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Systematic screening for TB in children, especially among those at high risk of TB, can promote early diagnosis and treatment of TB. The World Health Organization (WHO) recently recommended C-Reactive Protein as a TB screening tool in adults and adolescents living with HIV (PLHIV). Thus, we aimed to assess the performance of point-of-care (POC) CRP as a screening tool for TB in children. A cross-sectional study was conducted at 2 primary health care facilities in Lusaka, Zambia between September 2020 -August 2021. Consecutive children (aged 5-14 years) presenting for TB services were enrolled irrespective of TB symptoms. All participants were screened for the presence of TB symptoms and signs, asked about TB contact history, and undertook a POC CRP test, chest X-ray, and sputum Xpert MTB/RIF Ultra test. The accuracy of CRP (≥10 mg/L cutoff) was determined using a microbiological reference standard (MRS) and a composite reference standard (CRS). Of 280 children enrolled and with complete results available, the median age was 10 years (IQR 7-12), 56 (20.0%) were HIV positive, 228 (81.4%) had a positive WHO symptom screen for TB, 62 (22.1%) had a close TB contact, and 79 (28.2%) had a positive CRP POC test. Five (1.8%) participants had confirmed TB, 71 (25.4%) had unconfirmed TB, and 204 (72.3%) had unlikely TB. When the MRS was used, the sensitivity of CRP was 80.0% (95%CI: 28.4-99.5%) and the specificity was 72.7% (95%CI: 67.1-77.9%). When the CRS was used, the sensitivity of CRP was 32.0% (95%CI: 23.3% - 42.5%), while the specificity was 74.0% (95%CI: 67.0% - 80.3%). Using the CRS, there were no statistically significant differences in sensitivity and specificity of CRP in the HIV positive and HIV negative individuals. Among children in Zambia, POC CRP had limited utility as a screening tool for TB. There remains a continued urgent need for better tools and strategies to improve TB detection in children., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kagujje et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Computer-aided detection (CAD) software packages quantify tuberculosis (TB)-compatible chest X-ray (CXR) abnormality as continuous scores. In practice, a threshold value is selected for binary CXR classification. We assessed the diagnostic accuracy of an alternative approach to applying CAD for TB triage: incorporating CAD scores in multivariable modeling., Methods: We pooled individual patient data from four studies. Separately, for two commercial CAD, we used logistic regression to model microbiologically confirmed TB. Models included CAD score, study site, age, sex, human immunodeficiency virus status, and prior TB. We compared specificity at target sensitivities ≥90% between the multivariable model and the current threshold-based approach for CAD use., Results: We included 4,733/5,640 (84%) participants with complete covariate data (median age 36 years; 45% female; 22% with prior TB; 22% people living with human immunodeficiency virus). A total of 805 (17%) had TB. Multivariable models demonstrated excellent performance (areas under the receiver operating characteristic curve [95% confidence interval]: software A, 0.91 [0.90-0.93]; software B, 0.92 [0.91-0.93]). Compared with threshold scores, multivariable models increased specificity (e.g., at 90% sensitivity, threshold vs model specificity [95% confidence interval]: software A, 71% [68-74%] vs 75% [74-77%]; software B, 69% [63-75%] vs 75% [74-77%])., Conclusion: Using CAD scores in multivariable models outperformed the current practice of CAD-threshold-based CXR classification for TB diagnosis., Competing Interests: Declarations of competing interest FAK currently holds a grant from CIHR to study CAD in Canada. FAK also reports salary support from the Fonds de Recherche du Quebec Santé. FAK reports that the following developers of computer-aided detection software provided his research group with either free or reduced pricing access to their software for evaluative research, governed by contracts with the Research Institute of the McGill University Health Centre that ensure that the groups did not have any role in the study design, analysis, result interpretation, or decision to publish previous research and the submitted work: Delft (Netherlands, makers of CAD4TB), qure.ai (India, makers of qXR), and Lunit (South Korea, makers of LUNIT INSIGHT). MB reports grants from European and Development Countries Clinical Trials Partnership during the conduct of the study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Globally, at least 3 million TB patients are missed every year. In Zambia, the TB treatment coverage increased from 66% in 2020 to 92% in 2022. Involvement of all levels of health care service delivery is critical to finding all the missing TB patients., Methods: A survey was undertaken in 15 private facilities in Lusaka district of Zambia using a structured tool administered by project team and a