Evaluation of a population-wide, systematic screening initiative for tuberculosis on Daru island, Western Province, Papua New Guinea.

BACKGROUND: A population-wide, systematic screening initiative for tuberculosis (TB) was implemented on Daru island in the Western Province of Papua New Guinea, where TB is known to be highly prevalent. The initiative used a mobile van equipped with a digital X-ray device, computer-aided detection (CAD) software to identify TB-related abnormalities on chest radiographs, and GeneXpert machines for follow-on diagnostic testing. We describe the results of the TB screening initiative, evaluate its population-level impact and examine risk factors associated with TB detection. METHODS: Through a retrospective review of screening data, we assessed the effectiveness of the screening by examining the enrolment coverage and the proportion of people with TB among screened subjects. A cascade analysis was performed to illustrate the flow of participants in the screening algorithm. We conducted univariate and multivariate analyses to identify factors associated with TB. Furthermore, we estimated the number of additional cases detected by the project by examining the trend of routine TB case notifications during the intervention period, compared to the historical baseline cases and trend-adjusted expected cases. RESULTS: Of the island's 18,854 residents, 8,085 (42.9%) were enrolled and 7,970 (98.6%) had chest X-ray interpreted by the CAD4TB software. A total of 1,116 (14.0%) participants were considered to have abnormal CXR. A total of 69 Xpert-positive cases were diagnosed, resulting in a detection rate of 853 per 100 000 population screened. 19.4% of people with TB had resistance to rifampicin. People who were in older age groups (aOR 6.6, 95%CI: 1.5-29.1 for the 45-59 age group), were severely underweight (aOR 2.5, 95%CI:1.0-6.1) or underweight (aOR 2.1, 95%CI: 1.1-3.8), lived in households < 5 people (aOR 3.4, 95%CI:1.8-6.6) and had a past history of TB (aOR 2.1, 95%CI: 1.2-3.6) were more likely to have TB. The number of bacteriologically confirmed TB notified during the intervention period was 79.3% and 90.8% higher than baseline notifications and forecasted notifications, respectively. CONCLUSION: The screening project demonstrated its effectiveness with the high Xpert-positive TB prevalence among the participants and by successfully yielding additional cases of bacteriologically confirmed TB including rifampicin-resistant TB. The results and lessons learnt from the project should inform future TB screening initiatives in Papua New Guinea.

Towards universal health coverage in Vietnam: a mixed-method case study of enrolling people with tuberculosis into social health insurance.

BACKGROUND: Vietnam's primary mechanism of achieving sustainable funding for universal health coverage (UHC) and financial protection has been through its social health insurance (SHI) scheme. Steady progress towards access has been made and by 2020, over 90% of the population were enrolled in SHI. In 2022, as part of a larger transition towards the increased domestic financing of healthcare, tuberculosis (TB) services were integrated into SHI. This change required people with TB to use SHI for treatment at district-level facilities or to pay out of pocket for services. This study was conducted in preparation for this transition. It aimed to understand more about uninsured people with TB, assess the feasibility of enrolling them into SHI, and identify the barriers they faced in this process. METHODS: A mixed-method case study was conducted using a convergent parallel design between November 2018 and January 2022 in ten districts of Hanoi and Ho Chi Minh City, Vietnam. Quantitative data were collected through a pilot intervention that aimed to facilitate SHI enrollment for uninsured individuals with TB. Descriptive statistics were calculated. Qualitative interviews were conducted with 34 participants, who were purposively sampled for maximum variation. Qualitative data were analyzed through an inductive approach and themes were identified through framework analysis. Quantitative and qualitative data sources were triangulated. RESULTS: We attempted to enroll 115 uninsured people with TB into SHI; 76.5% were able to enroll. On average, it took 34.5 days to obtain a SHI card and it cost USD 66 per household. The themes indicated that a lack of knowledge, high costs for annual premiums, and the household-based registration requirement were barriers to SHI enrollment. Participants indicated that alternative enrolment mechanisms and greater procedural flexibility, particularly for undocumented people, is required to achieve full population coverage with SHI in urban centers. CONCLUSIONS: Significant addressable barriers to SHI enrolment for people affected by TB were identified. A quarter of individuals remained unable to enroll after receiving enhanced support due to lack of required documentation. The experience gained during this health financing transition is relevant for other middle-income countries as they address the provision of financial protection for the treatment of infectious diseases.

