Samyra R. Cox

Background: Despite advancements in tuberculosis (TB) care and treatment, numerous individual and health system barriers prevent populations from engaging in TB services. We summarized these barriers to inform the development of implementation strategies that strengthen TB care and improve TB outcomes. Methods: We conducted an umbrella review of English-language studies of barriers to healthseeking, demand and access to TB services in high TB-burden countries, published January 2010 to June 2025 in PubMed. Barriers were analyzed using content analysis. To ground this work in the lived realities of individuals affected by TB, we consulted with community advisory board members throughout the project. Results: Of 1,325 studies screened, 104 underwent full-text review, and 63 studies met inclusion criteria. We identified 25 barriers across three levels: 13 patient/community-level barriers (knowledge and awareness, symptom perception and severity, cultural beliefs and perceptions, stigma and social barriers, social support and family dynamics, gender-specific barriers, health system mistrust and quality concerns, medication-related concerns, financial constraints and economic burden, employment and work-related constraints, mobility and distance from care, legal constraints, substance use), four HCW-level barriers (knowledge and training, diagnostics and clinical practices, attitudes and provider behavior, workload and human resource constraints), and eight health system-level barriers (inadequate supervision and support, geographic accessibility, workload and staffing, policy and governance, financing, public-private sector coordination, emergency contexts, service availability). Conclusions: This umbrella review offers a perspective on how barriers interact across the TB care cascade. Findings will be used to prioritize barriers using a community-based participatory approach, contributing to the development of a framework for enhancing TB service demand and access.

Objective: To comprehensively identify the multi-level barriers to tuberculosis prevention and care in high-burden settings, and prioritize them according to their perceived harm and modifiability. Methods: We conducted a multi-phase stakeholder-engaged study, synthesized barriers from two scoping reviews, and then convened regional workshops in Hyderabad, India, and Nairobi, Kenya, prioritizing TB survivors, community advocates, and frontline healthcare workers (HCWs). Participants refined existing barriers and added new ones. They then completed a Best-Worst Scaling (BWS) exercise to assess the perceived impact (harm) of each barrier, and Likert-based questions to assess perceived modifiability. Hierarchical Bayes (HB) modeling was used to generate mean impact scores (MIS) for each barrier, and mean scores for barrier modifiability (range, 1-4) were calculated. Findings: 81 stakeholders from 28 countries participated, and 65 completed the survey (24% community representatives/advocates, 36% frontline HCWs; 17% were TB survivors). Stakeholder input expanded the barrier set from 31 to 39, with most newly added barriers at the health systems level. The BWS identified systems-level drug and supply challenges (MIS=5.8), patient/community-level financial factors (MIS=5.2), and inadequate provision of holistic care (MIS=4.9) as the highest-impact barriers; 7 of the top 10 barriers overlapped across regions. Asia participants placed 5 barriers, and Africa participants 10 in the high-impact/high-modifiability priority quadrant; four were shared across both: patient/community knowledge, HCW knowledge, HCW attitudes, and lack of community engagement mechanisms. Conclusion: Incorporating the lived experience of TB-affected groups revealed substantial gaps in literature-derived TB care barriers. The high-impact, modifiable barriers identified provide actionable targets for programs in high-burden settings.

