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伊维菌素与阿苯达唑联合用药在坦桑尼亚大规模给药后抑制淋巴丝虫病传播中的疗效:一项前瞻性队列研究

Efficacy of ivermectin and albendazole combination in suppressing transmission of lymphatic filariasis following mass administration in Tanzania: a prospective cohort study.

作者信息

Fimbo Adam M, Mnkugwe Rajabu Hussein, Mlugu Eulambius Mathias, Kunambi Peter P, Malishee Alpha, Minzi Omary M S, Kamuhabwa Appolinary A R, Aklillu Eleni

机构信息

Department of Global Public Health, Karolinska Institutet at Karolinska University, Stockholm, Sweden.

Tanzania Medicines and Medical Devices Authority (TMDA), P. O, Box 77150, Dar Es Salaam, Tanzania.

出版信息

Infect Dis Poverty. 2024 Jun 12;13(1):44. doi: 10.1186/s40249-024-01214-3.

Abstract

BACKGROUND

Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health intervention to eliminate lymphatic filariasis (LF). Achieving this goal depends on drug effectiveness in reducing parasite reservoirs in the community to halt transmission. We assessed the efficacy of ivermectin and albendazole in clearing microfilariae and circulating filarial antigens (CFA) following MDA.

METHODS

This community-based prospective study was conducted in Mkinga district, Tanga region, Tanzania, from November 2018 to June 2019. A total of 4115 MDA-eligible individuals were screened for CFA using Filarial test strips. CFA positives were re-examined for microfilariae by microscopy. CFA and microfilariae positive individuals were enrolled and received IA through MDA campaign. The status of microfilariae and CFA was monitored before MDA, and on day 7 and six-month following MDA. The primary efficacy outcomes were the clearance rates of microfilariae on day 7 and six-months, and CFA at 6 months of post-MDA. The McNemar test assessed the proportions of microfilariae positive pre- and post-MDA, while Chi-square tests were utilized to examine factors associated with CFA status six months post-MDA.

RESULTS

Out of 4115 individuals screened, 239 (5.8%) tested positive for CFA, of whom 11 (4.6%) were also positive for microfilariae. Out of the ten microfilariae-positive individuals available for follow-up on day 7, nine tested negative, yielding a microfilariae clearance rate of 90% [95% confidence interval (CI): 59.6-98.2%]. Participants who tested negative for microfilariae on day 7 remained free of microfilariae six months after MDA. However, those who did not clear microfilariae on day-7 remained positive six-months post-MDA. The McNemar test revealed a significant improvement in microfilariae clearance on day 7 following MDA (P = 0.02). Out of 183 CFA-positive individuals who were available at 6-month follow-up, 160 (87.4%) remained CFA positive, while 23 became CFA negative. The CFA clearance rate at 6 months post-MDA was 12.6% (95% CI: 8.5-8.5%). There was no significant association of variability in ivermectin plasma exposure, measured by maximum concentration or area under the curve, and the clearance status of microfilariae or CFA post-MDA.

CONCLUSIONS

Preventive chemotherapy with IA effectively clears microfilariae within a week. However, it is less effective in clearing CFA at six months of post-MDA. The low clearance rate for filarial antigenemia underscores the need for alternative drug combinations and additional preventive measures to achieve LF elimination by 2030.

摘要

背景

在针对所有高危人群的群体药物给药(MDA)项目中,使用伊维菌素和阿苯达唑(IA)进行预防性化疗是消除淋巴丝虫病(LF)的核心公共卫生干预措施。实现这一目标取决于药物在减少社区寄生虫储存库以阻止传播方面的有效性。我们评估了伊维菌素和阿苯达唑在MDA后清除微丝蚴和循环丝虫抗原(CFA)的疗效。

方法

这项基于社区的前瞻性研究于2018年11月至2019年6月在坦桑尼亚坦噶地区的姆金加区进行。共有4115名符合MDA条件的个体使用丝虫检测试纸进行CFA筛查。CFA阳性者通过显微镜重新检查微丝蚴。CFA和微丝蚴阳性个体被纳入并通过MDA活动接受IA。在MDA前、MDA后第7天和6个月监测微丝蚴和CFA的状态。主要疗效指标是MDA后第7天和6个月时微丝蚴的清除率,以及MDA后6个月时CFA的清除率。McNemar检验评估MDA前后微丝蚴阳性的比例,而卡方检验用于检查与MDA后6个月CFA状态相关的因素。

结果

在4115名筛查个体中,239人(5.8%)CFA检测呈阳性,其中11人(4.6%)微丝蚴也呈阳性。在第7天可供随访的10名微丝蚴阳性个体中,9人检测为阴性,微丝蚴清除率为90%[95%置信区间(CI):59.6 - 98.2%]。在第7天微丝蚴检测为阴性的参与者在MDA后6个月仍未发现微丝蚴。然而,那些在第7天未清除微丝蚴的参与者在MDA后6个月仍呈阳性。McNemar检验显示MDA后第7天微丝蚴清除率有显著改善(P = 0.02)。在6个月随访时可获得的183名CFA阳性个体中,160人(87.4%)仍为CFA阳性,23人变为CFA阴性。MDA后6个月时CFA清除率为12.6%(95% CI:8.5 - 16.7%)。通过最大浓度或曲线下面积测量的伊维菌素血浆暴露变异性与MDA后微丝蚴或CFA的清除状态之间没有显著关联。

结论

IA预防性化疗可在一周内有效清除微丝蚴。然而,在MDA后6个月清除CFA的效果较差。丝虫抗原血症的低清除率凸显了需要替代药物组合和额外的预防措施以在2030年前实现消除LF的目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2028/11167743/47a2eaf7c038/40249_2024_1214_Fig1_HTML.jpg

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