Amplicon Sequencing as a Potential Surveillance Tool for Complexity of Infection and Drug Resistance Markers in Plasmodium falciparum Asymptomatic Infections.

Autor:	Wamae K; Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya., Kimenyi KM; Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya.; Centre for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya., Osoti V; Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya., de Laurent ZR; Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya., Ndwiga L; Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya., Kharabora O; Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Hathaway NJ; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Bailey JA; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA., Juliano JJ; Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.; Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Bejon P; Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Ochola-Oyier LI; Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2022 Sep 13; Vol. 226 (5), pp. 920-927.
DOI:	10.1093/infdis/jiac144
Abstrakt:	Background: Genotyping Plasmodium falciparum subpopulations in malaria infections is an important aspect of malaria molecular epidemiology to understand within-host diversity and the frequency of drug resistance markers. Methods: We characterized P. falciparum genetic diversity in asymptomatic infections and subsequent first febrile infections using amplicon sequencing (AmpSeq) of ama1 in Coastal Kenya. We also examined temporal changes in haplotype frequencies of mdr1, a drug-resistant marker. Results: We found >60% of the infections were polyclonal (complexity of infection [COI] >1) and there was a reduction in COI over time. Asymptomatic infections had a significantly higher mean COI than febrile infections based on ama1 sequences (2.7 [95% confidence interval {CI}, 2.65-2.77] vs 2.22 [95% CI, 2.17-2.29], respectively). Moreover, an analysis of 30 paired asymptomatic and first febrile infections revealed that many first febrile infections (91%) were due to the presence of new ama1 haplotypes. The mdr1-YY haplotype, associated with chloroquine and amodiaquine resistance, decreased over time, while the NY (wild type) and the NF (modulates response to lumefantrine) haplotypes increased. Conclusions: This study emphasizes the utility of AmpSeq in characterizing parasite diversity as it can determine relative proportions of clones and detect minority clones. The usefulness of AmpSeq in antimalarial drug resistance surveillance is also highlighted. Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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