district health team member. Data collected during the survey was analysed and results were used to determine the type of TB services that were offered as well as barriers and enablers to TB service provision. This was followed by a set of interventions that included; training and mentorship on active case finding and systematic TB screening, increased diagnostic capacity, provision of national recording and reporting tools and provision of TB medication through linkage with the National TB program (NTP). We report findings from the baseline survey and changes in presumptive TB identification and notification following interventions., Results: Major barriers to TB service delivery were the high cost of TB diagnostic testing and treatment in facilities where services were not supported by the National TB program; the mean cost was 33 (SD 33) and 93 (SD 148) for GeneXpert testing and a full course of treatment respectively. Pre-intervention, presumptive TB identification appeared to increase monthly by 4 (P = 0.000, CI=[3.00-5.00]). The monthly trends of presumptive TB identification during the intervention period increased by 5.32 (P = 0.000, [CI 4.31-6.33. Pre-intervention, the notification of TB appeared to decrease every month by -4.0 (P = 0.114, CI=[-9.00-0.10]) followed by an immediate increase in notifications of 13.94 TB patients (P = 0.001, CI [6.51, 21.36] in the first month on intervention. The monthly trends of notification during the intervention period changed by 0.34 (P = 0.000 [CI 0.19-0.48]). Private facility contribution to TB notification increased from 3 to 7%., Conclusion: Engagement and inclusion of private health facilities in TB service provision through a systems strengthening approach can increase contribution to TB notification by private health facilities., (© 2024. The Author(s).)

Background: Zambia is among the 30 high-burden countries for tuberculosis (TB), Human Immunodeficiency Virus (HIV)-associated TB, and multi-drug resistant/rifampicin resistant TB with over 5000 children developing TB every year. However, at least 32% of the estimated children remain undiagnosed. We assessed healthcare workers' (HCWs) knowledge, attitudes, and practices (KAP) towards childhood TB and the factors associated with good KAP towards childhood TB., Methods: Data was collected at two primary healthcare facilities in Lusaka, Zambia from July to August 2020. Structured questionnaires were administered to HCWs that were selected through stratified random sampling. Descriptive analysis was done to determine KAP. A maximum knowledge, attitude, and practice scores for a participant were 44, 10, and 8 points respectively. The categorization as either "poor" or "good" KAP was determined based on the mean/ median. Logistic regression analysis was performed to assess the associations between participant characteristics and KAP at statistically significant level of 0.05%., Results: Among the 237 respondents, majority were under 30 years old (63.7%) and were female (72.6%). Half of the participants (50.6%) were from the outpatient department (OPD) and antiretroviral therapy (ART) clinic, 109 (46.0) had been working at the facility for less than 1 year, 134 (56.5%) reported no previous training in TB. The median/mean KAP scores were 28 (IQR 24.0-31.0), 7 (IQR = 6.0-8.0) and 5 points (SD = 1.9) respectively. Of the participants, 43.5% (103/237) had good knowledge, 48.1% (114/237) had a good attitude, and 54.4% (129/237) had good practice scores on childhood TB. In the multivariate analysis, clinical officers and individuals with 1-5 years' work experience at the facility had higher odds, 2.61 (95% CI = 1.18-5.80, p = 0.018) and 3.09 (95% CI = 1.69-5.65, p = 0.001) of having good attitude respectively, and medical doctors had 0.17 lower odds (95% CI = 0.18-5.80, p = 0.018) of good childhood TB practice. Other participant characteristics didn't show a significant association with the scores., Conclusion: The study found suboptimal levels of knowledge, attitude, and practices regarding childhood TB among HCWs. Targeted programmatic support needs to be provided to address the above gaps., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kaumba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: In high TB burden settings, it is estimated that 10-20% of total notifications should be children, however, currently only 6-8% of the total TB notifications in Zambia are children. We assessed whether the implementation of a multicomponent strategy, at primary healthcare facilities, that systematically targets barriers at each step of the childhood TB diagnostic cascade can increase childhood TB case detection., Methods: We conducted a controlled, interrupted time series analysis to compare childhood TB case notifications before (January 2018-December 2019), and during implementation (January 2020-September 2021) in two intervention and two control Level 1 hospitals in Lusaka, Zambia. At each of the intervention facilities, we implemented a