Determinants of catastrophic costs among households affected by multi-drug resistant tuberculosis in Ho Chi Minh City, Viet Nam: a prospective cohort study.

BACKGROUND: Globally, most people with multidrug-resistant tuberculosis (MDR-TB) and their households experience catastrophic costs of illness, diagnosis, and care. However, the factors associated with experiencing catastrophic costs are poorly understood. This study aimed to identify risk factors associated with catastrophic costs incurrence among MDR-TB-affected households in Ho Chi Minh City (HCMC), Viet Nam. METHODS: Between October 2020 and April 2022, data were collected using a locally-adapted, longitudinal WHO TB Patient Cost Survey in ten districts of HCMC. Ninety-four people with MDR-TB being treated with a nine-month TB regimen were surveyed at three time points: after two weeks of treatment initiation, completion of the intensive phase and the end of the treatment (approximately five and 10 months post-treatment initiation respectively). The catastrophic costs threshold was defined as total TB-related costs exceeding 20% of annual pre-TB household income. Logistic regression was used to identify variables associated with experiencing catastrophic costs. A sensitivity analysis examined the prevalence of catastrophic costs using alternative thresholds and cost estimation approaches. RESULTS: Most participants (81/93 [87%]) experienced catastrophic costs despite the majority 86/93 (93%) receiving economic support through existing social protection schemes. Among participant households experiencing and not experiencing catastrophic costs, median household income was similar before MDR-TB treatment. However, by the end of MDR-TB treatment, median household income was lower (258 [IQR: 0-516] USD vs. 656 [IQR: 462-989] USD; p = 0.003), and median income loss was higher (2838 [IQR: 1548-5418] USD vs. 301 [IQR: 0-824] USD; p < 0.001) amongst the participant households who experienced catastrophic costs. Being the household's primary income earner before MDR-TB treatment (aOR = 11.2 [95% CI: 1.6-80.5]), having a lower educational level (aOR = 22.3 [95% CI: 1.5-344.1]) and becoming unemployed at the beginning of MDR-TB treatment (aOR = 35.6 [95% CI: 2.7-470.3]) were associated with experiencing catastrophic costs. CONCLUSION: Despite good social protection coverage, most people with MDR-TB in HCMC experienced catastrophic costs. Incurrence of catastrophic costs was independently associated with being the household's primary income earner or being unemployed. Revision and expansion of strategies to mitigate TB-related catastrophic costs, in particular avoiding unemployment and income loss, are urgently required.

What makes community health worker models for tuberculosis active case finding work? A cross-sectional study of TB REACH projects to identify success factors for increasing case notifications.

BACKGROUND: In the field of tuberculosis (TB), Community Healthcare Workers (CHWs) have been engaged for advocacy, case detection, and patient support in a wide range of settings. Estimates predict large-scale shortfalls of healthcare workers in low- and middle-income settings by 2030 and strategies are needed to optimize the health workforce to achieve universal availability and accessibility of healthcare. In 2018, the World Health Organization (WHO) published guidelines on best practices for CHW engagement, and identified remaining knowledge gaps. Stop TB Partnership's TB REACH initiative has supported interventions using CHWs to deliver TB care in over 30 countries, and utilized the same primary indicator to measure project impact at the population-level for all TB active case finding projects, which makes the results comparable across multiple settings. This study compiled 10 years of implementation data from the initiative's grantee network to begin to address key knowledge gaps in CHW networks. METHODS: We conducted a cross-sectional study analyzing the TB REACH data repository (n = 123) and primary survey responses (n = 50) of project implementers. We designed a survey based on WHO guidelines to understand projects' practices on CHW recruitment, training, activities, supervision, compensation, and sustainability. We segmented projects by TB notification impact and fitted linear random-effect regression models to identify practices associated with higher changes in notifications. RESULTS: Most projects employed CHWs for advocacy alongside case finding and holding activities. Model characteristics associated with higher project impact included incorporating e-learning in training and having the prospect of CHWs continuing their responsibilities at the close of a project. Factors that trended towards being associated with higher impact were community-based training, differentiated contracts, and non-monetary incentives. CONCLUSION: In line with WHO guidelines, our findings emphasize that successful implementation approaches provide CHWs with comprehensive training, continuous supervision, fair compensation, and are integrated within the existing primary healthcare system. However, we encountered a great degree of heterogeneity in CHW engagement models, resulting in few practices clearly associated with higher notifications.

