Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK; Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.
Disease Control Department, London School of Hygiene & Tropical Medicine, London, UK.
Lancet Glob Health. 2024 Oct;12(10):e1660-e1672. doi: 10.1016/S2214-109X(24)00261-4.
High-level resistance to sulfadoxine-pyrimethamine threatens the efficacy of WHO-recommended intermittent preventive treatment in pregnancy (IPTp) with single-dose sulfadoxine-pyrimethamine to prevent malaria. Monthly IPTp with dihydroartemisinin-piperaquine, a 3-day regimen, is an emerging alternative, but this regimen poses potential implementation and adherence challenges. We aimed to assess adherence to a multiday IPTp with dihydroartemisinin-piperaquine regimen and its delivery effectiveness in routine antenatal care settings in western Kenya.
We conducted a pragmatic, three-armed, open-label, cluster-randomised trial in antenatal clinics in 18 health-care facilities (six facilities per group) in Kisumu County and Homa Bay County in western Kenya. Clusters were facilities offering routine antenatal care services provided by trained Ministry of Health staff with 100 or more antenatal clinic attendances per month between July, 2018, and June, 2019. Private or mission hospitals, dispensaries, referral hospitals, and trial sites were excluded. Individuals in their first trimester, living with HIV, or who were not attending a scheduled antenatal clinic visit were excluded. The 18 antenatal clinics were grouped into matched triplets stratified by location and clinics in each matched triplet were randomly assigned to one of the three study groups (1:1:1). Masking was not possible. Two groups were given IPTp with dihydroartemisinin-piperaquine (one group with a targeted information transfer intervention and one group without any additional interventions) and one group was given the standard of care (ie, IPTp with sulfadoxine-pyrimethamine). The primary endpoint, adherence, was defined as the proportion of participants completing their most recent 3-day IPTp with dihydroartemisinin-piperaquine regimen. This completion was verified by pill counts during home visits no more than 2 days after participants' 3-day regimens ended. The secondary endpoint, delivery effectiveness, was defined as the proportion of participants who received the correct number of IPTp tablets and correctly repeated dosing instructions (ie, correctly recalled the instructions they received about self-administered dihydroartemisinin-piperaquine doses and the number of sulfadoxine-pyrimethamine tablets they had received) at their exit from the antenatal clinic. Individuals receiving treatment for malaria, visiting a clinic for registration only, or interviewed during IPTp drug stock-outs were excluded from analyses. We used generalised linear mixed models to compare endpoints among the IPTp with dihydroartemisinin-piperaquine groups. This trial was registered with ClinicalTrials.gov, NCT04160026, and is complete.
15 facilities (five per group) completed the trial, with 1189 participants having exit interviews (377 in the IPTp with sulfadoxine-pyrimethamine group, 408 in the IPTp with dihydroartemisinin-piperaquine only group, and 404 in the IPTp with dihydroartemisinin-piperaquine plus targeted information transfer intervention group) and 586 participants having home visits (267 in the IPTp with dihydroartemisinin-piperaquine only group and 319 in the IPTp with dihydroartemisinin-piperaquine plus targeted information transfer intervention group) from Sept 8 to Dec 10, 2020. Relative to the IPTp with dihydroartemisinin-piperaquine only group, adherence was 16% higher in the IPTp with dihydroartemisinin-piperaquine plus targeted information transfer intervention group (266 [83%] of 319 participants vs 196 [73%] of 267 participants; adjusted relative risk [RR] 1·16, 95% CI 1·03-1·31; p=0·0140). Delivery effectiveness in the IPTp with dihydroartemisinin-piperaquine plus targeted information transfer intervention group was not significantly different from that in the IPTp with sulfadoxine-pyrimethamine group (352 [87%] of 403 participants vs 335 [89%] of 375 participants; adjusted RR 0·97, 95% CI 0·90-1·05; p=0·4810). However, delivery effectiveness in the IPTp with dihydroartemisinin-piperaquine only group was significantly lower than in the IPTp with sulfadoxine-pyrimethamine group (300 [74%] of 404 participants vs 335 [89%] of 375 participants; 0·84, 0·75-0·95; p=0·0030).
Targeted information transfer interventions to health-care providers and pregnant individuals boost antenatal care delivery adherence to a multiday regimen with dihydroartemisinin-piperaquine.