multicomponent strategy constituting: (1) capacity development on childhood TB and interpretation of chest x-ray, (2) TB awareness-raising and demand creation activities, (3) setting up fast track TB services, (4) strengthening of household contact tracing, and (5) improving access to digital chest X-ray for TB screening and Xpert MTB/Rif Ultra for TB diagnosis, through strengthening sample collection in children., Findings: Among 5,150 children < 15 years screened at the two intervention facilities during the study period, 503 (9.8% yield) were diagnosed with TB. Of these, 433 (86.1%) were identified through facility-based activities (10.5% yield) and 70 (13.9%) were identified through household contact tracing (6.9% yield). Overall, 446 children (88.7%) children with TB were clinically diagnosed. Following implementation of the multicomponent strategy, the proportion children contributed to total TB notifications immediately changed by +1.5% (95%CI: -3.5, 6.6) and -4.4% (95%CI: -7.5, 1.4) at the intervention and control sites, respectively (difference 6.0% [95%CI: -0.7, 12.7]), p = 0.08); the proportion of childhood notifications increased 0.9% (95%CI: -0.7, 2.5%) each quarter at the intervention sites relative to pre-implementation trends, while declining 1.2% (-95%CI: -1.8, -0.6) at the control sites (difference 2.1% [95%CI: 0.1, 4.2] per quarter between, p = 0.046); this translated into 352 additional and 85 fewer childhood TB notifications at the intervention and control sites, respectively, compared to the pre-implementation period., Conclusion: A standardized package of strategies to improve childhood TB detection at primary healthcare facilities was feasible to implement and was associated with a sustained improvement in childhood TB notifications., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Kagujje et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Men and women with undiagnosed tuberculosis (TB) in high burden countries may have differential factors influencing their healthcare seeking behaviors and access to TB services, which can result in delayed diagnoses and increase TB-related morbidity and mortality. A convergent, parallel, mixed-methods study design was used to explore and evaluate TB care engagement among adults (≥18 years) with newly diagnosed, microbiologically-confirmed TB attending three public health facilities in Lusaka, Zambia. Quantitative structured surveys characterized the TB care pathway (time to initial care-seeking, diagnosis, and treatment initiation) and collected information on factors influencing care engagement. Multinomial multivariable logistic regression was used to determine predicted probabilities of TB health-seeking behaviors and determinants of care engagement. Qualitative in-depth interviews (IDIs; n = 20) were conducted and analyzed using a hybrid approach to identify barriers and facilitators to TB care engagement by gender. Overall, 400 TB patients completed a structured survey, of which 275 (68.8%) and 125 (31.3%) were men and women, respectively. Men were more likely to be unmarried (39.3% and 27.2%), have a higher median daily income (50 and 30 Zambian Kwacha [ZMW]), alcohol use disorder (70.9% [AUDIT-C score ≥4] and 31.2% [AUDIT-C score ≥3]), and a history of smoking (63.3% and 8.8%), while women were more likely to be religious (96.8% and 70.8%) and living with HIV (70.4% and 36.0%). After adjusting for potential confounders, the probability of delayed health-seeking ≥4 weeks after symptom onset did not differ significantly by gender (44.0% and 36.2%, p = 0.14). While the top reasons for delayed healthcare-seeking were largely similar by gender, men were more likely to report initially perceiving their symptoms as not being serious (94.8% and 78.7%, p = 0.032), while women were more likely to report not knowing the symptoms of TB before their diagnosis (89.5% and 74.4%; p = 0.007) and having a prior bad healthcare experience (26.4% and 9.9%; p = 0.036). Notably, women had a higher probability of receiving TB diagnosis ≥2 weeks after initial healthcare seeking (56.5% and 41.0%, p = 0.007). While men and women reported similar acceptability of health-information sources, they emphasized different trusted messengers. Also, men had a higher adjusted probability of stating that no one influenced their health-related decision making (37.9% and 28.3%, p = 0.001). In IDIs, men recommended TB testing sites at convenient community locations, while women endorsed an incentivized, peer-based, case-finding approach. Sensitization and TB testing strategies at bars and churches were highlighted as promising approaches to reach men and women, respectively. This mixed-methods study found important differences between men and women with TB in Zambia. These differences suggest the need for gender-tailored TB health promotion, including addressing harmful alcohol use and smoking among men, and sensitizing HCWs to prolonged delays in TB diagnosis among women, and also using gender-specific