Volume 81, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Although the yellow fever 17D strain live-attenuated vaccine has been widely used over the past seven decades with a long history of safe records, recent reports of serious, sometimes fatal, adverse events, raised concerns about its tolerance. We extracted all cases of serious neurologic adverse events that occurred within 30 days of yellow fever vaccination in our institution during 2000–2008. Four cases (meningitis, n = 2 and meningo-encephalitis, n = 2) were identified. The male:female ratio was 3:1, and ages ranged from 21 to 55 years. Cerebrospinal fluid examination showed pleocytosis (10–82 cells/mm, 64–84% lymphocytes), with slightly elevated protein levels (0.4–0.68 g/L). All symptoms resolved in three patients, but attention disorder and cerebellar syndrome persisted in one patient (at six months follow-up). The incidence of yellow fever vaccine–associated serious neurologic events was estimated to be 9.9/100,000 vaccine doses (95% confidence interval = 2.7–25.4/100,000) in this study, which was 10 times higher than previous estimates that did not include acute meningitis.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Monath TP, 2001. Yellow fever: an update. Lancet Infect Dis 1: 11–20. [Google Scholar]
  2. Monath TP, Cetron MS, 2002. Prevention of yellow fever in persons traveling to the tropics. Clin Infect Dis 34: 1369–1378. [Google Scholar]
  3. Sanders EJ, Marfin AA, Tukei PM, Kuria G, Ademba G, Agata NN, Ouma JO, Cropp KB, Karabatsos N, Reiter P, Moore PS, Gubler DJ, 1998. First recorded outbreak of yellow fever in Kenya, 1992–1993. I. Epidemiologic investigations. Am J Trop Med Hyg 59: 644–649. [Google Scholar]
  4. Barnett ED, 2007. Yellow fever: epidemiology and prevention. Clin Infect Dis 44: 850–856. [Google Scholar]
  5. Centers for Disease Control and Prevention, 2001. Fever, jaundice, and multiple organ system failure associated with 17D-derived yellow fever vaccination, 1996–2001. MMWR Morb Mortal Wkly Rep 50: 643–645. [Google Scholar]
  6. Centers for Disease Control and Prevention, 2002. Adverse events associated with 17D-derived yellow fever vaccination–United States, 2001–2002. MMWR Morb Mortal Wkly Rep 51: 989–993. [Google Scholar]
  7. Centers for Disease Control and Prevention, 2002. Adverse events associated with 17D-derived yellow fever vaccination–United States, 2001–2002. JAMA 288: 2533–2535. [Google Scholar]
  8. Chan RC, Penney DJ, Little D, Carter IW, Roberts JA, Rawlinson WD, 2001. Hepatitis and death following vaccination with 17D-204 yellow fever vaccine. Lancet 358: 121–122. [Google Scholar]
  9. Martin M, Tsai TF, Cropp B, Chang GJ, Homes DA, Tseng J, Shieh W, Zaki SR, Al-Sanouri I, Cutrona AF, Ray G, Weld LH, Cetrom MS, 2001. Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases. Lancet 358: 98–104. [Google Scholar]
  10. Vasconcelos PF, Luna EJ, Galler R, Silva LJ, Coimbra TL, Barros VL, Monath TP, Rodigues SG, Laval C, Costa ZG, Vilela MF, Santos CL, Papaiordanou PM, Alves VA, Andrade LD, Sato HK, Rosa ES, Froguas GB, Lacava E, Almeida LM, Cruz AC, Rocco IM, Santos RT, Oliva OF; Brazilian Yellow Fever Vaccine Evaluation Group, 2001. Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases. Lancet 358: 91–97. [Google Scholar]
  11. Lindsey NP, Schroeder BA, Miller ER, Braun MM, Hinckley AF, Maranao N, Slade BA, Barnett ED, Brunette GW, Horan K, Staples JE, Kozarsky PE, Hayes EB, 2008. Adverse event reports following yellow fever vaccination. Vaccine 26: 6077–6082. [Google Scholar]
  12. McMahon AW, Eidex RB, Marfin AA, Russell M, Sejvar JJ, Markoff L, Hayes EB, Chen RT, Ball R, Braun MM, Cetron M; Yellow Fever Working Group, 2007. Neurologic disease associated with 17D-204 yellow fever vaccination: a report of 15 cases. Vaccine 25: 1727–1734. [Google Scholar]
  13. Jennings AD, Gibson CA, Miller BR, Mathews JH, Mitchell CJ, Roehrig JT, Wood DJ, Taffs F, Sil BK, Whitby SN, 1994. Analysis of a yellow fever virus isolated from a fatal case of vaccine-associated human encephalitis. J Infect Dis 169: 512–518. [Google Scholar]
  14. Fernandes GC, Camacho LA, Sa Carvalho M, Batista M, de Almeida SM, 2007. Neurological adverse events temporally associated to mass vaccination against yellow fever in Juiz de Fora, Brazil, 1999–2005. Vaccine 25: 3124–3128. [Google Scholar]
  15. Khromava AY, Eidex RB, Weld LH, Kohl KS, Bradshaw RD, Chen RT, Cetron MS; Yellow Fever Vaccine Safety Working Group, 2005. Yellow fever vaccine: an updated assessment of advanced age as a risk factor for serious adverse events. Vaccine 23: 3256–3263. [Google Scholar]
  16. Kitchener S, 2004. Viscerotropic and neurotropic disease following vaccination with the 17D yellow fever vaccine, ARILVAX. Vaccine 22: 2103–2105. [Google Scholar]
  17. Tuboi SH, Costa ZG, da Costa Vasconcelos PF, Hatch D, 2007. Clinical and epidemiological characteristics of yellow fever in Brazil: analysis of reported cases 1998–2002. Trans R Soc Trop Med Hyg 101: 169–175. [Google Scholar]
  18. Cetron MS, Marfin AA, Julian KG, Gubler DJ, Sharp DJ, Barwick RS, Weld LH, Chen R, Clover RD, Deseda-Tous J, Marchessault V, Offit PA, Monath TP, 2002. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 51: 1–11. [Google Scholar]

Data & Media loading...

  • Received : 29 May 2009
  • Accepted : 03 Aug 2009

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error