The performance of digital technologies for measuring tuberculosis medication adherence: a systematic review.

INTRODUCTION: Digital adherence technologies (DATs), such as phone-based technologies and digital pillboxes, can provide more person-centric approaches to support tuberculosis (TB) treatment. However, there are varying estimates of their performance for measuring medication adherence. METHODS: We conducted a systematic review (PROSPERO-CRD42022313526), which identified relevant published literature and preprints from January 2000 to April 2023 in five databases. Studies reporting quantitative data on the performance of DATs for measuring TB medication adherence against a reference standard, with at least 20 participants, were included. Study characteristics and performance outcomes (eg, sensitivity, specificity and predictive values) were extracted. Sensitivity was the proportion correctly classified as adherent by the DAT, among persons deemed adherent by a reference standard. Specificity was the proportion correctly classified as non-adherent by the DAT, among those deemed non-adherent by a reference standard. RESULTS: Of 5692 studies identified by our systematic search, 13 met inclusion criteria. These studies investigated medication sleeves with phone calls (branded as '99DOTS'; N=4), digital pillboxes N=5), ingestible sensors (N=2), artificial intelligence-based video-observed therapy (N=1) and multifunctional mobile applications (N=1). All but one involved persons with TB disease. For medication sleeves with phone calls, compared with urine testing, reported sensitivity and specificity were 70%-94% and 0%-61%, respectively. For digital pillboxes, compared with pill counts, reported sensitivity and specificity were 25%-99% and 69%-100%, respectively. For ingestible sensors, the sensitivity of dose detection was ≥95% compared with direct observation. Participant selection was the most frequent potential source of bias. CONCLUSION: The limited number of studies available suggests suboptimal and variable performance of DATs for dose monitoring, with significant evidence gaps, notably in real-world programmatic settings. Future research should aim to improve understanding of the relationships of specific technologies, settings and user engagement with DAT performance and should measure and report performance in a more standardised manner.

Barriers to engagement in the care cascade for tuberculosis disease in India: A systematic review of quantitative studies.

BACKGROUND: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. METHODS AND FINDINGS: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. CONCLUSIONS: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade.

Improving measurement of tuberculosis care cascades to enhance people-centred care.

Care cascades represent the proportion of people reaching milestones in care for a disease and are widely used to track progress towards global targets for HIV and other diseases. Despite recent progress in estimating care cascades for tuberculosis (TB) disease, they have not been routinely applied at national and subnational levels, representing a lost opportunity for public health impact. As researchers who have estimated TB care cascades in high-incidence countries (India, Madagascar, Nigeria, Peru, South Africa, and Zambia), we describe the utility of care cascades and identify measurement challenges, including the lack of population-based disease burden data and electronic data capture, the under-reporting of people with TB navigating fragmented and privatised health systems, the heterogeneity of TB tests, and the lack of post-treatment follow-up. We outline an agenda for rectifying these gaps and argue that improving care cascade measurement is crucial to enhancing people-centred care and achieving the End TB goals.

Spatializing stigma-power: Mental health impacts of spatial stigma in a legally-excluded settlement in Mumbai, India.

In disadvantaged neighborhoods such as informal settlements (or "slums" in the Indian context), infrastructural deficits and social conditions have been associated with residents' poor mental health. Within social determinants of health framework, spatial stigma, or negative portrayal and stereotyping of particular neighborhoods, has been identified as a contributor to health deficits, but remains under-examined in public health research and may adversely impact the mental health of slum residents through pathways including disinvestment in infrastructure, internalization, weakened community relations, and discrimination. Based on analyses of individual interviews (n = 40) and focus groups (n = 6) in Kaula Bandar (KB), an informal settlement in Mumbai with a previously described high rate of probable common mental disorders (CMD), this study investigates the association between spatial stigma and mental health. The findings suggest that KB's high rate of CMDs stems, in part, from residents' internalization of spatial stigma, which negatively impacts their self-perceptions and community relations. Employing the concept of stigma-power, this study also reveals that spatial stigma in KB is produced through willful government neglect and disinvestment, including the denial of basic services (e.g., water and sanitation infrastructure, solid waste removal). These findings expand the scope of stigma-power from an individual-level to a community-level process by revealing its enactment through the actions (and inactions) of bureaucratic agencies. This study provides empirical evidence for the mental health impacts of spatial stigma and contributes to understanding a key symbolic pathway by which living in a disadvantaged neighborhood may adversely affect health.

