Malaria Consortium, London, United Kingdom.
PLoS One. 2021 May 24;16(5):e0251101. doi: 10.1371/journal.pone.0251101. eCollection 2021.
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.
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.
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.
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.
在已经存在高发病率的其他传染病（包括可能改变对二次感染的免疫反应的疟疾）的非洲国家，病毒爆发构成了一个特殊挑战。埃博拉病毒病（EVD）就是这样一个问题；了解疟原虫属和埃博拉病毒（EBOV）如何相互作用对于未来的爆发很重要。
我们在 PubMed 和 Web of Science 上进行了系统综述，以查找具有原始数据文献的同行评议论文，以确定 1）EBOV/疟原虫属混合感染的流行率，2）EBOV/疟原虫属混合感染对 EVD 病理学和免疫反应的影响，3）EBOV/疟原虫属混合感染对 EVD 相关死亡率结果的影响。使用 R 包 meta 进行随机效应荟萃分析，以产生总体比例和效应估计值，并测量研究之间的异质性。
从 322 篇同行评议论文中，有 17 篇被纳入定性综述，9 篇被纳入荟萃分析。混合感染的流行率在 19%至 72%之间。一项研究报告称，混合感染病例的凝血反应生物标志物显著降低，但炎症标志物无差异。EBOV(+)/Pl(+)和 EBOV(+)/Pl(-)病例的病死率相似（分别为 62.8%，95%CI 49.3-74.6 和 56.7%，95%CI 53.2-60.1），且死亡率无显著差异（RR 1.09，95%CI 0.90-1.31），尽管研究之间存在高度异质性。一项体内小鼠模型实验室研究发现，感染状态对死亡率没有影响，但另一项研究发现，先前急性疟原虫 yoeli 感染通过 IFN-γ 信号通路对发病率和死亡率具有保护作用。
文献结果并不一致；研究差异很大，很少有尝试调整混杂变量。实验室研究可能是回答病原体如何在体内相互作用的最佳选择，但改善数据收集和分析以及诊断方法将有助于未来的患者研究。
