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Background Tuberculosis case-finding interventions often involve several activities to enhance patient pathways, and it is unclear which activity defines the type of case-finding intervention. When conducting studies to identify the most effective case-finding intervention it is important to have a clear understanding of these interventions for meaningful comparisons. This review aimed to construct a systems-based logic model of all pathways to tuberculosis case detection through a synthesis of intervention designs. Methods We identified an existing systematic review on the effectiveness of interventions to increase tuberculosis case detection and updated the search from December 2016 to October 2020. We included randomized controlled trials, as these designs encourage detailed description of interventions. Taking each study in turn, intervention descriptions were read in detail. The texts were analysed qualitatively by constantly comparing emerging codes to construct patient journeys, visualized as logical chains. Actions taken as part of interventions were positioned along patient journeys to theorize the sequence of outcomes. Patient journeys formed the basis of the model, which was refined through discussion. Results Based on intervention descriptions from 17 randomized controlled trials, our model distinguishes two care-seeking pathways and four screening pathways. An open invitation to people with tuberculosis symptoms creates care-seeking pathways. On care-seeking pathways, systematic screening can be conducted at general health services, but not at specific TB care services. People invited to tuberculosis services regardless of symptoms follow tuberculosis screening pathways and may be identified with presumptive tuberculosis even if they do not seek care for tuberculosis symptoms. Tuberculosis screening pathways include screening offered to all people accessing care at general health services, screening at a mobile clinic or health facility with open invitation to a whole population or tuberculosis contacts, screening personally offered to a whole population or tuberculosis contacts at home, work or school, and screening offered to people receiving care for human immunodeficiency virus or other clinical risk-group care. Conclusion This systems-based logic model of tuberculosis case-finding pathways may support standardized terminology, consistency, transparency and improved communication among researchers, policy-makers, health workers and community members when implementing and evaluating interventions to improve tuberculosis case detection.

Finding individuals with drug-resistant tuberculosis (DR-TB) is important to control the pandemic and improve patient clinical outcomes. To our knowledge, systematic reviews assessing the effectiveness, cost-effectiveness, acceptability, and feasibility of different DR-TB case-finding strategies to inform research, policy, and practice, have not been conducted and the scope of primary research is unknown. We therefore assessed the available literature on DR-TB case-finding strategies. We looked at systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that sought to improve DR-TB case detection specifically. We excluded studies that included patients seeking care for tuberculosis (TB) symptoms, patients already diagnosed with TB, or were laboratory-based. We searched the academic databases of MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL (Cumulated Index to Nursing and Allied Health Literature), Epistemonikos, and PROSPERO (The International Prospective Register of Systematic Reviews) using no language or date restrictions. We screened titles, abstracts, and full-text articles in duplicate. Data extraction and analyses were carried out in Excel (Microsoft Corp). We screened 3646 titles and abstracts and 236 full-text articles. We identified 6 systematic reviews and 61 primary studies. Five reviews described the yield of contact investigation and focused on household contacts, airline contacts, comparison between drug-susceptible tuberculosis and DR-TB contacts, and concordance of DR-TB profiles between index cases and contacts. One review compared universal versus selective drug resistance testing. Primary studies described (1) 34 contact investigations, (2) 17 outbreak investigations, (3) 3 airline contact investigations, (4) 5 epidemiological analyses, (5) 1 public-private partnership program, and (6) an e-registry program. Primary studies were all descriptive and included cross-sectional and retrospective reviews of program data. No trials were identified. Data extraction from contact investigations was difficult due to incomplete reporting of relevant information. Existing descriptive reviews can be updated, but there is a dearth of knowledge on the effectiveness, cost-effectiveness, acceptability, and feasibility of DR-TB case-finding strategies to inform policy and practice. There is also a need for standardization of terminology, design, and reporting of DR-TB case-finding studies.

Consensus case definitions for childhood tuberculosis have been proposed by an international expert panel, aiming to standardize the reporting of cases in research focusing on the diagnosis of intrathoracic tuberculosis in children. These definitions are intended for tuberculosis diagnostic evaluation studies of symptomatic children with clinical suspicion of intrathoracic tuberculosis, and were not intended to predefine inclusion criteria into such studies. Feedback from researchers suggested that further clarification was required and that these case definitions could be further improved. Particular concerns were the perceived complexity and overlap of some case definitions, as well as the potential exclusion of children with acute onset of symptoms or less severe disease. The updated case definitions proposed here incorporate a number of key changes that aim to reduce complexity and improve research performance, while maintaining the original focus on symptomatic children suspected of having intrathoracic tuberculosis. The changes proposed should enhance harmonized classification for intrathoracic tuberculosis disease in children across studies, resulting in greater comparability and the much-needed ability to pool study results.

