Abstract
BackgroundPregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy (IPTp-SP) is widely implemented to prevent these negative effects of malaria. However, resistance against SP by P. falciparum may decrease efficacy of IPTp-SP. Combinations of point mutations in the dhps (codons A437, K540) and dhfr genes (codons N51, C59, S108) of P. falciparum are associated with SP resistance. In this study the prevalence of SP resistance mutations was determined among P. falciparum found in pregnant women and the general population (GP) from Nanoro, Burkina Faso and the association of IPTp-SP dosing and other variables with mutations was studied.MethodsBlood spots on filter papers were collected from pregnant women at their first antenatal care visit (ANC booking) and at delivery, from an ongoing trial and from the GP in a cross-sectional survey. The dhps and dhfr genes were amplified by nested PCR and products were sequenced to identify mutations conferring resistance (ANC booking, n = 400; delivery, n = 223; GP, n = 400). Prevalence was estimated with generalized estimating equations and for multivariate analyses mixed effects logistic regression was used.ResultsThe prevalence of the triple dhfr mutation was high, and significantly higher in the GP and at delivery than at ANC booking, but it did not affect birth weight. Furthermore, quintuple mutations (triple dhfr and double dhps mutations) were found for the first time in Burkina Faso. IPTp-SP did not significantly affect the occurrence of any of the mutations, but high transmission season was associated with increased mutation prevalence in delivery samples. It is unclear why the prevalence of mutations was higher in the GP than in pregnant women at ANC booking.ConclusionThe high number of mutants and the presence of quintuple mutants in Burkina Faso confirm concerns about the efficacy of IPTp-SP in the near future. Other drug combinations to tackle malaria in pregnancy should, therefore, be explored. An increase in mutation prevalence due to IPTp-SP dosing could not be confirmed.
Highlights
Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes
COSMIC: mutation prevalence and predicting factors About half of the samples collected at antenatal care (ANC) booking (591/1175, 50.3%) were tested positive for P. falciparum by real-time PCR while this was 17.9% (223/1248) at delivery
Sequence results for the three codons associated with SP resistance in the dhps gene (S436, A437, K540) could be obtained from 359 (89.8%) ANC samples and 175 (78.5%) delivery samples
Summary
Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. In areas where malaria transmission is stable, women have acquired partial immunity, but they remain vulnerable to malaria when they get pregnant due to specific surface antigens on Plasmodium falciparum-infected erythrocytes that are almost exclusively presented by the malaria parasite during pregnancy [4]. This leaves in particular primigravidae, who are exposed to these antigens for the first time, more vulnerable to malaria infection. Accumulation of single point mutations in these genes leads to increasing SP resistance, the combined triple dhfr (N51, C59, S108) and double dhps (A437, K540) mutations (quintuple mutant) [19]
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