); the larynx becomes involved in parainfluenza. Diagnosis should be differential from measles, pertussis, abdominal fever, and other acute infectious diseases which begin with the absence of their characteristic symptoms (see the corresponding sections). Epidemiological data can be of great assistance, i.e. whether the same illness has occurred in the child's family or in the institution it attends. Diagnosis is much easier, of course, during an epidemic. Isolation of the virus on chick embryos, and serological reactions haemagglutination-inhibition and neutralization reactions, and the complement-fixation test are laboratory methods used for diagnosis. The serological reactions are performed twice: once at the beginning of the disease (not later than the sixth day) and once during convalescence, but not' earlier than the 12th to 14th day. A four-fold (or greater) increase of antibody titre is considered diagnostic. Unfortunately, virological and serological tests are of no value for early diagnosis as they require much time. A relatively quick and simple tentative method is cytological diagnosis with determination of the presence of intraplasmatic viral inclusions in 'print' preparations from the mucous membrane of the patient's nose. Fluorescent microscopy of these preparations stained with acridine orange is used for this purpose; influenza inclusions containing ribonucleic acid display bright red fluorescence. In contrast to influenza, intranuclear and intraplasmatic inclusions in adenoviral infection contain desoxyribonucleic acid, which gives a greenish-yellow fluorescence when stained with acridine orange. A rapid and specific method of diagnosing influenza and other viral respiratory diseases is the technique of immunofluorescenee. Purified immune horse sera labelled with fluorescein isocyanate are utilized. Reacting with the viral antigens present in the affected epithelial cells, fluorescent antibodies form luminous complexes detectable by fluorescent microscopy. Immunofluorescent method is now being widely employed in clinical practice.
PROGNOSIS The outcome of influenza depends above all on the resistance of the organism. The course of the disease is most severe and has its highest mortality in infants, in children suffering from hypotrophy or rickets, and in persons enfeebled by certain acute or chronic infections. Prognosis is less favourable when complications supervene (pneumonia, encephalopathy, etc.). The character of an epidemic, which apparently depends to some extent on the properties of the causative agent, is also of major importance. The outcome of influenza depends largely on proper management. Modern methods of treatment and a well organized health service (as in the USSR) reduce mortality from influenza among children to the minimum. TREATMENT Strict bed rest should be enjoined for children during the whole period of illness. The sick-room should be regularly and thoroughly ventilated. The patient must be kept warm; warm baths give a good effect. Food should be nourishing and rich in vitamins. Warm or hot drinks are prescribed. When symptoms of neurotoxicosis appear, therapeutic measures are applied described in 'Introductory Part'. 136
Pediatrics Infection In the presence of indications, expectorants and cardiac preparations are prescribed. Diphenylhydramine hydrochloride, chloropyra-mine, pipolphen, ephedrine, and adrenalin are indicated with an asthmatic syndrome. In serious cases hormonal preparations are used. Vikasol, rutin and calcium preparations are given in haemorrha-gic syndrome. To bring about dehydration in patients with a cerebral syndrome (racking headache, vomiting, convulsions, loss of consciousness), intramuscular injections of a 25 per cent solution of magnesium sulphate and diuretics are given as well as hypertonic glucose solution. A short course of corticosteroid therapy (from six to eight days) and neuroplegic agents (chlorpromazine, propazine, etc.) are also recommended in such cases. In severe influenza with marked initial toxaemia (particularly in infants) intramuscular injection of specific gammaglobulin is effective. The preparation should have high titre of the anti-influenza antibodies (0.15-0.2 ml/kg). The measure is only efficacious on the condition that gamma-globulin is given not later than on the first or second day of the disease. Human leucocytic interferon is also recommended for treatment of influenza. This preparation is efficacious for prophylactic purpose. The reports on the clinical trial of interferon are controversial. When there is a danger of complications from secondary bacterial infection in severe cases, it is advisable to prescribe antibiotics, especially to small children (under two), and to children with concurrent respiratory diseases. Complications (laryngitis, sinusitis, pneumonia, otitis, etc.) are treated on general lines. Antibiotics active against secondary bacterial flora are widely used. When there are symptoms of stenosis of the upper respiratory passages with laryngitis, a combination of the methods used in conservative therapy of diphtheritic croup is employed (except serum injections). Intubation or tracheostomy is resorted to when there are corresponding indications. Plastic flattened-bent endotracheal tubes are used for intubation. Their size should correspond to the age of the child. Anaesthesia is required before intubation. Surface anaesthesia (inhalation, non-inhalation) in combination with depolarizing muscle relaxants is used for the purpose. There are 4 techniques, by which the endotracheal tube is inserted: (a) through the mouth with direct laryngoscopy; (b) through the mouth but without visual control; the tube is guided into the larynx by the finger; (c) through the nose without visual control; (d) through the nose with direct laryngoscopy. The tube is fixed by an adhesive tape and allowed to remain inside the larynx from a few hours to 5-7 days. The secretion should regularly be withdrawn from the trachea by suction. Intubation may involve some complications: the tube may flatten at the point of bend to obstruct air passage, the lips, teeth, mucosa of the mouth and the vocal cords may be injured; oedema of the larynx beneath the vocal cords may occur, etc. Metal tubes, that were formerly used for decades, still remain a useful tool for intubation. In the absence of a specialist, an O'Dwyer's metal tube should be used. Lower tracheostomy is usually given to children. The operation requires general anaesthesia. Compared with intubation, tracheostomy involves higher risk of injuries and subsequent pneumonia. Both intubation and tracheostomy should be performed by highly skilled specialists at the intensive therapy departments.
PROPHYLAXIS 137
Pediatrics Infection The most important general sanitary-prophylactic measure during an influenza epidemic is the organization of a proper regimen and hygiene of children's institutions, hospitals, hostels, canteens, cinemas and theatres, bus and railway stations, and other frequented places. Premises should be regularly ventilated and washed. The washing of floors with a 0.2 per cent solution of chloride of lime is recommended. The air in the children's institutions, clinics, and hospitals should be regularly irradiated by mercury-quartz lamps for the secondary effect. Strict observance of the rules of personal hygiene is most important. The medical personnel tending patients should wear gauze masks; so also should all personnel looking after infants (in creches, maternity homes, etc.). Great attention needs to be paid to measures improving fitness (morning exercises, sponge baths, physical culture, etc.), hardening the child organism, and increasing resistance to infection. Broad health education also helps. In the presence of immediate danger of infection with influenza (e.g. in an epidemic focus), prophylactic use of interferon is recommended: 0.25 ml of the solution should be sprayed into each nostril two times a day (any spraying system can be used). Instillation of two drops of interferon into each meatus can be used instead of spraying the solution. Experimental use of interferonogens (apathogenic viruses, pro-digiosan), which stimulate the production of endogenic interferon, has given good results. During an epidemic rise of influenza, a 0.25 per cent oxolin ointment is recommended for application to the nose mucosa two times a day, in the course of 25 days. The efficacy of prophylactic use of the anti-influenza preparation remantadine in children has not been reliably proved. Live tissue dry influenza vaccine is given per os for immunopro-phylaxis of influenza in infants over one year of age. (The instructions for use are appended to the preparation.) This vaccine is given three times at a 10-15 day interval (0.5 ml to infants under 3, 1 ml to children from 3 to 7, and 2 ml to children over 8 and to adults). The vaccination is carried out 2-3 months before the expected epidemic rise. Variability of the influenza virus and type-specificity of the vaccineinduced immunity are a serious hindrance to vaccination. The experience in anti-influenza immunization of children is insufficient. Measures in an epidemic focus. The earliest detection and segregation of patients are essential. Patients should be isolated at home, in a separate room or behind a screen; experience has shown that even such primitive early isolation reduces the danger of spread of infection. Only in severe complicated cases, with concomitant diseases (chronic pneumonia, nephritis, cardiovascular diseases, etc.), or when conditions at home are unfavourable is hospitalization necessary. Patients should be isolated (on condition of complete recovery) till the 7th day of the disease. The sick-room should be freely ventilated, and the floors washed with disinfectant (an 0.2 per cent solution of chlorinated lime). Members of the family should avoid contact with the patient as far as possible. The person nursing him should wear a gauze mask. The patient's eating and drinking utensils should be boiled. Handkerchiefs, sputum dishes, and other objects around the patient are disinfected with a solution of chlorinated lime or of chloramine. All these measures should be carried out most thoroughly when influenza cases occur in children's institutions.
Acute Respiratory Viral Infections Acute respiratory viral infections form a large non-homogenous aetiological group of very common viral diseases. These infections used to be classed under the collective name of acute catarrhs of the respiratory tract' or 'seasonal catarrhs', and were considered to be bacterial in origin. 138
Pediatrics Infection Their aetiology has been largely deciphered and clinically studied in recent years, thanks to the brilliant achievements of virology. The following individual nosological groups are now distinguished, apart from influenza: adenoviral, parainfluenzal, rhinoviral, syncytial-viral, and reoviral infections. Each form is aetiologically related to various serological types of the corresponding virus. Other forms caused by various types of enterovirus (Coxsackie and ECHO viruses) should also be classed as influenza-like diseases. A diagram proposed by R. Dreizin (1968) (according to the data of his own research) gives an illustration of the proportion of each infection in this group. The relative frequency of said nosological forms depends on some conditions: (a) efficiency of laboratory examination and the number of antigens contained in the set for serological tests; even if the laboratory investigations are performed at the appropriate lepel, part of respiratory viral diseases remains undeciphered; (b) epidemiological situation; the incidence of each infection may vary by seasons and undergo periodical variations due to changes in the epidemic phase; (c) the study of the aetiological structure of the hospitalized (i.e. grave in-patients), or patients treated at home or policlinically; (d) age of the patient; the structure of respiratory viral infections in infants differs substantially from that of adults. Respiratory viral infections are widely spread among children, especially infants. Some of them (para-influenza, respiratory syn-cytial, adenoviral infection) occur mostly in children. During their first months of lives, many infants are protected by immunity inherited from their mothers by transplacental routes. But even neonates can be affected by the diseases. At the age over six months and during their 2nd and 3nd years of life infants are often infected with respiratory viruses and develop repeatedly acute respiratory infections. Older children and adults, who had these infections in their infancy, develop them less frequently. Secondary bacterial infection (developing as a result of activation of endogenic bacterial flora or superinfection) is of great importance in pathogenesis of respiratory viral diseases. Bacterial infection aggravates viral" diseases and is the cause of many pathological processes and complications. Mixed viral infection often occurs. It develops in cases with simultaneous, or almost simultaneous, infection with two respiratory viruses (e.g. influenza virus and adenovirus, adenovirus and para-influenza virus). This combination would aggravate the disease as a rule. Respiratory viral infections have certain commonness of their clinical manifestations. Acute catarrh of the airways (with a feverish condition) develops as a result of the primary localization of the causative agents in the respiratory tract, and their epitheliotropic properties. Catarrh is thus the most common and significant clinical syndrome of the respiratory viral infections. Other syndromes in combination with catarrhs (or without them) can also attend most of these infections. Despite complete identity of the causative agent, each of these infections will cause different syndromes because of individual differences in the reactivity of patients. In other words, each of these infections may have quite different clinical forms despite the possible identity of the causative agent. At the same time one syndrome (e.g. asthmatic syndrome, croup, etc.) can be caused by various causative agents. This accounts for the difficulties in differential diagnosis. Respiratory viral infections are characterized epidemiologically by some common features. The source of infection is the sick human or a carrier. The main route of infection spreading is by air-borne droplets, which accounts for the rapid spreading of the infection. Adeno-viral, enteroviral, and reoviral infections can, in addition, be transmitted through the faecal-oral routes. Respiratory viral infections can recur many times within short periods because of the type-specificity of the acquired immunity and wide circulation of various serotypes. 139