We analyzed a pharmacy dataset to assess the 20% decline in tuberculosis (TB) cases reported to the US National Tuberculosis Surveillance System (NTSS) during the coronavirus disease pandemic in 2020 compared with the 2016-2019 average. We examined the correlation between TB medication dispensing data to TB case counts in NTSS and used a seasonal autoregressive integrated moving average model to predict expected 2020 counts. Trends in the TB medication data were correlated with trends in NTSS data during 2006-2019. There were fewer prescriptions and cases in 2020 than would be expected on the basis of previous trends. This decrease was particularly large during April-May 2020. These data are consistent with NTSS data, suggesting that underreporting is not occurring but not ruling out underdiagnosis or actual decline. Understanding the mechanisms behind the 2020 decline in reported TB cases will help TB programs better prepare for postpandemic cases.

Background Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality. Methods At 22 clinics, ART enrollees > 12 years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation. Results We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/μL in SOC, 246/μL in EC, and 241/μL in EC+X). By 6 months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61–0.97, p  = 0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees. Conclusions Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed. Trial registration Retrospectively registered: ClinicalTrials.gov ( NCT02538952 )

Tuberculosis (TB) among hospitalized patients is underdiagnosed. This study assessed systematic TB-screening, followed by an enhanced TB-diagnostic package for hospitalized patients implemented by trained lay health workers in KwaZulu-Natal, South Africa. In this before-and-after study we included patients ≥ 18 years. The intervention consisted of systematic clinical screening for TB, HIV and diabetes mellitus by lay health workers and provision of an enhanced TB-diagnostic package including sputum Xpert MTB/Rif Ultra, urine lateral-flow lipoarabinomannan assay (LF-LAM), chest x-ray, and sputum culture. We compared TB case findings with people hospitalized one year preceding the intervention. In the pre-intervention phase, 5217 people were hospitalized. Among 4913 (94.2%) people not on TB treatment, 367 (7.5%) were diagnosed with TB. In the intervention phase, 4015 eligible people were hospitalized. Among 3734 (93.0%) people not on TB treatment, 560 (15.0%) were diagnosed with TB. The proportion of patients diagnosed with TB was higher in the intervention phase (15.0% vs. 7.5%, p < 0.001). Overall in-hospital mortality was lower in the intervention phase [166/3734(4.5%) vs. 336/4913(6.8%), p < 0.001]. Lay health worker-led implementation of systematic TB-screening, coupled with provision of an enhanced TB-diagnostic package significantly improved TB case detection and mortality among hospitalized adults.

Background In many low and middle-income countries, Tuberculosis (TB) surveillance systems miss out on reporting on detected cases suggesting gaps in the TB case detection and documentation systems. The World Health Organisation estimates that less than half of TB cases in Ghana are notified. Capture-recapture (CR) techniques that involve data linkages have been applied in various settings to estimate the total number of tuberculosis cases, including those unreported. This study evaluated the completeness of reporting of TB in a region of Ghana using CR techniques. Methods We evaluated the completeness of TB case notification data reported between 2016 and 2017 by performing record linkage in five out of 26 districts in the Eastern Region of Ghana. We linked data of all bacteriologically confirmed pulmonary TB (PTB) cases recorded in three registries, namely the district, laboratory, and treatment centre registers, to identify gaps in notification. Regression analysis was used to assess linkages of the three records based on name, age and sex. We estimated overall completeness with log-linear modelling. Results There were 2,035 cases across the three registers, of which 773 (38%) were bacteriologically confirmed. The district, laboratory and treatment centre registers had recorded 369 (47.7%), 368 (47.6%) and 404 (52.3%) of the confirmed cases respectively. Only 82 (10.6%) cases were consistent across all three registers. There were 115 (14.9%), 238 (30.8%) and 134 (17.3%) cases that were exclusively in the district, laboratory and treatment centre registers. Log-linear capture-recapture model estimated 2,483 (95%CI: 1,797; 3,813) as expected number of confirmed cases. On that basis, overall completeness of reporting of the district TB registry was 14.9% (369/2,483; 95%CI: 13.5, 16.3). Conclusion We found low levels of completeness of TB case reporting in the study area. A more wider assessment of the surveillance system in Ghana is needed to identify gaps in reporting.

