Lindsey M Locks, Vaishnavi Kaipilyawar, Komal Jain, Arthur VanValkenburg, Meagan Karoly, Madolyn R Dauphinais, Chelsie Cintron, Senbagavalli Prakash Babu, Kimberly Maloomian, Sheetal Verma, Noyal Mariya Joseph, Sonali Sarkar, Nonika Rajkumari, W Evan Johnson, C Robert Horsburgh, Jerrold J Ellner, Padmini Salgame, Natasha S Hochberg, Subitha Lakshminarayanan, Prakash Babu Narasimhan, Pranay Sinha
Six months of combined food rations and daily MMS was followed by improved antigen-specific Th1 cytokine responses, suggesting this impairment may be partially reversible on a clinically feasible timescale. As a single-arm study without a concurrent comparator with undernutrition measured at follow-up, observed changes cannot be causally attributed to the intervention. Trial registration: NCT03598842.
BACKGROUND: Undernutrition is the leading population-attributable risk factor for tuberculosis (TB), yet whether associated immune impairments are reversible with nutritional rehabilitation remains unclear.
METHODS: In TB LION (Puducherry, India), 105 QuantiFERON-positive household contacts were stratified by BMI (<18.5 vs ≥18.5 kg/m2). Participants with low BMI (n=53) received 6 months of food rations plus daily multiple micronutrient supplement (MMS) without iron. Fourteen cytokines were measured by Luminex in supernatants from the unstimulated (Nil) and M. tuberculosis (Mtb)-antigen-stimulated (TB2) IGRA assay at baseline and 6 months; 11 with acceptable detection rates constituted the primary analytic set. Linear regression tested associations of weight and hemoglobin change with composite immune pathway scores.
RESULTS: At baseline, participants with low BMI had attenuated Mtb-specific Th1 cytokine responses (interaction GMR 0.70 for IFN-γ, 0.55 for IL-2; both p=0.005), despite comparable or elevated innate and regulatory cytokines. After 6 months, Th1 responses increased (IFN-γ change GMR 1.41, 95% CI 1.10-1.80, p=0.005, q=0.06; IL-2 1.63, 1.01-2.63, p=0.046, q=0.25, suggestive). This increase reflected falling unstimulated background, not higher stimulated output. Weight gain was unrelated to composite scores but associated with elevated concentrations of 7 of 14 cytokines (all p<0.05). Hemoglobin gain was inversely associated with Th17 and pro-inflammatory scores but not Th1.
CONCLUSIONS: Six months of combined food rations and daily MMS was followed by improved antigen-specific Th1 cytokine responses, suggesting this impairment may be partially reversible on a clinically feasible timescale. As a single-arm study without a concurrent comparator with undernutrition measured at follow-up, observed changes cannot be causally attributed to the intervention. Trial registration: NCT03598842.