Intermittent preventive treatment with dihydroartemisinin-piperaquine and risk of malaria following cessation in young Ugandan children: a double-blind, randomised, controlled trial
Intermittent preventive treatment with dihydroartemisinin-piperaquine and risk of malaria following cessation in young Ugandan children: a double-blind, randomised, controlled trial
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DOI：
10.1016/s1473-3099(19)30299-3
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发表时间：
2019-09-01
影响因子：
56.3
通讯作者：
Kamya, Moses R.
中科院分区：
文献类型：
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作者：
Muhindo, Mary K.;Jagannathan, Prasanna;Kamya, Moses R.
背景 使用双氢青蒿素-哌喹对疟疾进行间歇性预防治疗（IPT）是非洲幼儿预防疟疾的一种有前景的策略。然而，最佳剂量策略尚不清楚，并且关于停止化学预防后发生疟疾的风险存在相互矛盾的证据。我们的目的是比较乌干达幼儿中IPT与双氢青蒿素哌喹的两种给药策略，并评估停止IPT后患疟疾的风险。 方法 在这项双盲、随机对照2期试验中，招募了托罗罗地区医院（乌干达托罗罗）的妇女及其未出生的孩子。符合资格的参与者是年龄 16 岁或以上且可怀孕（胎龄 12-20 周）的 HIV 阴性女性。根据妇女在怀孕期间接受的 IPT 干预，妇女及其未出生的孩子被随机分配（1:1:1:1）到四个治疗组之一，所有治疗组均接受双氢青蒿素哌喹治疗：妇女每 8 周一次，儿童每 4 周一次；女性每 4 周一次，儿童每 4 周一次；女性每 8 周一次，儿童每 12 周一次；女性每 4 周一次，儿童每 12 周一次。区组随机化由独立研究者使用计算机生成的随机化列表（排列区组大小为 6 和 12）完成。我们根据随机分配接受双氢青蒿素哌喹（20 毫克/160 毫克片剂）的儿童进行了分析，每天一次，连续 3 天，每 4 周或 12 周一次。儿童从 8 周至 24 个月大时接受研究药物，并随访至 36 个月大。参与者和研究人员对治疗分配情况不知情。主要结局是干预期间和干预停止后有症状的疟疾的发生率，并根据潜在的混杂因素进行了调整。主要结局和安全性在修改后的意向治疗人群中进行评估，其中包括所有达到 8 周龄并接受至少一剂研究药物的儿童。该试验在ClinicalTrials.gov上注册，编号为NCT02163447。调查结果2014年10月21日至2015年5月18日期间，共有191名儿童出生，其中183名已满8周，并接受了至少一剂研究药物，因此被纳入主要分析（4周组有96名儿童，12周组有87名儿童）。干预期间，每 4 周接受治疗的儿童的症状性疟疾发病率显着低于每 12 周接受治疗的儿童；每 4 周接受治疗的儿童中发生 3 次发作（发病率为每人每年 0.018 次），而每 12 周接受治疗的儿童则发生 61 次发作（发病率为每人每年 0.39 次；调整后的发病率比 [aIRR] 0.041，95% CI 0. 012-0. 150，p
Background Intermittent preventive treatment (IPT) of malaria with dihydroartemisinin-piperaquine is a promising strategy for malaria prevention in young African children. However, the optimal dosing strategy is unclear and conflicting evidence exists regarding the risk of malaria after cessation of chemoprevention. We aimed to compare two dosing strategies of IPT with dihydroartemisinin-piperaquine in young Ugandan children, and to evaluate the risk of malaria after cessation of IPT.Methods In this double-blind, randomised controlled phase 2 trial, women and their unborn children were recruited at Tororo District Hospital (Tororo, Uganda). Eligible participants were HIV-negative women aged 16 years or older with a viable pregnancy (gestational age 12-20 weeks). Women and their unborn children were randomly assigned (1:1:1:1) to one of four treatment groups, all receiving dihydroartemisinin-piperaquine, on the basis of the IPT intervention received by the woman during pregnancy: women every 8 weeks, children every 4 weeks; women every 4 weeks, children every 4 weeks; women every 8 weeks, children every 12 weeks; and women every 4 weeks, children every 12 weeks. Block randomisation was done by an independent investigator using a computer-generated randomisation list (permuted block sizes of six and 12). We analysed children on the basis of their random assignment to receive dihydroartemisinin-piperaquine (20 mg/160 mg tablets) once daily for 3 consecutive days every 4 weeks or 12 weeks. Children received study drugs from age 8 weeks to 24 months and were followed-up to age 36 months. Participants and investigators were masked to treatment allocation. The primary outcome was the incidence of symptomatic malaria during the intervention and following cessation of the intervention, adjusted for potential confounders. The primary outcome and safety were assessed in the modified intention-to-treat population, which included all children who reached 8 weeks of age and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , number NCT02163447.Findings Between Oct 21, 2014, and May 18, 2015, 191 children were born, of whom 183 reached 8 weeks of age and received at least one dose of study drug and thus were included in the primary analysis (96 children in the 4-week group and 87 in the 12-week group). During the intervention, the incidence of symptomatic malaria was significantly lower among children treated every 4 weeks than children treated every 12 weeks; three episodes occurred among children treated every 4 weeks (incidence 0.018 episodes per person-year) compared with 61 episodes among children treated every 12 weeks (incidence 0.39 episodes per person-year; adjusted incidence rate ratio [aIRR] 0.041, 95% CI 0. 012-0. 150, p