Impact of zooprophylaxis on zoonotic cutaneous leishmaniasis transmission

 描述（由申请方提供）：人畜共患皮肤利什曼病（ZCL）是一种由大型利什曼原虫引起的病媒传播疾病，通过白蛉叮咬传播。肥胖沙鼠（Psammomys obesus）和沙威沙鼠（Meriones shawi）是该寄生虫的主要贮存宿主。皮肤利什曼病被世界卫生组织认为是一种被忽视的热带疾病，每年影响全球约150万人。这种疾病在中美洲和南美洲、地中海盆地以及与贫穷密切相关的近东和远东国家广泛流行。虽然ZCL不是致命的，但产生的病变可能会对感染者造成严重的毁容和严重的痛苦，并造成终身的心理和社会后果。没有疫苗可用，对人类的治疗主要基于化学疗法（五价锑/葡聚糖）。迄今为止，L. 40多年来，葡聚糖时间是发展中国家唯一负担得起的药物，但这一主要问题已成为一个重大关切。迫切需要新的替代品来控制ZCL。在突尼斯，ZCL是一种在社会经济地位低下的农村地区流行的围产期疾病，年发病率为669.7/100，000。帕氏白蛉（Phlebotomus papatasi）是白蛉的主要媒介。主要在突尼斯和北非。目前只有葡聚糖时间的化学疗法可用，既没有媒介也没有狗控制计划。杀死或转移感染的沙蝇可以减少ZCL的传播。虽然室内残留喷洒杀虫剂能有效降低ZCL的发病率，但它需要每年施用一次，费用昂贵，因此其适用性受到低收入国家财政限制的限制。 收入国家。经杀虫剂处理的窗帘或蚊帐可有效预防帕帕塔斯疟原虫;但在停止这些措施后，传播仍如以前一样继续。尽管它们在阻断ZCL传播方面有效，但在许多流行国家，以分发驱虫蚊帐为基础的方案执行得很差，而且超出了ZCL流行村庄许多家庭的能力。虽然用磷化锌毒害ZCL啮齿动物水库已经降低了ZCL的发病率，但这种方法在生态上是不合理的。我们的目标是开发一种可持续的方法，该方法的基础是从人类身上转移白蛉媒介，以减少ZCL在流行地区的传播。大量研究表明，宿主多样性可通过稀释效应降低人畜共患病媒传播疾病的发病率。病媒宿主群落中的高度物种多样性会稀释最有能力的疾病宿主的影响，从而降低疾病的发病率，从而降低病媒的感染流行率或数量。动物预防是利用不是特定疾病的宿主的野生或家养动物，使病媒偏离人类，从而产生稀释效应。房屋周围牲畜的存在可能会减少疾病的传播，并保护人类免受受感染的白蛉的叮咬。我们的初步研究表明，在位于家庭周边地区的人工洞穴中繁殖兔子显着减少了室内的P. papatasi。兔子强烈吸引沙蝇，但对L。少校我们推测，在位于家庭周边地区的人工地下洞穴中饲养的兔子作为稀释宿主，对ZCL在流行区的传播发挥动物预防作用。本建议的目的是建立一个新的媒介控制策略的基础上，动物预防，以减少传播ZCL在地方病疫源地。该方案将在突尼斯得到验证，原因如下：（1）疾病的地方性;（2）目前控制方案有限;（3）能够使用实验室模型和实地地点测试干预战略;（4）能够在政治稳定的代表性地区进行实地研究。事实上，从该项目中吸取的经验教训应该会影响政治敏感的中东和北非国家的公共卫生政策当局。这个为期两年的项目将开发一种新的方法来控制ZCL传输，该方法建立在从美国向突尼斯转移专业知识的基础上，促进能力建设和创新。

 DESCRIPTION (provided by applicant): Zoonotic cutaneous leishmaniasis (ZCL) is a vector-borne disease caused by Leishmania major, transmitted by the bites of phlebotomine sand flies. The fat sand rat (Psammomys obesus) and the desert's gird (Meriones shawi ) are the main reservoir hosts of this parasite. Cutaneous leishmaniasis is considered by the WHO to be a neglected tropical disease, affecting about 1.5 million people per year worldwide. The disease is widespread in Central and South America, the Mediterranean basin, and the near and far east countries where it is strongly correlated with poverty. Although ZCL is not fatal, the lesions produced may cause substantial disfigurement and severe distress to infected individuals with lifelong psychological and social consequences. No vaccine is available and treatment of humans is largely based on chemical therapy (pentavalent antimony/glucantime). To date, resistance of L. major to glucantime, the only affordable drug in developing countries for more than 40 years, has become a major concern. New alternatives to control ZCL are urgently needed. In Tunisia, ZCL is a peridomestic disease endemic in rural areas with low socio-economic status with an annual incidence rate of 669.7/100,000 per year. Phlebotomus papatasi is the main vector of L. major in Tunisia and in North Africa. Only chemical therapy with glucantime is currently available, with neither vector nor dog control programs. Killing or diverting infected sand flies from humans can reduce the transmission of ZCL. Although indoor residual spraying (IRS) of insecticides is effective in reducing the incidence of ZCL, it requires expensive yearly applications and its applicability is thus limited by financial constraints in low income countries. Insecticide-treated curtains or bednets offer effective protection against P. papatasi; but transmission continues as before after cessation of these measures. Despite their efficacy in the interruption of ZCL transmission, programs based on the distribution of ITNs are poorly implemented in many endemic countries and are beyond the means of many families in ZCL-endemic villages. Although poisoning ZCL rodent reservoirs with zinc phosphide has reduced the incidence of ZCL, this approach is ecologically unsound. We aim to develop a sustainable method based on diverting sand fly vectors from humans to reduce the transmission of ZCL in endemic areas. Numerous studies show that host diversity could reduce the incidence of zoonotic vector- borne diseases by a dilution effect. A high species diversity in the community of vector hosts reduces the infection prevalence or abundance of the vectors by diluting the effects of the most competent disease reservoir and subsequently reducing the incidence of the disease. Zooprophylaxis is the use of wild or domestic animals, which are not reservoir hosts of a given diseases, to deflect vectors from humans creating a dilution effect. The presence of livestock around houses may diminish transmission of the disease and protect humans from the bites of infected sand flies. Our preliminary studies have shown that breeding rabbits in artificia burrows located in peri-domestic areas significantly reduces the indoor abundance of P. papatasi within houses. Rabbits strongly attract sand flies but are a dead-end host for L. major. We hypothesize that rabbits bred in man-made underground holes located in the peri-domestic areas act as a dilution hosts and exert a zooprophylactic effects on the transmission of ZCL in endemic areas. The objective of this proposal is to establish a new vector control strategy based on zooprophylaxis to reduce transmission of ZCL in endemic focus. This program will be validated in Tunisia for several reasons: (1) endemicity of disease; (2) limited current control options; (3) access to laboratory models and field sites for testing intervention strategies; and (4) ability to conduct field-based research in a representative region that is stable politically. Indeed, lessons learned from this project should impact public health policy authorities in the politically sensitive Middle East and North African (MENA) nations. This two-year project will develop a new approach to control ZCL transmission built upon the transfer of expertise from the US to Tunisia, fostering both capacity building and innovation.