Fever of Unknown Origin

Updated classification includes :

(1) classic FUO, (2) nosocomial FUO, (3) neutropenic FUO, and (4) FUO associated with HIV infec!on.
Type Definition
• Classic FUO corresponds closely to the earlier definition of FUO, differing only
Classic FUO with regard to the prior requirement for 1 week's study in the hospital. The
newer definition is broader, stipulating :
- 3 outpatient visits or
- 3 days in the hospital without elucida!on of a cause or
- 1 week of "intelligent and invasive" ambulatory inves!ga!on.
• A temperature of 38.3°C (101°F) develops on several occasions :
nosocomial FUO, - in a hospitalized patient who is receiving acute care and in whom
infection was not manifest or incubating on admission.
Three days of inves!ga!on, including at least 2 days' incuba!on of cultures, is the
minimum requirement for this diagnosis.
• A temperature of 38.3°C (101°F) on several occasions:
occasions
Neutropenic FUO - in a pa!ent whose neutrophil count is <500/L or
- is expected to fall to that level in 1–2 days.

The diagnosis of neutropenic FUO is invoked if a specific cause is not identified

a-er 3 days of inves!ga!on, including at least 2 days' incuba!on of cultures.
A temperature of 38.3°C (101°F) on several occasions over a period of: of
HIV-associated FUO > 4 weeks for outpa!ents or
> 3 days for hospitalized pa!ents with HIV infec!on.

This diagnosis is invoked if appropriate inves!ga!on over 3 days, including 2

days' incubation of cultures, reveals no source.
 Treatment of tropical bacterial infections / Source: Harrison & Oxford tropical medicine
Tetanus
All patients should receive:
Overall aims of care :
the entry wound should be identified, cleaned, and debrided of necrotic material in order to
remove anaerobic foci of infection & prevent further toxin production. • Maintain adequate arterial PaO2 and O2
saturation.
Drug Dose, Route & Duration
• Maintain fluid, electrolyte, and acid
acid-base
Antibiotics balance.
• Metronidazole 500 mg IV 3 @mes/day for 7-10 days .
• Maintain circulatory support in grade IV
Alternative : hypotensive patient.
• benzylpenicillin 1.2 g IM or IV 3 @mes daily for 8 days .
Anti-toxin Critical care and nursing is essential
• Human TIG 3000–6000
6000 IU Single IM dose • Reduce external stimuli — physical
examination must be gentle.
• Equine antiserum 10,000–20,000
20,000 U Single IM dose
• Keep airway patent — use gentle suction to
Spasms control remove saliva and secretions at the back of
• Magnesium Sulph. - Intravenous
ntravenous loading dodose
se of 40 mg/kg over 30 minutes,
the throat.
- followed by intravenous infusion of 2 g/hour for pa@ents >45 kg and
• Take exquisite care of the tracheostomy.
1.5 g/hour for pa@ents ≤45 kg.
• Keep up pa@ent's nutri@on: 3500
3500-4000
• Benzodiazepines Chlorpromazine or phenobarbital calories (including >100 g protein) by NG
Cardiovascular stability is improved by : tube is required each day.
Treatment of C.V - increasing sedation with IV magnesium sulfate (plasma concentra@on, 2–4
2
mmol/L),
instability - morphine, or other sedatives. ( Recovery from tetanus may take 44–6 weeks )
- Drugs
rugs acting specifically on the cardiovascular system (e.g.,
esmolol, calcium antagonists, and inotropes) may be required.
Vaccination Patients must be given a full primary course of immunization as
tetanus toxin is poorly immunogenic
immunogenic.
• If Hyperpyrexia Paracetamol
aracetamol and wet cloths
• Secure airway early in severe tetanus tracheostomy is preferred on endotracheal intubation.
• Shut up !! Patients
atients should be nursed in calm, quiet environments because light & noise trigger spasm
Grading of tetanus severity
Grade I (mild): Grade II (moderate): Grade III (severe): Grade IV (very severe):
• mild to moderate trismus; • moderate trismus; •
severe trismus; • features of grade III plus
• general spasticity; • well-marked
marked rigidity; •
generalized spasticity; • violent autonomic disturbances involving
volving the CVS.
• no respiratory problems; • mild to moderate but short-lasting
short spasms; •
reflex and often spontaneous prolonged These include:
• no spasms; • moderate respiratory failure with spasms; - episodes of severe hypertension & tachycardia
• little or no dysphagia. tachypnoea >30-35/min; • respiratory failure with tachypnoea alternating with hypotension & bradycardia;
• mild dysphagia. >40/min; apnoeic spells; - severe persistent hypertension (diastolic
(diast >110)
• severe dysphagia; tachycardia >120/min. - severe persistent hypotension (systolic <90).
- Beware complications of septic wound. As for grade I but increase sedation/muscle Treat as for grade II but also paralyse & ventilate. As above, with addition of drugs that act on the CVS if
- Observe carefully since grade I tetanus can relaxation. deemed essential for grossly deranged haemodynamics.
progress to more severe disease. • Increase dose of diazepam up to 4-fold4 in adults, 1- Reduce diazepam dose to 30
30-40 mg over 24 h. • Hypotension :
Give by slow IV infusion over 24 h. 2- Give pancuronium 2-4 mg - give volume load;
For sedation/muscle relaxation: (alterna@ve: gallamine 20 20-40 mg) IV, - if ineffective or contraindicated, use dopamine
• Diazepam 5 mg PO tds (neonatal dose 2 mg PO tds). (do not exceed 80-100100 mg/day because of titrated for each patient to give sufficient to keep systolic BP >100 mmHg .
respiratory depression). neuromuscular blockade for efficient
Alternative: • Hypertension (systolic lic >200, diastolic >100 mmHg
• Chlorpromazine 50 mg (adult), • Perform a tracheostomy (may prevent death ventilation.
- propranolol 5-10 mg PO or
25 mg (child), due to prolonged ed laryngeal spasm and anoxia). - Ini@ally, give every 11-1.5 h (1st 1-2 wks), then extend - nifedipine 5 mg sublingual.
12.5 mg (neonate) interval as the patient improves.
If laryngeal spasm occurs, promptly give: • Treatment of Bradyarrhythmia or tachyarrhythmias.
IM qds (phenobarbital can be added if essential). - Check with periodic arterial blood analysis
chlorpromazine 50 mg IV
- pancuronium can be stopped when spasms cease.
alternative: diazepam 10-20
20 mg IV . Continue ventilation until patient can be weaned off.
Meningitis Enteric Fever
• On suspicion, give immediate antibiotics : — see below. Duration
Indication Agent Dosage & Route
• Give supportive measures: fluids, oxygen, maintain normal electrolytes, generous pain relief, and tepid sponging
to reduce temperature. Empirical Treatment
• IV dexamethasone 0.4 mg/kg 12-hrly
hrly × 2 days is recommended for adults and children with acute bacterial Ceftriaxone 1–2 g/d (IV) 7–14
meningitis in developed countries. Azithromycin 1 g/d (PO) 5
Initial empiric antibiotic regimens
Pediatric Adult
Fully Susceptible
Penicillin G 400,000 (U/kg)/d, q4h 20–24
24 million U/d, q4h
Ciprofloxacin (first line) 500 mg bid (PO) or 400 mg q12h (IV) 5–7
Benzylpenicillin 50-100
100 mg/kg 66-8 hourly 2.4 g IV q4 h .. for 10-14 days Amoxicillin (second line) 1 g @d (PO) or 2 g q6h (IV) 14
chloramphenicol 50-100
100 mg/kg 66-8 hourly 12.5 -25 mg/kg (or 1 g IV) q6 h.. for 10 days. Chloramphenicol 25 mg/kg @d (PO or IV) 14 - 21
Ampicillin 50-100
100 mg/kg 66-8 hourly 2g IV q6h for 10 days
Trimethoprim- 160/800 mg bid (PO) 7 - 14
Ceftriaxone 50--100 mg/kg/d 4 g IV q12h for 7-10 days sulfamethoxazole
Cefotaxime 200 mg/kg
mg/kg/d, q6h 12 g/d, q4h
Multidrug
Multidrug-Resistant
Vancomycin 60 mg/kg
mg/kg/d, q6h 2 g/d, q12hb
Preterm infants to infants <1 month Ampicillin + cefotaxime Ciprofloxacin 500 mg bid (PO) or 5-7
Infants 1- 3 months Ampicillin + cefotaxime or ceftriaxone 400 mg q12h (IV)
Immounocompetent children > 3 mon & adults <55 Vancomycin + Cefotaxime or ceftriaxone Ceftriaxone 2–3 g/d (IV) 7-14
Adult > 55 AND adult of any age with debilita@ng disease Vancomycin+Cefotaxime or ceftriaxone+Ampicillin Azithromycin 1 g/d (PO) or 5
1g on day 1 followed by 500 mg/d PO for 6 days.
ANTIMICROBIAL THERAPY OF CNS BACTERIAL INFECTIONS BASED ON PATHOGEN: Nalidixic Acid
Acid–Resistant
Ceftriaxone 2–3 g/d (IV) 7–14
Neisseria meningitidis
Azithromycin 1 g/d (PO) 5
Penicillin-sensitive
sensitive Penicillin G or ampicillin
High-dose ciprofloxacin 750 mg bid (PO) or 10-14
Penicillin-resistant
resistant Ceftriaxone or cefotaxime
400 mg q8h (IV)
Streptococcus pneumoniae
Penicillin-sensitive Penicillin G Brucellosis
Penicillin-intermediate
intermediate Ceftriaxone or cefotaxime Adult Pediatric
Penicillin-resistant
resistant (Ceftriaxone or cefotaxime) + vancomycin The gold standard for the treatment of in adults is :
Streptomycin 1 g IM daily for 14–21 days (A) SYSTEMIC :
• Rifampicin 15 mg/kg (max 600 mg) PO od for 6
Haemophilus influenzae Ceftriaxone or cefotaxime +
weeks.
Doxycycline 100 mg twice daily for 6 weeks
• co-trimoxazole: sulphamethoxazole 20 mg/kg
Chemoprophylaxis: only for household contacts of cases: Gentamicin
entamicin (5
(5–6 mg/kg/day for at least 2 weeks) +
Rifampicin 600 mg (10 mg/kg for a child, 5 mg/kg for children <1 yr) PO bd for 2 days. instead of streptomycin. trimethorpim 4 mg/kg (max 800 mg + 160 mg)
PO bd for 6 weeks.
Relapse occurs in 55-10% and should be treated with
Alternative: the same regimen.
(B) LOCALIZED :
Ciprofloxacin 500 mg (child 2-55 years 125 mg; child 55-12
12 year 250 mg) PO as a single dose Alternativee (1) : current WHO recommendation : gentamicin 2.5 mg/kg IV or IM tds for 2 weeks.
Doxycycline 100 mg twice PO for 6 weeks
INCREASED INTRACRANIAL PRESSURE +
Emergency treatment of increased ICP includes: Rifampicin
ifampicin 600-900 mg PO for 6 weeks
(A) eleva@on of the pa@ent’s head to 30°
30°–45°,
(B) intubation and hyperventilation (PaCO2 25–30
30 mmHg), and mannitol. Alternativee (2) :
Ciprofloxacin/O
Ciprofloxacin/Ofloxacin + Rifampicin
(C) Patients with increased ICP should be managed in an in
intensive
tensive care unit; accurate ICP
measurements are bestest obtai
obtained with an ICP monitoring device. PRGNANCY:
NANCY:
Rifa
Rifampicin + co-trimoxazole
 Gardenella Vaginalis:
- Normal inhibitant of the Vagina
- Association with anaerobic bacteria “Mobilluncus” they cause
Bacterial Vaginosis .
Diagnosis
A) 4 criteria are used for diagnosis of bacterial vaginosis
and known as " Amsel's criteria " [1 of 4 is enough] :
1- Foul smelling discharge
2- Detection of “Clue cells” :
epithelial cells coated with gram variable cocco-bacilli
of G. Vaginalis, found in cervical or high vaginal swab.
3- Whiff test: consist of trea ng Vaginal discharge with 10%
KOH smelling pungent fishy odour often +ve .
4- Vaginal pH > 4.5
Culture characters
- Discharge is cultured anaerobically - Facultative anaerobes
- better growth at anaerobic humid atmosphere at 37 C, pH 6 .
Media : Enriched with blood, serum or starch.
Identification :
- Clearing of starch around it - Hemolytic action on blood agar
- High sensitivity to Metronidazole. - By microscope: Small Gram -ve Rods.
Haemophilus ducreyi:
- It causes “Chancroid”, STD which is an ulcer on the
external genitalia.
- Lymph nodes are tender and enlarged.
Diagnosis
Specimens:
1- Smears from lesions or
2- Aspirate from draining Lymph nodes.
- Staining shows Gram –ve Cocco-bacilli that may be intracellular
- It grows with difficulty on Chocolate agar [Requiring X but not Y factor]
- PCR Used for Direct Detection of the organism in smears.
- ELISA Detection of IgG or IgM Antibodies.
Morphology
- Gram +ve lancent- shaped cocci ( i.e: oval with pointed ends )
- Arranged in pairs ( diplococci ) or short chains
- They are capsulated , capsules may appear a unstained
halos around organism. Non motile, Non sporing
They grow on blood agar producing alpha-hemolysis or
greenish discolouration similar to viridans streptococci.
( Check page 15 , volume II )
Mycoplasma Vulvo-Vagnitis Chlamydia
- They lack cell wall consequently the are pleomorphic. - They lack mechanisms of production of metabolic energy (can't
- Varying in size from 50 – 300 nm. sunthesize ATP) consequently, they need to Multiplay
- Differ from bacteria due to small size,lack of cell wall, extreme pleomorphism intracellularly where the host cell provides energy.
- Stain poorly with gram BUT can be stained with Geimsa. ( obligate intracellular parasites )
- 2 types: - They are small /250-400 nm/
1- Ureaplasma Urealyticum 20% of non-Gonoccal Urethritis - Closely related to gram-ve bacteria.
2- Mycoplasma Genitalium Non-Gonoccal Urethritis
Because Small size + obligate intracellular multiplication
Diagnosis classified as viruses in past !!
- They can grow in 2-days culture and is identified by:
1- Its colony morphology [poorly stained with Gram] - BUT differ from viruses & simulate bacteria in:
2- Urease production ( for ureaplasma urealyticum ) 1- They posses RNA & DNA like bacteria
3- Sensitive to Quinolones, Trovafloxacin and Sparfloxacin 2- They have a rigid cell wall like gram –ve bacteria.
4- Resistant to Cell wall inhibitors: Penicillins and Cephalosporins 3- They multiply by binary fission.
[due to absence of Cell wall]
4- The posses ribosomes & synthesize their own proteins.
5- They contain cholesterol in cell wall.
5- They have variety of metabolically active enzymes.
6 – They can be grown on enriched media( beef heart infusion in PPLO broth or PPLO
agar supplemented with serum(has cholesterol),yeast extract,and other ingredients 6- They contain plasmids.
Culture characters 7- They are sensitive to antibiotics.
- They are facultative anaerobe,
- Better growth at10% CO2, Diagnosis
- They grow slowly and require at least 1 week to form visible
Specimen:
colonies, which have a " Fried egg appearance " . Conjunctival & Urethral discharge,Cervical Scrapings, Sputum & Urine
A) Direct Detection:
- Cultures can be identified by PCR. 1- Intracytoplasmic Inclusions: by Giemsa or ImmunoFluorescent staining.
Maroxella Catarrhalis: 2- Chlamydial antigens: in exudates or urine by ELISA, IFA or DNA probes
- Gram –ve diplococcus, 3- Nucleic acid: in specimens by PCR
- Although it's a member of normal flora in human oropharynx , B) Isolation on tissue cultures:
it can cause : ( Mccoy cells or Hela cells )
bronchitis, pneumonia, sinusitis, otitis media & conjunctivitis, and detection of inclusion bodies in cell structures
particularly in Immunocompromised patients
C) Seriological diagnosis :
Characteristics:
− produce B-Lactamase.
by detection of specific IgM or a rising titres of IgG using ELISA
− doesn’t ferment Carbohydrates [but this is not useful in diagnosis of Genital tract Chlamydial infection because the
− Oxidase +ve frequency of infection is so high that many people already have Antibodies]
− DNase +ve
Culture characters
− Butyrate esterase +ve
− Sensitive to amoxicillin/Clavulanic acid, Cephalosporins, - They stained by : Giemsa & Macchiavello stain
macrolides & Fluoroquinolones. - They grow in : tissue culture & yolk sac of chick embryo.
Streptococcus pneumoniae:
1) Direct microscopic examination of Gram stained sputum spears will show the organism prevalent among pus cells
2) Quellung test : Fresh emulsified sputum (or CSF deposits in Meningitis) mixed with polyvalent anti-pneumococcal serum & methylene blue
Under microscope reveals Swollen Capsules " +ve quellung reaction" ,,,,, This is done for rapid identification.
3) Sputum is Cultured on Blood agar (in 5-10% CO2) : Alpha-Hemolytic colonies should be differentiated from Viridans Streptococci by applying an optochin
disc on the inoculum, o by the other tests ( check page 15 , volume II )
4) Intraperitoneal injection of Sputum into mice They die in 24-48 hr.s & organisms seen in tissue smears. (very sensitive , rarely used) ( not pathogenic to viridans str.)
5) Blood Cultures are +ve in 15-25% of pneumococcal infections as they are commonly accompanied by bacteraemia
 organism Morphology Culture characters Biochemical activites Diagnosis
- They ferment: - The specimen is: Urine, stool, pus ..etc
• Glucose
- Gram –ve bacilli,
- Facultative anaerobes. • Maltose - They are cultured on macConkey medium :resulting in(look previous) , and
• Mannite further identified by their morphology and biochemical reactions.
- motile,
- On macConkey agar: • Sucrose
they produce rose-pink colonies due to • Salicin In case of diarrhea :
Escherichia - some capsulated
lactose fermentation. With production of acid and gas. Isolated E.Coli should be futher tested serologically and virulence proved :