An evaluation of automated chest radiography reading software for tuberculosis screening among public- and private-sector patients.

Computer-aided reading (CAR) of medical images is becoming increasingly common, but few studies exist for CAR in tuberculosis (TB). We designed a prospective study evaluating CAR for chest radiography (CXR) as a triage tool before Xpert MTB/RIF (Xpert).Consecutively enrolled adults in Dhaka, Bangladesh, with TB symptoms received CXR and Xpert. Each image was scored by CAR and graded by a radiologist. We compared CAR with the radiologist for sensitivity and specificity, area under the receiver operating characteristic curve (AUC), and calculated the potential Xpert tests saved.A total of 18 036 individuals were enrolled. TB prevalence by Xpert was 15%. The radiologist graded 49% of CXRs as abnormal, resulting in 91% sensitivity and 58% specificity. At a similar sensitivity, CAR had a lower specificity (41%), saving fewer (36%) Xpert tests. The AUC for CAR was 0.74 (95% CI 0.73-0.75). CAR performance declined with increasing age. The radiologist grading was superior across all sub-analyses.Using CAR can save Xpert tests, but the radiologist's specificity was superior. Differentiated CAR thresholds may be required for different populations. Access to, and costs of, human readers must be considered when deciding to use CAR software. More studies are needed to evaluate CAR using different screening approaches.

Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries.

BACKGROUND: The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. METHODS: We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. RESULTS: All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. CONCLUSIONS: The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation. The study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues as well as the many different approaches to programmatic MTB/RIF implementation.

Early user experience and lessons learned using ultra-portable digital X-ray with computer-aided detection (DXR-CAD) products: A qualitative study from the perspective of healthcare providers.

BACKGROUND: Recent technological and radiological advances have renewed interest in using X-rays to screen and triage people with tuberculosis (TB). The miniaturization of digital X-ray (DXR), combined with automatic interpretation using computer-aided detection (CAD) software can extend the reach of DXR screening interventions for TB. This qualitative study assessed early implementers' experiences and lessons learned when using ultra-portable (UP) DXR systems integrated with CAD software to screen and triage TB. METHODS: Semi-structured interviews were conducted with project staff and healthcare workers at six pilot sites. Transcripts were coded and analyzed using a framework approach. The themes that emerged were subsequently organized and presented using the Consolidated Framework for Implementation Research (CFIR). RESULTS: There were 26 interviewees with varying roles: supervisory, clinicians, radiographers, and radiologists. Participants recognized the portability as the main advantage, but criticize that it involves several compromises on throughput, internet dependence, manoeuvrability, and stability, as well as suitability for patients with larger body sizes. Furthermore, compared to using hardware and software from the same supplier and without digital health information systems, complexity increases with interoperability between hardware and software, and between different electronic health information systems. Currently, there is a limited capacity to implement these technologies, especially due to the need for threshold selection, and lack of guidance on radiation protection suitable for UP DXR machines. Finally, the respondents stressed the importance of having protected means of sharing patient medical data, as well as comprehensive support and warranty plans. CONCLUSION: Study findings suggest that UP DXR with CAD was overall well received to decentralize radiological assessment for TB, however, the improved portability involved programmatic compromises. The main barriers to uptake included insufficient capacity and lack of guidance on radiation protection suitable for UP DXR.

Comparing Catastrophic Costs: Active vs. Passive Tuberculosis Case Finding in Urban Vietnam.

Active case finding (ACF) is a strategy that aims to identify people with tuberculosis (TB) earlier in their disease. This outreach approach may lead to a reduction in catastrophic cost incurrence (costs exceeding 20% of annual household income), a main target of WHO's End TB Strategy. Our study assessed the socio-economic impact of ACF by comparing patient costs in actively and passively detected people with TB. Longitudinal patient cost surveys were prospectively fielded for people with drug-sensitive pulmonary TB, with 105 detected through ACF and 107 passively detected. Data were collected in four Vietnamese cities between October 2020 and March 2022. ACF reduced pre-treatment (USD 10 vs. 101, p < 0.001) and treatment costs (USD 888 vs. 1213, p < 0.001) in TB-affected individuals. Furthermore, it reduced the occurrence of job loss (15.2% vs. 35.5%, p = 0.001) and use of coping strategies (28.6% vs. 45.7%, p = 0.004). However, catastrophic cost incurrence was high at 52.8% and did not differ between cohorts. ACF did not significantly decrease indirect costs, the largest contributor to catastrophic costs. ACF reduces costs but cannot sufficiently reduce the risk of catastrophic costs. As income loss is the largest driver of costs during TB treatment, social protection schemes need to be expanded.

