7) AKONA -YAIEDRANE » Manipal =~" > Preo Manual of Medicine Second Edition Ly > =) 2 Manthappa M NBS, MD Ctra Meine) Associate Professor Department of Medicine JSS Medical College, JSS University ‘Mysuru, Karnataka ite Pcfesse,Departent of Necicine Ni Email: risthappa@yahoo com cBS CBS Publishers & Distributors evi iid New Delhi * Bengaluru * Chennai * Kochi * Kolkata * Mumbai Hydetobod + Nagpur * Patna + Pune + Vjayawada‘lece ogy 9 coat ear os New reach cd epemnce Gooden he scp ematen (raieooge hecunarhnessba nena oroten (rate ne ane pang Pe Te Fs bok Samexgh ob sre nove bean mace fo ore otra ‘sua the rela ot betes x rig rave been wh wnaraces Pe patho net Grane cater wet boro epeebe any Fado ‘rom omisorse racovaci Medicine ISBN: 978-81-259-2950-7 Copyright © Authok and Publisher : Second Edition: 2016 7 Repiint: 2017 Fest Ecition: 2011 Reprint: 2015 ‘Aight reserved, No par of this book ay be reproduced or onsmited in a fon or by ary means electonic or mechonica, incucing polocopying, recoding, or any infomation storage and retioval system without pamsson, in wing, from the author and the pubishe. Publsned by Salish Kumar Jain andi Poduced by Varun Jan tor (CBS Publishers & Distributors Pvt ic 481994 Prohlad Stee, 24 Ansar Rood, Doryagan, New Den 11900, Inco, re 25089280, a2, 23266667 Rac 017-252150 tet: wctspacsm ‘ema senigcosdoon: counogateratn Corporate Office 204 FE, Industial eo, Potpargan, Dem 1aa%2 Pre $934 938 Fee anne 235, emo pasunngscoracor: puoich@enadeam Branches * tenga: Soom House 2975, 17h Cas KR Road, Sonasorin 2nd Stage, Bonga 560 O72, Koma re sslapasnonoe ac esas ‘tem ongioebeecn * henna: No.7. Subboroy0 Steet Sheray Nagar, Chena €00 1, fom Nod * Woeni Asoo Howe, 391904 My onos Road, Vonjaribaiam.Enokucrn 682 018 Moc Wet * olka: No 8 Gouna Foot Rarewcr Shaw Rood, KOKGED TCD O14 We! Sera, da emg am ik a 8 rt mages + Mumbai 8; Dr E Mes Road, We, mrBo-409 O18, Meher Representatives + WrdrabedDSB8E17050 > Nagpur OUI THE 7 pana OPS RBD + Fane sses1%4 + Miorado. osonieosn Pineda Rosye Aries, Diba Garten, Dai nto 20 ¢FIV” 7 3 2 5 w 3 Contents Foreword by H Basavana Gowdappa vil Foreword by Raviraja V Acharya ix Preface to the Second Edition xi Preface to the First Edition xii 1. Infectious Diseases : 1 2. Diseases of Respiratory System 98 “3. Diseases of Cardiovascular System _ _ 149 “A. Diseases of Gastrointestinal System CO 5. Diseases of Nervous Systern = _ _ 299 6. Diseases of Blood eeeaer sc eeteceanantts 00377, 7. Diseases of Liver and Biliary System 8 8. Diseases of Kidney and Urinary Tract ee _ ATT 9. Endocrinology and Diabetes Mellitus == SOR 10. Diseases of Immune System, Connective Tissue, and Joints =—s§s—/§s <5 = 546 14. Nutritional Disorders «56 19. Psychiatric Disorders _ 588 13, Fluid and Electrolyte Disorders 602 VS (ladle _ on 45. Genetic Disorders = fmeuuedisee se eccceee enc r616) 46. Diseases ofthe Skin ee ey 17. Poisoning, Venomous Bites and Environmental Diseases 652 18. Emergency Medicine and Critical Care 674 19. Case Scenario Based Discussion 683 Index Z 703eo 8 8@. Define the terms infection, colonization, . ‘and infestation. Infection: lavasion by and multiplication of pathogenic . microorganisms in a bodily part or tissue, which may produce subsequent tissue injury and progress to overt > disease tough a variety of cellular or toxic mechanisms. Infection can be localized, as in pharyngitis, or Widespread as in sepsis. Colonization: It is the simple presence of potentially pathogertic microbes in or om a host. Infestation: Refers ta presence of parasites inside ar on 7 the host &. Discuss the serological (immunological methods used in the diagnosis of infectious diseases. + Serological (immunological) methods involve detection of antigen or antibody of a microorganism in a given sample. These are a follows: \ Enzyme-linked immunosorbent assay (ELISA) Rapid immunochromatographic test — Wester blot (immunoblot) test — Immanofluorescence test = Complement fixation test ~ Agglutination test Immunodiffusion ~ Tmmunoelectrophioresis Enzyme-linked Immunosorbent Assay (ELISA) + ELISA or the enzyme immiunoassay (ELA) makes use of enzyme-labeled immunoglobulin to detect antigens ot antibodies. It is a sensitive and specific test for the detection and quantification of antigens or antibodies. + BLISA tests are usually performed in microwell plats. Microwells in ELISA plates are coated with antibodies to the target proteins (antibodies o antigens). Clinica) sample is added into these microwells. If a specific [7] Antgenatached to wol in AER se — colored product Sustate Enryme's substrate is added, and reaction produces a visible color change Fig. 1.1: ELISA antigen or antibody is present in the clinical specimen, it is captured by the coated antibodies on the ELISA plate. AA second antibody to the target protein conjugated with ‘an enzyme is then added which is captured by the target protein. The unbound material is washed ont. A. chromogenic substrate (to the enzyme) is therr added.2 Development of color by the action of hydrolyzing enzyme on chromogenic substrate indicates the presence of the specific antigen or antibody. Color intensity is measured by the specwophotometer, * There are many vatiations of ELISA, but the basic principle remains the same as described above. In the first-generation ELISAS either crude antigen of single antigen is used for the test. In the secors- and. thicd- generation ELISAS multiple antigens of recombinant antigen or/and specific peptides are used, which improves the sensitivity ae specificity of the test. + ELISA is routinely used to detect antibodies against HIV and hepatitis A virus. Rapid Immunochromatagraphic Test *+ Here, the principle is same as ELISA, but the technique is embedded in a nitrocellulose membrane ofa test strip. ‘This allows rapid detection of antigen or antibodies in patient’s body fluids such as blood of serum. The presence of specific proteins is indicated by the development of colored bands on the strip. These diagnostic strip testsare simple, rapid, cheap and reliable andcan be used at home and clinics. Such Kits have been developed for dengue, malaria, etc. Urine pregnancy test Kit is also an example of immunochromatographic test which uses specific antibostes to selectively identify MCG. fn urine. ‘Western Biot (Immunobiol) Test + In Western blot, antibodies to nniiple specific proteins are detected. Hence, it has high specificity, Microbial protein is run on gel electrophoresis to separate the ligands, which are then transferred on toa nitrocellulose membrane strip. Patient’s serum is added to this nitrocellulose strip. If there are antibodies to a specific tnieroorganism, they bind to antigens present on the strip. Enzymaticably tabelled anti-immunoglobulins can be aided now which bind to the antibodies and visualised by the addition ofanentzyme substrate to produce colored bands, This test is commonly used to confirm the diagnosis of HIV infection, Immunofluorescence Test ‘This test makes use of immunoglobulin (antibody) labeled with fluorescent dye to detect antigens or antibodies. It requires a fluorescent microscope to read the signal. It is commonly used to detect infections with herpes virus, dengue virus and rabies virus Direct Immunoftuorescence * Direct immunofluorescence or direct fluorescent antibody (DEA) tes uses a single antibody labeled with Manipal Prep Manual of Medicine fluorescent dye to detect the presence of a specific antigen. Ifa specific antigen of a microorganist is present in patient's serum, it combines with the antibody labeled with a luorescent dye which can be detected as a fiuofescent signal. This testis highly sensitive and specific. Indirect immunofluorescence ° Here two antibodies are used. The first antibody recognizes the target antigen and binds to it, and the second antibody, which is labeled with a fluorescent dye cecognises the frst antibody and binds to + This test is more complex than the dicect immuno fluorescence test and takes more time but allows more flexibility, Patients serum is incubated with a specific microbial antigen. IF specific antibodies are present in the patient serum, they combine with the antigen. Next, flyorescent-labeled antisera is added and the fluorescent signal is looked for. Complement Fixation Test + This test is used to detect presence of specific antibodies ‘ta a microorganism, It depends on the antigen-antibody reaction which uses complement. Patient's serum is heat treated to renlove any free complement. It is then mixed with a specific antigen and sensitized