Impact of the 99DOTS digital adherence technology on tuberculosis treatment outcomes in North India: a pre-post study.

BACKGROUND: 99DOTS is a cellphone-based digital adherence technology. The state of Himachal Pradesh, India, made 99DOTS available to all adults being treated for drug-sensitive tuberculosis (TB) in the public sector in May 2018. While 99DOTS has engaged over 500,000 people across India, few studies have evaluated its effectiveness in improving TB treatment outcomes. METHODS: We compared treatment outcomes of adults with drug-sensitive TB before and after Himachal Pradesh's 99DOTS launch using data from India's national TB database. The pre-intervention group initiated treatment between February and October 2017 (N = 7722), and the post-intervention group between July 2018 and March 2019 (N = 8322). We analyzed engagement with 99DOTS and used multivariable logistic regression to estimate impact on favorable treatment outcomes (those marked as cured or treatment complete). RESULTS: In the post-intervention group, 2746 (33.0%) people called 99DOTS at least once. Those who called did so with a wide variation in frequency (< 25% of treatment days: 24.6% of callers; 25-50% of days: 15.1% of callers, 50-75% of days: 15.7% of callers; 75-100% of days: 44.6% of callers). In the pre-intervention group, 7186 (93.1%) had favorable treatment outcomes, compared to 7734 (92.9%) in the post-intervention group. This difference was not statistically significant (OR = 0.981, 95% CI [0.869, 1.108], p = 0.758), including after controlling for individual characteristics (adjusted OR = 0.970, 95% CI [0.854, 1.102]). CONCLUSIONS: We found no statistically significant difference in treatment outcomes before and after a large-scale implementation of 99DOTS. Additional work could help to elucidate factors mediating site-wise variations in uptake of the intervention.

Divided infrastructure: legal exclusion and water inequality in an urban slum in Mumbai, India.

Inadequate water access is central to the experience of urban inequality across low- and middle-income countries and leads to adverse health and social outcomes. Previous literature on water inequality in Mumbai, India's second largest city, offers diverse explanations for water disparities between and within slums.(1) This study provides new insights on water disparities in Mumbai's slums by evaluating the influence of legal status on water access. We analyzed data from 593 households in Mandala, a slum with legally recognized (notified) and unrecognized (non-notified) neighborhoods. Relative to households in a notified neighborhood, households in a non-notified neighborhood suffered disadvantages in water infrastructure, accessibility, reliability, and spending. Non-notified households used significantly fewer liters per capita per day of water, even after controlling for religion and socioeconomic status. Our findings suggest that legal exclusion may be a central driver of water inequality. Extending legal recognition to excluded slum settlements, neighborhoods, and households could be a powerful intervention for reducing urban water inequality.

Sources of exposure and risk among employees infected with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in a large, urban, tertiary-care hospital in the United States.

Objective: Hospital employees are at risk of SARS-CoV-2 infection through transmission in 3 settings: (1) the community, (2) within the hospital from patient care, and (3) within the hospital from other employees. We evaluated probable sources of infection among hospital employees based on reported exposures before infection. Design: A structured survey was distributed to participants to evaluate presumed COVID-19 exposures (ie, close contacts with people with known or probable COVID-19) and mask usage. Participants were stratified into high, medium, low, and unknown risk categories based on exposure characteristics and personal protective equipment. Setting: Tertiary-care hospital in Boston, Massachusetts. Participants: Hospital employees with a positive SARS-CoV-2 PCR test result between March 2020 and January 2021. During this period, 573 employees tested positive, of whom 187 (31.5%) participated. Results: We did not detect a statistically significant difference in the proportion of employees who reported any exposure (ie, close contacts at any risk level) in the community compared with any exposure in the hospital, from either patients or employees. In total, 131 participants (70.0%) reported no known high-risk exposure (ie, unmasked close contacts) in any setting. Among those who could identify a high-risk exposure, employees were more likely to have had a high-risk exposure in the community than in both hospital settings combined (odds ratio, 1.89; P = .03). Conclusions: Hospital employees experienced exposure risks in both community and hospital settings. Most employees were unable to identify high-risk exposures prior to infection. When respondents identified high-risk exposures, they were more likely to have occurred in the community.

