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Background: TB REACH is a grant-making initiative launched by the Stop TB Partnership in January 2010 to support innovative approaches and technologies to find and treat people with active TB disease, drugresistant TB, or TB infection. Since then, TB REACH has launched eight Waves of funding to pilot untested, but promising technologies, tools, and approaches. The objective of this paper was to review the grants implemented in Pakistan in the decade since TB REACH's inception and to summarize the approaches used, document the results, and assess the impact of these projects on local and international policy. Methods: We searched the TB REACH's Grant Management System (GMS), which is a database for information on all grants awarded through the initiative, for recipient organisations in Pakistan from 2010 until June 2020. Data was abstracted for the following topic areas: type of grant, focus of work, case finding strategies, risk groups screened and impact on case finding. Results: Through eight waves of funding, TB REACH has supported 28 grants for 21 different interventions in Pakistan worth a total of USD 13.4 million. Overall, 19 of these projects aimed to improve detection, linkage to treatment and reporting of TB and two were product innovation grants for developing resources and materials to aide TB service delivery. Conclusion: TB REACH support has facilitated the introduction of new technologies, establishment of innovative processes in both public and private sector and approaches for addressing TB in key populations. The TB response in Pakistan and globally will continue to require innovation and disruption of 'business as usual' approaches if we are to End TB. [ABSTRACT FROM AUTHOR]

Pakistan ranks fifth among high tuberculosis (TB) burden countries and also has seventh highest burden for diabetes mellitus (DM). DM increases the risk of developing TB and contributes to adverse TB treatment outcomes hence screening and integrated management for both diseases in high burden countries is suggested. Computer-Aided Detection for TB (CAD4TB) can potentially be used as triage tool in low resource settings to pre-screen individuals for Xpert MTB/RIF testing. The aim of this study was to evaluate the diagnostic accuracy and performance of CAD4TB software in people with diabetes (PWD) enrolled in a TB screening program in Karachi, Pakistan. A total of 694 individuals with a diagnosis of DM (of whom 31.1% were newly diagnosed) were screened with CAD4TB and simultaneously provided sputum for Xpert MTB/RIF testing. Of the 74 (10.7%) participants who had bacteriologically positive (MTB+) results on Xpert testing, 54 (73%) had a CAD4TB score >70; and 155 (25%) participants who tested MTB-negative had scores >70. The area under the receiver operator curve was 0.78 (95% CI: 0.77–0.80). Our study findings indicate that CAD4TB offers good diagnostic accuracy as a triage test for TB screening among PWD using Xpert MTB/RIF as the reference standard. [ABSTRACT FROM AUTHOR]

Background: Currently, only 62% of incident tuberculosis (TB) cases are reported to the national programme in Pakistan. Several innovative interventions are being recommended to detect the remaining ‘missed’ TB cases. One such intervention involved expanding contact investigation to the community using the Xpert MTB/RIF test. Methods: This was a before and after intervention study involving retrospective record review. Passive case finding and household contact investigation was routinely done in the pre-intervention period July 2011-June 2013. Four districts with a high concentration of slums were selected as intervention areas; Lahore, Rawalpindi, Faisalabad and Islamabad. Here, in the intervention period, July 2013-June 2015, contact investigation beyond household was conducted: all people staying within a radius of 50 metres (using Geographical Information System) from the household of smear positive TB patients were screened for tuberculosis. Those with presumptive TB were investigated using smear microscopy and the Xpert MTB/RIF test was performed on smear negative patients. All the diagnosed TB patients were linked to TB treatment and care. Results: A total of 783043 contacts were screened for tuberculosis: 23741(3.0%) presumptive TB patients were identified of whom, 4710 (19.8%) all forms and 4084(17.2%) bacteriologically confirmed TB patients were detected. The contribution of Xpert MTB/RIF to bacteriologically confirmed TB patients was 7.6%. The yield among investigated presumptive child TB patients was 5.1%. The overall yield of all forms TB patients among investigated was 22.3% among household and 19.1% in close community. The intervention contributed an increase of case detection of bacteriologically confirmed tuberculosis by 6.8% and all forms TB patients by 7.9%. Conclusion: Community contact investigation beyond household not only detected additional TB patients but also increased TB case detection. However, further long term assessments and cost-effectiveness studies are required before national scale-up. [ABSTRACT FROM AUTHOR]

