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.

消除淋巴丝虫病全球方案于2000年启动，目标是通过每年大规模药物管理来阻止淋巴丝虫病的传播。对马里人口的初步调查表明，班氏吴策线虫（W.班克罗夫特）感染在锡卡索地区是高度地方性的。 W. 2001年（在阿苯达唑和伊维菌素的年度MDA开始之前），在6个村庄的基线人类和昆虫学研究中证实了该地区班氏体的流行和传播，并在MDA期间从2002年至2007年每年监测。用校正后的厚片夜血涂片法测定成人志愿者的微丝蚴血症，用ICT法测定<5岁儿童的循环丝虫抗原。从7月到12月，通过人类登陆捕获收集蚊子。在第6轮MDA后12个月，686名受试者中无一人出现微丝蚴血症。更重要的是，在120名接受检测的儿童中，没有检测到循环抗原，相比之下，在建立MDA之前，这一比例为53%（103/194）。感染性咬伤人数从2002年的4.8人/年下降到2007年的0.04人/年。尽管这些数据与正在进行的非常低水平的传播相一致，但它们符合基于当前世卫组织传播评估调查（TAS）的传播中断标准。 为了评估TAS方法的效用，我们使用标准TAS方法（6-7奥尔兹ICT阳性患病率），并将其与马里南部Sikasso地区6个村庄停止MDA后5年（2009-2014年）内的异种监测、夜间血微丝蚴计数和Wb 123 IgG 4抗体（过去3年）进行比较。2009年（监测期开始时），所有289名6-7岁儿童的循环丝虫抗原（CFA）均为阴性，这些检测方法包括ICT、夜间采集的校准厚血涂片和抗Wb 123的IgG 4抗体。尽管如此，2/4391（0.11%）解剖蚊子的班氏丝虫（Wb）幼虫呈阳性。在2011年，在6-7奥尔兹中，ICT的CFA患病率为2.6%（8/301），Wb 123抗体应答的患病率为1.09%（1/92），但异种监测结果为阴性。在随后的2年（2012年和2013年）中，CFA的患病率（趋势卡方2 = 11.49，p=0.0007）持续显著增加，2012年为3.9%（11/285），2013年为4.1%（13/316），抗Wb 123 IgG 4的患病率持续显著增加，2013年为3.2%（10/316）。 尽管ICT和Wb 123 IgG 4抗体流行率均有所增加，但2011年、2012年和2013年未发现受感染的按蚊。 这些数据表明，尽管在监测开始时达到了MDA停止的标准，但似乎出现了低水平的Wb传播，并且抗体监测可能提供比标准TAS工具更好的早期预警工具。 为了开始确定TAS评估的明显成功的传播阻断后再次出现感染的潜在原因，对6个村庄随机选择的成年居民进行问卷调查，以评估系统性不遵守MDA的患病率和原因。那些村庄的覆盖率在MDA的7年中从67%到89.6%不等，在监测期开始时满足了所有停止标准。共询问了486名受试者（170名男性和316名女性），其中16.1%（79/486）报告从未吞咽过MDA药物。最常见的原因是不知道MDA（24/486; 4.9%），怀孕或哺乳（8/486; 1.6%）和不愿意服用药物（6/486; 1.2%）。 尽管系统性不依从者更可能是年轻人，OR = 1.7（1.006-2.921）对于15-30岁与>30岁的个体，依从性和系统性不依从的受试者在参与者的指导水平方面相似，OR = 1.2（0.59-2.51）和存在淋巴水肿/鞘膜积液OR = 0.5（0.11-2.63）。这些数据表明，尽管总体覆盖率足够，但系统性不合规的比例仍可能很高。 系统性不依从者的持续感染是否为6个研究村庄再次出现传播提供了水库，需要进一步研究。