Long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort study

Abstract Background The long-term health effects of ebolavirus disease (EVD) caused by the Sudan ebolavirus (SUDV) strain remain poorly characterized. Here, we assessed the nature, frequency, and persistence of post-EVD clinical symptoms among SUDV survivors 2 years after infection by comparing them...

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Main Authors: Haruna Muwonge, Carolyne Nasimiyu, Barnabas Bakamutumaho, Peter Elyanu, Moses L. Joloba, Silvia Situma, John Schieffelin, Bronwyn Gunn, Shuangyi Bai, Robert F. Breiman, Isaac Ssewanyana, Susan Nabadda, Julius Lutwama, Yonas Tegen, Allan Muruta, Bruce Kirenga, Charles Olaro, Jane Ruth Aceng, Henry Kyobe Bosa, M. Kariuki Njenga
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-025-04271-z
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author Haruna Muwonge
Carolyne Nasimiyu
Barnabas Bakamutumaho
Peter Elyanu
Moses L. Joloba
Silvia Situma
John Schieffelin
Bronwyn Gunn
Shuangyi Bai
Robert F. Breiman
Isaac Ssewanyana
Susan Nabadda
Julius Lutwama
Yonas Tegen
Allan Muruta
Bruce Kirenga
Charles Olaro
Jane Ruth Aceng
Henry Kyobe Bosa
M. Kariuki Njenga
author_facet Haruna Muwonge
Carolyne Nasimiyu
Barnabas Bakamutumaho
Peter Elyanu
Moses L. Joloba
Silvia Situma
John Schieffelin
Bronwyn Gunn
Shuangyi Bai
Robert F. Breiman
Isaac Ssewanyana
Susan Nabadda
Julius Lutwama
Yonas Tegen
Allan Muruta
Bruce Kirenga
Charles Olaro
Jane Ruth Aceng
Henry Kyobe Bosa
M. Kariuki Njenga
author_sort Haruna Muwonge
collection DOAJ
description Abstract Background The long-term health effects of ebolavirus disease (EVD) caused by the Sudan ebolavirus (SUDV) strain remain poorly characterized. Here, we assessed the nature, frequency, and persistence of post-EVD clinical symptoms among SUDV survivors 2 years after infection by comparing them with matched community controls. Methods The primary objective was determining the prevalence of clinical symptoms over the 24-month period. Using a prospective matched cohort approach, 87 laboratory-confirmed SUDV survivors from the 2022–2023 Ugandan outbreak and 176 age-, sex- and village-matched controls were followed at 3, 9, 12, 15 and 24 months. Symptom data were collected through structured interviews and targeted clinical examinations. A secondary objective was investigating the duration of viral RNA shedding in semen and breast milk of survivors collected during follow-up, using the PCR test. Results Of the 87 SUDV survivors, 57.5% reported significantly higher frequencies of clinical symptoms involving musculoskeletal (45.0%, P < 0.001), central nervous system (36.3%, p < 0.001), ophthalmologic (20%, P < 0.001), and respiratory (10%, P < 0.001) systems than those observed among controls. The risk ratio of occurrence was highest for ophthalmologic (20% vs 3.4%, RR = 5.9; p < 0.001) and central nervous systems symptoms (36.3% vs 6.8%, RR = 5.3, p < 0.001), and lowest for reproductive system (13.8% vs 8.5%; RR = 1.6; p > 0.005). Importantly, 50% of the survivors reported persistent multi-systemic symptoms, including low back pain, hand and feet numbness, confusion, and diarrhoea that resulted in an inability to perform basic activities of living. Viral RNA was detected in semen for up to 210 post-infection (median = 131 days, range: 111–210 days) and in breast milk for up to 199 days (median = 149 days, range: 111–199 days). Conclusions This study demonstrates that SUDV survivors develop long-term clinical sequelae characterized by persistent multi-systemic clinical symptoms. Detection of viral RNA in semen and breastmilk for up to 7 months post-infection suggests prolonged persistence, opening the possibility of latency and reactivation of the virus.
