{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:59:28Z","timestamp":1791932368699,"version":"4.3.4"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Viral outbreaks present a particular challenge in countries in Africa where there is already a high incidence of other infectious diseases, including malaria which can alter immune responses to secondary infection. Ebola virus disease (EVD) is one such problem; understanding how <jats:italic>Plasmodium spp<\/jats:italic>. and Ebolavirus (EBOV) interact is important for future outbreaks.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a systematic review in PubMed and Web of Science to find peer-reviewed papers with primary data literature to determine 1) prevalence of EBOV\/<jats:italic>Plasmodium spp<\/jats:italic>. coinfection, 2) effect of EBOV\/<jats:italic>Plasmodium spp<\/jats:italic>. coinfection on EVD pathology and the immune response, 3) impact of EBOV\/<jats:italic>Plasmodium spp<\/jats:italic>. coinfection on the outcome of EVD-related mortality. Random effects meta-analyses were conducted with the R package meta to produce overall proportion and effect estimates as well as measure between-study heterogeneity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>From 322 peer-reviewed papers, 17 were included in the qualitative review and nine were included in a meta-analysis. Prevalence of coinfection was between 19% and 72%. One study reported significantly lower coagulatory response biomarkers in coinfected cases but no difference in inflammatory markers. Case fatality rates were similar between EBOV(+)\/Pl(+) and EBOV(+)\/Pl(-) cases (62.8%, 95% CI 49.3\u201374.6 and 56.7%, 95% CI 53.2\u201360.1, respectively), and there was no significant difference in risk of mortality (RR 1.09, 95% CI 0.90\u20131.31) although heterogeneity between studies was high. One in vivo mouse model laboratory study found no difference in mortality by infection status, but another found prior acute <jats:italic>Plasmodium yoeli<\/jats:italic> infection was protective against morbidity and mortality via the IFN-\u03b3 signalling pathway.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The literature was inconclusive; studies varied widely and there was little attempt to adjust for confounding variables. Laboratory studies may present the best option to answer how pathogens interact within the body but improvement in data collection and analysis and in diagnostic methods would aid patient studies in the future.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0251101","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T17:27:18Z","timestamp":1621877238000},"page":"e0251101","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["The impact of malaria coinfection on Ebola virus disease outcomes: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8706-0732","authenticated-orcid":true,"given":"Hannah M.","family":"Edwards","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Counihan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Bonnington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Achan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prudence","family":"Hamade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-4597","authenticated-orcid":true,"given":"James K.","family":"Tibenderana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"pone.0251101.ref001","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1056\/NEJMoa031349","article-title":"Transmission of the Severe Acute Respiratory Syndrome on Aircraft","volume":"349","author":"SJ Olsen","year":"2003","journal-title":"N Engl J Med"},{"key":"pone.0251101.ref002","unstructured":"Department of Communicable Disease Surveillance and Response. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). Consens Doc Epidemiol Sev acute Respir Syndr [Internet]. 2003;1\u201347. Available from: https:\/\/www.who.int\/csr\/sars\/en\/WHOconsensus.pdf"},{"key":"pone.0251101.ref003","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0065-308X(05)62009-X","article-title":"Global Transport Networks and Infectious Disease Spread","volume":"62","author":"AJ Tatem","year":"2006","journal-title":"Adv Parasitol"},{"key":"pone.0251101.ref004","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ijsu.2020.02.034","article-title":"World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)","volume":"76","author":"C Sohrabi","year":"2020","journal-title":"Int J Surg"},{"issue":"3","key":"pone.0251101.ref005","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/ije\/dyaa033","article-title":"The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?","volume":"49","author":"NC Peeri","year":"2020","journal-title":"Int J Epidemiol"},{"key":"pone.0251101.ref006","unstructured":"Centers for Disease Control and Prevention. Ebola (Ebola virus disease). Ebola Virus Disease Distribution Map: Cases of Ebola Virus Disease in Africa Since 1976. [Internet]. [cited 2020 Jun 30]. Available from: https:\/\/www.cdc.gov\/vhf\/ebola\/history\/distribution-map.html"},{"issue":"4","key":"pone.0251101.ref007","doi-asserted-by":"crossref","first-page":"e00111","DOI":"10.1128\/CMR.00111-17","article-title":"Virological and immunological outcomes of coinfections","volume":"31","author":"N Kumar","year":"2018","journal-title":"Clin Microbiol Rev"},{"issue":"49","key":"pone.0251101.ref008","article-title":"Infection against infection: Parasite antagonism against parasites, viruses and bacteria","volume":"8","author":"SS Shen","year":"2019","journal-title":"Infect Dis Poverty"},{"key":"pone.0251101.ref009","unstructured":"World Health Organization. World Malaria Report: Malaria Country Profiles. 2014."},{"key":"pone.0251101.ref010","unstructured":"USAID. PRESIDENT\u2019S MALARIA INITIATIVE Guinea Malaria Operational Plan FY 2014 [Internet]. 