Development of a rodent model for anthelmintic testing against multidrug resistant hookworms

开发用于针对多重耐药钩虫进行驱虫测试的啮齿动物模型

基本信息

  • 批准号:
    10569256
  • 负责人:
  • 金额:
    $ 24.23万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-11 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Hookworms are serious parasites of humans and animals, causing anemia and even death in heavy infections and vulnerable populations. Nearly 500 million people are infected with hookworms, primarily in developing countries lacking sanitation infrastructure. Canine hookworms are the most important gastrointestinal parasite of dogs. Hookworms can be controlled using several anthelmintics, which in the absence of a vaccine, remain the only available control for hookworm infections. However, heavy use of anthelmintics has led to the development of genetic resistance to all the major anthelmintics used to treat parasitic nematodes in livestock. Increased use of anthelmintics to treat humans is predicted to lead to anthelmintic resistance (AR) in hookworms as well. Indeed, heavy use of anthelmintics in racing greyhounds has led to the emergence of multidrug resistant (MDR) canine hookworms (Ancylostoma caninum). These MDR isolates are resistant to all classes of anthelmintics approved for use in dogs in the US. Recently, MDR hookworms have spread from greyhounds into the general pet dog population and are predicted to continue this spread in the future. Not only will MDR hookworms negatively affect the ability to treated infected dogs, they will also severely limit treatment options for zoonotic hookworm infections in humans such as cutaneous larva migrans, eosinophilic enteritis and diffuse unilateral subacute neuroretinitis. Therefore, there is an urgent need to develop new drugs to treat infections with MDR hookworms. Development of anthelmintics requires adult parasites to test potential compounds for activity in vitro, and infected hosts to test the efficacy of potential drugs. This is hampered by the lack of a small animal model for hookworm infections in which to test new drugs. Ancylostoma caninum can currently only be maintained in dogs, making anthelmintic development and testing costly and ethically problematic. Therefore, we propose a two-pronged approach to developing a rodent model for canine hookworm infection. In Aim 1, we will use drugs to immunosuppress potential rodent hosts before and during infection to determine if the animals can be permissive to MDR hookworm infection. We will also test immunodeficient rodents for their ability to host A. caninum. In Aim 2, we will use the rodent model to test current anthelmintics as a proof of principle. A small animal model of canine hookworm infection would greatly facilitate the development of anthelmintics effective against MDR worms and would provide insights into the development of AR in hookworms that are applicable to hookworm infections of humans.
钩虫是人类和动物的严重寄生虫,严重感染会导致贫血甚至死亡

项目成果

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会议论文数量(0)
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JOHN M HAWDON其他文献

JOHN M HAWDON的其他文献

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{{ truncateString('JOHN M HAWDON', 18)}}的其他基金

Potential of the bitter melon Momordica charantia as a source of anthelmintics
苦瓜苦瓜作为驱虫药来源的潜力
  • 批准号:
    10646710
  • 财政年份:
    2023
  • 资助金额:
    $ 24.23万
  • 项目类别:
Dissecting the mechanism of pyrantel resistance in hookworm
剖析钩虫对噻嘧啶的抗性机制
  • 批准号:
    10666263
  • 财政年份:
    2023
  • 资助金额:
    $ 24.23万
  • 项目类别:
Determining the molecular mechanism of anthelmintic resistance in hookworms
确定钩虫抗蠕虫药的分子机制
  • 批准号:
    9089987
  • 财政年份:
    2015
  • 资助金额:
    $ 24.23万
  • 项目类别:
Determining the molecular mechanism of anthelmintic resistance in hookworms
确定钩虫驱虫药耐药性的分子机制
  • 批准号:
    8807346
  • 财政年份:
    2015
  • 资助金额:
    $ 24.23万
  • 项目类别:
Developing tools for genetic manipulation of hookworms
开发钩虫基因操作工具
  • 批准号:
    8508586
  • 财政年份:
    2013
  • 资助金额:
    $ 24.23万
  • 项目类别:
Developing tools for genetic manipulation of hookworms
开发钩虫基因操作工具
  • 批准号:
    8649018
  • 财政年份:
    2013
  • 资助金额:
    $ 24.23万
  • 项目类别:
Role of insulin-like signaling in the hookworm infective process
类胰岛素信号在钩虫感染过程中的作用
  • 批准号:
    7846597
  • 财政年份:
    2009
  • 资助金额:
    $ 24.23万
  • 项目类别:
Role of insulin-like signaling in the hookworm infective process
类胰岛素信号在钩虫感染过程中的作用
  • 批准号:
    7907635
  • 财政年份:
    2007
  • 资助金额:
    $ 24.23万
  • 项目类别:
Role of insulin-like signaling in the hookworm infective process
类胰岛素信号在钩虫感染过程中的作用
  • 批准号:
    7321296
  • 财政年份:
    2007
  • 资助金额:
    $ 24.23万
  • 项目类别:
Role of insulin-like signaling in the hookworm infective process
类胰岛素信号在钩虫感染过程中的作用
  • 批准号:
    7489422
  • 财政年份:
    2007
  • 资助金额:
    $ 24.23万
  • 项目类别:

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