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spelling doaj-art-cf3d2fdf5b334222b9d5a1e77e79daa52025-08-20T03:46:07ZengBMCBMC Medicine1741-70152025-07-0123111010.1186/s12916-025-04271-zLong-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort studyHaruna Muwonge0Carolyne Nasimiyu1Barnabas Bakamutumaho2Peter Elyanu3Moses L. Joloba4Silvia Situma5John Schieffelin6Bronwyn Gunn7Shuangyi Bai8Robert F. Breiman9Isaac Ssewanyana10Susan Nabadda11Julius Lutwama12Yonas Tegen13Allan Muruta14Bruce Kirenga15Charles Olaro16Jane Ruth Aceng17Henry Kyobe Bosa18M. Kariuki Njenga19Makerere University Medical SchoolCenter for Research in Emerging Infectious Diseases-East and Central Africa, Washington State University Global Health-KenyaUganda Virus Research InstituteBaylor College of Medicine Children Foundation-UgandaMakerere University Medical SchoolCenter for Research in Emerging Infectious Diseases-East and Central Africa, Washington State University Global Health-KenyaWest Africa Research Network of Infectious Disease, Tulane UniversityCenter for Research in Emerging Infectious Diseases-East and Central Africa, Washington State University Global Health-KenyaPaul G. Allen School for Global Health, Washington State UniversityEmory UniversityUganda Central Public Health LaboratoriesUganda Central Public Health LaboratoriesUganda Virus Research InstituteIndependent Global Health ConsultantMinistry of Health UgandaMakerere University Medical SchoolMinistry of Health UgandaMinistry of Health UgandaMinistry of Health UgandaCenter for Research in Emerging Infectious Diseases-East and Central Africa, Washington State University Global Health-KenyaAbstract Background The long-term health effects of ebolavirus disease (EVD) caused by the Sudan ebolavirus (SUDV) strain remain poorly characterized. Here, we assessed the nature, frequency, and persistence of post-EVD clinical symptoms among SUDV survivors 2 years after infection by comparing them with matched community controls. Methods The primary objective was determining the prevalence of clinical symptoms over the 24-month period. Using a prospective matched cohort approach, 87 laboratory-confirmed SUDV survivors from the 2022–2023 Ugandan outbreak and 176 age-, sex- and village-matched controls were followed at 3, 9, 12, 15 and 24 months. Symptom data were collected through structured interviews and targeted clinical examinations. A secondary objective was investigating the duration of viral RNA shedding in semen and breast milk of survivors collected during follow-up, using the PCR test. Results Of the 87 SUDV survivors, 57.5% reported significantly higher frequencies of clinical symptoms involving musculoskeletal (45.0%, P < 0.001), central nervous system (36.3%, p < 0.001), ophthalmologic (20%, P < 0.001), and respiratory (10%, P < 0.001) systems than those observed among controls. The risk ratio of occurrence was highest for ophthalmologic (20% vs 3.4%, RR = 5.9; p < 0.001) and central nervous systems symptoms (36.3% vs 6.8%, RR = 5.3, p < 0.001), and lowest for reproductive system (13.8% vs 8.5%; RR = 1.6; p > 0.005). Importantly, 50% of the survivors reported persistent multi-systemic symptoms, including low back pain, hand and feet numbness, confusion, and diarrhoea that resulted in an inability to perform basic activities of living. Viral RNA was detected in semen for up to 210 post-infection (median = 131 days, range: 111–210 days) and in breast milk for up to 199 days (median = 149 days, range: 111–199 days). Conclusions This study demonstrates that SUDV survivors develop long-term clinical sequelae characterized by persistent multi-systemic clinical symptoms. Detection of viral RNA in semen and breastmilk for up to 7 months post-infection suggests prolonged persistence, opening the possibility of latency and reactivation of the virus.https://doi.org/10.1186/s12916-025-04271-zEbola virus diseaseSudan ebolavirus diseasePost-Ebola sequelaeEbola survivorsLong-term health outcomesViral persistence
spellingShingle Haruna Muwonge
Carolyne Nasimiyu
Barnabas Bakamutumaho
Peter Elyanu
Moses L. Joloba
Silvia Situma
John Schieffelin
Bronwyn Gunn
Shuangyi Bai
Robert F. Breiman
Isaac Ssewanyana
Susan Nabadda
Julius Lutwama
Yonas Tegen
Allan Muruta
Bruce Kirenga
Charles Olaro
Jane Ruth Aceng
Henry Kyobe Bosa
M. Kariuki Njenga
Long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort study
BMC Medicine
Ebola virus disease
Sudan ebolavirus disease
Post-Ebola sequelae
Ebola survivors
Long-term health outcomes
Viral persistence
title Long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort study
title_full Long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort study
title_fullStr Long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort study
title_full_unstemmed Long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort study
title_short Long-term clinical sequelae among Sudan ebolavirus disease survivors 2 years post-infection: a matched cohort study
title_sort long term clinical sequelae among sudan ebolavirus disease survivors 2 years post infection a matched cohort study
topic Ebola virus disease
Sudan ebolavirus disease
Post-Ebola sequelae
Ebola survivors
Long-term health outcomes
Viral persistence
url https://doi.org/10.1186/s12916-025-04271-z
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