Identifying overlooked factors associated with multidrug-resistant tuberculosis: an ecological study across 201 countries and regions, 1990-2021.

Abstract

Background: 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.

Methods: 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; the primary analyses included 4,019 country-years from 186 countries. 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.

Results: 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 of the thirteen principal exposures remained significantly associated with MDR-TB prevalence, 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.

Conclusions: 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.