蒿甲醚-本芴醇在三种不同化学预防方案背景下治疗非复杂性疟疾的疗效和安全性。

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria in the setting of three different chemopreventive regimens.

作者信息

Kapisi James, Bigira Victor, Clark Tamara, Kinara Stephen, Mwangwa Florence, Achan Jane, Kamya Moses, Soremekun Seyi, Dorsey Grant

机构信息

Infectious Diseases Research Collaboration, Mulago Hospital Complex, PO Box 7475, Kampala, Uganda.

Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA.

出版信息

Malar J. 2015 Feb 5;14:53. doi: 10.1186/s12936-015-0583-9.

DOI:10.1186/s12936-015-0583-9

PMID:25652127

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4333162/

Abstract

BACKGROUND

The burden of malaria remains high for children in parts of Africa despite the use of insecticide-treated bed nets (ITNs). Chemoprevention has the potential of reducing the malaria burden; however, limited data exist on the efficacy and safety of anti-malarial therapy in the setting of chemoprevention.

METHODS

600 children 4-5 months of age were enrolled in Tororo, Uganda, an area of high transmission intensity. Participants were given ITNs, and caregivers instructed to bring their child to a study clinic whenever they were ill. Starting at six months of age, 579 were randomized to no chemoprevention, monthly sulphadoxine-pyrimethamine (SP), daily trimethoprim-sulphamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered unsupervised at home until 24 months of age. Episodes of uncomplicated malaria were treated with artemether-lumefantrine (AL) with active follow-up for 28 days. The cumulative risk of recurrent malaria within 84 days and the risk of adverse events within 28 days were compared across study arms using a Cox proportional hazards model and generalized estimating equations, respectively.

RESULTS

A total of 1007, 919, 736, and 451 episodes of malaria were treated in the no chemoprevention, SP, TS, and DP arms, respectively. Only 19 (0.6%) treatments were for severe malaria. Early response to therapy with AL was excellent with 96.5% fever clearance and 99.4% parasite clearance by day 3. However, over 50% of AL treatments were followed by recurrent parasitaemia within 28 days. Compared to the no chemoprevention arm, the cumulative risk of recurrent malaria within 84 days following treatment of uncomplicated malaria with AL was significantly lower in the DP arm (HR = 0.77, 95% CI 0.63-0.95, p = 0.01) but not the SP or TS arms. Compared to the no chemoprevention arm, none of the chemopreventive regimens were associated with an increased risk of adverse events following treatment of malaria with AL.

CONCLUSIONS

The risk of severe malaria was very low in this cohort of young children living in a high transmission setting. In the setting of chemoprevention, treatment of uncomplicated malaria with AL was safe and efficacious, with moderate protection against recurrent malaria among children assigned monthly DP.

TRIAL REGISTRATION

ClinicalTrials.gov NCT00948896 .

摘要

背景

尽管使用了经杀虫剂处理的蚊帐（ITN），非洲部分地区儿童的疟疾负担仍然很高。化学预防有降低疟疾负担的潜力；然而，关于化学预防背景下抗疟治疗的疗效和安全性的数据有限。

方法

在乌干达托罗罗（疟疾高传播强度地区）招募了600名4 - 5个月大的儿童。参与者获得了ITN，并指导看护者在孩子生病时将其带到研究诊所。从6个月大开始，579名儿童被随机分为不进行化学预防组、每月服用磺胺多辛 - 乙胺嘧啶（SP）组、每日服用甲氧苄啶 - 磺胺甲恶唑（TS）组或每月服用双氢青蒿素 - 哌喹（DP）组。研究药物在无监督的情况下在家中给药，直至24个月大。非复杂性疟疾病例用蒿甲醚 - 本芴醇（AL）治疗，并进行28天的积极随访。使用Cox比例风险模型和广义估计方程分别比较各研究组在84天内复发性疟疾的累积风险和28天内不良事件的风险。

结果

在不进行化学预防组、SP组、TS组和DP组中分别治疗了1007、919、736和451例疟疾病例。只有19例（0.6%）治疗的是重症疟疾。AL治疗的早期反应良好，到第3天时发热清除率为96.5%，寄生虫清除率为99.4%。然而，超过50%的AL治疗在28天内出现寄生虫血症复发。与不进行化学预防组相比，在使用AL治疗非复杂性疟疾后84天内复发性疟疾的累积风险在DP组显著较低（HR = 0.77，95% CI 0.63 - 0.95，p = 0.01），但在SP组或TS组中并非如此。与不进行化学预防组相比，在使用AL治疗疟疾后，没有一种化学预防方案与不良事件风险增加相关。