Effectiveness of Intermittent Preventative Treatment with Sulfadoxine-Pyrimethamine During Pregnancy on Maternal and Infant Outcomes in Malawi Open Access
Zhang, Amy (Spring 2020)
Abstract
Malaria during pregnancy is associated with low birthweight and other adverse birth outcomes. Increasing drug resistance may undermine the efficacy of intermittent preventative treatment (IPTp) with sulfadoxine-pyrimethamine (SP). A cross-sectional study enrolled HIV-negative women at the time of delivery from July to October 2015 at two district hospitals in southern Malawi. The exposure of interest was the number of IPTp-SP doses received during pregnancy, coded as <3 vs ≥3 doses in primary analyses. The primary outcome was infant birthweight. Secondary outcomes included peripheral and placental malaria infection and a composite birth outcome indicator comprised of low birthweight, preterm birth, and small for gestational age. SP resistance markers were assessed by polymerase chain reaction (PCR). Of 536 women enrolled, 49% received <3 SP doses. Controlling for gravidity, average infant birthweight among women who received three or more SP doses was 91.4 g higher than that among women who received less than three doses of SP (p=0.02). The association between 3+ SP doses (versus <3) and peripheral infection was marginally protective (adjusted prevalence ratio=0.53, 95% CI: 0.28-1.03, p=0.06). Increasing number of SP doses was not statistically significantly associated with protection against placental malaria infection or the composite birth outcome. A total of 91 (17%) samples were PCR positive; 82 (90.1%) samples were successfully genotoyped. All harbored the A437G and K540E mutations associated with the quintuple mutant for SP resistance, which confers high level resistance; only two samples harbored the A581G mutation associated with the “super resistant” sextuple mutant. None of the samples harbored mutations at codons 436 or 613. IPTp-SP provides benefit to Malawian pregnant women and their infants, with a higher mean birthweight and less peripheral malaria among women who received three or more doses of SP, even in a setting of high SP drug resistance.
Table of Contents
Chapter I: Background and Literature Review.................................................................1
Malaria Epidemiology..................................................................................................1
Malaria in Pregnancy (MiP).........................................................................................3
Malaria in Malawi........................................................................................................4
Policies for MiP Prevention in Malawi.........................................................................5
Challenges to IPTp-SP................................................................................................. 5
Chapter II: Manuscript.....................................................................................................8
Abstract........................................................................................................................8
Introduction.................................................................................................................9
Methods.......................................................................................................................11
Results..........................................................................................................................15
Discussion....................................................................................................................18
References........................................................................................................................22
Tables...............................................................................................................................29
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