Advancing diagnosis and prevention of pediatric tuberculosis in HIV-endemic settings

The National Institute of Child Health and Human Development awarded Emory University $110,228 on December 8, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to advance diagnosis and prevention of pediatric tuberculosis in HIV-endemic settings.

The research evaluates prediction models integrating serum-based MTB cell-free DNA and ESAT-6/CFP-10 IgA antibody biomarkers with clinical data to diagnose tuberculosis disease in children living with HIV, addressing the poor sensitivity of standard culture-based diagnostics in pediatric populations. The project also examines household contact interventions to prevent TB transmission from adults to children, the single greatest risk factor for TB among young children and children with HIV.

Emory University's Office of Sponsored Programs is the recipient. Performance occurs in Atlanta, Georgia, with work completing November 30, 2028.

Abstract

Tuberculosis (TB), caused by mycobacterium tuberculosis (MTB), is responsible for a third of all deaths among people living with HIV and is the number one cause of death in children living with HIV worldwide. Compared to adults, young children and children living with HIV are at increased risk for developing active TB disease and more severe presentations of TB, including TB meningitis. Nearly 96% of pediatric TB deaths occur among children who are never diagnosed. However, pediatric TB mortality is preventable if identified and treated. Efforts to reduce morbidity and mortality from pediatric TB globally will require evidence-based interventions to facilitate earlier diagnosis of TB disease in pediatric patients and prevent TB transmission to vulnerable children. Culture of mycobacterium tuberculosis (MTB), the gold-standard diagnostic test for TB, exhibits poor sensitivity (30-40%) in children due to the paucibacillary nature of pediatric TB disease and challenges obtaining respiratory tract samples. Given poor reliability and accessibility of microbiologic testing in children, there exists a need to develop more reliable, non-sputum based point-of-care tools for diagnosing TB disease in children. Serum-based MTB cell-free DNA (MTB-cfdna) and esat-6/CFP-10 IGA antibodies have been identified as promising biomarkers for detecting TB disease in children with HIV. In aim 1, we will evaluate the accuracy of different prediction models to integrate MTB-specific biomarkers with available clinical data to diagnose TB disease in children living with HIV. In the absence of better diagnostic tests for pediatric TB disease, preventing TB-related harms in children must start with preventing TB transmission from adults to children. Household contact with an adult TB case is the single greatest risk factor for TB among young children and children with HIV. Therefore, preventing the introduction of TB into households from the community will disproportionately reduce TB-related mortality in vulnerable children. In genome-based studies of drug-resistant TB (DR-TB) transmission in durban, south africa, our research group has shown that close contacts account for only a minority (30%) of DR-TB cases in adults; the remaining majority (70%) of TB transmission likely occurs in community settings but is poorly characterized. In aim 2, we will integrate epidemiologic contact tracing and genomic data to compare maps of "activity hotspots" for DR-TB cases associated with named VS. Unnamed contacts and identify potential sources of community- based TB transmission. The long-term goal of the proposed research is to inform evidence-based strategies to prevent, diagnose, and treat TB disease in children. The overall objective of this proposal is to increase TB diagnostic capacity in children living with HIV (aim 1) and to advance our awareness of population-level TB transmission dynamics in HIV-prevalent settings (aim 2). Moreover, the proposed aims reflect my long-term career goal of conducting interdisciplinary research to address complex research questions that bridge clinical medicine and population health. The proposed aims and training plan will equip me with foundational knowledge and experience in epidemiologic research and prepare me for a successful career as a physician-scientist.