Pediatrics Infection Respiratory viruses often cause epidemic outbreaks at children's institutions and hospitals to involve great number of children. The diseases may occur during the entire year, but their incidence is normally higher during the cold season. The role of the respiratory viral infections in pathology of childhood is very great. In association with secondary bacterial flora they are the main cause of pneumonia and one of the causes of chronic diseases of the airways; they aggravate other diseases, provoke their exacerbation and unfavourable course; they also may be involved in the genesis of chronic tonsillitis. When the infection occurs during prophylactic vaccination, they inhibit the process of immunogenesis (especially in grave and complicated cases) and provoke postvaccinal complications. Frequent respiratory infections cause a sensitizing effect on the child. They can cause allergic reactions in a sensitized child that develop by the parallergic mechanism. The respiratory viral infections, and pathologies developing with their participation, are important factors in mortality among infants. PARA-INFLUENZAL INFECTION According to the literature para-influenza accounts for between 10 to 30 per cent and over of the total number of viral respiratory illnesses in children. The causative agents are para-influenza or haemadsorbing viruses (Myxouiruses parainfluenzae) first isolated by Chanock in 1956. Viral particles are spheric, oval, and sometimes dumbbell-shaped; according to the data of electron microscopy they size from 150 to 250 nm. They contain ribonucleic acid (RNA) and are capable of agglutinating the erythrocytes of man, guinea-pigs, hens, and certain other animals. The viruses proliferate in kidney tissue cultures, and are nonpathogenic for laboratory animals, causing latent infection in some of them. They are of low stability in the environment. Four serological types (1, 2, 3, and 4) are known. Epidemiology. Infection is conveyed from a sick person by the aerial-droplet route. Infants are particularly susceptible. According to serological examinations carried out by the American authors, many children get infected with parainfluenza during their first years of life. Adults and older children, who usually have an attack of this disease in early childhood, contract the disease much less frequently; the disease runs a milder course. Para-influenza occurs either sporadically or in the form of outbreaks in organized groups of children, involving considerable part of them. Clinical picture. Incubation continues for 3-4 days (from 1 to 7 days). Being epitheliotropic, para-influenza viruses get into the airway epithelial cells where they are reproduced. Cytoplasmic RNA-containing inclusions are formed in the cells. The onset of the disease is less acute than in influenza. The temperature elevation is moderate and in uncomplicated cases it persists only for 2-5 days. A second rise in the body temperature sometimes occurs in 1-2 day apyrexia. This would normally be associated with the involvement of bacterial infection. In some patients the disease is attended by subfebrile or even normal temperature. The feverish condition is attended by headache, flaccidity, deranged sleep and appetite. But the symptoms of pronounced intoxication, that are typical of influenza, are relatively rare. Most frequent and typical manifestation of the para-influenza infection is the catarrh of the upper airways. Rhinitis is first manifested by difficult nasal breathing, which is then followed by more or less ample serous and seromucous discharge. Rhinoscopy reveals hyperaemia and swelling of the nasal mucosa. Moderate hyperaemia of the fauces, more frequently of only the arches, would be normally revealed. Para-influenzal rhinitis tends to a protracted course. It can persist for two weeks. A permanent symptom is persistent coughing which is the manifestation of tracheitis or tracheobronchitis; it is first
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Pediatrics Infection dry and then becomes wet. A tympanic character of the percussion sound is heard during examination of the lungs; the respiration is harsh with multiple dry rales. Bronchitis in infants sometimes becomes asthmatic. Laryngitis is typical of para-influenzal infection. It shows in dry coarse cough and a slight or moderate coarseness of the voice. It can sometimes be attended by symptoms of the laryngeal stenosis (the picture of croup). Croup develops in parainfluenzal infection of any type. Among all croups, the share of para-influenza is 30 per cent and over. Stenotic phenomena (depression of the yielding parts of the chest during inspiration, tension of the respiratory muscles, etc.) are moderate. They normally persist from a few hours to one day and operative intervention is required in very rare cases. Laryngoscopy reveals catarrhal laryngitis with oedema of the anterior laryngeal and subglottic mucosa. Pneumonia is the most frequent complication of para-influenza in infants. It is usually focal and sometimes is of grave course. If pneumonia develops during the first days of the disease, para-influenza viruses may be involved in association with the bacterial flora. Blood findings are normal during the first days of the disease;leucocytosis occurs less frequently; moderate neutrophilia is possible; ESR is normal or slightly increased. Tendency to leucopenia and increased percentage of mononuclear cells is further observed. More pronounced shifts are revealed in some patients with pneumonia. Diagnosis. The clinical picture of para-influenza resembles that of influenza and other respiratory viral infections. Differential diagnosis is therefore difficult and in some cases impossible. In contrast to influenza, the onset of parainfluenza is less acute. The intoxication symptoms are absent or only slightly pronounced, the catarrhal symptoms are more pronounced, frequent laryngeal affections are typical. The diagnosis becomes less difficult in epidemic outbreaks. Laboratory diagnosis, which is of decisive importance, is based on isolation of para-influenza viruses from nasopharyngeal washings and on serological methods (haemagglutination inhibition reaction, complement-fixation, neutralization, and haemadsorption tests). Like in other respiratory viral infections, rapid fluorescence techniques are of great help. RESPIRATORY SYNCYTIAL INFECTION (RS-VIRAL INFECTION) According to the data of various authors, RS-viral infection accounts for a considerable part of respiratory viral infections in children (15-25 per cent). The causative agents of this disease were isolated in 1956-7 by Morris, Chanock and others. They were named respiratory syncytial viruses because of their capacity to provoke the formation of syncytium (a structure produced as a result of the confluence of several cells) in tissue culture. The respiratory syncytial virus belongs to the group of myxoviruses. It contains RNA and sizes from 90 to 120 nm. It can be cultivated in the human tissue culture. Its resistance to the environmental effects is poor. Two sero-types of the RS-virus are now distinguished. Epidemiology. The source of infection is a sick person or a carrier. The infection is spread by the aerial-droplet route. The patient remains contagious probably for 5-7 days. The susceptibility to the RS infection is very high, especially in the nurslings who develop the disease in almost 100 per cent of cases during epidemics. Most infants fall ill during their first two or four years of life. The incidence of the disease in older children is much rarer. In adults it occurs as reinfection, often in a symptomless form. Seasonal variations are quite marked: the highest incidence occurs in the cold seasons. Clinical picture. The incubation period lasts for 3 to 7 days (5 days on the average). The onset is usually gradual, with affections of the upper and lower respiratory tracts. The affection of the upper airways is manifested by rhinitis with scanty serous or seromucous discharge, cough, sometimes hoarse voice. Laryngeal stenosis is not typical. The general condition is almost unaffected, the temperature is 141
Pediatrics Infection either normal or subfebrile, even in the presence of pronounced catarrhs. The temperature rises over 38C only in rare cases. Lower respiratory tracts are very frequently involved in infants (especially in nurslings under one year of age). A picture of diffuse bronchitis and bronchiolitis is observed. Incidence of bronchiolitis in infants to 1 year of age is from 30 to 70 per cent; it is much lower in older children. Bronchiolitis is characterized by a strong dyspnoea of the mixed type with prevalence of difficult expiration. Marked asthmatic syndrome is not infrequent. The examination of the lungs reveals fine or medium bubbling rales and symptoms of emphysema. The picture of respiratory insufficiency is supplemented by cyanosis. All these symptoms subside completely (or almost completely) in 2-6 days. The X-ray picture of the lung roots is more distinct, and the lungs appear inflated; focal changes are absent. Pneumonia (mi-crofocal, segmental) occurs in 25 per cent of cases on the average. The liver and the spleen are often found to enlarge. The general intoxication is usually not pronounced even in the presence of marked catarrh of the lower respiratory tract. The temperature is subfebrile and increases transiently to 38-39C only in few patients. Normocytosis or slight leucocytosis are found in the blood; neutro-philia often shifts to the left. The ESR may be slightly increased. When pneumonia joins in the process, the changes are more marked. The overall length of an uncomplicated RS infection is from 2 to 10 days (sometimes longer). Most frequent complications are pneumonia and catarrhal otitis caused by secondary bacterial flora. Grave pneumonia in infants is the cause of lethal outcomes. Diagnosis. During clinical diagnostication of the RS-infection in children, frequent affections of the lower respiratory tract (bron-chiolitis), that are characteristic of the disease, and also the disagreement between the gravity of the affection of the respiratory tract and the symptoms of general intoxication (e. g. temperature reaction) should be taken into consideration. In addition to isolation of the RS-virus, serological methods are also used in the laboratory diagnostication, namely: complement-fixation test (of little use in infants), and the neutralization test. Rapid immunofluorescence methods are quite valuable. RHINOVIRAL INFECTION (ACUTE CONTAGIOUS VIRAL COLD) Causative agents. Acute contagious common cold is a frequent and widespread disease, the viral character of which has long been established. But the properties of the causative agents, which were named rhinoviruses, have only been subjected to exhaustive study in recent years. Tyrrell and associates (1960) developed a method for cultivating viruses (in kidney tissue culture of human embryo and monkeys), and then determined the existence of various serological types; others have since been discovered by other investigators (at present they account for more than 50). Rhinoviruses are very small (15-30 nm); they contain ribonucleic acid, and are picorna viruses. Epidemiology. Infection is spread from a patient or virus carrier by the aerial-droplet route. Contagiousness lasts not more than 5 or 7 days. All ages are susceptible, but incidence is greatest in adults. Postinfectious immunity does not last long, its type is specific, and the antibody titre falls in two years. This explains the frequency of relapses of the disease during short lapses of time (2-4 times a year). Chilling is a promoting factor in the development of illness. Infection constantly circulates in a population, and under favourable conditions assumes the character of an epidemic outbreak. Seasonal elevations are noted in autumn and spring.
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Pediatrics Infection Clinical picture. The incubation period is between one and six days. Onset is characterized by the appearance of copious watery discharge from the nose and sneezing; later the discharge becomes more viscid, mucous, or mucopurulent as a result of concomitant bacterial flora. The nasal mucosa swells, obstructing the nasal passages. Sense of smell is impaired or lost entirely. Injections of the conjunctival vessels and sclera, and slight hyperaemia of the faucial mucosa occur. Herpetic eruptions appear sometimes on the lips and the skin adjacent to the nostrils. Cough, which appears in some instances, points to tracheitis or tracheobronchitis. Headache, malaise, and pain in the extremities are common. There are usually no constitutional symptoms, and temperature remains normal; a subfebrile temperature is met only in some patients, and a fever up to 38C or above is rare. The illness lasts for six or seven days, rarely longer. Secondary bacterial infection, which may cause various complications (sinusitis, otitis, angina, pneumonia, etc.), sometimes supervenes. For laboratory diagnosis viruses are isolated from nasopharyngeal washings and mucus collected by tampon, and antibody titre is determined; a rise is of diagnostic value. ADENOVIRAL INFECTION Virological examinations demonstrated adenoviral infection to account for 3 per cent of the cases in adults and from 12 to 21 per cent in children of the total number of acute diseases of the upper respiratory tract. Causative agents. Viruses causing these diseases were discovered by Rowe and Huebner in 1953 in adenoids and tonsils removed in operations from clinically healthy children. They were given the name of adeno-agents or 'adeno viruses'. Thirty two serological types of adeno viruses are now known; of this number types 3, 7 and 7a have the greatest significance in human diseases in the USSR. Other serotypes circulate in foreign countries. These are usually serotypes 4, 8, and 21. Types 1, 2, 5, and 6 are called latent. They infest the tonsils and adenoid growths where they persist for long periods of time to become involved in formation of chronic tonsillitis. There is evidence that they may be responsible for acute respiratory diseases as well. Pathogenicity of some adenoviruses for man has not been proved. Adenoviruses isolated from man have limited pathogenicity to laboratory animals. It was shown experimentally that types 12, 18, and 31 are oncogenic to newbom hamsters. Adenovirus particles are spheric or polyhedral, sizing 80-120 nm. They contain desoxyribonucleic acid (DNA). Adenoviruses are characterized by location inside the cell nucleus, common complement-fixing antigen, and marked stability to environmental effects. Epidemiology. The source of infection is a sick person or a carrier of the virus. The causative agents are liberated with he secretion of the respiratory mucosa and faeces. Liberation may continue for 2-3 weeks and even longer. Infection is spread through the aerial-droplet route, and also the routes characteristic of intestinal infections. There is evidence that the infection can be transmitted through the eye conjunctiva in swimming pools. Children from six months to three years of age are particularly susceptible to these infections. Children under six months are still protected by passive immunity obtained from their mothers; the low susceptibility in older children and adults is accounted for by immunity acquired in infancy. Adenoviral infection occurs sporadically or in the form of mild epidemics in organized groups of children, but extensive epidemics have also been reported.
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Pediatrics Infection Pathogenesis and pathological anatomy. Adenoviruses infest the respiratory and intestinal mucosa. They are accumulated in the epithelial cells and regional lymph nodes. Virusaemia is probably important in the pathogenesis of the disease. Catarrhal inflammation of the nasal, pharyngeal, and tonsillar mucosa with a marked exudative component is almost constant. The trachea and bronchi are involved in the process. Intranuclear inclusions containing DNA are found in the affected epithelium cells. The cells themselves are often necrotized and enucleated. Focal and confluent, polysegmental pneumonias are frequent. The regional lymph nodes are affected by hyperplasia. Inflammation of the eye conjunctiva, often with formation of fibrinous coats, is characteristic. The tendency to a gradual spreading of the process over onto new regions, which is accompanied by the intensification of the general symptoms of the disease, is characteristic as well. Immunity in persons recovering from adenoviral infection is type-specific and it does not protect from other viruses. Clinical picture. The incubation period is between four and seven days, sometimes longer. The principal clinical forms are pharyngo-conjunctival fever, catarrh of the respiratory tract, and pneumonia. Isolated or predominant affections of the pharynx or of the conjunctiva (adenoviral tonsillopharyngitis and adenoviral conjunctivitis and keratoconjunctivitis, serotype 8), the intestine (intestinal form), and mesenteric nodes (mesadenitis) are less frequent. At least slight catarrhs of the upper airways attend these 'isolated' forms. The onset of pharyngoconjunctival fever may be either acute or gradual. Temperature rises to 38-39C, and there is usually moderate general toxaemia. Headache, adynamia, loss of appetite are noted. Vomiting is not uncommon at the onset, particularly in infants. Constant symptoms are rhinitis with copious serous or seromucous discharge, bronchitis or tracheobronchitis, pharyngitis, and conjunctivitis. An asthmatic syndrome and laryngitis sometimes develop. The fauces and posterior and lateral walls of the pharynx are hyper-aemic; lymphatic follicles are swollen. The tonsils are rather enlarged, and a film sometimes covers the lacunae. Conjunctivitis may appear from the first day, but more often from the second or third. It usually starts on one side and may later spread to the other eye. Catarrhal, follicular, and membranous conjunctivitis are distinguished according to the character of the inflammation. The last-named is most typical of adenoviral infection. The conjunctiva of the eyelids looks hyperaemic, granular, and rather swollen. There is a sparse seromucous and seropurulent discharge. Fine white or greyish-white membranous films appear on the conjunctiva or plica semilunaris in one to three days. Oedema of the eyelids of soft consistency, sometimes sharply pronounced, is a frequent symptom. Enlargement of the cervical lymph nodes, and in infants liquid stool, sometimes with mucus, are not uncommon. Sometimes there is enlargement of the liver and spleen. The blood picture is approximately the same in all forms of adenoviral infection: a normal leucocyte count or a slight leucocytosis (less frequentlyleucopenia), neutrophilosis; the ESR is normal or moderately increased. With further development of the disease the fever becomes fluctuating; it may last for five or six to nine or ten days (longer in some cases) and terminates by lysis. In some patients the pyrexia is double- or even triple-wave; the second wave follows the first in several days. The catarrhal phenomena, particularly cold in the nose, are usually persistent and protracted. Subsidence of the conjunctivitis is relatively slow; the membranes persist for several days (sometimes up to the tenth or fourteenth day). Adenoviral catarrh of the respiratory tract is a frequent form of this infection, and the mildest. There is fever (for three to six days on average and longer), moderate or mild disturbance of the patient's general Condition and marked symptoms of catarrh of the respiratory tract, cold in the nose, bronchitis. Development of an asthmatic syndrome or laryngitis is possible. Frequent symptoms are pharyngitis and swelling of the cervical lymph nodes. Occasionally there is vomiting at the onset, and frequent liquid stool for several days. Not uncommonly the disease, which starts with a syndrome of re144