Novel methodology to assess sputum smear microscopy quality in private laboratories.

BACKGROUND: In South Asia, it is estimated that 80% of patients choose to attend a private facility for their healthcare needs. Although patients generally believe that the private-sector provides high quality services, private diagnostic laboratories are largely unregulated and little is known about the accuracy of results provided. This study assesses the accuracy of sputum smear microscopy for pulmonary tuberculosis diagnosis in private laboratories operating in Karachi, Pakistan. A novel evaluation methodology was designed in which patient-actors submitted sputum specimens spiked with cultured Mycobacterium tuberculosis (Mtb) for testing such that laboratories were not aware that they were being assessed. METHODS: Smear-negative sputum specimens from Indus Hospital TB Program patients were collected and combined with an attenuated, cultured Mtb strain to create Mtb-spiked samples; for negative standards, no Mtb was added to the smear-negative sputum specimens. Seven of the largest private laboratories across Karachi were chosen for evaluation and were sent six Mtb-spiked and one Mtb-negative sputum specimens. Patient-actors pretending to be laboratory customers submitted these specimens to each laboratory for testing over a three day period. RESULTS: Only three laboratories accurately classified all the Mtb-spiked specimens which were submitted. A further three misclassified all the Mtb-spiked specimens as smear-negative, thus providing the 'patients' with false negative results. CONCLUSIONS: TB sputum smear microscopy services are highly variable across private laboratories and are often of extremely poor quality. Engagement, capacity building and rigorous monitoring of standards at private laboratories are of vital importance for the control of TB. Our findings, while specific for TB diagnostic tests, could be symptomatic of other tests performed in private laboratories and warrant further investigation.

Evaluating novel engagement mechanisms, yields and acceptability of tuberculosis screening at retail pharmacies in Ho Chi Minh City, Viet Nam.

Pharmacies represent a key health system entry point for people with TB in Viet Nam, but high fragmentation hinders their broader engagement. Professional networking apps may be able to facilitate pharmacy engagement for systematic TB screening and referral. Between September and December 2019, we piloted the use of a social networking app, SwipeRx, to recruit pharmacists for a TB referral scheme across four districts of Ho Chi Minh City, Viet Nam. We measured chest X-ray (CXR) referrals and TB detection yields at participating pharmacies and fielded 100 acceptability surveys, divided into pharmacists who did and did not make a CXR referral. We then fitted mixed-effect odds proportional models to explore acceptability factors that were associated with making a CXR referral. 1,816 push notifications were sent to pharmacists via the SwipeRx app and 78 indicated their interest in participating; however, only one was within the pilot's intervention area. Additional in-person outreach resulted in the recruitment of 146 pharmacists, with 54 (37.0%) making at least one CXR referral. A total of 182 pharmacy customers were referred, resulting in a total of 64 (35.2%) CXR screens and seven people being diagnosed with TB. Compared to pharmacists who did not make any CXR referrals, pharmacists making at least one CXR referral understood the pilot's objectives more clearly (aOR = 2.6, 95% CI: 1.2-5.8) and they believed that TB screening increased customer trust (aOR = 2.7, 95% CI: 1.2-5.8), benefited their business (aOR = 2.8, 95% CI: 1.3-6.2) and constituted a competitive advantage (aOR = 4.4, 95% CI: 1.9-9.9). They were also more confident in using mHealth apps (aOR = 3.1, 95 CI%: 1.4-6.8). Pharmacies can play an important role in early and increased TB case finding. It is critical to highlight the value proposition of TB referral schemes to their business during recruitment. Digital networking platforms, such as SwipeRx, can facilitate referrals for TB screening by pharmacists, but their ability to identify and recruit pharmacists requires optimization, particularly when targeting specific segments of a nation-wide digital network.

Independent evaluation of 12 artificial intelligence solutions for the detection of tuberculosis.

