Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest, 399 Avenue de la Liberté, 01, BP 545, Bobo-Dioulasso 01, Burkina Faso.
Yale Schools of Public Health and Medicine, Laboratory of Epidemiology and Public Health, 60 College Street, Room 724, New Haven, CT, 06520, USA.
Malar J. 2020 Jul 6;19(1):238. doi: 10.1186/s12936-020-03311-8.
Since 2014, seasonal malaria chemoprevention (SMC) with amodiaquine-sulfadoxine-pyrimethamine (AQ-SP) has been implemented on a large scale during the high malaria transmission season in Burkina Faso. This paper reports the prevalence of microscopic and submicroscopic malaria infection at the outset and after the first round of SMC in children under 5 years old in Bama, Burkina Faso, as well as host and parasite factors involved in mediating the efficacy and tolerability of SMC.
Two sequential cross-sectional surveys were conducted in late July and August 2017 during the first month of SMC in a rural area in southwest Burkina Faso. Blood smears and dried blood spots were collected from 106 to 93 children under five, respectively, at the start of SMC and again 3 weeks later. Malaria infection was detected by microscopy and by PCR from dried blood spots. For all children, day 7 plasma concentrations of desethylamodiaquine (DEAQ) were measured and CYP2C8 genetic variants influencing AQ metabolism were genotyped. Samples were additionally genotyped for pfcrt K76T and pfmdr1 N86Y, molecular markers associated with reduced amodiaquine susceptibility.
2.8% (3/106) of children were positive for Plasmodium falciparum infection by microscopy and 13.2% (14/106) by nested PCR within 2 days of SMC administration. Three weeks after SMC administration, in the same households, 4.3% (4/93) of samples were positive by microscopy and 14.0% (13/93) by PCR (p = 0.0007). CYP2C8*2, associated with impaired amodiaquine metabolism, was common with an allelic frequency of 17.1% (95% CI 10.0-24.2). Day 7 concentration of DEAQ ranged from 0.48 to 362.80 ng/mL with a median concentration of 56.34 ng/mL. Pfmdr1 N86 predominated at both time points, whilst a non-significant trend towards a higher prevalence of pfcrt 76T was seen at week 3.
This study showed a moderate prevalence of low-level malaria parasitaemia in children 3 weeks following SMC during the first month of administration. Day 7 concentrations of the active DEAQ metabolite varied widely, likely reflecting variability in adherence and possibly metabolism. These findings highlight factors that may contribute to the effectiveness of SMC in children in a high transmission setting.
自 2014 年以来，布基纳法索在疟疾高发季节大规模实施季节性疟疾化学预防（SMC），用阿莫地喹-磺胺多辛-乙胺嘧啶（AQ-SP）进行预防。本文报告了布基纳法索巴马地区儿童在开始接受 SMC 以及在第一轮 SMC 后，5 岁以下儿童的微观和亚微观疟疾感染率，以及宿主和寄生虫因素对 SMC 疗效和耐受性的影响。
2017 年 7 月下旬至 8 月，在布基纳法索西南部的一个农村地区，连续进行了两次横断面调查。在 SMC 开始时和 3 周后，分别采集了 106 至 93 名 5 岁以下儿童的 106 至 93 份血样和干血斑。通过显微镜检查和从干血斑中进行 PCR 检测来检测疟疾感染。对所有儿童，在第 7 天测量去乙基阿莫地喹（DEAQ）的血浆浓度，并对影响 AQ 代谢的 CYP2C8 遗传变异进行基因分型。此外，还对 pfcrt K76T 和 pfmdr1 N86Y 进行基因分型，这两种分子标记与降低阿莫地喹的敏感性有关。
在 SMC 给药后 2 天内，3%（3/106）的儿童通过显微镜检查和 13.2%（14/106）的巢式 PCR 检查呈恶性疟原虫感染阳性。SMC 给药 3 周后，在同一家庭中，4.3%（4/93）的样本通过显微镜检查和 14.0%（13/93）的 PCR 检查呈阳性（p=0.0007）。与阿莫地喹代谢受损相关的 CYP2C8*2 等位基因频率为 17.1%（95%CI 10.0-24.2），较为常见。第 7 天的 DEAQ 浓度范围为 0.48-362.80ng/ml，中位数为 56.34ng/ml。Pfmdr1 N86 在两个时间点均占主导地位，而第 3 周时 pfcrt 76T 的流行率呈上升趋势，但无统计学意义。
本研究显示，在 SMC 给药后 3 周内，儿童中存在中等程度的低水平疟疾寄生虫血症。活性 DEAQ 代谢物的第 7 天浓度差异很大，可能反映了药物依从性和代谢的变异性。这些发现突出了可能影响高传播环境中儿童 SMC 有效性的因素。
