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.

Modeling the impact of tuberculosis interventions on epidemiologic outcomes and health system costs.

BACKGROUND: Tuberculosis (TB) programs must invest in a variety of TB specific activities in order to reach ambitious global targets. Uncertainty exists surrounding the potential impact of each of these activities. The objective of our study was to model different interventions and quantify their impact on epidemiologic outcomes and costs from the health system perspective. METHODS: Decision analysis was used to define the TB patient trajectory within the health system of three different countries. We considered up to seven different interventions that could affect either the natural history of TB, or patient trajectories within the health system. The expected impact of interventions were derived from published studies where possible. Epidemiologic outcomes and associated health system costs were projected for each scenario. RESULTS: With no specific intervention, TB related death rates are high and less than 10% of the population starts on correct treatment. Interventions that either prevent cases or affect all patients with TB disease early in their trajectory are expected to have the biggest impact, regardless of underlying epidemiologic characteristics of the setting. In settings with a private sector, improving diagnosis and appropriate treatment across all sectors is expected to have a major impact on outcomes. CONCLUSION: In all settings, the greatest benefit will come from early diagnosis of all forms of TB. Once this has been achieved more specific interventions, such as those targeting HIV, drug resistance or the private sector can be integrated to increase impact.

Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test.

Rapid progress has been made in the development of new diagnostic assays for tuberculosis in recent years. New technologies have been developed and assessed, and are now being implemented. The Xpert MTB/RIF assay, which enables simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance, was endorsed by WHO in December, 2010. This assay was specifically recommended for use as the initial diagnostic test for suspected drug-resistant or HIV-associated pulmonary tuberculosis. By June, 2012, two-thirds of countries with a high tuberculosis burden and half of countries with a high multidrug-resistant tuberculosis burden had incorporated the assay into their national tuberculosis programme guidelines. Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event, clinical and programmatic effects and cost-effectiveness remain to be defined. We review the rapidly growing body of scientific literature and discuss the advantages and challenges of using the Xpert MTB/RIF assay in areas where tuberculosis is endemic. We also review other prospects within the developmental pipeline. A rapid, accurate point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. Investment in the tuberculosis diagnostics pipeline should remain a major priority for funders and researchers.

Opportunities and challenges for cost-efficient implementation of new point-of-care diagnostics for HIV and tuberculosis.

Stakeholders agree that supporting high-quality diagnostics is essential if we are to continue to make strides in the fight against human immunodeficiency virus (HIV) and tuberculosis. Despite the need to strengthen existing laboratory infrastructure, which includes expanding and developing new laboratories, there are clear diagnostic needs where conventional laboratory support is insufficient. Regarding HIV, rapid point-of-care (POC) testing for initial HIV diagnosis has been successful, but several needs remain. For tuberculosis, several new diagnostic tests have recently been endorsed by the World Health Organization, but a POC test remains elusive. Human immunodeficiency virus and tuberculosis are coendemic in many high prevalence locations, making parallel diagnosis of these conditions an important consideration. Despite its clear advantages, POC testing has important limitations, and laboratory-based testing will continue to be an important component of future diagnostic networks. Ideally, a strategic deployment plan should be used to define where and how POC technologies can be most efficiently and cost effectively integrated into diagnostic algorithms and existing test networks prior to widespread scale-up. In this fashion, the global community can best harness the tremendous capacity of novel diagnostics in fighting these 2 scourges.