Genomic Epidemiology of 2023-2024 Oropouche Outbreak in Iquitos, Peru reveals independent origin from a concurrent outbreak in Brazil

Abstract Oropouche virus is an arbovirus endemic to the Americas. Periodic outbreaks have occurred since its description in 1955. In late 2023, an outbreak occurred in Peru, centered in and around Iquitos in the Eastern Peruvian Amazon. An existing acute febrile illness (AFI) surveillance program was able to document its emergence and characterize arthralgia and dysuria and the absence of diarrhea as distinctive clinical features of Oropouche virus-associated febrile illness relative to other causes of AFI. Sequencing of isolates from the outbreak demonstrated that strains from this region were distinct from those causing disease in Brazil, despite the large-scale movement of people along the Amazon corridor, but highly similar to strains from Colombia and Ecuador. Our findings suggest that the current outbreak in South America is fundamentally multifocal in origin and not the result of geographic spread from Brazil, which experienced an outbreak between 2022 and 2024. Competing Interest Statement The authors have declared no competing interest. Funding Statement This project is supported by the Centers for Disease Control and Prevention of the U.S. Department of Health and Human Services (HHS) as part of a cooperative agreement award with CDC/HHS, award number U01GH002270 to MNK. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention. Additional training and capacity-building support was obtained through the National Institutes of Health/Fogarty International Center (D43TW010913 to MNK; K43TW012298 to FS), the National Institutes of Health/National Institute for Allergies and Infectious Diseases (K01AI168493 to JMC), the Infectious Diseases Training Program 5T32AI007046-48 and the Division of Infectious Diseases and International Health of the University of Virginia. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The RIVERA study has been approved by the Institutional Review Board of Asociacion Benefica Prisma (CE0855.20) (FWA00001219), University of Virginia (FWA0006183), and Hospital Regional de Loreto. Additional approval has been obtained by the Research Commission of the Regional Health Direction of Loreto. Written informed consent was obtained for all participants. For children aged 10 to 18 years of age, both parental written informed consent and written informed assent were obtained. All participants consented to the further use of biological specimens. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All genomic data is publicly available under accession numbers referenced in the manuscript.