ArticleThe Journal of infectious diseases2016
Alterations in Systemic Extracellular Heme and Hemopexin Are Associated With Adverse Clinical Outcomes in Ugandan Children With Severe Malaria.
Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
- Population Pharmacokinetics and Pharmacodynamics of Paracetamol in Malaysian Patients With Plasmodium knowlesi Malaria.CPT: pharmacometrics & systems pharmacology · 2026Article
- Transcriptomic and proteomic profiling of piroplasmosis resistance in Yunnan humped cattle.BMC genomics · 2026Article
- Serum Proteomics Provides Novel Biomarkers of Inflammation, Tissue Injury, and Therapeutic Response in Experimental Chagas Disease.Microorganisms · 2026Article
- Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria.BMC nephrology · 2025Article
- Animal Models of Malaria-Associated Acute Kidney Injury.Seminars in nephrology · 2025Review
- Clinical, immune and genetic risk factors of malaria-associated acute kidney injury in Zambian children: A study protocol.PloS one · 2025Observational
- Article
- Targeting circulating labile heme as a defense strategy against malaria.Life science alliance · 2024Article
- Xanthine oxidase levels and immune dysregulation are independently associated with anemia in Plasmodium falciparum malaria.Scientific reports · 2023Article
- Renin as a Biomarker of Acute Kidney Injury and Mortality in Children With Severe Malaria or Sickle Cell Disease.Cureus · 2023Article
- Article
- Safety and feasibility of the gene transfer of hemopexin for conditions with increased free heme.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Double-edged functions of hemopexin in hematological related diseases: from basic mechanisms to clinical application.Frontiers in immunology · 2023Review
- The spectrum of clinical biomarkers in severe malaria and new avenues for exploration.Virulence · 2022Review
- Blackwater fever and acute kidney injury in children hospitalized with an acute febrile illness: pathophysiology and prognostic significance.BMC medicine · 2022Observational
- Pathophysiology of Acute Kidney Injury in Malaria and Non-Malarial Febrile Illness: A Prospective Cohort Study.Pathogens (Basel, Switzerland) · 2022Article
- Acute kidney injury in hospitalized children with sickle cell anemia.BMC nephrology · 2022Article
- Falciparum malaria associated acute kidney injury with polyneuropathy and intra-arterial thrombosis (stroke).European journal of medical research · 2022Article
- Hemozoin: a Complex Molecule with Complex Activities.Current clinical microbiology reports · 2021Article
- Oxidative Stress and Pathogenesis in Malaria.Frontiers in cellular and infection microbiology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundMalaria remains a major cause of global mortality. Extracellular heme, released during malaria-induced hemolysis, mediates a number of pathogenic processes associated with vascular and organ injury. Hemopexin (hpx) facilitates the degradation of extracellular heme. In this study, we explore the hypothesis that dysregulation of the heme-hpx axis is associated with disease severity, acute kidney injury (AKI), and outcome.
methodsPlasma levels of hemin and hpx (at admission, day 3, and day 14) were assessed in children with severe malaria in Jinja, Uganda.
resultsThe ratio of heme to hpx was higher at admission and decreased with recovery (median, 0.043 [interquartile range {IQR}, 0.007-0.239] on day 1, 0.024 [IQR, 0.005-0.126] on day 3, and 0.008 [IQR, 0.002-0.022] on day 14; P < .001). Ratios of heme to hpx at admission were higher in children with as compared to those without severe anemia (median, 0.124 [IQR, 0.024-0.431] vs 0.016 [IQR, 0.003-0.073]; P < .0001), children with as compared to those without respiratory distress (median, 0.063 [IQR, 0.017-0.413] vs 0.020 [IQR, 0.004-0.124]; P < .01), and children with as opposed to those without stage 3 AKI (median, 0.354 [IQR, 0.123-2.481] vs 0.037 [IQR, 0.005-0.172], P < .01). The heme to hpx ratio at admission was associated with 6-month mortality (median, 0.148 [IQR, 0.042-0.500] vs 0.039 [IQR, 0.007-0.172]; P = .012).
conclusionsThe ratio of heme to hpx is associated with disease severity and adverse clinical outcomes in Ugandan children, and dysregulation of the heme axis may contribute to malaria pathogenesis.
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