Effect of sulfadoxine-pyrimethamine doses for prevention of malaria during pregnancy in hypoendemic area in Tanzania

(2020) 19:160 Mikomangwa et al. Malar J https://doi.org/10.1186/s12936-020-03234-4 Malaria Journal Open Access RESEARCH Effect of sulfadoxine‑pyrimethamine doses for prevention of malaria during pregnancy in hypoendemic area in Tanzania Wigilya P. Mikomangwa1*, Omary Minzi1, Ritah Mutagonda1, Vito Baraka2, Eulambius M. Mlugu3, Eleni Aklillu4 and Appolinary A. R. Kamuhabwa1 Abstract Background: Malaria in pregnancy increases the risk of deleterious maternal and birth outcomes. The use of ≥ 3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (IPTp-SP) is recommended for preventing the consequences of malaria during pregnancy. This study assessed the effect of IPTp-SP for prevention of malaria during pregnancy in low transmission settings. Methods: A cross-sectional study that involved consecutively selected 1161 pregnant women was conducted at Mwananyamala regional referral hospital in Dar es Salaam. Assessment of the uptake of IPTp-SP was done by extracting information from antenatal clinic cards. Maternal venous blood, cord blood, placental blood and placental biopsy were collected for assessment of anaemia and malaria. High performance liquid chromatography with ultraviolet detection (HPLC-UV) was used to detect and quantify sulfadoxine (SDX). Dried blood spots (DBS) of placental blood were collected for determination of sub-microscopic malaria using polymerase chain reaction (PCR). Results: In total, 397 (34.2%) pregnant women reported to have used sub-optimal doses (≤ 2) while 764 (65.8%) used optimal doses (≥ 3) of IPTp-SP at the time of delivery. The prevalence of placental malaria as determined by histology was 3.6%. Submicroscopic placental malaria was detected in 1.4% of the study participants. Women with peripheral malaria had six times risk of maternal anaemia than those who were malaria negative (aOR, 5.83; 95% CI 1.10–30.92; p = 0.04). The geometric mean plasma SDX concentration was 10.76 ± 2.51 μg/mL. Sub-optimal IPTp-SP dose was not associated with placental malaria, premature delivery and fetal anaemia. The use of ≤ 2 doses of IPTp-SP increased the risk of maternal anaemia by 1.36-fold compared to ≥ 3 doses (aOR, 1.36; 95% CI 1.04–1.79; p = 0.02). Conclusion: The use of < 2 doses of IPTp-SP increased the risk of maternal anaemia. However, sub-optimal doses (≤ 2 doses) were not associated with increased the risk of malaria parasitaemia, fetal anaemia and preterm delivery among pregnant women in low malaria transmission setting. The use of optimal doses (≥ 3 doses) of IPTp-SP and complementary interventions should continue even in areas with low malaria transmission. Keywords: Malaria, Pregnancy, Intermittent-preventive treatment, Sulfadoxine-pyrimethamine, Anaemia, Tanzania *Correspondence: 1 Clinical Pharmacy and Pharmacology Department, Muhimbili University of Health and Allied Sciences, Dar es Salaam, United Republic of Tanzania Full list of author information is available at the end of the article Background Despite the efforts to control and eliminate malaria worldwide, malaria in pregnancy (MiP) has remained a significant contributor of maternal, neonate and infant morbidity and mortality. The recent World Health Organization (WHO) malaria report indicated that 219 million malaria cases and 435,000 deaths were reported © The Author(s) 2020. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Mikomangwa et al. Malar J (2020) 19:160 worldwide, of which 80% were from sub-Saharan Africa and India [1]. Following the implementation of integrated strategies to curb malaria globally, some regions have attained low level of malaria transmission [1]. In Tanzania, the prevalence of malaria has declined for more than 50% in 10 years (7.3%, in 2017 compared to 18% in 2007) [2, 3]. The implemented strategies include the use of insecticide-treated nets (ITNs), indoor residual spray and larval source reduction using biolarvicides [4]. The other major strategies include intermittent preventive treatment of malaria in pregnant women using sulfadoxinepyrimethamine (IPTp-SP) and prompt malaria diagnosis and treatment with effective anti-malarial drugs [5]. Sulfadoxine (1500 mg)/Pyrimethamine (75 mg) is given to pregnant women as a single therapeutic dose on direct observed therapy (DOT) during visits to the antenatal clinics (ANC). The drug is readily absorbed (bioavailability > 90%) and reaches peak plasma concentration of about 183 μg/mL (sulfadoxine) and 0.55 ng/mL (pyrimethamine) 2–8 h after oral administration [6]. Sulfadoxine (SDX) is eliminated through glomerular filtration and 70% of it undergoes tubular reabsorption which contributes to its long elimination half-life [6–8]. SDX can stay in the plasma for up to 9 weeks, while pyrimethamine is fast cleared and up to 30% excreted through the urine [7–9]. For SP to be safe and well tolerated, the doses of IPTp-SP should be administered from the earliest second trimester (14 weeks of gestation) to delivery, with each dose given at one-month interval [10–12]. The beneficial effect of IPTp-SP is believed to be due to suppression rather than complete clearance of parasites in the peripheral and placenta [10, 11]. The uptake of IPTp-SP during the course of pregnancy prevents deleterious maternal and fetal outcomes associated with malaria in pregnancy (MiP) [13–15]. The widespread SP resistance due to mutations in the parasite’s dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, rendered the previous recommended 2-doses ineffective in averting adverse birth and maternal outcomes due to MiP [16–19]. Instead, the uptake of at least three doses of IPTp-SP (≥ 3 doses) during pregnancy was considered optimum [19]. The IPTp-SP ≥ 3 doses are associated with reduced odds of adverse birth outcomes such as low birth weight (LBW) and maternal anaemia in areas with moderate to high malaria transmission [20–22]. However, such beneficial effects of IPTp-SP uptake in low malaria (...truncated)