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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL087713-04
Application #
7679591
Study Section
Special Emphasis Panel (ZHL1-CSR-R (O1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2006-09-30
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2009
Total Cost
$169,937
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Musisi, Emmanuel; Matovu, Denis Kasozi; Bukenya, Andrew et al. (2018) Effect of anti-retroviral therapy on oxidative stress in hospitalized HIV-infected adults with and without TB. Afr Health Sci 18:512-522
Gingo, Matthew R; Nouraie, Mehdi; Kessinger, Cathy J et al. (2018) Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals. Ann Am Thorac Soc 15:192-199
Qin, Shulin; Clausen, Emily; Nouraie, Seyed Mehdi et al. (2018) Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation. PLoS One 13:e0205065
Li, Yijia; Nouraie, Seyed Mehdi; Kessinger, Cathy et al. (2018) Factors Associated With Progression of Lung Function Abnormalities in HIV-Infected Individuals. J Acquir Immune Defic Syndr 79:501-509
Tipton, Laura; Cuenco, Karen T; Huang, Laurence et al. (2018) Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model. BioData Min 11:12
Tipton, Laura; Müller, Christian L; Kurtz, Zachary D et al. (2018) Fungi stabilize connectivity in the lung and skin microbial ecosystems. Microbiome 6:12
Farr, Katherine; Ravindran, Resmi; Strnad, Luke et al. (2018) Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV. PLoS One 13:e0206119
Worodria, William; Chang, Emily; Andama, Alfred et al. (2018) Predictors of Mortality Among Hospitalized Patients With Lower Respiratory Tract Infections in a High HIV Burden Setting. J Acquir Immune Defic Syndr 79:624-630
Walter, Nicholas D; Moore, Camille M; Kayigire, Xavier A et al. (2018) Does discovery of differentially culturable M tuberculosis really demand a new treatment paradigm? Longitudinal analysis of DNA clearance from sputum. BMC Infect Dis 18:293
Shenoy, Meera K; Iwai, Shoko; Lin, Din L et al. (2017) Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia. Am J Respir Crit Care Med 195:104-114

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