The World Health Organization recommends TB contact investigation in high-burden countries. We examined the implementation reach of two contact investigation strategies in South Africa . Kharitode TB, a cluster-randomized crossover trial, compared household- and incentive-based contact investigation in 28 clinics (July 2016-January 2020). Clinics used each strategy for 18 months (separated by a six-month “washout”). Adults recently diagnosed with TB (index participants) were enrolled. In the household-based arm, contact persons were screened and provided sputum samples at home. In the incentive-based arm, index participants distributed referral coupons to their contacts, who received a $3.50 incentive upon presenting for screening at clinics. We used mixed-effects logistic regression with random intercepts for clinics to examine factors associated with index participant enrollment and sputum collection from contact persons. In the household-based arm, 782/1,269 (61.6%) index participants consented, 1,882 contact persons were enrolled and sputum samples were collected from 988/1,882 (52.5%). In the incentive-based arm, 780/1,295 (60.2%) index participants consented, 1,940 contact persons were enrolled and sputum was collected from 1,431/1,940 (73.8%). Index participants living with HIV (adjusted odds ratio, aOR=0.56, 95% CI 0.38-0.83) or unknown HIV status (aOR=0.12, 95% CI 0.07-0.20) were less likely to participate in the study. Contact persons in the incentive-based arm were more likely to provide a sputum sample compared to those in the household-based arm (aOR=2.12, 95% CI 1.80-2.50). Regardless of the study arm, cough (aOR=2.27, 95% CI 1.87-2.77), current smoking (aOR=2.22, 95% CI 1.63-3.02), and living with HIV (aOR=1.89, 95% CI 1.36-3.62) were associated with higher likelihood of sputum collection. There were gaps in implementation reach at the stages of contacting and enrolling index participants, enrolling individuals with HIV, and obtaining sputum, especially among those under 18 years and household contact persons.

Background: An estimated 10% of tuberculosis (TB) survivors who recently completed treatment in India develop TB again. We sought to develop a parsimonious model for predicting TB recurrence that can help target post-treatment active case finding among the highest-risk TB survivors. Methods: The TB Aftermath trial enrolled TB survivors at treatment completion from 6 public TB clinics in Maharashtra, India, and assessed participants at 6-month intervals. Our prediction endpoint was recurrent TB diagnosed within 18 months of treatment completion. Candidate variables included risk factors for recurrence identified a priori and lung function assessments. We used LASSO (Least Absolute Shrinkage and Selection Operator) regression to shortlist predictors and estimated probability of recurrence using logistic regression. We conducted internal validation, assessed discrimination, and plotted calibration. Model selection was based on practical utility and predictive accuracy. For our selected model, we identified a cutoff for achieving 90% sensitivity. Results: Among 1033 participants, we identified 85 (8.2%) recurrences. Several 5-item models measurable at treatment completion had moderate discrimination. Our selected model included sex, household income, body mass index, peak expiratory flow from spirometry, and history of multiple TB episodes. The selected model had a cross-validated c-statistic of .69 (95% CI: .56–.77) and acceptable calibration (intercept: .03 [95% CI: −.03, .09]; slope: .66 [.08–1.24]). TB survivors with a predicted probability ≥3.7% accounted for 90% of recurrences. Conclusions: A 5-item tool, measurable at treatment completion, showed moderate predictive accuracy for recurrent TB. At scale, a simple 5-item prediction tool may increase efficiency of post-treatment active case finding.

Rationale: C-reactive protein (CRP) has demonstrated utility as a point-of-care triage test for tuberculosis (TB) in clinical settings, particularly among people with human immunodeficiency virus (HIV), but its performance for general-population TB screening is not well characterized. Objective: To assess the accuracy of CRP for detecting pulmonary TB disease among individuals undergoing community-based screening or presenting for evaluation of TB symptoms in Kampala, Uganda. Methods: We pooled data from two case–control studies conducted between May 2018 and December 2022 among adolescents and adults (⩾15 yr) in Kampala, Uganda. We conducted community-based screening for TB, regardless of symptoms. We enrolled people with Xpert MTB/RIF Ultra–positive (including trace) sputum results and a sample of people with Ultra-negative results. We also enrolled symptomatic patients diagnosed with TB and controls with negative TB evaluations from ambulatory care settings. Participants underwent further evaluation, including sputum culture, CRP, and HIV testing. We assessed the accuracy of CRP alone or with symptom screening against a bacteriologic reference standard. Our primary analysis evaluated the sensitivity and specificity of CRP at a cutoff of 5 mg/L. Diagnostic performance was summarized by calculating the area under the receiver operating curve (AUC). Results: In the community setting (n = 544), CRP ⩾ 5 mg/L had a sensitivity of 55.3% (95% confidence interval, 47.0–63.4%) and specificity of 84.7% (79.7–88.8%) for confirmed TB; AUC was 0.75 (0.70–0.79). Screening for CRP ⩾ 5 mg/L or positive symptoms increased sensitivity to 92.0% (86.4–95.8%) at the expense of specificity (57.1% [50.8–63.2%]). In the ambulatory care setting (n = 944), sensitivity of CRP ⩾ 5 mg/L was 86.7% (81.8–90.7%), specificity was 68.6% (64.8–72.2%), and AUC (0.84 [0.81–0.87]) did not differ significantly by HIV status. CRP ⩾ 5 mg/L was >90% sensitive among individuals with a medium or high semiquantitative Xpert result in both settings. Conclusions: Although CRP did not meet World Health Organization (WHO) TB screening benchmarks in the community, it demonstrated high specificity, and sensitivity was high among individuals with high sputum bacillary burden who are likely to be most infectious. In ambulatory care, estimated sensitivity and specificity were each within 4 percentage points of WHO benchmarks, with no meaningful difference in performance by HIV status.

