Hospital and Household Studies of Respiratory Cryptosporidiosis and Transmission

呼吸道隐孢子虫病及其传播的医院和家庭研究

• 批准号: 8822820
• 负责人: Jeffrey K Griffiths
• 金额: $ 67.86万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8822820
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Address; Adult; Aerosols; Affect; Age; Antibodies; Antigens; Characteristics; Child; Clinical; Consent; Coughing; Cryptosporidiosis; Cryptosporidium; Data; Diarrhea; Disease Outcome; Eligibility Determination; Enrollment; Enteral; Environmental Pollution; Evolution; Exposure to; Feces; Frequencies; Funding; Genotype; HIV; Handwashing; Hemoglobin; Hospitalization; Hospitalized Child; Hospitals; Household; Human; Human immunodeficiency virus test; In Vitro; Indirect Fluorescent Antibody Technique; Indirect Immunofluorescence; Infection; Influenza; Laboratories; Lead; Life; Link; Lung; Malnutrition; Masks; Massachusetts; Measures; Methods; Microbiology; Nutritional status; Oral; Organism; Outcome; Parasites; Participant; Persons; Pneumonia; Population; Population Study; Preparation; Preventive; Procedures; Public Health; Pulse Oximetry; Recording of previous events; Research; Respiratory System; Respiratory Tract Diseases; Respiratory Tract Infections; Respiratory tract structure; Restriction fragment length polymorphism; Risk; Route; Salivary; Sample Size; Sampling; Serum; Serum Albumin; Severities; Specimen; Sputum; Staining method; Stains; Symptoms; Testing; Thinking; Time; Tuberculosis; Uganda; Visit; Water; Work; aged; base; clinically significant; co-infection; effective therapy; foodborne; immunological status; indexing; innovation; member; mortality; novel; pediatric human immunodeficiency virus; prevent; prospective; public health relevance; research study; respiratory; screening; transmission process; volunteer

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.

描述（由申请人提供）：人类隐孢子虫（Cr。）的传播被认为仅通过粪便，水或粮食式路线进行。我们最近发现，有35％的乌干达儿童患有CR。腹泻和咳嗽是PCR痰阳性的，表明呼吸道（RT）感染经常发生在CR儿童中。感染（R21AI 068474）。这表明Cr。咳嗽过程中可能通过气溶胶或呼吸液滴进行传播。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感染具有临床后遗症。并事先接触CR。与营养不良或HIV相比，可能会限制RT感染 可能有助于或恶化临床RT感染。此外，我们推测寄生虫物种会影响RT感染的倾向。最后，我们假设患有RT感染的儿童具有增加CR传播的倾向。给别人。 AIM 1是一项基于医院的研究，它将评估RT疾病的严重性和可能的​​修改因素。我们将招募9-36个月的乌干达儿童（A组）患有原发性腹泻和无法解释的咳嗽或tachypnea；或（B组）原发性临床肺炎，有或没有腹泻。所有儿童的呼吸状态将经过严格评估，包括脉搏血氧饱和度。两组将被筛选以进行CR。在粪便中，临床和实验室测试后的痰液诱导资格确认该程序可以安全执行。先前的Cr。暴露将通过两种新型免疫学方法来判断，唾液抗体的GP15和针对复制CR的间接免疫荧光测定法。体外生长。营养状态将通过拟人化，血红蛋白和血清白蛋白来衡量。如果同意，将进行HIV测试。 Cr的痰分离株。将通过RFLP分析指定。并发的RT感染将通过标准微生物学，多重PCR和HIV相关生物染色进行详尽的评估。然后，在AIM 1中确定的儿童将作为AIM 2A下的家庭传播研究的指数儿童。我们将访问指数儿童的家庭，以介绍临床病史，肠和RT CR。状态和暴露历史（带有GP的唾液抗体 15）家庭成员，在索引儿童介绍时，2周后。然后，我们将比较有或没有RT CR的儿童家庭的传播率。以回顾性和潜在的方式感染。解决RT CR的成年人的假设。可以充当传播的代理，在AIM 2B下，我们将确定是否有RT CR的证据。在使用廉价，高效的方法测试数千个标本的成年人中，通过重新筛查CR进行结核病测试的Sputa。这个群体充满了艾滋病毒的人。