Case Control Study of Vitamin D Status and Adult Multidrug-resistant Pulmonary Tuberculosis in Maharashtra, India

To combat the substantial global burdens of TB and MDR-TB, novel treatment strategies and expanded prevention efforts are critical. Although vitamin D supplementation shows promise in both of these areas, additional observational evidence is needed to support future randomized clinical trials. This case-control study in Mumbai, India will clarify associations between vitamin D status, active MDR-TB disease and TB infection to expand the evidence-base and inform the design of future trials of vitamin D supplementation for use in MDR-TB infection. This study will assess vitamin D status, diet, and anthropometry among adult outpatient MDR-TB cases and controls in Mumbai, India and assess TB infection among controls. The specific aims are: 1) evaluate the association between vitamin D status and active MDR-TB infection; 2) evaluate the association between vitamin D status and TB infection among controls; 3) collect formative data to inform the design of future randomized clinical trials evaluating vitamin D supplementation and other interventions in MDR-TB treatment and prevention. To fulfill the first aim, a case-control study will be conducted comparing vitamin D status between pulmonary MDR-TB cases (including extensively drug-resistant (XDR) and pre-XDR cases) and two sets of controls: 1) household controls (recruited from the cases' household contacts) and 2) non-household controls (recruited from non-respiratory departments of local hospitals). The second aim will involve a cross-sectional study among controls assessing the association between vitamin D status and TB infection using QuantiFERON-TB (QFT-TB) interferon-gamma release assays.

• Inclusion criteria for cases:

• Currently receiving outpatient treatment for MDR-TB according to standard of care (including new cases and those who have been on treatment for no more than one month)
• Residence in Mumbai M/E, M/W or H/E ward for at least six months
• 18-60 years old
• Permanently living with at least two eligible controls
• Confirmation that they have disclosed their TB status to household and will allow inclusion of their household members in the study
• Inclusion criteria for household contact controls:

• Was a permanent member of the index case's household for at least one year prior to the case's DR TB diagnosis
• No symptoms of active TB disease
• Residence in Mumbai M/E, M/W or H/E ward for at least six months
• 18-60 years old
• Inclusion criteria for non-household controls:

• 18 - 60 years of age
• Residence in Mumbai M/E, M/W or H/E ward for at least six months
• No symptoms of active TB disease
• No history of household contact with a TB patient in last 2 years

Exclusion criterion for both cases and controls:

• Pregnancy.