approaches as part of community-based, active case-finding strategies to improve TB diagnosis in high burden settings., Competing Interests: The authors have read the journal’s policy and have the following competing interests: ADK is an Academic Editor for PLOS Global Public Health. JMP is a guest editor for PLOS Global Public Health. KAC has received investigator-initiated research support from and served as a medical advisory board member for Gilead Sciences outside of the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Kerkhoff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To evaluate the performance of point-of-care C-reactive protein (CRP) as a screening tool for tuberculosis (TB) using a threshold of 10 mg/L in both people living with HIV (PLHIV) and HIV-negative individuals and compare it to symptom screening using a composite reference for bacteriological confirmation of TB., Methods: Prospective cross-sectional study., Setting: A primary healthcare facility in Lusaka, Zambia., Participants: Consecutive adults (≥18 years) presenting for routine outpatient healthcare were enrolled. Of the 816 individuals approached to participate in the study, 804 eligible consenting adults were enrolled into the study, of which 783 were included in the analysis., Primary Outcome Measures: Sensitivity, specificity, positive predictive value and negative predictive value (NPV) of CRP and symptom screening., Results: Overall, sensitivity of WHO-recommended four-symptom screen (W4SS) and CRP were 87.2% (80.0-92.5) and 86.6% (79.6-91.8) while specificity was 30.3% (26.7-34.1) and 34.8% (31.2-38.6), respectively. Among PLHIV, sensitivity of W4SS and CRP was 92.2% (81.1-97.8) and 94.8% (85.6-98.9) while specificity was 37.0% (31.3-43.0) and 27.5% (22.4-33.1), respectively. Among those with CD4≥350, the NPV for CRP was 100% (92.9-100). In the HIV negative, sensitivity of W4SS and CRP was 83.8% (73.4-91.3) and 80.3% (69.5-88.5) while specificity was 25.4% (20.9-30.2) and 40.5% (35.3-45.6), respectively. Parallel use of CRP and W4SS yielded a sensitivity and NPV of 100% (93.8-100) and 100% (91.6-100) among PLHIV and 93.3% (85.1-97.8) and 90.0% (78.2-96.7) among the HIV negatives, respectively., Conclusion: Sensitivity and specificity of CRP were similar to symptom screening in HIV-positive outpatients. Independent use of CRP offered limited additional benefit in the HIV negative. CRP can independently accurately rule out TB in PLHIV with CD4≥350. Parallel use of CRP and W4SS improves sensitivity irrespective of HIV status and can accurately rule out TB in PLHIV, irrespective of CD4 count., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Digital chest X-ray (dCXR) computer-aided detection (CAD) technology uses lung shape and texture analysis to determine the probability of tuberculosis (TB). However, many patients with previously treated TB have sequelae, which also distort lung shape and texture. We evaluated the diagnostic performance of 2 CAD systems for triage of active TB in patients with previously treated TB., Methods: We conducted a retrospective analysis of data from a cross-sectional active TB case finding study. Participants ≥15 years, with ≥1 current TB symptom and complete data on history of previous TB, dCXR, and TB microbiological reference (Xpert MTB/RIF) were included. dCXRs were evaluated using CAD4TB (v.7.0) and qXR (v.3.0). We determined the diagnostic accuracy of both systems, overall and stratified by history of TB, using a single threshold for each system that achieved 90% sensitivity and maximized specificity in the overall population., Results: Of 1884 participants, 452 (24.0%) had a history of previous TB. Prevalence of microbiologically confirmed TB among those with and without history of previous TB was 12.4% and 16.9%, respectively. Using CAD4TB, sensitivity and specificity were 89.3% (95% CI: 78.1-96.0%) and 24.0% (19.9-28.5%) and 90.5% (86.1-93.3%) and 60.3% (57.4-63.0%) among those with and without previous TB, respectively. Using qXR, sensitivity and specificity were 94.6% (95% CI: 85.1-98.9%) and 22.2% (18.2-26.6%) and 89.7% (85.1-93.2%) and 61.8% (58.9-64.5%) among those with and without previous TB, respectively., Conclusions: The performance of CAD systems as a TB triage tool is decreased among persons previously treated for TB., Competing Interests: Potential conflicts of interests. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes., Objective: To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services., Design, Setting, and Participants: A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was used to identify segments of participants with unique preferences. Multiscenario simulations were used to estimate shares of preferences for different TB service improvement strategies., Main Outcomes and Measures: The main outcomes were patient preference archetypes and estimated shares of preferences for different strategies to improve TB diagnostic services. Collected data were analyzed between January 3, 2022, to July 2, 2022., Results: Among 326 adults with TB (median [IQR] age, 34 [27-42] years; 217 [66.8%] male; 158 [48.8%] HIV positive), 3 groups with distinct preferences for TB service improvements were identified. Group 1 (192 participants [58.9%]) preferred a facility that offered same-day TB test results, shorter wait times, and financial incentives for testing. Group 2 (83 participants [25.4%]) preferred a facility that provided same-day TB results, had greater privacy, and was closer to home. Group 3 (51 participants [15.6%]) had no strong preferences for service improvements and had negative preferences for receiving telephone-based TB test results. Groups 1 and 2 were more likely to report at least a 4-week delay in seeking health care for their current TB episode compared with group 3 (29 [51.3%] in group 1, 95 [35.8%] in group 2, and 10 [19.6%] in group 3; P < .001). Strategies to improve TB diagnostic services most preferred by all participants were same-day TB test results alone (shares of preference, 69.9%) and combined with a small financial testing incentive (shares of preference, 79.3%), shortened wait times (shares of preference, 76.1%), or greater privacy (shares of preference, 75.0%). However, the most preferred service improvement strategies differed substantially by group., Conclusions and Relevance: In this study, patients with TB had heterogenous preferences for TB diagnostic service improvements associated with differential health care-seeking behavior. Tailored strategies that incorporate features most valued by persons with undiagnosed TB, including same-day results, financial incentives, and greater privacy, may optimize reach by overcoming key barriers to timely TB care engagement.

Background: The "trace call" results on Xpert® Ultra indicates extremely low TB levels and may be difficult to interpret. The prevalence of trace results among presumptive TB patients in high TB-HIV infection settings is unknown, as is the significance of divergent "trace call" result interpretations., Methods: Presumptive TB patients attending a public health facility in Lusaka, Zambia, were prospectively enrolled. Participants underwent several TB investigations, including sputum smear microscopy, Ultra testing, and culture. The diagnostic accuracy of Ultra (culture-based reference) and the number of patients recommended for TB treatment was assessed according to several different interpretation criteria for "trace call" results., Results: Among the 740 participants, 78 (10.5%) were Ultra-positive and an additional 37 (5.0%) had a "trace call" result. The prevalence of trace results did not differ according to HIV status (5.3% vs. 4.8%) or prior TB status (5.6% vs. 4.9%). Differing interpretations of trace results had modest effects on Ultra's sensitivity (range 79.3-82.6%) and specificity (range 94.3-99.2%), but increased the number of patients recommended for treatment by up to 44.9%., Conclusions: Ultra trace results were common in this setting. The interpretation of trace results may substantially impact TB case yield., (© 2022 The Union.)

Objective: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and the subsequent implementation of tuberculosis response measures on tuberculosis notifications in Zambia., Methods: We used an interrupted time-series design to compare monthly tuberculosis notifications in Zambia before the pandemic (January 2019 to February 2020), after implementation of national pandemic mitigation measures (April 2020 to June 2020) and after response measures to improve tuberculosis detection (August 2020 to September 2021). The tuberculosis response included enhanced data surveillance, facility-based active case-finding and activities to generate demand for services. We used nationally aggregated, facility-level tuberculosis notification data for the analysis., Findings: Pre-pandemic tuberculosis case notifications rose steadily from 2890 in January 2019 to 3337 in February 2020. After the start of the pandemic and mitigation measures, there was a -22% (95% confidence interval, CI: -24 to -19) immediate decline in notifications in April 2020. Larger immediate declines in notifications were seen among human immunodeficiency virus (HIV)-positive compared with HIV-negative individuals (-36%; 95% CI: -38 to -35; versus -12%; 95% CI: -17 to -6). Following roll-out of tuberculosis response measures in July 2020, notifications immediately increased by 45% (95% CI: 38 to 51) nationally and across all subgroups and provinces. The trend in notifications remained stable through September 2021, with similar numbers to the predicted number had the pandemic not occurred., Conclusion: Implementation of a coordinated public health response including active tuberculosis case-finding was associated with reversal of the adverse impact of the pandemic and mitigation measures. The gains were sustained throughout subsequent waves of the pandemic., ((c) 2022 The authors; licensee World Health Organization.)

