A Randomized Controlled Pilot Trial of Azithromycin or Artesunate Added to Sulfadoxine-Pyrimethamine as Treatment for Malaria in Pregnant Women

Linda Kalilani,Innocent Mofolo,Marjorie Chaponda,Alisa P Alker,Jesse J Kwiek,Stephen J Rogerson,Steven R Meshnick,Piero Olliaro

doi:10.1371/journal.pone.0001166

Linda Kalilani, Innocent Mofolo + Show 6 more

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https://doi.org/10.1371/journal.pone.0001166

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Abstract

ObjectiveNew anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance. We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre, Malawi.Methods/FindingsThis was a randomized open-label clinical trial, conducted at two rural health centers in Blantyre district, Malawi. A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and randomly allocated to 3 treatment groups: sulfadoxine-pyrimethamine (SP; 3 tablets, 500 mg sulfadoxine and 25 mg pyrimethamine per tablet); SP plus azithromycin (1 g/day×2 days); or SP plus artesunate (200 mg/day×3 days). Women received two doses administered at least 4 weeks apart. Heteroduplex tracking assays were performed to distinguish recrudescence from new infections. Main outcome measures were incidence of adverse outcomes, parasite and fever clearance times and recrudescence rates. All treatment regimens were well tolerated. Two women vomited soon after ingesting azithromycin. The parasite clearance time was significantly faster in the SP-artesunate group. Recrudescent episodes of malaria were less frequent with SP-azithromycin [Hazard Ratio 0.19 (95% confidence interval 0.06 to 0.63)] and SP-artesunate [Hazard Ratio 0.25 (95% confidence interval 0.10 to 0.65)] compared with SP monotherapy. With one exception (an abortion in the SP-azithromycin group), all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes. Because of the small sample size, the effect on birth outcomes, maternal malaria or maternal anemia could not be evaluated.ConclusionsBoth SP-artesunate and SP-azithromycin appeared to be safe, well tolerated and efficacious for the treatment of malaria during pregnancy. A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes.Trial RegistrationClinialTrials.gov NCT00287300

Highlights

More than 30 million women become pregnant in malaria-endemic areas in Africa each year [1,2]
The proportion of HIVinfected women was higher in the SP [33.3%, (9/27)] and SPazithromycin groups [34.5%, (10/29)] than in the SP-artesunate group [21.2%, (7/33)]
Our results show that in Malawi, where P. falciparum resistance to SP has been detected [33,34], SP plus azithromycin or artesunate were more efficacious in treating malaria in pregnant women than SP monotherapy

Summary

Introduction

More than 30 million women become pregnant in malaria-endemic areas in Africa each year [1,2]. Infection with Plasmodium falciparum during pregnancy can cause maternal anemia, abortions, stillbirths, preterm deliveries and low birth weight [3,4]. All pregnant women in these areas should be provided with intermittent preventive therapy (IPT) at antenatal visits to prevent infection [6]. Sulfadoxine-pyrimethamine (SP), first introduced in Malawi in 1993, has been adopted by many countries in sub-Saharan Africa as the drug of choice for IPT. Studies have shown that IPT significantly reduces the prevalence of placental malaria and low birth weight [7,8,9,10,11,12]

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