European and Developing Countries Clinical Trials Partnership 2, UK Joint Global Health Trials Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust; and Swedish International Development Cooperation Agency.
高水平的磺胺多辛-乙胺嘧啶耐药性威胁到世界卫生组织推荐的单次磺胺多辛-乙胺嘧啶剂量用于预防妊娠疟疾的间歇性预防治疗（IPTp）的疗效。二氢青蒿素-哌喹，一种 3 天疗程，是一种新兴的替代方案，但这种方案存在潜在的实施和坚持挑战。我们旨在评估在肯尼亚西部常规产前保健环境中使用二氢青蒿素-哌喹多日 IPTp 方案的依从性及其交付效果。
我们在肯尼亚基苏木县和霍马贝县的 18 个卫生保健设施（每组 6 个设施）的产前诊所进行了一项实用、三臂、开放标签、集群随机试验。集群是提供由经过培训的卫生部工作人员提供的常规产前护理服务的设施，每月有 100 次或以上的产前诊所就诊，时间为 2018 年 7 月至 2019 年 6 月。私人或教会医院、诊所、转诊医院和试验地点被排除在外。处于妊娠早期、感染艾滋病毒或未参加预定的产前诊所就诊的个体被排除在外。18 个产前诊所被分为匹配的三胞胎，按位置和每个匹配的三胞胎中的诊所进行分层，然后随机分配到三个研究组之一（1:1:1）。不可能进行掩蔽。两组给予二氢青蒿素-哌喹 IPTp（一组给予有针对性的信息传递干预，一组不给予任何额外干预），一组给予标准护理（即磺胺多辛-乙胺嘧啶剂量的 IPTp）。主要终点是依从性，定义为最近一次完成 3 天二氢青蒿素-哌喹 IPTp 方案的参与者比例。通过参与者 3 天疗程结束后不超过 2 天的家访时进行药片计数来验证完成情况。次要终点是交付效果，定义为正确接受正确数量的 IPTp 片数并正确重复剂量说明（即正确回忆他们收到的关于自我管理二氢青蒿素-哌喹剂量的说明以及他们收到的磺胺多辛-乙胺嘧啶片数）的参与者比例。在从产前诊所离开时，正在接受疟疾治疗、仅来诊所登记或在 IPTp 药物缺货期间接受访谈的个体被排除在分析之外。我们使用广义线性混合模型比较了三组二氢青蒿素-哌喹 IPTp 方案的结局。该试验在 ClinicalTrials.gov 上注册，编号为 NCT04160026，现已完成。
15 个设施（每组 5 个）完成了试验，共有 1189 名参与者接受了出院访谈（磺胺多辛-乙胺嘧啶组 377 名，二氢青蒿素-哌喹组 408 名，二氢青蒿素-哌喹加靶向信息传递干预组 404 名），586 名参与者接受了家访（二氢青蒿素-哌喹组 267 名，二氢青蒿素-哌喹加靶向信息传递干预组 319 名），时间为 2020 年 9 月 8 日至 12 月 10 日。与仅接受二氢青蒿素-哌喹 IPTp 的组相比，接受二氢青蒿素-哌喹加靶向信息传递干预的组依从性提高了 16%（319 名参与者中的 266 名[83%]与 267 名参与者中的 196 名[73%]；调整后的相对风险[RR] 1.16，95%CI 1.03-1.31；p=0.0140）。二氢青蒿素-哌喹加靶向信息传递干预组的交付效果与磺胺多辛-乙胺嘧啶组无显著差异（403 名参与者中的 352 名[87%]与 375 名参与者中的 335 名[89%]；调整后的 RR 0.97，95%CI 0.90-1.05；p=0.4810）。然而，仅接受二氢青蒿素-哌喹 IPTp 的组的交付效果明显低于磺胺多辛-乙胺嘧啶组（404 名参与者中的 300 名[74%]与 375 名参与者中的 335 名[89%]；0.84，0.75-0.95；p=0.0030）。
向卫生保健提供者和孕妇提供有针对性的信息传递干预措施可提高对二氢青蒿素-哌喹多日方案的产前保健依从性。
欧洲和发展中国家临床试验伙伴关系 2、英国联合全球卫生试验计划的外交、联邦和发展办公室、医学研究委员会、国家卫生和保健研究理事会和惠康信托基金会；以及瑞典国际开发合作署。
