Tuberculosis - Learning the Impact of Nutrition

The proposed work is based on the finding that one-third of the world is infected with the bacteria Mycobacterium tuberculosis (Mtb) and only 10% of these individuals develop TB. The study aims to identify factors that drive progression to disease and study signals (markers of the immune response) that detect who will progress to active TB and why this happens. Armed with these markers, the study will address how malnutrition and worms alter this signal profile to cause active TB. The work will be conducted in India, where there are 2.8 million TB cases each year - more than any other country - and where the government has committed to eliminating TB by 2035. Data suggest that malnutrition and parasites increase risk of TB disease so the investigators will feed malnourished household contacts and have those with parasites receive medication to treat these. Using this infrastructure, the investigators will evaluate the immunologic impact of feeding on TB pathogenesis. An additional aim is to understand the role of parasitic worms with the goal of determining the utility of low-cost ($.02 per dose) worm treatment as part of TB control efforts. Risk of developing TB will be evaluated for 120 household contacts of TB patients in the setting of their malnutrition and parasites. There are four study arms comprised of thirty participants each -- malnourished with parasite infection, malnourished with no parasite infection, well-nourished with parasite infection, and well-nourished with no parasite infection. Correlates of risk of disease will be assessed using blood messenger RNA/micro RNA (mRNA/miRNA) sequencing and T cell immune markers. The TB LION study will confirm that malnutrition and worms increase the risk of active TB and will provide the basis for effective interventions that could change the face of the TB pandemic and have a profound impact on the health of people worldwide. Participants in this study will be household contacts of tuberculosis index cases. The index cases in this study do not participate in the study once a household contact is established. All interventions and follow up are only being conducted within the household contact cohort. All intervention supplies, treatments, and biologics will be purchased internationally.