Pediatrics Infection spiratory catarrh, later assumes the character of pharyngoconjunctival fever or is aggravated by supervening pneumonia or membranous conjunctivitis. Pneumonia is the most severe form of adenoviral infection occurring mostly in infants under 1 year of age. Pneumonia is of viral aetiology with subsequent supervention of bacterial flora. The active involvement of adenovirus is confirmed by special pathoanatomic changes in the lungs, which are characteristic of adenoviral infection; viral inclusions are found in the alveolocyte nuclei (A. Tsinzerling). It is often combined with a syndrome of catarrh of the respiratory tract or of pharyngoconjunctival fever. It may be microfocal, macro-focal, or confluent; there are marked auscultatory signs, namely copious varied rales and not infrequently distinct dullness of percussion sound. Dyspnoea, cyanosis, and general toxaemia are noted. Attacks of clonicotonic convulsions may occur. Vomiting and diarrhoea are common; fever is irregular. X-ray studies reveal massive affections of the lung tissues; focal shadows are found, usually in several segments; the tendency to confluence is observed. The disease, particularly in nursing babies, has a tendency to a protracted relapsing course and can terminate by death. Mortality has been high in some epidemics. The intestinal form of adenoviral infection occurs mostly in infants under 1; it is characterized by prevalence of symptoms of acute gas-trointestinal disorders, viz., liquid medium-frequency dyspeptic stools, sometimes containing mucus, and deranged appetite; some patients develop vomiting. The body temperature is moderately elevated; catarrh of the respiratory ducts is a constant symptoms The gastrointestinal disorders persist for 3-4 days (R. Dreizin, M. Su-khareva, N. Nisevich, et al.). A. Tsinzerling characterizes this form by its morphological signs as "acute enteritis or enterocolitis with a marked alternative component'. Intestinal disorders are probably due not only to the pathogenic action of adenoviruses (types 3, 7, and 'latent' types 1, 2, 5; N. Nisevich et al.) but also due to involvement of the conventionally pathogenic bacterial flora; dysentery and coli-infection may concur. Mesadenitis (inflammation of mesenteric lymph nodes) is a rare manifestation of adenoviral infection which develops either against the background of another syndrome (e. g. pharyngoconjunctival fever) or as a prevailing syndrome, but almost always in combination with at least a slight catarrh of the upper respiratory ducts and the pharynx. Mesadenitis is characterized by an acute onset of fit-like abdominal pain, fever, nausea, and infrequent vomiting. The tongue is coated, stools are retained. The pain is felt predominantly in the lower part of the abdomen, often in the right iliac region. Peritoneal irritation is either absent or nonmanifcst. Appendicitis is often misdiagnosed and the patient is operated. Mesadenitis is sometimes complicated by intussusception. An abortive form of adenoviral infection appears as a rudimentary syndrome of pharyngoconjunctival fever or catarrh of the respiratory tract. Fever may be absent. Complications (otitis, sinusitis, secondary angina and bacterial pneumonia, pleurisy) are caused by secondary lacterial infection. They are the most common in infants with a severe course of the disease. Adenoviral infection can provoke exacerbation of chronic diseases (chronic tonsillitis, otitis, pneumonia, etc.), and may participate in the development of chronic tonsillitis. Clinical diagnosis of adenoviral infection can only be made with typical pharyngoconjunctival fever and membranous conjunctivitis. Conjunctivitis is an informative sign for differentiation of this infection from other respiratory viral diseases. During epidemics, in the course of which both typical and atypical forms are observed, diagnosis can be established even in the absence of a typical symptom complex and the disease differentiated from other respiratory infections (particularly influenza) by tracing the epidemiological connections. For laboratory diagnosis isolation of the virus from garglings and faeces, and serological examination (complementfixation test, neutralization and haemagglutination inhibition reactions identifying the type of causative agent) during the 145
Pediatrics Infection first days and after two or three weeks, are used; a four-fold increase of antibody titre at the minimum is considered diagnostic. The adenoviral nature of the disease can rapidly and conveniently be identified by luminescent microscopy of imprints from the nasal mucosa by which typical intranuclear DNA inclusions can be revealed. Fluorescent antibodies are quite valuable and specific for rapid diagnostication of viral aetiology.
REOVIBAL INFECTION The causative agents of this infection were first classified as the ECHO viruses (type 10) and in 1959 they were united in a special group of reoviruses (Sabin). The size of reoviruses is from 70 to 80 nm; they contain RNA, and are highly stable. The reoviruses are represented by three serotypes. Epidemiology and clinic of this infection are not well studied. The source of infection is a diseased man and persons who develop symptomless infection; the infection is transmitted by the aerial-droplet and probably faecal-oral route. Both sporadic and local epidemic outbreaks of the disease occur. Infants mostly fall ill. , The onset of the disease is acute and can develop either with catarrh of the upper respiratory ducts alone or in combination of the latter with intestinal disorders. Patients with the catarrh of the upper airways do not complain of impairment of the general condition; the temperature is subfebrile or normal. Rhinitis, cough, moderate hyperaemia of the fauces, catarrhal conjunctivitis, and moderately enlarged liver are the main symptoms. The disease lasts for 8-10 days on the average. When catarrh of the upper airways concurs with intestinal dysfunction, the temperature reaction may be pronounced (to 38C). The patient may complain of weakness and absence of appetite, abdominal pain, slight meteorism, frequent and liquid foamy stools with an objectionable odour. The liver increases in size considerably. The peripheral blood does not change substantially. The disease lasts slightly longer. The disease is diagnosed by isolating the virus from the nasal mucus and faeces (in the monkey kidney culture). The complement-fixation test is used as a serological method. The type of the causative agent is identified accurately by the haemagglutination inhibition and neutralization reactions. TREATMENT AND PROPHYLAXIS OF ACUTE RESPIRATORY VIRAL INFECTIONS The treatment and general prophylaxis of acute respiratory viral infections is largely the same as for influenza (see the corresponding section). The therapeutic effect of interferon has been tested. The data obtained are contradictory. Use of desoxyribonuclease by instillation into the nose or the conjunctival sac (3-4 drops of Quid preparation, 3-4 times a day) has been suggested in adenoviral infection; good results were obtained in the treatment of adenoviral conjunctivitis; efficacy of this preparation for treatment of other forms of this infection is doubted. This method has not gained wide popularity. Antibiotics are not effective against respiratory viral infections. They are only indicated in complications of bacterial aetiology and in the presence of especially favourable conditions for their development (in infants especially). Specific prophylactic measures against some of these infections are now being developed. The great variety of causative agents and their numerous serotypes present a great difficulty for prophylactic vaccination. Working out associated vaccines against most common types of leading respiratory viral infections seems to offer good prospects. Favourable results were obtained during prophylactic use of human leucocytic interferon (see 'Influenza') and interferonogens (U-V virus1 and prodigiosan). Prophylactic administration of gamma-globulin to asthenic and especially vulnerable children in the epidemic foci is recommended. 146
Pediatrics Infection Measures in the infection focus. All patients should be isolated at home or hospitals. Indications for hospitalization are the same as in influenza. There are no official standards for hospitalization terms, but the patient should be isolated until the clinical signs of the disease disappear, not less than for 7 days from the onset. The terms for home isolation are the same. Children who were in contact with the diseased should be surveyed for 7-10 days. Children from groups where respiratory viral diseases were reported should be kept away from the others at children's institution for the same terms. Children from the 'affected' group may not be moved to other children's bodies; neither may new children be allowed to join the 'affected' group.
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*Viral hepatitis* *MCQ*
4. Duration of incubation period at HBV: a. 10-21 days b. 21-60 days c. 60-180 days
1. The main way of transmission of virus of HAV: a. Transplacentaly b. fecal-oral c. Parenterally d. Sexual 2. The main way of transmission of HBV: a. aerial-droplet b. fecal-oral c. Parenterally d.Transmisivly 3. Duration of incubation period at HAV: a. 7-10 days b. 15-45 days c. 45-180 days d. Over 180 days 148
d. Over 180 days 5. How many periods of HAV courses are? a. 1 b.2 c. 3 d. 4 6. Compare duration of preicteric period at HAV and HBV: a. Identical b. More shorten at hepatitis A c. More shorten at hepatitis B 7. What type of preicteric period more often occurs at HAV? a. Mixed, Catarrhal, dyspeptic b. Abdominal, arthralgic c. Asteno-vegetatic d. Asymptomatic
Pediatrics Infection 8. What happened with symptoms of intoxication at HAV when the jaundice appear? a. Does not change b. Diminishes c. Increased d. The symptoms of intoxication disappear 9. What happened with symptoms of intoxication at HBV when the jaundice appear? a. Does not change b. Diminishes c. Increased d. The symptoms of intoxication disappear 10. Atypical forms of HAV are: a. Hemorrhagic, extrabuccal, anginal b. the non-icteric hepatitis, subclinical c. Catarrhal, abdominal, d. Dyspeptic, pneumonic 11. The size of liver at mild form at HAV: a. Normal b. Less than 3sm 149 c. 3-6 sm d.More 6 sm 12. The laboratory index of severity of HAV is: a. Level of general bilirubin b. Activity of ALT and AST c. Level of B-lipoprotein d. Activity of alkaline phosphates 13. At mild form of HAV the level of general bilirubin is less than: a. 20 mmol/l b. 50 mmol/l c. 80-85 mmol/l d. 120-150 mmol/l 14. Physiological ratio of free and conjugated fractions of bilirubin: a. 1:1 b. 3:1 c. 5:1 d. 10:1 15. What fraction of bilirubin is increased at viral hepatitis? a. Free
Pediatrics Infection b. Conjugated c. General d. Intestinal 16. What fraction of bilirubin is increased at hemolytic anemia? a. Free b. conjugated c. General d. Intestinal 17. What enzyme characterizes the liver cytolysis ? a. Amylases b. ALT c. Creatinin d. Alkaline phosphotise 18. What enzyme characterizes the process of cholestatis at HBV? a. Amylases b. ALT c. Creatinin d. Alkaline phosphotise 19. Indexes of thymol test at hepatitis: 150 a. Does not change b. Decreased d. Increased c. No information 20. Indexes of sublimit test at hepatitis: a. Does not change b. Decreased c. Increased d. No information 21. The disorder of what function of liver the changes of sublimit and thymol tests does reflect? a. Production of Protein b. Heamopoesis c. Detoxication d. Production of bile 22. The course of acute HAV is less then: a. 1 month b. 3 months c. 6 months d. 12 months
Pediatrics Infection c. s Ag 23. The protracted course of HBV is less then: a. 1 month b. 3 months c. 6 months d. 12 months 24. Antigen structure of HAV virus includes: a. 1 antigen b. 2 antigens c. 3 antigens d. 4 and more 25. Antigen structure of HBV includes: a. 1 antigen b. 2 antigens c. 3 antigens d. 4 and more 26. What antigens of VHB virus is it possible to found in blood: a. s Ag, eAg b. eAg 151 d. Ag 27. Antibodies against what antigens of virus HBV are present in blood: a. s Ag b. Ag c. eAg d. To all of them 28. Based therapy of HAV consists on: a. Intake a lot of fluid b. Diet c. Vitamin d. All is indicated 29. The immunization against HBV started in: a. 1 month b. 6 months c. 1days d. 3 months 30. Protection against HAV consists of: a. immunization
Pediatrics Infection b. specific -globulin c. sanitary prophylactics d. all of this 31. What kind of antibody present in blood at HDV-patient (Surerinfection)
*Shigellosis* *MCQ*
1. What is a causative agent at Shigellosis?
32. What kind of antibody present in blood at HDV-patient (Coinfection)
a. S. typhi abdominalis b. Sh. Flexner c. S. typhimurim d. E. coli
2. What bacteria do produce exotoxin? a. Sh. flexneri b. Sh. boydii c. Sh. dysenteriae (Grigoreva-Shiga) d. Sh. Sonnei
3. The mechanism of transmission of Shigellosis is: a. aerial-droplet b. Feacal-oral 152
Pediatrics Infection c. Transmisivly d. Parenterally 7. What symptom does not use as local criteria of severity at Shigellosis? a. Abdominal pain b. Tenesmus c. Headache d. Blood in stool d. Hypertoxic
4. The main way of transmission of Shigellosis Flexner is: a. aerial-droplet b. Water c. Fly factor d. Food-born
5. What symptom characterizes typical Shigellosis? a. Gastritis b. Duodenitis c. Gastroenteritis d. Distal colitis 8. What pathological admixtures is observed in stool at severe form of Shigellosis ? a. Abundant and watery b. Green mucus c. Blood and pus 6. Which symptom is atypical for Shigellosis? a. Gastroenterocolitis b. Colitis c. Enteritis 153 9.Chronic Shigellosis lasts more than: a. 2 weeks b. 2 months d. Rice-like
Pediatrics Infection c. 3 months d. 6 months 13. Antibacterial therapy at Shigellosis is not used at : 10. What is observed at palpation of abdomen at Shigellosis ? a. Hepatosplenomegalia b. Symptoms of irritation of peritoneum c. Spastic condition of sigma d. any symptoms 14. At Shigellosis the control stool bacteriological test is indicated : 11. What of auxiliary methods of researching is not used at Shigellosis? a. Bacteriological b. Serological c. Coprological test d. Method of haemoculture a. In the last day of antibacterial therapy b. In 2 days after declension of antibiotics c. Not conducted d. In 5 days after declension of antibiotics a. Severe forms b. Mild forms c. Complication d. Immunocompromized children d. 1:500
12. Diagnostic titre at Shigellosis is: a. 1:50 b. 1:100 c. 1:200 154
*Whooping cough (Pertussis)* *MCQ*

