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Unfortunately, the burden of COVID-19 in Africa has been further exacerbated by the simultaneous epidemics of Ebola virus disease (EVD) and Lassa Fever (LF) which has created a huge burden on African healthcare systems. As Africa struggles to contain the spread of the second (and third) waves of the COVID-19 pandemic, the number of reported cases of LF is also increasing, and recently, new outbreaks of EVD. Before the pandemic, many of Africa\u2019s frail healthcare systems were already overburdened due to resource limitations in staffing and infrastructure, and also, multiple endemic tropical diseases. However, the shared epidemiological and pathophysiological features of COVID-19, EVD and LF as well their simultaneous occurrence in Africa may result in misdiagnosis at the onset of infection, an increased possibility of co-infection, and rapid and silent community spread of the virus(es). Other challenges include high population mobility across porous borders, risk of human-to-animal transmission and reverse zoonotic spread, and other public health concerns. This review highlights some major clinical and public health challenges toward responses to the COVID-19 pandemic amidst the deuce-ace of recurrent LF and EVD epidemics in Africa. Applying the One Health approach in infectious disease surveillance and preparedness is essential in mitigating emerging and re-emerging (co-)epidemics in Africa and beyond.<\/jats:p>","DOI":"10.1186\/s41182-021-00390-4","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T03:02:39Z","timestamp":1640833359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The deuce-ace of Lassa Fever, Ebola virus disease and COVID-19 simultaneous infections and epidemics in West Africa: clinical and public health implications"],"prefix":"10.1186","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1656-6194","authenticated-orcid":false,"given":"Nnabueze Darlington","family":"Nnaji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-847X","authenticated-orcid":false,"given":"Helen","family":"Onyeaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rine Christopher","family":"Reuben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-9027","authenticated-orcid":false,"given":"Olivier","family":"Uwishema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinasa Valerie","family":"Olovo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-7728","authenticated-orcid":false,"given":"Amarachukwu","family":"Anyogu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,30]]},"reference":[{"issue":"18","key":"390_CR1","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","volume":"382","author":"WJ Guan","year":"2020","unstructured":"Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. 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