- On Blood agar: •
coli +ve to : Serotyping
by slide agglutination for EPEC and EHEC strains.
strains causing UTI produce hemolysis on • Indole
blood agar. • M.R.
• When HEHC infection is suspected,
- Simple media : -ve to : • rapid diagnostic methods are used to detect the verotoxin by ELISA,
- Normal inhabitants of grow on simple media • Oxidase. • or to detect the organism by immunofluorescence in stools.
the intestine of the man • Urease
and animals,
-XLD and CLED agar: Yellow colonies • H2S. Vivo assays, tissue cultures , immunoassay, DNA probes, PCR maybe used for
- some can cause disease • P.V. detection of toxin production or its ge
in man • Citrate

- Can generate energy by reducing nitrates to

nitrites.

- They ferment:
- Gram -ve Bacilli - On macConkey agar: • Glucose - They are cultured on macConkey medium: resulting in(look previous) , and
they produce pink colonies due to lactose • Sucrose further identified by their morphology and biochemical reactions.
- non-motile. fermentation. • Salicin
Klebsiella • Maltose
• Mannite
- in smears from tissues stained by gram :
capsulated organisms can be seen
- capsulated. - The colonies are mucoid due to the
With production of acid and gas.
production of abundant extracellular - It's highly pathogenic to the mice
slime. -ve to : +ve to: and cause their death within 24-48 hours when injected intra
indole V.P
M.R. Citrate

- Facultative anaerobes. - They ferment:

- Gram -ve Bacilli • Glucose By:
Proteus - Highly motile.
• Sucrose
• Salicin • Colony morphology.
- On MacConkey agar:
With production of acid and gas.
they produce pale non-lactose fermenting • Biochemical
- Very pleomorphic.
* Species are found in:
colonies. +ve to :
- phenylalanine deaminase.
• soil -Non-capsulated
• water - On nutrient agar: - urease ,
- which catalyzes the hydrolysis of urea to ammonia
* The genus includes two
Due to their highly motility, they give - differentiate them from salmonella & shigella .
important species: colonies which swarm in successive waves
over the surface on nutrient agar with
- H2S Which blackens the butt of triple sugar iron (TSI) agar.
• Pr.vulgaris – Indole
• Pr.mirabilis
"fishy odour"
- MR