There have been few independent evaluations of computer-aided detection (CAD) software for tuberculosis (TB) screening, despite the rapidly expanding array of available CAD solutions. We developed a test library of chest X-ray (CXR) images which was blindly re-read by two TB clinicians with different levels of experience and then processed by 12 CAD software solutions. Using Xpert MTB/RIF results as the reference standard, we compared the performance characteristics of each CAD software against both an Expert and Intermediate Reader, using cut-off thresholds which were selected to match the sensitivity of each human reader. Six CAD systems performed on par with the Expert Reader (Qure.ai, DeepTek, Delft Imaging, JF Healthcare, OXIPIT, and Lunit) and one additional software (Infervision) performed on par with the Intermediate Reader only. Qure.ai, Delft Imaging and Lunit were the only software to perform significantly better than the Intermediate Reader. The majority of these CAD software showed significantly lower performance among participants with a past history of TB. The radiography equipment used to capture the CXR image was also shown to affect performance for some CAD software. TB program implementers now have a wide selection of quality CAD software solutions to utilize in their CXR screening initiatives.

Can the High Sensitivity of Xpert MTB/RIF Ultra Be Harnessed to Save Cartridge Costs? Results from a Pooled Sputum Evaluation in Cambodia.

Despite the World Health Organization recommending the use of rapid molecular tests for diagnosing tuberculosis (TB), uptake has been limited, partially due to high cartridge costs. Other infectious disease programs pool specimens to save on diagnostic test costs. We tested a sputum pooling strategy as part of a TB case finding program using Xpert MTB/RIF Ultra (Ultra). All persons were tested with Ultra individually, and their remaining specimens were also grouped with 3-4 samples for testing in a pooled sample. Individual and pooled testing results were compared to see if people with TB would have been missed when using pooling. We assessed the potential cost and time savings which different pooling strategies could achieve. We tested 584 individual samples and also grouped them in 153 pools for testing separately. Individual testing identified 91 (15.6%) people with positive Ultra results. One hundred percent of individual positive results were also found to be positive by the pooling strategy. Pooling would have saved 27% of cartridge and processing time. Our results are the first to use Ultra in a pooled approach for TB, and demonstrate feasibility in field conditions. Pooling did not miss any TB cases and can save time and money. The impact of pooling is only realized when yield is low.

Will more sensitive diagnostics identify tuberculosis missed by clinicians? Evaluating Xpert MTB/RIF testing in Guatemala.

OBJECTIVE: To assess the impact of introducing Xpert as a follow-on test after smear microscopy on the total number pulmonary TB notifications. METHOD: Genexpert systems were installed in six departments across Guatemala, and Xpert was indicated as a follow-on test for people with smear-negative results. We analyzed notifications to national tuberculosis (TB) programmes (NTP) and the project's laboratory data to assess coverage of the intervention and case detection yield. Changes in quarterly TB notifications were analyzed using a simple pre/post comparison and a regression model controlling for secular notification trends. Using a mix of project and NTP data we estimated the theoretical yield of the intervention if testing coverage achieved 100%. RESULTS: Over 18,000 smear-negative individuals were eligible for Xpert testing during the intervention period. Seven thousand, one hundred and ninety-three people (39.6% of those eligible) were tested on Xpert resulting in the detection of 199 people with smear-negative, Xpert positive results (2.8% positivity rate). In the year before testing began 1098 people with smear positive and 195 people with smear negative results were notified in the six intervention departments. During the intervention, smear-positive notification remained roughly stable (1090 individuals, 0.7%), but smear-negative notifications increased by 167 individuals (85.6%) to an all-time high of 362. After controlling for secular notifications trends over an eight-quarter pre-intervention period, combined pulmonary TB notifications (both smear positive and negative) were 19% higher than trend predictions. If Xpert testing coverage approached 100% of those eligible, we estimate there would have been a+41% increase in TB notifications. CONCLUSIONS: We measured a large gain in pulmonary notifications through the introduction of Xpert testing alone. This indicates a large number of people with TB in Guatemala are seeking health care and being tested, yet are not diagnosed or treated because they lack bacteriological confirmation. Wider use of more sensitive TB diagnostics and/or improvements in the number of people clinically diagnosed with TB have the potential to significantly increase TB notifications in this setting, and potentially in other settings where a low proportion of pulmonary notifications are clinically diagnosed.

An Evaluation of Programmatic Community-Based Chest X-ray Screening for Tuberculosis in Ho Chi Minh City, Vietnam.

