在坦桑尼亚，使用青蒿琥酯-咯萘啶治疗的五岁以下儿童中，第 7 天血中咯萘啶浓度对疟疾治疗结局的预测作用。

Usefulness of day 7 lumefantrine plasma concentration as a predictor of malaria treatment outcome in under-fives children treated with artemether-lumefantrine in Tanzania.

机构信息

Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P. O. BOX 65013, Dar es Salaam, Tanzania.

Department of Research, National Institute of Medical Research, Tanga Centre, P O Box 5004, Tanga, Tanzania.

出版信息

Malar J. 2020 Feb 11;19(1):66. doi: 10.1186/s12936-020-3150-y.

DOI:10.1186/s12936-020-3150-y

PMID:32046718

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7014606/

Abstract

BACKGROUND

Day 7 plasma lumefantrine concentration is suggested as a predictor for malaria treatment outcomes and a cut-off of ≥ 200 ng/ml is associated with day 28 cure rate in the general population. However, day 7 lumefantrine plasma concentration can be affected by age, the extent of fever, baseline parasitaemia, and bodyweight. Therefore, this study assessed the usefulness of day 7 lumefantrine plasma concentration as a predictor of malaria treatment outcome in under-fives children treated with generic or innovator drug-containing artemether-lumefantrine (ALu) in Tanzania.

METHODS

This study was nested in an equivalence prospective study that aimed at determining the effectiveness of a generic ALu (Artefan) in comparison with the innovator's product (Coartem). Children with uncomplicated malaria aged 6-59 months were recruited and randomized to receive either generic or innovator's product. Children were treated with ALu as per World Health Organization recommendations. The clinical and parasitological outcomes were assessed after 28 days of follow up. PCR was performed to distinguish recrudescence and re-infections among children with recurrent malaria. Analysis of day 7 lumefantrine plasma concentration was carried out using a high-performance liquid chromatographic method with UV detection.

RESULTS

The PCR corrected cure rates were 98.7% for children treated with generic and 98.6% for those treated with the innovator product (p = 1.00). The geometric mean (± SD) of day 7 plasma lumefantrine concentration was 159.3 (± 2.4) ng/ml for the generic and 164 (± 2.5) ng/ml for the innovator groups, p = 0.87. Geometric mean (± SD) day 7 lumefantrine plasma concentration between cured and recurrent malaria was not statistically different in both treatment arms [158.5 (± 2.4) vs 100.0 (± 1.5) ng/ml, (p = 0.28) for generic arm and 158.5 (± 2.3) vs 251.2 (± 4.2) ng/ml, (p = 0.24) for innovator arm]. Nutritional status was found to be a determinant of recurrent malaria (adjusted hazardous ratio (95% confidence interval) = 3(1.1-8.2), p = 0.029.

CONCLUSION

Using the recommended cut-off point of ≥ 200 ng/ml, day 7 plasma lumefantrine concentration failed to predict malaria treatment outcome in children treated with ALu in Tanzania. Further studies are recommended to establish the day 7 plasma lumefantrine concentration cut-off point to predict malaria treatment outcome in children.

摘要

背景

第 7 天的血浆中咯萘啶浓度被认为是预测疟疾治疗结果的指标，一般人群中，浓度≥200ng/ml 与第 28 天的治愈率相关。然而，第 7 天的咯萘啶血浆浓度会受到年龄、发热程度、基线寄生虫载量和体重的影响。因此，本研究评估了第 7 天的血浆中咯萘啶浓度作为预测坦桑尼亚接受含青蒿素-咯萘啶通用或创新药物治疗的 5 岁以下儿童疟疾治疗结果的指标的有用性。

方法

本研究嵌套在一项等效性前瞻性研究中，旨在确定通用青蒿素-咯萘啶（Artefan）与创新产品（Coartem）的疗效。招募了年龄在 6-59 个月的患有无并发症疟疾的儿童，并将其随机分配接受通用或创新产品的治疗。儿童按照世界卫生组织的建议接受青蒿素-咯萘啶治疗。在 28 天的随访后评估临床和寄生虫学结局。对于出现复发性疟疾的儿童，采用聚合酶链反应（PCR）来区分复发和再感染。使用高效液相色谱法结合紫外检测法对第 7 天的血浆中咯萘啶浓度进行分析。

结果

接受通用药物治疗的儿童 PCR 校正治愈率为 98.7%，接受创新产品治疗的儿童为 98.6%（p=1.00）。第 7 天的血浆中咯萘啶浓度的几何平均值（±标准差）在通用组为 159.3（±2.4）ng/ml，在创新组为 164（±2.5）ng/ml，p=0.87。在两个治疗组中，治愈和复发性疟疾之间的第 7 天的血浆中咯萘啶浓度的几何平均值（±标准差）没有统计学差异[通用组为 158.5（±2.4）比 100.0（±1.5）ng/ml，（p=0.28），创新组为 158.5（±2.3）比 251.2（±4.2）ng/ml，（p=0.24）]。研究发现营养状况是复发性疟疾的一个决定因素（调整后的危险比（95%置信区间）=3（1.1-8.2），p=0.029）。