sheep RBCS are added. Complement is added next. If antibodies are present in the patient’s blood, there is formation of ‘antigen-antibody complex and complement is sed up. If there is no antibody, complement remains unused and itlyses the sensitized sheep RBCs, Absence of hemolysis ‘means complement fixation testis positive which means that specific antibodies are present, This test has been largely superseded by other methods such as ELISA and PCR. Agglutination Test Direct Agglutination » Here, the patient's serum is added toa known antigen. antibodies are present in the patient’s serum, it leads to ‘egglutination, Weil-Felix test for serub typhus and direct agglutination test (DAT) for visceral leishmaniasis are ‘examples of this test. nclirect (Passive) Agglutination Test *+ Here, carier particles such as RBCs, latex, or gelatin, are coated with a soluble antigen and are mixed with patients serum. These particles aelutinae ifthe patent's serum contains antibodies In Latex agglutination test, latex particles coated with specific antibody ave mixed with patient's setum. I there 5 a bes 29.0 0 QO, a are specific antigens in the patient's serum, there is agglutination of antibody coated latex particles. This test is used to detect toxins of Vibrio cholerae dnd staphylo- cocci + In hemagglutination test, RBCs are coated with known antigens. [f mixed with serum containing specific antibodies, there i$ agglutination of RBCs. This is used in the diagnosis of syphilis and herpesvirus infections. Immun fusion Iinmnodiffusion is a diagnostic test which involves: diffusion through a substance such as agar gel, Here a specific antigen ot antibody is placed in ore well and. patient’s serum or body fluid is placed in another well ad left for 48 hours. The antigen and antibody diffuse thitough the agarose get towards each other and a precipitatfon line is formed between the two wells Immunoelechophoresis Inmunoelectrophoresis isa general name for a number of biochemical methods where proteins are separated by electrophoresis and identified using specific antibodies. ‘This teat is conducted om agarose. gel. Four types of immunoeleettophoresis (IEP) have been used: electro- immunoassay (BIA also called rocket-immuno- electrophoresis), classical immunoelectrophoresis (IEP), immunofixation electrophoresis (IFE) and immuno- precipitaion of proteins ater capiflary electrophoresis. ‘The procedure used in most laboratories is immuno- fixation electrophoresis (IFE). IFE is widely used for identifying Bence Jones proteins seen in multiple myeloma, @. Discuss the molecular methods isc in the diagnosis of infectious diseases. Molecular methods involve detection of RNA or DNA of amicroorganism. These ate polymerase chain reaction (PCR), southern blotting and northern blotting, Polymerase Chain Reaction (PCR) + Thisisthe mast specific and sensitive test ofall molecular techniques. Here the nucleic acid sequence of a microorganism is amplified so that it becomes easily detectable. Since each microorganisn has unique DNAS RNA sequences, it is possible to select a PCR primer that specifically identifies « particular microorganism, Multiple microorganisms can be identified in single clinical sample using ‘multiplex’ PCR. + Fluorescent dyes can be atached to different primers and the final nuclei¢ acid polymers examined by light spectroscopy. Infectious Diseases cet + Reverse transcriptase (RT)-PCR amplifies very small ‘amounts of any kind of RNA (mRNA, rRNA) ancl makes, complementary DNA, which is then amplified with conventional PCR. HAV viral copies are estimated by this method Real-time PCR is used to quantify the organisms and is used in estimation of HIV viral load. The disadvantages of PCR are its high cost and false positive results. False positive results happen if there is any contamination from laboratory ot other sources. Southem Blotfing * Southem blot isa method for detection ofa specific DNA sequence in DNA samples. Southent blot is named for biologist Edwin Southern who developed this technique. DNA fragments are separated by gel electrophoresis and transferred on to abloting paper. A DNA prote (this is piect of single stranded DNA with knows sequence, label with a radioactive isotope ora fluorescent signal) is then added to the bloting paper. DNA probe will bind toitscomplementary DNA if present, Tiss then washed to remove any unbound DNA probe, Even after washing if there is radioactivity ot fhuote- scence, it means that a specific DNA complementary to DNA probe is present. Since each snicroorganism has specific DNA sequences, it indicates the presence ofthat particular microorganism in the ctinical specimen. Northern Blotting + This is saine as Southern, blotting except that RNA fraginenis are used hereto detect mictobial RNA instead of DNA, @. Define fever of unknown origin (FU). Enumerate the couses of FUO, How do you approach a case of FUO? Earlier Definition + Fever of unknown origin (FUO) or pyrexia of unknown origin (PUO) is defined as fever of >38.3°C (>101°R) ‘on several occasions for at least 3 weeks and failure to reach a diagnosis even after 1 week of inpatient investigation. New Definition [As per new definition, FUO is elasified into the following categories: 1. Classic FUO_ 2. Nosocomial FUO- 3. Neutropenic FUO 4, FUO associated with HLV infection Infectious Diseases+ Classic FUO closely resembles the earlier cetinivion of FUO, Classic FUO is defined as fever of 238.3°C (2101°F) on several occasions which remains undiagnosed even after three outpatient visits o 3 days in the hospital or | week of “intelligent and invasive ambulatory investigation. + Nosocomial FUO is defined asa temperature of 238.5°C (2101°F) on several oscasions in a hospitalized patient in whom infection was not manifestor incubating atthe time of admission which remains undiagnosed even attr 3 days of investigation, including at least 2 days incubation of cultures. Infections (most common cause of FUO) Bacteria! + Tuberculosis (very common cause of FUO} + Typhoid * Brucellosis +. Infective endocarditis + Syphilis, Melicidosis * Sinusitis Osteomyelitis Prostatitis + Dental abscesses Cholangitis Intraabdominal abscesses (subphrenic, renal, retroperito ‘eal, and paraspinal abscesses) Viral” HIV * Chionic hepatitis (B,C, D) * Infectious mononucleosis + Q fever (Covel burmetth Parasitic + Malaria + Amebiasis + Letshmaniasis + Malaria + Strongyloigiasis + Toxocariasis ‘Toxoplasmosis Trichinetlosis Babesiosis Rickettsia infections + Qtever + Rckettsiapox ‘+ Rocky Mountain spotted fever + Sonu typhus Manipal Prep Manual of Medicine + Neutropenic FUO is defined asa temperature of 238.3°C (ELOI°F) on several occasions in a patient whose neutrophil count is 4 weeks for outpatients or >3 days for hospitalized patients with HIV infection which reinains undiagnosed even after 3 days of investigation, including 2 days incubation of cultures. Fungal + Candidiasis, «+ Histoplasmosis + Mucomycosis, + Blastomnyeosis * Cryptococcal disease Neoplasms (second most common cause of FUO) + Lymphoma y ‘+ Leukemia and other hematologic malignancies ‘+ iver involvement with hepatoma or metastases ‘+ Renal cell carcinoma * Colon carcinoma + bial myxoma Inflammatory and connective tissue disorders ‘+ Pheumatoid arthritis + Systemic lupus erythematosus (SLE) + Sarcoidosis + Inflammatory bowel disease (IBD) + Polyartertis nodosa (PAN) + Giant coll arteritis (common in elderly patients) + Polynyalgia theumatica * Crohn's cisease * Granulomatous hepatitis * Kikuchi disease Miscellaneous + Dugtever + Factitious fever * Periodic fever (familial Mediterranean fever) Undiagnosed ‘+ Even after extensive watk up some FUOs may remain Undiagnosed. Some of them may resnlve spontaneously «— 5 ee Approach to a Case of FUO Clinical History + Get a detailed history of general symptoms (eg, fever, ‘weight loss, night sweats, headache, rashes). Inquire about symptoms involving all major organ systems. + Contact with infection (tuberculosis) or animals (cat scratch disease, brucellosis) or birds (psittacosis). + High risk sexual behavior (HIV, hepatitis B). + Travel history (suspectinfections endesnc in places visite), Drug therapy (suspect drug fever). Occupation (e.g. farmers prone for leptospirosis, veterinary workers prone for brucellosis). + Recent dental treatment (possibility of endocarditis) + 1/0 immnosuppression such as HIV infection or steroid therapy (suspect oppactunistic infections) 11/0 previous abdominal surgery, tauma, endoscopy, of gynecologic procedures increase the likelihood