Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children.
Humans
Artemether, Lumefantrine Drug Combination
/ therapeutic use
Antimalarials
/ therapeutic use
Plasmodium falciparum
/ drug effects
Child, Preschool
Child
Male
Malaria, Falciparum
/ drug therapy
Female
Parasitemia
/ drug therapy
RNA, Ribosomal, 18S
/ genetics
Malaria
/ drug therapy
Infant
HIV Infections
/ drug therapy
Artemisinins
/ therapeutic use
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 May 2024
07 May 2024
Historique:
received:
12
10
2023
accepted:
24
04
2024
medline:
8
5
2024
pubmed:
8
5
2024
entrez:
7
5
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38714692
doi: 10.1038/s41467-024-48210-7
pii: 10.1038/s41467-024-48210-7
doi:
Substances chimiques
Artemether, Lumefantrine Drug Combination
0
Antimalarials
0
RNA, Ribosomal, 18S
0
Artemisinins
0
Banques de données
ClinicalTrials.gov
['NCT03453840']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
3817Subventions
Organisme : NICHD NIH HHS
ID : R01 HD068174
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD110110
Pays : United States
Organisme : NICHD NIH HHS
ID : F31 HD109060
Pays : United States
Informations de copyright
© 2024. The Author(s).
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