2014. Available from: http:\/\/www.pmi.gov\/countries\/mops\/fy13\/liberia_mop_fy13.pdf"},{"issue":"3","key":"pone.0251101.ref011","doi-asserted-by":"crossref","first-page":"394","DOI":"10.9745\/GHSP-D-16-00186","article-title":"Successful implementation of a multicountry clinical surveillance and data collection system for Ebola virus disease in West Africa: Findings and lessons learned","volume":"4","author":"R Roshania","year":"2016","journal-title":"Glob Heal Sci Pract"},{"issue":"53","key":"pone.0251101.ref012","article-title":"Understanding Ebola: The 2014 epidemic","volume":"12","author":"J Kaner","year":"2016","journal-title":"Global Health"},{"issue":"6","key":"pone.0251101.ref013","doi-asserted-by":"crossref","first-page":"E82","DOI":"10.1016\/S1473-3099(16)00077-3","article-title":"Sequelae of Ebola virus disease: the emergency within the emergency","volume":"16","author":"P Vetter","year":"2016","journal-title":"Lancet Infect 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Hartgers","year":"2008","journal-title":"Infect Immun"},{"issue":"5","key":"pone.0251101.ref017","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1128\/CVI.00051-15","article-title":"Coinfection with blood-stage Plasmodium promotes systemic type I interferon production during pneumovirus infection but impairs inflammation and viral control in the lung","volume":"22","author":"CL Edwards","year":"2015","journal-title":"Clin Vaccine Immunol"},{"issue":"5","key":"pone.0251101.ref018","doi-asserted-by":"crossref","first-page":"e1004049","DOI":"10.1371\/journal.ppat.1004049","article-title":"Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function","volume":"10","author":"KL Lokken","year":"2014","journal-title":"PLoS Pathog"},{"issue":"9455","key":"pone.0251101.ref019","first-page":"233","article-title":"Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the 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Heal"},{"issue":"2","key":"pone.0251101.ref027","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/jebm.12191","article-title":"Meta-epidemiological study: a step-by-step approach by using R","volume":"9","author":"Z Zhang","year":"2016","journal-title":"J Evid Based Med"},{"issue":"11","key":"pone.0251101.ref028","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"JPT Higgins","year":"2002","journal-title":"Stat Med"},{"issue":"557","key":"pone.0251101.ref029","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"JPT Higgins","year":"2003","journal-title":"Br Med J"},{"key":"pone.0251101.ref030","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions","author":"JJ Deeks","year":"2020"},{"issue":"25","key":"pone.0251101.ref031","article-title":"The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is 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units in Liberia and Sierra Leone: A retrospective cohort study","volume":"64","author":"MA Smit","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"6","key":"pone.0251101.ref041","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/S1473-3099(17)30112-3","article-title":"Characteristics and survival of patients with Ebola virus infection, malaria, or both in Sierra Leone: a retrospective cohort study","volume":"17","author":"M Waxman","year":"2017","journal-title":"Lancet Infect Dis"},{"issue":"7","key":"pone.0251101.ref042","doi-asserted-by":"crossref","first-page":"ofz250","DOI":"10.1093\/ofid\/ofz250","article-title":"Effect of Mass Artesunate-Amodiaquine Distribution on Mortality of Patients with Ebola Virus Disease during West African Outbreak","volume":"6","author":"SC Garbern","year":"2019","journal-title":"Open Forum Infect Dis"},{"issue":"9","key":"pone.0251101.ref043","first-page":"e00827","article-title":"Metagenomic next-generation sequencing of the 2014 Ebola virus disease outbreak in the Democratic Republic of the Congo","volume":"57","author":"T Li","year":"2019","journal-title":"J Clin Microbiol"},{"issue":"11\u201312","key":"pone.0251101.ref044","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.medmal.2014.09.009","article-title":"Ebola outbreak in Conakry, Guinea: Epidemiological, clinical, and outcome features","volume":"44","author":"M Barry","year":"2014","journal-title":"Med Mal Infect"},{"issue":"6","key":"pone.0251101.ref045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0129333","article-title":"Ebola virus disease outbreak in Isiro, democratic Republic of the Congo, 2012: Signs and symptoms, management and outcomes","volume":"10","author":"T Kratz","year":"2015","journal-title":"PLoS One"},{"issue":"suppl_3","key":"pone.0251101.ref046","doi-asserted-by":"crossref","first-page":"S250","DOI":"10.1093\/infdis\/jiw269","article-title":"Analysis of Diagnostic Findings from the 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meta-analyses","volume":"335","author":"JPA Ioannidis","year":"2007","journal-title":"BMJ"},{"issue":"12765","key":"pone.0251101.ref054","article-title":"Summary of discordant results between rapid diagnosis tests, microscopy, and polymerase chain reaction for detecting Plasmodium mixed infection: a systematic review and meta-analysis","volume":"10","author":"M Kotepui","year":"2020","journal-title":"Sci Rep"},{"issue":"10","key":"pone.0251101.ref055","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1093\/cid\/cix625","article-title":"Performance of Rapid Diagnostic Testing in Patients with Suspected Malaria in Cambodia, a Low-Endemicity Country Aiming for Malaria Elimination","volume":"65","author":"G Rossi","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"3","key":"pone.0251101.ref056","first-page":"173","article-title":"Rapid diagnosis of severe malaria based on the detection of Pf-Hrp-2 antigen","volume":"37","author":"Y Birku","year":"1999","journal-title":"Ethiop Med J"},{"issue":"1","key":"pone.0251101.ref057","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12936-018-2371-9","article-title":"How long do rapid diagnostic tests remain positive after anti-malarial treatment?","volume":"17","author":"U Dalrymple","year":"2018","journal-title":"Malar J"},{"issue":"6","key":"pone.0251101.ref058","doi-asserted-by":"crossref","first-page":"613","DOI":"10.4269\/ajtmh.1996.54.613","article-title":"Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations","volume":"54","author":"C Rogier","year":"1996","journal-title":"Am J Trop Med Hyg"},{"issue":"470","key":"pone.0251101.ref059","article-title":"Characterizing microscopic and submicroscopic malaria parasitaemia at three sites with varied transmission intensity in Uganda","volume":"15","author":"J Rek","year":"2016","journal-title":"Malar 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