Tropical Infection Diseases Gatot Sugiharto, MD, Internist Internal Medicine Department Faculty of Medicine, Wijaya Kusuma University Surabaya GSH - Tropmed Area kompetensi GSH - Tropmed 3 4 5 TYPHOID FEVER AND PARATYPHOID FEVER GSH - Tropmed Gatot Sugiharto, MD, Internist Internal Medicine Department Faculty of Medicine, Wijaya Kusuma University Surabaya Typhoid and Paratyphoid Definition Etiology Pathogenesis Epidemiology Clinical manifestations The laboratory and other examinations Complications Diagnosis and differential diagnosis Prognosis Treatment Paratyphoid Fever GSH - Tropmed Definition of Typhoid fever Acute enteric & sistemic infectious disease caused by Salmonella typhi (S.Typhi). Major symptom : prolonged fever, relative bradycardia, apathetic facial expressions, roseola, splenomegaly, hepatomegaly, leukopenia. GSH - Tropmed S. typhi Serotype : D group of Salmonella, Gram-negative, rod, non-spore, flagella (+), produced endotoxin Antigens: located in the cell capsule : H (flagellar antigen). O (Somatic or cell wall antigen). Vi (polysaccharide virulence) Hidup 2-3 minggu dalam air. 1-2 bulan dalam tinja. Mati dengan cepat di musim panas, ketahanan terhadap pengeringan dan pendinginan Widal test : identified antigen H & O GSH - Tropmed A schematic diagram of a single Salmonella typhi cell showing the locations of the H (flagellar), O (somatic), and Vi (K envelope) antigens. GSH - Tropmed Epidemiology GSH - Tropmed Transmission Rute: rute fecal-oral Risiko: kontak dekat dengan pasien atau operator Media: air dan makanan yang terkontaminasi Vector: lalat dan kecoak. GSH - Tropmed GSH - Tropmed Perlu setidaknya 10 5 bacteria untuk mengembangkan infeksi Incubation period : Agent ingested orally stomach barrier (some Eliminated) masuk kedalam usus halus penetrate the mucus layer enter mononuclear phagocytes of ileal peyer's patches and mesenteric lymph nodes proliferate in mononuclear phagocytes menyebar ke darah initial bacteremia 16GSH - Tropmed Pathogenesis (1) Pathogenesis (2) Second bacteriemia After 1st bacteriemia masuk ke limpa, hati dan sumsum tulang (sistem retikulo-endotel) proliferasi lebih lanjut banyak bakteri memasuki darah Recovery GSH - Tropmed S.Typhi. stomach Lower ileum peyer's patches & mesenteric lymph nodes 1st bacteremia (Incubation stage) 10-14d mononuclear phagocytes ( mononuclear phagocytes ) 2nd bacteremia liver spleen gall BM,ect early stage&acme stage (1-3W LN Proliferate, swelling, necrosis defervescence stage 3-4w S.Typhi eliminated convalvescence stage (4-5w) Bac. In gall Bac. In feces Enterorrhagi a, intestinal perforation thoracic duct GSH - Tropmed Pathology (lower ileum) (1) Lesi paling khas: ulserasi dari mukosa di wilayah patch yang Peyer usus kecil Tahap Hiperplasia (1 minggu): pembengkakan jaringan limfoid dan proliferasi makrofag. Tahap Necrosis (2 minggu): nekrosis pembengkakan kelenjar getah bening atau folikel soliter. GSH - Tropmed Pathology (lower ileum) (2) Tahap ulserasi (minggu ke-3): penumpahan nekrosis jaringan dan pembentukan ulkus perdarahan usus, perforasi. Tahap penyembuhan (dari minggu ke-4): penyembuhan ulkus, tidak ada cicatrices dan tidak ada kontraksi GSH - Tropmed Clinical manifestations (1) GSH - Tropmed Incubation period: 7 14 hari (3 60 hari ) Periode / tahap awal (minggu pertama) -Insidious onset. -Fever up to 39~40 0 C pada 5~7 hari -Menggigil Insidious onset, lelah, sakit tenggorokan, batuk, perut tidak nyaman dan sembelit dll. Clinical manifestations (2) GSH - Tropmed The fastigium stage (during 2nd & 3rd weeks) Demam tinggi yg berlanjutan, partly remittent fever or irregular fever (10 14 days) Gastro-intestinal symptoms: anorexia nyeri abdomen, diarrhea or constipation Neuropsychiatric manifestations: bingung, respon tumpul/lambat, delirium and coma or meningism GSH - Tropmed Circulation system: relative bradycardia or dicrotic pulse. Splenomegaly, hepatomegaly toxic hepatitis. roseola : 30%, maculopapular rash a faint pale color, slightly raised round or lenticular, fade on pressure 2-4 mm in diameter, kurang dari 10 in number on the trunk, menghilang dalam 2-3 days. First week: The disease classically presents with step- ladder fashion rise in temperature ( C) over 4 to 5 days, accompanied by headache, vague abdominal pain, and constipation. Second week: Between the 7 th -10 th day of illness, mild hepato-splenomegally occurs in majority of patients. Relative bradycardia may occur and rose-spots may be seen. Third week: The patient will appear in the "typhoid state" which is a state of prolonged apathy, toxaemia, delirium, disorientation and/or coma. Diarrhoea will then become apparent. If left untreated by this time, there is a high risk (5-10%) of intestinal hemorrhage and perforation. GSH - Tropmed Defervescence stage fever & most symptoms resolve by the forth week of infection. Fever come down, gradual improvement in all