Hospital and Household Studies of Respiratory Cryptosporidiosis and Transmission

描述（由申请方提供）：人隐孢子虫（Cr.）传播被认为仅通过粪-口、水或食物传播途径发生。我们最近发现，35%的乌干达儿童与铬。腹泻和咳嗽PCR阳性，提示呼吸道（RT）感染在儿童Cr。感染（R21 AI 068474）。这表明Cr。传播可能通过咳嗽时喷出的气溶胶或呼吸道飞沫发生。使用链接的医院和家庭研究，我们将评估RT感染的临床和公共卫生意义。我们假设RT感染有临床后遗症，并且先前暴露于Cr。与营养不良或艾滋病毒相比， 这可能促进或加重临床RT感染。此外，我们推测寄生虫种类影响RT感染的倾向。最后，我们假设RT感染的儿童传播Cr的倾向增加。对其他人来说 目的1是一项以医院为基础的研究，将评估RT疾病的严重程度和可能的修正因素。我们将招募9-36个月的乌干达儿童，他们（A组）患有原发性腹泻和不明原因的咳嗽或呼吸急促;或（B组）患有原发性临床肺炎伴或不伴腹泻。所有儿童的呼吸状况将得到严格评估，包括脉搏血氧饱和度。将对两组进行Cr筛查。在粪便中，并且在临床和实验室测试确认该程序可以安全进行后，符合痰诱导的资格。普赖尔溪将通过两种新的免疫学方法，即针对gp 15的唾液抗体和针对复制Cr的间接免疫荧光测定来判断暴露。在试管中生长。营养状况将通过人体测量、血红蛋白和血清白蛋白进行测量。如果同意，将进行艾滋病毒检测。痰分离的克雷伯氏菌。将通过RFLP分析进行物种化。将通过标准微生物学、多重PCR和HIV相关微生物染色对并发RT感染进行彻底评估。目标1中确定的儿童将作为目标2A下家庭传播研究的指标儿童。我们将访问索引儿童的家庭，以描述临床病史、肠道和RT Cr。状态和暴露史（有唾液抗gp抗体 15)家庭成员，在指数儿童出现时和2周后。然后，我们将比较有和没有RT Cr的儿童家庭的传播率。以回顾性和前瞻性的方式。为了解决这一假设，成人RT Cr。在目标2B下，我们将确定是否有任何RT Cr的证据。在成年人中使用一种廉价，有效的方法测试数千个标本-通过重新筛选收集的结核病检测Cr。这一群体中有大量艾滋病毒感染者。 公共卫生相关性：隐孢子虫通常会导致腹泻，这可能是致命的。我们希望了解它是否可以像流感或肺结核一样从肺部传播或传播到肺部。如果它可以通过这种方式传播，那么我们可以通过戴口罩和咳嗽后洗手等行动来防止人们感染。 公共卫生相关性：隐孢子虫通常会导致腹泻，这可能是致命的。我们希望了解它是否可以像流感或肺结核一样从肺部传播或传播到肺部。如果它可以通过这种方式传播，那么我们可以通过戴口罩和咳嗽后洗手等行动来防止人们感染。

DESCRIPTION (provided by applicant): Human Cryptosporidium (Cr.) transmission has been thought to occur only via fecal-oral, water-, or food-borne routes. We recently found that 35% of Ugandan children with Cr. diarrhea and cough were PCR sputum-positive, suggesting that respiratory tract (RT) infection occurs frequently in children with Cr. infection (R21AI 068474). This suggests that Cr. transmission may occur via aerosols or respiratory droplets ejected during coughing. Using linked hospital and household studies, we will assess the clinical and public health significance of RT infection. We hypothesize that RT infection has clinical sequelae; and that prior exposure to Cr. may limit RT infection, in contrast to malnutrition or HIV which may facilitate or worsen clinical RT infection. Further, we surmise that parasite species affects the propensity for RT infection. Finally, we hypothesize that children with RT infection have increased propensity for transmission of Cr. to others. Aim 1 is a hospital-based study that will assess severity of RT illness and possible modifying factors. We will enroll Ugandan children aged 9-36 months who (Group A) have primary diarrhea and unexplained cough or tachypnea; or (Group B) primary clinical pneumonia with or without diarrhea. The respiratory status of all children will be rigorously assessed, including pulse oximetry. Both groups will be screened for Cr. in the stool, and eligibility for sputum induction after clinical and laboratory testing affirms the procedure can be safely performed. Prior Cr. exposure will be judged via two novel immunological methods, salivary antibody to gp15 and an indirect immunofluorescence assay against replicating Cr. grown in vitro. Nutritional status will be gauged via anthropometrics, hemoglobin, and serum albumin. HIV testing, if consented to, will be performed. Sputum isolates of Cr. will be speciated via RFLP analysis. Concurrent RT infections will be exhaustively assessed by standard microbiology, multiplex PCR, and staining for HIV-related organisms. Children identified in Aim 1 will then serve as index children for household transmission studies under Aim 2A. We will visit households of index children to characterize the clinical history, enteric and RT Cr. status, and exposure history (with salivary antibody to gp 15) of household members, at the time of presentation of the index child and 2 weeks later. We will then compare transmission rates in households of children with and without RT Cr. infection in both a retrospective and prospective fashion. To address the hypothesis that adults with RT Cr. could act as agents of transmission, under Aim 2B we will establish whether there is any evidence of RT Cr. in adults using an inexpensive, efficient approach testing thousands of specimens - by re-screening sputa collected for tuberculosis testing for Cr. This group is enriched with persons with HIV. Public health relevance: Cryptosporidium commonly causes diarrhea which can be fatal. We wish to see if it can be spread from, or to, the lungs, like influenza or tuberculosis. If it can spread in this way, then we can prevent people from getting infected by actions such as wearing masks and washing hands after coughing. PUBLIC HEALTH RELEVANCE: Cryptosporidium commonly causes diarrhea which can be fatal. We wish to see if it can be spread from, or to, the lungs, like influenza or tuberculosis. I it can spread in this way, then we can prevent people from getting infected by actions such as wearing masks and washing hands after coughing.