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Critical Care129 papers

Yellow fever

Last edited: 4/14/2026

Overview

Yellow fever is a viral hemorrhagic fever endemic to tropical regions of Africa and South America, preventable primarily through vaccination. Despite its efficacy, rare severe adverse events including viscerotropic and neurotropic disease following vaccination persist as safety concerns 127101215161820212224262729.

Diagnosis

  • Clinical presentation includes fever, jaundice, hemorrhagic symptoms, and organ dysfunction 22.
  • Laboratory tests may reveal elevated liver enzymes, thrombocytopenia, and leukopenia 22.
  • Viral RNA detection and serological testing confirm yellow fever infection 622.
  • Imaging and organ function tests assess extent of organ involvement 22.

    • Management

  • Supportive care is central, including fluid management, blood product transfusions for bleeding, and organ support (e.g., mechanical ventilation, dialysis) 522.
  • Therapeutic plasma exchange has shown efficacy in refractory cases with extreme hyperferritinemia 5.
  • Antiviral therapy is not standard; management focuses on symptom control and organ support 22.

    • Special Populations

  • Pregnancy: Limited data; vaccination is generally contraindicated unless risk of exposure is high 15.
  • Pediatrics: Vaccination is safe and recommended for endemic areas, though rare adverse events exist 15.
  • Elderly: Higher risk of severe adverse events following vaccination; immunological senescence may contribute 24.
  • Comorbidities: Patients with underlying conditions may face increased risk of severe adverse events post-vaccination 1524.

    • Key Recommendations

  • Vaccinate individuals at genuine risk of yellow fever exposure to prevent infection 215 (Evidence: Strong).
  • Exercise caution in elderly and immunocompromised individuals due to increased risk of severe adverse events post-vaccination 2415 (Evidence: Moderate).
  • Consider vaccination only in endemic or high-risk travel areas to minimize unnecessary exposure 215 (Evidence: Moderate).
  • Monitor closely for signs of viscerotropic disease, especially in older adults, post-vaccination 724 (Evidence: Weak).
  • Implement enhanced surveillance for adverse events following yellow fever vaccination, particularly in vulnerable populations 11620 (Evidence: Moderate).