Background: In Asia, over 50% of patients with symptoms of tuberculosis (TB) access health care from private providers. These patients are usually not notified to the National TB Control Programs, which contributes to low notification rates in many countries.Methods: From January 1, 2011 to December 31, 2012, Karachi's Indus Hospital - a private sector partner to the National TB Programme - engaged 80 private family clinics in its catchment area in active case finding using health worker incentives to increase notification of TB disease. The costs incurred were estimated from the perspective of patients, health facility and the program providing TB services. A Markov decision tree model was developed to calculate the cost-effectiveness of the active case finding as compared to case detection through the routine passive TB centers. Pakistan has a large private health sector, which can be mobilized for TB screening using an incentivized active case finding strategy. Currently, TB screening is largely performed in specialist public TB centers through passive case finding. Active and passive case finding strategies are assumed to operate independently from each other.Results: The incentive-based active case finding program costed USD 223 per patient treated. In contrast, the center based non-incentive arm was 23.4% cheaper, costing USD 171 per patient treated. Cost-effectiveness analysis showed that the incentive-based active case finding program was more effective and less expensive per DALY averted when compared to the baseline passive case finding as it averts an additional 0.01966 DALYs and saved 15.74 US$ per patient treated.Conclusion: Both screening strategies appear to be cost-effective in an urban Pakistan context. Incentive driven active case findings of TB in the private sector costs less and averts more DALYs per health seeker than passive case finding, when both alternatives are compared to a common baseline situation of no screening. [ABSTRACT FROM AUTHOR]

Summary: Background: In many countries with a high burden of tuberculosis, most patients receive treatment in the private sector. We evaluated a multifaceted case-detection strategy in Karachi, Pakistan, targeting the private sector. Methods: A year-long communications campaign advised people with 2 weeks or more of productive cough to seek care at one of 54 private family medical clinics or a private hospital that was also a national tuberculosis programme (NTP) reporting centre. Community laypeople participated as screeners, using an interactive algorithm on mobile phones to assess patients and visitors in family-clinic waiting areas and the hospital''s outpatient department. Screeners received cash incentives for case detection. Patients with suspected tuberculosis also came directly to the hospital''s tuberculosis clinic (self-referrals) or were referred there (referrals). The primary outcome was the change (from 2010 to 2011) in tuberculosis notifications to the NTP in the intervention area compared with that in an adjacent control area. Findings: Screeners assessed 388 196 individuals at family clinics and 81 700 at Indus Hospital''s outpatient department from January–December, 2011. A total of 2416 tuberculosis cases were detected and notified via the NTP reporting centre at Indus Hospital: 603 through family clinics, 273 through the outpatient department, 1020 from self-referrals, and 520 from referrals. In the intervention area overall, tuberculosis case notification to the NTP increased two times (from 1569 to 3140 cases) from 2010 to 2011—a 2·21 times increase (95% CI 1·93–2·53) relative to the change in number of case notifications in the control area. From 2010 to 2011, pulmonary tuberculosis notifications at Indus Hospital increased by 3·77 times for adults and 7·32 times for children. Interpretation: Novel approaches to tuberculosis case-finding involving the private sector and using laypeople, mobile phone software and incentives, and communication campaigns can substantially increase case notification in dense urban settings. Funding: TB REACH, Stop TB Partnership. [Copyright &y& Elsevier]

Tuberculosis (TB) is the leading cause of avoidable deaths from an infectious disease globally and a large of number of people who develop TB each year remain undiagnosed. Active case-finding has been recommended by the World Health Organization to bridge the case-detection gap for TB in high burden countries. However, concerns remain regarding their yield and cost-effectiveness. Data from mobile chest X-ray (CXR) supported active case-finding community camps conducted in Karachi, Pakistan from July 2018 to March 2020 was retrospectively analyzed. Frequency analysis was carried out at the camp-level and outcomes of interest for the spatial analyses were mycobacterium TB positivity (MTB+) and X-ray abnormality rates. The Global Moran's I statistic was used to test for spatial autocorrelation for MTB+ and abnormal X-rays within Union Councils (UCs) in Karachi. A total of 1161 (78.1%) camps yielded no MTB+ cases, 246 (16.5%) camps yielded 1 MTB+, 52 (3.5%) camps yielded 2 MTB+ and 27 (1.8%) yielded 3 or more MTB+. A total of 79 (5.3%) camps accounted for 193 (44.0%) of MTB+ cases detected. Statistically significant clustering for MTB positivity (Global Moran's I: 0.09) and abnormal chest X-rays (Global Moran's I: 0.36) rates was identified within UCs in Karachi. Clustering of UCs with high MTB positivity were identified in Karachi West district. Statistically significant spatial variation was identified in yield of bacteriologically positive TB cases and in abnormal CXR through active case-finding in Karachi. Cost-effectiveness of active case-finding programs can be improved by identifying and focusing interventions in hotspots and avoiding locations with no known TB cases reported through routine surveillance., (© 2023. The Author(s).)