Can digital adherence technologies reduce inequity in tuberculosis treatment success? Evidence from a randomised controlled trial.

INTRODUCTION: Tuberculosis (TB) is a global health emergency and low treatment adherence among patients is a major barrier to ending the TB epidemic. The WHO promotes digital adherence technologies (DATs) as facilitators for improving treatment adherence in resource-limited settings. However, limited research has investigated whether DATs improve outcomes for high-risk patients (ie, those with a high probability of an unsuccessful outcome), leading to concerns that DATs may cause intervention-generated inequality. METHODS: We conducted secondary analyses of data from a completed individual-level randomised controlled trial in Nairobi, Kenya during 2016-2017, which evaluated the average intervention effect of a novel DAT-based behavioural support programme. We trained a causal forest model to answer three research questions: (1) Was the effect of the intervention heterogeneous across individuals? (2) Was the intervention less effective for high-risk patients? nd (3) Can differentiated care improve programme effectiveness and equity in treatment outcomes? RESULTS: We found that individual intervention effects-the percentage point reduction in the likelihood of an unsuccessful treatment outcome-ranged from 4.2 to 12.4, with an average of 8.2. The intervention was beneficial for 76% of patients, and most beneficial for high-risk patients. Differentiated enrolment policies, targeted at high-risk patients, have the potential to (1) increase the average intervention effect of DAT services by up to 28.5% and (2) decrease the population average and standard deviation (across patients) of the probability of an unsuccessful treatment outcome by up to 8.5% and 31.5%, respectively. CONCLUSION: This DAT-based intervention can improve outcomes among high-risk patients, reducing inequity in the likelihood of an unsuccessful treatment outcome. In resource-limited settings where universal provision of the intervention is infeasible, targeting high-risk patients for DAT enrolment is a worthwhile strategy for programmes that involve human support sponsors, enabling them to achieve the highest possible impact for high-risk patients at a substantially improved cost-effectiveness ratio.

Lessons from SARS-CoV-2 in India: A data-driven framework for pandemic resilience.

India experienced a massive surge in SARS-CoV-2 infections and deaths during April to June 2021 despite having controlled the epidemic relatively well during 2020. Using counterfactual predictions from epidemiological disease transmission models, we produce evidence in support of how strengthening public health interventions early would have helped control transmission in the country and significantly reduced mortality during the second wave, even without harsh lockdowns. We argue that enhanced surveillance at district, state, and national levels and constant assessment of risk associated with increased transmission are critical for future pandemic responsiveness. Building on our retrospective analysis, we provide a tiered data-driven framework for timely escalation of future interventions as a tool for policy-makers.

Tuberculosis care cascade in Zambia - identifying the gaps in order to improve outcomes: a population-based analysis.

OBJECTIVE: Tuberculosis (TB) remains a leading cause of morbidity and mortality in Zambia, especially for people living with HIV (PLHIV). We undertook a care cascade analysis to quantify gaps in care and align programme improvement measures with areas of need. DESIGN: Retrospective, population-based analysis. SETTING: We derived national-level estimates for each step of the TB care cascade in Zambia. Estimates were informed by WHO incidence estimates, nationally aggregated laboratory and notification registers, and individual-level programme data from four provinces. PARTICIPANTS: Participants included all individuals with active TB disease in Zambia in 2018. We characterised the overall TB cascade and disaggregated by drug susceptibility results and HIV status. RESULTS: In 2018, the total burden of TB in Zambia was estimated to be 72 495 (range, 40 495-111 495) cases. Of these, 43 387 (59.8%) accessed TB testing, 40 176 (55.4%) were diagnosed with TB, 36 431 (50.3%) were started on treatment and 32 700 (45.1%) completed treatment. Among all persons with TB lost at any step along the care cascade (n=39 795), 29 108 (73.1%) were lost prior to accessing diagnostic services, 3211 (8.1%) prior to diagnosis, 3745 (9.4%) prior to initiating treatment and 3731 (9.4%) prior to treatment completion. PLHIV were less likely than HIV-negative individuals to successfully complete the care cascade (42.8% vs 50.2%, p<0.001). Among those with rifampicin-resistant TB, there was substantial attrition at each step of the cascade and only 22.8% were estimated to have successfully completed treatment. CONCLUSIONS: Losses throughout the care cascade resulted in a large proportion of individuals with TB not completing treatment. Ongoing health systems strengthening and patient-centred engagement strategies are needed at every step of the care cascade; however, scale-up of active case finding strategies is particularly critical to ensure individuals with TB in the population reach initial stages of care. Additionally, a renewed focus on PLHIV and individuals with drug-resistant TB is urgently needed to improve TB-related outcomes in Zambia.