-ve to:
- VP
- Citrate Variable

Pseudomonas
* Species are found in
• soil
• sewage
• and water
- some are commensals in
the intestine.
* The commonest human
pathogen of this group is :
Ps.aeruginosa
Candida
Albicans
- Is the most important species of
Candida.
It is part of the normal flora of the
mucous membrane of the upper
respiratory, gastrointestinal &
female genital tract.
In these sites, it may predominate
and cause super infection
Helicobacter
pylori
- It Causes chronic gastritis
peptic and duodenal ulcer .
- It is a risk factor for gastric
carcinoma , linked to mucosa
associated lymphoid tissue (
MALT ) & iron deficiency
anemia .
- Gram -ve Bacilli
- Motile.
- some strains are
encapsulated .
- Non-sporing
gram +ve
large oval budding yeast with
pseudohypae
Direct microscopic
examination, of smear or
exudates from the lesions
shows the previous
morphology.
It's similar to campylobacters
in morphology :
small gram –ve rods with
comma ,S, or "gullwing
shapes".
Motile like campylobacter
BUT different having multiple
sheathed monopolar flagella
while campylobacter have
single unsheathed at one or
both poles.
- Aerobe. - Ps. Aeruginosa is
1- P. aeruginosa can be isolated in:
- On MacConkey agar:
they produce pale non-lactose fermenting
Oxidase +ve - (blood agar)
colonies. - (MacConkey agar)
- On Blood agar: - Acid is produced from glucose by Identification is based on the results of biochemical and other
Haemolyze the blood. oxidation only. diagnostic tests
- On nutrient agar:
Grow on nutrient agar leading to greenish - Doesn't ferment any sugar. - ( Nutrient agar )
colouration of the medium due to its
diffusible exopigment which consists of : – ve to :
- pyocyanin (blue) H2S 2- Pus from the lesion maybe greenish blue.
- pyoverdin or fluorescein
(yellow- green fluorescent) VP
MR 3- Smears stained by gram show gram -ve bacilli among pus cells.
- Cultures have a sweet grap-like odour
-Metallic appearance.
Cultures are done on:
- nutrient agar, They ferment: By:
- corn meal agar glucose
- Sabouraud Dextrose Agar.
maltose • Colony morphology.
Colonies are soft, cream-colored with a yeasty • Culture characters.
odour. with acid and gas production
• Biochemical activites
Colonies are also identified by :
1- Morphology
2- Germ tube formation in serum
3- Chlamydospore formation on corn meal agar
4 -Biochemical reactions
1- Gastric biopsy specimens :
- Obtained b endoscopy are minced in saline and cultured as in campylobacter (they
+ve to : are microaerophillic ; grows best in presence of 5% oxygen and 10% co2) but
incubated at 37c in a humid atmosphere for 7 days
- urease - Smears stained with gram and histologic sections stained with special stains, show
the curved or spiral organisms.
while campylobacter is urease –ve
2- Rapid urease test :
- in which gastric biopsy material is placed onto a medium containing urea with a
- oxidase colour indicator.
- If H.pylori is present, the urease splits the urea and results in shift of the ph and
- catalse leading to colour change.
3-Non-invasive methods for the diagnosis include:
a- Urea breath test: A capsule of 14C –labeled urea is ingested by the patient. If the
organism is present the urease activity generates radiolabelled CO2 that can be
detected in patient’s exhaled breath .
b- Direct detection of H.pylori antigen by ELISA in stools is a useful test for diagnosis
& follow up the results of treatment .
c- PCR, applied on gastric juice, faeces or biopsy specimens.
d- Serologic detection of H.pylori antibodies by ELISA: high titers are found in
chronically infected patients.
 Neisseriae
Meningitis is the most common complication of meningococcaemia.
Usually begins suddenly, with severe headache, fever, vomiting & rigidity of the neck & back of muscles …. It may progress to coma within few hours
Morphology Culture characters Biochemical activites
Aerobes - Oxidase test :
- Gram Negative –ve diplococci arranged in pairs. All neisseria species give a +ve Oxidase Reaction (because they possess
- Enriched media for growth containing heated blood (e.g. Chocolate agar)
- Selective Modified Thayer Martin (MTM) medium containing antibiotics that inhibit Enzyme cytochrome c) where a deep purple colour develops.
- Kidney shaped appearance.
growth of other organisms . Colony is smooth, translucent, and non pigmented. - Acid production from sugars:
- Can be used to differentiate it from other species.
- Occur intracellularly in Pus cells & Extracellularly. Cultures incubated in a humid atmosphere containg 5-10% CO2 at 35-37 C
- N. gonorrhea Glucose +ve only .
- N. meningitides glucose & maltose +ve .

N. gonorrhea N. meningitides
- Meningitis is the most common complication of meningococcaemia.
They cause gonorrhoea which is a sexually transmitted disease (STD) - Usually begins suddenly, with severe headache, fever, vomiting & rigidity of the neck & back of muscles, It
may progress to coma within few hours
Diagnosis Diagnosis
1. The CSF by lumbar puncture,under complete aseptic conditions ,
• In Acute male urethritis : On physical examination In meningitis ,The CSF is under tension and turbid due to large
……………………………………………number of pus cells ( 20 000/cmm ) .
The urethral discharge is examined by direct smear stained by GRAM . the presence of gram –ve
On chemical examination the proteins are elevated … Glucose is reduced
diplococcic intracellularly and extracellularly in pus cells is diagnostic.
a) CSF is centrifuged ,Deposit is examined Microscopically after staining with GRAM.

The presence of grame –ve diplococcic in puss cells intracellularly is diagnostic

• In chronic male infection, acute and chronic female infection and when facing medicolegal
problems as in sexual abuse : b) Detection of MENINGOCOCCAL POLYSACHARIDE ANTIGENS in CSF by Coagglutination test

Latex agglutination kits for detection of antigens in CSF. ( useful for rapid diagnosi
Specimens : Discharge from urethra, cervix, rectum, conjunctiva, throat or synovial fluid. Examined by:
c) The deposits is cultured on Chocolate agar and incubated at 35-37 C in a humid atmosphere containing 5-
• Direct smears stained by gram are usually difficult to interpret due to presence of the organism in small
10% CO2…colonies appear in 2-3 days ,idenEfied by:
numbers mixed with normal flora
• Morphology gram –ve diplococcic
• Two rapid tests are used to detect gonococcal nucleic acids in the patient’s specimens .In one test the
nucleic acid is not amplified and in the second test it is amplified .Latter can be used on urine samples • Biochemical reactions Oxidase production ,Acid production from maltose &glucose
obviating the need for more invasive collection techniques
• Agglutination with anti-meningococcal serum
• Cultures are done on chocolate agar or MTM medium incubated at 35-37C in a humid atmosphere in 5- • Fluorescent antibody staining may be use for identification
10%CO2. Suspected colonies are idenEfied by Morphology,Bio. AcEvity (Oxidase +ve and acid producEon
from glucose only) ,or serologically by fluorescent antibody staining or coagglutination tests ,using specific 2) Blood cultures : commonly give +ve results
antisera.
3) PCR test : detect meningococcal DNA in Blood and CSF
• Blood cultures may be needed for diagnosis od DGI (disseminated gonococcal infections)
NB. For Diagnosis of meningococcal Carrier:
NB: Other STDs e.g.syphilis,non-gonococcal urethritis caused by Chlamydia & HIV can coexist with gonorrhoea
1- Nasopjharyngeal swabs are cultured on Enriched media (MTM) ;

2- isolated gram –ve diplococcic should be differentiated from commensal neisseria by the difference in in
cultural character, biochemical reactions & SEROLOGIC identification with specific antimeningococcal serum
 Anaerobic infections
- The obligate anaerobes form the major part of the indigenous flora in the intestine, mouth, and female genital tract of humans.
- They are the cause of a wide range of infections and most of them are of endogenous origin.

- Classification of anaerobes:
I- Spore-forming gram positive bacilli : Clostridia
II- Non Spore forming:
Gram positive bacilli: Actinomyces – Propionibacterium – Lactobacillia – Eubacterium
Gram Positive cocci: Peptostreptococcus – Peptococci
Gram negative bacilli: Bacteroids – Fusobacterium – Prevotella – porphyromonas - Leptotrichia
Gram negative cocci: Veillonella
III- Spirochetes: Treponema

Bacteroids species are the most important anaerobic pathogens :

- They are normal inhabitants of the intestinal tract and female genital tract. B.fragilis is the commonest pathogen.

- Abscess formation is a characteristic of lesions caused by bacteroids and most lesions are below the diaphragm and
are associated with bacteremia and endocarditis. They cause abdominal,lung,brain abscesses,epmyema,suppuration
of surgical wounds and peritonitis.

- They are resistant to penicillins as they produce beta-lactamase.

- Factors that predispose to anaerobic infections:

- A fall in oxidation-reduction potential (Eh) is the major factor that favors proliferation and invasion of tissue by anaerobes.

- Reduced Eh in tissues may occur due to:

1- Trauma, which leads to deep lacerated wounds, loss of blood supply and tissue necrosis
2- Foreign bodies, e.g: Clothing or soil inserted into a wound following an accident or war injury.
3- Decreased blood supply to a limb due to, pressure by a cast or ischemic arterial disease as in diabetic patients.
4- Mixed infections with facultative anaerobes which consume sufficient oxygen to allow the anaerobe to flourish.

- Sites and types of anaerobic infections:

Upper respiratory tract Lower respiratory tract Intra-abdominal infections Gynecological & obstetrical
infections infections infections

- periodontitis, - aspiration pneumonia, - appendicitis, - vulvovaginitis,

- chronic sinusitis, - empyema, - peritonitis, - endometritis,
- otitis media, - lung abscesses - abscesses - salpingitis,
- mastoiditis, - tubo-ovarian abscesses
- vincent angina - septic abortion

Soft tissue infections Blood Brain

- gas gangerene, Bacteremia leading to

- necrotizing fasciitis, thrombophlebitis,
Brain abscesses
- cellulitis. This affects mainly the endocarditts, and septic shock
compromised hosts. E.g: diabetes
- Diagnosis of anaerobic infections:
Anaerobic infections are suspected clinically when there is :

1- foul-smelling discharge,

2- gas in tissue,

3- the wound is deep lacerated,

4- tissues are necrotic

5- aerobic cultures are negative.

N.B. 1- Unless specific anaerobic techniques for sampling, transport, processing, and culture are used, these sesititve anaerobes will fail to grow.

2- Large samples should be aspirated from deep sites away from atmospheric oxygen and rapidly transported to the lab in closed syringes or on
….reduced transport media.

A) Naked eye examination of pus :

may show sulphur granules in case of actionmycosis or red fluorescence under UV light in case of prevotella infections

B) Specimens :

1- Specimens are directly examined after staining with gram.

- The presence of organisms in the absence of growth in aerobic culture, points to the presence of anaerobic infection.
- Vincent angina caused by fusobacteria and spirochetes, can be diagnosed by gram stained smears

2- Specimens are cultured on two plates of blood agar,

- one incubated aerobically to differentiate between anaerobes and facultative anaerobes.
- The strict anaerobes will grow on the anaerobic plate only.
• Selective media for different anaerobes may be use.
• They are incubated at 37 C in anaerobic jar (Gaspak system) with 10% Co2 for 2-5 days as anaerobes are usually slow growers.

3-Colonies are identified by their morphology, biochemical reactions (API-A) gas liquid chromatography to
detect short chain fatty acids, serology, and nucleic acid probes

- Treatment:
- Surgical drainage of pus, debridement and removal of necrotic tissues.
- Clindamycin,Metronidazole, cefoxitin and chloramphenicol are effective.
- Penicillin is effective against most anaerobes except B.fragilis.
- Clindamycin use may be complicated with pseudo-membranous colitis
- Morphology and Cultural characters of B.Fragilis:
- They are non motile, non sporing gram negative bacilli that are highly plemorphic.
- Coccobacillary and branching forms are frequently observed.
- They are strict anaerobes.
- Growth occurs after 48 hours or more on enriched media, e.g: Freshly prepared blood agar.
- B.fragilis appear pearl-grey while P.melaninogenica colonies are light brown to black.
- B.fragilis is resistant to penicillin while B.melaninogenica is sensitive
 Summary of different parasites
Trematoda
Habitat Definitive Host Intermediate Host Diagnostic Stage Infective Stage Mode of Infection Name of Disease
S. haematobium:- S. Haematobium :
Egg, containing Full formed
Penetration of skin of people
Pelvic and Vesical plexus Bulinus truncates snail Schistosomiasis,
Schistosoma spp. Miracidium Fercocercus Cercaria in infected water
Swimmers itch
(egg, Adult, cercaria)
S. mansoni:-
Radicals of the inferior - Man Schistosoma Mansoni: (oval in shape with terminal spine in
sch.haematobium, lateral spine in
by Fercocercus Cercaria
mesenteric plexus Biomphalaria Alexandrina sch.mansoni)

Fasciola Gigantica
Eggs Ingestion of encysted
Fasciola Spp. Bile Duct
- Man &
Lymnaea cailliaudi snail
Fasciola (Oval operculated with thin shell E ncysted Metacercaria
Metacercaria in improperly
washed vegetables or drink
Fascioliasis
(adult, egg, Cercaria) - Herbivorous animals Hepatica containing immature ovum)

