背景:在针对所有高危人群的大规模药物管理(MDA)计划中,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清除MDA后的微丝虫和循环丝虫抗原(CFA)中的功效。
方法:这项基于社区的前瞻性研究在姆金加地区进行,Tanga地区,坦桑尼亚,从2018年11月到2019年6月。使用Filarial试纸条对总共4115名符合MDA资格的个体进行了CFA筛选。通过显微镜重新检查CFA阳性的微丝虫。CFA和微丝虫阳性个体被招募并通过MDA运动接受IA。MDA前监测微丝虫和CFA的状态,在MDA之后的第7天和第6个月。主要疗效结果是第7天和第6个月的微丝虫清除率,MDA后6个月的CFA。McNemar试验评估了MDA前和后的微丝虫阳性比例,而卡方检验用于检查MDA后六个月与CFA状态相关的因素。
结果:在筛选的4115个人中,239(5.8%)CFA检测呈阳性,其中11人(4.6%)也为微丝虫阳性。在第7天可进行随访的10个微丝虫阳性个体中,有9个测试为阴性,产生90%的微丝虫清除率[95%置信区间(CI):59.6-98.2%]。在第7天测试微丝虫阴性的参与者在MDA后六个月没有微丝虫。然而,在第7天未清除微丝虫的患者在MDA后6个月保持阳性。McNemar测试表明,MDA后第7天,微丝虫的清除率显着提高(P=0.02)。在6个月随访的183名CFA阳性患者中,160(87.4%)保持CFA阳性,而23例成为CFA阴性。MDA后6个月的CFA清除率为12.6%(95%CI:8.5-8.5%)。伊维菌素血浆暴露的变异性没有显着关联,通过曲线下的最大浓度或面积来衡量,以及MDA后微丝虫或CFA的清除状态。
结论:IA预防性化疗可在一周内有效清除微丝虫。然而,在MDA后六个月清除CFA的效果较差。丝虫病抗原血症的清除率较低,这突出表明需要替代药物组合和额外的预防措施,以实现到2030年消除LF。
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.