Evidence map›Paper›PMID 42251252›Full record

ArticleBMC infectious diseases2026

Identifying viral infections through metagenomic Next Generation Sequencing of undiagnosed respiratory fevers in Madagascar (2014-2019).

Sophie Lockwood, Hafaliana Christian Ranaivoson, Tsiry Hasina Randriambolamanantsoa, Norosoa Razanajatovo, Vololoniaina Raharinosy, Vida Ahyong, Jean-Michel Héraud, Philippe Dussart, Vincent Lacoste, Cara E Brook

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Article in BMC infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Sophie LockwoodDepartment of Integrative Biology, University of California Berkeley, Berkeley, CA, USA. slockwood@berkeley.edu.
Hafaliana Christian RanaivosonDepartment of Integrative Biology, University of California Berkeley, Berkeley, CA, USA.
Tsiry Hasina RandriambolamanantsoaVirology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Norosoa RazanajatovoVirology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Vololoniaina RaharinosyVirology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Vida AhyongChan Zuckerberg Biohub, San Francisco, CA, USA.
Jean-Michel HéraudVirology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Philippe DussartVirology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Vincent LacosteVirology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Cara E BrookDepartment of Integrative Biology, University of California Berkeley, Berkeley, CA, USA.

Funding

Bill and Melinda Gates Foundation GCE/ID OPP1211841U.S. Department of Education P200A210054
6 · The paper itself

Abstract

backgroundRespiratory illness contributes to substantial global morbidity and mortality. In Madagascar, an island nation off the southeastern coast of the African continent, hospital-based public health surveillance for respiratory pathogens screens for common respiratory viruses. However, many cases remain undiagnosed.

methodsWe conducted metagenomic Next Generation Sequencing (mNGS) to identify the pathogen profile of 102 undiagnosed febrile patients who presented to public hospitals with respiratory symptoms and screened negative on a 14-virus multiplex RT-qPCR. We analyzed the diversity of the respiratory microbiome of each patient from mNGS data and identified viral infections potentially linked to undiagnosed fever. We assembled whole genome consensus sequences of viruses with sufficient read depth and coverage, characterized each phylogenetically, and identified any discrepancies with the primers used in the multiplex RT-qPCR panel. Finally, we compared all whole genome sequences against publicly available global databases in a phylogenetic analysis.

resultsWe identified evidence of infection by a wide range of known human viruses in approximately two thirds (64.7%) of study participants from nine different families of viruses and generated 30 complete or nearly complete consensus sequences of known respiratory viruses including orthopneumoviruses, metapneumoviruses, rhinoviruses, coronaviruses, parainfluenza virus, and bocaparvovirus. mNGS-attributed evidence of infection was predominantly due to orthopneumovirus (also called respiratory syncytial virus [RSV]; n = 24; n = 8 previously diagnosed) and rhinovirus (n = 18) detections, despite previous negative RT-qPCR results for the majority of these cases. Finally, phylogenetic analysis identified two distinct phylogenetic clusters of RSV subtype A, suggesting local transmission following distinct international introductions for this virus.

conclusionmNGS provides a sensitive pan-pathogenic tool for virus detection. We demonstrate the diversity of viruses associated with undiagnosed respiratory fevers in Madagascar, emphasize the importance and relevance of the existing respiratory surveillance in the country, and highlight the interconnectedness of regional respiratory infection dynamics with global networks of respiratory pathogen transmission.

Indexed as

Fever of Unknown OriginHigh-Throughput Nucleotide SequencingMetagenomicsRespiratory Tract InfectionsRNA VirusesAdolescentAdultChildChild, PreschoolFemaleGenome, ViralHumansInfantInfant, NewbornMadagascarMalemNGSPublic health surveillanceRespiratory viruses

Identifiers

PMID42251252
PMCPMC13386818

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.