1. Case discussion and topic review
PRESENTER- DR. PRADIP KATWAL
Moderator â DR. PURU KOIRALA
12/24/2011 1
pradip katwal
2. Clinical case
⢠Age â 36 yrs
⢠Sex- Male
⢠Add- Morang
⢠Presenting complaints:-
⢠fever with chills and rigors (4 days)
⢠Vomiting --4 days
⢠Headache --4 days
12/24/2011
3. ⢠G/C â ill looking, conscious oriented to time
place and person
⢠No pallor, No icterus
⢠Vitals:-
⢠Pulse= 78 beats/minute
⢠BP= 110/80 mmhg
⢠RR= 16 breaths/ minute
⢠Temp= 101 áľF
12/24/2011
4. systemic examination
⢠Chest â B/L equal air entry
B/L normal vesicular breath sounds
traube space dullness
⢠P/A-Soft, non tender
-spleen just palpable
⢠CVS- S1 + S2 heard
No murmur
⢠CNS- No neck rigidity
WNL
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8. ENTERIC FEVER
⢠Systemic illness characterized by fever and
abdominal symptoms
⢠The syndrome associated with enteric fevers
are produced only by a few of the Salmonella
⢠Salmonella typhi most important
⢠Salmonella paratyphi A, B,C
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10. Distinguished from other bacteria by
Biochemical and antigen structure
⢠Forms acid on glucose fermentation
⢠Do not ferment lactose
⢠Divided into serotypes on basis of
ďO antigen
ďH antigen
ďVi antigen
After 24 hours, this inoculated XLD agar culture plate
cultivated colonial growth of Gram-negative, rod-shaped and
facultatively anaerobic Salmonella sp. bacteria
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11. EPIDEMIOLOGY
⢠22 million cases of enteric fever occurs each
year
⢠600,000 deaths
⢠Major public health problem in developing
countries
⢠endemic in Nepal
Sharma N, Koju R, Karmacharya B et al. Typhoid fever in Dhulikhel Hospital,
Nepal, Kathmandu Univ Med J 2003; 2: 188-92.
WHO. Background document: The diagnosis, treatment and
prevention of typhoid fever
12/24/2011
12. Pubic health problem
⢠poor sanitation
⢠lack of a safe drinking water supply
⢠low socio economic conditions in resource-
poor countries
⢠evolution of multidrug resistant salmonellae
with reduced susceptibility to Fluoroquinolone
⢠Chronic asymptomatic carrier stage
.
Kanungo S, Dutta S, Sur D; Epidemiology of typhoid and paratyphoid fever in India
Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata,
India, Beliaghata, Kolkata-700010, India.
12/24/2011
13. Paratyphoid fevers on rise
⢠Salmonella enterica serovar Typhi (S. Typhi)
the most common aetiologic agent
⢠S. Paratyphi A (SPA) with an apparently
increasing number of cases.
Indian J Med Microbiol. 2010 Jan-Mar;28(1):51-3.
Emerging Salmonella Paratyphi A enteric fever and changing trends
in antimicrobial resistance pattern of salmonella in Shimla.
Verma S, Thakur S, Kanga A, Singh G, Gupta P
12/24/2011
16. TRANSVERSE THE MUCOUS
LAYER OF SMALL INTESTINE
INTERACTS WITH ENTEROCYTES AND MICROFOLD
CELLS THAT OVERLIES PAYER PATCHES
THEY ARE INTERNALIZED TRANSPORTED TO
SUBMUCOSAL LYPHOID TISSUE
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17. INTERACT WITH MACROPHAGES AND
LYMPHOCYTES OF PAYER PATCHES
ENLARGEMENT AND NECROSIS OF
PAYER PATCHES
SALMONELLA SURVIVE WITH IN MACROPHAGE
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19. Clinical features
Characterized by
ď Fever
ď Disturbances of bowel function
Headache, malaise
ď Anorexia, cough
ď Exanthem (rose spots), on the chest,
abdomen and back.
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20. Early physical findings
⢠Toxic ill looking
⢠Rash ârose spotsâ(30%)
⢠Realtive
bradycardia(50%)
⢠Hepatosplenomegaly
⢠Abdominal pain on deep
palpation
⢠Cholecystitis (3%)
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27. Serological test
⢠Non of the serological test is sensitive specific
or Rapid enough for diagnosis including the
classical widal test.
