Tuberculosis Pathways to Care and Transmission of Multidrug Resistance in India.

Rationale: India is experiencing a regional increase in cases of multidrug-resistant tuberculosis (MDR-TB). Objectives: Given the complexity of MDR-TB diagnosis and care, we sought to address key knowledge gaps in MDR risk factors, care delays, and drivers of delay to help guide disease control. Methods: From January 2018 to September 2019, we conducted interviews with adults registered with the National TB Elimination Program for MDR (n = 128) and non-MDR-TB (n = 269) treatment to quantitatively and qualitatively study care pathways. We collected treatment records and GeneXpert-TB/RIF diagnostic reports. Measurements and Main Results: MDR-TB was associated with young age and crowded residence. GeneXpert rifampicin resistance diversity was measured at 72.5% Probe E. Median time from symptom onset to diagnosis of MDR was 90 days versus 60 days for non-MDR, Wilcoxon P < 0.01. Delay decreased by a median of 30 days among non-MDR patients with wider access to GeneXpert, Wilcoxon P = 0.02. Pathways to care were complex, with a median (interquartile range) of 4 (3-5) and 3 (2-4) encounters for MDR and non-MDR, respectively. Of patients with MDR-TB, 68% had their first encounter in the private sector, and this was associated with a larger number of subsequent healthcare encounters and catastrophic expenditure. Conclusions: The association of MDR with young age, crowding, and low genotypic diversity raises concerns of ongoing MDR transmission fueled by long delays in care. Delays are decreasing with GeneXpert use, suggesting the need for routine use in presumptive TB. Qualitatively, we identify the need to improve patient retention in the National TB Elimination Program and highlight patients' trust relationship with private providers.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.

Management and control of multidrug-resistant tuberculosis (MDR-TB): Addressing policy needs for India.

Multidrug-resistant tuberculosis (MDR-TB) challenges TB control efforts because of delays in diagnosis plus its long-term treatment which has toxic effects. Of TB high-incidence countries, India carries the highest burden of MDR-TB cases. We describe policy issues in India concerning MDR-TB diagnosis and management in a careful review of the literature including a systematic review of studies on the prevalence of MDR-TB. Of 995 articles published during 2001-2016 and retrieved from the PubMed, only 20 provided data on the population prevalence of MDR-TB. We further reviewed and describe diagnostic criteria and treatment algorithms in use and endorsed by the Revised National TB Control Program of India. We discuss problems encountered in treating MDR-TB patients with standardized regimens. Finally, we provide realistic suggestions for policymakers and program planners to improve the management and control of MDR-TB in India.Journal of Public Health Policy advance online publication, 6 May 2016; doi:10.1057/jphp.2016.14.

Risk factors associated with MDR-TB at the onset of therapy among new cases registered with the RNTCP in Mumbai, India.

BACKGROUND: Multidrug - resistant TB (MDR - TB) has emerged as a major threat to global TB control efforts in recent years. Facilities for its diagnosis and treatment are limited in many high - burden countries, including India. In hyper - endemic areas like Mumbai, screening for newly diagnosed cases at a higher risk of acquiring MDR - TB is necessary, for initiating appropriate and timely treatment, to prevent its further spread. OBJECTIVE: To assess risk factors associated with MDR - TB among Category I, new sputum smear-positive cases, at the onset of therapy. MATERIALS AND METHODS: The study applied an unmatched case - control design for 514 patients (106 cases with MDR - TB strains and 408 controls with non - MDR - TB strains). The patients were registered with the Revised National Tuberculosis Control Program (RNTCP) in four selected wards of Mumbai during April 2004 - January 2007. Data were collected through semi - structured interviews and drug susceptibility test results. RESULTS: Multivariate analysis indicated that infection with the Beijing strain (OR = 3.06; 95% C.I. = 1.12 - 8.38; P = 0.029) and female gender (OR = 1.68; 95% C.I. = 1.02 - 2.87; P = 0.042) were significant predictors of MDR-TB at the onset of therapy. CONCLUSION: The study provides a starting point to further examine the usefulness of these risk factors as screening tools in identifying individuals with MDR-TB, in settings where diagnostic and treatment facilities for MDR-TB are limited.

Multidrug-resistant tuberculosis (MDR-TB) in India: an attempt to link biosocial determinants.

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a possible threat to global tuberculosis control efforts in recent years. It is a challenge not only from a public health point of view but also in the context of global economy, especially in the absence of treatment for MDR-TB at national-level programs in developing countries. Biological accounts are insufficient to understand the emergence and dynamics of drug resistance. This article focuses essentially on the need for a holistic perspective, linking biosocial determinants that would probably lead to better insights into MDR-TB control strategies.

Cultural concepts of tuberculosis and gender among the general population without tuberculosis in rural Maharashtra, India.

Gender-specific patterns of experience, meaning, and behaviour for tuberculosis (TB) require consideration to guide control programmes. To clarify concepts of gender, culture, and TB in a rural endemic population of Maharashtra, India, this study of 80 men and 80 women employed qualitative and quantitative methods of cultural epidemiology, using a locally adapted semi-structured Explanatory Model Interview Catalogue (EMIC) interviews are instruments for cultural epidemiological study of the distribution of illness-related experiences, meanings, and behaviours. This interview queried respondents without active disease about vignettes depicting a man and woman with typical features of TB. Emotional and social symptoms were frequently reported for both vignettes, but more often considered most distressing for the female vignette; specified problems included arranging marriages, social isolation, and inability to care for children and family. Job loss and reduced income were regarded most troubling for the male vignette. Men and women typically identified sexual experience as the cause of TB for opposite-sex vignettes. With wider access to information about TB, male respondents more frequently recommended allopathic doctors and specialty services. Discussion considers the practical significance of gender-specific cultural concepts of TB.