Prevention of Household Tuberculosis with Optimal Nutrition (PHOTON) (360G-Wellcome-347480_Z_26_Z)

The Prevention of Household Tuberculosis with Optimal Nutrition (PHOTON) study investigates whether targeted nutritional supplementation can reduce tuberculosis (TB) transmission among household contacts (HHCs) of TB index cases in Indonesia and Tanzania, two high-burden settings where undernutrition is a major modifiable driver of TB risk. Emerging evidence suggests B vitamins, particularly B3 (niacin), enhance nicotinamide adenine dinucleotide (NAD+)-dependent immune pathways critical for Mycobacterium tuberculosis control, while multiple micronutrient supplementation (MMS) and balanced energy-protein (BEP) food product address broader nutrient deficiencies in TB- endemic populations. PHOTON is a multi-site, cluster-randomized controlled trial evaluating the efficacy of six months of daily high-dose B vitamins (HB), MMS, and BEP in reducing the incidence of bacteriologically confirmed symptomatic TB (BCsTB) among HHCs. Four intervention arms (placebo, HB, HB+MMS, and HB+MMS+BEP) will allow component-specific and combined efficacy assessment. Secondary objectives include evaluating effects on NAD/NADP status, vitamin and protein biomarkers, clinical TB, morbidity, mortality, and adherence. Exploratory objectives include assessing the cost-effectiveness of nutritional TB prevention strategies and establishing harmonized biorepositories. PHOTON will generate robust evidence on whether nutritional intervention can reduce TB incidence, informing scalable, low-cost interventions for high-burden communities. Keywords: tuberculosis, household contacts, nutrition, B-vitamins, niacin, NAD+, micronutrients, balanced energy-protein, prevention, randomized controlled trial.