Across Asia, a large proportion of people with tuberculosis (TB) do not report symptoms, have mild symptoms or only experience symptoms for a short duration. These individuals may not seek care at health facilities or may be missed by symptom screening, resulting in sustained TB transmission in the community. We evaluated the yields of TB from 114 days of community-based, mobile chest X-ray (CXR) screening. The yields at each step of the TB screening cascade were tabulated and we compared cohorts of participants who reported having a prolonged cough and those reporting no cough or one of short duration. We estimated the marginal yields of TB using different diagnostic algorithms and calculated the relative diagnostic costs and cost per case for each algorithm. A total of 34,529 participants were screened by CXR, detecting 256 people with Xpert-positive TB. Only 50% of those diagnosed with TB were detected among participants reporting a prolonged cough. The study's screening algorithm detected almost 4 times as much TB as the National TB Program's standard diagnostic algorithm. Community-based, mobile chest X-ray screening can be a high yielding strategy which is able to identify people with TB who would likely otherwise have been missed by existing health services.

Performance of algorithms for tuberculosis active case finding in underserved high-prevalence settings in Cambodia: a cross-sectional study.

Background: Most studies evaluate active case findings (ACF) for bacteriologically confirmed TB. Adapted diagnostic approaches are needed to identify cases with lower bacillary loads. Objectives: To assess the likelihood of diagnosing all forms of TB, including clinically diagnosed pulmonary and extra-pulmonary TB, using different ACF algorithms in Cambodia. Methods: Clients were stratified into 'high-risk' (presumptive TB plus TB contact, or history of TB, or presumptive HIV infection; n = 12,337) and 'moderate-risk' groups (presumptive TB; n = 28,804). Sputum samples were examined by sputum smear microscopy (SSM) or Xpert MTB/RIF (Xpert). Initially, chest X-ray using a mobile radiography unit was a follow-up test after a negative sputum examination [algorithms A (Xpert/X-ray) and B (SSM/X-ray)]. Subsequently, all clients received an X-ray [algorithms C (X-ray+Xpert) and D (Xray+SSM/Xpert)]. X-rays were interpreted on the spot. Results: Between 25 August 2014 and 31 March 2016, 2217 (5.4%) cases with all forms of TB cases were diagnosed among 41,141 adults. The majority of TB cases (1488; 67.1%) were diagnosed using X-ray. When X-rays were taken and interpreted the same day the sputum was collected, same-day diagnosis more than doubled. Overall, the number needed to test (NNT) to diagnose one case was 18.6 (95%CI:17.9-19.2). In the high-risk group the NNT was lower [algorithm D: NNT = 17.3(15.9-18.9)] compared with the 'moderate-risk group' [algorithm D: NNT = 20.8(19.6-22.2)]. In the high-risk group the NNT was lower when using Xpert as an initial test [algorithm A: NNT = 12.2(10.8-13.9) or algorithm C: NNT = 11.2(9.6-13.0)] compared with Xpert as a follow-up test [algorithm D: NNT = 17.3(15.9-18.9)]. Conclusion: To diagnose all TB forms, X-ray should be part of the diagnostic algorithm. The combination of X-ray and Xpert testing for high-risk clients was the most effective ACF approach in this setting.

Systematic screening for tuberculosis among hospital outpatients in Cameroon: The role of screening and testing algorithms to improve case detection.

BACKGROUND: Better screening and testing approaches are needed to improve TB case finding, particularly in health facilities where many people with TB seek care but are not diagnosed using the existing approaches. OBJECTIVE: We aimed to evaluate the performance of various TB screening and testing approaches among hospital outpatients in a setting with a high prevalence of HIV/TB. METHODS: We screened outpatients at a large hospital in Cameroon using both chest X-ray and a symptom questionnaire including current cough, fever, night sweats and/or weight loss. Participants with a positive screen were tested for TB using smear microscopy, the Xpert MTB/RIF assay, and culture. RESULTS: Among 2051 people screened, 1137 (55%) reported one or more TB symptom and 389 (19%) had an abnormal chest X-ray. In total, 1255 people (61%) had a positive screen and 31 of those screened (1.5%) had bacteriologically confirmed TB. To detect TB, screening with cough >2 weeks had a sensitivity of 61% (95% CI, 44-78%). Screening for a combination of cough >2 -weeks and/or abnormal chest X-ray had a sensitivity of 81% (95% CI, 67-95%) and specificity of 71% (95% CI, 69-73%), while screening for a combination of cough >2 weeks or any of 2 or more symptoms had a similar performance. Smear microscopy and Xpert MTB/RIF detected 32% (10/31) and 55% (17/31), respectively, of people who had bacteriologically-confirmed TB. CONCLUSIONS: Screening hospital outpatients for cough >2 weeks or for at least 2 of current cough, fever, night sweats or weight loss is a feasible strategy that had a high relative yield to detect bacteriologically-confirmed TB in this population. Clinical diagnosis of TB is still an important need, even where Xpert MTB/RIF testing is available.

