Malaria in pregnancy and drug therapies in Malawi Public Deposited

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  • March 21, 2019
Creator
  • Kalilani, Linda Vanessa
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • In this dissertation, I investigated the effect of timing and frequency of Plasmodium falciparum infection during pregnancy on the risk of low birth weight and maternal anemia. I also investigated the efficacy of sulfadoxine-pyrimethamine combined with azithromycin or artesunate compared with sulfadoxine-pyrimethamine monotherapy as treatment for uncomplicated Plasmodium falciparum infection in pregnant women. We conducted a prospective observational study recruiting 2,462 pregnant women in Malawi. Malaria was assessed during follow-up and delivery. Birth weight and hemoglobin concentration were measured at delivery. The prevalence of low birth weight increased with the number of malaria episodes: [1 episode (prevalence ratio [PR] =2.17; 95% C.I. 1.22-3.86), and 2 episodes (PR=3.68; 95% C.I. 1.81-7.47)]. The prevalence of anemia increased with the number of episodes of malaria: [1 episode (PR= 1.16; 95% C.I. 0.77-1.77) and 2 episodes (PR= 1.82 95% C.I. 1.04-3.19)]. The prevalence of low birth weight was higher with infection in the second trimester (PR=2.97; 95% CI 1.60-5.53) than in the third trimester (PR=1.42; 95% CI 0.63-3.22). The prevalence of maternal anemia was higher with infection in the third trimester (PR=1.44; 95% CI 0.90-2.29) than in the second trimester (PR=0.94; 95% CI 0.51-1.71). Timing and frequency of infection affect the risk of maternal anemia and low birth weight. We conducted a randomized open-label clinical trial, recruiting 141 pregnant women. They were randomly allocated to 3 treatment groups: sulfadoxine-pyrimethamine (SP; 3 tablets, 500mg sulfadoxine and 25mg pyrimethamine per tablet); SP plus azithromycin (1g/day x 2 days); or SP plus artesunate (400mg/day x 3 days). All treatment regimens were well tolerated. Two women vomited soon after ingesting azithromycin. Recrudescent episodes of malaria were less frequent with SP-azithromycin [Hazard Ratio 0.14 (95% confidence interval 0.02 to 0.78)] and SP-artesunate [Hazard Ratio 0.13 (95% confidence interval 0.03 to 0.53)] compared with SP monotherapy. There were more abortions in the SP-azithromycin group, and more stillbirths in the SP-artesunate groups, but they were probably unrelated to treatment. A larger study is needed to determine its safety and efficacy in preventing poor birth outcomes.
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Advisor
  • Meshnick, Steven R.
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