In India, tuberculosis (TB) notification has been required since 2012. Notwithstanding, notification rates remain low. Non-reporting of tuberculosis cases not only results in an underestimation of cases, but also impedes the country's TB control strategy. Our research aims to assess practitioners' awareness, perception, and practice of tuberculosis case notification, as these factors can help reduce the TB burden. A cross-sectiol study of 142 physicians was conducted between August 2018 and December 2019. Doctors were interviewed and given evaluation forms. Seventy-seven percent of the 142 physicians polled worked in medicine-related specialties, while 33% worked in surgery. Public sector physicians (64.7%) knew more about the Nikshay App than private practitioners (40.8%). The vast majority of public-sector doctors were only notified through their hospital's tiol Tuberculosis Elimition Programme (NTEP) center. However, the majority of private practitioners (47.8%) notified cases directly through the hospital, the local District Tuberculosis Officer (DTO) or NTEP medical officer (24 percent), or the Nikshay portal (28%), whereas the majority of public sector doctors notified only through the hospital NTEP center (85.9%). The primary reasons for non-notification are the high patient load on doctors, a lack of understanding about Nikshay App and its functiolity, technological difficulties in using the Nikshay App, and the stigma associated with tuberculosis. The Nikshay App must be popularized as a notification mechanism through the NTEP program. To increase notification rates, practitioners must overcome the challenges they face. In terms of notification, more semirs and training, particularly hands-on training, should be held on a regular basis.

Background: Tuberculosis remains one of the biggest global public health problems today. The objective of this study was to evaluate the diagnostic methods, clinical outcomes, patient compliance, and mortality rates in patients diagnosed with extrarespiratory tuberculosis. Methods: 105 cases of extrarespiratory tuberculosis were analyzed over a five-year period (2018–2023). Data from medical records were reviewed and processed. Diagnostic methods included Ziehl–Nielsen staining, Löwenstein–Jensen cultures, GeneXpert, and histopathological analysis. Diagnosis was supplemented by a specialist organ examination and, in cases with concurrent pulmonary involvement, by a chest X-ray and sputum examination. For negative cases, a probabilistic diagnosis was made. Results: Most patients presented pleural TB (38%), osteo-articular TB (26.67%), and ganglionary TB (19%). Patients were mostly men (56.19%), in the 18–40 years-old category (40%), and lived in rural areas (61%). In total, 94.29% were newly diagnosed and most observed comorbidites were chronic smoking (11.37%), chronic lung diseases (10.20%), and malnutrition (9.02%). Moreover, 68% had a negative microscopic examination, while 55% had negative cultures on Löwenstein–Jensen. Conclusions: This study highlights the importance of a multi-modal approach to diagnosing extrarespiratory tuberculosis, especially in negative bacteriological and histopathological results. Imaging, combined with clinical and epidemiological data, is critical for a probabilistic diagnosis. GeneXpert proved useful in difficult cases. This study emphasizes the need for a comprehensive diagnostic strategy to effectively manage extrarespiratory tuberculosis.

Background The incidence of tuberculosis (TB) is high in Uganda; yet, TB case detection is low. The population-based survey on the prevalence of TB in Uganda revealed that only 16% of presumptive TB patients seeking care at health facilities were offered sputum microscopy or chest-X ray (CXR). This study aimed to determine the magnitude of, and patient factors associated with missed opportunities in TB investigation at public health facilities of Wakiso District in Uganda. Methods A facility-based cross-sectional survey was conducted at 10 high volume public health facilities offering comprehensive TB services in Wakiso, Uganda, among adults (≥18 years) with at least one symptom suggestive of TB predefined according to the World Health Organisation criteria. Using exit interviews, data on demographics, TB symptoms, and clinical data relevant to TB diagnosis were collected. A missed opportunity in TB investigation was defined as a patient with symptoms suggestive of TB who did not have sputum and/or CXR evaluation to rule out TB. Poisson regression analysis was performed to determine factors associated with missed opportunities in TB investigation. Results Two hundred forty-seven (247) patients with presumptive TB exiting at antiretroviral therapy (ART) clinics ( n  = 132) or general outpatient clinics ( n  = 115) at public health facilities were recruited into this study. Majority of participants were female (161/247, 65.2%) with a mean + SD age of 35.1 + 11.5 years. Overall, 138 (55.9%) patients with symptoms suggestive of TB disease did not have sputum and/or CXR examinations. Patients who did not inform health workers about their TB related symptoms were more likely to miss a TB investigation (adjusted prevalence ratio (aPR): 1.68, 95%CI; 1.36–2.08, P  < 0.001). However, patients who reported duration of cough of 2 weeks or more were less likely to be missed for TB screening (aPR; 0.69, 95%CI; 0.56–0.86, p  < 0.001). Conclusion There are substantial missed opportunities for TB diagnosis in Wakiso District. While it is important that patients should be empowered to report symptoms, health workers need to proactively implement the WHO TB symptom screen tool and complete the subsequent steps in the TB diagnostic cascade.