Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania Public Deposited

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  • Topazian, Hillary M.
    • Other Affiliation: Imperial College, London
  • Moser, Kara A.
    • Affiliation: School of Medicine, Institute for Global Health and Infectious Disease
  • Ngasala, Billy
    • Other Affiliation: Muhimbili University of Health and Allied Sciences
  • Oluoch, Peter O.
    • Other Affiliation: University of Massachusetts Chan Medical School
  • Forconi, Catherine S.
    • Other Affiliation: University of Massachusetts Chan Medical School
  • Mhamilawa, Lwidiko E.
    • Other Affiliation: Muhimbili University of Health and Allied Sciences
  • Aydemir, Ozkan
    • Other Affiliation: Brown University
  • Kharabora, Oksana
    • Affiliation: School of Medicine, Institute for Global Health and Infectious Disease
  • Deutsch-Feldman, Molly
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Read, Andrew F.
    • Other Affiliation: Penn State University
  • Denton, Madeline
    • Affiliation: School of Medicine, Institute for Global Health and Infectious Disease
  • Lorenzo, Antonio
    • Other Affiliation: University of Toronto
  • Mideo, Nicole
    • Other Affiliation: University of Toronto
  • Ogutu, Bernhards
    • Other Affiliation: Kenyan Medical Research Institute
  • Moormann, Ann M.
    • Other Affiliation: University of Massachusetts Chan Medical School
  • Mårtensson, Andreas
    • Other Affiliation: Uppsala University
  • Odwar, Boaz
    • Other Affiliation: Kenyan Medical Research Institute
  • Bailey, Jeffrey A.
    • Other Affiliation: Brown University
  • Akala, Hoseah
    • Other Affiliation: Kenyan Medical Research Institute
  • Ong'echa, John Michael
    • Other Affiliation: Kenyan Medical Research Institute
  • Juliano, Jonathan J.
    • Affiliation: School of Medicine, Institute for Global Health and Infectious Disease
Abstract
  • Background Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs) is a threat to malaria elimination. ACT-resistance in Asia raises concerns for emergence of resistance in Africa. While most data show high efficacy of ACT regimens in Africa, there have been reports describing declining efficacy, as measured by both clinical failure and prolonged parasite clearance times. Methods Three hundred children aged 2–10 years with uncomplicated P. falciparum infection were enrolled in Kenya and Tanzania after receiving treatment with artemether-lumefantrine. Blood samples were taken at 0, 24, 48, and 72 h, and weekly thereafter until 28 days post-treatment. Parasite and host genetics were assessed, as well as clinical, behavioral, and environmental characteristics, and host anti-malarial serologic response. Results While there was a broad range of clearance rates at both sites, 85% and 96% of Kenyan and Tanzanian samples, respectively, were qPCR-positive but microscopy-negative at 72 h post-treatment. A greater complexity of infection (COI) was negatively associated with qPCR-detectable parasitemia at 72 h (OR: 0.70, 95% CI: 0.53–0.94), and a greater baseline parasitemia was marginally associated with qPCR-detectable parasitemia (1,000 parasites/uL change, OR: 1.02, 95% CI: 1.01–1.03). Demographic, serological, and host genotyping characteristics showed no association with qPCR-detectable parasitemia at 72 h. Parasite haplotype-specific clearance slopes were grouped around the mean with no association detected between specific haplotypes and slower clearance rates. Conclusions Identifying risk factors for slow clearing P. falciparum infections, such as COI, are essential for ongoing surveillance of ACT treatment failure in Kenya, Tanzania, and more broadly in sub-Saharan Africa.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Frontiers in Epidemiology
Journal volume
  • 2
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  • English
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  • 2674-1199
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