The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5′UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes.

Yellow fever (YF) is an acute arboviral hemorrhagic disease caused by the yellow fever virus (YFV), species Orthoflavivirus flavi, of the Flaviviridae family. YF remains a significant public health threat in endemic regions of Africa and South America, where recurrent outbreaks have occurred, despite the availability of a safe and effective vaccine. In recent years, YF has reemerged in previously unaffected areas, including densely populated regions of Brazil, highlighting ecological shifts, vaccine coverage gaps, and increased vulnerability of populations, raising concerns about its potential global impact. This chapter provides an updated and comprehensive overview of YF, addressing virological characteristics, transmission cycles, epidemiological trends, and pathogenesis. Special emphasis is placed on recent scientific findings, including sylvatic transmission of YFV in Brazil, which has played a central role in recent outbreaks and presents a continued risk of reurbanization. The clinical spectra of YF are reviewed, ranging from mild febrile illness to severe, multisystem disease associated with high case-fatality rates. Diagnostic strategies are discussed, including molecular and serological tools, as well as biomarkers associated with disease severity. Particular attention is given to the host immune response, including cytokine dysregulation, which contributes to the pathogenesis and outcomes of severe cases. Recent findings on immune-mediated mechanisms of late-relapsing hepatitis are also discussed. Finally, prevention strategies are addressed, with a focus on the safety and efficacy of the vaccine 17D/17DD and the occurrence of rare adverse events following vaccination. The chapter underscores the importance of sustained surveillance strategies, immunization, and research to mitigate the burden of this reemerging disease.