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计划 (GPELF) 于 2000 年启动，目标是通过每年大规模用药 (MDA) 来阻止淋巴丝虫病 (LF) 的传播。对马里人口的初步调查表明，班克罗夫蒂乌切菌（W. bancrofti）感染在锡卡索地区高度流行。 2001 年（在每年一次使用阿苯达唑和伊维菌素的 MDA 开始之前），在 6 个村庄进行的基线人类和昆虫学研究证实了班克罗夫蒂在该地区的流行和传播，并在 2002 年至 2007 年 MDA 期间每年进行监测。通过成年志愿者夜间血液的校准厚涂片确定微丝虫血症，并使用 ICT 测试测量 <5 岁儿童的循环丝虫抗原。 7 月至 12 月间，人类通过登陆捕获蚊子。第 6 轮 MDA 后 12 个月后，686 名接受测试的受试者均未出现微丝丝血症。更重要的是，在接受检测的 120 名儿童中，没有检测到循环抗原，而在建立 MDA 之前，这一比例为 53% (103/194)。传染性叮咬人数/人/年从 2002 年的 4.8 例下降到 2007 年的 0.04 例。尽管这些数据与持续传播的水平非常低相符，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 方法的实用性，我们使用标准 TAS 方法（6-7 岁儿童中 ICT 阳性患病率），并将其与马里南部 Sikasso 地区 6 个村庄停止 MDA 后五年（2009-2014 年）的异种监测、夜间血液微丝蚴计数和 Wb123 IgG4 抗体（过去 3 年）进行比较。 2009 年（监测期开始时），通过 ICT、夜间采集的校准厚血涂片和 Wb123 IgG4 抗体检测，所有 289 名 6-7 岁儿童的循环丝虫抗原 (CFA) 均为阴性。尽管如此，2/4391 (0.11%) 解剖的蚊子对 Wuchereria bancrofti (Wb) 幼虫呈阳性。 2011年，6-7岁儿童中ICT的CFA患病率为2.6% (8/301)，Wb123抗体反应的患病率为1.09% (1/92)，但异种监测呈阴性。在随后的两年（2012 年和 2013 年）中，CFA 患病率（趋势 Chi2 = 11.49，p = 0.0007）持续显着增加，2012 年增加至 3.9% (11/285)，2012 年增加至 4.1% (13/316)，抗 Wb123 IgG4 患病率增加至 3.2% (10/316) 2013 年。尽管 ICT 和 Wb123 IgG4 抗体流行，2011 年、2012 年和 2013 年没有发现受感染的按蚊。这些数据表明，尽管在监测开始时已达到停止 MDA 的标准，但 Wb 传播的出现率似乎较低，并且抗体监测可能比更标准的 TAS 工具提供更好的早期预警工具。 为了开始确定在经 TAS 评估明显成功阻断传播后重新出现感染的潜在原因，我们向六个村庄中随机选择的成年居民进行了一份调查问卷，以评估系统性不遵守 MDA 的流行情况和原因。在 MDA 的 7 年里，村庄的覆盖率从 67% 到 89.6% 不等，并且在监测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）接受了询问，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%）以及不愿意服用药物（6/486；1.2%）。 尽管15-30岁个体与>30岁个体相比，系统性不合规者更可能是年轻的OR = 1.7 (1.006-2.921)，但就参与者指导水平OR = 1.2 (0.59-2.51)和淋巴水肿/鞘膜积液的存在OR = 0.5 (0.11-2.63)而言，合规性和系统性不合规受试者相似。这些数据表明，尽管总体覆盖率足够高，但系统性不合规率仍然很高。 系统性不合规者的持续感染是否为 6 个研究村庄重新出现传播提供了储存库，需要进一步研究。