    • References

    1 Liang G, Liu Q, Song Y. Pharmacovigilance assessment of adverse events following yellow fever vaccination: Disproportionality analysis of VAERS reports, 2015-2025. Human vaccines & immunotherapeutics 2025. link 2 Schnyder JL, Bache BE, Welkers MRA, Spijker R, Schaumburg F, Goorhuis A et al.. Yellow fever breakthrough infections after yellow fever vaccination: a systematic review and meta-analysis. The Lancet. Microbe 2024. link 3 Gonçalves ANA, Costa PR, Thomazella MV, Correia CA, Marmorato MP, Dias JZC et al.. Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients. Journal of medical virology 2024. link 4 Mayfield JB. Founding Physicians of the Medical College of Georgia and Their Connections to Crawford Long and the First Surgical Anesthetic. Journal of anesthesia history 2020. link 5 Sztajnbok J, Sant'Ana Malaque CM, Nihei CH, Duayer IF, Leme Britto ZM, Beraldo EG et al.. Severe Yellow Fever and Extreme Hyperferritinemia Managed with Therapeutic Plasma Exchange. The American journal of tropical medicine and hygiene 2019. link 6 Chen Z, Liu L, Lv Y, Zhang W, Li J, Zhang Y et al.. A fatal yellow fever virus infection in China: description and lessons. Emerging microbes & infections 2016. link 7 Thomas RE. Yellow fever vaccine-associated viscerotropic disease: current perspectives. Drug design, development and therapy 2016. link 8 Lindsey NP, Rabe IB, Miller ER, Fischer M, Staples JE. Adverse event reports following yellow fever vaccination, 2007-13. Journal of travel medicine 2016. link 9 Martorano Raimundo S, Amaku M, Massad E. Equilibrium analysis of a yellow Fever dynamical model with vaccination. Computational and mathematical methods in medicine 2015. link 10 van de Pol EM, Gisolf EH, Richter C. A case suspected for yellow fever vaccine-associated viscerotropic disease in the Netherlands. Journal of travel medicine 2014. link 11 Engelmann F, Josset L, Girke T, Park B, Barron A, Dewane J et al.. Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model. PLoS neglected tropical diseases 2014. link 12 Seligman SJ. Risk groups for yellow fever vaccine-associated viscerotropic disease (YEL-AVD). Vaccine 2014. link 13 Biscayart C, Carrega ME, Sagradini S, Gentile A, Stecher D, Orduna T et al.. Yellow fever vaccine-associated adverse events following extensive immunization in Argentina. Vaccine 2014. link 14 Runge JS. Lost trust: a yellow fever patient response. The Yale journal of biology and medicine 2013. link 15 Thomas RE, Lorenzetti DL, Spragins W, Jackson D, Williamson T. The safety of yellow fever vaccine 17D or 17DD in children, pregnant women, HIV+ individuals, and older persons: systematic review. The American journal of tropical medicine and hygiene 2012. link 16 Thomas RE, Lorenzetti DL, Spragins W, Jackson D, Williamson T. Reporting rates of yellow fever vaccine 17D or 17DD-associated serious adverse events in pharmacovigilance data bases: systematic review. Current drug safety 2011. link 17 Garcia MT, Hermosa Y, Aguirre JI. Does breeding status influence haematology and blood biochemistry of yellow-legged gulls?. Acta biologica Hungarica 2010. link 18 Monath TP. Suspected yellow fever vaccine-associated viscerotropic adverse events (1973 and 1978), United States. The American journal of tropical medicine and hygiene 2010. link 19 Muñoz J, Vilella A, Domingo C, Nicolas JM, de Ory F, Corachan M et al.. Yellow fever-associated viscerotropic disease in Barcelona, Spain. Journal of travel medicine 2008. link 20 Lindsey NP, Schroeder BA, Miller ER, Braun MM, Hinckley AF, Marano N et al.. Adverse event reports following yellow fever vaccination. Vaccine 2008. link 21 Belsher JL, Gay P, Brinton M, DellaValla J, Ridenour R, Lanciotti R et al.. Fatal multiorgan failure due to yellow fever vaccine-associated viscerotropic disease. Vaccine 2007. link 22 Barnett ED. Yellow fever: epidemiology and prevention. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2007. link 23 Gerasimon G, Lowry K. Rare case of fatal yellow fever vaccine-associated viscerotropic disease. Southern medical journal 2005. link 24 Monath TP, Cetron MS, McCarthy K, Nichols R, Archambault WT, Weld L et al.. Yellow fever 17D vaccine safety and immunogenicity in the elderly. Human vaccines 2005. link 25 Struchiner CJ, Luz PM, Dourado I, Sato HK, Aguiar SG, Ribeiro JG et al.. Risk of fatal adverse events associated with 17DD yellow fever vaccine. Epidemiology and infection 2004. link 26 . Adverse events associated with 17D-derived yellow fever vaccination--United States, 2001-2002. MMWR. Morbidity and mortality weekly report 2002. link 27 Martin M, Tsai TF, Cropp B, Chang GJ, Holmes DA, Tseng J et al.. Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases. Lancet (London, England) 2001. link05327-2) 28 Chan RC, Penney DJ, Little D, Carter IW, Roberts JA, Rawlinson WD. Hepatitis and death following vaccination with 17D-204 yellow fever vaccine. Lancet (London, England) 2001. link05341-7) 29 Vasconcelos PF, Luna EJ, Galler R, Silva LJ, Coimbra TL, Barros VL et al.. Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases. Lancet (London, England) 2001. link05326-0) 30 Slee J, Nelson J, Dickinson J, Kendall P, Halbert A. Yellow nail syndrome presenting as non-immune hydrops: second case report. American journal of medical genetics 2000. link

    Original source

    1. [1]
      Pharmacovigilance assessment of adverse events following yellow fever vaccination: Disproportionality analysis of VAERS reports, 2015-2025. — Liang G, Liu Q, Song Y Human vaccines & immunotherapeutics (2025)
    2. [2]
      Yellow fever breakthrough infections after yellow fever vaccination: a systematic review and meta-analysis. — Schnyder JL, Bache BE, Welkers MRA, Spijker R, Schaumburg F, Goorhuis A et al. The Lancet. Microbe (2024)
    3. [3]
      Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients. — Gonçalves ANA, Costa PR, Thomazella MV, Correia CA, Marmorato MP, Dias JZC et al. Journal of medical virology (2024)
    4. [4]
      Founding Physicians of the Medical College of Georgia and Their Connections to Crawford Long and the First Surgical Anesthetic. — Mayfield JB Journal of anesthesia history (2020)
    5. [5]
      Severe Yellow Fever and Extreme Hyperferritinemia Managed with Therapeutic Plasma Exchange. — Sztajnbok J, Sant'Ana Malaque CM, Nihei CH, Duayer IF, Leme Britto ZM, Beraldo EG et al. The American journal of tropical medicine and hygiene (2019)
    6. [6]
      A fatal yellow fever virus infection in China: description and lessons. — Chen Z, Liu L, Lv Y, Zhang W, Li J, Zhang Y et al. Emerging microbes & infections (2016)
    7. [7]
      Yellow fever vaccine-associated viscerotropic disease: current perspectives. — Thomas RE Drug design, development and therapy (2016)
    8. [8]
      Adverse event reports following yellow fever vaccination, 2007-13. — Lindsey NP, Rabe IB, Miller ER, Fischer M, Staples JE Journal of travel medicine (2016)
    9. [9]
      Equilibrium analysis of a yellow Fever dynamical model with vaccination. — Martorano Raimundo S, Amaku M, Massad E Computational and mathematical methods in medicine (2015)
    10. [10]
      A case suspected for yellow fever vaccine-associated viscerotropic disease in the Netherlands. — van de Pol EM, Gisolf EH, Richter C Journal of travel medicine (2014)
    11. [11]
      Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model. — Engelmann F, Josset L, Girke T, Park B, Barron A, Dewane J et al. PLoS neglected tropical diseases (2014)
    12. [12]
      Risk groups for yellow fever vaccine-associated viscerotropic disease (YEL-AVD). — Seligman SJ Vaccine (2014)
    13. [13]
      Yellow fever vaccine-associated adverse events following extensive immunization in Argentina. — Biscayart C, Carrega ME, Sagradini S, Gentile A, Stecher D, Orduna T et al. Vaccine (2014)
    14. [14]
      Lost trust: a yellow fever patient response. — Runge JS The Yale journal of biology and medicine (2013)
    15. [15]
      The safety of yellow fever vaccine 17D or 17DD in children, pregnant women, HIV+ individuals, and older persons: systematic review. — Thomas RE, Lorenzetti DL, Spragins W, Jackson D, Williamson T The American journal of tropical medicine and hygiene (2012)
    16. [16]
      Reporting rates of yellow fever vaccine 17D or 17DD-associated serious adverse events in pharmacovigilance data bases: systematic review. — Thomas RE, Lorenzetti DL, Spragins W, Jackson D, Williamson T Current drug safety (2011)
    17. [17]
      Does breeding status influence haematology and blood biochemistry of yellow-legged gulls? — Garcia MT, Hermosa Y, Aguirre JI Acta biologica Hungarica (2010)
    18. [18]
      Suspected yellow fever vaccine-associated viscerotropic adverse events (1973 and 1978), United States. — Monath TP The American journal of tropical medicine and hygiene (2010)
    19. [19]
      Yellow fever-associated viscerotropic disease in Barcelona, Spain. — Muñoz J, Vilella A, Domingo C, Nicolas JM, de Ory F, Corachan M et al. Journal of travel medicine (2008)
    20. [20]
      Adverse event reports following yellow fever vaccination. — Lindsey NP, Schroeder BA, Miller ER, Braun MM, Hinckley AF, Marano N et al. Vaccine (2008)
    21. [21]
      Fatal multiorgan failure due to yellow fever vaccine-associated viscerotropic disease. — Belsher JL, Gay P, Brinton M, DellaValla J, Ridenour R, Lanciotti R et al. Vaccine (2007)
    22. [22]
      Yellow fever: epidemiology and prevention. — Barnett ED Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2007)
    23. [23]
      Rare case of fatal yellow fever vaccine-associated viscerotropic disease. — Gerasimon G, Lowry K Southern medical journal (2005)
    24. [24]
      Yellow fever 17D vaccine safety and immunogenicity in the elderly. — Monath TP, Cetron MS, McCarthy K, Nichols R, Archambault WT, Weld L et al. Human vaccines (2005)
    25. [25]
      Risk of fatal adverse events associated with 17DD yellow fever vaccine. — Struchiner CJ, Luz PM, Dourado I, Sato HK, Aguiar SG, Ribeiro JG et al. Epidemiology and infection (2004)
    26. [26]
      Adverse events associated with 17D-derived yellow fever vaccination--United States, 2001-2002. MMWR. Morbidity and mortality weekly report (2002)
    27. [27]
      Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases. — Martin M, Tsai TF, Cropp B, Chang GJ, Holmes DA, Tseng J et al. Lancet (London, England) (2001)
    28. [28]
      Hepatitis and death following vaccination with 17D-204 yellow fever vaccine. — Chan RC, Penney DJ, Little D, Carter IW, Roberts JA, Rawlinson WD Lancet (London, England) (2001)
    29. [29]
      Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases. — Vasconcelos PF, Luna EJ, Galler R, Silva LJ, Coimbra TL, Barros VL et al. Lancet (London, England) (2001)
    30. [30]
      Yellow nail syndrome presenting as non-immune hydrops: second case report. — Slee J, Nelson J, Dickinson J, Kendall P, Halbert A American journal of medical genetics (2000)
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