1. The caursative agent of pertussis is : a. Bordetella pertussis b. Bordetella parapertussis c. Chlamidia psittaci d. Brucella melitensis
b. development of a stable focus of excitation in the central nervous system c. As a result of bronchospasm d. Irritation of respiratory tracts by mucous
4. Catarrhal period of whooping-cough characterized by : a. Acute oncet with fever b. The catarrhal phenomena are expressed c. Gradually growing cough d. Symptoms of intoxication, cough, conjunctivitis
2. Susceptibility to whooping-cough of new-born and first-months-old child? a. Unsusceptibil due to trancplacental antibodies b. Susceptibil from the moment of birth c. Unsusceptibil, if child was ill a whooping-cough in childhood d. Unsusceptibil, if mother was ill a whooping-cough during pregnancy 5. What is the whoop: a. Whistling inhalation is forced during the fit of coughing b. Stop of breathing c. Precursors of fit of coughing d. Bronchopulmonal changes
3. Spastic cough at whooping-coughpresent due to: a. Inflammatory process of mucus respiratory tracts 155
6. What changes are not typical at whooping-coughin lungs? a. tympanitic or bandbox quality in percussion sound b. Dry and dull moist rales
Pediatrics Infection c. signs of emphysema d. Increased peribronchail lymphnords c. shortening of paroxysmal period d. presence of apnoe
7. At moderate form the number of fits varies a. Upto 5 on day b. 5-10 on day c. 15 20 on day d. 20 -30 on day
10. Haematological changes at whooping-cough : a. Anaemia, increased ESR b. leucocytosis, shiftto the left, increased ESR c. Leucopenia, leucocytosis, increased ESR d. leucocytosis, lymfocytosis, lowered or normal ESR
8. The number of whoop during the fit of coughing at moderate form of whooping-cough: a. Upto 3 b. 3-5 c. 5 -10 d. over 10
11. For treatment of patient with pertussis does not use : a. Ampicillinum b. Penicillinum c. Levomicetinum d. Eritromicinum
9. For a whooping-cough in new-born and children of the first months of life is not typical : a. shortening of latent period b. shortening of catarrhal period 156
12. A patient with whooping-cough is isolated for: a. 10 days b. 21 day c. 30 days
Pediatrics Infection d. 45 days 13. Immunization against whooping-cough start: a. in 2 weeks b. in 6 months c. in 3 months d. in 12 months 1. ausative agent of scarlet fever is: a. Staphylococcus b. Beta-gemolytic streptococcus of group A 14. A vaccin against whooping-cough consists of : a. 3-injection of ADPT, interval 30-45 days b. 2-injection of ADPT , interval 30-45 days c. 4-injection of ADPT, interval 45 days d. 1-injection of ADPT 0,5 2. The source of infection at scarlet fever is: a. Patients by a scarlatina b. Patients by a streptococcus angina 15. Revaccination is recommended after a complete primary vaccination after: a. 30 days b. 1,5 - 2 months c. 3 months d. 6 months 3. Main ways of transmission at scarlet fever: a. Aerial- droplets b. Contact with skin lesions 157 c. Early convalescent of streptococcus infection d. All of answers are correct c. Gamma-gemolytic streptococcus d.. Pneumococcus
*Scarlet fever* *MCQ*
Pediatrics Infection c. Transmisivly d. Fecal-oral route 7. Most more frequent scarlet fever is differentiated with the followings illnesses: a. By pseudotuberculosis b. By german measles c. By serum illness d. All of answers are correct 8. Convalescents of scarlet fever are admitted to child's institution: 5. Most more frequent complications of scarlet fever: a. Otitis b. Nephritis c. Myocarditis d. All of answers are correct 9. Quarantine measures of contacts with scarlet fever is spreaded 6. What clinical coarse of scarlet fever is not typical? a. Without allergic waves b. With allergic waves c. Abortive coarses 158 to: a. Children to 3 years b. Children of preschool age c. Children of preschool age and schoolboy of 1-2 classes a. After clinical recavery b. After desqamation of skin c. In 5 days after normalization of temperature of body d. Not early than 21 day from the beginning of disease with clinical convalescence d. Protracted coarses
4. The erytrogenic toxin has a tropism mainly to: a. ardiovascula system b. Lymphatic system c.Vegetative nervous system d. Endocrine system
Pediatrics Infection d. Quarantine measures are not conducted 14. Minimum incubation period at scarlet fever: 10. Duration of quarantine at scarlet fever: a. To 5 days b. 7 days c. 10 days d. 14 days 15. Maximal incubation period at scarlet fever: 12. General symptoms for a german measles and scarlet fever are: a. Rash b. Catharal fenomen c. Demige of CNS d. All of answers are correct 16. After scarlet fever is made: 13. Not characteristic portal of entry at scarlet fever is: a. Pharyngs b. Aper respiratory tracts c. Lungs d. Undemiged skin 159 a. Stable antitoxic immunity b. Stable antimicrobial immunity c. Stable group antimicrobial immunity d. Stable typospecifical antimicrobial immunity a. 3 days b. 5 days c. 7 days d. 14 days a. 1 day b. 2 days c. 5 days d. 7 days
Pediatrics Infection 17. What terms of isolation of patient with scarlet fever? a. Up to clinical convalescence b. Up to clinical convalescence, but not early than 10 day from the beginning of disease c. After period of desquamation d. After disappiarance of exudate on the tonsils body: a. At external surfaces of extremities b. To the nosolabial triangle c. Folds of skin d. Trunk 20. Scarlet fever's rash is not practically on the followings parts of
18. At scarlet fever can the factors of transmitted of infection be: a. Toys b. Dressed c. Tableware d. All of answers are correct
21. Scarlet fever's angina can be as: a. Catarrhal b. Follicular c. Lakunar d. All of answers are correct
19.To the typical forms of scarlet fever do not belong to: a. Rudimentary b. Hypertoxic c. Extrapharyngeal d. Late receipt
22. In peripheral blood of patient with scarlet fever is observed: a. Leukocytosis b. Neutrophilosis c. Elevated ESR d. All of answers are correct
160
Pediatrics Infection 23. The desquamation of skin at scarlet fever usualy begins: a. After the normalization of body's temperature b. On the second week from the beginning of illness c. On the third week from the beginning of illness d. After deflorescence of the rash 1. Causative agent of Salmonellosis a. Sh. sonnei b. S. typhi abdominalis c. S. typhimurium d. E. coli
*Salmonellosis* *MCQ*
2. Reason of development of diarrhea at a salmonellosis : a. Increased permeabilty of intestinal epithelium cells b. Increased oncotic pressure in bowel c. Activation of adenylatecyclase of enterocytes d. Replication of Salmonellae in an intestine
3. What forms of salmonellosis is not typical ? 161
Pediatrics Infection a. Gastrointestinal b. Typhoid c. Septic d. Subclinical 7. For salmonellosis is typical : a. Swelling of abdomen 4. Palpation of abdominal at salmonellosis characterize by: a. Symptoms of irritation of peritoneum b. Pain in an epigastrium and umbillican region c. Spastic condition of sigma d. Painless 8. Which symptoms is not typical for Salmonellosis ? a. Gepatosplenomegaliya 5. Characteristic of stool at salmonellosis? a. Like a rectal gob b. Like raspberry jelly c. Like rice-water d. Green, mucus 6. Degidratation of the II degree characterize by the loss of b.w. : a. Up to 3 % b.Up to 5% 162 9. What of laboratory method is not used at Salmonellosis? a. Bacteriological b. Virusological c. Coprological b. Moderate flatulence c. Pain in the region of salmonellosis triangle d. Mezadenitis b. Gepatosplenomegaliya c. Intact abdomen d. Symptoms of irritation of peritoneum c. 6 to 9 % d. More 10 %
Pediatrics Infection d. Serological 13. At Salmonellosis the control stool bacteriological test is indicated: 10. A diagnostic value has at a Salmonellosis : a. Title of antibodies 1:40 in RNGA b. Growth of title of antibodies in twice c. Growth of title of antibodies in 4 times and more d. Title of antibodies 1:100 in RA 14. Volume of liquid at degidratation of the II degree: 11. Antibiotic therapy is not conducted at a Salmonellosis a. At the complicated forms b. At severe forms c. At mild forms d. For early age child a. 50 ml/kg b. 100-150 ml/kg c. 175-200 ml/kg d. 220-250 ml/kg a. In the last day of antibacterial therapy b. In 2 days after declension of antibiotics c. Not conducted d. in 5 days after declension of antibiotics
12. What is specific therapy at a Salmonellosis? a. Antibiotic b. Chemotherapy c. Bacteriofag d. Biologics druges 163
*Pseudotuberculosis* *MCQ*
1. The causative agent of pseudotuberculosis is : a. Yersinia pestis b. Pseudomonas aeroginosae c. Yersinia pseudotuberculosis d. Bacilus tuberculosis 2. The features of causative agent of pseudotuberculosis is : a. Capacity for self-preservation b. Ability to growth at low temperatures (1-4 With) c. Capacity for optimum growth at temperature 370 d. Antagonism with the concomitant bacterial flora. 3. What group of pseudotuberculosis presente? a. Anthroponotic b. Invasion infections c. Transmissiv d. Zoonosis 164 infections does causative agent of
4. The source of infection at pseudotuberculosis can be : a. Cattle b. Fich c. Wild and home animals and birds d. Parrots, pigeons 5. What is the basic reservoir of infection at pseudotuberculosis ? a. Chickens b. Rodents, earthen soil c. Guinea-pigs d. Milk prodacts 6. The reflection of allergic component of pseudotuberculosis is : a. Inlargement of liver b. Arthralgia, rash c. Txicosis d. Microabscesses 7. The character of pseudotuberculosis's rash : a. Macula- papular b. vesicula c. Herpetic
Pediatrics Infection d. Erythematous 8. The rash at pseudotuberculosis is characterized : a. By the symptom of white spots b. By pseudopolymorphism c. By appearance of ulcers d. By the symptom of socks, gloves, hood 9. What clinical sings are not characteristic for pseudotuberculosis? a. Arthralgia b. Abdominal c. Meningeal d. Scarlatiniform 10. The basic in diagnostics of pseudotuberculosis is : a. Contact with home animals b. Contact with sick of intestinal diseases c. Use of raw green-stuffs d. Bacteriological and serum research 11. In what terms does bacteriological tests of blood and mucus from a pharynx at pseudotuberculosis conduct ? a. In the first 2 days from the beginning of illness b. During the first week of illness 165 c. During all of period of illness d. In early period of illness 12. Optimum terms of bacteriologic examination of fecal and urine at pseudotuberculosis : a. Before administretion of antibiotics therapy b. During all period of disease c. After canselled of antibiotics d. In prodromal period of illness 13. The diagnostic titre of RA at pseudotuberculosis is : a. Increas of titre of antibodies in 4 times and more b. Titre 1:4 in a dynamics 1:10 c. Titre 1:80 and any more d. Titre 1:32, in a dynamics 1:16 14. Pseudotuberculosis is differentiated more frequent than all : a. Scarlatina b. By rheumatism c. Infectious nonucleosis d. Viral hepatitis 15. Etiopathogenetic therapy at pseudotuberculosis is : a. Levomycetin, ampicillin,
Pediatrics Infection b. Penicillin c. Preparations of iodine d. Nesteroid hormons 16. Terms of discharg out of convalescents of pseudotuberculosis from hospital : a. Not early than 10 days from the moment of hospitalization b. On 7-10 day of normal temperature c. On 3 days of normal temperature d. After abolition of antibiotics 1. What family does the virus of Parotitis belong to? a. Picornaviruss b. Paramyxoviruss c. Herpesvirus d. Adenovirus