Using artificial intelligence to read chest radiographs for tuberculosis detection: A multi-site evaluation of the diagnostic accuracy of three deep learning systems.

Deep learning (DL) neural networks have only recently been employed to interpret chest radiography (CXR) to screen and triage people for pulmonary tuberculosis (TB). No published studies have compared multiple DL systems and populations. We conducted a retrospective evaluation of three DL systems (CAD4TB, Lunit INSIGHT, and qXR) for detecting TB-associated abnormalities in chest radiographs from outpatients in Nepal and Cameroon. All 1196 individuals received a Xpert MTB/RIF assay and a CXR read by two groups of radiologists and the DL systems. Xpert was used as the reference standard. The area under the curve of the three systems was similar: Lunit (0.94, 95% CI: 0.93-0.96), qXR (0.94, 95% CI: 0.92-0.97) and CAD4TB (0.92, 95% CI: 0.90-0.95). When matching the sensitivity of the radiologists, the specificities of the DL systems were significantly higher except for one. Using DL systems to read CXRs could reduce the number of Xpert MTB/RIF tests needed by 66% while maintaining sensitivity at 95% or better. Using a universal cutoff score resulted different performance in each site, highlighting the need to select scores based on the population screened. These DL systems should be considered by TB programs where human resources are constrained, and automated technology is available.

Will more sensitive diagnostics identify tuberculosis missed by clinicians? Evaluating Xpert MTB/RIF testing in Guatemala / ¿Pueden las pruebas diagnósticas más sensibles identificar los casos de tuberculosis que se escapan a los clínicos? Evaluación de Xpert MIB/RIF en Guatemala

OBJECTIVE: To assess the impact of introducing Xpert as a follow-on test after smear microscopy on the total number pulmonary TB notifications. METHOD: Genexpert systems were installed in six departments across Guatemala, and Xpert was indicated as a follow-on test for people with smear-negative results. We analyzed notifications to national tuberculosis (TB) programmes (NTP) and the project's laboratory data to assess coverage of the intervention and case detection yield. Changes in quarterly TB notifications were analyzed using a simple pre/post comparison and a regression model controlling for secular notification trends. Using a mix of project and NTP data we estimated the theoretical yield of the intervention if testing coverage achieved 100%. RESULTS: Over 18,000 smear-negative individuals were eligible for Xpert testing during the intervention period. Seven thousand, one hundred and ninety-three people (39.6% of those eligible) were tested on Xpert resulting in the detection of 199 people with smear-negative, Xpert positive results (2.8% positivity rate). In the year before testing began 1098 people with smear positive and 195 people with smear negative results were notified in the six intervention departments. During the intervention, smear-positive notification remained roughly stable (1090 individuals, 0.7%), but smear-negative notifications increased by 167 individuals (85.6%) to an all-time high of 362. After controlling for secular notifications trends over an eight-quarter pre-intervention period, combined pulmonary TB notifications (both smear positive and negative) were 19% higher than trend predictions. If Xpert testing coverage approached 100% of those eligible, we estimate there would have been a+41% increase in TB notifications. CONCLUSIONS: We measured a large gain in pulmonary notifications through the introduction of Xpert testing alone. This indicates a large number of people with TB in Guatemala are seeking health care and being tested, yet are not diagnosed or treated because they lack bacteriological confirmation. Wider use of more sensitive TB diagnostics and/or improvements in the number of people clinically diagnosed with TB have the potential to significantly increase TB notifications in this setting, and potentially in other settings where a low proportion of pulmonary notifications are clinically diagnosed

