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enteric fever

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  • 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%.
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    • 1. Case discussion and topic review PRESENTER- DR. PRADIP KATWAL Moderator – DR. PURU KOIRALA12/24/2011 pradip katwal 1
    • 2. Clinical case• Age – 36 yrs• Sex- Male• Add- Morang• Presenting complaints:-• fever with chills and rigors (4 days)• Vomiting --4 days• Headache --4 days12/24/2011
    • 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 ᵒF12/24/2011
    • 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 WNL12/24/2011
    • 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= negative12/24/2011
    • 6. DIAGNOSISCase of Acute febrile illness with splenomegaly with bicytopeniaD/D-Enteric fever -Malaria12/24/2011
    • 7. Treatment• INJ CEFTRIAXONE 1 gm IV BD for 7 days• TAB PARACETAMOL 500 mg sos12/24/2011
    • 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,C12/24/2011
    • 9. Bacteriology –Typhoid feverFamily- EnterobactericiaeGenus- SalmonellaSpecies-entericaSEROVARS 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 and12/24/2011 facultatively anaerobic Salmonella sp. bacteria
    • 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 fever12/24/2011
    • 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 P12/24/2011
    • 14. 12/24/2011
    • 15. Pathogenesis FOOD FOMITES WATER ENTRY INTO GIT INGESTED HOST DOSE FACTORS12/24/2011
    • 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 TISSUE12/24/2011
    • 17. INTERACT WITH MACROPHAGES AND LYMPHOCYTES OF PAYER PATCHES ENLARGEMENT AND NECROSIS OF PAYER PATCHES SALMONELLA SURVIVE WITH IN MACROPHAGE12/24/2011
    • 18. Lymphatic channel Thoracic duct Primary silent bacteremia Iocalisation in macrophages of RES in spleen, liver, bone marrow secondary bacteremia12/24/2011
    • 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%)• Abortion12/24/2011
    • 22. • Neurological manifestation• Pancreatitis• Hepatic and splenic abscess• Endocarditis• Glomerulonephritis• Pyelonephritis• Hemolytic uremic syndromes12/24/2011
    • 23. • Disseminated intravascular coagulation• Arthritis• Osteomylitis• Parotitis• Hepatitis• Pericarditis12/24/2011
    • 24. Typhoid state• Coma vigil• Picking at bed clothes and at imaginary objects• Muscle twitching• CSF ANALYSIS- NORMAL12/24/2011
    • 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 levels12/24/2011
    • 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 EDITION12/24/2011
    • 28. Widal testWe thus conclude that in endemic areas the Widal test is still ofsignificant diagnostic value provided judicious interpretation of thetest is made against a background of pertinent information, especiallyData which related agglutinin levels in normal individuals. 12/24/2011
    • 29. reasons• Use of empirical antibiotics• Baseline titer depends upon geographic area• Strain variation12/24/2011
    • 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 test12/24/2011
    • 32. Retrospective study Determine the changing burden of salmonella septicaemia Proportion of Salmonella paratyphi A Emergence of drug-resistant organisms.82467 blood cultures performeda bacterium was isolated from 122526447 (70.7%) Salmonella enterica serotype Typhi (S. typhi)2677 (29.3%) Paratyphi A (S. paratyphi A)9124 (74.5%) Salmonella12/24/2011
    • 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 ciprofloxacinTrans 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 sensitivity12/24/2011
    • 35. drugs• Chloramphenicol• Ampicillin• Cotrimoxazole• Quinolones• 3rd generation cephalosporin• Azithromycin12/24/2011
    • 36. Treatment• Empirical treatmentCetriaxoneAzithromycin• Fully susceptibleCiprofloxacinAmoxycillinChloramphenicalTrimethoprim-sulphamethoxazole12/24/2011
    • 37. • Multi drug resistanceCiprofloxacinCeftriaxoneAzithromycin• Nalidaxic acid resistanceCeftriaxoneAzithromycinHigh-does ciprofloxacin12/24/2011
    • 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 drug12/24/2011
    • 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 citys 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 POPUL12/24/2011 NUTR 2007 Mar;25(1):82-87
    • 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 cotrimoxazole12/24/2011
    • 45. Vaccines for Typhoid Prevention• HEAT KILLED WHOLE ORGANISM VACCINCE• PHENOL• ACETONE12/24/2011
    • 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 vaccine12/24/2011
    • 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 boosterVaccines are not effective in prevention of Paratyphoid fevers12/24/2011
    • 49. Simple hand hygiene and washing can reduce several cases of Typhoid12/24/2011
    • 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):82-8712/24/2011
    • 51. • Basudha Khanal et al;AntimicrobialSusceptibility Patterns of Salmonella enterica Serotype Typhi in Eastern NepalJ HEALTH POPUL NUTR 2007 Mar;25(1):82-87• Harrisons 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
    • 52. THANK YOU Thank you12/24/2011

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