of an ccult intra-abdominal abscess, Clinical Examination : + Do a complete physical examination + Document the height and pattern of fever. Measure the fever more than once and in the presence of a nurse to exclude factitious fever Dociment BP, pulse, respiratory rate and SPO,. BP may be low in septic shock and myocarditis. Pulse rate usually increases by 10 per degree celeius tse in. temperature. Relative bradycardia (i.e. pulse rate does not correspond to the raise in temperature) may be seen in enteric fever, brucellosis and some viral infections. Relative tachycardia, ie, pulserate more than expected tothe raise in temperature may be seen in myocarditis, sepsis, hypo- volemia and thyrotoxicosis, High respiratory rate usually points to some respiratory pathology such as pneurnonia, empyema, ARDS, etc. Look for lymphadenopathy (tuberculosis, infectious mononucteosis, HIV, lymphoma, malignancy), skin and mucosal lesions (skin rashes in connective tissue diseases, oral ulcers in Behget’s disease), pallor (may point to hematological malignancy, or a disseminated process such as TB involving bone marrow), jaundice (points to hepatobiliary disease) sternal tendemess (hematological malignancy), spinal tenderness (Pot's spine, epidural abscess), clubbing (TB, chronic suppurative lung disease) and for signs of meningeal imitation like neck stiffness and Kernig’s sign (meningitis. Carefully examine heart for any murmurs (infective endocarditis), abdomen for any tendesness (deep abdominal infections) hepatosplenomegaly (enteric feves, Infectious Diseases malaria, hepatitis, hemolytic anemia) or splenomegaly (malaria, hematological malignancies) Always examine the fundus avd retina (papilloedema in meningitis, retinal leisons in CMV infection, diss- eminated candidiasis, tuberculosis) Investigations + Common things are common. First try ro rule out common illnesses such as enteric fever, tuberculosis, malaria, UTI, HIV infection etc, and then only think of ‘axe illnesses. Order routine investigations like Hb, total WBC count, RBC count, differential cout, platelet count, ESR and peripheral smear study. Cytopenias may s logic process involving bone marrow such as disseminated tuberculosis, hematological malignancies, etc. A high leucocyte count is common in infections, A very high leucocyte count may suggest leukemia, A very high ESR (2100 by Westergren method) often indicates active tuberculosis, collagen vascular disease or malignancy. Urine microscopy and culture sensitivity (to R/O UTD). If there is cough and sputumn production, send it for Grams stain, fungus stain, AFB, malignant cells and cculture/sensitivity Blood culture and sensitivity or both aerobic and ancrobic organisms (infecting organisin may be picked up by ths). Complete LET and RFT to look for any liver and renal involvement Culture and examination of the stool for any ova Parasites and occult blood. Chest radiograph (tuberculosis, pneumonia, sarcoidosis). + Mantows test can help in diagnosing TB. ECG, echocardiogram (to look for signs of infective endocarditis). + Ultrasound abdomen and pelvis to R/O any intra- abxiominal pathology. Ultrasound can help in many ways. It can document any organomegaly, intra-abdominal lymphadenopathy or masses, ascites, any change in the texture of organs, any intra-abdominal collections of pus. Lumbar puncture and CSF examination if suspecting meningitis + Serological investigations (WIDAL test, ASO titre, HIV- ELISA, VDRL, TPHA, rheumatoid factor, antinuclear antibodies, viral antibody titres, Paul-Bunnell test, Brucella agglutination test). + CT/MRI scanning (abdominal lymph glands, tumors, meningitis, abscesses) + Tissue diagnosis (lymph node FNAC/biopsy, liver biopsy, bone marrow examination) + Diagnostic surgical procedures lke laparoscopy. explora- ‘ory laparotomy, etc may be required in undiagnosed cases Sahai 1 Infectious Disease:aia 8 Treaiment + ‘Treatment depends on the underlying cause. + Unlil a diagnosis is made, it is better to use only symptomatic treatinent, Blind antibiotic therapy may make diagnosis of an occult infection more dificult, and empirical steroid therapy may mask an inflammatory response without treating the underlying cause + Sometimes when all the tests are negative and the cause + of fever remains undiagnosed, a therapeutic trial may be Manipal Prep Manual of Medicine indicated. For example, antiuberculosis therapy (ATT) in suspected tuberculosis and steroid therapy in suspected connective tissue diseases Periodic review is very important in cases of FUO as development of new signs and symptoms may help in identifying the underlying cause. Insome cases a ‘second opinion’ by another physician can also be very helpf as different people think from different angles. Many uuidiagnosed cases of FUO will spontaneously resolve, Goal Shomoprophylaxis damage Meningitis + Due to meningocoeri + Due to H. influenzae type'o Twerculosis “To prevent recurrence and further cardiac ‘To provert infection in close contacts Phenoxymethy! peniilin 250 mg twice caiy 0° inj Benzathine penicilin once a month for many years as recommended To reduce and prevent infection in lose contacts and nasopharyngeal canfage Fitapicin 600 bd for 2 days Altomatives (single dose) ciprotixacin 500 mg (po) oF cetiaxone 250 mg (IM) Fifampicn 600 mg daly for 4 cays, “To prevent infection in exposed tuberculin- ‘negative individuals, infants of infected ‘mothers and immunosuppressed patients Oral isoniazid 300 mg dally for 6 months Valvular heart disease Prosthetic heart valves Malaria Prevention of malaria HIV infected pationt with CDS count below 200 cells HIV infected patient with toxoplasma IgG antibody postive and CD44 T coll count <100iut HIV infected pationt with CD4 ‘count below 50 colli! Prevention of toxoplasmosis infection To prevent infective endocarditis Prevention of Mycobacterium avium complex. Dental, ora, or upper respiratory tract procedures: Aroxiiin, 2g orally one rout betore the procedure, It allergic to penicilin, azithromycin 500 mg can be used . Genitourinary or gastrointestinal procedures: ighisk patients arogven ampicillin (2 g intravenously or intra muscularly) plus gentamicin (1.5 mg/kg. up to @ maximum dose of 120 ma) 30 minutes before the procedure followed by ampicilin (1 intravenously or intra- rmusculary) Or amoxiiin (1 oral) six [rou later, Patients who ar allergic to penilin shoud receive the sare tose gentamicin plus vancomycin (1 @ 1) one toto hours porto the procedre Coroquine one double strength tablet or weak oF meioquine 250 mg ance week ‘Prevention of Pasumacystisjroveci pneumonia| Trimethoprim-suifamethoxazole, cone double- strength tablet {260 ms) daly ‘Trimethoprim-sulfamethoxazole, one double-strength tablet (960 mg) daly ‘Azithromycin (1200 mg orally weekly) or clarithromycin (500 mg orally twice daily) LoQ. Cremoprophylanis (fable 1.2). + Chemopropiylaxis refers tothe administration ofamedica- tion fr the purpose of preventing an infection or disease, + Forexample, antibiotics may be administered to immune suppressed patients to prevent certain opportunistic infections. Antibiotics may also be given to healthy individuals o limit the spread of an epider, or to patients who have repeated infections (such as urinary uwac infections) (o prevent recurrence. @. Opportunistic infections (Table 1.3). + Opportunistic infection is an infection by a micro organism that normally does not cause disease, but becomes pathogenic when the body’s immune system is Impaired. Opportunistic infections are common in the following conditions: ~ Primary immune deficiency disorders ~ HIV infection ~ Steroid therapy — Chemotherapy for cancer Immunosuppressing agents for organ transplant recipients Malnutrition Prolonged antibiotic therapy + Opportunistic infections can be due to bacteria, viruses, protozoa or fungi, ' @. Nosocomial infections (hospital acquired infections). + The term nosocomial infection or hospital acquired infection is applied to any clinical infection that was HRESESERE orvorsisi stecton Infectious Diseases neither present nor was in its incubation period ‘when the patient entered the hospital. Infections are ‘considered nosocomial if they first appear 48 hows oc ‘more afler hospital admission or within 30 days of discharge. ‘They can manifest as urinary tract infection, pneumonia, postoperative wound infection and other systemic infections. Most common nosocomial infections urinary tract infection, Organisras + Bacteria: Staphylococcus epidermidis is the most ‘common organist causing nosocomial