AUTHOR=Weiss Sonja L. , Bbosa Nicholas , Orf Gregory S. , Berg Michael G. , Ssemwanga Deogratius , Kalungi Sam , Balinandi Stephen , Mata Maximillian , Bosa Henry Kyobe , Nabirye Stella E. , Buule Joshua , Lutalo Tom , Havron Angela , Downing Robert , Rodgers Mary A. , Averhoff Francisco , Cloherty Gavin A. , Kaleebu Pontiano TITLE=A novel post-mortem pathogen discovery program detects an outbreak of Echovirus E7: Uganda, 2022–2023 JOURNAL=Frontiers in Microbiology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1557576 DOI=10.3389/fmicb.2025.1557576 ISSN=1664-302X ABSTRACT=ObjectivesUtilizing post-mortem examination for routine monitoring of infectious diseases and pandemic preparedness is a common-sense, yet uncommon, public health measure. Here, we established a novel mortuary surveillance program in Uganda that leverages the unbiased nature of metagenomic next-generation sequencing (mNGS) to detect pathogens in recently deceased individuals.MethodsBetween October 2022 and December 2023, specimens and patient metadata were collected from 2,607 individuals across five mortuary sites around Kampala. Specimens were pre-screened for hemorrhagic fever viruses by RT-qPCR and a subset (n = 134) of RT-qPCR negatives were sequenced by mNGS.ResultsA variety of DNA (herpes, parvovirus, bufavirus) and RNA (Saffold, Salivirus, HAV) viruses, vectored (Bartonella, Rickettsia) and nosocomial (Enterobacter, Klebsiella) bacterial infections, and potentially lethal respiratory pathogens (e.g., Cryptococcus neoformans, Corynebacterium diphtheria) were detected. A localized outbreak of Enterovirus B (EV-B), specifically a recombinant Echovirus E7, was observed in Kampala. An epidemiologic assessment indicated that most identified pathogens were acquired via direct and/or indirect contact (e.g., fecal-oral, fomites) and that other modes of transmission (e.g., food-borne, insect-vectored) played a less significant role.ConclusionIntegration of mortuary surveillance, coupled with mNGS, into public health systems represents a powerful strategy for identifying unrecognized outbreaks and monitoring the (re-) emergence of infectious diseases.