Tuberculosis - Learning the Impact of Nutrition
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 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.
Inclusion Criteria: Household Contacts

 -  Household contact that has been roommate of eligible index case for at least two of
 the previous four months (See index case criteria below).

 -  HIV seronegative

 -  Willing to be tested for pregnancy

 -  Age 18-55 years

 -  Willingness by the patient to attend scheduled follow-up visits and undergo study
 assessments

 -  Able to provide informed consent

 Exclusion Criteria: Household Contacts

 -  In the team's judgement, individual is not expected to survive for 12 months

 -  HIV infection or not willing to undergo HIV testing (if no documented HIV test)

 -  Pregnant at enrollment

 -  Known diabetes mellitus or evidence of diabetes on HA1C

 -  Xpert positive among those able to produce sputum

 -  TB symptoms (night sweats, weight loss, cough)

 -  Any history of TB disease during their lifetime

 -  We will retrospectively exclude household contacts of presumed TB cases whose cultures
 do not confirm Mtb or who are Xpert negative.

 -  Recall receiving anti-parasitic treatment within the past 6 months

 -  Evidence of kwashiorkor (pitting edema of foot or lower leg)

 -  Abnormal K, Mg, Phos in those with BMI <16

 Inclusion Criteria: Index Case

 -  Sputum Ziehl-Neelsen stain positive for AFB (≥1+)

 -  Culture or Xpert positive for Mtb; those who are smear+ but ultimately Xpert or
 culture negative, will be included until their culture results return at which time
 they will retrospectively be removed from the study.

 -  No history of TB treatment (i.e., no history of partial or complete treatment for a
 previous TB episode)

 -  Has at least 1 household contact with whom they have shared a room during the previous
 four months

 -  Agrees to have household contact notified about study

 Exclusion Criteria: Index Case

 -  No Xpert or culture confirmation and unable to provide sputum sample

 -  No household contacts who share room

 -  Known MDR or XDR TB case

 -  BMI <16 kg/m2

 -  Lower extremity edema/kwashiorkor

 -  Reported neuropathy in lower extremities (may result from thiamine deficiency)