Lymnaea Truncatula snail

Cestoda
Diphyllobothrium 1st: Cyclops Unembryonated egg plerocercoid larva Ingestion of Diphyllobothriasis
2nd: Fresh water fish pass in feces
Latum (salmon,cyprinoid fish)
plerocercoid larva in
improperly cooked fish
(mature segment)
- Cattle Egg Ingestion of
cysticercus bovis
Taenia Saginata (egg,
gravid segment)
Man - pig
(spherical operculated with thick radially
shell containing hexacanth embryo) (larval stage)
undercooked beef containing
viable cysticercus bovis
Intestinal taeniasis

Small Intestine
Hymenolepis - Man or
Egg
(spherical double walled translucent
Egg 1- Ingestion of Eggs with
Contaminated food Hymenolepiasis nana
Nana - larva of rat flea containing mature hexacanth embryo) 2- Autoinfection
(Adult, egg) 3- faeco-oral route

Echinococcus - Dogs & - Cattle

Hydatid cyst Embryonated egg Ingestion of
In Man
(Hydatid Disease ( Hydatidosis ) )
- sheep
Granulosus - Other canines
- occasionally Man in liver, lungs, etc in feces
Eggs with contaminated food
or drink
In Dogs (Echinococcosis)
(adult, Hydatid cyst in tissue)

Nematoda
Small Intestine Pigs or Eating under cooked pork
Trichenella spiralis (embedded in mucosa)
rats or The same as DH - Trichenella spiralis larva Encapsulated (teased) meat containing encysted
Trichenelliasis
(teased larva) - or encysted larva in striated muscle larva within Trichenella
Man capsule
Dogs & Cats ingestion of embryonated
Toxocara spp. Small intestine of
dogs & cats Man is an accidental host No Egg
Embryonated eggs
cantaining
eggs with food or drink Visceral larva migrans
(Toxocara canis, Toxocara cati) (egg) where life cycle not immature larva
completed .
Small Intestine 1- Pirenella conica snail Mature eggs Eating insufficiently cooked or
Heterophyes ( deeply embedded between The
:
(oval with thick operculum and knob at Encysted Metacercaria salted infected fish containing
Heterophyiasis
2- Mugil (boury) &
Heterophyes villi of
Jejunum & upper ileum) Tilapia (bolti) Fish
the end, golden yellow, with mature
Miracidium) in Fish encysted Metacercaria

(Adult, egg)
Small Intestine Egg
Ascaris ( free in the lumen with mucosal folds
(oval brown, coarse mammilated shell
Embryonated egg Ingestion of embryonated
Ascariasis
pressed against it )
Lumbricoides containing one cell embryo) containing 2nd stage
rhabditiform larva
eggs with food or drink

(Adult, egg)
Ancylostoma Small Intestine Eggs in stool Penetration of human skin by Ancylostomiasis
Mainly: - Jejunum 3rd Stage Filariform
duodenale - illum ( contain immature ovum
in 4-cell stage ) larva
3rd stage filariform larva (Hookworm Disease)
(filariform larva)

Trichuris Trichura
(adult, egg)
Large Intestine
Mainly: - Caecum Man No Eggs in stool
( Barrel-Shaped with thick shell
containing ovum in one cell stage)
Embryonated egg
containing 1st
stage
Rhabditiform larva
Ingestion of embryonated
eggs contain 1st rhabditiform
larva in food or drink
Trichuriasis
(Trichocephaliasis)

Enterobius Large Intestine Eggs in perianal region

1) Ingestion of Eggs in
contaminated food or drink or
Mainly: - Caecum,
Vermicularis - Appendix
Eggs inhalation through ai
Enterobiasis
(D-shaped double walled 2) Autoinfection .
- illum containing Mature Larva
(adult, egg) containing mature larva) 3) Retro infection: - migration
of larvae back to large
intestine after hatching

wuchereria Lymphatics & Microfilaria in blood

3rd stage filariform
escape of 3rd stage filariform
larva from mosquito (female
lymph nodes Bancroftian filariasis
Bancrofti of - lower limb & between 10pm and 2am larva culex) to skin through blood
meal (bite) (elephantiasis)
(Microfilaria) - external genitalia

Amoeba
all forms of parasite are Congenital ( Placenta )
Obligate intracellular Man & - Tachyzoites or
Toxoplasma gondii parasite Cats other Domestic animals and - cysts
infective (Trophozoites,
Pseudocysts, cysts, mature
Acquired
A) Ingestion of sporulated oocysts in food or Toxoplasmosis
tissue cysts in under cooked meat
(cyst) rats (accidental hosts) oocysts) B) Organ transplantation, Bl. Transfusio
(invade any nucleated cell)
In p.vivax 1) Bite of Infected female
( Ring, Trophozoites, schizonts, Anopheles Mosquito
Plasmodium spp. Red Blood Cells Vector gametocyte) stages in blood Malaria
Man Sporozoites 2) Blood Transfusion or
Female Anopheles In p. falciparum
(falciparum, vivax) (intra-erythrocytic) organ transplantation
mosquito (only ring, Trophozoites) stages in from infected donor
blood

Trichomonas Genitourinary system

Trophozoite Trophozoite
Sexual intercourse or contact
with contaminated toilet seats
Trichomoniasis
Vaginalis urethra, vagina, prostate,
urinary bladder
or congenital through birth
canal
(trophozoite)
Giardia lambia Small Intestine
especially Duodenum and
- Trophozoites or Cysts Ingestion of
cysts with contaminated food
Giardiasis
( Cyst ) - cysts (Quadrinucleated cyst) (Travelers Diarrhea)
upper jejunum or Drink
Entamoeba - Cyst in formed stool or Cysts Ingestion of
- Trophozoites in diarrheic mature cysts in food or drink Amoebiasis
Histolytica stool
( Mature Quadrinucleated
cyst)
(cyst, Trophozoites) Large Intestine
Balantidium Coli (cyst,
Trophozoites)
Man No - Cyst in formed stool or
- Trophozoites in diarrheic
stool
cyst Ingestion of
Cyst in food or Water
contaminated with pig faeces
Balantidiasis
(Balantidial Dysentery)

L.Donovani complex 1) Bite of infected female sand fly - Visceral leishmaniasis

Leishmania Spp.
( donovani (promastigote) )
Reticuluoendothelial system in inoculate (Kala-Azar)
all viscera (spleen, liver, etc) Amastigotes Promastigotes Promastigotes
L.tropica, L. Mexicana, 2) Direct contact or auto infection - Cutaneous Leishmaniasis
L.Braziliensis (Oriental Sore)
Reticuluoendothelial system in
skin and mucus membrane
Parasitology Slides
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Infectious diseases (Tick-Borne diseases & Parasitic infections) USMLE-WORLD www.mediconotes.com
Tick-Borne Diseases
Disease Description Clinical Features Diagnosis & Treatment
- Is a protozoal disease caused by the genus plasmodium, - Hallmark is cyclical fever (which it coincides with RBC lyses by parasites)  Dx is made from :
(which is a RBC parasite) . Fever patter : Giemsa-stained peripheral blood smear
 Fever occurs every 48 hours with vivax & ovale. TTT:
- Transmitted by tick bite of infected: anopheles every 72 hours with malarieae, A) Treatment:
mosquitoes.  Periodicity is NOT seen with falciparum (constant fever) - Chloroquine (safe in pregnancy) If chloroquine resistance :
a- Quinine & Tetracycline or
(P. falciparum  IV Quinidine & Doxycycline)
Malaria - You have 4 species:
 Falciparum: Most deaths are due to falciparum
- The typical episode consists of 3 stages :
1- Cold stage: chills & shivering  followed by b- & Mefloquine & Atovaquone–proguanil
# in Pregnancy & CRD
 vivax, ovale: are responsible for several relapse. 2- Hot stage: high grade fever  2-6 hours later B) Prophylaxis : to all travels to malarious regions
 malariae. 3- Sweating stage: diaphoresis & resolution of the fever.
1- Mefloquine :is the DOC for chemoprophylaxis against
Contraindicated in Seizures & Psych. chloroquine-resistant malaria.
- Started 1 week before travel  continued until 4 weeks after
Add a 2-week regimen of : Primaquine
departure from an endemic area.
Contraindicated in patients with G6PD deficiency
2- Primaquine (both for prophylaxis & ttt ) is indicated against:
p. vivax or p. ovale, (which can cause persistence in the liver).
- Parasite enters the patient’s RBC and causes hemolysis.
Babesiosis - Is a protozoal disease caused by the genus babesia . - Clinical manifestations vary from :  Definitive dx is made from :
Giemsa-stained thick & thin blood smear.
 Asymptomatic infection to
- Transmitted by tick bite of infected: ixodes tick , in
Clinically significant illness  Hemolytic anemia associated with:
usually occurs in people: endemic area: TTT:
jaundice, hemoglobinuria, renal failure, and death.
1- Over age 40, pts Etiology: B. microti in the northern & midwestern of US. 1- Quinine-Clindamycin or
 Unlike other tick-borne illnesses, rash is NOT a feature of babesiosis,
2- Without a spleen, or 2- Atovaquone-Azithromycin.
except in severe infection where thrombocytopenia may cause a
3- Immunocompromised. secondary petechial or purpuric rash.
1- Early localized stage:  Dignosis clinical / +ve (ELISA) & Western Blot tests for antibodies.
- Is a tick-borne illness caused by the spirochete Borrelia - Skin: erythema chronicum migrans (Bull's eye) at site of tick
Burgdorferi . 2- Early disseminated stage: (days to weeks to months after skin rash) TTT:
- Fever + Chills, fatigue, arthralgias, headache
- Transmitted by tick bite of infected: ixodes scapularis - Early Lyme Disease (Rash / Joint / Bell's palsy) :
- Neuro : -- Bell palsy (Cranial neuritis)
Lyme disease - History of: Outdoor activities (e.g., hiking, camping). -- sensory-motor neuropathies 1- Doxycycline (Oral) for 21 days
 Contraindicated in: Pregnant / Child <8 y  Amoxicillin
-- Aseptic meningitis (Brudzinski & Kernig signs negative).
-- Encephalitis Allergy: Erythromycin
- Cardiac: AV block / Myocarditis / Pericarditis 2- Amoxicillin / Cefuroxime
3- Late disseminated stage: (few months to years later) :
- For Cardiac & CNS (other than Bell's palsy) :
- Joint: Monoarthritis(Large especially knee) / chronic synovitis
Ceftriaxone (IV)
- Neuro: Encephalitis / Transverse myelitis
Typically 1 week after the tick bite.  Dx requires a high index of clinical suspicion
- Is a tick-borne illness caused by the intracellular bacteria
Rickettsia Rickettsii - In the first 3 days: TTT:
Rocky - Transmitted by tick bite of ticks feeding on animals
Indistinguishable from a self-limiting viral illness
FAHM: Fever, Anorexia, Headache, Myalgias / Nausea, vomiting
ABC’s should always come first when treating any pt. check vitals
to make sure that the pt is stable.
mountain - History of: Outdoor activities - After 3 days of fever  Rash : - If signs of shock (hypotensive) :
1- Maculopapular rash: The best NEXT best step is: IV fluids to replete intravascular volume.
spotted fever Organisms enter the host cells via tick bites multiply in the Starts peripherally (palms & soles)  Spread centrally (limbs/trunk/face) - After he is stable: DOC :
vascular endotheliumDamage to the vascular endothelium Doxycycline (Oral/IV) for both adults & children.
2- then petechiae:
- The most serious tick- results in : microhemorrhages, and microinfarcts.
Micro vascular damage as disease progress : - In pregnant:
borne disease in the US
- Petechiate + Hypotension & Non-cardiogenic pulmonary edema Chloramphenicol
- Is a tick-borne illness caused by one of 3 different Incubation period varies from 1 to 3 weeks.
 Dx : Confirm by serology
Ehrlichiosis intracellular gram -ve bacteria , genus Ehrlichia - FAHM
- Transmitted by tick bite. - No Rash  its description as : “spotless rocky mountain spotted fever.” TTT:
- Complications: Renal Failure / GIT bleeding
It infects and kills WBCs  show - Doxycyline (for 1 week)
intracellular inclusions (morulae) LABS:
 leucopenia / thrombocytopenia  aminotransferases.

