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.
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