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Systemic biological mechanisms underpin poor post-discharge growth among severely wasted children with HIV

Author

Listed:
  • Evans O. Mudibo

    (KEMRI-Wellcome Trust Research Programme
    Wageningen University & Research
    The Childhood Acute Illness and Nutrition Network
    Ghent University)

  • Jasper Bogaert

    (Ghent University)

  • Caroline Tigoi

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Moses M. Ngari

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Benson O. Singa

    (The Childhood Acute Illness and Nutrition Network
    Kenya Medical Research Institute)

  • Christina L. Lancioni

    (The Childhood Acute Illness and Nutrition Network
    Oregon Health and Science University)

  • Abdoulaye Hama Diallo

    (University Joseph Ki-Zerbo
    Centre Muraz Research Institute)

  • Emmie Mbale

    (Kamuzu University of Health Sciences)

  • Ezekiel Mupere

    (Makerere University College of Health Sciences)

  • John Mukisa

    (Department of Immunology and Department of Molecular Biology Makerere University College of Health Sciences)

  • Johnstone Thitiri

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Molline Timbwa

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Elisha Omer

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Narshion Ngao

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Robert Musyimi

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Eunice Kahindi

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Roseline Maïmouna Bamouni

    (University Joseph Ki-Zerbo)

  • Robert H. J. Bandsma

    (Hospital for Sick Children
    University of Toronto)

  • Paul Kelly

    (Queen Mary University of London
    University of Zambia School of Medicine)

  • Andrew J. Prendergast

    (Queen Mary University of London
    Zvitambo Institute for Maternal and Child Health Research)

  • Christine J. McGrath

    (The Childhood Acute Illness and Nutrition Network
    University of Washington)

  • Kirkby D. Tickell

    (The Childhood Acute Illness and Nutrition Network
    University of Washington)

  • Judd L. Walson

    (The Childhood Acute Illness and Nutrition Network
    Johns Hopkins University)

  • James A. Berkley

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network
    University of Oxford)

  • James M. Njunge

    (KEMRI-Wellcome Trust Research Programme
    The Childhood Acute Illness and Nutrition Network)

  • Gerard Bryan Gonzales

    (Wageningen University & Research
    The Childhood Acute Illness and Nutrition Network
    Ghent University)

Abstract

In sub-Saharan Africa, children with severe malnutrition (SM) and HIV have substantially worse outcomes than children with SM alone, facing higher mortality risk and impaired nutritional recovery post-hospitalisation. Biological mechanisms underpinning this risk remain incompletely understood. This case-control study nested within the CHAIN cohort in Kenya, Uganda, Malawi, and Burkina Faso examined effect of HIV on six months post-discharge growth among children with SM and those at risk of malnutrition, assessed proteomic signatures associated with HIV in these children, and investigated how these systemic processes impact post-discharge growth in children with SM. Using SomaScanTM assay, 7335 human plasma proteins were quantified. Linear mixed models identified HIV-associated biological processes and their associations with post-discharge growth. Using structural equation modelling, we examined directed paths explaining how HIV influences post-discharge growth. Here, we show that at baseline, HIV is associated with lower anthropometry. Additionally, HIV is associated with protein profiles indicating increased complement activation and decreased insulin-like growth factor signalling and bone mineralisation. HIV indirectly affects post-discharge growth by influencing baseline anthropometry and modulating proteins involved in bone mineralisation and humoral immune responses. These findings suggest specific biological pathways linking HIV to poor growth, offering insights for targeted interventions in this vulnerable population.

Suggested Citation

  • Evans O. Mudibo & Jasper Bogaert & Caroline Tigoi & Moses M. Ngari & Benson O. Singa & Christina L. Lancioni & Abdoulaye Hama Diallo & Emmie Mbale & Ezekiel Mupere & John Mukisa & Johnstone Thitiri & , 2024. "Systemic biological mechanisms underpin poor post-discharge growth among severely wasted children with HIV," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54717-w
    DOI: 10.1038/s41467-024-54717-w
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    References listed on IDEAS

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