Emergence of drug resistance in patients with tuberculosis cared for by the Indian health-care system: a dynamic modelling study.

BACKGROUND: India has the highest number of patients with tuberculosis and multidrug-resistant tuberculosis in the world. We used a transmission model to project the emergence of drug resistance in India due to incorrect tuberculosis management practices in multiple sectors, including public and private providers, chemists, and non-allopathic practitioners.

METHODS: We constructed a dynamic Markov model to represent India's tuberculosis epidemic, including a probabilistic framework reflecting complex treatment-seeking pathways. Underlying drug resistance and the acquisition of drug resistance during treatment were included. India-specific epidemiological data, including tuberculosis management practices, were obtained from published literature. Outcomes, which included annual risk of infection, incidence of new disease, prevalence of untreated tuberculosis, and tuberculosis-related mortality, were stratified by underlying drug resistance, as well as by health sector to understand how each sector contributes to the emergence of drug resistance.

FINDINGS: If tuberculosis management practices across sectors in India remain unchanged over the next 20 years, we estimated a 47% increase in the incidence of isoniazid resistance, a 152% increase in multidrug-resistant tuberculosis incidence, a 242% increase in prevalent untreated multidrug-resistant tuberculosis, and a 275% increase in the risk of multidrug-resistant tuberculosis infection. By 2032, an estimated 85% of multidrug-resistant tuberculosis will be primary multidrug-resistant tuberculosis compared with only 15% in 2012. The public sector contributed 87% of acquired multidrug-resistant tuberculosis, related to irregular adherence; the remainder came from the private sector, related to treatment non-completion. Chemists and non-allopathic practitioners do not treat with rifampicin, but because of the high rates of inappropriate isoniazid-containing regimens, and treatment non-adherence, this would generate isoniazid resistance.

INTERPRETATION: We predict a gradual transformation from the current epidemic of drug-susceptible tuberculosis to a drug-resistant epidemic. Evidence-based strategies to improve provider practices and patient adherence across health sectors are urgently needed to prevent this.

FUNDING: United States Agency for International Development and the Canadian Institutes for Health Research.