High prevalence of dhfr and dhps molecular markers in Plasmodium falciparum in pregnant women of Nchelenge district, Northern Zambia

Abstract

BackgroundSulphadoxine-pyrimethamine (SP) is the recommended drug for intermittent preventive treatment in pregnancy (IPTp) in most African countries, including Zambia. However, malaria is still one of the leading causes of morbidity and mortality in pregnant women despite reports of greater than 50% of women taking at least two doses of SP in IPTp. Studies have shown that resistance to SP is associated with mutations in the dhfr and dhps gene of Plasmodium falciparum. This study examined the prevalence of dhfr and dhps polymorphisms in P. falciparum found in pregnant women of Nchelenge district.MethodThis cross-sectional study was conducted in 2013 in Nchelenge, a holoendemic area with malaria prevalence estimated at 50% throughout the year. Three rural health centres were randomly selected and a census survey carried out at each health centre. A questionnaire was administered and malaria testing done using RDT and microscopy, with collection of a dried blood spot. A chelex extraction was done to extract parasite DNA from dried blood spots followed by nested PCR and enzyme restriction digestion.ResultsOf the enrolled participants (n = 375), the median age of the women was 23. The prevalence of malaria by PCR was 22%. The PCR positive samples examined (n = 72) showed a high prevalence of dhfr triple (Asn-108 + Arg-59 + Ile-59) mutant (68%) and dhps double (Gly -437 + Glu-540) mutant (21%). The quintuple haplotype was found in 17% with 2 samples with an additional Gly-581mutation. In addition 6% mutations at Val-16 were found and none found at Thr-108 respectively, these both confer resistance to cycloguanil. Multivariate analysis showed that there was an association between malaria and women aged 30-34 years old p < 0.05(AOR: 0.36) at 95% CI.ConclusionThis study showed a high number of mutations in the dhfr and dhps genes. The high malaria endemicity in the general population of this area may have contributed to the high prevalence of resistant parasites in pregnant women, suggesting a need to examine the efficacy of SP given that it is the only approved drug for IPTp in Zambia.

High burden of malaria infection in pregnant women in a rural district of Zambia: a cross-sectional study

“…The prevalence of malaria among 375 pregnant women in the study conducted in Nchelenge District between February and April 2013 by Siame et al was much lower than what was observed in the current study, 15.0 % by microscopy and 22.0 % by PCR [ 45 ]. The differences in the prevalence of malaria in the two studies could be attributed to a number of factors.…”

Assessment of antimalarial drug resistant markers in asymptomatic Plasmodium falciparum infections after 4 years of indoor residual spraying in Northern Ghana

“…We observed a high prevalence of S108N (83.8% -95.0%), C59R (49.3% -81.3%) and N51I (44.8% -73.3%) followed by the A437G (46.2% -54.2%) mutations, and eventually A613S, S436F and A581G were implicated. These findings are consistent with results reported in other settings in Africa [53,[80][81][82][83]. Similar to the report by Mockenhaupt and colleagues, we detected pfdhps-G581 and S613 among parasites from the same region in Ghana (Northern Region) [84].…”

Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso

“…The more the mutations, the stronger the resistance. The Pfdhfr triple mutant (N51I + C59R + S108N) and Pfdhps double mutant (A437G + K540E) have been strongly associated with potential resistance in sub-Saharan Africa [9–12]. …”