Interactions between antenatal sulfadoxine-pyrimethamine, drug-resistant Plasmodium falciparum parasites, and delivery outcomes in Malawi

Abstract

Background. Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients. Methods. We measured SP-resistance allele frequencies in Malawian women participating in a trial comparing IPTp with SP against intermittent screening by rapid diagnostic tests (ISTp). We genotyped polymerase chain reaction-detected parasites using deep sequencing of SP-resistance alleles. Results. Among 125 placental infections, A581G-bearing parasites were associated with reduced birth weight (mean difference [MD], 252 g; 95% confidence interval [CI], 46-457; P =.017). Relative to ISTp, IPTp-SP was associated with higher birth weights in women with wild-type parasites (MD, 116 g; 95% CI, −40 to 272; P =.142) and lower birth weights in women with A581Gbearing parasites (MD, 192 g; 95% CI, −264 to 648; P =.385) (Pinteraction =.033). Similar associations were noted on gestational age (Pinteraction =.075). Amongst only IPTp-SP recipients, relative to women who last received SP > 4 weeks before delivery, recent SP receipt was associated with lower birth weight in women with wild-type parasites (MD, 118 g; 95% CI, −376 to 139; P =.361) and higher birth weight in women with A581G-bearing parasites (MD, 783 g; 95% CI, −20 to 1586; P =.054) (Pinteraction =.005). Conclusions. The effectiveness in birth weight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP. iSRCTN Registry: www.isrctn.com/ISRCTN69800930.