PROJET DREPANOCYTOSE ET PALUDISME
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PROVIDER: EGAS00001006008 | EGA |
REPOSITORIES: EGA
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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.
2026-01-04 | GSE302727 | GEO
Project description:Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal outcome of Plasmodium falciparum infection. Yet, the underlying mechanisms driving the pathogenesis of malaria-associated hypoglycemia remain poorly understood. Here we report that labile heme, an alarmin generated as a byproduct of hemolysis during the blood stage of Plasmodium spp. infection, plays a central role in the development of malaria-associated hypoglycemia. Labile heme recapitulated the hypometabolic response to Plasmodium (chabaudi chabaudi; Pcc) infection in mice, including the development of anorexia, transcriptional repression of hepatic glucose production (HGP) and reduction of glycemia, energy expenditure (EE) as well as core body temperature. While this hypometabolic response is protective against immune-mediated liver damage and anemia, when sustained over time it can lead to hypoglycemia and compromise EE as well as thermoregulation. I response, asexual stages of Plasmodium spp. activate a transcriptional program that reduces virulence in favor of sexual commitment and presumably malaria transmission. In conclusion, malaria-associated hypoglycemia represents a trade-off of a hypometabolic defense strategy against Plasmodium infection.
2021-12-31 | E-MTAB-10939 | biostudies-arrayexpress
Project description:Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal outcome of Plasmodium falciparum infection. Yet, the underlying mechanisms driving the pathogenesis of malaria-associated hypoglycemia remain poorly understood. Here we report that labile heme, an alarmin generated as a byproduct of hemolysis during the blood stage of Plasmodium spp. infection, plays a central role in the development of malaria-associated hypoglycemia. Labile heme recapitulated the hypometabolic response to Plasmodium (chabaudi chabaudi; Pcc) infection in mice, including the development of anorexia, transcriptional repression of hepatic glucose production (HGP) and reduction of glycemia, energy expenditure (EE) as well as core body temperature. While this hypometabolic response is protective against immune-mediated liver damage and anemia, when sustained over time it can lead to hypoglycemia and compromise EE as well as thermoregulation. In response, asexual stages of Plasmodium spp. activate a transcriptional program that reduces virulence in favor of sexual commitment and presumably malaria transmission. In conclusion, malaria-associated hypoglycemia represents a trade-off of a hypometabolic defense strategy against Plasmodium infection.
2021-12-31 | E-MTAB-10935 | biostudies-arrayexpress
Project description:Paper: Transcriptional Profiling of Plasmodium falciparum Parasites from Patients with Severe Malaria Identifies Distinct Low vs. High Parasitemic Clusters Milner et al Plos One July 18, 2012 Plasmodium falciparum Parasites from Patients with Severe Malaria
2016-06-24 | E-GEOD-83667 | biostudies-arrayexpress
Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. Vaccinees received 3 doses of 1.8 X 106 irradiated sporozoites. Efficacy was measured by challenged by controlled human malaria infections (CHMI), and against naturally occurring Pf Infections in Malian adults during the malaria transmission season
2022-08-20 | GSE211599 | GEO
Project description:Severe presentations of malaria emerge as parasites from Plasmodium spp. proliferate and lyse red blood cells (RBC), producing extracellular hemoglobin (HB). The heme prosthetic groups are released upon HB oxidation generating circulating labile heme. Here we asked whether scavenging of extracellular HB and/or labile heme, by haptoglobin (HP) and/or hemopexin (HPX), respectively, is protective against severe presentations of malaria. We found that circulating labile heme is an independent risk factor for cerebral and non-cerebral severe presentations of P. falciparum malaria. Labile heme was negatively correlated with HP and HPX, which were however, not risk factors for severe P. falciparum malaria. Genetic HP and/or HPX deletion in mice led to accumulation of labile heme in plasma and kidneys in response to Plasmodium (chabaudi chabaudi) infection. This was associated with increased mortality and acute kidney injury (AKI) in ageing but not adult mice, corroborated in P. falciparum malaria by a an inverse correlation between HPX and heme with serological markers of AKI. In conclusion, HP and HPX exert an age-dependent protective effect against malaria that counters the pathogenesis of AKI in mice and presumably in humans.
2024-01-30 | GSE253390 | GEO
Project description:Gene expression data from whole-blood collected from Kenyan children with Plasmodium falciparum malaria infection at acute hospital admission (n=15) and at convalescence (n=9). A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Disease State: with Plasmodium falciparum malaria infection at acute hospital admission and at convalescence
2016-02-15 | GSE35860 | GEO
Project description:Replication origin mapping in the malaria parasite Plasmodium falciparum
2022-08-04 | GSE210010 | GEO
Project description:Gene expression data from whole-blood collected from Kenyan children with Plasmodium falciparum malaria infection at acute hospital admission (n=15) and at convalescence (n=9). A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Disease State: with Plasmodium falciparum malaria infection at acute hospital admission and at convalescence clinical_history_design
2016-02-15 | E-GEOD-35860 | biostudies-arrayexpress
Project description:Gene expression data from Vietnamese subjects admitted to hospital with acute uncomplicated (n=6) or complicated (n=6) Plasmodium falciparum malaria infection had whole-blood samples collected at admission, 1 week later and 1 month later. Groups of assays that are related as part of a time series. Disease State: patient with complicated or uncomplicated Plasmodium falciparum malaria infection or Healthy control
2016-02-15 | GSE35859 | GEO