*Mumps (Parotitis)* *MCQ*
2. In what biological liquids is it possible to find out viruses at mumps? a. In blood b. In CSF c. In saliver d. All of answers are faithful
3. The main way of tramsmisstion at mumps: 166
Pediatrics Infection a. Watery b. Contact c. aerial-droplet d. fecal-oral 7. What action does pain increase at mumps? 4. Clinical forms of mumps : a. Nervous b. Glandular c. Combined d. All of answers are faithful 8. Laboratory and instrumental researches for diagnosis of mumpss pancreatitis : a. Determination of level of diastase in blood and urine b. Determination of level of lipasa c. Ultrasound invastigation of pancreas d. All of answers are faithful a. Mastication b. Turn of head c. Swallowing d. Breathing b. Orchitis c. Parotitis d. Meningitis
5. Incubation period of mumps: a. 11-21 day b. 30 days c. 1-2 days d. A few hours
6. Define the most frequent form of mumps: a. Pancreatitis 167
9. Complication of mumps orchitis is : a. Chronic prostatitis b. Atrophy of testicle with azospermia
Pediatrics Infection c. Cancer of testicle d. Impotence 13. What term of isolation of patient at mumps? 10. Mumpss meningitis characterized by : a. Pleocytosis b. Limfocytosis in CSF c. Level of sugar in CSF decrease d. Turbid CSF 14. Term of quarantine at mumps: 11. The clinical manifistation of mumps is : a. Headache b. Nausea and vomiting c. Meningia symptoms are moderatly incraesed d. All of answers are faithful 15. In what age a child should be immunized against mumps ? 12. Differential diagnostics of mumps and tuberculous meningitis based on : a. Color and turbidy of CSF b. Amount of lymphocytis in CSF c. concentration of electrolytis in CSF 168 a. 15 -18 months b. 12 months c. 12 months, 6 or 11 years, 16 years (boys) d. 3- 4-5 months a. 21 day b. 30 days c. 2 months d. 10 days a. 3 weeks b. 9 days c. 1 month d. 2 weeks d. Presence of films (membrane) on-the-spot of CSF
*Measles* *MCQ*
1. The virus of measles belongs to: a. To the Arboviruses b. To the picornaviruses c. To the paramyxoviruses. d. Togaviruses 2. The basic component of pathogenesis at measles is: a. Toxemia b. Bakteriemia c. Virusemia d. Cardiovascular disturbances
d. 15-30 days
4. In the focus of measles does not conduct next measures: a. Disinfections b. Quarantine measures c. Introduction of immunoglobulin d. Extraordinary vaccination
5. Patients with measles are contagious: a. In a catarrhal period b. In the eruptive stage c. To the fifth day from the beginning of diseas d. All of answers are correct
6. The catarrhal period of measles is characterized by: a. Conjunctivitis b. Hyperemia of pharynx c. Spots of Belsky - Filatov - Koplik d. Angina
3. Duration of incubation period at measles: a. 5-7 days b. 1-10 days c. 9-17 days
169
Pediatrics Infection 7. For measles not characteristically: a. Acute beginning of disease b. Fever c. Gepato-lienal syndrome d. Exantema 11. What kind of antibodies does not eleborite at measles a. Virusneutralization 8. Measles rash usualy appears to: a. On the first day of illness b. On the second day of illness c. On 4 - 5 day of illness d. After the 7th day of illness 12. In peripheral blood at measles is observed: a. Neutrophilosis 9. Characteristic of temperature curve at measles: a. Two-waves b. One- wave c. Line d. All of answers are correct 13. Not specific complications of measles are: a. Pneumonia 10. For measles rash is not characteristically? a. Macula- papula rash 170 b. Otitis b. Eosinophilia c. Thrombocytopenia d. Leukopenia, lymphocytosis b. Hemagglutination-inhibition antibodies c. Antitoxic d. A right answer is not present b. Rash finely spotted c. Tendency to confluence of rash d. Stages of appearance of rash
Pediatrics Infection c. Encephalitis d. All of answers are correct 14. Where do the first elements of rash appear at measles? a. On lower extremities b. On the back 1. The main caursative agent of bacterial meningitis is: c. After ears d. On the abdomin b) B. Lefflera c) meningococcus, pneumococcus 15. A child is ill for 5 days. A disease began acute. The temperature of body 38,1, cough, photophobia, edema of eyelids. On the 5 days macula-papula rash is appeared on the skin of the fase, neck and after ears. What is most reliable diagnosis? a. Adenovirus infection. c. German measles. b. Measles. d. Scarlet fever. d) all of answers are correct a) streptococcus, staphylococcus
*Meningococcal infection* *MCQ*
2. The most typical variant of rash at meningococcemia: a) papules b) Vesicula
16. The general signs of allergic and measles rash can be: a. Appearance of rash without a catarrhal period. b. Absence of stages of rash. c. Kind of rash d. Absence of pigmentation after disappearance of rash. 171
c) hemorragic d) maculopapules
3. The main criteria of meningitis at children of first-year of life: a) repitet vomiting b) cramps
Pediatrics Infection c) protrusion of the anterior fontanelle d) all of answers are correct 7. What component of pathogenesis play the important role in meningococcaemia : a) bacteriemia b) Cerebral hypertenson syndrome c) Hypertermia d) all of answers are correct d) nasopharyngitis
4. The main way of dessimination of meningococcal infection : a) by limpha b) by blood c) perineural d) through the ethmoid bone
5. What is a main mechanism of the toxic shock at MI: a) bacterial blood clots b) disorder of heamodynamics c) massive destruction of meningococcus with endotoxins eleboration d) all of answers are correct
8. Whom meningococc was first described by: a) Leffler b) Gvarnieri c) Vekselbaum d) Mechnikov
6. What form of meningococcal infection is more important epidemiologycaly: a) healthy carrier b) meningococcaemia c) pneumonia 172
9. What of antibiotic shoud be prescribed at meningococcaemia: a) penicillin b) Ceporin c) Chloramphenicol d) Gentamicin
10. Is it possible to decrease the dose of antibiotic at meningococcal meningitis during of clinical improvement: a) possibly after normalization of temperature b) possibly after disappearance of meningeal symptoms c) it is impossible until the normalization of blood test d) it is impossible until the normalization of CSF
13. Choose the optimum doses of penicillinum at MI meningitis for first-year old children: a) 100 000 per kg b) 50 000 per kg c) 800 000 per kg d) 300 000-500 000 per kg
11. To the r forms of meningococcal infection belong: a) nasopharyngitis b) chorioiditis c) iridocyclitis d) artritis
14. Normal concentration of protein in the CSF: a) 1,22 g/l b) 0,33g/l c) 0,15 g/l d) 0,9 g/l
12. For confirmation of diagnosis of MI it is necessary next laboratory researches: a) clinical blood test b) biochemical analisis of CSF c) bacteriological examination of CSF, blood, mucus of nasopharyng d) all of answers are correct 173
15. The main route of transmission at MI is: a) parenterally b) fecal-oral c) aerial-droplet d) Transmissivly
Pediatrics Infection 16. The most typical places of localization of rash at meningococcaemia: a) trunk, hands b) face c) buttocks, feet d) all of answers are correct a) albumin b) sugar, chlorides c) neutrophils d) lymphocitis 20. Clinical symptoms of edema of brain a) cramps b) loss of consciousness 17. The incresed doses of penicillin shoud be prescribed: a) hospitalization on 5-7 day or later b) complicated forms of disease c) to patient of the first months of life d) all of answers are correct 21. The main signs of infectious toxic shock a) total cyanosis b) loss of consciousness 18. Choose antibiotic at treat of bacterial meningitis: a) Chloramphenicol b) Ceporinum c) Canamycinum d) Penicillinum c) decline of blood pressure d) all of answers are correct 22. Complication of meningococcal meningitis a) hydrocephalia b) demencia c) bleeding 19. In normal CSF absent: 174 c) convulsions d) all of answers are faithful
Pediatrics Infection d) necrosis of extremities a) in the first day b) in 12 hours 23. Classification of meningococcal infection a) Local forms b) generalized forms c) rare forms d) all of answers are correct 24. Seasonal variations of meningococcal infection a) autumn b) winter-spring c) winter d) spring- summer 28. Incubation period of meningococcal infection a) five days 25. Meningeal syndrome at meningitis a) Rigidity of neck b) symptom of Brudzinski (upper, middle, low) c) symptom of Kernigs d) all of answers are correct 26. When a haemorrhagic rash appears at fulminant form of meningococcaemia 175 Correct answers b) fifteen days c) two - ten days d) twenty two day 27. When a haemorrhagic rash appears at typical meningococcaemia a) in 2 hours b) at the end of 2th day c) at the end of the first on the begining of the second day d) at the end of the third day c) at first hours of illness d) in 8 hours
*Influenza* *MCQ*
1-c 2c 3-d 4-b 5-c 6-d 7-c 8-c 9-c 15 - c 16 - c 17 - d 18 - d 19 c 20 d 21 d 2. The source of infection at an influenza is : 22 a a. Sick man 23 d b. Rekonvalescent 10 - d 24 b c. Animals 11 - c 25 d d. Birds 12 - c 26 c 13 - d 27 c 14 - b 28 c 3. Mechanism of transmission of influenza: a. Food b. Aerial- droplet c. Transplacental 176 1. The causative agent of influenza presents a group: a. Rotaviruses b. Pikornaviruses c. Ortomyksoviruses d. Arboviruses
Pediatrics Infection d. fecal-oral route 7. Laboratory express - diagnostics of influenzais carried out: 4. Seasonality of disease at influenza: a. Spring - summer b. Autumn - winter c. Summer d. Not characteristic 8. The incubation period at influenza is more frequent: 5. Mane components of pathogeny of influenza: a. Introduction in the mucousa of epithelium and reproduction of virus b. Viremia c. Demiged of the central and vegetative nervous system d. All of answers are correct 9. There are such clinical forms at influenza: a. Toxic, subtoxic 6. At clinical diagnostics of influenza taken into account: a. Massiv character of disease b. Defeat of all of age groups of population c. High contagious d. All of answers are correct 177 b. Catarrhal, toxicocatarrhal c. hemorrhagic d. All of answers are correct a. A few hours b. To two days c. To 5 days d. To 14 days a. By the method of immunofluorescence b. RSK c. RNGA d. Cultivating of virus is in the culture of fabric
Pediatrics Infection 10. The severe forms of influenza are accompanied: a. By a fever b. By the dispnoe, cough c. By the decreasing of diuresis d. All of answers are correct 14. Therapy of the uncomplicated forms of influenza is : 11. For the children of early age at influenza not characteristic is: a. Demige of the nervous system b. Respiratory insufficiency c. Dispeptic disorders d. Development of croup a. Etiotropic b. Nosotropic c. Symptomatic d. All of answers are correcr a. At hyperthermia b. At bacterial complications c. At the syndrome of croup d.At the bright catarrhal phenomena
12. To the clinical symptoms of edema of brain at influenza belong: a. Repited vomiting b. Psychomotor excitation, convulsions c. disturbances of conscicousnes d. All of answers are correct 15. Therapy of the complicated forms of influenza is : a. Antibiotics b. Infusion solutions c. Corticosteroids d. All of answers are correct 13. Administere of antibioticstherapy at influenza is indicated: 178
Pediatrics Infection 16. For the clinical manifistation of mild forms of influenza is not typical : a. Fever b. Muscles's pains c. Petechia rash on the skin d. Cough
*Infectious mononucleosis* *MCQ*

