阿莫地喹-青蒿琥酯与蒿甲醚-本芴醇治疗加纳儿童非复杂性疟疾的疗效与安全性比较：一项为期一年随访的随机对照试验

Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up.

作者信息

Adjei George O, Kurtzhals Jorgen A L, Rodrigues Onike P, Alifrangis Michael, Hoegberg Lotte C G, Kitcher Emmanuel D, Badoe Ebenezer V, Lamptey Roberta, Goka Bamenla Q

机构信息

Department of Child Health, Korle Bu Teaching Hospital, University of Ghana Medical School, P.O. Box KB 4236, Accra, Ghana.

出版信息

Malar J. 2008 Jul 11;7:127. doi: 10.1186/1475-2875-7-127.

BACKGROUND

Artesunate-amodiaquine (AS+AQ) and artemether-lumefantrine (AM-L) are efficacious artemisinin combination therapy (ACT) regimens that have been widely adopted in sub-Saharan Africa. However, there is little information on the efficacy of these regimens on subsequent episodes beyond 28 days, or on the safety of repeated treatments.

METHODS

Children aged six months to 14 years with uncomplicated malaria were randomly assigned to treatment with AS+AQ (n = 116), or AM-L (n = 111). Recruited subjects were followed-up, initially for 28 days, and then monthly for up to one year. All subsequent attacks of uncomplicated malaria after 28 days were treated with the same regimen as at randomization. Investigations aimed at determining efficacy and side effects were conducted.

RESULTS

Adequate clinical and parasitological response in subjects with evaluable end-points were, 97.1% (100/103) and 98.2% (107/109) on day 14, and 94.2% (97/103) and 95.3% (102/107) on day 28 in the AM-L and AS+AQ groups, respectively. Similar results were obtained after PCR correction. The incidence of malaria attacks in the year following recruitment was similar between the two treatment groups (p = 0.93). There was a high incidence of potentially AQ-resistant parasites in the study area. The incidence of adverse events, such as pruritus, fatigue and neutropaenia were similar in the two treatment groups. No patient showed signs of hearing impairment, and no abnormal neurological signs were observed during one year of follow-up. Other adverse events were mild in intensity and overlapped with known malaria symptomatology. No adverse event exacerbation was observed in any of the subjects who received multiple treatment courses with these ACT regimens during one year follow-up.

CONCLUSION

AS+AQ and AM-L were efficacious for treatment of children with uncomplicated malaria in Ghana and drug-related adverse events were rare in treated subjects during one year of follow-up. The high prevalence of potentially AQ resistant parasites raises questions about the utility of AQ as a partner drug for ACT in Ghana. The efficacy of AS+AQ in Ghana requires, therefore, continuous monitoring and evaluation.

TRIAL REGISTRATION

NCT 00406146 http://www.clinicaltrials.gov.

背景

青蒿琥酯-阿莫地喹（AS+AQ）和蒿甲醚-本芴醇（AM-L）是有效的青蒿素联合疗法（ACT）方案，已在撒哈拉以南非洲广泛采用。然而，关于这些方案在28天以后的后续发作中的疗效，或重复治疗的安全性，几乎没有相关信息。

方法

年龄在6个月至14岁的无并发症疟疾儿童被随机分配接受AS+AQ治疗（n = 116）或AM-L治疗（n = 111）。招募的受试者最初随访28天，然后每月随访直至一年。28天后所有后续无并发症疟疾发作均采用随机分组时的相同方案治疗。开展了旨在确定疗效和副作用的调查。

结果

在可评估终点的受试者中，AM-L组和AS+AQ组在第14天的充分临床和寄生虫学反应分别为97.1%（100/103）和98.2%（107/109），在第28天分别为94.2%（97/103）和95.3%（102/107）。经PCR校正后获得了类似结果。两个治疗组在招募后一年中的疟疾发作发生率相似（p = 0.93）。研究地区存在对AQ潜在耐药的寄生虫的高发生率。两个治疗组中瘙痒、疲劳和中性粒细胞减少等不良事件的发生率相似。没有患者出现听力损害迹象，在一年的随访期间未观察到异常神经体征。其他不良事件强度较轻，与已知的疟疾症状重叠。在一年随访期间接受这些ACT方案多个疗程治疗的任何受试者中，均未观察到不良事件加重情况。