Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria.
Malar J. 2010 Nov 22;9:335. doi: 10.1186/1475-2875-9-335.
Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance. Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) are efficacious regimens that have been widely adopted in sub-Saharan Africa. However, most study designs ignore the effects of these regimens on peripheral parasitaemia in the first 24 hours of therapy. The study protocol was designed to evaluate more closely the early effects and the standard measures of efficacies of these two regimens.
In an open label, randomized controlled clinical trial, children aged 12 months to 132 months were randomized to receive AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days. Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h, and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic identification and quantification of Plasmodium falciparum.
A total of 193 children were randomized to receive either AL (97) or AA (96). In children that received both medications, early response of peripheral parasitaemia showed that 42% of children who received AL and 36.7% of those who received AA had an immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a rapid fall. The rise in parasitaemia was significant and seems to suggest a mobilization of asexual parasites from the deep tissues to the periphery. Days 3, 7, 14, 28, and 42 cure rates in the per protocol (PP) population were > 90% in both groups of children. Both drug combinations were well tolerated with minimal side effects.
The study showed the high efficacy of AL and AA in Nigerian children. In addition the study demonstrated the mobilisation of asexual parasites from the deep to the periphery in the early hours of commencing ACT treatment in a subset of patients in both study groups. It is unclear whether the early parasite dynamics discovered in this study play any role in the development of drug resistance and thus it is important to further evaluate this discovery. It may be useful for studies investigating delay in parasite clearance of artemisinin derivatives as a way of monitoring the development of resistance to artemisinin to assess the early effects of the drugs on the parasites.
联合治疗方案，最好包含青蒿素衍生物，被推荐用于提高疗效和预防疟原虫耐药性。青蒿琥酯-咯萘啶（AL）和青蒿琥酯-阿莫地喹（AA）是在撒哈拉以南非洲广泛采用的有效方案。然而，大多数研究设计忽略了这些方案在治疗的前 24 小时内对周围寄生虫血症的影响。本研究方案旨在更密切地评估这两种方案的早期效果和标准疗效指标。
在一项开放标签、随机对照临床试验中，年龄在 12 个月至 132 个月的儿童被随机分为接受 AL（5-14 kg，1 片；15-24 kg，2 片；25-34 kg，3 片，每日 2 次）或青蒿琥酯（4mg/kg，每日 1 次）加阿莫地喹（10mg/kg，每日 1 次）治疗 3 天。在第 1 天的前 4 小时、8 小时、16 小时、24 小时以及第 2 至 7 天的每小时进行外周血涂片，并在第 7、14、21、28、35 和 42 天进行显微镜鉴定和定量检测疟原虫。
共有 193 名儿童被随机分为接受 AL（97 名）或 AA（96 名）治疗。在接受两种药物治疗的儿童中，早期外周寄生虫血症的反应表明，42%接受 AL 治疗的儿童和 36.7%接受 AA 治疗的儿童在治疗后 0-4 小时内出现外周寄生虫血症立即升高（治疗后），随后迅速下降。寄生虫血症的升高具有显著意义，似乎表明无寄生虫从深部组织向周围移动。在符合方案人群中，第 3、7、14、28 和 42 天的治愈率均>90%。两组儿童均耐受良好，副作用极小。
本研究表明 AL 和 AA 在尼日利亚儿童中具有很高的疗效。此外，该研究还表明，在 ACT 治疗开始后的早期小时内，两组研究对象中的一部分患者的无寄生虫从深部向周围移动。目前尚不清楚这种早期寄生虫动力学在耐药性的发展中是否起作用，因此进一步评估这一发现非常重要。这可能有助于研究延迟青蒿素衍生物清除率作为监测对青蒿素耐药性发展的一种方法，以评估药物对寄生虫的早期影响。
