Transmission and the respiratory tract in cryptosporidiosis

描述(申请人提供)：此R21申请响应PA-04-119，取代03-080，关于生物防御和新出现的传染病研究机会。隐孢子虫病是临床上引起腹泻的重要原因。由于腹泻的严重性和慢性，以及缺乏有效的治疗，这种感染在免疫缺陷患者中可能危及生命。隐孢子虫病通常被认为完全局限于肠道，传播方式完全是粪便-口腔。该提案将探讨隐孢子虫病对呼吸道感染的贡献(如果有的话)。我们根据大量数据(间接信息、人类病例报告和病例系列、动物研究、基于人群的研究和人类志愿者研究)推测，隐孢子虫的呼吸道感染是频繁发生的。然而，据我们所知，从来没有进行过前瞻性研究这种可能性的研究。我们设计了一项针对乌干达儿童的严谨研究，可以令人信服地证实或驳斥这一假设。这项研究的结果将具有重大的临床、生物学和流行病学影响，鉴于缺乏治疗，这可能是重要的。例如，呼吸道隐孢子虫病的发现可能导致改善临床护理(呼吸支持，如氧气)，并采取新的措施来阻断传播(因为肺部分泌物[痰]可能是传播的来源)。呼吸道感染有多常见--因此有多严重--尚不清楚。在这次修订的申请中，我们加强并专注于乌干达的临床研究，而放弃了先前旨在探索仔猪呼吸道传播问题的特定目标。如果我们在乌干达的项目显示呼吸道隐孢子虫病发生在儿童身上，那么我们将在下一步应用中再次解决这个问题。该项目将侧重于尝试从患有急性或持续性腹泻的儿童的诱导痰中恢复隐孢子虫卵囊，这些儿童同时伴有咳嗽，有或没有呼吸急促。这些研究将在乌干达坎帕拉穆拉戈医院的儿童身上进行，这些儿童患有急性或持续性腹泻和咳嗽，并伴有或不伴有呼吸急促。穆拉戈医院是一个网站，我们在那里进行了几年来关于3-59个月大儿童腹泻和营养不良的计划，并出版了几本书。在这次重新提交中，我们通过增加样本大小和建议对寄生虫分离株进行更全面的遗传分析来加强研究。这项研究对公众健康很重要，因为它可能有助于我们了解这种寄生虫是否也会导致儿童肺部感染。

DESCRIPTION (provided by applicant): This R21 application responds to PA-04-119, replacing 03-080, on Biodefense and Emerging Infectious Diseases Research Opportunities. Cryptosporidiosis is a clinically significant cause of diarrhea. The infection can be life-threatening in individuals with immunodeficiencies because of the severity and chronicity of the diarrhea, and lack of effective therapy. Cryptosporidiosis is usually considered to be wholly confined to the gut, and the mode of transmission to be exclusively fecal-oral. This proposal will explore the contribution, if any, of Cryptosporidiosis to respiratory tract infections. We hypothesize, based on a wealth of data (circumstantial information, human case reports and case series, animal studies, human population-based studies, and human volunteer studies), that respiratory infections with Cryptosporidium occur frequently. However, to our knowledge, no study has ever been conducted to prospectively study this possibility. We have designed a rigorous study of children in Uganda that should either convincingly confirm, or refute, this hypothesis. The outcome of this study will have significant clinical, biological and epidemiological implications, which could be important, given the lack of therapy. For example, the finding of respiratory Cryptosporidiosis may lead to improved clinical care (respiratory support, such as oxygen), and new measures to interrupt transmission (since pulmonary secretions [sputum] may be a source for transmission). How common - and consequently how significant - are infections of the respiratory tract, is unclear. In this revised application, we have strengthened and focused on the clinical study in Uganda, and dropped a prior specific Aim designed to explore the question of respiratory transmission in piglets. Should our project in Uganda show that respiratory Cryptosporidiosis occurs in children, then we will again address that question in a next-step application. The project will focus on attempts to recover Cryptosporidium oocysts from induced sputum of children with acute or persistent diarrhea concurrently experiencing cough, with or without fast breathing. These studies will be performed in children presenting to Mulago Hospital in Kampala, Uganda with acute or persistent diarrhea and cough with or without fast breathing. Mulago Hospital is a site where we have had an ongoing program on diarrhea and malnutrition in children aged 3-59 months for several years, which resulted in several publications. In this resubmission, we have strengthened the study by increasing the sample size, and by proposing to perform more complete genetic analysis of the parasite isolates. This study is important to public health because it may help us to understand if the parasite also causes a lung infection in children.