Case # 53presented

by

Mourad Mansourian

Summary Case 53Patient 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°CBlood pressure 115/75 mm HgPulse 104 b/min.

Passed out while walking to bathroomI.V. CefotaximeDischarged on oral Cefotaxime.Symptoms recurred 2 weeks later.

Green: Sporadic outbreaksOrange : Medium endemicity

Yellow: High endemicity

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 dayNausea and vomitingdehydrationLow blood pressure (dizziness-fainted in the hospital) Supine pulse 104 b/min

Blood and stool culture positive

Key information pointing to diagnosis

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. typhiElectron 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

Identification Blood agar-non hemolytic white colonies MacConkey-non lactose fermenting

smooth coloniesSS 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

PreventionNo 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