MANDELL, DOUGLAS AND BENNET; INFECTIOUS DISEASE PRINCIPLE AND
PRACTICE 5TH EDITION
12/24/2011
28. Widal test
We thus conclude that in endemic areas the Widal test is still of
significant diagnostic value provided judicious interpretation of the
test is made against a background of pertinent information, especially
Data which related agglutinin levels in normal individuals.
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29. reasons
⢠Use of empirical antibiotics
⢠Baseline titer depends upon geographic area
⢠Strain variation
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30. Serologic tests, like the agglutination
reaction (Widal reaction), are not reliable
because of false-positive results owing to
cross-reaction with other Salmonella spp.
and a sensitivity of only 70% (Maskalyk
2003)
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31. New serological test
⢠New serological tests
â Typhidot (better),
â high negative predictive value
â Dipstick test
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32. Retrospective study
ďś Determine the changing burden of salmonella
septicaemia
ďś Proportion of Salmonella paratyphi A
ďś Emergence of drug-resistant organisms.
82467 blood cultures performed
a bacterium was isolated from 12252
6447 (70.7%) Salmonella enterica serotype
Typhi (S. typhi)
2677 (29.3%) Paratyphi A (S. paratyphi A)
9124 (74.5%) Salmonella
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33. In comparing the period 1997-2000 to the
period 2001-2003 taken,
⢠salmonella septicaemia increase 6.2 to 13.6%
(P<0.001)
ď§ S. paratyphi A as a proportion of all salmonella
isolates rose from 23 to 34% (P<0.001)
ď§ Increased resistance to ciprofloxacin
Trans R Soc Trop Med Hyg. 2008 Jan;102(1):91-5. Epub 2007 Nov 26.
Emerging trends in enteric fever in Nepal: 9124 cases confirmed by blood culture 1993-2003.
Maskey AP, Basnyat B, Thwaites GE, Campbell JI, Farrar JJ, Zimmerman MD.
12/24/2011
37. ⢠Multi drug resistance
Ciprofloxacin
Ceftriaxone
Azithromycin
⢠Nalidaxic acid resistance
Ceftriaxone
Azithromycin
High-does ciprofloxacin
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38. Antibiotic resistance
⢠MDR is mediated by plasmid
⢠Quinolone resistance is frequently mediated
by single point mutations in the quinolone-
resistanceâdetermining region of the gyrA
gene
⢠Nalidixic acid resistant: MIC of
fluoroquinolones for these strains was 10
times that for fully susceptible strains.
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39. ďAzithromycin appears to be as good as the other
comparator drugs for most outcomes
ďAppears to be better than fluoroquinolones in
reducing clinical failure and duration of hospital
stay
ďBetter than ceftriaxone in reducing relapse
ďAzithromycin should be used guardedly to
prevent the emergence of strains resistant to the
drug
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40. ⢠In the summer of 2002, a total of 5963 cases of typhoid
fever were recorded in Bharatpur, Nepal
⢠This outbreak is the largest single-point source
outbreak of multidrug-resistant typhoid fever yet
reported
⢠traced to the city's single municipal water supply.
⢠Isolates were uniformly resistant to nalidixic acid,
⢠there was a decrease in their susceptibility as
measured by MIC of fluoroquinolones, and 90% of
isolates obtained were resistant to >1 antibiotic.
Lewis MD et al Typhoid fever: a massive, single-point source, multidrug-
resistant outbreak in Nepal. Clin Infect Dis. 2005 Feb 15;40(4):554-61. Epub
2005 Jan 21.
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41. ⢠MDR strains prevail in eastern Nepal. S.
⢠Typhi with reduced susceptibility to ciprofloxacin
has emerged.
⢠Resistance of nalidixic acid as a screening test for
detecting reduced susceptibility to the quinolone
group of drugs merits consideration.
⢠Determination of MIC confirms the less
susceptible strains which may indicate the
development of impending resistance among the
local isolates.