Understanding Nonadherence to Tuberculosis Medications in India Using Urine Drug Metabolite Testing: A Cohort Study.

BACKGROUND: Poor adherence to tuberculosis (TB) treatment is associated with disease recurrence and death. Little research has been conducted in India to understand TB medication nonadherence. METHODS: We enrolled adult drug-susceptible TB patients, approximately half of whom were people with human immunodeficiency virus (PWH), in Chennai, Vellore, and Mumbai. We conducted a single unannounced home visit to administer a survey assessing reasons for nonadherence and collect a urine sample that was tested for isoniazid content. We described patient-reported reasons for nonadherence and identified factors associated with nonadherence (ie, negative urine test) using multivariable logistic regression. We also assessed the association between nonadherence and treatment outcomes. RESULTS: Of 650 participants in the cohort, 77 (11.8%) had a negative urine test. Nonadherence was independently associated with daily wage labor (adjusted odds ratio [aOR], 2.7; confidence interval [CI], 1.1-6.5; P = .03), the late continuation treatment phase (aOR, 2.0; CI, 1.1-3.9; P = .03), smear-positive pulmonary disease (aOR, 2.1; CI, 1.1-3.9; P = .03), alcohol use (aOR, 2.5; CI, 1.2-5.2; P = .01), and spending ≥30 minutes collecting medication refills (aOR, 6.6; CI, 1.5-29.5; P = .01). People with HIV reported greater barriers to collecting medications than non-PWH. Among 167 patients reporting missing doses, reported reasons included traveling from home, forgetting, feeling depressed, and running out of pills. The odds of unfavorable treatment outcomes were 4.0 (CI, 2.1-7.6) times higher among patients with nonadherence (P < .0001). CONCLUSION: Addressing structural and psychosocial barriers will be critical to improve TB treatment adherence in India. Urine isoniazid testing may help identify nonadherent patients to facilitate early intervention during treatment.

Acceptability of the Medication Event Reminder Monitor for Promoting Adherence to Multidrug-Resistant Tuberculosis Therapy in Two Indian Cities: Qualitative Study of Patients and Health Care Providers.

BACKGROUND: Patients with multidrug-resistant tuberculosis (MDR-TB) face challenges adhering to medications, given that treatment is prolonged and has a high rate of adverse effects. The Medication Event Reminder Monitor (MERM) is a digital pillbox that provides pill-taking reminders and facilitates the remote monitoring of medication adherence. OBJECTIVE: This study aims to assess the MERM's acceptability to patients and health care providers (HCPs) during pilot implementation in India's public sector MDR-TB program. METHODS: From October 2017 to September 2018, we conducted qualitative interviews with patients who were undergoing MDR-TB therapy and were being monitored with the MERM and HCPs in the government program in Chennai and Mumbai. Interview transcripts were independently coded by 2 researchers and analyzed to identify the emergent themes. We organized findings by using the Unified Theory of Acceptance and Use of Technology (UTAUT), which outlines 4 constructs that predict technology acceptance-performance expectancy, effort expectancy, social influence, and facilitating conditions. RESULTS: We interviewed 65 patients with MDR-TB and 10 HCPs. In patient interviews, greater acceptance of the MERM was related to perceptions that the audible and visual reminders improved medication adherence and that remote monitoring reduced the frequency of clinic visits (performance expectancy), that the device's organization and labeling of medications made it easier to take them correctly (effort expectancy), that the device facilitated positive family involvement in the patient's care (social influences), and that remote monitoring made patients feel more cared for by the health system (facilitating conditions). Lower patient acceptance was related to problems with the durability of the MERM's cardboard construction and difficulties with portability and storage because of its large size (effort expectancy), concerns regarding stigma and the disclosure of patients' MDR-TB diagnoses (social influences), and the incorrect understanding of the MERM because of suboptimal counseling (facilitating conditions). In their interviews, HCPs reported that MERM implementation resulted in fewer in-person interactions with patients and thus allowed HCPs to dedicate more time to other tasks, which improved job satisfaction. CONCLUSIONS: Several features of the MERM support its acceptability among patients with MDR-TB and HCPs, and some barriers to patient use could be addressed by improving the design of the device. However, some barriers, such as disease-related stigma, are more difficult to modify and may limit use of the MERM among some patients with MDR-TB. Further research is needed to assess the accuracy of MERM for measuring adherence, its effectiveness for improving treatment outcomes, and patients' sustained use of the device in larger scale implementation.

