Yellow fever virus infection in non-human primates: a systematic review and meta-analysis of prevalence, seroprevalence, and epizootic case reports (1950-2025).

Introduction: Yellow fever remains a major mosquito-borne viral disease of global public health and ecological concern. Non-human primates (NHPs) are central to the sylvatic transmission cycle and serve as key sentinels of viral circulation. Yet, evidence on yellow fever virus (YFV) infection in NHPs is dispersed and has not been synthesized comprehensively. Objective: To systematically review and meta-analyze global data on the prevalence and seroprevalence of YFV infection in NHP, and to summarize molecular, clinical, and pathological findings from reported epizootic cases. Methods: We conducted a systematic search of Scopus, PubMed, Web of Science, and SciELO for studies published between 1950 and 2025, following PRISMA guidelines. Observational studies reporting YFV prevalence or seroprevalence in NHPs were included in the quantitative syntheses, and individual case reports were analyzed separately. Random-effects meta-analyses were performed, with subgroup analyses by geographic region, diagnostic method, and primate genus. Results: Thirty-nine articles assessing 7,183 NHP met the inclusion criteria; 28 contributed to meta-analyses, and 10 provided 19 individual case reports. Pooled molecular prevalence by RT-PCR was 30.7%, and prevalence by immunohistochemistry was 43.4%, both with substantial between-study heterogeneity. Seroprevalence estimates ranged from 5.0 to 36.4% across assays and settings. Higher infection metrics were observed in howler monkeys and titi monkeys. All reported individual cases were fatal and predominantly associated with severe hepatic and multisystemic pathology. Most data originated from the Americas, particularly Brazil, with limited representation from African endemic regions. Conclusion: YFV infection in NHP is widespread, often severe, and epidemiologically significant. Our findings underscore the critical sentinel role of NHPs and highlight the need to strengthen integrated One Health surveillance systems to inform prevention and control strategies, particularly in the context of the current resurgence of yellow fever in Latin America and persistent data gaps in Africa.