Molecular Epidemiology of Human P. carinii Pneumonia

人卡氏疟原虫肺炎的分子流行病学

• 批准号: 6670213
• 负责人: LAURENCE HUANG
• 金额: $ 12.16万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6670213
• 关键词: B lymphocyte; HIV infections; Pneumocystis carinii; Pneumocystis pneumonia; T lymphocyte; cellular immunity; clinical research; communicable disease transmission; epidemiology; flow cytometry; fungal genetics; hospitals; human subject; patient oriented research; polymerase chain reaction; questionnaires; virus infection mechanism; western blottings

DESCRIPTION (provided by applicant): This is a resubmission of a K23 grant application that is designed to enable Dr. Laurence Huang to acquire additional clinical research training and to develop a research program that will allow him to become an independent and successful clinical investigator. The plan emphasizes didactic training in clinical epidemiology, molecular methods in clinical research, and advanced statistical analysis techniques, which he will gain through completion of a Master's Degree Program in Clinical Research. This didactic training will be coupled with the opportunity to spend time in the laboratories of his scientific collaborators so that he may gain practical insights into the new and highly promising molecular techniques he proposes to use to examine the epidemiology and transmission of human Pneumocystis carinii pneumonia. These studies will involve the close collaboration of scientists from the CDC, NIH, and several university-based laboratories. and will be conducted under the guidance of his two co-mentors: Philip Hopewell, MD, one of the world's foremost experts in the molecular epidemiology of tuberculosis, and Dennis Osmond, PhD, a leading HIV/AIDS epidemiologist and biostatistician. Although the transmission of Pneumocystis carinii between mammals of the same species has been convincingly demonstrated in the laboratory, it is unproven whether a similar clinical model exists for human disease. In addition, it is debated whether PCP in humans develops solely from reactivation or of a latent infection acquired early in childhood or also from acquisition of a new infection due to a recent exposure. The proposed research plan will determine whether P. carinii and immune responses to P. carinii can be detected in household and hospital contacts living with and caring for HIV-infected patients with PCP and, if P. carinii is detected, whether the P. carinii genetic sequence from a contact matches that from the patient with PCP. This information will be used to develop future studies to examine whether PCP can result from acquisition of a new infection. Since PCP remains a leading cause of the moribiity and mortality in HIV-infected and other immunocompromised persons, insights into its epidemiology and transmission may have profound implications for clinical management and disease prevention.

描述（由申请人提供）： 这是 K23 拨款申请的重新提交，旨在使 Laurence Huang 博士能够获得额外的临床研究培训并制定研究计划，使他能够成为一名独立且成功的临床研究者。该计划强调临床流行病学、临床研究分子方法和先进统计分析技术方面的教学培训，他将通过完成临床研究硕士学位课程获得这些培训。这种教学培训将与在他的科学合作者的实验室中度过的机会相结合，以便他可以获得对他提议用来检查人类卡氏肺孢子虫肺炎的流行病学和传播的新的和非常有前途的分子技术的实际见解。这些研究将涉及疾病预防控制中心、美国国立卫生研究院和几所大学实验室的科学家的密切合作。并将在他的两位共同导师的指导下进行：菲利普·霍普韦尔医学博士（世界上最重要的结核病分子流行病学专家之一）和丹尼斯·奥斯蒙德博士（领先的艾滋病毒/艾滋病流行病学家和生物统计学家）。尽管卡氏肺囊虫在同一物种的哺乳动物之间的传播已在实验室中得到令人信服的证明，但尚未证实人类疾病是否存在类似的临床模型。此外，人类中的五氯苯酚是否仅由儿童早期获得的潜伏感染再激活或由于最近的暴露而获得新的感染而产生，这一点也存在争议。拟议的研究计划将确定是否可以在与 PCP 感染 HIV 患者生活和护理的家庭和医院接触者中检测到卡氏疟原虫和对卡氏疟原虫的免疫反应，如果检测到卡氏疟原虫，则接触者的卡氏疟原虫基因序列是否与 PCP 患者的基因序列相匹配。该信息将用于开展未来的研究，以检验 PCP 是否可能由新感染引起。由于五氯苯酚仍然是艾滋病毒感染者和其他免疫功能低下者发病和死亡的主要原因，因此深入了解其流行病学和传播可能对临床管理和疾病预防产生深远影响。