The Tuberculosis Cascade of Care in India’s Public Sector: A Systematic Review and Meta-analysis

Citation: Subbaraman R, Nathavitharana RR, Satyanarayana S, Pai M, Thomas BE, Chadha VK, et al. (2016) The Tuberculosis Cascade of Care in India’s Public Sector: A Systematic Review and Meta-analysis. PLoS Med 13(10): e1002149. doi:10.1371/journal.pmed.1002149
Published: October 25, 2016

Abstract
Tuberculosis-x-ray-1Background: India has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world’s “missing” patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The “cascade of care” is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions.
Methods and Findings: The care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India’s TB patients. We define the TB cascade as including the following patient populations: total prevalent active TB patients in India, TB patients who reach and undergo evaluation at RNTCP diagnostic facilities, patients successfully diagnosed with TB, patients who start treatment, patients retained to treatment completion, and patients who achieve 1-y recurrence-free survival. We estimate each step of the cascade for 2013 using data from two World Health Organization (WHO) reports (2014–2015), one WHO dataset (2015), and three RNTCP reports (2014–2016). In addition, we conduct three targeted systematic reviews of the scientific literature to identify 39 unique articles published from 2000–2015 that provide additional data on five indicators that help estimate different steps of the TB cascade. We construct separate care cascades for the overall population of patients with active TB and for patients with specific forms of TB—including new smear-positive, new smear-negative, retreatment smear-positive, and multidrug-resistant (MDR) TB.
The WHO estimated that there were 2,700,000 (95%CI: 1,800,000–3,800,000) prevalent TB patients in India in 2013. Of these patients, we estimate that 1,938,027 (72%) TB patients were evaluated at RNTCP facilities; 1,629,906 (60%) were successfully diagnosed; 1,417,838 (53%) got registered for treatment; 1,221,764 (45%) completed treatment; and 1,049,237 (95%CI: 1,008,775–1,083,243), or 39%, of 2,700,000 TB patients achieved the optimal outcome of 1-y recurrence-free survival.
The separate cascades for different forms of TB highlight different patterns of patient attrition. Pretreatment loss to follow-up of diagnosed patients and post-treatment TB recurrence were major points of attrition in the new smear-positive TB cascade. In the new smear-negative and MDR TB cascades, a substantial proportion of patients who were evaluated at RNTCP diagnostic facilities were not successfully diagnosed. Retreatment smear-positive and MDR TB patients had poorer treatment outcomes than the general TB population. Limitations of our analysis include the lack of available data on the cascade of care in the private sector and substantial uncertainty regarding the 1-y period prevalence of TB in India.
Conclusions: Increasing case detection is critical to improving outcomes in India’s TB cascade of care, especially for smear-negative and MDR TB patients. For new smear-positive patients, pretreatment loss to follow-up and post-treatment TB recurrence are considerable points of attrition that may contribute to ongoing TB transmission. Future multisite studies providing more accurate information on key steps in the public sector TB cascade and extension of this analysis to private sector patients may help to better target interventions and resources for TB control in India.

Author Summary
Why was this study done?

  • India is the country with the highest burden of tuberculosis (TB) in the world, with one-quarter of the world’s patients with active TB disease.
  •  The World Health Organization (WHO) estimates that India has nearly 1 million “missing” TB patients, who have not been reported to the national TB program and who therefore may not have received effective TB care.
  • Government reports and studies from local regions of India suggest that a considerable percentage of TB patients are evaluated at government health facilities but fail to be diagnosed with TB or fail to start TB treatment even if they are correctly diagnosed, but these reports and studies have not been collectively analyzed to provide national estimates of critical points at which patients are being “lost” from the government TB program.
  •  The purpose of our study is to estimate how many TB patients in India’s national TB program are not being detected, not enrolling in treatment, not completing treatment, and not surviving without TB recurrence for 1 y after finishing treatment, using a model called the “cascade of care.”

What did the researchers do and find?

  • To estimate different steps of the TB cascade of care in India in 2013, we collected data from multiple official reports published by the WHO and India’s national TB program.
  •  We also conducted three systematic searches of the medical literature to identify 39 studies published between 2000–2015 that describe patient loss to follow-up at different steps of India’s TB cascade; we synthesized some of these findings using an approach called meta-analysis.
  •  We estimate that, of about 2,700,000 prevalent TB patients in India in 2013, 1,938,027 (72%) were evaluated at government TB health facilities; 1,629,906 (60%) were successfully diagnosed with TB; 1,417,838 (53%) started TB treatment; 1,221,764 (45%) completed TB treatment; and about 1,049,237 (39%) achieved the optimal outcome of 1-y recurrence-free survival.
  •  Patients who had a history of TB in the past (also called retreatment patients) and patients with TB resistant to the two most effective medications (also called multidrug-resistant TB) have considerably worse outcomes compared to other TB patients.
  •  The critical points at which patients are being “lost” to the government system varies depending on the type of TB that a patient has.

What do these findings mean?

  • Our findings suggest that, for some forms of TB—such as smear-negative TB and multidrug-resistant TB—increasing detection and diagnosis of new patients by using new TB diagnostic tests may be the most important intervention for improving patient outcomes.
  •  For other types of TB patients—such as new smear-positive patients—reducing loss to follow-up immediately after TB is diagnosed and improving adherence to medications so that TB is less likely to recur might be the best interventions to improve patient outcomes.
  •  Since a considerable proportion of patients who complete TB therapy experience recurrence of TB, routine follow-up of all patients for 1 y after completion of TB therapy may be an efficient approach for identifying new TB patients.
  •  Our study is limited by the fact that very little information is available regarding treatment outcomes for TB patients receiving care in the private sector and by considerable uncertainty in the number of prevalent TB patients in India.
  •  We recommend that well-designed research be conducted at multiple sites in India’s national TB program and in the private sector to improve the accuracy of the TB cascade in the future and to monitor progress on TB control.

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