infection It most often causes wound infection, Other bacteria are Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter, methicillin resistant Staphylovoccus aureus (MRSA). Viruses: Hepatitis viruses (A, B, C), cytomegalovirus, influenza, respiratory syncytial virus, ete. * Fungi: Candida, Aspergiivs. Parasites: Toxoplasma gondii, Pneumocystis carini, scabies. Transmission © Spread of nosocomial infection may occur through different routes Spread through Contact * Contact with contaminated objects like bed pans, cathetets, aspiration and suction equipment, dialysers, gloves, sponges, surgical instruments, etc, may lead to infection Organism | Disease f Treatment Pheumocystis Interstal pneumonia Suiphomethorazole + trimethoprim Toxoplasma gondi' | Encephaltis, myocarditis, pneumonia | Suiphadiazine + pyrimethamine. Alternative ‘indamycin Cryptosporidium Diarthea Spiramyein Strongyloides Diarthea, episodes of septicaemia, pneumonia, | Thiabendazole Herpes simplex vius | Encephalitis Acyclovir Varicella zoster vitus | Disseminated herpes zoster Acyclovir Cytomegeiovinss | Interstitial pneumonia, retinitis, meningo- Gancyciovir ‘encephalitis, gastrointestinal tract ulcers Candida ‘Mucocutaneous, oesophageal, intestinal, Fluconazole, traconazoke, amphoteicin-B fenidocaratis, systemic infection Cryptococcus ‘meninges Disseminated infecton, especially ung and Amphotericin-B + flucytosine Infectious Diseases ONZe Spread through Vectors *+ Salmonellosis and shigellosis may spread through flies, malaria may spread through mosquito. Spread through Common Vehicle + Patients may be infected after contact with a common vehicle, e.g. sulmonellosis and hepatitis A may spread through infected food or water. Hepatitis B may spread through blood and blood products Airborne Spread * This occurs by droplet nuclei and is seen in tuberculosis, chickenpox, and measles. Prevention + Nosocomial infections increase medical expenditure and also cause significant morbidity and mortality. Hence all efforts should be made to prevent them. + Patients with infections should be isolated. * Aseptic measures should be enforced in wards, operation theatres and labor tooms, by arranging clean air, clean linen, adequate airspace, etc. There should be adequate space between beds. + Wound dressings and minor procedures like lumbar puncture, pleural and peritoneal tapping, etc. are better done in a separate procedure room and not bedside. * Pharmacy should check all intravenous fluids before supplying to wards, + The hospital kitchen staff should observe strict hygienic habits and should have periodic medical check up to detect and treat any infection + Every hospital should have an infection control committee which should monitor and control infections in the hospital @. Food poisoning. + Food poisoning is defined as an illness caused by the ‘consumption of food or water contaminated with bacteria and/or their toxins, or with parasites, viruses, or chemicals. Green leafy vegetables are the most common cause of food poisoning, followed by dairy items and poultry. * Food poisoning should be suspected when many people develop the illness after ingesting the same food and the illness bears a temporal relationship to food intake. Manipal Prep Manual of Medicine BEECREE ©2uses of food poisoning Infective Norvinfective Toxin mediated Plant toxins (flava beans), Preformed toxin: Staphylo- | paralytic shellfish toxin, coceal enterotoxin, bacillus | ciguatera fish poisoning, corous scombotoxic fish poisoning, heavy metals (arsenic, talium Toxin reduced inthe intos-| ree ny tine: Clostrigial spp. Vibrio cholerae, enterotoxigenic E. coli ‘Mucosal involvement Rotavirus, norwalk agent, shigella, giardiasis, Campyio- bbacter jejuni, Yersinia entero- coltica. Clinical features * The commonest manifestation of food poisoning is a ‘mixture of nausea, vomiting, fever, abdominal pain and diarthea. + {Usually symptoms occur in many persons who ingest the same food. ymptoms usually dev8lop within 48 hours after ingestion of food. In ease of preformed toxins and noninfective food poisoning symptoms develop within minutes to hous *+ Specific etiologic agent can be identified by examining the suspected food, vomitus, stool or blood. Management + Most cases of food poisoning are self-limiting. + Intravenous fluids and electrolytes should be given to patients with severe vomiting and diarrhea, * Antidiarrineal agents (codeine phosphate, loperamide) can be used to control diarrhea, However, they should be avoided in young children, elderly, and patients who have fever and pain abdomen suggesting infective diarrhea. * Antibiotics are not routinely indicated unless a specific pathogen is suspected. Prevention of Food Poisoning Following precautions can decrease the chances of food poisoning: * Do not drink raw (unpasteurized) milk or foods that contain unpasteurized milk. * Wash raw fruits and vegetables thoroughly before eating in running water. + Use precooked, perishable, or teady-to-eat food as soon as possible. ¢ €uo + Avoid «sss contamination; keep raw meat, fish, and poultry separate from other foots. + Thoroughly cook raw food from animal sources. Seafood, and sheltish should be cooked thoroughly to minimize the risk of food poisoning. + Refrigerate foods promptly, Never leave cooked foods at room temperature for more than two hours . Staphylococcal food poisoning. Staph. aureus is & common commensal of the anterior hares. Staph. aureus is eoagulase positive ands the most Virulent ofall staphylococcal species. All other staphylo- cocci have been collectively designated as coaguiase negative staphylococci and are less virulent. + Food handlers may transfer the bacteria via hands to foodstuissueh es dairy products, meats, eggs, and salads After the food is left at room temperatare, the onganisms ‘multiply and can produce a substantial quantity of heat stable enterotoxin, Ciinicet Features Following ingestion of comaminsted food, nausea, vomiting and abdominal cramps develop within 1~6 hours. Fever and/or diarrhea may also occur in a minority of patients. Most cases improve rapidly. Rarely severe dehydration ccan occur which can be fata. Management + Fluid replacement and antiemetics (domperidone, ‘ondansetron) should be given. Suspected food should be tested for the presence of enterotoxin and Staphylo- coccus if feasible. Public health authorities should be notified if food vending is involved ‘© Toric shock syndrome (ISS). + Toxic shock syndrome (TSS) is a toxin-mediated acute life-threatening illness, ustally caused by infection with either Staphylococcus aureus ot group A Streptococcus (GAS, also called Streptococcus pyogenes} + TSS was first described in asmait group of children with acute febrile illness. Subsequently, it was found in young, menstruating women who were using a highly absorbent tampon that was newly introduced to the market. This ‘was due o multiplication of vaginally colonized S. aureus and production of an exttoxin known as TSST-I and. enterotoxin B. However, tampon associated cases of TSS, hhave come down, and most cases are now secondary to ‘. aureus infections of skin ot other sites. Infectious Diseases + The criteria for the diagnosis of staphylococcal toxic shock syndrome are as follows: - Fever (usually >38.9°C ot 102°F) ~ Diffuse macular rsh, with desquamation 1-2 weeks after onset (including the palms an soies) ~ Hypotension (systolic blood pressure <90 mm He or orthostatic syncope) — Involvement of three or more ofthe following organ systems: Gastrointestinal (nausea and vomiting), ‘muscular (myalgias), mucous memibrane hyperemia), renal, hepatic, hematologic (decreased platelets), central nervous system, or pulmonary (acute respiratory distress syndrome) ~ Staph, aureus infection or mucosal colonization + TSS usually begins with nonspecific fluke symptoms such as fever and myalgia, In menstrual cases, the onset is osually 2 or 3 days after the stait of menstruation. When the severity of illness increases, patients develop hypotension, erythematous rash and symptoms of multiple organ involvement such as vomiting, diarrhea, confusion, myalgias, and abdominal pain. Mucosal involvement is common (¢-g. conjunctival hyperemia). Desquamation of he skin occuts during convalescence, usually 1-2 weeks after the onset of illness. Investigations + Investigations typically show leukocytosis, thrombo- cytopenia, increased urea, creatinine, hypoalburninemia sad liver function abnormalities. + Gram staining and coltuee sensitivity of the infected specimen. ‘+ Blood