Prevalence of mutations linked to antimalarial resistance in Plasmodium falciparum from Chhattisgarh, Central India: A malaria elimination point of view

Abstract

Antimalarial drug resistance is a major global challenge in malaria control and elimination. Mutations in six different genes of Plasmodium falciparum (crt, mdr1, dhfr, dhps, ATPase6 and K-13 propeller) that confer resistance to chloroquine, sulphadoxine-pyrimethamine and artemisinin-based combination therapy were analyzed in samples from Chhattisgarh. Seventy-eight percent of the samples were found to have a pfcrt mutation (53% double, 24% triple and 1% single mutant), and 59% of pfmdr1 genes were found to have an N86Y mutation. Double mutations were recorded in pfdhfr gene among 76% of the samples while only 6% of the samples harbored mutant genotypes in pfdhps. No mutation was found in the K-13 propeller gene, while only one sample showed a mutant genotype for the PfATPase6 gene. The Tajima test confirmed that there is no role of evolutionary natural selection in drug resistance, and gene pairwise linkage of disequilibrium showed significant intragenic association. The high level of pfcrt mutations suggests that parasite resistance to chloroquine is almost at a fixed level, whereas resistance to SP is evolving in the population and parasites remain sensitive to artemisinin derivatives. These findings provide potential information and understanding of the evolution and spread of different drug resistance alleles in Chhattisgarh.

Molecular surveillance of putative drug resistance markers of antifolate and artemisinin among importedPlasmodium falciparumin Qatar

“…High level of triple mutant genotypes was also found in the present study among isolates originates from Nigeria and Cameroon, which is in agreement with other studies [32,33]. Among the Indian sub-continent isolates, the double (59R/108N and 51I/108N) mutants genotypes were the most frequent genotypes followed by triple (51I/59R/108N) mutant genotypes, which are in agreement with previous reports from India [21,27,[34][35][36].…”

“…Single point mutation at codon 437G was higher in Indian subcontinents isolates followed by West & Central Africa and East Africa. These findings corroborate with earlier reports from India [21,34,35]. Additionally, we found a novel mutation at codon 431V in five isolates imported from Nigeria and one isolate imported from Ghana, which corroborates with previous findings of imported malaria infections in the UK, which also originated from Nigeria [38] and also pregnant women from Cameroon [39], suggesting that this mutation is emerging especially in West Africa.…”

“…The presence of key mutations in Pfdhfr and Pfdhps genes along with the emergence of new mutations and quadruple mutations at dhfr locus and quadruple/quintuple mutations in dhps locus are important findings which might be the cause for multidrug resistance of antifolate drugs. The emergence of these novel mutations might have enhanced the level of antifolate resistance to P. falciparum hence it should be taken into consideration when using the combination of antifolate drugs with artemisinin derivatives nationwide and also where the double mutant genotype of Pfdhfr (ACICNILYT) is common [21,41,42].…”

“…Alleles of the Pfdhfr, Pfdhps genes (for SP resistance) and K-13 propeller, PfATPase6 (for ART resistance) were determined using nested PCR followed by sanger sequencing, as previously described protocols with some minor modifications [21]. Primers for primary and nested PCR, and PCR cycling conditions are listed in the supplementary material [21]. The spanning codons 51-164 of Pfdhfr gene, codons 425-640 of Pfdhps gene codons 653-797 of PfATPase6 and codon 427-702 of K-13 propeller were amplified by PCR.…”

Prevalence of Plasmodium falciparum field isolates with deletions in histidine-rich protein 2 and 3 genes in context with sub-Saharan Africa and India: a systematic review and meta-analysis

“…Thus, the risk of severe falciparum malaria would increase as the RDTs will have failed to detect P. falciparum. This fact is particularly important in malaria-endemic areas where both the circulation of chloroquine-resistant P. falciparum isolates and chloroquine is preferentially used for treating vivax malaria, as this is the case in India [56][57][58][59][60]. In most endemic countries, chloroquine is firstline treatment of vivax malaria [1].…”