symptoms and signs, but still danger. Convalescence stage the fifth week. disappearance of all symptoms, but can relapse GSH - Tropmed Clinical spectrum (1) GSH - Tropmed Mild infection: very common, symptom & signs mild, good general condition, short period of diseases temperature is 38 0 C recovery expected in 1~3 weeks seen in early antibiotics users, young children, easy to misdiagnose Persistent infection: diseases continue than 5 weeks Ambulatory infection: mild symptoms, early intestinal bleeding or perforation. Clinical spectrum (2) GSH - Tropmed Fulminate infection: rapid onset, severe toxemia and septicemia. High fever, chill,circulation failure, shock, delirium, coma, myocarditis, bleeding and other complications, DIC Sepsis & shock Asymtomatic carrier Clinical manifestations reappear Less severe than initial episode Its temperature recrudesce when temperature start to step down but abnormal in the period of 2-3 weeks and persist 5~7 days then back to normal. Seen in patients with short therapy of antibiotics. 29GSH - Tropmed Recrudescence Relapse Serum positive of S.typhi after 1 3 weeks of temperature down to normal. Symptom and signs reappear the bacilli have not been completely removed Some cases relapse more than once GSH - Tropmed Laboratory findings (1) GSH - Tropmed Routine examinations : Leukocytopenia Recovery with improvement of diseases decreased in relapse Bacteriological examinations: Blood culture: The most common use 80~90% positive during the first 2 weeks of illness 50% in 3rd week Re-positive when relapse and recrudesce GSH - Tropmed The bone marrow culture The most sensitive test, specially in patients pretreated with antibiotics. Urine and stool cultures (after 1st week) Increase the diagnostic yield, less frequently positive Stool culture better in 3~4 weeks Serological tests (widal test) : 5 types of antigens O, H, and paratyphoid fever flagella A,B,C) Appear during 1st-2nd week 70% positive in 3~4 weeks and can prolong to several months, in some cases, antibodies appear slowly, or remain at a low level 10~30%) negative at all. Widal test interpretation GSH - Tropmed "O/H" agglutinin antibody titer 1:160 or "O" 4 times higher supports a diagnosis "O" rises alone, not "H : early of the disease Only "H" positive, but "O" negative : nonspecifically elevated by immunization or previous infections or anamnestic reaction. Antibody level maybe lower when have used antibiotics early. Complications GSH - Tropmed Intestinal hemorrhage Appear during the 2nd-3rd week Often caused by unsuitable food, diarrhea et al Serious bleeding : sudden drop in temperature, rise in pulse, signs of shock followed by melena/hematochezia Intestinal perforation: Appear during 2-3 week, involve lower end of ileum Abdominal pain, diarrhea, intestinal bleeding, sweating, drop in temperature, and increase in pulse rate, rebound tenderness, reduce or disappear bowel sound, liver dumping dissapear, leukocytosis (sign of peritonitis) Free air under x-ray. Toxic hepatitis : 1st-3rd weeks, hepatomegaly, ALT elevated Others : Myocarditis, encephalopathy, HUS, cholecystitis, meningitis, nephritis, etc Differential diagnosis GSH - Tropmed Viral infections Malaria Leptospirosis Louse borne typhus Riketsiosis Gram negative bacilli septicemia GSH - Tropmed Case fatality 0.5 1%, espesially in old ages & infant About 3% of patients become fecal chronic carriers Management (1) GSH - Tropmed General management Bed rest, good nursing care and supportive treatment Close monitoring VS, abdominal condition and stool. Easy digested food or half-liquid food, good hidration (enteral / par-enteral) Antipiretic drugs GSH - Tropmed Antibiotics Chloramphenicol : 500 mg, q6h (2 weeks) po/iv Thiamphenicol : 500 mg, q6h (10-14 days) po Cotrimoxazole : 2 adult tab, bid (2 weeks) po Ampicillin / amoxycillin : mg/kg BW in 3-4 divided dose (2 weeks) po/iv 3rd generation Cephalosporin : Ceftriaxone 2-4 g iv single/divided dose (3-5 days) Management (3) Quinolone : Norfloxacin : 400 mg, bid (2 weeks) po Ciprofloxacin : 500 mg, bid (7 days) po Ofloxacin : 400 mg, bid (7 days) Pefloxacin : 400 mg, OD (7 days) Corticosteroid Only for toxic/sepsis condition Dexamethasone 5 mg, tid iv GSH - Tropmed Paratyphoid fever A,B,C GSH - Tropmed Caused by Salmonella paratyphoid A,B,C. respectively. In no way different from typhoid fever in epidemiology, pathogenesis, pathology, clinical manifestations, diagnosis, treatment Homework Vaccination for S. Typhi, is it effective ? Gall culture, what make it a gold standard test & how to perform it ? New serologic test for S. Thypi GSH - Tropmed Yersinia infection Focus on Pes / Plaque Gatot Sugiharto, MD, Internist Internal Medicine Department Faculty of Medicine, Wijaya Kusuma University Surabaya GSH - Tropmed A zoonotic infection cause by Yersinia pestis, humans are accidental host Yersinia pestis : gram