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Meta-Analysis
. 2021 May 24;16(5):e0251101.
doi: 10.1371/journal.pone.0251101. eCollection 2021.

The impact of malaria coinfection on Ebola virus disease outcomes: A systematic review and meta-analysis

Hannah M Edwards  1 , Helen Counihan  1 , Craig Bonnington  1 , Jane Achan  1 , Prudence Hamade  1 , James K Tibenderana  1
Affiliations
Meta-Analysis

The impact of malaria coinfection on Ebola virus disease outcomes: A systematic review and meta-analysis

Hannah M Edwards et al. PLoS One. .

Abstract

Introduction: 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 Plasmodium spp. and Ebolavirus (EBOV) interact is important for future outbreaks.

Methods: 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/Plasmodium spp. coinfection, 2) effect of EBOV/Plasmodium spp. coinfection on EVD pathology and the immune response, 3) impact of EBOV/Plasmodium spp. 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.

Results: 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 49.3-74.6 and 56.7%, 95% CI 53.2-60.1, respectively), and there was no significant difference in risk of mortality (RR 1.09, 95% CI 0.90-1.31) 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 Plasmodium yoeli infection was protective against morbidity and mortality via the IFN-γ signalling pathway.

Conclusion: 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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA flow diagram for study selection.
Fig 2
Fig 2. Meta-analysis of the prevalence of Plasmodium infection among EVD(+) cases, overall and split by species of Ebolavirus.
Fig 3
Fig 3
Meta-analysis of CFR: A) crude CFR, B) CFR of EBOV(+)/Pl/(+) cases, C) CFR of EBOV(+)/Pl.(-) cases.
Fig 4
Fig 4. Meta-analysis of unadjusted risk ratio estimates for the effect of Plasmodium infection on EVD-related mortality (all ZEBOV).
Fig 5
Fig 5. Meta-analysis of unadjusted risk ratio estimates for the effect of Plasmodium infection on EVD-related mortality (all ZEBOV) including only studies with malaria RDT as the diagnostic.
Fig 6
Fig 6. Meta-analysis of adjusted risk ratio estimates.
A) all adjusted RR estimates, and B) only those that included adjustment for viral load.
See this image and copyright information in PMC

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