The Use of Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine for Preventing Malaria in Pregnant Women

Department of Microbiology, Immunology and Hematology, Faculty of Medicine and Biomedical Sciences, Biotechnology Center, University of Yaoundé 1, Yaoundé, Cameroon.
Clinical Infectious Diseases (Impact Factor: 8.89). 08/2011; 53(3):231-3. DOI: 10.1093/cid/cir383
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    • "Such P. falciparum parasites carrying quintuple mutations (triple pfdhfr with double pfdhps mutations) are highly prevalent in East Africa [16,17], but rare in West Africa [18], including Benin where a study from 2003 to 2005 showed that the most prevalent haplotype (85%) was the quadruple (triple pfdhfr, single pfdhps) mutant [19]. Although SP shows poor efficacy in children infected with quintuple mutant parasites, IPTp with SP seems to remain effective in preventing the adverse consequences of malaria on maternal and foetal outcomes in areas where a high proportion of P. falciparum parasites carry these quintuple mutations [20,21]. "
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    ABSTRACT: Background Despite widespread parasite resistance to sulphadoxine-pyrimethamine (SP) its use for intermittent preventative treatment during pregnancy remains the policy in Benin and throughout most of sub-Saharan Africa. Methods In a prospective study, 982 pregnant women were recruited in Benin and followed until delivery. The prevalence of point mutations in the pfdhfr and pfdhps genes associated with Plasmodium falciparum resistance to SP during consecutive antenatal visits was determined. Parasites clearance among women infected at SP intake was assessed by microscopy and PCR. Association between the persistence of parasites and malaria consequences, were investigated. Recurrent parasites were genotyped to identify recrudescences from re-infections. Results The prevalence of pfdhfr/pfdhps quadruple mutants (triple pfdhfr + single pfdhps) was consistently above 80% while quintuple and sextuple mutants remained low. Importantly the higly mutated parasites apparently never included the two key mutations, pfdhfr 164 L or pfdhps 540E. Based on PCR results, SP failed to clear existing parasitaemia in half (48%) of the women who were infected at IPTp schedule. The frequency of recrudescence reached 76% after the second dose. Women with persistent parasitaemia had an increased prevalence of anaemia (P = 0.03). Conclusion The data presented here, highlight the inability of SP to ensure optimal antiplasmodial protection in late pregnancy, and invite urgent consideration of an alternative drug or strategy.
    Malaria Journal 06/2013; 12(1):195. DOI:10.1186/1475-2875-12-195 · 3.11 Impact Factor
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    ABSTRACT: Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens. ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy. Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722-3239 g) and on average 56 g higher (95% CI, 29-83 g; I2 = 0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR, 0.80; 95% CI, 0.69-0.94; I 2 = 0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10-52]; number needed to treat = 31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had less placental malaria (RR, 0.51; 95% CI, 0.38-0.68; I 2 = 0%, in 6 trials, 63 vs 32 per 1000; absolute risk reduction, 31 per 1000 [95% CI, 20-39]). In primigravid plus secundigravid women, the risk of moderate to severe maternal anemia was lower in the ≥3-dose group (RR, 0.60; 95% CI, 0.36-0.99; I2 = 20%; in 6 trials, 36 vs 22 per 1000; absolute risk reduction, 14 per 1000 [95% CI, 0.4-23]). There were no differences in rates of serious adverse events. Among pregnant women in sub-Saharan Africa, intermittent preventive therapy with 3 or more doses of sulfadoxine-pyrimethamine was associated with a higher birth weight and lower risk of LBW than the standard 2-dose regimens. These data provide support for the new WHO recommendations to provide at least 3 doses of intermittent preventive therapy during pregnancy at each scheduled antenatal care visit in the second and third trimester.
    JAMA The Journal of the American Medical Association 02/2013; 309(6):594-604. DOI:10.1001/jama.2012.216231 · 35.29 Impact Factor
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    ABSTRACT: Malaria infection during pregnancy is a risk factor for fetus survival and is associated with abortion, premature delivery and low birth weight of infants in malaria endemic regions. In these regions, prophylactic measures and treatment mainly relies on chloroquine and sulphadoxine pyrimethamine, but their efficacy in reducing the placental pathology has not been studied. Therefore, the present study was designed to assess the effectiveness of chloroquine and sulphadoxine pyrimethamine treatment in reducing the placental pathology of Plasmodium berghei infected BALB/c mice. It was observed that pregnant-infected mice, treated either with chloroquine or sulphadoxine pyrimethamine had significantly lower percent parasitaemia, 100 % survival and delivered normally compared with untreated pregnant-infected mice. Interestingly, antimalarial treatment significantly reduced malondialdehyde (MDA) levels, measure of lipid peroxidation and number of apoptotic cells in the placentae of pregnant-infected treated mice. Histologically also no morphological and cellular alterations were observed in the placentae of pregnant-infected treated mice. Taken together, the study shows the effectiveness of chloroquine and sulphadoxine pyrimethamine treatment, when administered in second trimester in abrogating malaria induced oxidative stress, apoptosis and histopathological alterations in the placenta, leading to normal fetal development.
    Parasitology International 09/2013; 63(1). DOI:10.1016/j.parint.2013.08.016 · 1.86 Impact Factor