Objective: To determine the prevalence of tuberculosis (TB) and HIV in 13 Zambian correctional facilities., Methods: Cross-sectional study., Setting: 13 correctional facilities in seven of the 10 provinces in Zambia., Participants: All incarcerated individuals were eligible for TB and HIV screening and testing. Of the total study population of 9695 individuals, which represent 46.2% of total correctional population at the beginning of the study, 8267 and 8160 were screened for TB and HIV, respectively., Interventions: TB and HIV screening and testing was done between July 2018 and February 2019., Primary Outcome Measures: All forms of TB, bacteriologically confirmed TB, drug-resistant TB, HIV., Results: Prevalence of all forms of TB and bacteriologically confirmed TB was 1599 (1340-1894) per 100 000 population and 1056 (847-1301) per 100 000 population, respectively. Among those with bacteriologically confirmed TB, 4.6% (1.3%-11.4%) had drug-resistant TB.There was no statistically significant difference in the prevalence of all forms of TB, bacteriologically confirmed TB and drug resistant TB between adults and juveniles: (p=0.82), (p=0.23), (p=0.68) respectively. Of the bacteriologically confirmed TB cases, 28.7% were asymptomatic. The prevalence of HIV was 14.3% (13.6%-15.1%). The prevalence of HIV among females was 1.8 times the prevalence of HIV among males (p=0.01)., Conclusion: Compared with the study in 2011 which screened inmates representing 30% of the country's inmate population, then the prevalence of all forms of TB and HIV in correctional facilities has reduced by about 75% and 37.6%, respectively. However, compared with the general population, the prevalence of all forms of TB and HIV was 3.5 and 1.3 times higher, respectively. TB/HIV programmes in correctional facilities need further strengthening to include aspects of juvenile-specific TB programming and gender responsive HIV programming., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Active-case finding (ACF) programs have an important role in addressing case detection gaps and halting tuberculosis (TB) transmission. Evidence is limited on the cost-effectiveness of ACF interventions, particularly on how their value is impacted by different operational, epidemiological and patient care-seeking patterns., Methods: We evaluated the costs and cost-effectiveness of a combined facility and community-based ACF intervention in Zambia that utilized mobile chest X-ray with computer-aided reading/interpretation software and laboratory-based Xpert MTB/RIF testing. Programmatic costs (in 2018 US dollars) were assessed from the health system perspective using prospectively collected cost and operational data. Cost-effectiveness of the ACF intervention was assessed as the incremental cost per TB death averted over a five-year time horizon using a multi-stage Markov state-transition model reflecting patient symptom-associated care-seeking and TB care under ACF compared to passive care., Results: Over 18 months of field operations, the ACF intervention costed $435 to diagnose and initiate treatment for one person with TB. After accounting for patient symptom-associated care-seeking patterns in Zambia, we estimate that this one-time ACF intervention would incrementally diagnose 407 (7,207 versus 6,800) TB patients and avert 502 (611 versus 1,113) TB-associated deaths compared to the status quo (passive case finding), at an incremental cost of $2,284 per death averted over the next five-year period. HIV/TB mortality rate, patient symptom-associated care-seeking probabilities in the absence of ACF, and the costs of ACF patient screening were key drivers of cost-effectiveness., Conclusions: A one-time comprehensive ACF intervention simultaneously operating in public health clinics and corresponding catchment communities can have important medium-term impact on case-finding and be cost-effective in Zambia. The value of such interventions increases if targeted to populations with high HIV/TB mortality, substantial barriers (both behavioral and physical) to care-seeking exist, and when ACF interventions can optimize screening by achieving operational efficiency., Competing Interests: The authors have declared that no competing interests exist.

