Plasmodium falciparum isolate:Pregnant women
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ABSTRACT:
PROVIDER: PRJNA1220016 | ENA |
REPOSITORIES: ENA
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Project description:Background: Knowledge about extracellular vesicles (EV) and their molecular cargo in gestational parasitic infections, particularly by Plasmodium and soil-transmitted helminths (STH), is almost non-existent. Objective: To perform isolation and molecular characterization of plasma-derived EVs from Colombian pregnant women and compare quantity, size, concentration and protein cargo of those EVs according to the infectious status. Methodology: Five study groups were formed: 1), Pregnant women with Plasmodium infection. 2), Pregnant women with STH infection. 3), Pregnant women with coinfection Plasmodium and STH. 4), Pregnant women without infection with Plasmodium nor STH. 5), Non-pregnant women without infection with Plasmodium nor STH. Plasma-derived EVs were isolated by size exclusion chromatography (SEC) and fractions containing EVs identified by a bead-based flow cytometric assay for tetraspanin CD9; the size and concentration of EVs were quantified by nanoparticle tracking analysis, and proteins associated with EVs were identified by liquid chromatography-mass spectrometry (LC-MS) in a pool of samples per study group.
2024-11-26 | PXD051270 | Pride
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Project description:Background: Iron deficiency, anaemia and Plasmodium infection represent significant global health challenges with overlapping geographical distributions, particularly affecting pregnant women in Africa. Previous evidence suggests complex interactions between iron status and malaria susceptibility. However, the mechanisms and clinical implications of this relationship remain poorly understood. Methods: We employed a multi-layered approach to clarify the association between iron deficiency and malaria infection risk. First, we analysed clinical data from Malawian pregnant women (n=711) participating in the REVAMP clinical trial—an RCT of intravenous iron versus oral iron—to assess associations between iron status and P. falciparum parasitaemia detected by ultra-sensitive qPCR. All eligible women received intermittent preventive anti-malaria treatment. Then, we utilised a genetic mouse model (Tmprss6-knockout) to isolate the effect of iron deficiency on P. berghei infection and progression to clinical disease. Finally, we explored direct effects of iron chelation on cultured P. falciparum parasites through transcriptomic and proteomic analyses. Results: In REVAMP, iron deficiency was associated with a 50% reduced probability of P. falciparum qPCR positivity at baseline (95% CI [30%-64%], p<0·0001). Iron intervention given at baseline did not significantly modify the probability of subsequent parasitaemia across the pregnancy. In the murine model, iron-deficient Tmprss6-knockout mice exhibited significantly improved survival compared to controls (median survival 15·5 vs 7·0 days) and protection from cerebral malaria (survival 83% vs 17%). Iron chelation in P. falciparum cultures induced substantial transcriptomic (1,397 differentially expressed genes) and proteomic changes (121 differentially expressed proteins; 46 matched differentially expressed gene/protein pairs), primarily affecting processes involved in host cell invasion, protein export, and nutrient acquisition. Conclusion: Our findings consistently demonstrate that iron deficiency protects against Plasmodium infection across clinical, pre-clinical, and in vitro models. Importantly, in the presence of adequate malaria prevention intravenous iron supplementation did not significantly increase subsequent parasitemia prevalence. These results provide mechanistic insights into iron and malaria interactions and support current WHO recommendations for iron supplementation in pregnant women in malaria-endemic regions when coupled with adequate malaria prevention strategies.
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