Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study

Abstract

Abstract Background The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population. Methods Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population. Results The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively. Conclusion The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.

Keywords

• Intermittent preventive treatment of malaria in pregnancy (IPTp)
• Sulfadoxine-pyrimethamine (SP)
• DHPS double mutation (gly-437 + glu-540)
• DHFR triple mutation (asn-108 + ile-51 + arg-59)
• Quintuple mutation (DHFR triple + DHPS double)
• Sextuple mutation (DHFR triple + DHPS double + arg-581)