culture may show causative organism such as Staphylococcus of Streptococcus. Treatment ‘+ For staphylococcal toxic shock syndrome, large doses of a beta-lactamase-resistant, antistaphylococe: antibiotic should be given intravenously. Antibiotic choices are nafcillin or oxacillin. Vancomycin can be ‘wed in peniclleallergic patients. Clindamyein is also used in combination with above antibiatics for the first ‘few days to reduce synthesis of TSST-L + For patients with group A Streptococcus infection, the drug of choice is clindamycin (600-900 mg IV q8to. Penicilin G (4 million U IV qh) can also be combined ‘with clindamycin for better effect. + Duration of antibiotic treatment is 10 to 14 days, @. Enumerate the infections caused by © sireptocecci. Write briefly on scarlet fever and ~ erysipelas. Infectious Diseases SsStreptococci are gram-positive bacteria arranged in chains. ‘They cause a variety of infections in men which are as follows + Skin and soft tissue infections; cellulitis, erysipelas, necrotising fasciitis + Bone and joint infections + Tonsillitis + Scarlet fever + Glomerulonephnitis + Rheumatic fever + Puerperal sepsis + Endocarditis + Urinary tract infection + Neonatal infections including meningitis + Female pelvic infections + Pertonitis + Destal infections + Liver abscess. Scarlet Fever + Scarlet fever is syndrome characterized by exudative pharyngitis, fever, and bright-red exanthem. Scarlet fever is caused by toxin producing group A beta-hemolytic streptococci (GABHS). GABHS is found in secretions and discharge from the nose, ears, throat, and skin. + Exotoxin-mediated streptococcal infections range from localized skin infection (e.g. bullous impetigo) to the widespread eruption of scarlet fever to the highly lethal streptococcal toxic shock syndrome. Clinical Features * Scarlet fever is characterized by exudative pharyngitis, fever, and scardatinform rash. Initially patient develops fever, headache, vomiting and sore throat, followed within 24 hours by a punctate erythematous rash. Erythematous rash is caused by erythtogenic toxin, * Initially, the exanthem is seen on the tongue which becomes bright red with prominent red papillae, This appearance’ is called strawberry tongue. ‘The rash then appears onthe neck and spreads to trunk and extremities. ‘These rashes enlarge and join together to form a ‘generalized erythema, Usually the rash does not affect nose, lips, palms and soles. Since the lips are not affected itremains pale and stands out agains the red background ‘of flushed cheeks. Rash is more prominent in the skin folds and is called Pastia’s lines. Usually the rash becomes maximum by 2 days and fades by 7 days. Differentiat Diagnosis * Includes other causes of fever with generalized rash, such as: Manipal Prep Manual of Medicine Rubella, measles and other viol exanthems Kawasaki disease Toxic shock syndrome Systemic allergic reactions (eg. drug eruptions) Complications + Otitis media, pneumonia, septicemia, osteomyelitis, toxic shock syndrome, theumnatic fever, and acute glomerulo- nephritis Investigations + Complete blood count, Leukocytosis is seen. + Throat culture isthe most important test to confirm the diagnosis. + Direct antigen detecting kits allow immediate diagnosis but have less sensitivity. + Anti-deonyribonuclease B and antistreptalysin-O titers (antibodies to streptococcal extracellular products). Treatment + Penicillin is the drug of choice and is given for 7-10 ' days. Erythromycin isan alternative for patients allergic to peniciltin. Erysipelas + vis an infection of skin and soft issue. + Erysipelas usually involves the face and head but other areas may also be involved. + The skin becomes red, edematous and firm to hard in consistency due to cuticular lymphangitis. It may spread to adjacent parts and involve large areas, The margins of| the erythematous areas are raised and sometinies vesicles, ate also seen, The patient may appear sick + Erysipelas of the face has to be differentiated from cellulitis. Since cellulitis is an infection of subcutaneous Lissues, it does not involve the external ear Which has no subcutaneous tissue, while facial erysipelas can involve external ear (Millian’s sign). + Penicillin is the drug of choice for erysipelas. Q. Usteriosis. + Listeria monocytogenes isan aerobic, gram-positive rd, It isan intcacellular organism and is capable of invading several cell types. Liseriosis is rare and occurs mainly in newborn infants, elderly patients, and immuno- ‘compromised patients. Transmission + Man gets infected through contact with infected animals such as rodents or ruminants, or by ingestion ofwo Wy wy | | \ | contaminated foods. The main route of acquisition of Listeria is through the ingestion of contaminated food products, + Venereal transmission occurs occasionally. + Perinatal infection causes still birth or a septicaemic illness in the newborn. Ciinical Features + The disease is seen mainly in neonates and young children. Mother can get infected in late pregnancy which can lead to stillbirth, It presents as a febrile illness. The mother recovers after delivery but, occasionally, the organism persists in the genitalia to cause habitual abortions. If the neonate survives, the picture is one of severe infection, Neonates die in about three days but survivors develop suppurative meningitis + Listeria infection in tealthy adults is uncommon but affects immunocompromised persons like AIDS patiens diabetics, alcoholics and those with debilitating diseases. Listeriais an opportunistic infection in AIDS. Meningitis is often the clinical manifestation Investigations + Organism can be isolated by blood culture, and culture of any infected body fluid such as CSF. Treatment + The response to treatment is slow. + ‘The treatment of choice is intravenous ampicillin often incombination with an aminoglycoside. Penicillin G can ‘be used as an alternative to ampicillin + Trimethoprim-sulphamethoxazale is second fine drug and can be used ifthe patient is allergic to ampicilin ot penicillin, © Q. Discuss the etiology, pathogenesis, clinical ® features and complications of diphtheria. How do you investigate and manage a case of diphtheria? Etiology + Diphtheria is a localized infection of mucous membranes ‘or skim that is caused by Corynebacterium diphtheriae Itis associated with a characteristic pseudomembrane at the site of infection C. diphtheriae isa gram positive bacillus and resembles, Chinese letter patterns on Albert's stain. + There are 3 strains of C. diphtheriae; mits, intermedius and gravis. Gravis causes the most severe disease. Infectious Diseases A 4 Fig. 1.2: Diphtheria bacilt Epidemiology + Diphtheria affects people all over the world. But now it is uncommon due to immunization practices. tis more ‘common during winter. Itis mainly a disease of children. Humans are the main eservoi of C pluheriae. However, some cases have also occurred due to transmission from livestock. Spread occurs in close-contact settings through respira- tory droplets orby direet contact with respiratory secretions or skin lesions. Fomite transmission can also occur, Pathogenesis + Diphtheria is initiated by entry of C. diphtheriae into the nose ot pharynx. It multiplies locally without blood. stream invasion, Ttproducesa powerful exotoxin which causes local tissue necrosis, and fotmation of a tough, adherent pseudo- ‘membrane, composed of a mixture of fibrin, dead cells, and bacteria, The membrane usually begins on the tonsils, ‘or posterior pharynx and can spread to fauces, soft palate, and into the larynx, which may result in respiratory obstruction. Toxin entering the blood stream causes issue damage at distant sites, particularly the heart (myocarditis), nerves (demyelination), and kidney (tubular necrosis). Nontoxigenic strains may cause mild local respiratory disease, sometimes including a membrane. Clinical Features Respiratory Diphtheria + Nose infection presents as a chronic serosanguineous or seropurulent discharge without fever or significant toxicity. A whitish membrane may be observed on the septum. aS 1 Infectious Diseases+ The faucial (pharyngeal) form is most common. Aster an incubation period of 1 t0 7 days, the illness begins with a sore throat, malaise, and mild to moderate fever. Grayish membrane my be present that is tightly adherent and bleeds on attempted removal. In severe eases, the patient appears toxic. Cervical lymphadenopathy and soft Uissue edema may occur, resulting inthe typical bull neck appearance and stridor. * Laryngeal involvement pr and