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Case discussion and topic review
PRESENTER- DR. PRADIP KATWAL
Moderator – DR. PURU KOIRALA
12/24/2011 1
pradip katwal
Clinical case
• Age – 36 yrs
• Sex- Male
• Add- Morang
• Presenting complaints:-
• fever with chills and rigors (4 days)
• Vomiting --4 days
• Headache --4 days
12/24/2011
• G/C – 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 ᵒF
12/24/2011
systemic examination
• Chest – 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
12/24/2011
Lab investigations
• TLC- 1700 mm3
• DLC-N 25% L45% M25% E 05%
• HB- 13.8 gm/dl
• platelates-47000 mm3
• Urine RE/ME- WNL
• Blood culture- sterile
• Urine culture- sterile
• PS for MP, optimal test= negative
12/24/2011
DIAGNOSIS
Case of Acute febrile illness
with splenomegaly
with bicytopenia
D/D-Enteric fever
-Malaria
12/24/2011
Treatment
• INJ CEFTRIAXONE 1 gm IV BD for 7 days
• TAB PARACETAMOL 500 mg sos
12/24/2011
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
12/24/2011
Bacteriology –Typhoid fever
Family- Enterobactericiae
Genus- Salmonella
Species-enterica
SEROVARS 2300+
Serotype typhi
• Facultative anaerobe
• Gram negative bacilli
• Peritrichous flagella
12/24/2011
Distinguished from other bacteria by
Biochemical and antigen structure
• Forms acid on glucose fermentation
• Do not ferment lactose
• Divided into serotypes on basis of
O antigen
H antigen
Vi antigen
After 24 hours, this inoculated XLD agar culture plate
cultivated colonial growth of Gram-negative, rod-shaped and
facultatively anaerobic Salmonella sp. bacteria
12/24/2011
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
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
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
12/24/2011
Pathogenesis
FOOD FOMITES WATER
ENTRY INTO GIT
INGESTED
DOSE
HOST
FACTORS
12/24/2011
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
12/24/2011
INTERACT WITH MACROPHAGES AND
LYMPHOCYTES OF PAYER PATCHES
ENLARGEMENT AND NECROSIS OF
PAYER PATCHES
SALMONELLA SURVIVE WITH IN MACROPHAGE
12/24/2011
Thoracic duct
Lymphatic channel
Iocalisation in macrophages of RES
in spleen, liver, bone marrow
Primary silent bacteremia
secondary bacteremia
12/24/2011
Clinical features
Characterized by
 Fever
 Disturbances of bowel function
Headache, malaise
 Anorexia, cough
 Exanthem (rose spots), on the chest,
abdomen and back.
12/24/2011
Early physical findings
• Toxic ill looking
• Rash “rose spots”(30%)
• Realtive
bradycardia(50%)
• Hepatosplenomegaly
• Abdominal pain on deep
palpation
• Cholecystitis (3%)
12/24/2011
complications
• Gastrointestinal bleeding
• Intestinal perforation
• Relapse(10%)
• Abortion
12/24/2011
• Neurological manifestation
• Pancreatitis
• Hepatic and splenic abscess
• Endocarditis
• Glomerulonephritis
• Pyelonephritis
• Hemolytic uremic syndromes
12/24/2011
• Disseminated intravascular coagulation
• Arthritis
• Osteomylitis
• Parotitis
• Hepatitis
• Pericarditis
12/24/2011
Typhoid state
• Coma vigil
• Picking at bed clothes and at imaginary
objects
• Muscle twitching
• CSF ANALYSIS- NORMAL
12/24/2011
DIAGNOSIS
• DEFINITIVE DIAGNOSIS
• Isolation of organism from blood, bone
marrow, rose spots, stool, intestinal secretion.
• Bone marrow culture-55-90% sensitive
• Advantage over blood culture
• Culture of intestinal secretions
(duodenal string test)
12/24/2011
Other lab parmeters
• Leukopenia
• Neutropenia
• thrombocytopenia
• Moderately elevated liver enzymes
• Mod. Elevated muscle enzyme levels
12/24/2011
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
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.
