The Effect of Plasmodium on the Outcome of Ebola Virus Infection in a Mouse Model

Rosenke, Kyle; Mercado-Hernandez, Reinaldo; Cronin, Jacqueline; Conteh, Solomon; Duffy, Patrick E.; Feldmann, Heinz; Wit, Emmie de

doi:10.1093/infdis/jiy236

Cited by 3 publications

(6 citation statements)

References 9 publications

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“…Our findings demonstrate that acute Plasmodium infection generates sufficient IFN-g to protect against a low, but uniformly lethal, dose of EBOV; however, we found that it is not protective against higher EBOV doses. The inability of Py infection to overcome higher doses of EBOV is consistent with an earlier report that showed that Py infection does not alter morbidity or mortality associated with the administration of 100 LD 50 of EBOV to mice (Rosenke et al, 2018). Recombinant IFN-g administration also protected against low doses, but not high doses, of rVSV/ EBOV GP in Ifnar À/À mice, in a manner similar to protection conferred by acute Py in ma-EBOV studies.…”

Section: Discussionsupporting

confidence: 88%

“…Similarly, IFN-g did not provide protection to pmacs challenged with a 10-fold higher dose of wild-type EBOV (Figure S5C). These data are consistent with our in vivo ma-EBOV findings (Figure 1) and recent reports from others (Rosenke et al, 2018) showing that experimental malaria fails to modulate the course of EVD when mice are challenged with large doses (eg, 100 lethal dose 50 [LD 50 ]) of ma-EBOV. For all experiments, C57BL/6 Ifnar À/À mice were inoculated with 1 3 10 6 Py iRBCs or left untreated.…”

Section: Plasmodium-elicited Protection From Rvsv/ebov Gp Wanes Over Timesupporting

confidence: 93%

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Acute Plasmodium Infection Promotes Interferon-Gamma-Dependent Resistance to Ebola Virus Infection

et al. 2020

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During the 2013-2016 Ebola virus (EBOV) epidemic, a significant number of patients admitted to Ebola treatment units were co-infected with Plasmodium falciparum, a predominant agent of malaria. However, there is no consensus on how malaria impacts EBOV infection. The effect of acute Plasmodium infection on EBOV challenge was investigated using mouse-adapted EBOV and a biosafety level 2 (BSL-2) model virus. We demonstrate that acute Plasmodium infection protects from lethal viral challenge, dependent upon interferon gamma (IFN-g) elicited as a result of parasite infection. Plasmodium-infected mice lacking the IFN-g receptor are not protected. Ex vivo incubation of naive human or mouse macrophages with sera from acutely parasitemic rodents or macaques programs a proinflammatory phenotype dependent on IFN-g and renders cells resistant to EBOV infection. We conclude that acute Plasmodium infection can safeguard against EBOV by the production of protective IFN-g. These findings have implications for anti-malaria therapies administered during episodic EBOV outbreaks in Africa.

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Section: Discussionsupporting

confidence: 88%

Section: Plasmodium-elicited Protection From Rvsv/ebov Gp Wanes Over Timesupporting

confidence: 93%

Acute Plasmodium Infection Promotes Interferon-Gamma-Dependent Resistance to Ebola Virus Infection

et al. 2020

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“…In addition to these observational studies in the field, the two laboratory studies also report the effect of coinfection on mortality in murine models. Rosenke et al 2018 found no effect of coinfection on mortality in mice when challenged with a high dose of MA-EBOV at 100-median lethal dose. In contrast, Rogers et al found that acute Plasmodium infection protected from lethal virus challenge at low (1-iu) MA_EBOV challenge but less so with moderate to high (10-iu and 100-iu) doses.…”

Section: Plos Onementioning

confidence: 80%

“…The model in one study was of CD1 mice infected via intraperitoneal inoculation with Plasmodium yoeli (Py) at a dose of 10 4 parasitized erythrocytes, followed by challenge with mouse-attenuated EBOV (MA-EBOV) at a 100 median lethal dose at different time points post Py infection. In each time-group, 6 mice were followed for survival to 28 days post infection (dpi), and four were euthanised on day 4-dpi to analyse blood and liver RNA concentrations for Py and MA-EBOV [ 49 ].…”

Section: Resultsmentioning

confidence: 99%

“…The protective effect observed from the laboratory study by Rogers et al was not observed in the second laboratory study identified, however, this second study used only a very high lethal dose of MA-EBOV (100-iu) [ 49 ]. Use of similarly high doses by Rogers et al (10-iu and 100-iu) also showed limited effect on morbidity and outcomes compared to the low EBOV dose (1-iu) which was significantly protective, thus suggesting high viral load overrides any potential protection from coinfection [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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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RNA Viruses, Pregnancy and Vaccination: Emerging Lessons from COVID-19 and Ebola Virus Disease

Dhanya¹,

Shailaja

Mary

et al. 2022

Pathogens

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Pathogenic viruses with an RNA genome represent a challenge for global human health since they have the tremendous potential to develop into devastating pandemics/epidemics. The management of the recent COVID-19 pandemic was possible to a certain extent only because of the strong foundations laid by the research on previous viral outbreaks, especially Ebola Virus Disease (EVD). A clear understanding of the mechanisms of the host immune response generated upon viral infections is a prime requisite for the development of new therapeutic strategies. Hence, we present here a comparative study of alterations in immune response upon SARS-CoV-2 and Ebola virus infections that illustrate many common features. Vaccination and pregnancy are two important aspects that need to be studied from an immunological perspective. So, we summarize the outcomes and immune responses in vaccinated and pregnant individuals in the context of COVID-19 and EVD. Considering the significance of immunomodulatory approaches in combating both these diseases, we have also presented the state of the art of such therapeutics and prophylactics. Currently, several vaccines against these viruses have been approved or are under clinical trials in various parts of the world. Therefore, we also recapitulate the latest developments in these which would inspire researchers to look for possibilities of developing vaccines against many other RNA viruses. We hope that the similar aspects in COVID-19 and EVD open up new avenues for the development of pan-viral therapies.

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The Effect of Plasmodium on the Outcome of Ebola Virus Infection in a Mouse Model

Cited by 3 publications

References 9 publications

Acute Plasmodium Infection Promotes Interferon-Gamma-Dependent Resistance to Ebola Virus Infection

Acute Plasmodium Infection Promotes Interferon-Gamma-Dependent Resistance to Ebola Virus Infection

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

RNA Viruses, Pregnancy and Vaccination: Emerging Lessons from COVID-19 and Ebola Virus Disease

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