dyspnea. + Myocarditis presents with signs of low cardiac output and congestive failure. Conduction disturbances, ST-T wave abnormalities, arrhythmias, and heart block can occur + Neurologic involvement manifests as cranist nerve palsies and peripheral neuritis. Palatal and/or pharyngea) paralysis occurs during the acute phase sents as hoarseness, stridor, Cutaneous Diphtheria * Cutaneous diphtheria lesions are classically indolent, deep, punched-out ulcers, which may have a grayish white: membrane Invasive Disease + This is rare and may cause endocarditis, osteomyelitis, septic arthritis, and meningitis. Frequently, these patients have underlying immunosuppression Investigations * Gram’s stain: A presumptive diagnosis of C. diphtheriae can be made by identifying gram-positive rods in a “Chinese letter” distribution on Gram’s stain. * Cultures from beneath the membrane, from the nasopharynx, and from suspicious skin lesions. Cultares may be negative if the patient has received antibiotics * Toxigenicity testing should be performed on all C, diphtheriae isolates, *+ Polymerase chain reaction test may allow both detection of the organisms and determination of toxigenicity + ECG may show ST-T wave changes, heart block, and dysrhythmia, Treatment * The goals of treatment aré to neutralize the toxin, climinate the infecting organism, provide supporivecare, and prevent further transmission. Antitoxin + Diphtheria antitoxin is a hyperimmune antiserum produced in horses, which binds to and inactivates the diphtheria toxin, Manipal Prep Manual of Medicine * The antitoxin is only effective before toxin enters the cell and thus must be administered as early as possible, + There is risk of allergic reactions to antitoxin since it contains horse serum. Hence, a test dose should be given before administration. The dose of antitoxin depends upon the site and severity of infection. 20,000 to 40,000 units for pharyngeal! laryngeal disease, 40,000 to 60,000 units for nasopharyngeal disease, and 80,000 to 120,000 units For severe disease with “bull-neck”, The dose should be administered intravenously over 60 minutes Antibiotics *+ ‘They decrease toxin production indirectly by killing the organisms. *+ Penicilin isthe drug of choice. Penicillin G (25,000 to 50,000 uritstig IV Q12 h until the patient can take orally) followed by oral penicillin V (250 mg QID) for a total of 14 days + Erythromycin 500 mg QUD for 14 days is an alternative. Diphtheria Toxoid + Patients should be given diphtheria toxoid immunization during their convalescence since natural infetion does not induce immunity Prevention Isolate the patient. [Non immunised contacts shouldbe given bo antibioties and dihtheria antitoxin Immunised contacts are given a booster dose of diphtheria toxoid Fig. 1.3: Tetanus bacili 7000:2 3 ww |; @. Describe the etiology, pathogenesis, = clinical features and management of tetanus. ‘| Add. note on prevention of tetanus. + Tetanus isa serious illness caused by Clostridium reranus organism. it 18 characterized by an acuie onset of hhypertonia, painful muscular contractions (usally ofthe snuscles of the jaw and neck), and generalized muscle spasms. + Tetanus bas been desctibed by Hippoctates and in the Indian medical writings of Sushruta. Etiology + Ch tetanus is a Gram-positive, spore-forming, anaerobic bacillus: It has a drumstick appearance due t0 the presence of terminal spore, It is a normal commensal of human and animal gastrointestinal tracts and is widely distributed in soil. ls spores can survive for many years, even in adverse contitions. * Tetanus can occur in the following situations ~ Neonatal tetanus: Oceurs when the untbitical cord is, cut with an unsterile instrument or smeared wigh cowdung after cutting asis the practice in some areas, ~ After road trafic accidents where wounds may get contaminated easily with tetanus spores. Even a seemingly trivial injury may be able to cause tetanus, ~ People with otorrhoea may develop tetanus if the ear is probed with a wire of matchstick which may carry spores on it. ~ In women after illegal abortion due to unsterile handling of the genital tract through which organisms sain entry. ~ Intramuscular injections given with contaminated needles. ~ Necrotic or gangrendus tissues due to peripheral ‘vascular disease or any other cause, Pathagenesis + Spores inoculated into the wound develop into bacteria ‘These bacteria mhiply locally and produce nearatoxin tetanospasmin which is responsible for the clinical manifestations of tetanus, + Toxin released in the wound is disseminated throughout the body and binds to motoraveuron terminals in muscles, and ascends up the axon to reach nerve-cell body in the brainstem and spinal cord, The toxin then migrates actoss the synapse to presynaptic terminals where it blocks release of the inhibitory neurotransmitters glycine ‘and ‘-aminobutyric atid (GABA). As a result, minor stimuli result im uncontrolled spasms, and reflexes are exaggerated. ‘infectious Diseases, 2 SR +The time taken forthe toxin o ascend from nerve endings to CNS depends on the length of nerves. Since rain nerves are short, effect is first seen in cranial nerve tetttories like lock jaw. Clinical Features + The incubation period is 5 days to 15 weeks. + Tetaaus can present in one of four einical patterns — Generalized ~ Local = Cephalic ~ Neonatal ‘Generalized Tetanus + Thi8 is the most common and most severe form. + The classical clinical triad consists of wists (lock jaw) muscle rigidity, and reflex spasms. + Tetanie spasms mainly affect the muscles of the trunk: back and proximal parts of the limbs, and spare the pesipheries. ‘The patient first notices difficulty in opening the jaw dle to increased tone in the masseter muscles (ists, or lock jaw). Dyspllagia or stiffness or pain in the neck, shoulder, and back muscles appears concurrently or soon thereafter. Abdominal and limb musele involvement produces a rigid abdomen and stiff limbs. Sustained contraction ofthe facial muscles results in a grimace oF sneer (risus sardonicus), and contraction of the back muscles produces an arched back (opisthotonus), + Chest muscle spasms impair breathing. Laryngospasm may produce asphyxia + These spasms occur repetitively and may be spontaneous ‘of provoked by even the slightest stimulation. ‘They occur several hundred times a day. + Tetanic spasms cause contraction of both agonist and Antagonist groups of muscles together + Patient remains fully conscious and alert throughout, even during spasms, + Autonomic dysfunction is seen in severe cases and is characterized by labile or sustained hypertension, tachycardia, dysthythmia, hypespyrexia, profuse sweating, peripheral vasoconstriction, and increased plasma and urinary catecholamine levels. + Patient may develop many complications like aspiration Pneumonia, fractures, muscle rupture, chabdomyolysis, deep vein thrombophlebitis, pulioaary embolism. local Tetanus + Uncommon form in which manifestations are restricted to muscles near the wound. The prognosis is excellentnM Cephalic Tetanus + Rare form of local tetanus, follows head injury or ear infection. Tismus and dysfunction of one or more cranial nerves, often the seventh nerve, are found, Cephalic tetanus may remain localized or may progress to ‘generalized tetanus, The incubation period isa few days and the mortality is high, Neonatal Tetanus + Neonatal tetanus (tetanus neonatorum) is generalized tetanus that results from infection of a neonate. Differential Diagnosis + Inflammatory lesions inside the mouth can induce trismus (lock jaw). * Drug induced dystonic reactions (e.g. phenothiazines, metoclopramide). + Surychnine poisoning, + Hypocalcemic tetany. Treatment + The goals of therapy are to eliminate te source of toxin, neutralize unbound toxin, prevent muscle spasms, and support the patient until recovery. Patent should be kept in a quiet room to minimize stimulation. Patient should be continuously monitored for any sign of deterioration especially respiratory compromise. Antibiotic Therapy * Antibiotics are given to kill tetanus bacilli so that further production of toxin is prevented. + Penicilin is the drug of choice (10 to 12 million units intravenously, in divided doses daily for 10 days). Metronidazole is an alternative. Clindamyein and erythromycin can be wsed in those allergic to penicilfin. Antitoxin + Antitoxin is given to neutralize the free circulating and unbound toxin. It does not have any action on the bound toxin + Human anti-tetanus globulin (ATG) is the choice and is given in a dose of 