1. What is causative agent of infectious nnucleosis? a. Gerpes-virus of a 1 type b. Virus of Ebshteyn-Barr c. Bardotella pertussis
17. Characteristic complications of influenza is: a. Otitis b. Sinuitis c. Tracheobronchitis d. Pneumonia
d. Enteroviruss 2. Infectious nnucleosis is transmitted by: a. Food b. Transplacental c. Aerial- droplet d. fecal-oral
18. The features peculiar of influenzar in children of first-year of age is: a. Predominance of moderetely severe and severe forms b. More frequent there are bacterial complications c. High lethality d. All of answers are correct
3. For infectious nnucleosis is not characteristic: a. Limphadenopathia b. Hepatolienal syndrome c. Tonsilitis d. Pneumonia 5. At infectious nnucleosis is demiged rarely : a. Liver 179
Pediatrics Infection b. Spleen c. Heart d. Tonsils 6. Complications of infectious nnucleosis. a. Splenic rupture. b. Hepatic insufficiency c. Diseases of blood d. Otitis media 7. Changes in blood are not characteristic for infectious nnucleosis: a. Atypical mnnuclear cells b. Lymphocytosis c. Monocytozis d. Erythropenia 9. The most early symptoms of infectious nnucleosis it is been: a. Increas of temperature b. Inlargement of the cervical groupp of the lymph nodes c. Difical nasal breathing d. All of answers are correct d. All of answers are faithful 12. Antibiotics at infectious nnucleosis are prescribed: a. To the children of early age d. At the severe forms of disease c. At purulent angina d. All of answers are correct 13. Infectious nnucleosis usualy is registrated as: a. Sporadic cases b. Domestic focuses c. Epidemics 180 10. In the clinical manifistation of infectious nnucleosis at the children of early age characteristic: a. Cough, cold, conjunctivitis. b. Insignificant expressed of hepatolienal syndrome c. Dispeptic disorders d. All of answers are correct 11. Therapy of infectious nnucleosis includes: a. Antibiotics b. Symptomatic drags c. Hormones
*Chickenpox* *MCQ*
c. Through the third persons d. Fecal-oral route
4. The Duration of incubation period at chickenpox: 1. The causative agent of chickenpox is : a. Beta-gemolytic streptococcus of group A b. Herpes Zoster c. Herpesvirus I type d. Virus ECHO 5. The duration of contagious period at chickenpox: 2. The source of infection of chickenpox is : a. Sick person b. Carrier of chickenpox virus c. Home animals d. Convalescent of chickenpox a. Last date of latent period, all eruptive period and 5 days from the moment of appearance of the last element of rash b. 3 days c. All period of feveris d. Period of falling off of crusts a. 8-10 days b. 11-17 days c. 8-23 days d. 18 days
3. Main ways of transmission at chickenpox: a. Aerial- droplets b. Contact with skin lesions 181
6. What stages of development of chickenpox's rash? a. Macula, papula, vesicula b. Papula, erosion c. Roseola, vesicula, bulla
Pediatrics Infection d. Roseola, purpura 7. The rash at chickenpox is characterized : a. By appearance of stages b. By sudden disappearance 1. What is causative agent of diphtheria : c. By polymorphism . Corynebacterium diphtheria (Leffler bacillus) d. By appearance of necrosises, ulcers 8. The paticularyti of courses of chickenpox for hyposthenic children is: a. Predominance of mild forms of disease b. Predominance of abortive forms c. Haemorrhagic and gangrenous forms and complications d. Gastroenteric bleeding 9. The most frequent complication of chickenpox is : a. Stratification of bacterial flora and chickenpox's encephalitis b. Appendicitis c. Acute intestinal infection d. Flegmona of the soft tissues 3. What is most often localization of Corynebacterium diphtheriae? a. Diphtheria of nose b. Diphtherithic croup c. Diphtheria of faucial 182 2. Main way of transmission at diphtheria is: a. Food b. Transplacental c. Aerial- droplet d. fecal-oral route c. Adenovirus d. Staphylococcuss b. Spirocheta Vensana
*Diphtheria* *MCQ*
Pediatrics Infection d. Diphtheria of eyes 7. What is color of diphtheritic membrane ? 4. Who is the source of infection of diphtheria? a. Carrier of virulent streins of Corynebacterium diphtheriae. b. Patient by the typical forms of diphtheria c. Patient by the typical forms of diphtheria d. All of answers are correct a. Yellowish - white b. Dirty-white, c. Brownish-grey d. All of answers are correct.
5. What minimal level of diphtheritic antitoxin is protective (in RNGA)? a. 1:20 b. 1:40 c. 1:80 d. 1:320
8. Diffuse form of faucial diphtheria is diagnosed, if : a. The symptoms of intoxication are incrised. b. fibrinous membrane spreading beyond the tonsils. c. The mucous membane of the soft palate, pharynx is edematous. d. All of answers are correct.
6.Typical form of faucial diphtheria is characterized : a. fibrinous membrane b. Separate islands. c. Separate dots, or bands d. Absent of membrane 183
9. Characteristic of edema of subcutaneous cellular tissue of the neck: a. Shakes like a jelly. b. Hot at a touch. c. Rednes color of skin above infiltrate tissue. d. All of answers are correct.
Pediatrics Infection a. Antibiotics 11. What kind of smell mouth of patient is characterized at toxic diphtheria ? a. Sweetish-putrid b. Foetid-Sweetish c. Ammoniac. d. All of answers are correct. 15. What preparations are used for immunization against diphtheria ? a. APDT, DPT -vaccines 12. What symptoms are characteristic for a diphtheritic croup ? a. Hoarsenes of voice b. Barking cough c. Difficulty breathing d. All of answers are correct. b. ADT, DT - toxoids c. D, Td - toxoids d. All of answers are correct. b. Glucosae solutions c. Antitoxic serum d. Hormones
13. What most frequent complications at diphtheria ? a. Nephrosis b. Myocarditis c. Peripheral paralyses e. Bronchitis.
14. What drags are specific for treatment of diphtheria ? 184
*German measles* *MCQ*

