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Increased sensitivity of malaria parasites to common antimalaria drugs after the introduction of artemether-lumefantrine: Implication of policy change and implementation of more effective drugs in fight against malaria.
Okore, Winnie; Ouma, Collins; Okoth, Raphael O; Yeda, Redemptah; Ingasia, Luicer O; Mwakio, Edwin W; Ochora, Douglas O; Wakoli, Duncan M; Amwoma, Joseph G; Chemwor, Gladys C; Juma, Jackline A; Okudo, Charles O; Cheruiyot, Agnes C; Opot, Benjamin H; Juma, Dennis; Egbo, Timothy E; Andagalu, Ben; Roth, Amanda; Kamau, Edwin; Akala, Hoseah M.
Afiliación
  • Okore W; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Ouma C; Department of Biomedical Sciences and Technology, Maseno University, Kisumu, Kenya.
  • Okoth RO; Department of Biomedical Sciences and Technology, Maseno University, Kisumu, Kenya.
  • Yeda R; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Ingasia LO; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Mwakio EW; Sydney Brenner Institute of Molecular Biosciences, University of Witwatersrand, Johannesburg, South Africa.
  • Ochora DO; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Wakoli DM; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Amwoma JG; Department of Biological Sciences, Kisii University, Kisii, Kenya.
  • Chemwor GC; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Juma JA; Department of Biochemistry and Molecular Biology, Egerton University, Njoro, Kenya.
  • Okudo CO; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Cheruiyot AC; Department of Biological Sciences, University of Embu, Embu, Kenya.
  • Opot BH; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Juma D; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Egbo TE; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Andagalu B; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Roth A; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Kamau E; Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP), Kisumu, Kenya.
  • Akala HM; United States Army Medical Research Directorate-Africa (USAMRD-A), Kisumu, Kenya.
PLoS One ; 19(6): e0298585, 2024.
Article en En | MEDLINE | ID: mdl-38900782
ABSTRACT
Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin-based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU), amodiaquine (AQ), mefloquine (MQ), quinine (QN), and chloroquine (CQ) using malaria the SYBR Green I-based method to determine their in vitro drug sensitivity. Of the samples genotyped, polymorphism at Pfmrp1 codon I876V was the most frequent, with 59.3% (163/275) mutants, followed by F1390I, 7.2% (20/278), H191Y, 4.0% (6/151), and S437A, 3.3% (9/274). A significant decrease in median 50% inhibition concentrations (IC50s) and interquartile range (IQR) was noted; AQ from 2.996 ng/ml [IQR = 2.604-4.747, n = 51] in 2008 to 1.495 ng/ml [IQR = 0.7134-3.318, n = 40] (P<0.001) in 2019, QN from 59.64 ng/ml [IQR = 29.88-80.89, n = 51] in 2008 to 18.10 ng/ml [IQR = 11.81-26.92, n = 42] (P<0.001) in 2019, CQ from 35.19 ng/ml [IQR = 16.99-71.20, n = 30] in 2008 to 6.699 ng/ml [IQR = 4.976-9.875, n = 37] (P<0.001) in 2019, and ART from 2.680 ng/ml [IQR = 1.608-4.857, n = 57] in 2008 to 2.105 ng/ml [IQR = 1.266-3.267, n = 47] (P = 0.0012) in 2019, implying increasing parasite sensitivity to the drugs over time. However, no significant variations were observed in LU (P = 0.2692) and MQ (P = 0.0939) respectively, suggesting stable parasite responses over time. There was no statistical significance between the mutation at 876 and parasite sensitivity to selected antimalarials tested, suggesting stable sensitivity for the parasites with 876V mutations. These findings show that Kenyan parasite strains are still sensitive to AQ, QN, CQ, ART, LU, and MQ. Despite the presence of Pfmrp1 mutations in parasites among the population.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Malaria Falciparum / Polimorfismo de Nucleótido Simple / Combinación Arteméter y Lumefantrina / Antimaláricos Límite: Female / Humans / Male País/Región como asunto: Africa Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Kenia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Malaria Falciparum / Polimorfismo de Nucleótido Simple / Combinación Arteméter y Lumefantrina / Antimaláricos Límite: Female / Humans / Male País/Región como asunto: Africa Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Kenia Pais de publicación: Estados Unidos