3000 to 6000 units intramuscularly, usually in divided doses because the volume is large. ‘Human antitetanus immssoglobulin has a long half lite; hence repeated doses are not required Equine anti-etanus immunoglobulin can also be wsed but cartes risk of allergic reactions. However, itis cheaper. + The value of injecting antitoxin proximal to the wound ‘or infiltrating around the wound is unclear, Anttoxin does not penetrate the blood-brain barrier. The value of ‘nteathecal administration is still not cleat. ‘Manipal Prop Manual of Medicine Control of Muscle Spasms + Benzodiazepines like diazepam, lorazepam and midazolam can be used to control muscle spasins + Uncontrotied spasms even after giving benzodiazepines may reuire paralysis with a nondepolarizing neuro- ‘muscular blocking agent and mechanical ventilation, + General anesthesia with propofol may be required for continuous spasms. * Dantrolene and intrathecal baclofen can also be contsidered in severe spasms. Supportive Measures + Respiratory support with endotracheal intubation or tracheostomy, and mechanical ventilation, may be required. + IV fluids should be given to maintain hydration, + Hypertension due to autonomic dysfunction may be controlled by beta blockers, clonidine, and morphine sulfate, Hypotension or bradycardia may require volume expansion, use of vasopressors + Wound should be kept clean by debridement and removing any necrotic of foriegn material Prevention of Tetanus Immunization + All partially immunized and unimmunized adults should receive vaccine, as should those recovering from tetanus The primary series for adults consists of three doses: the first and second doses are given 4to 8 weeks apart, and the third dose is piven 6 to 12 months after the second, A booster dose is required therafter every 10 years, + Forpersons with unclean and major wounds, give tetanus immunoglobulin 250 units IM and also a dose of tetanus vaccine. Wound Core * Wounds should be washed thoroughly and any dead tissue and slough should be excised @. Discuss the etiology, pathogenesis, clinical {/ features, diagnosis and treatment of botulism. + Botulism is a paralytic disease caused by botulinum toxin, which is produced by Clastridiums botulinum. + C. botulinum san anaerobic gram-positive organism that forms subterminal spores. Itisis found in soil and marine environments throughout the world, Botulinusn toxin is the most potent bacterial toxin known. 9200, Pathogenesis + Under anaerobic conditions, the spores germinate and the bactecia multiply and release the exotoxin. Botulinum toxin inhibits release of acetylcholine at the neuco- ‘muscular junction and causes flaccid paralysis Botulinum toxin is extremely potent ancl is capable of Killing a person even in minute quantities. Kean be used as an agent of bioterrorism. + Naturally occurring botulism occurs in one of three forms: Food-bome botulism, infart botwlisis, ac wound botulism. Food-borne botulism is caused by ingestion of preformed toxin present in canned foods. Infant botulism occurs due to the practice of feeding honey to infants. Honey may contain botulism organisms and roligerate in the gut to produce toxin. Wound botulism usually occurs due to contamination of wound with organisms. Investigations ‘Toxin can be identified in serum, stool, vomitus, gastric aspirate, and suspected foods . botulinum may be grown on selective media from samples of stool or foods. Wound cultures that grow C. botulinum suggest wound botulism. Clinical Features Symmetric desvending patalysis is characteristic and usually starts in the extraocular muscles, and spreads to the pharynx, larynx, and respiratory muscles before inducing a generalised {laccid paralysis. Patient may have symptoms like ptosis, blurred vision, diplopia, pooling. of secretions, dysphagia and breathlessness, Nausea, vomiting and diarthea may occur if the source of toxin is intestine, Patalytic ileus may develop éve 10 intestinal mascles paralysis. + Fever is unisual + Patient is conscious and alert Sensory findings are usually absent Respiratory paralysis may lead to death in untreated cases, A diagnosis of botulism must be considered in patients with symmetsic descending paralysis who are afebrile and mentally intact, Treatment + Botulinum antitoxin should be given intravenoasty as early as possible. + Antibiotics are recommended for wound botulism along with incision and thorough debridement of the infected. ‘wound, Penicillin G or metronidazole can be used, Infectious Diseases + The immediate threat to life is respiratory failure, Close ‘monitoring for respisetary failure is important. If respiratory failure develops, endotracheal intubation and mechanical ventilation should be started, Tracheostomy is requied if the patient needs mechanical ventilation for a long time. . Gas gangrene. + Gas gangrene (also known as clostridial myonecrosis) is a bacterial infection that produces gas in tissues in gangrene. It usually occurs as a complication in, devitalised and devascularised tissues. It is a medical emergency. Etiology + 80% of cases are caused by Clostridium perfringens, while C. novyi, C.septicum, and C. histobticum cause the remaining cases. These organisms are true saprophytes and sre ubiquitous in soil and dust C. perfringens grows in anaerobic conditions and also produces a toxin, and enzymes like collagenases and ‘nyaluconidases which destroy the connective tissue and allow the infection o spread Clinical Features *+ The incubation period of gas gangrene is usually short; less than 3 days. ‘The first symptom is pain, along with numbness of the affected limb. There may be swelling around the wound, with pale surrounding skin, Serosanguinous foul- smelling discharge may be there from the wound. Crepitus can be elicited on palpation in and around the ‘wound due to gas formation Constitutional symptoms are severe with tachycardia and hypotension and the patient may be stuporose. Mild to moderate fever may be there. Sometimes uterine infection can occur following criminal abortion or poor aseptic technique during labor Laboratory Findings + Gas gangrene isa clinical diagnosis, and empiric therapy should be started if the diagnosis is suspected. + X-rays may show presence of ges inthe tissues. + The smear shows the presence af gram-positive rods, + Anaerobic culture confirms the diagnosis, Treatment + Wounds should be thoroughly cleansed and debrided. + ‘Traditionally, the antibiotic of choice for clostridial infection has been penicillin G (4 million units every 15 Sy { Infectious Diseasessale four hours IV). Recently clindamycin has shown to be superior to penicillin G. Combination of lizdamycin and penicillin is superior to penicillin alone. Metronidazole can be used instead of clindamycin, + Antitoxin is of doubtful value. + Hypetbaric oxygen may relieve constitutional symptoms but its effect on mortality is not clear [ @. Describe the etiology, pathogenesis, clinical i features and treatment of pseudomembranous colitis, Etiology + Pseudomembranous colitis is inflammatioi ofthe colon that oecurs in some people who have taken antibiotics. Itis usually caused by Clostridium difficile and occurs a few days afer starting antibiotic therapy. + Broad spectrum antibiotics such as clindamycin and ampicillin have been implicated most often, but tetracyclines and cephalosporins ae other causal agents Pathogenesis + C.difficecolonizes the intestinal tract after the normal gut flora has been altered by antibiotic therapy. + After colonization, C. difficile elaborates two large toxins: Toxin A an enterotoxin, and toxin B a cytotoxin, ‘These toxins initiate an inflamonatory process in the intestinal mucosa resulting in the disruption of epithelial- cell barrier function, diarrhea, and pseudomembrane formation, Clinical Features + Bloody diathea + Fever and abdominal pain. «+ Signs of dehydration may be there due to diarrhea, + Toxic megacolon and colonic perforation (rigid abdomen and rebound tenderness) can oocur in most severe cases. Investigations + Stool examination may show presence of WBCS. + Culture for C. difficile is slow and expensive, hence not recommended, + Stool assay for C. difficile toxins (mostly toxin B). Itis considered positive when cultured cells undergo cytopathiechanges when exposed to stool which contains toxin + Enzyme-linked immunoabsorbent assay (ELISA) for toxin A, + Sigmoidoscopy may reveal erythematous mucosa covered by adherent membranes over the coionic mucosa. ‘Manipal Prep Manual of Medicine Treatment + Allantbioties should be stopped