Prevalence of the molecular marker of Plasmodium falciparum resistance to chloroquine and sulphadoxine/pyrimethamine in Benin seven years after the change of malaria treatment policy

Abstract

BackgroundIn Benin, the National Malaria Control Programme (NMCP) changed the policy of malaria treatment in 2004 following increasing of failure rate of treatment with chloroquine (CQ) and sulphadoxine-pyrimethamine (SP). The objective of this study was to determinate the prevalence of Plasmodium falciparum molecular markers that are associated with resistance to CQ and SP in Benin seven years after the new policy was instituted.MethodsThe study was conducted in southern Benin, a region characterized by a perennial malaria transmission. Blood samples were collected in 2011 from children presenting with symptomatic and asymptomatic P. falciparum infections and living in the same area. The prevalence of critical point mutations in the genes of pfcrt (codon 76), pfmdr1 (codon 86), pfdhfr (codons, 51, 59 and 108) and pfdhps (codons 437, 540) was examined in parasite isolates by mutation-specific restriction enzyme digestion of nested PCR products.ResultsA high prevalence of parasites carrying point mutations in all studied targets was found: T76: 93.9% [89.8; 96.7], I51: 96.2% [92.7; 98.4], R59: 93, 9% [89.7; 96.7], N108: 97.6% [94.6; 99.2] and G437: 71.4% [64.8; 77.4]. No mutation was found at codon 540 of the pfdhps gene. The proportion of parasite isolates carrying triple mutation in the pfdhfr gene IRN (I51, R59 andN108) and quadruple mutation on the combination of pfdhfr/pfdhps IRNG (I51, R59, N108 and G437) was 91.5% [86.9; 94.9] and 65.7% [58.9; 72.1], respectively. Analysis of mutation in relation to the clinical status (symptomatic or asymptomatic) and according to age (younger or older than 10 years) showed similar very high frequencies in each category without significant difference between two groups.ConclusionsThese results suggest a persistence level of resistance of P. falciparum to CQ and SP, seven years after the recommendation of the change of malaria treatment policy in Benin. The distribution of mutations studied was neither related to age nor to clinical status.

Characterising temporal trends in asymptomatic Plasmodium infections and transporter polymorphisms during transition from high to low transmission in Zanzibar, 2005–2013

“…Frequencies of the pfmdr1 86Y, 1246Y SNPs and the pfmdr1 YYY and YYD haplotypes were significantly higher in asymptomatic infections than in symptomatic infections in 2013. Similar findings have recently been reported in Uganda and Benin, where the prevalence of wild-type genotypes were significantly higher in febrile children compared to asymptomatic children, suggesting greater virulence for wild type parasites (Ogouyemi-Hounto et al, 2013;Tukwasibwe et al, 2014). It could be that asymptomatic infections represent an important reservoir for resistance genes that confer a fitness disadvantage relative to wild-type alleles and may therefore contribute to the epidemiology of drug resistant malaria (Brown et al, 2012).…”

Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia

“…However, the reported prevalence rates in Peninsular Malaysia (5.3%, p  = 0.000), Cambodia (2.15%, p  = 0.000), western Thailand (3.1%, p  = 0.000), and the upper southern part of Thailand (36.4%, p  = 0.000) differed from ours [19, 33–36]. Other studies have described almost equal prevalence rates for pfmdr1 86Y in African countries such as Kenya (81.6%, p  = 0.545) or even lower prevalence in Benin (57.1%, p  = 0.000), Malawi (22.7%, p  = 0.000), and Senegal (14.9%, p  = 0.000) [13, 14, 30, 37]. Note that one of the lowest prevalence rates for the mutant genotype 86Y was reported from Malawi, where the prevalence of the mutant pfcrt also decreased dramatically [16, 30].…”

Prevalence of Plasmodium falciparum Resistance Markers to Sulfadoxine-Pyrimethamine among Pregnant Women Receiving Intermittent Preventive Treatment for Malaria in Uganda

“…In a recent study in Benin, the prevalence of Pfdhfr and Pfdhps quadruple mutations was high, and SP could not clear parasites in half of the women infected with malaria with recrudescence in 76% of women after the second dose. Although in these countries Pfdhfr and Pfdhps triple and quadruple mutations were frequent, there was no evidence of a correlation between these haplotypes and the efficacy of SP-IPTp (21)(22)(23).…”