Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria

Details

• Alternative Title:
  Malar J
• Personal Author:
  Idowu, Abel O. ; Oyibo, Wellington A. ; Bhattacharyya, Sanjib ; Khubbar, Manjeet ; Mendie, Udoma E. ; Bumah, Violet V. ; Black, Carolyn ; Igietseme, Joseph ; Azenabor, Anthony A.
• Description:
  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.
  
  
• Subjects:
  Antimalarials Drug Resistance Membrane Transport Proteins Multidrug Resistance-Associated Proteins Mutation Plasmodium Falciparum Polymorphism, Genetic Prevalence Protozoan Proteins
• Source:
  Malar J. 18
• Pubmed ID:
  31533729
• Pubmed Central ID:
  PMC6751857
• Document Type:
  Journal Article
• Funding:
  15160886/Nigeria-US Fulbright Commission/
• Place as Subject:
  Nigeria
• Volume:
  18
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d0bb5d4d448f5ea08e8a6a75e901b2707cc6fbde7b6a42d3ca31b3edd8809107
• Download URL:
  https://stacks.cdc.gov/view/cdc/88987/cdc_88987_DS1.pdf
• File Type:
  [PDF - 888.15 KB ]