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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
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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
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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 nonfimbriated
 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 colonies
 SS agar-black center with clear
edges
 Biochemistry
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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.
Food and drink precautions
vaccine type
Vaccine
name
How
given
Oral
attenuated
TY21a
Capsular
polysacch.
ViCPS
Number
of doses
Time
between
doses
Min. age
Capsule Four
by mouth
Two
days
six years Five
old
years
Injection
N/A
Two
Two
years old years
One
Booster
need
every
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