negative bacilli, facultatif anerob, susceptible to drying, produce endotoxin (lipid A Natural reservoir : tikus, tupai, kelinci & hewan domestik Menusuk oleh gigitan kutu, kontak langsung dengan jaringan yang terinfeksi (darah, unggas) atau inhalasi aerosol Pes / plaque Epidemiology of Plague Outbreaks are cyclical corresponding to rodent reservoir and arthropod vector populations Plague recorded more than 2000 years ago The pandemics : 14 th century; Black Death; 25 million dead in Europe alone (>1/4 of entire population) 1990s; From Burma, China, Hong Kong spread to other continents via rat-infected ships; 20 million dead in India alone Clinical evaluation Clinical Forms of Plague Bubonic plague : with swollen and painful axillary & inguinal lymph nodes (buboes) Transmitted from mammalian reservoirs by flea (arthropod) bites or contact with contaminated animal tissues Pneumonic plaque Person-to-person spread Diagnosis : culture & isolation Therapy : Streptomycin, tetracyclin, chloramphenicol or cotrimoxazole GSH - Tropmed TETANUS Gatot Sugiharto, MD, Internist Internal Medicine Department Faculty of Medicine, Wijaya Kusuma University Surabaya GSH - Tropmed Introduction Tetanus is an illness characterized by an acute onset of hypertonia, painful muscular contractions (usually of the muscles of the jaw and neck), and generalized muscle spasms coused by clostridium tetani infection Despite widespread immunization of infants and children in the United States since the 1940s, tetanus still occurs in the United States. Clostridium tetani Genus Clostridium : gram-positive, spore-forming species, several of which are able to produce disease in humans. Most species are obligate anaerobes, some will grow under microaerophilic conditions. Natural habitat: soil and the intestinal tracts of animals and humans. Very active metabolisms, ferment a variety of sugars, very short generation times. C. tetani Large, spore-forming, motile, obligate anaerobic bacillus, gram positive, drumstick appearence (see above) Ferments: proteins or amino acids. Produces: acetic acid, fatty acids, NH 3, CO 2, H 2, and a strong exotoxin Tetanospasmin (a powerful neurotoxin) & tetanolysin Clostridium tetani Gram Stain NOTE: Round terminal spores give cells a drumstick or tennis racket appearance. Tetanus : characteristic Does not follow typical tranmission from host to host. Soils or materials in contact with animal wastes are usually heavily contaminated with C. tetani Tetanus often resulted from wounds received in battle. In clean wounds with good blood supply and high oxygen tension, germination rarely occurs. In necrotic and infected wounds, anaerobic conditions will permit germination. Contaminated puncture wounds can be particularly dangerous, especially when a foreign body is present. Spores may occasionally lay dormant in a healed wound for months or years; trauma to the area may then cause germination and disease. Symptoms & signs Tetanus is an acute, potentially deadly, systemic infection characterized by painful involuntary contraction of skeletal muscles. Other symptoms include Febrile (feverish), irritability, heavy sweating A stiff neck, a tight jaw (lockjaw/trismus) Facial muscle spasms (risus sardonicus) and difficulty swallowing Spasm paravertebral muscle (opistotonus) Mechanism of Action of Tetanus Toxin A soldier dying from tetanus. Painting by Charles Bell Opisthotonos (spastic paralysis of the back) Risus sardonicus In advanced stages, tetanus spasms can break bones. Respiratory complications are common and death rates high, especially in children and elderly persons. Opisthotonos in Tetanus Patient Diagnosis of tetanus Made on the basis of the clinical manifestation, and the patients history may indicate inadequate immunization. Since C. tetani is a common contaminant of wounds and may be found in patients who do not develop tetanus isolation of the bacteria from a patient may not be diagnostic. Treatment Antitoxin (tetanus immune globulin) to neutralized toxin should be administered immediately. Wounds should be debrided to remove dead tissue or foreign bodies. Antibiotics should be given to inhibit growth of C. tetani. A tetanus toxoid booster immunization should be given to patients who have not received one within the last 5 years. If spasms occur, antispasmodic drugs should be used and respiration maintained by a breathing apparatus if necessary. As soon as clinical tetanus is suspected, steps to neutralize existing toxin and prevent the formation of new toxin must begin. Prevention Tetanus carries a 35% mortality rate, making prevention very important! Death may occur from tetanus, often from cardiac (heart) and respiratory (lung) effects or secondary complications from the infection The best course is childhood immunizations, with consistent booster doses, and prompt cleaning of wounds with hydrogen peroxide.