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Typhoid fever

Typhoid fever. John Schmidt. Overview 1. Causal org: Salmonella enterica, subtype typhi ( S. typhi ) and S. paratyphi Transmission: fecal-oral route via contaminated food/water Common sx : fever, headache, malaise, anorexia/ abd pain, >> rose-colored spots, hepatosplenomegaly

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Typhoid fever

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  1. Typhoid fever John Schmidt

  2. Overview 1 • Causal org: Salmonella enterica, subtype typhi (S. typhi) and S. paratyphi • Transmission: fecal-oral route via contaminated food/water • Common sx: fever, headache, malaise, anorexia/abd pain, >> rose-colored spots, hepatosplenomegaly • Prevention: vaccine • Treatment: antibiotics

  3. Epidemiology • 200-300 US cases/yr 2 • 80% of cases endemic areas 3 • 80% of these from six countries: 4-5 • Mexico, India, the Philippines, Pakistan, El Salvador, and Haiti • US cases from fecal contamination, esp. in kids 4-5

  4. Pathogenesis • SEST enter GIT via ingested food/water (ID >10 3) 6 • Enter Peyer’s patches of SI and reproduce • M-cell of MALT 7 • Direct entry (CFTR)8-9 • Enter bloodstream, eventually settling in macrophages of liver, spleen, and bone marrow 10-11

  5. Symptoms • Initially none6 • 10-20% infection rate • 12-21 day incubation • Early sx: vomiting, constipation = diarrhea, anorexia 8-9 • Late sx: fever, fatigue, hepatosplenomegaly, rash, headache, encephalopathy 10-11

  6. Differential Diagnosis • Bacterial gastroenteritis • Malaria • Amebiasis • Dengue fever • Leishmaniasis

  7. Diagnostic Testing • Culture • Blood: 40-80% sensitive 12 • Stool: 30-40% sensitive 13 • Bone Marrow: >90% sensitive 14 • Serology 15 • Test for anti-O and anti-H antibodies • Titer > 4 is positive, 46-94% sensitive • More useful in non-endemic areas

  8. Complications • Bacterial superinfection (10%)16 • SI rupture (3-10%) 16-17 • Carrier state (1-6%) 18 • + stool >12 mo • ↑ risk in women, colelithiasis • ↑ risk of gallbladder carcinoma (esp. in carrier state) 19

  9. Treatment 20 • Adults • Ciprofloxacin 500mg BID x 7-10 days • RESISTANCE!!! • Ceftriaxone 2-3g qD x 7-14 days • Children • Ceftriaxone100mg/kg IV qD x 10-14 days • Azithromycin 10-20mg/kg qD x 5-7 days • Ciprofloxacin 30mg/kg qD x 7-10 days

  10. Follow up • Labs • Serum culture should be negative • F/U with 3 stool cultures one month apart (carrier state)

  11. Prevention 21 • Oral vaccine

  12. A 19 y/o white female college student is brought into the ED by her roommate after returning from a short-term mission trip to Mexico ten days ago. She did not receive any vaccinations prior to travel. The roommate states she initially was fine, but after a day or so she felt feverish throughout the day and seemed to be getting worse. Both girls, however, were confused because the patient’s temperatures were normal when they checked in the mornings. Yesterday night the patient developed severe abdominal pain and a headache, and when she awoke this morning the roommate states she “was cloudy in the head.” Full history and physical are unobtainable due to the patient’s altered mental status.Vital signs: T 102.5 F, BP 108/62, P 98, RR 18Physical exam significant for MMSE 20/30 and two blanching maculopapular spots on the trunk, each 3cm in diameter.Which of the following is the most likely causal organism for this patient’s condition? • Escherichia coli • Plasmodium falciparum • Rickettsia rickettsii • Salmonella typhus Answer Now

  13. References 1. Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med 2002; 347:1770. 2. Lynch MF, Blanton EM, Bulens S, et al. Typhoid fever in the United States, 1999-2006. JAMA 2009; 302:859. 3. Centers for Disease Control and Prevention (CDC). Salmonella Surveillance: Annual Summary, 2006. CDC; US Department of Health and Human Services, Atlanta, GA 2006. 4. Olsen SJ, Bleasdale SC, Magnano AR, et al. Outbreaks of typhoid fever in the United States, 1960-99. Epidemiol Infect 2003; 130:13. 5. Loharikar A, Newton A, Rowley P, et al. Typhoid fever outbreak associated with frozen mamey pulp imported from Guatemala - Western United States, 2010. Clin Infect Dis 2012. 6. Blaser MJ, Newman LS. A review of human salmonellosis: I. Infective dose. Rev Infect Dis 1982; 4:1096. 7. Kohbata S, Yokoyama H, Yabuuchi E. Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study. MicrobiolImmunol 1986; 30:1225. 8. Pier GB, Grout M, Zaidi T, et al. Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature 1998; 393:79. 9. van de Vosse E, de Visser AW, Al-Attar S, et al. Distribution of CFTR variations in an Indonesian enteric fever cohort. Clin Infect Dis 2010; 50:1231. 10. Hornick RB, Greisman SE, Woodward TE, et al. Typhoid fever: pathogenesis and immunologic control. N Engl J Med 1970; 283:686. • Meals RA. Paratyphoid fever: a report of 62 cases with several unusual findings and a review of the literature. Arch Intern Med 1976; 136:1422. 12. Hoffman SL, Punjabi NH, Rockhill RC, et al. Duodenal string-capsule culture compared with bone-marrow, blood, and rectal-swab cultures for diagnosing typhoid and paratyphoid fever. J Infect Dis 1984; 149:157. 13. Edelman R, Levine MM. Summary of an international workshop on typhoid fever. Rev Infect Dis 1986; 8:329. 14.. Gotuzzo E, Echevarría J, Carrillo C, et al. Randomized comparison of aztreonam and chloramphenicol in treatment of typhoid fever. Antimicrob Agents Chemother 1994; 38:558.

  14. References 2 15. Shukla S, Patel B, Chitnis DS. 100 years of Widal test & its reappraisal in an endemic area. Indian J Med Res 1997; 105:53. 16. Butler T, Islam A, Kabir I, Jones PK. Patterns of morbidity and mortality in typhoid fever dependent on age and gender: review of 552 hospitalized patients with diarrhea. Rev Infect Dis 1991; 13:85. 17. Gupta SP, Gupta MS, Bhardwaj S, Chugh TD. Current clinical patterns of typhoid fever: a prospective study. J Trop Med Hyg 1985; 88:377. 18. Hofmann E, Chianale J, Rollán A, et al. Blood group antigen secretion and gallstone disease in the Salmonella typhi chronic carrier state. J Infect Dis 1993; 167:993. 19. Crawford RW, Rosales-Reyes R, Ramírez-Aguilar Mde L, et al. Gallstones play a significant role in Salmonella spp. gallbladder colonization and carriage. Proc NatlAcadSci U S A 2010; 107:4353. 20. Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med 2002; 347:1770. 21. Centers for Disease Control and Prevention: National Center for Emerging and Zoonotic Infectious Diseases. Typhoid Fever; Getting Vaccinated: http://www.cdc.gov/nczved/divisions/dfbmd/diseases/ typhoid_fever/#where

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