Background: Delays in the diagnosis of tuberculosis (TB) contribute to a substantial proportion of TB-related mortality, especially among people living with HIV (PLHIV). We sought to characterize the diagnostic journey for HIV-positive and HIV-negative patients with a new TB diagnosis in Zambia, to understand drivers of delay, and characterize their preferences for service characteristics to inform improvements in TB services., Methods: We assessed consecutive adults with newly microbiologically-confirmed TB at two public health treatment facilities in Lusaka, Zambia. We administered a survey to document critical intervals in the TB care pathway (time to initial care-seeking, diagnosis and treatment initiation), identify bottlenecks and their reasons. We quantified patient preferences for a range of characteristics of health services using a discrete choice experiment (DCE) that assessed 7 attributes (distance, wait times, hours of operation, confidentiality, sex of provider, testing incentive, TB test speed and notification method)., Results: Among 401 patients enrolled (median age of 34 years, 68.7% male, 46.6% HIV-positive), 60.9% and 39.1% were from a first-level and tertiary hospital, respectively. The median time from symptom onset to receipt of TB treatment was 5.0 weeks (IQR: 3.6-8.0) and was longer among HIV-positive patients seeking care at a tertiary hospital than HIV-negative patients (6.4 vs. 4.9 weeks, p = 0.002). The time from symptom onset to initial presentation for evaluation accounted for the majority of time until treatment initiation (median 3.0 weeks, IQR: 1.0-5.0)-an important minority of 11.0% of patients delayed care-seeking ≥8 weeks. The DCE found that patients strongly preferred same-day TB test results (relative importance, 37.2%), facilities close to home (18.0%), and facilities with short wait times (16.9%). Patients were willing to travel to a facility up to 7.6 kilometers further away in order to access same-day TB test results. Preferences for improving current TB services did not differ according to HIV status., Conclusions: Prolonged intervals from TB symptom onset to treatment initiation were common, especially among PLHIV, and were driven by delayed health-seeking. Addressing known barriers to timely diagnosis and incorporating patients' preferences into TB services, including same-day TB test results, may facilitate earlier TB care engagement in high burden settings., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We conducted an implementation science study to increase TB case detection through a combination of interventions at health facility and community levels. We determined the impact of the study in terms of additional cases detected and notification rate and compared the yield of bacteriologically confirmed TB of facility based and community based case finding., Methodology: Over a period of 18 months, similar case finding activities were conducted at George health facility in Lusaka Zambia and its catchment community, an informal peri-urban settlement. Activities included awareness and demand creation activities, TB screening with digital chest x-ray or symptom screening, sputum evaluation using geneXpert MTB/RIF, TB diagnosis and linkage to treatment., Results: A total of 18,194 individuals were screened of which 9,846 (54.1%) were screened at the facility and 8,348 (45.9%) were screened in the community. The total number of TB cases diagnosed during the intervention period were 1,026, compared to 759 in the pre-intervention period; an additional 267 TB cases were diagnosed. Of the 563 bacteriologically confirmed TB cases diagnosed under the study, 515/563 (91.5%) and 48/563 (8.5%) were identified at the facility and in the community respectively (P<0.0001). The TB notification rate increased from 246 per 100,000 population pre-intervention to 395 per 100,000 population in the last year of the intervention., Conclusions: Facility active case finding was more effective in detecting TB cases than community active case finding. Strengthening health systems to appropriately identify and evaluate patients for TB needs to be optimised in high burden settings. At a minimum, provider initiated TB symptom screening with completion of the TB screening and diagnostic cascade should be provided at the health facility in high burden settings. Community screening needs to be systematic and targeted at high risk groups and communities with access barriers., Competing Interests: The authors have declared that no competing interests exist

Background: Uptake of Isoniazid Preventive Therapy (IPT) among People Living with HIV in Zambia has continued to be low despite various evidence for its added benefit in reducing TB incidence and mortality when taken with antiretroviral therapy. In 2017, only 18% of People Living with HIV newly enrolled in care were initiated on IPT in Zambia., Main Text: Various challenges including policy and management level factors, supply chain factors, health worker perceptions about IPT, monitoring and evaluation factors and limited demand creation activities have constrained the scale up of IPT in Zambia. Lessons that have been learnt while addressing the above challenges are shared and they can be applied by government ministries, project managers, public health specialists to strengthen IPT activities in their settings., Conclusion: Zambia has both a high burden of TB and HIV and without preventing new cases of TB from reactivation of latent TB infection, it will be difficult to control TB. All stakeholders involved in prevention of TB among PLHIV need to commit to addressing the challenges limiting scale up of IPT.