Hospital and Household Studies of Respiratory Cryptosporidiosis and Transmission

描述(申请人提供)：人隐孢子虫(Cr.)传播被认为只能通过粪便-口腔、水或食物传播途径。我们最近发现，35%的乌干达儿童患有肌萎缩侧索硬化症。腹泻和咳嗽均为聚合酶链式反应阳性，提示呼吸道(RT)感染在慢性阻塞性肺疾病儿童中常见。感染(R21AI 068474)。这表明铬。传播可能通过咳嗽时喷出的气雾剂或呼吸道飞沫发生。利用医院和家庭相关研究，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，并且先前接触铬。可以限制RT感染，而不是营养不良或艾滋病毒 这可能会促进或加重临床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感染的儿童增加了铬传播的倾向。对其他人来说。目标1是一项以医院为基础的研究，将评估RT疾病的严重性和可能的修改因素。我们将招募9-36个月大的乌干达儿童，他们(A组)有原发腹泻和不明原因的咳嗽或呼吸急促；或(B组)原发临床肺炎伴或不伴腹泻。将严格评估所有儿童的呼吸状况，包括脉搏血氧仪。这两组人都将接受铬筛查。在临床和实验室检测后，有资格进行诱导痰，可以安全地进行该程序。之前的Cr.将通过两种新的免疫学方法来判断接触情况，一种是针对GP15的唾液抗体，另一种是针对复制铬的间接免疫荧光分析。在体外培养。营养状况将通过人体测量、血红蛋白和血清白蛋白来衡量。如果得到同意，将进行艾滋病毒检测。痰中分离出的铬。将通过RFLP分析进行物种划分。并发RT感染将通过标准微生物学、多重聚合酶链式反应和艾滋病毒相关生物染色进行彻底评估。然后，目标1中确定的儿童将作为目标2A下的家庭传播研究的索引儿童。我们将走访症状儿童的家庭，以了解其临床病史、肠道和RT-CR的特征。状况和接触史(有唾液GP抗体 15)家庭成员在提出索引子女时和两周后。然后，我们将比较患有和不患有RT-CR儿童的家庭的传播率。既有追溯性的也有前瞻性的感染。来解决这样一种假设，即患有RT-CR的成年人。可以作为传播媒介，在目标2B下，我们将确定是否有任何RT-CR证据。在成人中，使用一种廉价、有效的方法检测数千个样本-通过重新筛查收集的结核杆菌进行铬检测。这一群体中有许多艾滋病毒携带者。

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.