Observational studyMalaria journal2015
Dysregulation of the haem-haemopexin axis is associated with severe malaria in a case-control study of Ugandan children.
Observational study in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Population Pharmacokinetics and Pharmacodynamics of Paracetamol in Malaysian Patients With Plasmodium knowlesi Malaria.CPT: pharmacometrics & systems pharmacology · 2026Article
- Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria.BMC nephrology · 2025Article
- Targeting circulating labile heme as a defense strategy against malaria.Life science alliance · 2024Article
- Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria.Memorias do Instituto Oswaldo Cruz · 2023Article
- Brain endothelial STING1 activation byProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice.Nature communications · 2022Article
- Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria.Scientific reports · 2021Article
- Hemozoin: a Complex Molecule with Complex Activities.Current clinical microbiology reports · 2021Article
- The effect of blood transfusion on outcomes among African children admitted to hospital with Plasmodium falciparum malaria: a prospective, multicentre observational study.The Lancet. Haematology · 2020Observational
- New insights into microvascular injury to inform enhanced diagnostics and therapeutics for severe malaria.Virulence · 2019Review
- Changes in monocyte subsets are associated with clinical outcomes in severe malarial anaemia and cerebral malaria.Scientific reports · 2019Article
- Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Chitinase-3-like 1 is a biomarker of acute kidney injury and mortality in paediatric severe malaria.Malaria journal · 2018Article
- Adjunctive therapy for severe malaria: a review and critical appraisal.Malaria journal · 2018Review
- Synthetic oleanane triterpenoids enhance blood brain barrier integrity and improve survival in experimental cerebral malaria.Malaria journal · 2017Article
- Identification of oxidative modifications of hemopexin and their predicted physiological relevance.The Journal of biological chemistry · 2017Article
- Alterations in Systemic Extracellular Heme and Hemopexin Are Associated With Adverse Clinical Outcomes in Ugandan Children With Severe Malaria.The Journal of infectious diseases · 2016Article
- Host Biomarkers Are Associated With Response to Therapy and Long-Term Mortality in Pediatric Severe Malaria.Open forum infectious diseases · 2016Article
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundMalaria is associated with haemolysis and the release of plasma haem. Plasma haem can cause endothelial injury and organ dysfunction, and is normally scavenged by haemopexin to limit toxicity. It was hypothesized that dysregulation of the haem-haemopexin pathway contributes to severe and fatal malaria infections.
methodsPlasma levels of haemin (oxidized haem), haemopexin, haptoglobin, and haemoglobin were quantified in a case-control study of Ugandan children with Plasmodium falciparum malaria. Levels at presentation were compared in children with uncomplicated malaria (UM; n = 29), severe malarial anaemia (SMA; n = 27) or cerebral malaria (CM; n = 31), and evaluated for utility in predicting fatal (n = 19) vs non-fatal (n = 39) outcomes in severe disease. A causal role for haemopexin was assessed in a pre-clinical model of experimental cerebral malaria (ECM), following disruption of mouse haemopexin gene (hpx). Analysis was done using Kruskall Wallis tests, Mann-Whitney tests, log-rank tests for survival, and repeated measures ANOVA.
resultsIn Ugandan children presenting with P. falciparum malaria, haemin levels were higher and haemopexin levels were lower in SMA and CM compared to children with UM (haemin, p < 0.01; haemopexin, p < 0.0001). Among all cases of severe malaria, elevated levels of haemin and cell-free haemoglobin at presentation were associated with subsequent mortality (p < 0.05). Compared to ECM-resistant BALB/c mice, susceptible C57BL/6 mice had lower circulating levels of haemopexin (p < 0.01), and targeted deletion of the haemopexin gene, hpx, resulted in increased mortality compared to their wild type littermates (p < 0.05).
conclusionsThese data indicate that plasma levels of haemin and haemopexin measured at presentation correlate with malaria severity and levels of haemin and cell-free haemoglobin predict outcome in paediatric severe malaria. Mechanistic studies in the ECM model support a causal role for the haem-haemopexin axis in ECM pathobiology.
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