Maiteki-Sebuguzi Catherine, Jagannathan Prasanna, Yau Vincent M, Clark Tamara D, Njama-Meya Denise, Nzarubara Bridget, Talisuna Ambrose O, Kamya Moses R, Rosenthal Philip J, Dorsey Grant, Staedke Sarah G
Department of Medicine, Makerere University, Kampala, Uganda.
Malar J. 2008 Jun 11;7:106. doi: 10.1186/1475-2875-7-106.
Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children.
A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP), artesunate + amodiaquine (AS+AQ), or artemether-lumefantrine (AL). Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment.
Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 - 12.3 years). At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 - 9.17; weakness: RR 5.40, 95% CI 1.86 - 15.7), or AS+AQ (anorexia: RR 2.10, 95% CI 1.04 - 4.23; weakness: RR 2.26, 95% CI 1.01 - 5.05). Extending the analysis to 42 days of follow-up had little impact on the findings.
This study confirms the safety and tolerability of AS+AQ and AL in Ugandan children, and suggests that AQ+SP is safe, but less well-tolerated, particularly in younger children. As newer antimalarial regimens are deployed, collecting data on their safety and tolerability will be essential.
Current Controlled Trials Identifier ISRCTN37517549.
在非洲，推荐联合抗疟疗法用于治疗非复杂性恶性疟；然而，对于新疗法的安全性和耐受性仍存在一些担忧。本研究比较了三种联合抗疟方案在一群乌干达儿童中的安全性和耐受性。
2004年11月至2007年5月在乌干达坎帕拉对儿童进行了一项纵向、单盲、随机临床试验。一旦诊断为首次非复杂性疟疾病例，参与者被随机分配接受阿莫地喹+磺胺多辛-乙胺嘧啶（AQ+SP）、青蒿琥酯+阿莫地喹（AS+AQ）或蒿甲醚-本芴醇（AL）治疗。一旦随机分组，参与者在所有后续非复杂性疟疾病例中均接受相同方案治疗。在每次治疗后的前14天对参与者进行不良事件的主动监测，然后进行被动随访，直至其接受下一次研究药物治疗或退出研究。观察指标包括治疗后14天和42天不良事件的风险。
在601名登记儿童中，382名被诊断患有至少一次非复杂性疟疾病例并接受了研究药物治疗。治疗时的中位年龄为6.3岁（范围1.1 - 12.3岁）。在随访14天时，与AL治疗相比，AQ+SP治疗与更高的厌食、虚弱及主观发热风险相关，与AS+AQ治疗相比，有更高的虚弱及主观发热风险。AL治疗与体温升高风险较高相关。在一名参与者中检测到与AS+AQ相关的反复中性粒细胞减少发作。仅考虑五岁以下儿童，接受AQ+SP治疗的儿童发生中度或重度厌食和虚弱的风险高于接受AL治疗的儿童（厌食：RR 3.82，95%CI 1.59 - 9.17；虚弱：RR 5.40，95%CI 1.86 - 15.7），或高于接受AS+AQ治疗的儿童（厌食：RR 2.10，95%CI 1.04 - 4.23；虚弱：RR 2.26，95%CI 1.01 - 5.05）。将分析延长至随访42天对研究结果影响不大。
本研究证实了AS+AQ和AL在乌干达儿童中的安全性和耐受性，并表明AQ+SP是安全的，但耐受性较差，尤其是在幼儿中。随着更新的抗疟方案的应用，收集其安全性和耐受性数据至关重要。
当前受控试验标识符ISRCTN37517549 。
