Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children

Justin Goodwin, Richard Kajubi, Kaicheng Wang, Fangyong Li, Martina Wade, Francis Orukan, Liusheng Huang, Meghan Whalen, Francesca T. Aweeka, Norah Mwebaza and Sunil Parikh ()
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Justin Goodwin: Yale School of Public Health
Richard Kajubi: Infectious Disease Research Collaboration
Kaicheng Wang: Yale School of Public Health
Fangyong Li: Yale School of Public Health
Martina Wade: Yale School of Public Health
Francis Orukan: Infectious Disease Research Collaboration
Liusheng Huang: San Francisco
Meghan Whalen: San Francisco
Francesca T. Aweeka: San Francisco
Norah Mwebaza: Infectious Disease Research Collaboration
Sunil Parikh: Yale School of Public Health

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- versus 5 day artemether-lumefantrine in 303 children with and without HIV (ClinicalTrials.gov number NCT03453840). The prevalence of parasite-derived 18S rRNA is >70% in children throughout follow-up, and the ring-stage marker SBP1 is detectable in over 15% of children on day 14 despite effective treatment. We find that the extended regimen significantly lowers the risk of recurrent ring-stage parasitemia compared to the standard 3 day regimen, and that higher day 7 lumefantrine concentrations decrease the probability of ring-stage parasites in the early post-treatment period. Longitudinal amplicon sequencing reveals remarkably dynamic patterns of multiclonal infections that include new and persistent clones in both the early post-treatment and later time periods. Our data indicate that post-treatment parasite dynamics are highly complex despite efficacious therapy, findings that will inform strategies to optimize regimens in the face of emerging partial artemisinin resistance in Africa.

Date: 2024
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DOI: 10.1038/s41467-024-48210-7

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