and this alone may halt the diarrhoea. + Ifpatientis very sick, vancomycin (125 mg orally 4 times daily for 14 days) or metronidazole (500 mg orally 3 times daly for (4 clays) may be used to teat diarrhea. + Fidaxomicin is a macrolide antibiotic that és more effective than vancomycin in cancer patients. + Probiotics such as lactobacitfus may be considered but benefit is doubtful + Surgery:may be required for complications such as toxic megacolon, perforation and necrotizing colitis @. Anthrax (malignant pustule, woolsorters, : disease, Siberian ulcer, charbon). + Anthrax is a zoonotic infection caused by Bacillus anthracis. Anthrax is also known by various names like ‘malignant pustule, woolsortes’ disease, ccharbon, ete iberian ulcer, Etiology "6B. anthracis is a sporulating gram-positive rod + Actually it is a zoonotic infection which affects sheep, cattle horses and goats, Humans are alfected when spores are ingested or inhaled of inoculated into broken skin. This can happen either by direct contact with these. animals or contact with their products + Recently anthrax has attained notoriety because of its possible use in biological warfare. into the body, the spores germinate into vegetative bacteria and multiply locally. + Spores entering the lungs are ingested by macrophages and carried via lymphatics to regional lymph nodes, where they rapidly multiply and cause hemorrhagic |ymphadenitis + Invasion of the bloodstream leads to sepsis, killing the hast. Clinical Features ‘+ The incubation period is from I to 5 days. + Depending on the route of entry, anthrax cecurs in three forms: cutaneous, inhalational, and gastrointestinal forms. + Cutaneous anthrax is the most common presentation (95%). Spores inoculate a host through skin lacerations, abrasions, or biting flies. This form most commonly affects the exposed areas of the upper extremities. Initially the cutaneous lesion appears as a’small erythematous, maculopapular lesion, which subsequently| 1 undergoes vesiculation and ulceration to form a black eschar (malignant pustule). Sometimes sloughing of the eschar is associated with hematogenous spread, sepsis, and shock + Respiratory involvement (woolsorters’ disease) is due to inhalation of spores, resulting in nonproductive cough, fever and settostestal discomfort. Occasionally initial clinical improvement is followed by severe dyspnoea, stridor, cyanosis and death. Neck and chest wall edema may develop, Gastointestial infection occurs after ingestion of spores and presents as diarthea and vomiting, which can be bloody. Investigations + Chest X-ray may show mediastinal widening in inhalational anthrax, + Gram stain—geam-positive rods seen + Culture may grow B. andhracis. * Serological studies may demonstrate antibodies to Anthrax bacillus, Treatment + Firstline agent Ciproffoxacin, doxycycline. Secontl-line agents: Amoxicillin, penicillin G. Combination therapy is more likely to result in a cure than monotherapy, Systemic anthrax should always be treated with combination of three drugs. Fig. 1.4: Ganacocct @. Gonomhea; Gonococeal urethritis. Gonorrhea is a sexually transmitted disease (STD) characterized by purulent infection of the mucous membrane surfaces. + Itis one of the commonest STDs world over. = Infectious Diseases > Etiology + Itis caused by a gram-negative diplococeus Neisseria Infemaes, cervix is infected more often than the urethra Vaginal discharge, discomfort and dysuria are commen ssymptorns . Rectal gonorthea (proctitis) occurs in homosexual males and heterosexual females as a result of ano-genital sex. ‘The symptoms vary from mild anal pruritus and ‘mucopurulent discharge to symptoms of severe proctitis, with rectal pain and tenesmus, Pharyngeal gonorthea (pharyngitis) may occur as a consequence of of0-genital sex and may be seen in either sex. This is generally asymptomatic Ocular gonorthea is rare in adults. It occurs in neonates, as a result of contact of eyes withthe infected maternal bith canal. It presents a8 acute purulent conjunctivitis that may affect deeper structures of the eye and may cccasionally result in panophthalmits Complications In mtales—epididymitis In females—endometrtis, salpingitis, tubo-ovarian abscess, battholintis, peritonitis, and pelvic inflamuna tory disease. Disseminated gonococcal infection may lead to skin lesions, tenosynovitis, arthritis, and (in rare cases) endocarditis or meningitis Investigations Gram stain: Presence of typical gram-negative intra cellular diplococci establishes a diagnosis of gonontiea. * Culture + Polymerase chain reaction (PCR) { Infectious Diseases18 Treatment + Ceftriaxone 250 mg intramuscular (IM) single dose PLUS, azithromycin | g POsingle dose OR doxycycline 100 mg PO twiee day for 7 days + Quinolones like ciprofloxacin (500 mg} or levofloxacin (250 mg) are alternatives but resistance is emerging + Spectinomycin, 1 g intramuscularly once, nay be used for the penicilin-atlergc patient. @, Chancroid. + Chaneroid also known as “Soft chancre”, is a sexually transmitted disease (STD) characterized by painful genital ulcers that may be accompanied by inguinal lymphadenopathy. Etiopathogenesis © + Chanctoid is caused by Haemophilus ducreyi which is a small gram-negative bacillus. When examined by gram stain, organisms from culture often clump in long parallel strands, producing a so-called “school of fish” appearance. Its highly infectious + Itis pathogenic only in humans, with no intermediary host. ducreyi transmitted sexually by direct contact ‘with puculent lesions and by atoinoculation to nonsexual sites, such asthe eye and skin, H. ducreyi enters the skin through disrupted mucosa and causes a local inflamma- tory reaction. {t produces a cytotoxin which plays a role in epithelial injury and development of an ulcer. Epidemiology + Itis seen worldwide, and is associated with low socio- ‘economic and poor hygienic conditions. Chancroid is ‘most often seen in uncircumcised men. In women it may bbe asymptomatic. . Clinical Features * Incubation period is 4-7 days. * The ulcer is seen on the prepuce in. men and on the labia in women, It begins as a papule with surrounding erythema which ruptures and forms an ulcer. Ulers are usually multiple, painful, non-indurated and soft, bas undermined edges with a base of granulation tissue and slough. + Tender inguinal lymphadenopathy occurs in about half the patiests. These lymph nodes may become fluctuant (bubo) and rupture spontaneously Diagnosis * Gram stain of material from a bubo reveals large numbers of gram-negative coccobacilli, arranged in a ‘school of fish’ pattern, ‘Manipal Prep Manual of Mecicine + Culture isthe most definitive method of diagnosis, but the organist is fastidious. + Immunofluorescence test and serologic assays for antibodies are newer laboratory tests Differential Diagnosis + Chancroid ulcer has tobe differentiated from genital ulcer due to syphilis, lymphogranuloma venesexm, herpes simplex virus-2, and granuloma inguinal Treatment + Asingle 1 g oral dose of azithromycin will cure most people + Alternative regimens include ceftriaxone (250-meg intra- muscularly as a single dose), or ciprofloxacin (500 mg orally twice a day for 3 days), or erythromycin (500 mg orally three times a day for 7 days), + Fluctuant lymph nodes may require needle aspiration oF incision and drainage. @. Pertussis (whooping cough). * Pertussis (per: intensive, tussis: cough) is an acute respatory tract infection Caused by Bordetella pertussis, a gram-negative coccobacillus, + A severe bout of cough i followed by a deep inspiration with characteristic sound (whoop). Hence the name “whooping cough.” + The Chinese name for pertussis is “the 100-day cough,” which accurately describes the course of the disease. Epidemiology + Pertussis occurs workdwide but the incidence has come down due to vaccination, Periodic epidemics, however, continue world over. © The infection is mote common and serious in infancy and early childhood. Its highly communicable. + Even with the decline after vaccination, pertussis still continues (0 be a major health hazard, Pathogenesis * The organism is spread by deoplets from patents * Infection is initiated by attachment ofthe organism to the ciliated epithelial cells of the nasopharynx. Atach- rent is mediated by surface adhesions. At the site of attachment, the organism multiples, producing a variety ‘of toxins that cause local mucosal damage and systemic effects. There is local celtelar invasion, but systemic dissemination does not occut. Systemic manifestations are due (0 toxit