Case # 53 presented by Mourad Mansourian

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.

Green: Sporadic outbreaks Orange : Medium endemicity Yellow: High endemicity

Key information pointing to diagnosis 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

Drumming, food and drink last for days

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

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

Salmonella invasion of epithelial cells

Pathogenesis

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)

S. typhi Electron microscopy Flagellar stain

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

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

SS agar-black center with clear edges 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

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

Prevention No typhoid vaccine is 100% effective Prevention No typhoid vaccine is 100% effective. Food and drink precautions vaccine type Vaccine name How given Number of doses Time between doses Min. age Booster need every Oral attenuated TY21a Capsule by mouth Four Two days six years old Five years Capsular polysacch. ViCPS Injection One N/A Two years old Two years

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

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

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