Mali International Center for Excellence in Research: Filariasis

马里国际卓越研究中心：丝虫病

• 批准号: 8946450
• 负责人: Thomas Nutman
• 金额: $ 9.46万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8946450
• 关键词: 5 year old; 7 year old; Address; Adult; Age-Years; Albendazole; Anopheles Genus; Antibodies; Antibody Formation; Antigens; Area; Bite; Blood; Breast Feeding; Child; Clinical; Communicable Diseases; Country; Culicidae; Data; Deglutition; Dentistry; Developing Countries; Emerging Communicable Diseases; Endemic Diseases; Faculty; Filaria bancrofti; Filarial Elephantiases; Filariasis; Fostering; Future; Goals; HIV; Human; Hydrocele; IgG4; India; Individual; Infection; Institution; Instruction; Interruption; Ivermectin; Larva; Lymphedema; Malaria; Mali; Measures; Medicine; Microfilaria; Monitor; Participant; Pharmaceutical Preparations; Pharmacy facility; Physicians; Population; Prevalence; Questionnaires; Reporting; Research; Scientist; Survey Methodology; Surveys; Testing; Thick; Training; Tuberculosis; Uganda; Universities; Woman; aged; base; burden of illness; international center; laboratory facility; man; meetings; men; non-compliance; pregnant; programs; tool; transmission process; trend; volunteer

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of stopping transmission of lymphatic filariasis (LF) through yearly mass drug administration (MDA). Preliminary surveys of the human population in Mali suggested that Wuchereria bancrofti (W. bancrofti) infection was highly endemic in the Sikasso district. W. bancrofti prevalence and transmission in this region were confirmed in baseline human and entomologic studies in 6 villages in 2001 (prior to the start of yearly MDA with albendazole and ivermectin) and monitored yearly from 2002 to 2007 during MDA. Microfilaremia was determined by calibrated thick smear of night blood in adult volunteers and circulating filarial antigen was measured using the ICT test in children <5 years old. Mosquitoes were collected by human landing catch from July to December. None of the 686 subjects tested were microfilaremic 12 months after the 6th MDA round. More importantly, circulating antigen was not detected in any of the 120 children tested, as compared to 53% (103/194) prior to the institution of MDA. The number of infective bites/man/year decreased from 4.8 in 2002 to 0.04 in 2007. Although these data were consistent with ongoing transmission at a very low level, they met criteria for transmission interruption based on current WHO transmission assessment survey (TAS). To assess the utility of TAS approach, we used standard TAS methodology (ICT positive prevalence in 6-7 year olds) and compared it to xenomonitoring, night blood microfilariae counts and IgG4 antibody to Wb123 (for the last 3 years) over a five year period (2009-2014) following the cessation of MDA in 6 villages in the region of Sikasso in southern Mali. In 2009 (at the start of the surveillance period) all 289 children aged 6-7 years were negative for circulating filarial antigen (CFA) by ICT, by calibrated thick smears of blood collected at night, and by IgG4 antibody to Wb123. Despite this, 2/4391 (0.11%) dissected mosquitoes were positive for larvae of Wuchereria bancrofti (Wb). In 2011, there was a CFA prevalence by ICT of 2.6% (8/301) in the 6-7 year olds, a prevalence of 1.09% (1/92) for antibody responses to Wb123, but negative xenomonitoring. In the subsequent 2 years (2012 and 2013), there were consistent and significant increases in the prevalence of CFA (Trend Chi2= 11.49, p=0.0007) to 3.9% (11/285) in 2012, and 4.1% (13/316) and in the prevalence of anti-Wb123 IgG4 to 3.2% (10/316) in 2013. Despite this increase in both ICT and Wb123 IgG4 antibody prevalence, no infected anopheles mosquito was found in 2011, 2012 and 2013. These data suggest that despite having met the criteria for cessation of MDA at the beginning of the surveillance, that there appears to be low level emergence of Wb transmission and that antibody monitoring may provide a better early warning tool than more standard TAS tools. To begin to identify potential causes for re-emergence of infection after apparently successful transmission interruption as assessed by TAS, a questionnaire was administered to randomly selected adult residents of the six villages to assess the prevalence of and reasons for systematic non-compliance with MDA. Coverage rates in the villages ranged from 67% to 89.6% over the 7 years of MDA and all stopping criteria were met at the beginning of the surveillance period. A total of 486 subjects (170 men and 316 women) were questioned, of whom 16.1% (79/486) reported never swallowing MDA drugs. The most common reasons given were being unaware of MDA (24/486; 4.9%), being pregnant or breast-feeding (8/486; 1.6%) and not willing to take the drugs (6/486; 1.2%). Although systematic non-compliers were more likely to be younger OR = 1.7 (1.006-2.921) for individuals 15-30 vs. >30 years of age, compliant and systematically non-compliant subjects were similar with respect to participants instruction level OR = 1.2 (0.59-2.51) and the presence of lymphoedema / hydrocele OR = 0.5 (0.11-2.63). These data suggest that significant rates of systematic non-compliance can be present despite adequate overall coverage rates. Whether persistent infection in systematic non-compliers provided the reservoir for re-emergence of transmission in the 6 study villages requires further study.