1. Patient with german measles is contagious: a. In a catarrhal period b. To the 5th day from the beginning of exanthem c. During all period of fever d. To the end of eruptive period 2. The duration of isolation of contacts whith german measles ? a. Quarantine on 7 days b. Quarantine on 7 -14 days c. Quarantine on 21 day d. Contacts are not segregated. 3. For the german measles's rash is characteristic: a. Stages of appearance of rash b. Localization of the rash on the flexor surfaces of extremities c. Localization of rash on extenzor surfaces of extremities d. All of answers are correct 4. For the german measles of pregnant characteristically: a. absence of clinical signs of illness. 185
b. Typical forms of illness c. Atypical forms of illness d. All of answers are correct 5. The german measles is differentiated: a. with a measles b. With a scarlet fever c. Infectious nnucleosis d. All of answers are correct 6. The like signs of medicinal exanthem and german measles are: a. Inlarge of lymph. nodes b. Itching of skin c. Deflorescence after the use of antihistaminic preparations d. Pigmentation of rash 7. Therapy of mild forms of german measles: a. Antiviral drags b. Antibiotics c. Symptomatic d. Hormonal
Pediatrics Infection 4. Vomiting at Escherichiosis characterized by:
*Escherichiosis* *MCQ*
1. Causative agent of Escherichiosis: a. Sh. Sonne b. Pathogenic cultures of Escherichia c. Salmonella d. Normal cultures of Escherichia 2. What is a main way of transmission of Escherichia (EPEC)? a. Watery b. Parenterally c. Contact d. Endogenous 3. Main clinical form of Escherichiosis (EPEC) a. Gastritis b. Enterocolitis c. Gastroenteritis d. Enteritis 186
a. Unbridled b. Incessant c. Repeated d. Non-permanent 5. What color of stool at EPEC Escherichiosis? a. Green b. Brown c. Bloody d. Yellow-orange 6. Main syndrome of Escherichiosis at early age children a. Neirotoxicosis b. Toxicosis c. Exicosis d. Exicosis with toxicosis 7. Where is replication of pathogenic Escherichia? a. intercellular b. On-the-spot of intestinal epithelium c. In mesenterical lymphonoduss
Pediatrics Infection d. In intercellular space 8. The main factor of pathogenesis at Escherichiosis is: a. Exotoxin b. Endotoxin c. Exo- and Enterotoxin d. Serotonin 9. Escherichiosis more often occurs in? a. Winter b. During throughout the year c. Summer-autumn 10. At what term after declension of antibiotics bacteriologic stool test is carried out? a. After a week b. In 2 days c. In 3 days d. In the day of declension of antibiotics 12. What laboratory test are conducted to child who has a contact with Escherichiosis? 187 a. Bacteriological stool test b. Carpological c. Clinical blood test d. Serological test 13. Term of a quarantine at Escherichiosis a. 1 month b. 3 months c. 10 days d. 7 days 14. What stool is typical for EPEC Escherichiosis? a. Green color, like bog wattle-fences, liquid b. Yellow with unoverboiling meal, without pathological admixture c. Liquid, with the admixtures of mucus, sometimes - blood d. Small portions, with the admixtures of mucus, pus, blood 15. What toxin is elaborated by ETEC? a. Cholera-like b. Dysentery-like c. Dick Toxin d. Erytrogenic toxin
Pediatrics Infection d. All of age
*Acute respiratory viral infections* *MCQ*
4. For Rinoviral infection is not typical: a. Swollen of nasal mucous b. High fever c. Acute onset
1. The main features of ARVI: a. Etiologic heterogeneous illnesses (different causative agents) b. Spread quickly c. Mass character of disease (plenty of people fall ill) d. All answers are correct 2. Laboratory express-diagnostics of Rinovirus infection is carried out: a. Cultivation on tissue cultures b. By immunofluorescence methods c. By the method of complement-fixation test d. By the reaction of neutralization 3. Rinoviral infection more typical for: a. One-year-old children b. Preschool age c. School-year-old children 188
d. Watery excretions from to the nose, sneeze 5. The source of infection at a parainfluenza is: a. Animals b. Birds c. Sick man d. Reconvalescent 6. Mechanism of transmisstion at parainfluenza: a. Transmisivlly b. Aerial-droplet route c. By contact d. By food 7. For clinical manifistation of parainfluenzais not typical: a. Moderate fever b. Barking cough
Pediatrics Infection c. Syndrome of croup d. Nephritis 8. The clinical forms of parainfluenza are: a. Rinitis b. Pharyngitis c. Laryngitis d. All of answers are faithful 9. The most frequent complications of parainfluenza is: a. Myocarditis b. Pneumonia c. Otitis d. Artritis 10. Typical symptoms in the initial period of parainfluenza is: a. Acute oncet b. Dry cough c. Hoarseness of voice d. All of answers are faithful 11. The main clinical manifistation of parainfluenza is: a. Intestinal syndrome 189 b. Syndrome of croup c. Cardio-vascular insufficiency d. Kidney insufficiency 12. The treatment of uncomplicated parainfluenza is: a. Antibacterial therapy b. Corticosteroid therapy c. Symptomatic therapy d. All of answers are faithful 13. The indication for antibacterial preparations at parainfluenza: a. One-year-old children b. Syndrome of croup c. Pneumonia d. Fever 14. Mechanism of transmisstion of Adenoviral infection: a. Contact b. aerial-droplet route c. By food d. By water 15. Adenoviral infection does not characterize by:
Pediatrics Infection a. Conjuctivitis b. pharyngoconjunctival fever c. Pneumonia d. Otitis 16. Complications of Adenoviral infection: a. Pneumonia b. Croup c. Activation of chronic diseases d. All of answers are faithful 17. The most typical signs of Adenoviral infection are: a. Catarrhal phenomena of upper respiratory tracts b. Conjuctivitis c. Fever d. All of answers are faithful 18. Adenoviral conjunctivitis differs from diphtheria of eyes: a. By a hemilesion b. By absence of membrane (films) outside of conjunctiva c. By the overwhelming involving of lower eyelids d. All of answers are faithful 190 19. RS- infection is more frequent for: a. Early age children b. School age c. Adults d. All of age 20. Clinical picture of RS-infection characterized by: a. Bronchitis

