Zongo Issaka, Milligan Paul, Compaore Yves Daniel, Some A Fabrice, Greenwood Brian, Tarning Joel, Rosenthal Philip J, Sutherland Colin, Nosten Francois, Ouedraogo Jean-Bosco
Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso London School of Hygiene & Tropical Medicine, London, United Kingdom
London School of Hygiene & Tropical Medicine, London, United Kingdom
Antimicrob Agents Chemother. 2015 Aug;59(8):4387-96. doi: 10.1128/AAC.04923-14. Epub 2015 Apr 27.
The WHO recommends that children living in areas of highly seasonal malaria transmission in the Sahel subregion should receive seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ). We evaluated the use of dihydroartemisinin-piperaquine (DHAPQ) as an alternative drug that could be used if SPAQ starts to lose efficacy. A total of 1,499 children 3 to 59 months old were randomized to receive SMC with SPAQ or DHAPQ over 3 months. The primary outcome measure was the risk of clinical malaria (fever or a history of fever with a parasite density of at least 3,000/μl). A cohort of 250 children outside the trial was followed up as a control group. Molecular markers of drug resistance were assessed. The risk of a malaria attack was 0.19 in the DHAPQ group and 0.15 in the SPAQ group, an odds ratio of 1.33 (95% confidence interval [CI], 1.02 to 1.72). Efficacy of SMC compared to the control group was 77% (67% to 84%) for DHAPQ and 83% (74% to 89%) for SPAQ. pfdhfr and pfdhps mutations associated with antifolate resistance were more prevalent in parasites from children who received SPAQ than in children who received DHAPQ. Both regimens were highly efficacious and well tolerated. DHAPQ is a potential alternative drug for SMC. (This trial is registered at ClinicalTrials.gov under registration no. NCT00941785.).
世界卫生组织建议，生活在萨赫勒次区域季节性疟疾传播高发地区的儿童应接受以磺胺多辛-乙胺嘧啶加阿莫地喹（SPAQ）进行的季节性疟疾化学预防（SMC）。我们评估了双氢青蒿素-哌喹（DHAPQ）作为一种替代药物的使用情况，若SPAQ开始失效则可使用该药物。共有1499名3至59个月大的儿童被随机分组，在3个月内接受以SPAQ或DHAPQ进行的SMC。主要结局指标为临床疟疾风险（发热或有发热史且寄生虫密度至少为3000/μl）。对试验外的250名儿童组成的队列进行随访作为对照组。评估了耐药性的分子标志物。DHAPQ组疟疾发作风险为0.19，SPAQ组为0.15，比值比为1.33（95%置信区间[CI]，1.02至1.72）。与对照组相比，DHAPQ进行SMC的疗效为77%（67%至84%），SPAQ为83%（74%至89%）。与抗叶酸耐药相关的pfdhfr和pfdhps突变在接受SPAQ的儿童体内的寄生虫中比在接受DHAPQ的儿童体内更为普遍。两种方案均具有高效性且耐受性良好。DHAPQ是SMC的一种潜在替代药物。（该试验已在ClinicalTrials.gov注册，注册号为NCT00941785。）