Basudha Khanal et al; Antimicrobial Susceptibility Patterns of
Salmonella enterica Serotype Typhi in Eastern Nepal J HEALTH POPUL
NUTR 2007 Mar;25(1):82-87
12/24/2011
42. ďąbased on a randomized, double blind, placebo
controlled trial carried out in Indonesia
ďąThis study showed a significant reduction in mortality
in patients with severe typhoid fever treated with
chloramphenicol and dexamethasone
as compared with chloramphenicol-treated control
patients
(case-fatality rate, 10% versus 56%).
On the basis of this study
ďą dexamethasone, 3 mg/kg intravenously,
ďąfollowed by eight doses of 1 mg/kg every 6 hours
⢠should be considered for the treatment of severe
typhoid fever with altered mental status or shock.
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43. A chronic carrier is defined as someone who excretes
S. Typhi in stool or urine for more than one year.
(1-4%)
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44. SALMONELLA AND AIDS
⢠20-100 FOLD RISK OF SALMONELLA
⢠CD4 COUNTS < 100/mm3
⢠Fulminant diarrhoea
⢠Recurrent bacterimia
⢠Acute enterocolitis
⢠Zidovudine and cotrimoxazole
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46. Ty 21a
⢠live oral vaccine ( typhoral )
⢠stable mutant of S.typhi strain Ty 21a
⢠43-90% in endemic population
⢠One capsule given orally taken before food,
with glass of water or milk
⢠Four doses
⢠Booster series
No antibiotics should be taken during the
period of administration of vaccine
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47. Vi Capsular polysaccharide
⢠The injectable vaccine
⢠purified Vi polysaccharide antigen of S.typhi strain ty21
⢠single subcutaneous or intramuscular injection
⢠Single dose is adequate.
⢠74% efficacy
⢠Booster doses every 2 years
⢠Modified Vi vaccine conjugated to a nontoxic
recombinant Pseudomonas aeruginosa exotoxin A )
evaluated in Vietnam-(protective efficacy was 91.5
percent)
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48. Vaccines for Typhoid
Both vaccines are given to only > 5 years of age.
Immunity lasts for 3 years
Need a booster
Vaccines are not effective in prevention of
Paratyphoid fevers
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49. Simple hand hygiene and washing
can reduce several cases of Typhoid
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50. Refrences
⢠Sharma N, Koju R, Karmacharya B et al. Typhoid fever in Dhulikhel
Hospital, Nepal, Kathmandu Univ Med J 2003; 2: 188-92.
⢠Kanungo S, Dutta S, Sur D; Epidemiology of typhoid and paratyphoid fever
in India
⢠Division of Epidemiology, National Institute of Cholera and Enteric
Diseases, Kolkata, India, Beliaghata, Kolkata-700010, India.
⢠MANDELL, DOUGLAS AND BENNET; INFECTIOUS DISEASE PRINCIPLE AND
PRACTICE 5TH EDITION
⢠Maskey AP, Basnyat B, Thwaites GE, Campbell JI, Farrar JJ, Zimmerman
MD.Emerging trends in enteric fever in Nepal: 9124 cases confirmed by
blood culture 1993-2003Trans R Soc Trop Med Hyg. 2008 Jan;102(1):91-5.
Epub 2007 Nov 26.
⢠Basudha Khanal et al;AntimicrobialSusceptibility Patterns of Salmonella
enterica Serotype Typhi in Eastern NepalJ HEALTH POPUL NUTR 2007
Mar;25(1):82-87
12/24/2011
51. ⢠Basudha Khanal et al;AntimicrobialSusceptibility Patterns of Salmonella
enterica Serotype Typhi in Eastern NepalJ HEALTH POPUL NUTR 2007
Mar;25(1):82-87
⢠Harrison's Principles of Internal Medicine18th Edition
⢠Typhoid Fever
⢠Christopher M. Parry et al. N Engl J Med 2002; 347:1770-1782 November
28, 2002
⢠Lewis MD et al Typhoid fever: a massive, single-point source, multidrug-
resistant outbreak in Nepal. Clin Infect Dis. 2005 Feb 15;40(4):554-61.
Epub 2005 Jan 21.
12/24/2011
Brodie in his study of the 1964 Aberdeen outbreak involving 403 cases of bacteriologically proven typhoid cases reported that H agglutinins didnot develop in 15%ofpatients tested and 0 anti bodies did not develop in as many as 41%.