Cysticercosis
NCC is the most common
parasitic infection of brain
Echinococcosis
Hydatid cyst is a fluid filled
cyst with an inner germinal
layer and an outer acellular
laminated membrane
- Is a parasitic disease caused by larval stage of the pork
tapeworm: Taenia solium
Normal Life cycle of Taenia Solium:
* Definitive Host: Humans (only)
* Intermediate host: pig
* Infective stage: larva
* Mode of infection: humans eat larvae in meat such as
infected, undercooked pork.
* Habitat: adult in upper jejunumexcretes its eggs into feces
If a pig consumes these eggs, it becomes an
intermediate host, with larvae encysting in its tissues.
- Echinococcus tape worm has two main species:
1- E.Granulosus  causes: cystic echinococcosis (CE)
2- E. multilocularis causes: alveolar echinococcosis (AE)
Normal Life cycle of E.Granlosus:
* Definitive Host: Dogs (& other canines)
* Intermediate host: Cattle / Sheep
* Infective stage: Embryonated Eggs in feces.
* Mode of infection: Eating food contaminated with egg.
* Habitat: Small intestine
Cestode
If a person (rather than a pig"intermediate host") consumes the T. TTT:
solium eggs excreted in human feces  Cysticercosis results. Treatment of Neurocysticercosis :
- After ingestion, the embryos are released in the intestine  larvae
Albendazole
invade the intestinal wall  disseminate hematogenously to encyst in:
1- Brain: Neurocysticercosis
-- multiple, small (usually <1cm ) , fluid-filled cysts in the brain
… parenchyma and have a membranous wall
-- On neuroimaging: invaginated scolex
2- Skeletal muscle
3- Subcutaneous tissue
4- Eye
- If a human (rather than sheep) consumes infectious eggs excreted by  Both be diagnosed with a combination of imaging and serology
dogs in the feces  Echinococcosis results.  In the absence of a positive serologic test: percutaneous aspiration
or biopsy (may be required to confirm the diagnosis).
- After ingestion, the oncospheres are hatched in the intestine 
penetrate the bowel wall  disseminate hematogenously to various
visceral organs  Formation Hydatid Cyst, mostly in : TTT:
1- Liver : RUQ pain, rupture to peritoneal cavity  anaphylaxis 1- Surgical resection as in liver cycts.
2- Lung: cough / chest pain / dyspnea / hemoptosis 2- Percutaneous management
3- Medical:
 Germinal layer gives rise to numerous secondary daughter cysts. Albendazole: 1 week prior to surgery/ 4 weeks postoperatively

Nematode
- It is caused by the roundworm trichinella spiralis 3 phases + Eosinophilia.  Dx: Triad clinical symptoms confirmed by serology.
- It is acquired by eating undercooked pork that contains • Initial phase: in 1st week  larvae invade the intestinal wall.
GIT symptoms: abdominal pain, nausea, vomiting, diarrhea. TTT:
Trichinosis encysted trichenella larva
Triad :
• 2nd phase: in 2nd week of infection  larval migration : 1- mild infection : No Antiparasitics
Local & Systemic hypersensitivity reaction Symptomatic treatment with analgesia & Antipyretics
(trichinellosis)
1- Muscle pain (myositis) Nail : “splinter” hemorrhages, 2- In Systemic Symptoms :
2- Periorbital edema Eye: conjunctival & retinal hemorrhages/per orbital edema/chemosis. - Albendazole / Mebendazole
3- Eosinophilia • 3rd phase: larvae enter the pt’s skeletal muscle: - together with corticosteroids
after eating raw meat = Trichinella spiralis (trichinosis) Muscle symptoms: muscle pain, tenderness, swelling, weakness.

- It is caused by the roundworm Ascaris Lumbricoides
- It is acquired by eating food that contains Embryonated egg
Ascariasis (containing 2nd stage rhabditiform larva)
Notes :
Ascariasis can also present with GIT symptoms + eosinophilia
Ascariasis often presents as :  Dx : Egg seen in stool examination.
1- Lung phase with non productive cough  followed by : TTT:
2- Asymptomatic intestinal phase 1- First line: Albendazole / Mebendazole
 Contraindicated in: Pregnant  Pyrantel Pamoate
Symptoms result from obstruction caused by the organisms, as:
small bowel or biliary obstruction. 2- Alternative: Ivermectin / Nitazoxanide

- It is caused by the hookworm: Ancylostoma duodenale
- Penetration of human skin by 3rd stage filariform larva 
tense pruritis at the site of injury
Ancylostomiasis - Migration through veins to the lungs and are swallowed 
then habitat in small intestine which have teeth to attach to
(Hookworm disease) mucosa and can remain up to 5 years where they mate and
produce eggs.
- Clinical Presentations: Morbidity from blood loss  Lab: Esinophilia
1- Iron deficiency anemia  Eggs can be identified on fecal smear
2- Hypoalbuminemia  Edema & anasarca
3- Cough TTT:
4- Abdominal pain , anorexia & diarrhea 1- First line: Albendazole / Mebendazole
5- Green-Yellow skin discoloration known as: Chlorosis ( seen in  Contraindicated in: Pregnant  Pyrantel Pamoate
chronic infection) 2- Ferruos Sulphate: If iron deficient

- It is caused by the pinworm Enterobius Vermicularais. At night, females migrate out through the rectum onto the perianal skin  Dx is by the “scotch tape test”  demonstrates presence of eggs.
Enterobiasis - Adult parasite thrives in the Cecum / appendix. to deposit eggs  Nocturnal Perianal Pruritis.  TTT: Albendazole or Mebendazole

Cutaneous - It is caused by dog & cat hookworm ancylostoma braziliense.

- It's acquired after skin contact with soil/sand contaminated
larva migrans with dog or cat feces containing the infective larvae
Notes :
(creeping eruption) Most common seen in the LE / but the UE can also be involved.
- Initially :
multiple pruritic, erythematous papules at the site of larval entry
 Dx is clinical in cutaneous disease/ & pulmonary disease : dry cough
TTT:
- Followed by: Migration
Severely pruritic, elevated, serpiginous, reddish brown lesions on
1- Preferred : Ivermectin
2- Alternative: Albendazole
the skin, which elongate at the rate of several millimeters per day as
the larvae migrate in the epidermis. No Antiparasites in Pulmonary disease since illness is mild & self-limited
Treatment of Parasitic infections
Helminthic infections
Ascariasis lumbricoides
(Roundworm)
Ancylostoma duodenale
Filariasis
Schistosomiasis
(Blood flukes)
Fasciola hepatica
(Liver flukes)
Heterophyes Heterophyes
(intestinal flukes)
E.granulosus (Hydatid disease)
Anti-Helminthic
Helminthic
Nematodes
Doses
• Albendazole 400 mg PO once (half dose in children <3 yrs)
yrs). (Albendazole tablet contains 200mg)
• Mebendazole 500 mg PO once (Alterna(ve for adults and children >1 yr)
• Ivermectin 150–200 mg/kg once.
• Albendazole 400 mg PO once (half dose in children <3 yrs).
• Mebendazole 500 mg PO once (Alternative for adults and children >1 yr)
• Pyrantel pamoate 11 mg/kg for 3 days .
• Diethylcarbamazine (DEC), 6 mg/kg daily for 12 days
days, has macro- and microfilaricidal properties
remains the drug of choice for the treatment of active lymphatic filariasis (defined by microfilaremia, antigen positivity, or
adult worms on ultrasound), although
• Albendazole (400 mg twice daily for 21 days) has also macrofilaricidal efficacy.
• Doxycycline
oxycycline , 4- to 6-week (targeting the intracellular Wolbachia)) also has significant
signifi macrofilaricidal activity.
The
he addi on of DEC to a 3-week
3 week course of doxycycline has recently been shown to be efficacious in lymphatic filariasis.
- Combination:
Combination Regimens that combine single doses of albendazole (400 mg) with either DEC (6 mg/kg) or ivermec n (200
g/kg) all have a sustained microfilaricidal effect and are the mainstay of programs for the eradication of lymphatic filarias
filariasis
in Africa (albendazole/ivermectin) and elsewhere (albendazole/DEC)
(albendazole/DEC).
Trematodes ( Flukes )
Effective on all For S. mansoni & S. haematobium
haematobium, give 20 mg/kg 2 doses PO for one day;
day
Praziquantel
species for S. japonicum give 20 mg/kg 3 doses PO for one day only;
Oxamniquine Effective only on:
20 mg/kg PO for 3 days.
S. mansoni
Metrifonate Effective only on:
7.5 - 10 mg/kg PO on 3 days, each 2 weeks apart.
S.haematobium
Triclabendazole 10 mg/kg once (harrsion's source)
Bithionol 10 -18
18 mg/kg PO tds on alternate days for 10 - 15 days.
Bithionol
(Alternative: dehydroeme(ne 1 mg/kg IM od for 10 days may be effec(ve during the acute stage.)
Praziquantel 25 mg/kg 3 doses per day , in one day.
Cestodes ( tape worms )
1- Cystectomy offers the best chance of cure.
cure
2- Albendazole , in hight dose ( 20 mg/kg/day ) (or 400 mg ) for 6 weeks up to 6 months.
Use pre-
pre and post-operatively is thought to give lower recurrence rates, and for many months.

Anti-Protozoal
Protozoal
Malaria
Drugs effective against erythrocytic forms Drugs effective against exoerythrocytic forms
Chloroquine Primaquine
• Drug
rug of choice in the treatment of erythrocytic P. falciparum malaria, except in resistant strains 8-aminoquinoline
aminoquinoline that eradicates :
• Mechanism of action : • Primary exoerythrocytic forms of P. falciparum & P. vivax
- The heme is toxic to the parasite To protect itself, the parasite polymerizes the heme to
hemozoin (a pigment), which is sequestered in the parasite's food vacuole. • Secondary exoerythrocytic forms of recurring malarias
- Chloroquine specifically
ically binds to heme, preventing its polymerization to hemozoin (P.
P. vivax and P. ovale).
increased pH & the accumulation of heme result in oxidative damage to the membranes,
leading to lysis of both the parasite & the red blood cell. Combination therapy :
Chloroquine-resistent
resistent P.falciparum : Primaquine is not effective against the erythrocytic stage of
These drugs are reserved for severe infestations and for malarial strains that are resistant to other malaria, therefore, is often used in conjunction with a blood
agents, such as chloroquine. schizonticide
schizonticide.

