Prevalence of mutations in the cysteine desulfurase IscS (Pfnfs1) gene in recurrent Plasmodium falciparum infections following artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) treatment in Matayos, Western Kenya

Malaria Journal

Research

Noah Onchieku¹  Kelvin Thiong’o¹  Francis Kimani¹  Peter Mwitari²  Jeremiah Gathirwa²  Brenda Muriithi³  Daniel Kiboi⁴  Beatrice Gachie⁵  Jean Chepngetich⁵  Gabriel Magoma⁶ 

[1] Centre for Biotechnology Research and Development (CBRD), Kenya Medical Research Institute, P.O. Box 54840-00200, Off Raila Odinga Way, Nairobi, Kenya;Centre for Traditional Medicine and Drug Research (CTMDR), Kenya Medical Research Institute, P.O. Box 54840-00200, Off Raila Odinga Way, Nairobi, Kenya;Centre for Traditional Medicine and Drug Research (CTMDR), Kenya Medical Research Institute, P.O. Box 54840-00200, Off Raila Odinga Way, Nairobi, Kenya;Centre for Biotechnology Research and Development (CBRD), Kenya Medical Research Institute, P.O. Box 54840-00200, Off Raila Odinga Way, Nairobi, Kenya;Department of Biochemistry, Jomo Kenyatta University of Agriculture and Technology (JKUAT), P.O. Box 62000 -00200, Nairobi, Kenya;Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences, Technology and Innovation, P.O. Box 62000-00200, Nairobi, Kenya;Centre for Traditional Medicine and Drug Research (CTMDR), Kenya Medical Research Institute, P.O. Box 54840-00200, Off Raila Odinga Way, Nairobi, Kenya;Centre for Biotechnology Research and Development (CBRD), Kenya Medical Research Institute, P.O. Box 54840-00200, Off Raila Odinga Way, Nairobi, Kenya;Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences, Technology and Innovation, P.O. Box 62000-00200, Nairobi, Kenya;Department of Biochemistry, Jomo Kenyatta University of Agriculture and Technology (JKUAT), P.O. Box 62000 -00200, Nairobi, Kenya;

关键词: Plasmodium falciparum;    Cysteine desulfurase;    Artemether-lumefantrine;    Dihydroartemisinin-piperaquine;    Recurrent infections;   

DOI  :  10.1186/s12936-023-04587-2

 received in 2023-01-31, accepted in 2023-05-11,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMalaria remains a public health concern globally. Resistance to anti-malarial drugs has consistently threatened the gains in controlling the malaria parasites. Currently, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the treatment regimens against Plasmodium falciparum infections in many African countries, including Kenya. Recurrent infections have been reported in patients treated with AL or DP, suggesting the possibility of reinfection or parasite recrudescence associated with the development of resistance against the two therapies. The Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) K65 selection marker has previously been associated with decreased lumefantrine susceptibility. This study evaluated the frequency of the Pfnfs1 K65 resistance marker and associated K65Q resistant allele in recurrent infections collected from P. falciparum-infected individuals living in Matayos, Busia County, in western Kenya.MethodsArchived dried blood spots (DBS) of patients with recurrent malaria infection on clinical follow-up days after treatment with either AL or DP were used in the study. After extraction of genomic DNA, PCR amplification and sequencing analysis were employed to determine the frequencies of the Pfnfs1 K65 resistance marker and K65Q mutant allele in the recurrent infections. Plasmodium falciparum msp1 and P. falciparum msp2 genetic markers were used to distinguish recrudescent infections from new infections.ResultsThe K65 wild-type allele was detected at a frequency of 41% while the K65Q mutant allele was detected at a frequency of 22% in the recurrent samples. 58% of the samples containing the K65 wild-type allele were AL treated samples and while 42% were DP treated samples. 79% of the samples with the K65Q mutation were AL treated samples and 21% were DP treated samples. The K65 wild-type allele was detected in three recrudescent infections (100%) identified from the AL treated samples. The K65 wild-type allele was detected in two recrudescent DP treated samples (67%) while the K65Q mutant allele was identified in one DP treated (33%) recrudescent sample.ConclusionsThe data demonstrate a higher frequency of the K65 resistance marker in patients with recurrent infection during the study period. The study underscores the need for consistent monitoring of molecular markers of resistance in regions of high malaria transmission.

【 授权许可】

CC BY   
© The Author(s) 2023

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