Identifying overlooked factors associated with multidrug-resistant tuberculosis: an ecological study across 201...

Multidrug-resistant tuberculosis (MDR-TB) is a critical global health challenge. Whether environmental, nutritional, and socioeconomic factors are associated with MDR-TB remains insufficiently investigated.

We analyzed outcome and exposure data from the Global Burden of Disease (GBD) Study and four additional databases covering 201 countries and territories from 1990 to 2021. Sex ratio, diabetes prevalence, and HIV/AIDS burden were regressed out of each outcome before analysis. Every candidate exposure was then both regressed against the confounder-adjusted outcome and correlated with it. Benjamini-Hochberg adjusted P values, together with correlation strength, determined which factors were retained for display. Effects are expressed as the absolute change per interquartile range (IQR) increase in exposure. Drug-susceptible tuberculosis served as a control outcome.

Per IQR of exposure, unsafe sanitation was associated with 13.9 more prevalent cases per 100,000 (95% CI 13.0-14.7) and 2.87 more deaths per 100,000 (2.72-3.03); unsafe water source with 11.2 (10.5-12.0) and 2.64 (2.49-2.78); and polluting fuels for cooking with 10.7 (9.8-11.6) and 2.74 (2.58-2.89). After further adjustment for GDP per capita and health expenditure, six associations remained significant, including unsafe sanitation, unsafe water source, absence of handwashing facilities and underweight (e.g., unsafe sanitation 2.8 per 100,000 per IQR, P < 0.001). Most of these associations were stronger for drug-susceptible disease than for MDR-TB, with the exception of diet low in fruits.

Unsafe sanitation, unsafe water source, and polluting fuels for cooking are the population-level factors most strongly associated with MDR-TB burden. These associations are largely shared with drug-susceptible tuberculosis, supporting their integration into tuberculosis control efforts as a whole.