Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria

Abstract

Accurate assessment and monitoring of the Plasmodium falciparum Kelch 13 (pfk13) gene associated with artemisinin resistance is critical to understand the emergence and spread of drug-resistant parasites in malaria-endemic regions. In this study, we evaluated the genomic profile of the pfk13 gene associated with artemisinin resistance in P. falciparum in Nigerian children by targeted sequencing of the pfk13 gene. Genomic DNA was extracted from 332 dried blood (DBS) spot filter paper samples from three Nigerian States. The pfk13 gene was amplified by nested polymerase chain reaction (PCR), and amplicons were sequenced to detect known and novel polymorphisms across the gene. Consensus sequences of samples were mapped to the reference gene sequence obtained from the National Center for Biotechnology Information (NCBI). Out of the 13 single nucleotide polymorphisms (SNPs) detected in the pfk13 gene, five (F451L, N664I, V487E, V692G and Q661H) have not been reported in other endemic countries to the best of our knowledge. Three of these SNPs (V692G, N664I and Q661H) and a non-novel SNP, C469C, were consistent with late parasitological failure (LPF) in two States (Enugu and Plateau States). There was no validated mutation associated with artemisinin resistance in this study. However, a correlation of our study with in vivo and in vitro phenotypes is needed to establish the functional role of detected mutations as markers of artemisinin resistance in Nigeria. This baseline information will be essential in tracking and monitoring P. falciparum resistance to artemisinin in Nigeria.

Molecular surveillance of artemisinin resistance-related pfK13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015–2019

“…The all 3 Q613H were detected in the migrant workers from Nigeria, which was similar as reported before [31]. C469C, a common synonymous mutant allele of pfK13 found in African isolates, the proportion in our study was similar as that in Burkina Faso and Senegal [32][33][34]. The pfK13 mutation allele S549S, to our knowledge, was rstly identi ed in the migrant workers from Guinea, Equatorial Guinea, and The Democratic Republic of the Congo (Congo DRC).…”

Molecular surveillance of artemisinin resistance-related Pfk13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015 to 2019

“…The all 3 Q613H were detected in the migrant workers from Nigeria, which was similar as reported before [ 34 ]. The synonymous mutant allele C469C, which was common in Africa, was identified in this study and the proportion was similar as reported in Burkina Faso and Senegal [ 35 – 37 ]. The Pfk13 mutant allele S549S, to our knowledge, was firstly identified in the migrant workers from Guinea, Equatorial Guinea, and Congo DRC.…”

Nanopore sequencing for real-time genomic surveillance ofPlasmodium falciparum

“…No mutations in kelch13 were identified that have previously been associated with artemisinin resistance. Five kelch13 mutations were identified, three synonymous changes (A627A and S649S (both in Navrongo), and a sample from Accra with C469C), and two non-synonymous mutations: Q613H (in Accra) and N629Y (in Navrongo), which have previously been reported in West Africa [78,79] and are not considered to be associated with artemisinin resistance ( Supplementary Notes ).…”

“…Q613H (in Accra) and N629Y (in Navrongo), which have previously been reported in West Africa [78,79] and are not considered to be associated with artemisinin resistance (Supplementary Notes).…”