High multiple mutations of Plasmodium falciparum-resistant genotypes to sulphadoxine-pyrimethamine in Lagos, Nigeria

Abstract

Background: Plasmodium falciparum-resistance to sulphadoxine-pyrimethamine (SP) has been largely reported among pregnant women. However, the profile of resistance markers to SP dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) in the general population are varied and not frequently monitored. Currently, SP is used as partner drug for artemisinin combination therapy (SP-artesunate) in some sub-Saharan African countries or as a prophylactic drug in intermittent preventive treatment of malaria during pregnancy and infants and in seasonal malaria chemoprevention (SMC). Profiling of P. falciparum-resistant genotypes to SP is dynamic and critical in providing data that would be useful for malaria control programmes. This study assessed the profile of dhfr and dhps genes genotypes among individuals with malaria in Lagos, Nigeria. Methods: Molecular markers of SP resistance were identified by nested PCR and sequenced among malaria positive dried blood spots (DBS) that were collected from individuals attending health facilities from

Low prevalence of highly sulfadoxine‐resistant dihydropteroate synthase alleles in Plasmodium falciparum isolates in Benin

“…Interestingly, to date, the I431 V mutation has not been observed in other parts of Africa. In concordance with previous studies [ 42 , 49 ], this mutation was observed in combination with other Pfdhps mutations (S436 A /A437 G /A581 G /A613 S ), suggesting this mutation may have occurred only in the presence of the other Pfdhps mutations. The implications of this combination of Pfdhps mutations remain unclear.…”

“…Results from this study demonstrate that the prevalence of the Pfdhfr IRN triple mutant is very high, implying these mutants are well established in this region, similar to observations made previously in Benin and in many African countries [ 16 , 18 , 39 , 40 ]. In contrast, the prevalence of multiple mutations in the Pfdhps gene was low, with the majority of parasites having only a single mutation at codon A437 G and 29.3% of the parasites with a double mutant (S436 A /A437 G ), as commonly observed in West Africa [ 18 , 21 , 41 , 42 ]. Only a handful of isolates had mutations at codons K540 E (2.6%), A581 G (2.6%), and A613 S (4.6%).…”

Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique

“…Polymorphism data from our study showed high prevalence of mutant I 51 (88.9%) and N 108 (80.8%) dhfr alleles and mutant G 437 (82.3%) dhps allele. Similar prevalence of these mutant dhfr and dhps alleles have been recorded in Nigeria 11 , 13 and other West African countries 14 , 15 . Although prevalence of these mutant alleles are generally high in West Africa 16 , lower prevalence (26.5–56.25) have been recorded in other West African countries 4 , 17 .…”

“…Since the deployment of SP in Nigeria as IPTp in 2001 10 and SMC in 2013 11 , there have been various reports of these point mutations in both dhfr and dhps genes associated with SP resistance in various parts of the country 11 , 12 . Reports of high prevalence of the triple mutant genotype of dhfr (N 51 I, C 59 R and S 108 N) in addition to the A 437 G mutation in the dhps gene is common in Nigeria 13 . However, occurrence of the quintuple dhfr + dhps mutation comprising of N 51 I, C 59 R and S 108 N + A 437 G and K 540 E is scarce 13 .…”

“…Reports of high prevalence of the triple mutant genotype of dhfr (N 51 I, C 59 R and S 108 N) in addition to the A 437 G mutation in the dhps gene is common in Nigeria 13 . However, occurrence of the quintuple dhfr + dhps mutation comprising of N 51 I, C 59 R and S 108 N + A 437 G and K 540 E is scarce 13 .…”