Molecular Epidemiology of Human P. carinii Pneumonia

描述（由申请人提供）： 这是K23资助申请的重新提交，旨在使Laurence Huang博士能够获得额外的临床研究培训，并制定一项研究计划，使他能够成为一名独立和成功的临床研究者。该计划强调临床流行病学，临床研究中的分子方法和先进的统计分析技术的教学培训，他将通过完成临床研究硕士学位课程获得。这种教学培训将与机会，花时间在他的科学合作者的实验室，使他可以获得实际的见解，他建议使用新的和非常有前途的分子技术，以检查流行病学和人类肺孢子虫肺炎的传播。这些研究将涉及来自CDC，NIH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：Philip Hopewell，医学博士，世界上最重要的结核病分子流行病学专家之一，Dennis Osmond，博士，领先的艾滋病毒/艾滋病流行病学家和生物统计学家。虽然卡氏肺孢子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，但尚未证明人类疾病是否存在类似的临床模型。此外，人们对五氯苯酚在人体中的形成是否仅仅是由于再活化或在儿童早期获得的潜伏感染，还是由于最近接触五氯苯酚而获得新的感染存在争议。拟议的研究计划将确定是否可以在与感染艾滋病毒的五氯苯酚患者生活在一起并照顾他们的家庭和医院接触者中检测到卡氏肺孢子虫和对卡氏肺孢子虫的免疫反应，如果检测到卡氏肺孢子虫，则确定接触者的卡氏肺孢子虫基因序列是否与五氯苯酚患者的卡氏肺孢子虫基因序列相匹配。这些信息将用于开发未来的研究，以检查PCP是否会因获得新的感染而导致。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濒死和死亡的主要原因，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。

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.