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在坦桑尼亚姆万扎,青蒿琥酯-本芴醇和双氢青蒿素-哌喹治疗非复杂性恶性疟原虫疟疾感染儿童的疗效

Artemether-lumefantrine and dihydroartemisinin-piperaquine treatment outcomes among children infected with uncomplicated Plasmodium falciparum malaria in Mwanza, Tanzania.

作者信息

Marwa Karol J, Konje Eveline T, Kapesa Anthony, Kamugisha Erasmus, Mwita Stanley, Swedberg Göte

机构信息

Department of Pharmacology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.

Department of Epidemiology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.

出版信息

Trop Med Health. 2021 Nov 27;49(1):94. doi: 10.1186/s41182-021-00383-3.

Abstract

BACKGROUND

Artemisinin based combination therapies (ACTs) have been a cornerstone in the treatment of malaria in the world. A rapid decline in dihydroartemisinin piperaquine (DHP) and artemether lumefantrine (ALU) efficacies has been reported in some parts of South East Asia, the historical epicenter for the antimalarial drug resistance. Prolonged drug use is associated with selection of resistant parasites due to exposure to inadequate drug levels hence effects on treatment outcomes in malaria. ALU and DHP are used as first line and alternative first line, respectively, in Tanzania. This study was carried in Igombe, Tanzania to assess the efficacies of ALU and DHP in routine treatment of uncomplicated malaria among children.

METHODS

This was a prospective study involving children up to 10 years and followed up for 28 and 35 days as per the WHO protocol, 2015 for monitoring antimalarial drug efficacy. The primary end points were crude and adjusted Adequate Clinical and Parasitological Response (ACPR), parasite clearance rate and reported adverse events.

RESULTS

A total of 205 children with uncomplicated malaria were enrolled. One hundred and sixteen participants were treated with ALU, while 89 participants were treated with DHP. Two participants in the ALU group were lost within the 24 h of follow-up. The PCR unadjusted ACPR was108 (94.7%) for ALU and 88 (98.9%) for DHP, while the PCR adjusted ACPR was 109(95.6%) and 88(98.9%) for ALU and DHP, respectively, at 28 day follow-up. No treatment failure was observed in both groups. Cumulative risk of recurrent parasitemia was similar in both groups (p = 0.32). Age and parasite density were strong predictors for persistent day 1 parasitemia (p = 0.034 and 0.026, respectively). Nausea and vomiting, abdominal pain and headache were the most clinical adverse events reported in both groups of patients.

CONCLUSION

The present study shows that ALU and DHP are still efficacious after more than a decade of use with PCR corrected efficacies greater than 95% implying a failure rate less than 5% which is below the WHO minimum threshold requirement for recommendation of a change in the treatment policy. Both drugs were well tolerated with no major adverse events reported.

摘要

背景

以青蒿素为基础的联合疗法(ACTs)一直是全球疟疾治疗的基石。在东南亚部分地区,曾是抗疟药物耐药性的历史高发中心,已有报告称双氢青蒿素哌喹(DHP)和蒿甲醚苯芴醇(ALU)的疗效迅速下降。由于药物水平不足,长期用药与耐药寄生虫的选择有关,从而影响疟疾的治疗效果。在坦桑尼亚,ALU和DHP分别用作一线和替代一线药物。本研究在坦桑尼亚的伊贡贝进行,以评估ALU和DHP在儿童非复杂性疟疾常规治疗中的疗效。

方法

这是一项前瞻性研究,纳入了10岁以下的儿童,并按照2015年世界卫生组织的方案进行了28天和35天的随访,以监测抗疟药物的疗效。主要终点是粗略和校正后的充分临床和寄生虫学反应(ACPR)、寄生虫清除率以及报告的不良事件。

结果

共纳入205例非复杂性疟疾儿童。116名参与者接受了ALU治疗,而89名参与者接受了DHP治疗。ALU组有两名参与者在随访的24小时内失访。在28天随访时,ALU的PCR未校正ACPR为108例(94.7%),DHP为88例(98.9%);而ALU和DHP的PCR校正ACPR分别为109例(95.6%)和88例(98.9%)。两组均未观察到治疗失败。两组复发性寄生虫血症的累积风险相似(p = 0.32)。年龄和寄生虫密度是第1天持续性寄生虫血症的有力预测因素(分别为p = 0.034和0.026)。恶心和呕吐、腹痛和头痛是两组患者报告的最常见临床不良事件。

结论

本研究表明,在使用十多年后,ALU和DHP仍然有效,PCR校正后的疗效大于95%,这意味着失败率低于5%,低于世界卫生组织推荐改变治疗政策的最低阈值要求。两种药物耐受性良好,未报告重大不良事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a08/8627025/2f2e4f238ad5/41182_2021_383_Fig1_HTML.jpg

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