Lilian Njagi, MBChB, MSc, DTM&H, PhD
LILIAN NJAGI
Nominated From: University of Washington
Research Site: Kenya Medical Research Institute
Research Area: Tuberculosis, HIV
Primary Mentor: Thomas R. Hawn, MD, PhD
Research Project
Immunopathogenesis of TB infectiousness in HIV Coinfection
Mycobacterium tuberculosis (Mtb) transmission is central to maintaining the TB/HIV epidemic, but knowledge gaps hinder the development of targeted interventions to halt transmission. These gaps include a lack of knowledge of the determinants of infectiousness in the context of TB-HIV co-infection and a lack of diagnostic tools that can identify all TB-infected contacts and distinguish recent from remote infections. The goal of the proposed study is to investigate the mechanisms of Mtb transmission in people living with HIV (PLWH) to address existing knowledge gaps, ultimately leading to the development of targeted interventions for TB control in people with and without HIV. Building on existing work suggesting that HIV coinfection may be associated with lower Mtb transmission, we will leverage an ongoing prospective, observational TB Aerobiology, Immunology, and Transmission (TBAIT) study in Nairobi, Kenya to determine epidemiologic, microbiologic, and immunologic features of TB transmission in PLWH in Aim 1 by undertaking investigations, including genome-wide transcriptional profiling to understand the immune pathways modulating infectivity assessed by Mtb aerosolization in PLWH. In Aim 2, we will evaluate Mtb-specific T-cell responses and markers of Mtb exposure in household contacts (HHCs), as well as their associations with HIV co-infection and Mtb aerosolization in the index case. Using multi-parameter flow cytometry, we will assess Mtb-specific polyfunctional CD4 and CD8 T-cell responses in HHC, identify IFN-γ-independent markers of Mtb exposure, evaluate HLA-DR expression as a marker of recent Mtb exposure, and assess associations with HIV co-infection and Mtb aerosolization in the index case. Using these approaches, we aim to understand the full breadth of responses following differential exposure to Mtb and identify additional markers that could enhance TB infection diagnosis, including identifying recently infected persons for targeted preventive therapy.
Research Significance
The findings of this study are relevant for identifying novel pathways that may lead to the discovery of biomarkers for infectiousness and transmission of TB. This has the potential to significantly enhance new interventions for TB diagnostics and targeted TB preventive therapy in people with and without HIV, contributing to the overall goal of ending TB as a global health problem in keeping with the WHO End TB Strategy goals.
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