Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children.
Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children.
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DOI：
10.1038/s41467-021-27051-8
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发表时间：
2021-11-18
影响因子：
16.6
通讯作者：
Savic RM
中科院分区：
文献类型：
--
作者：
Wallender E;Ali AM;Hughes E;Kakuru A;Jagannathan P;Muhindo MK;Opira B;Whalen M;Huang L;Duvalsaint M;Legac J;Kamya MR;Dorsey G;Aweeka F;Rosenthal PJ;Savic RM
双氢青蒿素-哌喹（DP）间歇预防性治疗（IPT）对儿童疟疾具有高度保护作用，但在疟疾流行国家并非标准做法。最佳DP给药方案将最大限度地提高疗效，减少毒性和耐药性选择。我们分析了哌喹（PPQ）浓度（n = 4573）、疟疾发病率数据（n = 326）和恶性疟原虫耐药标记物，这些数据来自一项试验，该试验将2至24个月大的儿童随机分为每12周（n = 184）或每4周（n = 96）进行IPT和DP治疗（NCT02163447）。我们使用非线性混合效应建模来建立疟疾防护PPQ水平和次优防护的风险因素。与每12周服用一次化疗相比，每4周服用一次化疗与95%的保护效果相关（95% CI: 84-99%）。15.4纳克/毫升的PPQ水平可使疟疾危害降低95%。营养不良可减少PPQ暴露。在模拟中，我们表明，在传播强度范围内，每4周接种一次疫苗是最佳的，基于年龄的剂量可以改善年幼或营养不良儿童的疟疾保护。双氢青蒿素-哌喹（DP）间歇预防性治疗可保护儿童免受疟疾侵害。在这里，作者分析了乌干达一项临床试验的血浆药物浓度、疟疾发病率和耐药性标记物，并确定了最佳的DP给药方案。
Intermittent preventive treatment (IPT) with dihydroartemisinin-piperaquine (DP) is highly protective against malaria in children, but is not standard in malaria-endemic countries. Optimal DP dosing regimens will maximize efficacy and reduce toxicity and resistance selection. We analyze piperaquine (PPQ) concentrations (n = 4573), malaria incidence data (n = 326), and P. falciparum drug resistance markers from a trial of children randomized to IPT with DP every 12 weeks (n = 184) or every 4 weeks (n = 96) from 2 to 24 months of age (NCT02163447). We use nonlinear mixed effects modeling to establish malaria protective PPQ levels and risk factors for suboptimal protection. Compared to DP every 12 weeks, DP every 4 weeks is associated with 95% protective efficacy (95% CI: 84–99%). A PPQ level of 15.4 ng/mL reduces the malaria hazard by 95%. Malnutrition reduces PPQ exposure. In simulations, we show that DP every 4 weeks is optimal across a range of transmission intensities, and age-based dosing improves malaria protection in young or malnourished children. Intermittent preventive treatment with dihydroartemisinin-piperaquine (DP) is protective in children against malaria. Here, the authors analyze plasma drug concentration, malaria incidence, and drug resistance markers from a clinical trial in Uganda and determine the optimal DP dosing regimen.
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DOI：
10.1016/s0140-6736(20)32227-3
发表时间：
2020-12-05
期刊：
Lancet (London, England)
影响因子：
--
作者：
ACCESS-SMC Partnership
通讯作者：
ACCESS-SMC Partnership
影响因子：
3
作者：
D'Alessandro U;Ubben D;Hamed K;Ceesay SJ;Okebe J;Taal M;Lama EK;Keita M;Koivogui L;Nahum A;Bojang K;Sonko AA;Lalya HF;Brabin B
通讯作者：
Brabin B
影响因子：
9.3
作者：
Denoeud-Ndam L;Dicko A;Baudin E;Guindo O;Grandesso F;Diawara H;Sissoko S;Sanogo K;Traoré S;Keita S;Barry A;de Smet M;Lasry E;Smit M;Wiesner L;Barnes KI;Djimde AA;Guerin PJ;Grais RF;Doumbo OK;Etard JF
通讯作者：
Etard JF
影响因子：
4.9
作者：
Asua, Victor;Vinden, Joanna;Rosenthal, Philip J.
通讯作者：
Rosenthal, Philip J.
影响因子：
3.4
作者：
Chotsiri, Palang;Wattanakul, Thanaporn;Tarning, Joel
通讯作者：
Tarning, Joel