消除淋巴丝虫病（GPELF）的全球计划于2000年启动，目的是通过年度大规模药物管理局（MDA）停止淋巴丝虫病（LF）的传播。对马里人口的初步调查表明，西卡索地区的Wuchereria Bancrofti（W。Bancrofti）感染是高度流行的。 在2001年的6个村庄的基线人类和昆虫学研究中，Bancrofti的患病率和传播已得到证实（在MDA与Albendazole和ivermectin的年度MDA开始之前），并从2002年至2007年在MDA期间每年进行监测。通过校准成人志愿者的夜血的厚涂片来确定微毛皮血症，并使用5岁儿童的ICT测试测量循环丝状抗原。从7月至12月，人类着陆收集收集了蚊子。 686名受试者在第六次MDA回合后12个月均未进行过微量流行病。更重要的是，在接受测试的120名儿童中，未检测到循环抗原，而MDA机构之前的53％（103/194）。感染性叮咬的数量/人/年的数量从2002年的4.8降低到2007年的0.04。尽管这些数据与持续的传播相一致，但它们符合基于当前WHO传输评估调查（TAS）的当前传输中断标准。 To assess the utility of TAS approach, we used standard TAS methodology (ICT positive prevalence in 6-7 year olds) and compared it to xenomonitoring, night blood microfilariae counts and IgG4 antibody to Wb123 (for the last 3 years) over a five year period (2009-2014) following the cessation of MDA in 6 villages in the region of Sikasso in southern Mali.在2009年（监视期开始时），所有289名6-7岁的儿童对ICT的循环丝状抗原（CFA）均为阴性，夜间收集的血液的厚厚厚厚，以及对WB123的IgG4抗体。尽管如此，解剖的2/4391（0.11％）的蚊子对Wucheria Bancrofti（WB）的幼虫呈阳性。 2011年，6-7岁的年龄段的ICT患病率为2.6％（8/301），对WB123的抗体反应的患病率为1.09％（1/92），但负honomonitoring为负。在随后的2年（2012年和2013年）中，CFA（趋势CHI2 = 11.49，p = 0.0007）的患病率持续且显着提高，2012年至3.9％（11/285），4.1％（13/316）（13/316）以及抗抗W-WB123 IGG4至3.2％（13/316）的患病率（13/316）和10/316（10/10/10/10/10/10/10/10/10）。 WB123 IgG4抗体患病率，在2011年，2012年和2013年没有被感染的蚊子蚊。这些数据表明，在监视开始时符合MDA的标准，但在监视开始时，WB传输的出现似乎很低，并且该抗体监测可能会提供更好的早期Warning Warning Warning工具。 为了确定TAS评估的显然成功传播中断后的潜在原因导致感染的重新出现，对六个村庄的随机选择的成年居民进行了调查表，以评估与MDA系统不合规的流行和原因。在MDA的7年中，村庄的覆盖率在67％至89.6％之间，并且在监视期开始时满足了所有停止标准。共有486名受试者（170名男性和316名女性）受到质疑，其中16.1％（79/486）报告说从未吞咽MDA药物。给出的最常见原因是不知道MDA（24/486; 4.9％），怀孕或母乳喂养（8/486; 1.6％），并且不愿意服用药物（6/486; 1.2％）。 尽管对于参与者的教学水平或= 1.2（0.59-2.51），对15-30 vs.> 30岁的个人而言，有系统的不完整者更可能年轻或= 1.7（1.006-2.921），但合规性和系统性不完整的受试者相似。这些数据表明，尽管总体覆盖率足够，但仍可以存在明显的系统不合规率。 在系统不完整的人中，是否持续感染为6个研究村庄的传播重新出现提供了储层，都需要进一步研究。