In vivo efficacy of sulphadoxine-pyrimethamine for the treatment of asymptomatic parasitaemia in pregnant women in Machinga District, Malawi

Julie Gutman, Dyson Mwandama, Ryan E Wiegand, Joseph Abdallah, Nnaemeka C Iriemenam, Ya Ping Shi, Don P Mathanga, Jacek Skarbinski, Julie Gutman, Dyson Mwandama, Ryan E Wiegand, Joseph Abdallah, Nnaemeka C Iriemenam, Ya Ping Shi, Don P Mathanga, Jacek Skarbinski

Abstract

Background: The effectiveness of sulphadoxine-pyrimethamine (SP) intermittent preventive treatment of malaria in pregnancy (IPTp) might be compromised by high prevalence of resistance-associated Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations. As a proxy for IPTp-SP effectiveness, the in vivo efficacy of SP to clear parasitaemia and prevent reinfection in asymptomatic parasitaemic pregnant women in an area with high SP resistance prevalence was assessed.

Methods: Pregnant women 16-26 weeks' gestation with asymptomatic parasitaemia presenting for antenatal care were given IPTp-SP and followed for 42 days. The primary outcome was polymerase chain reaction (PCR) uncorrected 42-day survival rate; the per cent of patients without recrudescence or reinfection by day 42. PCR was used to distinguish recrudescence from reinfection. DNA was sequenced to detect resistance-associated dhfr and dhps mutations.

Results: Of 245 pregnant women included in the intention-to-treat analysis, 93.9% cleared their parasitaemia by day 7. The day 42 PCR-uncorrected survival rate was 58.1% (95% confidence interval (CI) 51.5-65.7) and day 42 PCR-corrected survival was 68.7% (CI 61.4-76.0). Recrudescence was more common among primi- than among multigravid women; recrudescence rate 33.3% (CI 25.1-42.4%) versus 21.4% (CI 15.0-29.0%) (log rank test p-value 0.006). The quintuple mutant was present in nearly all samples (95%), while 2% were sextuple mutants with an additional mutation at dhps A581G.

Conclusions: SP efficacy for acute malaria treatment has been compromised by resistance, but SP retains partial activity among pregnant women with asymptomatic parasitaemia, and thus might be useful for IPTp. Nonetheless, research on non-SP IPTp regimens should continue.

Trial registration: ClinicalTrials.gov NCT01120145 .

Figures

Figure 1
Figure 1
Enrolment flow diagram for sulphadoxine-pyrimethamine (SP) modified in vivo efficacy study in pregnant women*. *Study included pregnant women with asymptomatic malaria parasitaemia attending antenatal care for their first dose of intermittent preventive treatment in pregnancy with SP (IPTp-SP), Machinga District Hospital, Malawi 2009–2010. RDT = rapid diagnostic test.
Figure 2
Figure 2
Kaplan-Meier survival curve estimates for asymptomatic parasitaemic women following treatment with sulphadoxine-pyrimethamine at day 0 with 95% confidence intervals, by gravidity.
Figure 3
Figure 3
Mean haemoglobin levels with 95% confidence intervals broken down by gravidity.

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