Improving Childhood Tuberculosis Treatment Outcomes and Post-TB Lung Functioning and Quality of Life in Rural South Africa

  • Investigator: Meredith Brooks
  • Funding Source: Charles H. Hood Foundation

We will assess the TB care cascade in cihldren, expanding it to include a child-specific definition of post-TB lung disease (PTLD), among children in a high TB/HIV burden setting in Eastern Cape South Africa, and identify risk-factors for completing each step of the newly expanded TB care cascade. Additionally, we will collect rich data regarding nutritional status, air pollutant exposure, lung capacity, and quality of life to estimate their effect on TB disease and PTLD in children.

    Artificial Intelligence to Improve the Diagnosis of Pediatric Tuberculosis

    • Investigator: Meredith Brooks
    • Funding Source: William F. Milton Fund, Harvard University

    Tuberculosis is a preventable infectious disease, yet more than one million children fall sick with TB every year. Under-diagnosis remains a major challenge, because (1) children present with diverse and non-specific symptoms and (2) tests that diagnose TB in adults have low sensitivity in children, who often have paucibacillary TB or cannot produce sputum. Other challenges include complex diagnostic algorithms. Coupled with limited laboratory capacity in high Tb-burden settings and costly tests, these factors often preclude microbiological confirmation of TB in children. As a result, each year millions of children with Tb or sub-clinical TB infection are missed by TB services and never receive life-saving treatment. Effective diagnostic algorithms tailored for children need to be developed, ideally using large datasets to ensure validity. To address this knowledge gap, we leverage an existing dataset of children screened for TB in Kotri, Pakistan, providing a unique opportunity to assess age-specific barriers to TB diagnosis in children. We aim to: (1) identify age-specific gaps in the sequence of steps required for screening children for TB disease; and (2) refine diagnostic algorithms for classification of TB using age-specific predictors through machine-learning methods.

      Family-Centered Care to Improve Loss to Follow-Up in Children with TB who are Exposed at Home

      • Investigator: Meredith Brooks
      • National Institute of Allergy and Infectious Disease

      When children live in a household with someone with tuberculosis (TB) disease, young children in particular are at high risk of TB infection and often progress rapidly to active TB disease if they are not promptly initiated on appropriate TB preventive treatment. Using data from a prospective household contact cohort study in Lima, Peru, we aim to explore individual-level characteristics for children and their adult household member with TB disease to identify risk factors for children initiated on drug-susceptible TB treatment being loss to follow-up. This information may identify family-related characteristics associated with loss to follow-up that can be mitigated through a family-centered care management approach.

      Geospatial Signals in Pediatric Tuberculosis

      • Investigator: Meredith Brooks
      • Funding Source: American Lung Association

      Cases of children with tuberculosis are considered sentinel events because children become sick and die with this infection much faster than adults do. Yet children have been largely neglected in the study of how tuberculosis spreads and how to control it. Active case-finding efforts are essential to detecting missing cases of tuberculosis and identifying individuals who may benefit from preventive treatment. By using information about the geographic locations and links between child and adult cases of tuberculosis, our research will make children the cornerstone of new tuberculosis surveillance methods to evaluate strategies that can promptly identify tuberculosis transmission, reduce the number of undetected tuberculosis cases and, ultimately, drive down tuberculosis rates globally.

      Intensified Patient-Finding Intervention to Increase the Detection of Children with Tuberculosis

      • Investigator: Meredith Brooks
      • Funding Source: William F. Milton Fund at Harvard University; National Institute of Allergy and Infectious Disease

      Children with tuberculosis are vastly under detected and underdiagnosed. An intensified patient-finding intervention using systematic verbal screening at health facilities was undertaken in two locations–Pakistan and Bangladesh–to increase the detection of children who may be at high risk for tuberculosis disease. These projects aim to identify gaps along the pediatric tuberculosis care cascade; understand age-specific clinical presentation and risk factors for tuberculosis disease, extrapulmonary presentations, and poor treatment outcomes; refine clinical algorithms to expedite decision-making for treatment initiation; and explore other topics related to pediatric tuberculosis epidemiology.

        Providence/Boston CFAR Developmental Award: Counting Kids: Enhancing Detection of Pediatric Tuberculosis in Ukraine

        • Investigator: Helen Jenkins
        • Funding Source: National Institute of Allergy and Infectious Diseases

          Tuberculosis in Teens: A Geospatial Approach to Predict Community Transmission

          • Investigator: Meredith Brooks
          • Funding Source: National Institute of Allergy and Infectious Diseases

          Adolescents are a unique population that have been routinely neglected from tuberculosis guidelines. However, due to their ability to spread tuberculosis and their high number of social contacts, adolescents may be a key node fueling cycles of local community tuberculosis transmission in high incidence settings. Through a K01 Award from NIAID, NIH, we use geospatial and genotypic analyses to complete the following objectives: (1) To characterize the spatial heterogeneity of tuberculosis transmission events in adolescents. (2) To predict the spatial distribution of tuberculosis transmission events in adolescents. (3) To estimate and compare, through simulation, the impact of adolescent-tailored screening and treatment interventions on reducing community tuberculosis transmission.

          Understanding Multi-Level Barriers to Completing the Pediatric Latent Tuberculosis Infection Care Cascade

          • Investigator: Jeffrey Campbell
          • Funding Source: Firland Foundation

          This is a mixed methods study that seeks to understand facilitators and barriers to completing the pediatric TB infection care cascade. We are conducting interviews, focus group discussions, and surveys with clinicians and families to gather data that will enable subsequent interventional studies to improve TB infection care access in our local community.