12/24/2011
reasons
• Use of empirical antibiotics
• Baseline titer depends upon geographic area
• Strain variation
12/24/2011
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)
12/24/2011
New serological test
• New serological tests
– Typhidot (better),
– high negative predictive value
– Dipstick test
12/24/2011
Retrospective study
 Determine the changing burden of salmonella
septicaemia
 Proportion of Salmonella paratyphi A
 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
12/24/2011
In comparing the period 1997-2000 to the
period 2001-2003 taken,
• salmonella septicaemia increase 6.2 to 13.6%
(P<0.001)
 S. paratyphi A as a proportion of all salmonella
isolates rose from 23 to 34% (P<0.001)
 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
Typhoid epidemiology according to
drug sensitivity
12/24/2011
drugs
• Chloramphenicol
• Ampicillin
• Cotrimoxazole
• Quinolones
• 3rd generation cephalosporin
• Azithromycin
12/24/2011
Treatment
• Empirical treatment
Cetriaxone
Azithromycin
• Fully susceptible
Ciprofloxacin
Amoxycillin
Chloramphenical
Trimethoprim-sulphamethoxazole
12/24/2011
• Multi drug resistance
Ciprofloxacin
Ceftriaxone
Azithromycin
• Nalidaxic acid resistance
Ceftriaxone
Azithromycin
High-does ciprofloxacin
12/24/2011
Antibiotic resistance
• MDR is mediated by plasmid
• Quinolone resistance is frequently mediated
by single point mutations in the quinolone-
resistance–determining region of the gyrA
gene
• Nalidixic acid resistant: MIC of
fluoroquinolones for these strains was 10
times that for fully susceptible strains.
12/24/2011
Azithromycin appears to be as good as the other
comparator drugs for most outcomes
Appears to be better than fluoroquinolones in
reducing clinical failure and duration of hospital
stay
Better than ceftriaxone in reducing relapse
Azithromycin should be used guardedly to
prevent the emergence of strains resistant to the
drug
12/24/2011
• 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.
12/24/2011
• 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
based on a randomized, double blind, placebo
controlled trial carried out in Indonesia
This 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
 dexamethasone, 3 mg/kg intravenously,
followed 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.
12/24/2011
A chronic carrier is defined as someone who excretes
S. Typhi in stool or urine for more than one year.
(1-4%)
12/24/2011
SALMONELLA AND AIDS
• 20-100 FOLD RISK OF SALMONELLA
• CD4 COUNTS < 100/mm3
• Fulminant diarrhoea
• Recurrent bacterimia
• Acute enterocolitis
• Zidovudine and cotrimoxazole
12/24/2011
Vaccines for Typhoid Prevention
• HEAT KILLED WHOLE ORGANISM VACCINCE
• PHENOL
• ACETONE
12/24/2011
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
12/24/2011
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)
12/24/2011
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
12/24/2011
Simple hand hygiene and washing
can reduce several cases of Typhoid
12/24/2011
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
• 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
THANK YOU
Thank
you
12/24/2011

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enteric fever

  • 1. Case discussion and topic review PRESENTER- DR. PRADIP KATWAL Moderator – DR. PURU KOIRALA 12/24/2011 1 pradip katwal
  • 2. Clinical case • Age – 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 – 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 ᵒF 12/24/2011
  • 4. systemic examination • Chest – 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 12/24/2011
  • 5. Lab investigations • TLC- 1700 mm3 • DLC-N 25% L45% M25% E 05% • HB- 13.8 gm/dl • platelates-47000 mm3 • Urine RE/ME- WNL • Blood culture- sterile • Urine culture- sterile • PS for MP, optimal test= negative 12/24/2011
  • 6. DIAGNOSIS Case of Acute febrile illness with splenomegaly with bicytopenia D/D-Enteric fever -Malaria 12/24/2011
  • 7. Treatment • INJ CEFTRIAXONE 1 gm IV BD for 7 days • TAB PARACETAMOL 500 mg sos 12/24/2011
  • 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 12/24/2011
  • 9. Bacteriology –Typhoid fever Family- Enterobactericiae Genus- Salmonella Species-enterica SEROVARS 2300+ Serotype typhi • Facultative anaerobe • Gram negative bacilli • Peritrichous flagella 12/24/2011
  • 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 O antigen H antigen Vi antigen After 24 hours, this inoculated XLD agar culture plate cultivated colonial growth of Gram-negative, rod-shaped and facultatively anaerobic Salmonella sp. bacteria 12/24/2011
  • 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
  • 15. Pathogenesis FOOD FOMITES WATER ENTRY INTO GIT INGESTED DOSE HOST FACTORS 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 12/24/2011
  • 17. INTERACT WITH MACROPHAGES AND LYMPHOCYTES OF PAYER PATCHES ENLARGEMENT AND NECROSIS OF PAYER PATCHES SALMONELLA SURVIVE WITH IN MACROPHAGE 12/24/2011
