Patient-Oriented Research and Mentoring in Pneumocystis
Career Development and Mentoring Goals: (1) to continue my patient-oriented research in Pneumocystis; (2) to expand my research to include other respiratory pathogens, such as Mycobacterium tuberculosis (TB); (3) to devote more time to mentor junior patient-oriented researchers interested in pulmonary infections; and (4) to build an international clinical research program in Kampala, Uganda focused on pulmonary infections. The initial studies in Kampala will investigate the non-invasive diagnosis of Pneumocystis pneumonia (PCP) and TB and will examine trimethoprim-sulfamethoxazole drug resistance in Pneumocystis. We propose a prospective cross-sectional cohort study of HIV-infected patients with pneumonia who are admitted to Mulago Hospital in Kampala. A total of 200 enrolled subjects will provide oropharyngeal washing (OPW, gargle) specimens and will undergo bronchoscopy with bronchoalveolar lavage (BAL) for the diagnosis of PCP and TB. The OPW specimens will be analyzed using polymerase chain reaction (PCR) assays for Pneumocystis and M. tuberculosis and these results will be compared to the gold standard immunofluorescence testing (PCP) and mycobacterial culture (TB). Those subjects who are found to have PCP will have their BAL specimen genotyped at the dihydropteroate synthase (DHPS) locus to study trimethoprim-sulfamethoxazole drug resistance. Aim 1: To establish non-invasive OPW specimens using a PCR assay targeting the P. jirovecii (formerly P. carinii) major surface glycoprotein (MSG) gene as a clinical tool to diagnose PCP in a resource-limited setting (Mulago Hospital in Kampala). Aim 2: To examine potential trimethoprim-sulfamethoxazole drug resistance in P. jirovecii from HIV-infected persons residing in a resource-limited setting. Aim 3: To establish non-invasive OPW specimens using a PCR assay targeting the Mycobacterium secA1 gene as a clinical tool to diagnose TB in a resource-limited setting. Relevance to Public Health: PCP and TB are important causes of pneumonia, especially in persons with compromised immune systems. Typically, the diagnosis of these pneumonias requires invasive procedures that are often unavailable throughout the world. The development of rapid, non-invasive tests that can diagnosis PCP and TB effectively would be significant advances.