Exploring the alarming pre-diagnosis attrition rates among MDR-TB patients in Bhopal, India, and the global implications for tuberculosis care.
In the bustling health clinics of central India, a silent crisis unfolds daily—one that remains largely invisible in global health reports and public discourse. Imagine seven patients walking into a tuberculosis clinic, all displaying warning signs for a dangerous, drug-resistant strain of the disease. Now picture four of them never receiving the proper tests to confirm this life-threatening condition. This isn't hypothetical; it was the reality for 60% of presumptive multidrug-resistant TB patients in Bhopal district, India, according to a revealing 2017 study 1 6 .
Multidrug-resistant tuberculosis (MDR-TB) represents one of the most urgent global health crises of our time. Unlike regular TB, MDR-TB resists the two most powerful first-line treatment drugs, making it dramatically more difficult and expensive to treat.
The World Health Organization estimates that only about 23% of the estimated 580,000 MDR-TB cases globally were properly diagnosed in 2015, creating a massive gap in our ability to control this deadly disease 1 2 . What happens to these undiagnosed patients? They continue spreading drug-resistant strains in their communities, potentially developing more severe symptoms, and facing limited treatment options as their condition progresses unrecognized.
The story of MDR-TB diagnosis in Bhopal district offers a fascinating microcosm of this global challenge, revealing both the systemic weaknesses in our healthcare systems and the promising solutions emerging from operational research.
To understand the significance of the Bhopal findings, we first need to grasp what makes MDR-TB so menacing. Multidrug-resistant TB is defined as tuberculosis that resists treatment with both isoniazid and rifampicin—the cornerstone medications of standard TB treatment 5 . Treating MDR-TB requires switching to second-line drugs that are less effective, more toxic, and must be taken for much longer—up to 20-24 months in some cases 5 .
The diagnostic pathway for MDR-TB should be straightforward: identify patients with risk factors (called "presumptive MDR-TB"), conduct drug susceptibility testing (DST), and initiate appropriate treatment. In reality, this pathway full of potential breakdown points. Patients may never be identified as high-risk, samples may not reach laboratories, test results may get lost, and patients may drop out before treatment begins.
Globally, the statistics paint a grim picture of these systemic failures. A 2019 study in China showed that while pre-diagnosis attrition was relatively low at 3.1%, an alarming 36.2% of confirmed MDR-TB patients never began treatment 3 9 . The situation in India appears particularly challenging, with one study from Chennai reporting high pre-treatment attrition despite low pre-diagnosis losses 3 .
In 2014, researchers launched a comprehensive investigation into the MDR-TB diagnostic pathway within the Revised National Tuberculosis Control Programme (RNTCP) setting in Bhopal district, central India 1 . This wasn't a small, limited study—it involved tracking all 770 registered TB patients who met the criteria for presumptive MDR-TB throughout the entire year 1 6 .
Tracked in the study
Study duration (2014)
Analysis of program records
The study employed a retrospective cohort design, meaning researchers looked back at existing program records rather than following patients forward in time. This approach allowed them to capture the real-world performance of the health system without interfering with normal operations 1 .
The criteria for being classified as "presumptive MDR-TB" included:
Line Probe Assay (LPA) used for smear-positive samples
Data collection was meticulous, occurring between September 2015 and March 2016. Researchers compiled lists of eligible patients from TB treatment registers, then tracked each one through multiple record systems: referral registers at District TB Centers, laboratory registers at the National Reference Laboratory, and treatment registers at DR-TB centers 1 . Each patient was tracked for three months after becoming eligible for DST, with extended follow-up for cases with invalid results or smear-negative samples 1 .
The findings from Bhopal revealed a diagnostic pathway in crisis. Of the 770 patients who should have received drug susceptibility testing, only 311 (40%) actually underwent DST 1 6 . This meant 459 patients—60% of the total—slipped through the cracks before diagnosis, a phenomenon researchers termed "pre-diagnosis attrition" 1 .
Even more revealing was what happened to these "lost" patients. The overwhelming majority—417 out of 459 (91%)—were never even identified as presumptive MDR-TB by the healthcare system 1 6 . The problem wasn't primarily about patients refusing tests or samples being mishandled in labs—the system was failing at the most fundamental step: recognizing who needed testing.
| Step in Diagnostic Pathway | Number of Patients | Percentage |
|---|---|---|
| Eligible for DST | 770 | 100% |
| Underwent DST | 311 | 40% |
| Pre-diagnosis attrition | 459 | 60% |
| Identified as presumptive MDR-TB | 353 | 46% |
| Not identified (among attrition) | 417 | 91% of attrition |
| Confirmed MDR-TB cases | 20 | 6.4% of tested |
For those who successfully navigated the pathway, the time between becoming eligible for DST and actually undergoing testing was relatively swift—a median of 4 days 1 . This demonstrated that when the system successfully identified and referred patients, testing occurred promptly.
The final diagnosis numbers put the crisis in perspective: of the 311 patients tested, only 20 were confirmed to have MDR-TB 1 6 . While this might seem like a small number, it represents a significant caseload for a single district, especially considering these patients would have otherwise gone undiagnosed.
