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The impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria

Author

Listed:
  • S. Uyoga

    (KEMRI-Wellcome Trust Research Programme)

  • J. A. Watson

    (Mahidol University
    University of Oxford)

  • P. Wanjiku

    (KEMRI-Wellcome Trust Research Programme)

  • J. C. Rop

    (KEMRI-Wellcome Trust Research Programme)

  • J. Makale

    (KEMRI-Wellcome Trust Research Programme)

  • A. W. Macharia

    (KEMRI-Wellcome Trust Research Programme)

  • S. N. Kariuki

    (KEMRI-Wellcome Trust Research Programme)

  • G. M. Nyutu

    (KEMRI-Wellcome Trust Research Programme)

  • M. Shebe

    (KEMRI-Wellcome Trust Research Programme)

  • M. Mosobo

    (KEMRI-Wellcome Trust Research Programme)

  • N. Mturi

    (KEMRI-Wellcome Trust Research Programme)

  • K. A. Rockett

    (University of Oxford)

  • C. J. Woodrow

    (Mahidol University
    University of Oxford)

  • A. M. Dondorp

    (Mahidol University
    University of Oxford)

  • K. Maitland

    (KEMRI-Wellcome Trust Research Programme
    Institute of Global Health Innovation, Imperial College)

  • N. J. White

    (Mahidol University
    University of Oxford)

  • T. N. Williams

    (KEMRI-Wellcome Trust Research Programme
    Institute of Global Health Innovation, Imperial College)

Abstract

Severe falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. Plasma concentrations of P. falciparum Histidine-Rich Protein 2 (PfHRP2) have diagnostic and prognostic value in severe malaria. We investigate the potential use of plasma PfHRP2 and the sequestration index (the ratio of PfHRP2 to parasite density) as quantitative traits for case-only genetic association studies of severe malaria. Data from 2198 Kenyan children diagnosed with severe malaria, genotyped for 14 major candidate genes, show that polymorphisms in four major red cell genes that lead to hemoglobin S, O blood group, α-thalassemia, and the Dantu blood group, are associated with substantially lower admission plasma PfHRP2 concentrations, consistent with protective effects against extensive parasitized erythrocyte sequestration. In contrast the known protective ATP2B4 polymorphism is associated with higher plasma PfHRP2 concentrations, lower parasite densities and a higher sequestration index. We provide testable hypotheses for the mechanism of protection of ATP2B4.

Suggested Citation

  • S. Uyoga & J. A. Watson & P. Wanjiku & J. C. Rop & J. Makale & A. W. Macharia & S. N. Kariuki & G. M. Nyutu & M. Shebe & M. Mosobo & N. Mturi & K. A. Rockett & C. J. Woodrow & A. M. Dondorp & K. Maitl, 2022. "The impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30990-5
    DOI: 10.1038/s41467-022-30990-5
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    References listed on IDEAS

    as
    1. Silvia N. Kariuki & Alejandro Marin-Menendez & Viola Introini & Benjamin J. Ravenhill & Yen-Chun Lin & Alex Macharia & Johnstone Makale & Metrine Tendwa & Wilfred Nyamu & Jurij Kotar & Manuela Carrasq, 2020. "Red blood cell tension protects against severe malaria in the Dantu blood group," Nature, Nature, vol. 585(7826), pages 579-583, September.
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