Objectives: Despite WHO guidelines recommending household contact investigation, and studies showing the impact of active screening, most tuberculosis (TB) programmes in resource-limited settings only carry out passive contact investigation. The cost of such strategies is often cited as barriers to their implementation. However, little data are available for the additional costs required to implement this strategy. We aimed to estimate the cost and cost-effectiveness of active contact investigation as compared with passive contact investigation in urban Pakistan., Methods: We estimated the cost-effectiveness of 'enhanced' (passive with follow-up) and 'active' (household visit) contact investigations compared with standard 'passive' contact investigation from providers and the programme's perspective using a simple decision tree. Costs were collected in Pakistan from a TB clinic performing passive contact investigation and from studies of active contact tracing interventions conducted. The effectiveness was based on the number of patients with TB identified among household contacts screened., Results: The addition of enhanced contact investigation to the existing passive mode detected 3.8 times more cases of TB per index patient compared with passive contact investigation alone. The incremental cost was US$30 per index patient, which yielded an incremental cost of US$120 per incremental patient identified with TB. The active contact investigation was 1.5 times more effective than enhanced contact investigation with an incremental cost of US$238 per incremental patient with TB identified., Conclusion: Our results show that enhanced and active approaches to contact investigation effectively identify additional patients with TB among household contacts at a relatively modest cost. These strategies can be added to the passive contact investigation in a high burden setting to find the people with TB who are missed and meet the End TB strategy goals., 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.)

Background: Women in the rural districts of Pakistan face numerous barriers to healthcare, rendering gender-responsive health programming important, including for the disease of tuberculosis (TB). This study was conducted to assess the general understanding of TB and for women's access to healthcare, as a first step towards implementation of a gender responsive TB program in Tando Allahyar, a rural district of Pakistan., Methods: A total of 36 participants were interviewed for the study. The focus group discussion guide comprised of questions on: (1) family/household dynamics, (2) community norms, (3) healthcare systems, (4) women's access to healthcare, (5) TB Awareness, and (6) women's access to TB Care., Results: Limited autonomy in household financial decision-making, disapproval of unassisted travel, long travel time, lack of prioritization of spending on women's health and inadequate presence of female health providers, were identified as barriers to access healthcare for women, which is even higher in younger women. Facilitators to access of TB care included a reported lack of TB-related stigma, moderate knowledge about TB disease, and broad understanding of tuberculosis as a curable disease. Other suggested facilitators include health facilities closer to the villages and the availability of higher quality services., Conclusion: Significant barriers are faced by women in accessing TB care in rural districts of Pakistan. Program implementers in high burden countries should shift towards improved gender-responsive TB programming.

In a matched case-control study in Pakistan, we found that quantified tuberculosis (TB) exposure using a 10-point score is associated with prevalent TB disease in pediatric household contacts. A 1 unit increase in TB exposure score increased the odds of TB disease by 44% (conditional odds ratio: 1.44, 95% confidence interval: 1.33-1.56). Collecting well-documented exposure history can help TB diagnosis in resource-limited settings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The introduction of digital CXR with automated computer-aided interpretation, has given impetus to the role of CXR in TB screening, particularly in low resource, high-burden settings. The aim of this study was to evaluate the diagnostic accuracy of CAD4TB as a screening tool, implemented in the private sector in Karachi, Pakistan. This study analyzed retrospective data from CAD4TB and Xpert MTB/RIF testing carried out at two private TB treatment and diagnostic centers in Karachi. Sensitivity, specificity, potential Xperts saved, were computed and the receiver operator characteristic curves were constructed for four different models of CAD4TB. A total of 6,845 individuals with presumptive TB were enrolled in the study, 15.2% of which had MTB + ve result on Xpert. A high sensitivity (range 65.8-97.3%) and NPV (range 93.1-98.4%) were recorded for CAD4TB. The Area under the ROC curve (AUC) for CAD4TB was 0.79. CAD4TB with patient demographics (age and gender) gave an AUC of 0.83. CAD4TB offered high diagnostic accuracy. In low resource settings, CAD4TB, as a triage tool could minimize use of Xpert. Using CAD4TB in combination with age and gender data enhanced the performance of the software. Variations in demographic information generate different individual risk probabilities for the same CAD4TB scores.