OBJETIVO: Evaluar el impacto en la notificación de casos de tuberculosis pulmonar de la introducción de Xpert como prueba de continuación después del análisis microscópico. MÉTODO: Se instalaron sistemas Genexpert es seis departamentos de Guatemala y se indicó como prueba consecutiva en todos los resultados negativos en la baciloscopia microscópica. Se analizaron los datos del Programa Nacional y los del laboratorio del proyecto para medir la cobertura y la productividad en detección de casos. Las notificaciones trimestrales se compararon con los valores anteriores a la intervención y se adoptó un modelo de regresión para controlar por las tendencias temporales. Se estimó la contribución teórica de la intervención en términos de notificación si se obtuviera una cobertura del 100%. RESULTADOS: Durante el período de intervención, más de 18.000 personas con baciloscopia negativa fueron elegibles en los seis departamentos. El esputo de 7193 (36,9%) de ellos fue analizado también por Xpert y se detectaron 199 personas con baciloscopia negativa y Xpert positivo (positividad: 2,8%). En el año anterior a la intervención se notificaron 1098 casos de tuberculosis pulmonar y baciloscopia positiva, y 195 con baciloscopia negativa. Durante la intervención, la notificación de casos con baciloscopia positiva se mantuvo estable (1090 personas, 0,7%), pero las notificaciones con baciloscopia negativa, que incluía los casos con baciloscopia negativa y Xpert positivo, aumentó en 167 casos (85,6%), llegando a los 362 casos. Después de controlar por la tendencia temporal de notificación en los ocho trimestres anteriores, la notificación de tuberculosis pulmonar (con baciloscopia positiva o no) fue un 19% mayor que las predicciones de la tendencia. Si la cobertura de Xpert se acercase al 100%, se estima que se habría producido un incremento del 41% en las notificaciones. CONCLUSIONES: Se identifica un importante aumento de las notificaciones de tuberculosis pulmonar solo con la introducción de Xpert. Ello indica que un número importante de personas con tuberculosis en Guatemala son atendidos por los servicios de salud y son sometidos a bacteriología microscópica, pero no son diagnosticados ni tratados porque no disponen de confirmación bacteriológica. La utilización de técnicas diagnósticas más sensibles o la mejora en el diagnóstico clínico tienen potencial para aumentar significativamente las notificaciones de tuberculosis pulmonar en esta zona y en cualquier otro lugar donde exista una proporción baja de diagnósticos clínicos no confirmados por microscopía

The burden of non-communicable disease in transition communities in an Asian megacity: baseline findings from a cohort study in Karachi, Pakistan.

BACKGROUND: The demographic transition in South Asia coupled with unplanned urbanization and lifestyle changes are increasing the burden of non-communicable disease (NCD) where infectious diseases are still highly prevalent. The true magnitude and impact of this double burden of disease, although predicted to be immense, is largely unknown due to the absence of recent, population-based longitudinal data. The present study was designed as a unique 'Framingham-like' Pakistan cohort with the objective of measuring the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection in a multi-ethnic, middle to low income population of Karachi, Pakistan. METHODS: We selected two administrative areas from a private charitable hospital's catchment population for enrolment of a random selection of cohort households in Karachi, Pakistan. A baseline survey measured the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection. RESULTS: Six hundred and sixty-seven households were enrolled between March 2010 and August 2011. A majority of households lived in permanent structures (85%) with access to basic utilities (77%) and sanitation facilities (98%) but limited access to clean drinking water (68%). Households had high ownership of communication technologies in the form of cable television (69%) and mobile phones (83%). Risk factors for NCD, such as tobacco use (45%), overweight (20%), abdominal obesity (53%), hypertension (18%), diabetes (8%) and pre-diabetes (40%) were high. At the same time, infectious diseases such as hepatitis B (24%) and hepatitis C (8%) were prevalent in this population. CONCLUSION: Our findings highlight the need to monitor risk factors and disease trends through longitudinal research in high-burden transition communities in the context of rapid urbanization and changing lifestyles. They also demonstrate the urgency of public health intervention programs tailored for these transition communities.

Short report: Gender differences in tuberculosis notification in Pakistan.

Worldwide, the male to female ratio of new smear-positive tuberculosis (TB) cases is approximately two to one. However, in Pakistan, this is not the case. Rates of notified TB cases are 20-30% higher in young females compared with males, and female rates remain high regardless of increasing age. This is in stark contrast to neighboring India, which is characterized by an excess of male TB cases. It is currently unknown why rates of notified TB are so high in females in Pakistan, but it is clear that this epidemiology is a public health issue of importance that impacts transmission dynamics and disease control initiatives.