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Table of Contents

*Viral Hepatitis* *Lec 1*

Peculiarities of hepatitis for patients under 1 year:

Index of severity of infection is the same in hepatitis A.

3 genuses of hepatitis B antigens:

HCV is a simple strand RNA virus.

*Acute intestinal diseases* *Lec 2*

Shigella, salmonella, E.coli, belongs to the family enterobacteriocae.

Pediatrics Infection o o o Follicular. Croupous. Diphtheria

Criteria for severity:

Pediatrics Infection III. Odorless. Later mucus with blood.

Pediatrics Infection Nasocomial infections (contaminated medical instruments, pharmacological preparations).

Clinical signs of dehydration:

Dehydration and serum Na concentration:

3) Antibiotics therapy (etiopathogenic therapy):

*Scarlet fever & Measles* *Lec3*

Toxins of hemolytic streptococci:

Mechanism of pathogenesis Septic

Only on the 7th-10th day of the disease

Pediatrics Infection 3. Fever.

Pediatrics Infection 2. 3. 4. 5. Necrotic tonsillitis. Shock. Hyperthermia. Numerous rash elements.

To differentiate scarlet fever with measles:

To differentiate scarlet fever with German measles (Rubella):

To differentiate scarlet fever with Pseudotuberculosis:

Treatment of scarlet fever:

Pediatrics Infection 1. Toxic. 2. Abortive (in immunized patient).

Differential diagnosis (catarrhal stage):

*Meningococcal infection* *Lec 4*

Clinical classification by Pokrusky:

Pediatrics Infection 4. Aneisonophilia.

Chronic form of meningococcemia:

Ways of transmission: Areal droplet.

Variants of diphtheria according to localization and severity of the disease:

Laryngeal diphtheria (upper respiratory tract):

Surgery (in diphtheric stenosis): 1. Intubation. 2. Tracheostomy.

*Introduction to infectious diseases*

*Virus (Epidemic) Hepatitis A and B*

*Scarlet Fever (Scarlatina)*

*Mumps (Epidemic Parotitis)*

*German Measles (Rubella) (Rubeola Morbillosa)*

*Infectious Erythema (Erythema Infectiosum or Fifth Disease)*

*Sixth Disease (Exanthema Subitum Seu Criticum)*

*Viral hepatitis* *MCQ*

32. What kind of antibody present in blood at HDV-patient (Coinfection)

a. S. typhi abdominalis b. Sh. Flexner c. S. typhimurim d. E. coli

3. The mechanism of transmission of Shigellosis is: a. aerial-droplet b. Feacal-oral 152

12. Diagnostic titre at Shigellosis is: a. 1:50 b. 1:100 c. 1:200 154

*Whooping cough (Pertussis)* *MCQ*

12. A patient with whooping-cough is isolated for: a. 10 days b. 21 day c. 30 days

*Scarlet fever* *MCQ*

3. What forms of salmonellosis is not typical ? 161

*Mumps (Parotitis)* *MCQ*

3. The main way of tramsmisstion at mumps: 166

6. Define the most frequent form of mumps: a. Pancreatitis 167

9. Complication of mumps orchitis is : a. Chronic prostatitis b. Atrophy of testicle with azospermia

*Meningococcal infection* *MCQ*

2. The most typical variant of rash at meningococcemia: a) papules b) Vesicula

9. What of antibiotic shoud be prescribed at meningococcaemia: a) penicillin b) Ceporin c) Chloramphenicol d) Gentamicin

*Infectious mononucleosis* *MCQ*

17. Characteristic complications of influenza is: a. Otitis b. Sinuitis c. Tracheobronchitis d. Pneumonia

c. Through the third persons d. Fecal-oral route

14. What drags are specific for treatment of diphtheria ? 184

*German measles* *MCQ*

Viral Hepatitis Lec 1

Acute intestinal diseases Lec 2

Scarlet fever & Measles Lec3

Meningococcal infection Lec 4

Introduction to infectious diseases

Virus (Epidemic) Hepatitis A and B

Scarlet Fever (Scarlatina)

Mumps (Epidemic Parotitis)

German Measles (Rubella) (Rubeola Morbillosa)

Infectious Erythema (Erythema Infectiosum or Fifth Disease)

Sixth Disease (Exanthema Subitum Seu Criticum)

Viral hepatitis MCQ

Whooping cough (Pertussis) MCQ

Scarlet fever MCQ

Mumps (Parotitis) MCQ

Meningococcal infection MCQ

Infectious mononucleosis MCQ

German measles MCQ

Acute respiratory viral infections MCQ