The Bhopal study didn't just identify the scale of the problem—it revealed clear patterns in who was most likely to fall through the diagnostic cracks. Certain patient groups faced significantly higher risks of pre-diagnosis attrition 1 6 :
Those over 64 years were particularly vulnerable
Patients from medical colleges had higher attrition rates
Those eligible in the first quarter (before CbNAAT introduction)
Patients with extra-pulmonary TB (affecting body parts other than lungs)
The improved performance after the introduction of CbNAAT in the second quarter suggests that diagnostic technology plays a crucial role in reducing attrition 1 . The simpler, faster molecular tests likely made it easier for healthcare workers to follow through with testing protocols.
| Risk Factor Category | Specific Factors | Likely Reasons |
|---|---|---|
| Demographic | Age >64 years | Possible mobility issues, complex health needs |
| Health Facility Type | Medical colleges | Higher patient loads, coordination challenges |
| Clinical Characteristics | Extra-pulmonary TB, specific previously treated categories | Difficult sample collection, complex patient histories |
| System Timing | Quarter 1 (pre-CbNAAT) | Less optimized diagnostic protocols |
The battle against MDR-TB relies on an evolving arsenal of diagnostic technologies. The Bhopal study highlighted two crucial molecular diagnostic tools that have revolutionized MDR-TB detection:
This molecular test detects genetic mutations in the TB bacteria that confer resistance to key drugs like rifampicin and isoniazid. LPAs provide results within hours rather than the weeks required by traditional culture methods 5 .
Traditional phenotypic drug susceptibility testing required growing TB bacteria in culture media containing antibiotics, then observing whether growth occurred—a process that could take 2-3 months to yield results 5 . During this extended waiting period, patients might receive ineffective treatment, continue spreading drug-resistant strains, or drop out of care entirely.
Modern molecular tests like LPA and CbNAAT detect resistance directly from patient samples by identifying specific genetic mutations associated with drug resistance. For example, they can scan for changes in the rpoB gene (linked to rifampicin resistance) or katG gene and inhA promoter (associated with isoniazid resistance) 5 .
The WHO now recommends molecular tests like GeneXpert as the initial diagnostic for all TB patients, recognizing their potential to dramatically accelerate both diagnosis and treatment initiation 5 . The introduction of CbNAAT in Bhopal's second quarter likely contributed to the modest reduction in pre-diagnosis attrition observed later in the study 1 .
While technology plays a crucial role, the Bhopal findings underscore that the most significant bottlenecks often occur long before samples reach advanced laboratories. The fact that 91% of attrition resulted from failure to identify patients as presumptive MDR-TB points to fundamental challenges in healthcare delivery 1 6 .
Similar patterns emerge globally. A 2023 study in Jharkhand and Gujarat, India, found that 41% of pulmonary TB and 51% of extra-pulmonary TB patients experienced significant delays in their diagnosis and treatment journey . The causes were multifaceted, including lack of awareness about TB symptoms, limited access to healthcare facilities, and inadequate follow-up systems.
The Bhopal researchers identified several operational barriers contributing to the identification gap 1 6 :
These findings highlight that technological solutions alone cannot solve the MDR-TB diagnosis gap. Effective interventions must also address the human and systemic factors—training healthcare workers, improving patient tracking systems, streamlining referral processes, and raising community awareness.
The Bhopal study, while revealing significant system failures, also points toward concrete solutions. The reduction in attrition after introducing CbNAAT suggests that simplifying diagnostic processes can yield immediate benefits 1 . Similarly, identifying specific patient groups at higher risk enables targeted interventions.
Based on these findings, researchers recommended several key strategies 1 6 8 :
Improving identification and referral processes through better training, supervision, and job aids for healthcare workers
Developing more robust systems to ensure at-risk patients complete the diagnostic pathway
Focusing extra attention on identified high-risk groups, such as elderly patients and those with extra-pulmonary TB
Strategic deployment of rapid molecular tests like CbNAAT to simplify testing and reduce turnaround times
The lessons from Bhopal extend far beyond one Indian district. Similar challenges have been documented across high TB burden countries. In China, for instance, while pre-diagnosis attrition was lower, the country faced substantial pre-treatment attrition (36.2%) where diagnosed MDR-TB patients never began treatment 3 9 . The median total delay from DST eligibility to treatment initiation was 117 days in China—nearly four months of potential disease transmission and clinical deterioration 9 .
The Bhopal study represents a powerful example of how operational research—investigations conducted within routine healthcare settings—can identify specific bottlenecks and guide improvements in service delivery. By shining a light on the invisible crisis of pre-diagnosis attrition, it provides health systems worldwide with both a warning and a roadmap.
As we work toward the global goal of ending TB by 2030, understanding and addressing these diagnostic gaps becomes increasingly crucial. The silent missing patients in Bhopal and beyond represent not just statistical anomalies, but opportunities to strengthen our healthcare systems and save countless lives from this ancient yet evolving disease.