1- Quinine & Quinidine

• Mechanism of action : Similar to Chloroquine . Drugs effective against gametocyte forms
2- Pyrimethamine Primaquine
• Mechanism of action :
- Pyrimethamine inhibits plasmodial dihydrofolate reductase deprives the The sexual (gametocytic) forms of all four plasmodia are :
tetrahydrofolate ( a cofactor required in biosynthesis of purines & pyrimidines .
- destroyed in the plasma or
• Pyrimethamine alone is effective against P. falciparum. - prevented from maturing later in the mosquito,
• In combination with a sulfonamide, it is also used against P. malariae and Toxoplasma gondii.
3- Mefloquine : Mechanism of action : Similar to Chloroquine .
4- Artemisinin
Chemotherapy
Uncomplicated Malaria
Type of Disease or Treatment Regimen(s)
Chloroquine : 10 mg of base/kg stat , followed by 5 mg/kg at 12, 24, and 36 h or
Known chloroquine--sensitive strains of by 10 mg/kg at 24 h AND 5 mg/kg at 48 h
Plasmodium vivax, P. malariae, P. ovale, P. or
knowlesi, P. falciparum Amodiaquine : 10–12 mg of base/kg qd for 3 days
In addition to chloroquine or amodiaquine as detailed above,
Radical treatment for P. vivax or P. ovale Primaquine
rimaquine : (0.5 mg of base/kg qd) should be given for 14 days to prevent relapse.
infection In mild G6PD deficiency, 0.75 mg of base/kg should be given once weekly for 66–8
8 weeks. Primaquine should not be given in severe
G6PD deficiency.
Artesunate (4 mg/kg qd for 3 days) plus sulfadoxine (25 mg/kg)/pyrimethamine
pyrimethamine (1.25 mg/kg) as a single dose
Sensitive P. falciparum malaria or
Artesunate (4 mg/kg qd for 3 days) plus amodiaquine (10 mg of base/kg qd for 3 days)
Either artemether-lumefantrine (1.5/9 mg/kg bid for 3 days with food)
or
Artesunate
Artesuna (4 mg/kg qd for 3 days) plus
Multidrug-resistant P. fal
falciparum malaria
Mefloquine
Mefloqu (25 mg of base/kg—either g/kg on day 2 and then 10 mg/kg on day 3).
mg/kg qd for 3 days or 15 mg/kg
ither 8 m
 Either artesunate (2 mg/kg qd for 7 days) or quinine (10 mg of salt/kg d for 7 days)
plus 1 of the following 3:
1. Tetracycline (4 mg/kg qid for 7 days)
Second-line
line treatment/treatment of
2. Doxycycline (3( mg/kg qd for 7 days)
imported malaria 3. Clindamycin (10 mg/kg bid for 7 days)
or
Atovaquone-proguanil
Atovaquone (20/8 mg/kg qd for 3 days with food)
Severe Falciparum Malaria
Artesunate : 2.4 mg/kg stat IV , followed by 2.4 mg/kg at 12 and 24
24 h and then daily if necessary
or, if unavailable, one of the following :
Artemether : 3.2 mg/kg stat IM followed by 1.6 mg/kg qd .
or
Quinine dihydrochloride : 20 mg of salt/kg infused over 4 h, followed by 10 mg of salt/kg infused over 2–8 h q8h .
or
Quinidine : 10 mg of base/kg infused over 1–2 h, followed by 1.2 mg of base/kg per hour with electrocardiographic monitoring .

Chemoprophylaxis
hemoprophylaxis
Drug
- used for prophylaxis in pregnant women and - 200 mg PO od in adults, including pregnant women.
Proguanil non-immune
immune individuals in areas of low risk - Children <1 yr 25 mg/day; 1- 4 yrs 50 mg/day; 5-8 5 yrs 100 mg/day; and 9-14
14 yrs 150
only. mg/day.
- It is more commonly used in combination - A folic acid supplement should be taken during pregnancy.
with chloroquine
is used in combination with proguanil: - 300 mg (as base) PO weekly in adults, including pregnant women.
Chloroquine - in low-risk areas, - Children require 5 mg/kg weekly.
- in pregnant women, and • Chloroquine binds to melanin in the retina, causing concern that long-term
long term prophylaxis may lead
- other individuals who cannot tolerate to visual impairment/blindness. Total life (me exposure therefore should not exceed 100 g (~6 yrs
other antimalarials. of continuous usage).
• Twice-yearly
yearly retinal screenings should be perform
performed
ed in anyone who has taken 300 mg of
chloroquine weekly for >6 yrs.
Mefloquine is now a favoured drug for the prophylaxis of - 250 mg PO weekly in adults;
malaria in many areas where chloroquine - in children >45 kg 62.5 mg weekly in ch
children
ildren 3 months-
months 5 yrs, 125 mg for 6-8
8 yrs, 187.5 mg for 9-
9
resistance is present 14 yrs).
Mefloquine is not recommended in neonates.
Doxycycline useful as an alternate to mefloquine for short term - Dose: 1.5 mg/kg PO od, up to a max of 100 mg.
prophylaxis of up to 8 weeks. • Do not use in children <12 yrs and in pregnant and lacta ng women.
• Concep on should be avoided for >1 week aHer its use.
- 12.5 mg pyrimethamine + 100 mg dapsone (1 tablet of Maloprim) PO weekly for adults.
used in areas of chloroquine resistance (with
Pyrimethamine- - Children: 11-5 yrs ‫ ¼آ‬dose, 6-11 yrs ‫ ½آ‬dose, >11 yrs full adult dose.
chloroquine to cover P. vivax) when mefloquine or
dapsone (Maloprim®) doxycycline are contraindicated.
N.B.
Pyrimethamine-sulfadoxine
sulfadoxine (Fansidar®) is no longer used for prophylaxis due to the risk of Stevens Johnson
However, availability has become a limiting factor.
syndrome and bone marrow toxicity.

Amebiasis
Amebic Colitis or Amebic Liver Abscess (tissue amebiasis)
Tinidazole 2 g/d PO 3 days

Metronidazole 750 mg d PO or IV 10 days

5–10

Luminal amebiasis
Neither metronidazole nor tinidazole reach
reaches high levels in the gut lumen therefore, patients with amebic colitis or amebic liver abscess should also receive treatment with a luminal agent (paromomycin or
iodoquinol) to ensure eradication of the infection
infection.
Paromomycin 30 mg/kg qd PO in 3 divided doses 5–10
5 days

Iodoquinol 650 mg PO tid 20 days

Toxoplasmosis
Pyrimethamine + • Pyrimethamine 200 mg PO in divided
divided doses on day 1, then 75
75-100 mg PO , plus
• Sulfadiazine 1-1.5
1.5 g PO qds, plus
Sulfadiazine • Calcium folinate 5 mg PO every 3rd day
3-5
All for at least 6 weeks.
Calcium folinate
Maintenance therapy: pyrimethamine 25-50
25 mg PO daily AND sulfadiazine 0.5 - 1g qds daily for life.
Prevention:
- Pregnant women & immunocompromised people should be warned not to eat undercooked meat and to take care of personal hygiene
when in contact with domestic cats.
- Chemical prophylaxis with co-trimoxazole
co trimoxazole may be of value.
Giardiasis

Metronidazole 250 mg PO thrice daily for 5 days (Cure

Cure rates with metronidazole >90% )
In cases refractory to multiple treatment courses,
courses, prolonged therapy with metronidazole (750 mg thrice daily for 21 days) has been successful.

Tinidazole 2 g PO once .

Source: Harrison / Oxford tropical medicine

Viral Hepatitis (Source: Davidson, Kumar & Osama )
Viral hepatitis is a common cause of jaundice and must be considered in anyone presenting with hepatitic liver blood tests (high transaminases). The causes are :
Common causes Less common causes Rare causes
- All these viruses cause illnesses with similar clinical and pathological features
• Hepatitis A • Cytomegalovirus • Herpes simplex
• Hepatitis B ± hepatitis D • Epstein-Barr virus • Yellow fever
and which are frequently anicteric or even asymptomatic.
• Hepatitis C
- They differ in their tendency to cause acute & chronic infections. • Hepatitis E

- Features of the main hepatitis viruses : Clinical Features of acute infection :

Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
A) A non-specific prodromal illness :
Virus - Headache, myalgia, arthralgia, nausea & anorexia usually
Group Enterovirus Hepadna virus Flavivirus Incomplete virus Calicivirus precedes development of jaundice by a few days to 2 weeks.
Nucleic acid RNA DNA RNA RNA RNA - Vomiting, diarrhoea & abdominal discomfort may follow,
- Dark urine & pale stools may precede jaundice.
Size (diameter) 27 nm 42 nm 30-38 nm 35 nm 27 nm
Incubation There are usually few physical signs. :
1- The liver is often tender but only minimally enlarged.
(weeks) 2-4 4-20 2-26 6-9 3-8 2- Mild splenomegaly & cervical lymphadenopathy are seen.
Spread (These are more frequent in children or those with Epstein-Barr
Faeces Yes No No No Yes virus infection.)

Blood Uncommon Yes Yes Yes No B) Jaundice:

Saliva Yes Yes Yes Unknown Unknown - may be mild and the diagnosis may be suspected only after :
finding abnormal liver blood tests in the setting of non-specific
Sexual Uncommon Yes Uncommon Yes Unknown
symptoms.
Vertical No Yes Uncommon Yes No
- Symptoms rarely last longer than 3-6 weeks.
Chronic infection No Yes Yes Yes No
Prevention Complications may occur (rare) :
- Acute liver failure
Active Vaccine Vaccine No Prevented by No - Cholestatic hepatitis (hepatitis A)
hepatitis - Aplastic anaemia
Passive Immune serum Hyperimmune serum No B vaccination No - Chronic liver disease and cirrhosis (hepatitis B and C)
globulin globulin - Relapsing hepatitis

