Abstract
BackgroundMalaria in pregnancy is serious, and drug resistance in Africa is spreading. Drugs have greater risks in pregnancy and determining the safety and efficacy of drugs in pregnancy is therefore a priority. This study set out to determine the efficacy and safety of several antimalarial drugs and combinations in pregnant women with uncomplicated malaria.MethodsPregnant women with non-severe, slide proven, falciparum malaria were randomised to one of 4 regimes: sulfadoxine-pyrimethamine [SP]; chlorproguanil-dapsone [CD]; SP+amodiaquine [SP+AQ] or amodiaquine+artesunate [AQ+AS]. Randomisation was on a 1∶2∶2∶2 ratio. Women were admitted for treatment, and followed at days 7, 14, 21, 28 after the start of treatment, at delivery and 6 weeks after delivery to determine adverse events, clinical and parasitological outcomes. Primary outcome was parasitological failure by day 28.Results1433 pregnant women were screened, of whom 272 met entry criteria and were randomised; 28 to SP, 81 to CD, 80 to SP+AQ and 83 to AQ+AS. Follow-up to day 28 post treatment was 251/272 (92%), and to 6 weeks following delivery 91%. By day 28 parasitological failure rates were 4/26 (15%, 95%CI 4–35) in the SP, 18/77 (23%, 95%CI 14–34) in the CD, 1/73 (1% 95%CI 7–0.001) in the SP+AQ and 7/75 (9% 95%CI 4–18) in the AQ+AS arms respectively. After correction by molecular markers for reinfection the parasitological failure rates at day 28 were 18% for CD, 1% for SP+AQ and 4.5% for AQ+AS. There were two maternal deaths during the trial. There was no apparent excess of stillbirths or adverse birth outcomes in any arm. Parasitological responses were strikingly better in pregnant women than in children treated with the same drugs at this site.ConclusionsFailure rates with monotherapy were unacceptably high. The two combinations tested were efficacious and appeared safe. It should not be assumed that efficacy in pregnancy is the same as in children.Trial RegistrationClinicalTrials.gov NCT00146731
Highlights
Malaria in pregnancy is an important preventable cause of maternal and perinatal morbidity and mortality [1,2], and contributes substantially to maternal morbidity in Tanzania and elsewhere [3]
Women semi-immune to malaria carry substantial risks of severe maternal anaemia and low-birthweight which is greatest in the first pregnancy, and the malaria may be asymptomatic [6,7,8]
Throughout the study period SP was national firstline treatment for malaria, and this was taken as the comparator arm for this study
Summary
Malaria in pregnancy is an important preventable cause of maternal and perinatal morbidity and mortality [1,2], and contributes substantially to maternal morbidity in Tanzania and elsewhere [3]. Traditional exclusion of pregnant women from clinical trials has led to limited data on safety and efficacy of artemisinin based combinations considered for general deployment especially in Africa. Generating data on the efficacy and safety of antimalarials in pregnancy is a priority [10,11]. This trial was designed to assess the efficacy and tolerability of two antimalarial drug combinations and one novel form of monotherapy in pregnant Tanzanian women. This study set out to determine the efficacy and safety of several antimalarial drugs and combinations in pregnant women with uncomplicated malaria
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