Tuberculosis in Malawian children under five years old: exploring non-invasive diagnostic strategies and the impact of malnutrition on treatment pharmacokinetics

This project, supported through the Fogarty International Center's International Research Scientist Development Award (IRSDA) and led from Michigan State University with collaborators at Kamuzu University of Health Sciences (KUHeS), addresses critical gaps in the diagnosis and treatment of tuberculosis (TB) among Malawian children under five years old (U5s). Running from 2024 to 2029, the research targets an age group that experiences disproportionately high mortality from TB. The work has two complementary aims: first, to evaluate the accuracy of promising new diagnostic approaches that rely on noninvasively collected specimens; and second, to characterize how severe acute malnutrition, which co-prevalently affects this population, influences the pharmacokinetics of first-line antituberculosis therapy.

Accurate, child-appropriate diagnostics are essential to timely TB detection and treatment initiation in young children, but current approaches have limitations in sensitivity, feasibility and acceptability for U5s. This study will assess diagnostic strategies that utilize noninvasive specimen collection, offering the potential to improve case detection without subjecting children to invasive procedures that are difficult to perform and poorly tolerated. By rigorously evaluating the diagnostic accuracy of these noninvasive approaches in the Malawian pediatric population, the project aims to clarify their utility for routine clinical use and to inform guidelines for more effective screening and diagnosis of TB in young children in similar settings.

Concurrently, the research will document the pharmacokinetics of first-line antituberculosis medications in children who are also affected by severe acute malnutrition. Malnutrition is common in many high TB-burden settings and may alter drug absorption, distribution, metabolism, and elimination, potentially resulting in suboptimal drug exposures that compromise treatment efficacy or promote toxicity. By describing how severe acute malnutrition impacts drug behavior = in U5s receiving standard TB therapy, the project will generate evidence critical to optimizing dosing strategies and improving treatment outcomes in this vulnerable subgroup.

Taken together, these investigations will provide valuable insights into both diagnostic and treatment challenges for childhood TB in Malawi. The findings are intended to inform clinical practice and future research priorities, helping to refine diagnostic algorithms that are feasible for young children and to guide dosing recommendations that consider nutritional status. The project's partnership between Michigan State University and KUHeS exemplifies international collaboration to address global child health priorities and to generate contextually relevant evidence in sub-Saharan Africa. Ultimately, this work seeks to reduce morbidity and mortality from TB in Malawian U5s by advancing noninvasive diagnostic options and by clarifying the interplay between malnutrition and antituberculosis drug pharmacokinetics, setting the stage for expanded efforts to fill persistent knowledge gaps.