Virus Informations Investigations Management

- Type It belongs to the picorna virus group of enteroviruses.
- Spread by the faecal-oral route.
Patients excrete the virus in faeces for :
a- about 2-3 weeks before the onset of symptoms .
b- about 1-2 weeks after the clinical illness .
- Age Infection is common in children & young but often asymptomatic.
N.B. Up to 30% of adults will have serological evidence of past
Hepatitis A
infection but give no history of jaundice.
- Infection more common in areas of overcrowding and poor sanitation.
- In outbreaks water & shellfish have been the vehicles of transmission.
- In adults a cholestatic phase with elevated ALP levels may complicate infection.
- Acute liver failure is rare in hepatitis A (0.1%)
- No Chronic carrier state
- No Chronic hepatits.
- No Malignancy
- Type Caused by RNA flavivirus.
- Spread : - Mainly by blood transfusion (90% of cases)
- Saliva can be infected.
- Sexual & vertical transmission is uncommon.
- Clinical features (acute infections) :
- Most acute infections are a symptomatic.
- 10% will have 1- mild flu-like illness (fatigue, Nausea, anorexia , weight
loss ) with jaundice & 2-rise of serum aminotrasferases .
- Most individuals are unaware of when they became infected and are only
identified with routine biochemical test with mild elevations of
transaminases (ALT) or development of chronic liver disease .
Extrahepatic manifestations are:
1- Arithritis 2- glomerulonephritis associated with cryoglobulinaemia
3- porphyria cutanea tarda 4- there is a high incidence if diabetes
5- associations with lichen planus, sicca syndrome & non-hodgkin's lymphoma
Hepatitis C - Chronicity ( chronic infections ) :
- 85%- 90% of individuals exposed to the virus become chronically infected
There are at least 6 - Serum shows mild elevations or persistently normal ALT. ( important )
genotypes of hepatits C, - Late spontaneous viral clearance is rare.
genotype I account for
70%-80% of cases - Progression to cirrhosis :
- Progression from chronic hepatitis to cirrhosis occurs over 20-40 years in
about 20% of patients ( Not necessarily develop )
- Risk factors for progression include male gender, immunosuppression
(such as co-infection with HIV) & heavy alcohol misuse.
- Once cirrhosis has developed, 5- and 10-year survival rates are 95% & 81%.
- One-quarter of people with cirrhosis will develop complications within 10 years
once complications like ascites have arisen, the 5-year survival is around 50% C) Liver function tests
N.B. severe chronic hepatitis & even cirrhosis can be present with only minimal
elevation in aminotransferases
- Malignancy : Once cirrhosis is present, 2-5% per year will develop primary
hepatocellular carcinoma.
- Screening :
A) Blood donors:
- Blood donors are now screened for infection
- Hepatitis C is the cause of what known as 'non-A, non-B hepatitis', a syndrome of acute
hepatitis often with jaundice seen after a transfusion of blood or blood products.
B) Risk factors for infection :
- Intravenous drug misuse (95% of new cases in the UK)
- Unscreened blood products
- Vertical transmission (3% risk)
- Needlestick injury (3% risk)
- Iatrogenic parenteral transmission, (i.e. contaminated vaccination needles)
- Type :
- The hepatitis D virus (HDV) is an RNA-defective virus.
- It replicates only on the cells infected by HBV because HDV uses surface
antigen of HBV (HBsAg) as its envelope .
- Spread : as HBV .
• It is endemic in parts of the Mediterranean basin, Africa and South America,
where transmission is mainly by :
a- Close personal contact
b- Vertical transmission from mothers who also carry HBV.
Hepatitis D • In non-endemic areas, transmission is mainly by parenteral drug misuse.
(Delta virus) 1- It can infect individuals simultaneously with HBV ( co-infection ) :
- Giving rise to acute hepatitis, with +ve antiDelta IgM & HBcAB IgM .
- Fulminant hepatitis is more common with co-infection.
2- It can superinfect those who are already chronic carriers of HBV
( Super-infection ) :
- Giving rise to acute exacerbation of chronic HBV, with +ve antiDelta IgM
& HBcAB IgG.
- Chronic carrier who became super-infected are more severe & incidence
of complications as chronic active or fulminant hepatitis is much higher .
Chronic infection with HBV and HDV can also occur, & this frequently causes
rapidly progressive chronic hepatitis and eventually cirrhosis.
- Type Hepatitis E is caused by an RNA virus resembles calciviruses , and it has been categorized in an unclassified genus called Hepevirus .
- Endemic It is endemic in India and the Middle East An increase in prevalence has recently been noted in northern Europe and infection is no longer seen only in travellers from an endemic area.
Hepatitis E - The clinical presentation, spread ( via the faecal-oral route) and management of hepatitis E are similar to that of hepatitis A.
- in most cases, it presents as a self-limiting acute hepatitis and does not cause chronic liver disease.
- Diagnosis by detection HEV IgM or rising titre of IgG by RIA or ELISA . (In acute infection, IgM antibodies to HEV are positive).
Hepatitis E differs from hepatitis A in that infection during pregnancy is associated with the development of acute liver failure, which has a high mortality.
- HAV is only present in the blood transiently during the incubation period,
- Excretion of HAV in the stools occurs for only 1-2 weeks after the onset
of the clinical illness (can demonstrated in feces by E/M)
- There is only one HAV antigen
- Individuals infected with HAV make an antibody to this antigen (anti-HAV).
Anti-HAV of IgM type
- It indicates a primary immune response .
- It is already present in the blood at the onset of the clinical illness
and is diagnostic of an acute HAV infection.
- Titres of this antibody fall to low levels within 3 months of recovery.
Anti-HAV of the IgG type
- It indicates immunity to HAV.
- No diagnostic value,
- this antibody persists for years after infection, so can be used as a
marker of previous HAV infection.
A) Serology & virology :
- The HCV protein contains several antigens.
- Individuals infected with HCV make antibodies to these antigens.
1) Detection of anti-HCV antibodies:
- It takes 6-12 weeks for antibodies to appear in the blood following
acute infection
- Detection in the blood by ELISA & confirmation by a more specific
test RIBA ( recombinant immnuoblot assay ).
- Anti-HCV antibodies persist in serum even after viral clearance,
whether spontaneous or post-treatment.
2) Detection of the viral RNA by PCR :
- It takes 6-12 weeks for antibodies to appear in the blood following
acute infection such as a needlestick injury In these cases virus
can be identified in the blood as early as 2-4 weeks after infection
- Detection indicates the presence of circulating virus i.e. active
infection:
Active infection is confirmed by the presence of serum
hepatitis C RNA in anyone who is antibody-positive.
B) Molecular analysis
- There are six common viral genotypes
- Genotype has no effect on progression of liver disease
- but does affect response to treatment.
- Genotype 1 is most common in northern Europe & is less easy to
eradicate with current treatments.
- LFTs may be normal or show fluctuating serum transaminases
between : 50 & 200 U/L.
i.e. severe chronic hepatitis & even cirrhosis can be present with
only minimal elevation in aminotransferases
- Jaundice is rare & only usually appears in end-stage cirrhosis.
D) Liver histology ( invasive method ) :
- Serum transaminase levels in hepatitis C are a poor predictor of the
degree of liver fibrosis, and so a liver biopsy is often required to
stage the degree of liver damage.
- The degree of inflammation & fibrosis can be scored histologically
by Metavir system (most common with HCV) which scores:
fibrosis from 0(none) to 4 (cirrhosis),
Inflammation from 0 (none) to 4 ( severe )
- There is only one HDV antigen
- Individuals infected with HAV make an antibody to this antigen (anti-HDV).
1) Detection of viral RNA : By PCR .
2) Detection of HDV antigen :
Delta antigen appears in the blood only transiently, so in practice
3) Detection of anti-HDV antibodies :
- In practice diagnosis depends on detecting anti-HDV.
- Simultaneous infection with HBV & HDV:
• followed by full recovery is associated with the appearance of
low titres of anti-HDV of IgM type within a few days of the onset
of the illness.
• This antibody generally disappears within 2 months but persists
in a few patients.
- Superinfection of patients with chronic HBV infection
• leads to the production of high titres of anti-HDV, initially IgM &
later IgG.
• Such patients may then develop chronic infection with both
viruses, in which case anti-HDV titres plateau at high levels.
Prophylaxis :
- Improving social conditions, especially overcrowding & poor sanitation.
1- Active Immunization, by inactivated virus vaccine (Havrix):
- Indications :
1- Travelling to endemic area
2- Patients with chronic hepatitis B or C infections.
- Dose : 1ml/IM + booster dose after 6-12 month
- Validity: long life immunity (protection 100% for more than 10 years)
2- Passive immunization: by immune serum globulin(Abs contain HA Ab)
- Indications:
1- soon after exposure to the virus (within 6 days of exposure).
2- Travelling to endemic area (protection for 3-6 months).
3- Effective in an outbreak of hepatitis, in a school or nursery, as
injection of those at risk prevents secondary spread to families.
Other indications:
For those at particular risk, such as close contacts, the elderly, those with
other major disease and perhaps pregnant women.
Acute cases should be treated with interferon to prevent chronic disease.
Needle-stick injuries must be followed and treated early if there is evidence
of HCV viraemia
- There is no active or passive protection ( Vaccines ) against HCV .
--------------------------------------------------------------------------------------------
- The aim of treatment is to eradicate HCV RNA from serum.
- Indications of chronic infections:
1- Patients with chronic hepatitis on liver histology who have HCV RNA in
their serum & who have raised serum aminotransferases for more than 6
months.
2- Patients with persistently normal aminotransferases are also treated if
they have abnormal histology
3- Cirrhosis is not contraindications response is less likely .
A) The treatment of choice is :
SC pegylated α-interferon (180ug) given weekly,
together with +
oral ribavirin, ( 800 mg / day )
If HCV RNA PCR is negative at 3 months or has decreases by less
than 2 log, discontinue therapy .. if not continue treatment .
N.B.
1- Viremia less than 600 000 iu/ml has greater likehood of response to
antiviral therapy .
3- Protease inhibitors are currently in clinical trials; when given in
combination with interferon & ribavirin, they appear to increase efficacy.
Side effects :
- Ribavirin is haemolytic anaemia. Pruritus & nasal congestion .
- Interferon flu-like symptoms, irritability, and depression .
B) Liver transplantation :
- indication when complications of cirrhosis occur, such as diuretic
resistant ascites.
- Unfortunately, hepatitis C almost always recurs in the transplanted liver.
- Virological relapse can occur in first 3 months after stopping treatment.
- Cure is defined as loss of virus from serum 6 months after completing
therapy (sustained virological response, or SVR).
- The length of treatment & efficacy depend on viral genotype
• 12 months' treatment for genotype 1 results in a 40% SVR,
• 6 months' treatment for genotype 2/3 leads to an SVR in > 70%.
- Response to treatment is better in patients who have an early
virological response, as defined by negativity of HCV-RNA in
serum 1 month after starting therapy .
- Prevention of HBV infection by vaccination will condequently prevent
HDV infection.
- Vaccination dosen't prevent HBV carriers from super-infection by HDV.
 Hepatitis B
Three different types of particles are found in the patients serum :
1- Dane particle: ( 42 nm spherical particle ) :
- These are the complete infectious version of HBV
- It consists of :
1) Outer envelope which contains a protein called
the surface antigen (HBs Ag) , which is
important for laboratory diagnosis &
immunization.
2) Envelope surround the nucleocapsid core (HBc
Aa) which found in the liver but not in blood
3) Core surrounds: - Viral DNA ( genome ) .
- DNA polymerase.
4) HBe Ag is also a part of the core
2- Many 22mm spherical particles.
3- Many 22 nm tubular particles, that are over 200nm long
- Both are composed of HBsAg , and are non-infectious.

Mode of transmission
- Hepatitis B may cause an acute viral hepatitis which is often asymptomatic, particularly when acquired at birth. It should be assumed that all body fluids from HBV-infected patients may be infectious especially those who are
HBeAg positive.
- Many individuals with chronic hepatitis B are also asymptomatic.
1- Parenteral transmission :
- Chronic hepatitis, associated with elevated serum transaminases, may occur and can lead to cirrhosis, usually after
- By blood & plasma transfusion ( screening has reduced the risk.
decades of infection.
- Through the prick of contaminated needled, scalpels , tattooing or ear piercing.
Natural history of chronic hepatitis B : - Risk groups : Drug abusers, medical personnel, renal dialysis patients & those receiving
1- There is an initial immunotolerant phase with high levels of virus & normal liver biochemistry. repeated blood transfusion e.g. haemophiliacs.
2- An immunological response to the virus then occurs, with elevation in serum transaminases which causes liver 2- Carriers to close contact transmission :
damage: chronic hepatitis. - Sexual (homosexual and heterosexual)
3- If this response is sustained over many years and viral clearance does not occur promptly, chronic hepatitis may - Saliva can transmit the virus through bites.
result in cirrhosis. 3- Vertical transmisson :
4- In individuals where the immunological response is successful a- viral load falls, - From infected mother to the new born during birth or in the breast milk ( as it contains
b- HBe antibody develops low concentration of the virus ) .
c- there is no further liver damage.
5- Some individuals may subsequently develop HBV-DNA mutants, which escape from immune regulation, & viral load N.B. 1-The virus is found in saliva, semen & vaginal discharge.
again rises with further chronic hepatitis. 2- The risk of progression to chronic liver disease depends on the source of infection :
6- Mutations in the core protein result in the virus's inability to secrete HBe antigen despite high levels of viral replication; - Horizental 10% risk.
such individuals have HBeAg-negative chronic hepatitis. - Vertical 90% risk ( mosst common & higher risk ).
Investigations ( HBsAg is looked for initially; if it is found , a full viral profile is then performed )
1) Serology: Detection hepatitis markers by ELISA 1) The hepatitis B surface antigen (HBsAg):
Anti-HBc - It is an indicator of active & chronic infection , a negative test for HBsAg makes HBV infection very unlikely.
- HBsAg appears in the blood late in the incubation period but before the prodromal;
Interpretation HBsAg IgM IgG Anti-HBs - May be present for a few days only, then disappearing rapidly even before jaundice has developed,( HBc IgM ) Dignosis.

