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Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria.
Idowu, Abel O; Oyibo, Wellington A; Bhattacharyya, Sanjib; Khubbar, Manjeet; Mendie, Udoma E; Bumah, Violet V; Black, Carolyn; Igietseme, Joseph; Azenabor, Anthony A.
Afiliación
  • Idowu AO; Department of Biomedical Sciences, College of Health Sciences, University of Wisconsin, 2400 E. Hartford Avenue, Milwaukee, WI, 53211, USA.
  • Oyibo WA; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, Lagos, Nigeria.
  • Bhattacharyya S; ANDI Centre of Excellence in Malaria Diagnosis, College of Medicine, University of Lagos, Lagos, Nigeria.
  • Khubbar M; City of Milwaukee Health Department Laboratory, Milwaukee, USA.
  • Mendie UE; City of Milwaukee Health Department Laboratory, Milwaukee, USA.
  • Bumah VV; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, Lagos, Nigeria.
  • Black C; Department of Biology, North Life Science 317, San Diego State University, San Diego, CA, 92182, USA.
  • Igietseme J; Molecular Pathogenesis Laboratory, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Azenabor AA; Molecular Pathogenesis Laboratory, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Malar J ; 18(1): 319, 2019 Sep 18.
Article en En | MEDLINE | ID: mdl-31533729
BACKGROUND: Plasmodium falciparum, the deadliest causative agent of malaria, has high prevalence in Nigeria. Drug resistance causing failure of previously effective drugs has compromised anti-malarial treatment. On this basis, there is need for a proactive surveillance for resistance markers to the currently recommended artemisinin-based combination therapy (ACT), for early detection of resistance before it become widespread. METHODS: This study assessed anti-malarial resistance genes polymorphism in patients with uncomplicated P. falciparum malaria in Lagos, Nigeria. Sanger and Next Generation Sequencing (NGS) methods were used to screen for mutations in thirty-seven malaria positive blood samples targeting the P. falciparum chloroquine-resistance transporter (Pfcrt), P. falciparum multidrug-resistance 1 (Pfmdr1), and P. falciparum kelch 13 (Pfk13) genes, which have been previously associated with anti-malarial resistance. RESULTS: Expectedly, the NGS method was more proficient, detecting six Pfmdr1, seven Pfcrt and three Pfk13 mutations in the studied clinical isolates from Nigeria, a malaria endemic area. These mutations included rare Pfmdr1 mutations, N504K, N649D, F938Y and S967N, which were previously unreported. In addition, there was moderate prevalence of the K76T mutation (34.6%) associated with chloroquine and amodiaquine resistance, and high prevalence of the N86 wild type allele (92.3%) associated with lumefantrine resistance. CONCLUSION: Widespread circulation of mutations associated with resistance to current anti-malarial drugs could potentially limit effective malaria therapy in endemic populations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Polimorfismo Genético / Resistencia a Medicamentos / Proteínas Asociadas a Resistencia a Múltiples Medicamentos / Mutación / Antimaláricos Tipo de estudio: Prevalence_studies / Risk_factors_studies / Screening_studies País/Región como asunto: Africa Idioma: En Revista: Malar J Asunto de la revista: MEDICINA TROPICAL Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Polimorfismo Genético / Resistencia a Medicamentos / Proteínas Asociadas a Resistencia a Múltiples Medicamentos / Mutación / Antimaláricos Tipo de estudio: Prevalence_studies / Risk_factors_studies / Screening_studies País/Región como asunto: Africa Idioma: En Revista: Malar J Asunto de la revista: MEDICINA TROPICAL Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido