Prevalence ofPlasmodium falciparumparasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistantpfdhfr/pfdhpsalleles

Abstract

Objectives: To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles.Methods: pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP2 group (control) (n¼51)] or afterwards [SP+ group (n¼ 49)] were sequenced.Results: The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP2 group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P ¼ 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant.Conclusions: Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.

Profile of molecular mutations in pfdhfr, pfdhps, pfmdr1, and pfcrt genes of Plasmodium falciparum related to resistance to different anti-malarial drugs in the Bata District (Equatorial Guinea)

“…Some resistance genes were detected in Equatorial Guinea at frequencies similar to those reported for Cameroon by Chauvin et al [20], but other mutations were found for the first time in this part of Africa. In Equatorial Guinea, the pfdhfr 51/59/108 genotype was observed less frequently (71%) than in Cameroon (94%), but the partial resistant genotype ( pfdhfr 51/59/108 +  pfdhps 437) was the most common.…”

“…In West Africa, the prevalence has been relatively low; 6.25% in Gabon (2007), 0.8% in Congo (2004), 11% in Sao Tomé, 24% in Nigeria, and 2% in Cameroon [20]. In this study, the prevalence was low in urban samples (9%) but it reached 23% in rural samples.…”

“…It is considered fully resistant, when it appears together with the pfdhps 437/540 mutation [20]. In the mainland of Equatorial Guinea, this genotype pfdhfr 51/59/108/164 was found in only 2 samples from rural settings.…”

Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V

“…The I431V mutation was first described in a study by Sutherland and others (2009) in isolates from malaria patients returning to the UK from Nigeria. It has since been reported in neighbouring Cameroon (Chauvin et al., 2015) at a prevalence of 9.8% but not among the numerous dhps sequencing studies conducted on parasite populations in the rest of Africa (Naidoo and Roper, 2013). Published reports of the mutation are currently confined to Nigeria and Cameroon although one appears in a Ghanaian isolate among publicly available whole genome sequences (Plasmoview, http://pathogenseq.lshtm.ac.uk/plasmoview).…”

“…Reports of novel dhps mutations at codon 431(I431V) from UK imported malaria infections originating from Nigeria (Sutherland et al., 2009) and pregnant women from Cameroon (Chauvin et al., 2015) suggest this mutation is emerging. In Nigeria, there has been a dearth of molecular surveillance data (Naidoo and Roper, 2011, Drug resistance maps, http://www.drugresistancemaps.org/ipti/) which makes this difficult to substantiate.…”