Background: Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs). Methods: We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs < 6 years, by study arm, initiated on TPT after ruling out TB disease. Study staff will collect socio-demographic and clinical data to identify risk factors for TB recurrence and will measure post-TB lung impairment. In both arms, an 18-month “mop-up” visit will be conducted to ascertain outcomes. We will use the RE-AIM framework to characterize implementation processes and explore acceptability through in-depth interviews with index patients, HHCs and HCWs (n = 100). Cost-effectiveness will be assessed by calculating the incremental cost per TB case detected within 12 months and projected for disability-adjusted life years averted based on modeled estimates of morbidity, mortality, and time with infectious TB. Discussion: This novel trial will guide India’s scale-up of post-treatment ACF and provide an evidence base for designing strategies to detect recurrent and new TB in other high burden settings. Trial registration: NCT04333485, registered April 3, 2020. CTRI/2020/05/025059 [Clinical Trials Registry of India], registered May 6 2020.

Background: Unhealthy alcohol use is associated with increased morbidity and mortality among persons with HIV and tuberculosis (TB). Computer-based interventions (CBIs) can reduce unhealthy alcohol use, are scalable, and may improve outcomes among patients with HIV or TB. Objective: We assessed the acceptability, adaptability, and feasibility of a novel CBI for alcohol reduction in HIV and TB clinical settings in Pune, India. Methods: We conducted 10 in-depth interviews with persons with alcohol use disorder (AUD): TB (6/10), HIV (2/10), or HIV-TB co-infected (1/10) selected using convenience sampling method, no HIV or TB disease (1/10), 1 focus group with members of Alcoholics Anonymous (AA; n=12), and 2 focus groups with health care providers (HCPs) from a tertiary care hospital (n=22). All participants reviewed and provided feedback on a CBI for AUD delivered by a 3D virtual counselor. Qualitative data were analyzed using structured framework analysis. Results: The majority (9/10) of in-depth interview respondents were male, with median age 42 (IQR 38-45) years. AA focus group participants were all male (12/12), and HCP focus group participants were predominantly female (n=15). Feedback was organized into 3 domains: (1) virtual counselor acceptability, (2) intervention adaptability, and (3) feasibility of the CBI intervention in clinic settings. Overall, in-depth interview participants found the virtual counselor to be acceptable and felt comfortable honestly answering alcohol-related questions. All focus group participants preferred a human virtual counselor to an animal virtual counselor so as to potentially increase CBI engagement. Additionally, interaction with a live human counselor would further enhance the program’s effectiveness by providing more flexible interaction. HCP focus group participants noted the importance of adding information on the effects of alcohol on HIV and TB outcomes because patients were not viewed as appreciating these linkages. For local adaptation, more information on types of alcoholic drinks, additional drinking triggers, motivators, and activities to substitute for drinking alcohol were suggested by all focus group participants. Intervention duration (about 20 minutes) and pace were deemed appropriate. HCPs reported that the CBI provides systematic, standardized counseling. All focus group and in-depth interview participants reported that the CBI could be implemented in Indian clinical settings with assistance from HIV or TB program staff. Conclusions: With cultural tailoring to patients with HIV and TB in Indian clinical care settings, a virtual counselor–delivered alcohol intervention is acceptable and appears feasible to implement, particularly if coupled with person-delivered counseling.