Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women in Southeast Nigeria

Abstract

Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent preventive treatment of malaria in pregnancy in most of sub-Saharan Africa. Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium falciparum. This study determined the prevalence of Pfdhfr and Pfdhps polymorphisms found in asymptomatic pregnant women attending antenatal care in Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women attending antenatal care clinics were enrolled after obtaining informed consent. Malaria diagnosis testing was done using thick and thin smears. Dried blood spot filter papers were collected. Parasite DNA was extracted from the filter papers using a chelex extraction. Extraction was followed by nested PCR and restriction enzyme digestion. P. falciparum infection was detected by microscopy in 7% (32/459) participants. Twenty-eight P. falciparum isolates were successfully genotyped. In the Pfdhfr gene, the triple mutation was almost fixed; S108N mutation was (100%), N51I (93%) and C59R mutations (93%), whereas the I164L mutation was absent. The prevalence of Pfdhps S436A, A437G, A581G and A613S mutations was 82.1% (23/28), 96.4% (27/28), 71.4% (20/28) and 71.4% (20/28) respectively. The K540E mutation was absent. The prevalence of the Pfdhfr triple mutation IRNI was 92.9% (26/28). The efficacy of SP as IPTp in Southeast Nigeria may be severely threatened. The continuous monitoring of SP molecular markers of resistance is required to assess thresholds. The evaluation of alternative preventive treatment strategies and drug options for preventing malaria in pregnancy may be necessary.

Molecular surveillance of anti-malarial resistance Pfdhfr and Pfdhps polymorphisms in African and Southeast Asia Plasmodium falciparum imported parasites to Wuhan, China

“…As the most frequent mutation of Pfdhps, our findings illustrate the high prevalence of A437G at 79.0% (229/290), which has also been reported to be nearly at a saturation level in most African countries [27]. Furthermore, a higher proportion of A437G has been detected at 75.6% in Gabon [36], 87.9% in Kenya [37], 97.6% (1416/1451) in Congo [12], and 96.4% (27/28) in Nigeria [28]. Thus, it needs to be kept in mind that a high prevalence of SP-resistant parasites is present in these regions.…”

“…The current survey demonstrated an extremely high prevalence (> 84%) of three mutations (N51I, C59R, and S108N) in P. falciparum clinical isolates imported from Africa and SEA. In Africa, Pfdhfr nonsynonymous polymorphisms have also been reported at high frequencies in isolates from Uganda [26], Angola [27], the Democratic Republic of the Congo [12], Nigeria [28], and Sierra Leone [29]. Parasitic infections carrying the Pfdhfr triple mutant (IRNI) are significantly more likely to be resistant to SP treatment than infections with fewer Pfdhfr mutations [30].…”

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

“…been shown to have important implications for the effectiveness of SP in children less than 5 years of age and in pregnant women [41]. Reports from previous studies within Nigeria and in Africa were: 37.5% and 22.5% of A437G and K540E haplotype mutations respectively in Lagos (2011) [9] and 96.4% of 437G haplotype and no mutation at K540 codon in Calabar (2013/2014) [42], Table 6 Distribution of dhps mutations at the community locations in Lagos, Nigeria…”

Widespread resistance mutations to sulfadoxine-pyrimethamine in malaria parasites imported to China from Central and Western Africa

“…As The WHO recommends that SP-IPTi has been reported from recent surveys in Africa, we confirmed that virtually no cases imported into China in this temporal interval lacked drug-resistance mutations. For context, mutations N51I, C59R and S108N were reported as universal (or nearly so) in Gabon and southeast Nigeria (Bouyou-Akotet et al, 2015; Esu et al, 2018).…”