Measuring Tuberculosis Medication Adherence: A Comparison of Multiple Approaches in Relation to Urine Isoniazid Metabolite Testing Within a Cohort Study in India.

Background: Nonadherence to tuberculosis medications is associated with poor outcomes. However, measuring adherence in practice is challenging. In this study, we evaluated the accuracy of multiple tuberculosis adherence measures. Methods: We enrolled adult Indians with drug-susceptible tuberculosis who were monitored using 99DOTS, a cellphone-based technology. During an unannounced home visit with each participant, we assessed adherence using a pill estimate, 4-day dose recall, a last missed dose question, and urine isoniazid metabolite testing. We estimated the area under the receiver operating characteristic curve (AUC) for each alternate measure in comparison to urine testing. 99DOTS data were analyzed using patient-reported doses alone and patient- and provider-reported doses, the latter reflecting how 99DOTS is implemented in practice. We assessed each measure's operating characteristics, with particular interest in specificity-that is, the percentage of participants detected as being nonadherent by each alternate measure, among those who were nonadherent by urine testing. Results: Compared with urine testing, alternate measures had the following characteristics: 99DOTS patient-reported doses alone (area under the curve [AUC], 0.65; specificity, 70%; 95% CI, 58%-81%), 99DOTS patient- and provider-reported doses (AUC, 0.61; specificity, 33%; 95% CI, 22%-45%), pill estimate (AUC, 0.55; specificity, 21%; 95% CI, 12%-32%), 4-day recall (AUC, 0.60; specificity, 23%; 95% CI, 14%-34%), and last missed dose question (AUC, 0.65; specificity, 52%; 95% CI, 40%-63%). Conclusions: Alternate measures missed detecting at least 30% of people who were nonadherent by urine testing. The last missed dose question performed similarly to 99DOTS using patient-reported doses alone. Tuberculosis programs should evaluate the feasibility of integrating more accurate, objective measures, such as urine testing, into routine care.

Explaining Differences in the Acceptability of 99DOTS, a Cell Phone-Based Strategy for Monitoring Adherence to Tuberculosis Medications: Qualitative Study of Patients and Health Care Providers.

