Food for thought: addressing undernutrition to end tuberculosis

Abstract

Tuberculosis is the leading cause of deaths from an infectious disease worldwide. WHO's End TB Strategy is falling short of several 2020 targets. Undernutrition is the leading population-level risk factor for tuberculosis. Studies have consistently found that undernutrition is associated with increased tuberculosis incidence, increased severity, worse treatment outcomes, and increased mortality. Modelling studies support implementing nutritional interventions for people living with tuberculosis and those at risk of tuberculosis disease to ensure the success of the End TB Strategy. In this Personal View, we highlight nutrition-related immunocompromisation, implications of undernutrition for tuberculosis treatment and prevention, the role of nutritional supplementation, pharmacokinetics and pharmacodynamics of antimycobacterial medications in undernourished people with tuberculosis, and the role of social protection interventions in addressing undernutrition as a tuberculosis risk factor. To catalyse action on this insufficiently addressed accelerant of the global tuberculosis epidemic, research should be prioritised to understand the immunological pathways that are impaired by nutrient deficiencies, develop tools to diagnose clinical and subclinical tuberculosis in people who are undernourished, and understand how nutritional status affects the efficacy of tuberculosis vaccine and therapy. Through primary research, modelling, and implementation research, policy change should also be accelerated, particularly in countries with a high burden of tuberculosis.

Figure 1:. Geographic overlap between tuberculosis and undernutrition across the globe.

Representation of (a) Tuberculosis (TB) incidence rates and (b) Undernutrition prevalence globally which shows geographic overlap.^,

Figure 2:. Malnourished Tanzanian children with tuberculosis have altered rifampin dose-response and increased mortality.

Scatterplot of peak rifampin concentration versus rifampin dose among 51 pediatric PLWTB in Haydom, Tanzania with body mass index BMI z-scores less than −2, −2 to −4, and less than −4, with greater pharmacokinetic variability in those with lower BMI z-scores. Mortality is indicated in red: 9/51 (17%) died during treatment, with 8/9 (89%) deaths occurring in PLWTB with baseline BMI Z-score less than −2. (C_max: peak concentration; BMI: body mass index; PLWTB: persons living with TB)

Figure 3:. Conceptual framework of undernutrition as it relates to tuberculosis

Numerous social determinants of health and diseases contribute to an undernourished state which can then increase the risk of TB disease, increase severity of TB disease, and increase risk of poor outcomes. Several factors included in the conceptual framework such as poverty, HIV, age, parasites, and alcoholism influence disease progression and treatment outcomes independently of nutrition. For clarity, these effects have not been depicted in the schematic diagram. (TB: tuberculosis; HIV: human immunodeficiency virus; PK: pharmacokinetics; LTBI; latent tuberculosis infection)