  • 18. Thoracic duct Lymphatic channel Iocalisation in macrophages of RES in spleen, liver, bone marrow Primary silent bacteremia secondary bacteremia 12/24/2011
  • 19. Clinical features Characterized by  Fever  Disturbances of bowel function Headache, malaise  Anorexia, cough  Exanthem (rose spots), on the chest, abdomen and back. 12/24/2011
  • 20. Early physical findings • Toxic ill looking • Rash “rose spots”(30%) • Realtive bradycardia(50%) • Hepatosplenomegaly • Abdominal pain on deep palpation • Cholecystitis (3%) 12/24/2011
  • 21. complications • Gastrointestinal bleeding • Intestinal perforation • Relapse(10%) • Abortion 12/24/2011
  • 22. • Neurological manifestation • Pancreatitis • Hepatic and splenic abscess • Endocarditis • Glomerulonephritis • Pyelonephritis • Hemolytic uremic syndromes 12/24/2011
  • 23. • Disseminated intravascular coagulation • Arthritis • Osteomylitis • Parotitis • Hepatitis • Pericarditis 12/24/2011
  • 24. Typhoid state • Coma vigil • Picking at bed clothes and at imaginary objects • Muscle twitching • CSF ANALYSIS- NORMAL 12/24/2011
  • 25. DIAGNOSIS • DEFINITIVE DIAGNOSIS • Isolation of organism from blood, bone marrow, rose spots, stool, intestinal secretion. • Bone marrow culture-55-90% sensitive • Advantage over blood culture • Culture of intestinal secretions (duodenal string test) 12/24/2011
  • 26. Other lab parmeters • Leukopenia • Neutropenia • thrombocytopenia • Moderately elevated liver enzymes • Mod. Elevated muscle enzyme levels 12/24/2011
  • 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. 12/24/2011
  • 29. reasons • Use of empirical antibiotics • Baseline titer depends upon geographic area • Strain variation 12/24/2011
  • 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) 12/24/2011
  • 31. New serological test • New serological tests – Typhidot (better), – high negative predictive value – Dipstick test 12/24/2011
  • 32. Retrospective study  Determine the changing burden of salmonella septicaemia  Proportion of Salmonella paratyphi A  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 12/24/2011
  • 33. In comparing the period 1997-2000 to the period 2001-2003 taken, • salmonella septicaemia increase 6.2 to 13.6% (P<0.001)  S. paratyphi A as a proportion of all salmonella isolates rose from 23 to 34% (P<0.001)  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
  • 34. Typhoid epidemiology according to drug sensitivity 12/24/2011
  • 35. drugs • Chloramphenicol • Ampicillin • Cotrimoxazole • Quinolones • 3rd generation cephalosporin • Azithromycin 12/24/2011
  • 36. Treatment • Empirical treatment Cetriaxone Azithromycin • Fully susceptible Ciprofloxacin Amoxycillin Chloramphenical Trimethoprim-sulphamethoxazole 12/24/2011
  • 37. • Multi drug resistance Ciprofloxacin Ceftriaxone Azithromycin • Nalidaxic acid resistance Ceftriaxone Azithromycin High-does ciprofloxacin 12/24/2011
  • 38. Antibiotic resistance • MDR is mediated by plasmid • Quinolone resistance is frequently mediated by single point mutations in the quinolone- resistance–determining region of the gyrA gene • Nalidixic acid resistant: MIC of fluoroquinolones for these strains was 10 times that for fully susceptible strains. 12/24/2011
  • 39. Azithromycin appears to be as good as the other comparator drugs for most outcomes Appears to be better than fluoroquinolones in reducing clinical failure and duration of hospital stay Better than ceftriaxone in reducing relapse Azithromycin should be used guardedly to prevent the emergence of strains resistant to the drug 12/24/2011
  • 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. 12/24/2011
  • 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. based on a randomized, double blind, placebo controlled trial carried out in Indonesia This 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  dexamethasone, 3 mg/kg intravenously, followed 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. 12/24/2011
  • 43. A chronic carrier is defined as someone who excretes S. Typhi in stool or urine for more than one year. (1-4%) 12/24/2011
  • 44. SALMONELLA AND AIDS • 20-100 FOLD RISK OF SALMONELLA • CD4 COUNTS < 100/mm3 • Fulminant diarrhoea • Recurrent bacterimia • Acute enterocolitis • Zidovudine and cotrimoxazole 12/24/2011
  • 45. Vaccines for Typhoid Prevention • HEAT KILLED WHOLE ORGANISM VACCINCE • PHENOL • ACETONE 12/24/2011
  • 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 12/24/2011
  • 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) 12/24/2011
  • 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 12/24/2011
  • 49. Simple hand hygiene and washing can reduce several cases of Typhoid 12/24/2011
  • 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

Notas do Editor

  1. 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%.