BACKGROUND: 99DOTS is a cell phone-based strategy for monitoring tuberculosis (TB) medication adherence that has been rolled out to more than 150,000 patients in India's public health sector. A considerable proportion of patients stop using 99DOTS during therapy. OBJECTIVE: This study aims to understand reasons for variability in the acceptance and use of 99DOTS by TB patients and health care providers (HCPs). METHODS: We conducted qualitative interviews with individuals taking TB therapy in the government program in Chennai and Vellore (HIV-coinfected patients) and Mumbai (HIV-uninfected patients) across intensive and continuation treatment phases. We conducted interviews with HCPs who provide TB care, all of whom were involved in implementing 99DOTS. Interviews were transcribed, coded using a deductive approach, and analyzed with Dedoose 8.0.35 software (SocioCultural Research Consultants, LLC). The findings of the study were interpreted using the unified theory of acceptance and use of technology, which highlights 4 constructs associated with technology acceptance: performance expectancy, effort expectancy, social influences, and facilitating conditions. RESULTS: We conducted 62 interviews with patients with TB, of whom 30 (48%) were HIV coinfected, and 31 interviews with HCPs. Acceptance of 99DOTS by patients was variable. Greater patient acceptance was related to perceptions of improved patient-HCP relationships from increased phone communication, TB pill-taking habit formation due to SMS text messaging reminders, and reduced need to visit health facilities (performance expectancy); improved family involvement in TB care (social influences); and from 99DOTS leading HCPs to engage positively in patients' care through increased outreach (facilitating conditions). Lower patient acceptance was related to perceptions of reduced face-to-face contact with HCPs (performance expectancy); problems with cell phone access, literacy, cellular signal, or technology fatigue (effort expectancy); high TB- and HIV-related stigma within the family (social influences); and poor counseling in 99DOTS by HCPs or perceptions that HCPs were not acting upon adherence data (facilitating conditions). Acceptance of 99DOTS by HCPs was generally high and related to perceptions that the 99DOTS adherence dashboard and patient-related SMS text messaging alerts improve quality of care, the efficiency of care, and the patient-HCP relationship (performance expectancy); that the dashboard is easy to use (effort expectancy); and that 99DOTS leads to better coordination among HCPs (social influences). However, HCPs described suboptimal facilitating conditions, including inadequate training of HCPs in 99DOTS, unequal changes in workload, and shortages of 99DOTS medication envelopes. CONCLUSIONS: In India's government TB program, 99DOTS had high acceptance by HCPs but variable acceptance by patients. Although some factors contributing to suboptimal patient acceptance are modifiable, other factors such as TB- and HIV-related stigma and poor cell phone accessibility, cellular signal, and literacy are more difficult to address. Screening for these barriers may facilitate targeting of 99DOTS to patients more likely to use this technology.

Understanding pretreatment loss to follow-up of tuberculosis patients: an explanatory qualitative study in Chennai, India.

Introduction: Pretreatment loss to follow-up (PTLFU)-dropout of patients after diagnosis but before treatment registration-is a major gap in tuberculosis (TB) care in India and globally. Patient and healthcare worker (HCW) perspectives are critical for developing interventions to reduce PTLFU. Methods: We tracked smear-positive TB patients diagnosed via sputum microscopy from 22 diagnostic centres in Chennai, one of India's largest cities. Patients who did not start therapy within 14 days, or who died or were lost to follow-up before official treatment registration, were classified as PTLFU cases. We conducted qualitative interviews with trackable patients, or family members of patients who had died. We conducted focus group discussions (FGDs) with HCWs involved in TB care. Interview and FGD transcripts were coded and analysed with Dedoose software to identify key themes. We created categories into which themes clustered and identified relationships among thematic categories to develop an explanatory model for PTLFU. Results: We conducted six FGDs comprising 53 HCWs and 33 individual patient or family member interviews. Themes clustered into five categories. Examining relationships among categories revealed two pathways leading to PTLFU as part of an explanatory model. In the first pathway, administrative and organisational health system barriers-including the complexity of navigating the system, healthcare worker absenteeism and infrastructure failures-resulted in patients feeling frustration or resignation, leading to disengagement from care. In turn, HCWs faced work constraints that contributed to many of these health system barriers for patients. In the second pathway, negative HCW attitudes and behaviours contributed to patients distrusting the health system, resulting in refusal of care. Conclusion: Health system barriers contribute to PTLFU directly and by amplifying patient-related challenges to engaging in care. Interventions should focus on removing administrative hurdles patients face in the health system, improving quality of the HCW-patient interaction and alleviating constraints preventing HCWs from providing patient-centred care.

Evaluation of the Accuracy of 99DOTS, a Novel Cellphone-based Strategy for Monitoring Adherence to Tuberculosis Medications: Comparison of DigitalAdherence Data With Urine Isoniazid Testing.

99DOTS is a cellphone-based strategy for monitoring tuberculosis medication adherence. In a sample of 597 Indian patients with tuberculosis, we compared 99DOTS' adherence assessments against results of urine isoniazid tests collected during unannounced home visits. 99DOTS had suboptimal accuracy for measuring adherence, partly due to poor patient engagement with 99DOTS.