Incubation period + + - - - usually lasts up to 5 months. Its persistence for longer than 6 months indicates chronic live disease .or carrier
- In acute liver failure from hepatitis B the liver damage is mediated by viral clearance & so HBsAg is negative,
Acute hepatitis with evidence of recent infection shown by the presence of HBc IgM
Early + + - - 2) Antibody to HBsAg (anti-HBs) :
Established + + + - - Appears after disappearance of HBsAg, after about 3-6 months
- Persists for many years or perhaps permanently.
Established (occasional) - + + - - Anti-HBs implies either - Previous infection, in which case anti-HBc is usually also present, or
Convalescence ( the patient is immune ) - Previous vaccination, in which case anti-HBc is not present

(3-6 months) - ± + ± 3) The hepatitis B e antigen (HBeAg) :

- Appears during IP, shortly after appearance of HBsAg.
(6-9 months) - - + + - Detected in 1- the acute stage of the disease & 2- in some chronic carriers.
Post-infection - Its persistence implies: 1- Continued active replication of the virus in the liver infectivity & severity.
2- development of chronic liver disease & followed by the production of anti-HBe .
> 1 year - - + + Development of chronic hepatitis:
4) Antibody to HBeAg (anti-HBe) : - HBsAg persists and indicates a chronic infection (or carrier state)
Uncertain - - + - - Ag is followed by the production of anti-HBe (seroconversion), then Ag disappears & there is a rise in ALT ..
Chronic infection - HBeAg persists and correlates with
5) The hepatitis B core antigen (HBcAg) : 1- increased severity and infectivity and
Usual + - + - 2- the development of chronic liver disease.
- Not detected in the blood, and detected only in the nuclei of liver cells .
Occasional - - + - 6) Antibody to HBcAg (anti-HBc) : When anti-HBe develops (seroconversion) then Ag disappears &
Immunisation without - - - + - IgM appears with the onset of clinical illness (1st antibody to appear) and rapidly reaches a high titre there is a rise in ALT.
suggesting : 1- acute infection 2- continuing viral replication
infection - which subsides gradually within 6 months to be replaced by IgG which persists indicating past infection.. - HBV DNA suggests continual viral replication in Pre-c mutation .
These antigens & their antibodies are important - There is a period of several weeks when the HBsAg has disappeared & anti-HBs is not yet detectable Although the presence of anti-HBe usually implies low viral replication, the exception is anti-HBe -
in identifying HBV infection. positive replicating chronic hepatitis B (also called 'pre-core mutant' infection and discussed below),
know as window phase. At this time , the anti-HBc IgM is the only seological indicator of recent HBV in which high levels of serum HBV-DNA are seen, despite negative HBeAg.
infection
The site of HBV-DNA mutations.
2) Viral Load : - HBV-DNA encodes four proteins: a DNA polymerase needed
for viral replication (P), a surface protein (S), a core protein (C)
- Detection of the viral DNA by PCR is a strong evidence of viraemia . and an X protein.
- Viral loads are usually in excess of 105 copies/mL in the presence of active viral replication, as indicated by the presence of e antigen. - The pre-C and C regions encode core protein & e antigen.
- In contrast, in those with low viral replication, HBsAg- and anti-HBe-positive, viral loads are less than 105 copies/mL. - Pre-C encodes a signal sequence needed for the C protein to
be secreted from the liver cell into serum as e antigen.
- The exception is in patients who have a mutation in the pre-core protein, which means they cannot secrete e antigen into serum (Fig. ). - A mutation in the pre-core region leads to a failure of
secretion of e antigen into serum, so individuals have high levels
- Such individuals will be anti-HBe-positive but have a high viral load and often evidence of chronic hepatitis. of viral production but no detectable e antigen in the serum.
- They respond differently to antiviral drugs from those with classical e antigen-positive chronic hepatitis. - Mutations can also occur in the surface protein and may lead
to the failure of vaccination to prevent infection since surface
Measurement of viral load is important in monitoring antiviral therapy and identifying patients with pre-core mutants. antibodies are produced against the native S protein. Mutations
Specific HBV genotypes can also be identified using PCR. Genotypes B and C appear to have more aggressive disease that responds less also occur in the DNA polymerase during antiviral treatment with
well to interferon. lamivudine.

Management
Acute hepatitis B Prophylaxis
- Individuals are most infectious when markers of continuing viral replication, such as HBeAg, and high levels of HBV-DNA are present in the blood; they are least infectious when only
- Treatment is supportive with monitoring for acute liver failure, which occurs in less than 1% of cases. anti-HBe is present with low levels of virus. HBV-DNA can be found in saliva, urine, semen and vaginal secretions.
- There is no definitive evidence that antiviral therapy (e.g. lamivudine) reduces the severity or duration of acute hepatitis B. Pre-exposure prophylaxis : Post-exposure prophylaxis :
- Full recovery occurs in 90-95% of adults following acute HBV infection. - By active vaccination of those of high risk : Infection can also be prevented or minimised by the intramuscular injection
- The remaining 5-10% develop a chronic infection which usually continues for life, although later recovery occasionally occurs. Parenteral drug users, Men who have sex with men, Close contacts of of hyperimmune serum globulin prepared from blood containing anti-HBs.
infected individuals (Newborn of infected mothers, Regular sexual partners) This should be given within 24 hours, or at most a week, of exposure to
- Infection passing from mother to child at birth leads to chronic infection in the child in 90% of cases and recovery is rare. Patients on chronic haemodialysis , Patients with chronic liver disease, infected blood in circumstances likely to cause infection (e.g. needlestick
- Chronic infection is also common in immunodeficient individuals, such as those with Down's syndrome or HIV infection. Medical, nursing and laboratory personnel injury, contamination of cuts or mucous membranes)
- Fulminant liver failure due to acute hepatitis B occurs in less than 1% of cases. - It's made by recombinant DNA.
- It's given by IM injection 3 doses over 6 months ( 0,1,6 ) in deltoid. - Nonates born to hepatitis B-infected mothers should be:
- Each dose is 10ug for ( Recombivax ) & 20ug for ( Engerix ). 1- immunised at birth
Recovery from acute HBV infection occurs within 6 months and is characterised by the appearance of antibody to viral antigens. - The vaccine is ineffective in those already infected by HBV 2- and given immunoglobulin.
Persistence of HBeAg beyond this time indicates chronic infection. - To check vaccine, measure HBsAb at 7-9 months after the initial dose. 3- Hepatitis B serology should then be checked at 12 months of age..
Chronic hepatitis B
- Treatments are still limited, as no drug is able to eradicate hepatitis B infection completely (i.e. render the patient HBsAg-negative). The goals of treatment are 1) HBeAg seroconversion 2) reduction in HBV-DNA 3) normalisation of the LFTs.
- The indication for treatment is a high viral load in the presence of active hepatitis, as demonstrated by elevated serum transaminases and/or histological evidence of inflammation and fibrosis.
- The oral antiviral agents are more effective in reducing viral loads in patients with e antigen-negative chronic hepatitis B than in those with e antigen-positive chronic hepatitis B, as the pre-treatment viral loads are lower.
- Most patients with chronic hepatitis B are asymptomatic & develop complications such as cirrhosis and hepatocellular carcinoma only after many years. Cirrhosis develops in 15-20% of patients with chronic HBV over 5-20 years.(Proportion is higher in those who are e antigen +ve)
Interferon-alfa Lamivudine Adefovir Entecavir & telbivudine Tenofovir & other drugs Liver transplantation
-Indication : ( most effective ) in This is a nucleoside analogue which inhibits DNA - This is a nucleotide analogue that is - It was contraindicated in the
- These drugs are more effective than - Other drugs which also have action
1- patients with a low viral load and polymerase & suppresses HBV-DNA levels. phosphorylated to yield active drug which inhibits against chronic hepatitis B include presence of hepatitis B because
lamivudine and adefovir in reducing
2- serum transaminases greater than twice the upper limit of normal, - Indication : HBV-DNA polymerase. tenofovir and emcitabine; infection often recurred in the graft.
-Contraindication : It is effective in improving liver function in patients with - It reduces HBV-DNA levels by 3-4 logs, viral load in HBeAg-positive and
in the presence of cirrhosis, as it may cause a rise in serum decompensated cirrhosis. enhances the frequency of HBeAg HBeAg-negative chronic hepatitis - However, the use of post-liver
- these also have anti-HIV efficacy.
transaminases and precipitate liver failure. - Long-term therapy is complicated by the development seroconversion and leads to histological transplant prophylaxis with
improvement, - Antiviral resistance mutations occur
- Longer-acting pegylated interferons which can be given once weekly have been of HBV-DNA polymerase mutants (known as 'YMDD in only 1% after 3 years of entecavir - Tenofovir has recently been shown to 1- lamivudine &
evaluated in both HBeAg+ve and HBeAg-ve chronic hepatitis. - Adefovir is effective in suppressing most of the 2- hepatitis B immunoglobulins
variants'), which may occur after 9 months of ttt and is drug exposure. be superior to adefovir in the
characterised by a rise in viral load during treatment. lamivudine-induced DNA polymerase mutant treatment of chronic hepatitis B
- Other antiviral therapies are required because many patients with chronic hepatitis
B have high levels of viraemia and/or low transaminase levels, and are therefore - These viral mutants are less hepatotoxic than native viruses. has reduced the reinfection rate to 10%
- Contraindicated in renal failure. - Entecavir, unlike telbivudine, may
not candidates for interferon. virus. - The role of combination antiviral & increased 5-year survival to 80% .
have anti-HIV action and is
- Side-effects - Elevations in transaminases occur when lamivudine is - The HBV-DNA mutants develop at a lower rate therapy, as used in HIV infection, is
contraindicated in HIV patients who
stopped if mutant virus is present, as native virus than with lamivudine; 2% are identified after 2 still unclear.
fatigue, depression, irritability, bone marrow suppression and thyroid are not on antiretroviral therapy.
disease. replaces mutant virus. years of treatment but this figure increases to
- In the event of mutations occurring, other antiviral 18% after 3 years.
N.B:The drug appears to be better tolerated in patients with hepatitis B agents can be added (add-on therapy) but are less
compared to those with hepatitis C. - Relapse occurs on stopping treatment, and the
effective than when used in lamivudine-naïve patients. optimum length of treatment remains unknown.