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Case # 53 presented by Mourad Mansourian

Case # 53 presented by Mourad Mansourian. Summary Case 53. Patient 32 yr. old male attended funeral in Haiti. 4 days later d eveloped temp. 39.5 °C, myalgia, constipation After 3-weeks history of fever, nausea, vomiting, diarrhea (6 watery stool/day), dark urine. Hospitalized with

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Case # 53 presented by Mourad Mansourian

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  1. Case # 53presentedbyMourad Mansourian

  2. Summary Case 53 Patient 32 yr. old male attended funeral in Haiti. 4 days later developed temp. 39.5°C, myalgia, constipation After 3-weeks history of fever, nausea, vomiting, diarrhea (6 watery stool/day), dark urine. Hospitalized with Temp 37.7°C Blood pressure 115/75 mm Hg Pulse 104 b/min. Passed out while walking to bathroom I.V. Cefotaxime Discharged on oral Cefotaxime. Symptoms recurred 2 weeks later.

  3. Green: Sporadic outbreaksOrange : Medium endemicityYellow: High endemicity

  4. Traveled to 3rd world country. Attended Haitian funeral-unembalmed bodies (customary food and drinks served-etiologic agent) Started with constipation rather than diarrhea (common S. typhi infection) Developed fever 39.5°C six watery diarrhea per day Nausea and vomiting dehydration Low blood pressure (dizziness-fainted in the hospital) Supine pulse 104 b/min Blood and stool culture positive Key information pointing to diagnosis

  5. Drumming, food and drink last for days

  6. Classifications • Gram negative rods • Motile • Encapsulated • Facultative anaerobic • Non sporing • Growth MacConkey non lactose fermenting smooth colonies • Growth on BA non hemolytic white colonies • TSI K/A H2S no gas

  7. Pathogenesis • Ingest organism via contaminated food or water • Organism resists gastric acid • Reaches the proximal end of small intestine • Invades & penetrates intestinal mucosa (at this time patient experience constipation rather than diarrhea) • Gains entrance into the lymph nodes • Reaches the blood stream • Spreads to the liver, spleen, and bone marrow • Engulfed by mononuclear phagocytes

  8. Salmonella invasion of epithelial cells

  9. Pathogenesis

  10. Pathogenesis continued • Multiply intracellularly • Released into blood stream for 2nd time • Febrile episode more evident (now can be isolated from blood) • Invades gall bladder and Peyer’s patches of the bowel • Reach the intestinal tract via billary tract, initiates GI symptoms (diarrheal stage) • Gall bladder becomes foci for long term carriage of the organisms (now can be isolated from stool)

  11. S. typhiElectron microscopy Flagellar stain

  12. Virulence factors • Subject to speculation and still remain uncertain • Role of fimbriae has been cited • Fimbriated strains are more virulent than non-fimbriated • Ability to traverse intestinal mucosa • Factors that mediate this mechanism have not been established • Enterotoxin production by certain strains that cause gastroenteritis implicated as virulent vactor

  13. Diagnosis • Definitive diagnosis is isolation of S. typhi from blood, bone marrow, urine or specific anatomic lesion • *Blood culture is the mainstay of diagnosis* • Presence of clinical symptoms of typhoid fever or detection of specific antibody response is suggestive but not definitive (Widal test 4-fold rise in titer between acute and convalescent stage) • Stool culture useful for diagnosis of typhoid carriers

  14. Identification • Blood agar-non hemolytic white colonies • MacConkey-non lactose fermenting smooth colonies • SS agar-black center with clear edges • Biochemistry • TSI K/A H2S (gas small amount) • LIA K/K H2S • Urea – • Motility + • Citrate +/- • Indole - SS agar

  15. Treatment • Should be based on antibiotic susceptibility of patient’s culture • Fluoroquinolones drug of choice • Commonly used drugs Sulfonamides, Streptomycin, Tetracycline, Cefotaxime, Ampicillin, and Chloramphenicol • Diarrheal stage replace lost fluid • Chronic colonization of gallbladder-persistent shedding of the organisms ”Typhoid Mary” remove gallbladder • Once asymptomatic and after three 24 hr apart consecutive negative stool cultures, may return to work

  16. PreventionNo typhoid vaccine is 100% effective. Food and drink precautions

  17. Primary research article contributing to the preventing of disease caused by S. typhi Guzman C. et al. 2006, Vaccine against typhoid fever. Vaccine, 24(18) 3804-11 • Purpose • To activate cell mediated immune response, post vaccination of CVD 909 derived from strains of CVD 908-htrA • Method • Group one vaccinated with a single dose of CVD-909 • Group two vaccinated with double dose • Results • CVD 909 is immunogenic after one or two doses, as the parent strain or the licensed Ty21a vaccines which confers moderate protection following 3-4 doses. • Conclusion • The second immunization dose did not enhance the lymphopolifiration response • Single dose vaccination is enough

  18. Result cont’d. Response to vaccination with a single and a double dose of CVD 909

  19. References • Guzman c, Borsutzky S, Griot-Wenk M, Metcalfe IC, Pearman J, Collioud A, Favre D, Dietric G. Vaccines against typhoid fever 2006. Vaccine 24(18) 3804-11 • Chaicumpa W, Ruangkunaporin Y, Bur D, Chungsa-Nguan M, Echeveria P. Diagnosis of typhoid fever by detection of S. typhi antigen in urine 2000. J clinical Microbiol 30(9): 2513-5 • Ansong c, Yoon H, Norbeck A, Gustin J, McDermott J, Mottaz HM, Rue J, Adkin J, HeffronF, Smith,D. Proteomics analysis of the causitive agent of typhoid fever 2008. J. Proteo Res 7(2) 546-7 • House D, Bishop A, Parry C, Dougen G, WeinJ. Typhoid fever: Pathogenesis and disease 2001. Infect Dis 14: 573-8

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