Muhindo Mary K, Kakuru Abel, Jagannathan Prasanna, Talisuna Ambrose, Osilo Emmanuel, Orukan Francis, Arinaitwe Emmanuel, Tappero Jordan W, Kaharuza Frank, Kamya Moses R, Dorsey Grant
Infectious Diseases Research Collaboration, Mulago Hospital Campus, PO Box 7475, Kampala, Uganda.
Malar J. 2014 Jan 28;13:32. doi: 10.1186/1475-2875-13-32.
Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance.
Data from a cohort of Ugandan children four to five years old, enrolled in a longitudinal, randomized, clinical trial comparing two leading ACT, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), were analysed. For all episodes of uncomplicated P. falciparum malaria over a 14-month period, daily blood smears were performed for three days following the initiation of therapy. Associations between pre-treatment variables of interest and persistent parasitaemia were estimated using multivariate, generalized, estimating equations with adjustment for repeated measures in the same patient.
A total of 202 children were included, resulting in 416 episodes of malaria treated with AL and 354 episodes treated with DP. The prevalence of parasitaemia on days 1, 2, and 3 following initiation of therapy was 67.6, 5.6 and 0% in those treated with AL, and 52.2, 5.7 and 0.3% in those treated with DP. Independent risk factors for persistent parasitaemia on day 1 included treatment with AL vs DP (RR = 1.34, 95% CI 1.20-1.50, p < 0.001), having a temperature ≥38.0°C vs < 37.0°C (RR = 1.19, 95% CI 1.05-1.35, p = 0.007) and having a parasite density >20,000/μL vs <4,000/μL (RR = 3.37, 95% CI 2.44-4.49, p < 0.001). Independent risk factors for having persistent parasitaemia on day 2 included elevated temperature, higher parasite density, and being HIV infected.
Among Ugandan children, parasite clearance following treatment with AL or DP was excellent with only one of 752 patients tested having a positive blood slide three days after initiation of therapy. The type of ACT given, pre-treatment temperature, pre-treatment parasite density and HIV status were associated with differences in persistent parasitaemia, one or two days following therapy.
Current Controlled Trials Identifier NCT00527800.
基于青蒿素的联合疗法（ACT）被广泛推荐为全球范围内无并发症恶性疟原虫疟疾的一线治疗方法。目前在东南亚已报告出现青蒿素耐药性，其临床表型为寄生虫清除缓慢。尽管非洲尚无青蒿素耐药性的确切报告，但有必要更好地了解接受ACT治疗的非洲儿童体内寄生虫清除的动态情况，以便更好地检测青蒿素耐药性的出现。
分析了乌干达4至5岁儿童队列的数据，这些儿童参与了一项纵向、随机临床试验，比较两种主要的ACT，即蒿甲醚-本芴醇（AL）和双氢青蒿素-哌喹（DP）。在14个月期间，对于所有无并发症恶性疟原虫疟疾发作，在开始治疗后的三天内每天进行血涂片检查。使用多变量广义估计方程，并对同一患者的重复测量进行调整，以估计感兴趣的治疗前变量与持续性寄生虫血症之间的关联。
共纳入202名儿童，导致用AL治疗416例疟疾发作，用DP治疗354例发作。在开始治疗后的第1、2和3天，接受AL治疗的患者寄生虫血症患病率分别为67.6%、5.6%和0%，接受DP治疗的患者分别为52.2%、5.7%和0.3%。第1天持续性寄生虫血症的独立危险因素包括接受AL治疗而非DP治疗（RR = 1.34，95% CI 1.20 - 1.50，p < 0.001）、体温≥38.0°C而非<37.0°C（RR = 1.19，95% CI 1.05 - 1.35，p = 0.007）以及寄生虫密度>20,000/μL而非<4,000/μL（RR = 3.37，95% CI 2.44 - 4.49，p < 0.001）。第2天持续性寄生虫血症的独立危险因素包括体温升高（RR = 1.19，95% CI 1.05 - 1.35，p = 0.007）、寄生虫密度较高（RR = 3.37，95% CI 2.44 - 4.49，p < 0.001）和感染HIV（RR = 1.19，95% CI 1.05 - 1.35，p = 0.007）。
在乌干达儿童中，用AL或DP治疗后寄生虫清除情况良好，752名接受检测的患者中只有1人在开始治疗三天后血涂片呈阳性。所给予的ACT类型、治疗前体温、治疗前寄生虫密度和HIV状态与治疗后一天或两天的持续性寄生虫血症差异有关。
当前受控试验标识符NCT00527800。
