Richard Kwizera, MSc, PhD
Nominated From: University of Minnesota
Research Site: Makerere University, Gulu Regional Referral Hospital
Research Area: Pulmonary fungal infections
Primary Mentor: Dr. David Boulware
Research Project
Immunophenotyping persons living with HIV and PTB associated Chronic Pulmonary Aspergillosis in Uganda.
The prevalence of HIV among adults aged 15 to 64 in Uganda is 6.2%. An estimated 30 deaths and 223 people get sick with TB every day in Uganda. TB prevalence in Uganda is high at 253 TB cases per 100,000 population. Due to residual lung damage, pulmonary TB (PTB) is an important risk factor for other chronic respiratory diseases including aspergillosis. Chronic Pulmonary Aspergillosis (CPA) affects both immunocompetent and immunocompromised patients commonly with a previous or underlying lung disease. CPA and PTB can co-exist, posing a challenge in distinguishing the two infections clinically. CPA can also appear as post-TB lung disease. With the high burden of PTB in Uganda, mostly secondary to HIV, the incidence of CPA in HIV is probably higher, but the index of clinical suspicion is low. The underlying mechanisms of post-TB CPA are not well comprehended, especially in HIV patients. Aim: This study aims to evaluate and describe the Innate and Adaptive Immune Characteristics of persons living with HIV and PTB-associated CPA in Uganda. Methods: This will be a cross-sectional study to be conducted for 12 months at Makerere lung institute, Chest clinic and pulmonology ward of Mulago National Referral Hospital, Kampala, Uganda. We shall include HIV patients with PTB and signs of clinical CPA. We shall exclude HIV patients with other alternative lung diseases (e.g asthma) that could explain the persistent respiratory symptoms or confound the assessment of CPA. CPA will be diagnosed using standard diagnostic criteria. We will also collect sociodemographic data, presenting clinical data including history of PTB treatment and time that has elapsed since PTB treatment completion from enrolled participants. Laboratory procedures will include testing the Aspergillus LFA, fungal culture, flow cytometry and Luminex testing. Data analysis will be carried out using STATA version 18.0. Ethics clearances will be sought from the REC of Mulago hospital, and Uganda National Council of Science and Technology. Expected outcome: With the high burden of HIV-associated PTB in Uganda, as the major risk factor for CPA, identification of an immunological signature underlying post-TB CPA could enable precise diagnosis and treatment strategies. Additionally, the identified post-TB CPA immunological signature may play a role in disease monitoring serving as a predictive biomarker of disease severity or a prognostic biomarker of treatment response.
Research Significance
The underlying mechanisms of post-TB CPA are not well comprehended especially in HIV patients. With the high burden of HIV-associated PTB in Uganda, as the major risk factor for CPA, identification of an immunological signature underlying post-TB CPA could enable precise diagnosis and treatment strategies. Additionally, the identified post-TB CPA immunological signature may play a role in disease monitoring serving as a predictive biomarker of disease severity or a prognostic biomarker of treatment response.
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