Search

Co-administration of dihydroartemisinin-piperaquine (DP) and sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria in pregnancy (IPTp) may be superior in preventing adverse birth outcomes compared with either therapy alone, but potential drug-drug interactions require investigation. We conducted intensive and sparse pharmacokinetic (PK) studies in a subset of Ugandan women participating in a randomized controlled trial of monthly IPTp with SP vs. DP vs. DP + SP. Intensive PK sampling was performed from day 0 to 23 after dosing at 28 weeks gestation in 87 participants across treatment arms. Sparse sampling was performed on day 28 (trough) after dosing at 20 and 28 gestational weeks in additional 196 participants receiving SP vs. DP + SP. Intensive PK analysis demonstrated that compared with SP alone, co-administration of DP + SP was associated with lower maximal concentrations, the area under the concentration-time curves (AUC), and day 23 concentrations of sulfadoxine (25%, 25%, and 27%) and pyrimethamine (26%, 34%, and 32%) (P < 0.05 for all comparisons). Sparse PK results demonstrated participants co-administered DP + SP had lower trough concentrations after dosing at 20 and 28 gestational weeks for sulfadoxine (6%, P = 0.68 and 31%, P = 0.023, respectively) and pyrimethamine (18%, P = 0.032 and 33%, P < 0.001, respectively) compared with SP alone. Co-administration of DP + SP was associated with a 19% reduction in piperaquine AUC (P = 0.046), but no significant difference in other PK parameters compared with DP alone. In summary, co-administration of DP + SP was associated with significantly reduced SP exposure, with a greater magnitude during the third vs. second trimester. The clinical consequences of this interaction are yet unknown., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Background: In moderate-to-high malaria transmission regions, the World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) alongside insecticide-treated bed nets to reduce the adverse consequences of pregnancy-associated malaria. Due to high-grade Plasmodium falciparum resistance to SP, novel treatment regimens need to be evaluated for IPTp, but these increase pill burden and treatment days. The present qualitative study assessed the acceptability of IPTp-SP plus dihydroartemisinin-piperaquine (DP) in Papua New Guinea, where IPTp-SP was implemented in 2009., Methods: Individual in-depth interviews (IDIs) and focus group discussions were conducted at health facilities where a clinical trial evaluated IPTp-SP plus DP (three-day regimen) versus IPTp-SP plus DP-placebo. IDIs were conducted with: (1) trial participants at different stages of engagement with ANC and IPTp, e.g. first antenatal clinic visit, subsequent antenatal clinic visits and postpartum; (2) local health workers (nurses, community health workers, midwives, health extension officers, doctors); and (3) representatives of district, provincial and national health authorities involved in programming ANC and IPTp. Focus group discussions comprised pregnant women only, including those engaged in the clinical trial and those receiving routine ANC outside of the trial. All interviews were audio recorded and transcribed. Transcripts were analysed using inductive and deductive thematic analysis applying a framework assessing: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy., Results: Women expressed positive feelings and attitudes towards SP plus DP/DP-placebo; reported limited side effects; and found the size, number, colour, and taste of study medicines acceptable. Health workers and policymakers were concerned that, compared to SP alone, additional tablets, frequency (three-day regimen), and tablet size might be barriers to acceptability for users outside a non-trial setting. There was a high perceived effectiveness of SP plus DP; most women reported that they did not get malaria or felt sick during pregnancy. Broader healthcare benefits received through trial participation and the involvement of health workers, relatives and community members in the clinical trial enabled antenatal clinic attendance and perceived acceptability of this IPTp regimen., Conclusions: In the trial context, IPTp-SP plus DP was acceptable to both users and providers. Healthcare providers were concerned about the realities of acceptability and adherence to SP plus DP outside a clinical trial setting., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approvals for this study were obtained from the Charles Darwin University Human Research Ethics Committee (H22094), the Human Research Committee of the Northern Territory Department of Health and Menzies School of Health Research (2021-4107), the PNG IMR Institutional Review Board (2113), the Madang Provincial Health Authority Research Ethics Committee (04.21), and Medical Research Advisory Committee of PNG National Department of Health (22.10). All participants provided written informed consent for this study. Women involved in the parent trial also provided written informed consent, independent of participation in the clinical trial. Methods used in participants recruitment, data collection, storage, processing, and analysis were carried out according to the Declaration of Helsinki, the Principles of Good Clinical Practice and PNG regulatory guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: To evaluate the effectiveness and cost-effectiveness of integrating seasonal malaria chemoprevention (SMC) with mass drug administration for helminth control among school-aged children living in communities where the burden of malaria and helminths is high in Ghana, West Africa., Methods: This cluster randomised controlled trial will enrol 1200 children aged 5-10 years. Eligible children randomised to intervention clusters will receive SMC drugs (sulphadoxine-pyrimethamine plus amodiaquine) and anthelminthic drugs for soil-transmitted helminths-(albendazole), and for schistosomiasis (praziquantel), while children randomised to control clusters will receive SMC drugs alone. Pre- and post-intervention blood, urine and stool samples will be collected from children in both clusters. The effectiveness of the concomitant delivery will be determined by checking whether the combination of SMC and anthelminthic drugs prevents anaemia in the children randomised to the intervention clusters compared to the children in the control clusters. Cost analysis and cost-effectiveness of this integrated delivery approach will be determined by estimating the incremental costs and effects of co-administration of SMC drugs with mass drug administration of anthelminthic drugs compared to SMC alone, including cost savings due to cases of moderate and severe anaemia averted., Expected Findings: The findings of this study will provide evidence to inform public health recommendations for an integrated control of malaria and helminths among children living in the poorest countries of the world., (© 2024 The Author(s). Tropical Medicine & International Health published by John Wiley & Sons Ltd.)