1. Case # 53 presented by Mourad 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 outbreaks Orange : Medium endemicity Yellow: High endemicity

4. 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

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

9. 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

10. Salmonella invasion of epithelial cells

11. Pathogenesis

12. 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)

13. S. typhi Electron microscopy Flagellar stain

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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)
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

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

21. References
Guzman c, Borsutzky S, Griot-Wenk M, Metcalfe IC, Pearman J, Collioud A, Favre D, Dietric G. Vaccines against typhoid fever Vaccine 24(18)
Chaicumpa W, Ruangkunaporin Y, Bur D, Chungsa-Nguan M, Echeveria P. Diagnosis of typhoid fever by detection of S. typhi antigen in urine J clinical Microbiol 30(9):
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 J. Proteo Res 7(2) 546-7
House D, Bishop A, Parry C, Dougen G, WeinJ. Typhoid fever: Pathogenesis and disease Infect Dis 14: