A Clinician's Perspective on Yellow Fever Vaccine-Associated Neurotropic Disease

Yellow fever (YF) causes high fever, liver dysfunction, renal failure, hypercoagulopathy and platelet dysfunction and can lead to shock and death with a case-fatality ratio of 20 to 50%. Yellow fever vaccination results in long-lasting protective immunity. Serious adverse events, such as yellow fever vaccine-associated neurotropic disease (YEL-AND) are rare. We present a case of a 56-year-old Caucasian man with fever, headache, cognitive problems at the emergency department. He received a primary yellow fever vaccination 4 weeks prior to symptom onset. Cerebrospinal fluid tested positive for YF virus by RT-PCR and confirmed diagnosis of YEL-AND. The patient recovered with symptomatic treatment. We reviewed published clinical reports on YEL-AND indexed for MEDLINE. We identified and analyzed 53 case reports. Forty-five patients were male and eight were female. Twenty-nine cases met criteria for definite YEL-AND and twenty-four for suspected YEL-AND according to Yellow Fever Vaccine Safety Working Group. We applied the Brighton Collaboration diagnostic criteria to assess the diagnostic accuracy of the clinical diagnoses and found meningoencephalitis in 38 reported YEL-AND cases, Guillain Barré Syndrome (GBS) in 7, Acute Disseminated Encephalomyelitis (ADEM) in 6 and myelitis in 5. Thirty-five patients recovered or improved; however, not all cases had a complete follow-up. The prognosis of YEL-AND presenting with GBS, ADEM or myelitis was poor. Fourteen patients received therapy (corticosteroids, intravenous immunoglobulins and/or plasmapheresis). In conclusion, Yellow fever vaccine-associated neurotropic disease is a very rare but serious adverse event after yellow fever vaccination. We described a case of YEL-AND and propose a standardized clinical workup of this condition based on a review of the literature. Centralized registration of complications of yellow fever vaccination is encouraged.

Keywords: ADEM; GBS; encephalitis; meningitis; myelitis; serious adverse events; yellow fever vaccination.