Search

Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols  95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols

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: Tuberculous pleural effusion (TPE) is the most common form of extrapulmonary tuberculosis in many settings. The diagnostic performance of the frontline polymerase chain reaction-based GeneXpert MTB/RIF Ultra (Xpert Ultra) remains suboptimal (sensitivity of ∼30%), but data are limited. Improved diagnostic approaches are urgently needed to detect extrapulmonary tuberculosis (EPTB) in tuberculosis (TB)-endemic settings., Methods: This multicenter, prospective cohort study evaluated the diagnostic performance of a rapid (same-day) interferon gamma rapid immunosuspension assay (IRISA-TB) in patients with presumed TPE from South Africa and India. Participants underwent pleural biopsy, and testing with other available same-day diagnostic assays (adenosine deaminase [ADA], Xpert Ultra, and IRISA-TB) was concurrently undertaken. The reference standard for TB was microbiological and/or histopathological confirmation using pleural fluid and/or pleural biopsy samples., Results: A total of 217 participants with presumed TPE were recruited (106 from South Africa, 111 from India). The sensitivity of IRISA-TB (cut-point 20.5 pg/mL) was significantly better than that of Xpert Ultra (81.8% [70.4-90.2] vs 32.9% [22.1-45.1]; P < .001) and ADA at the 40 IU/mL cut-point used in India (81.8% [70.4-90.2] vs 53.8% [41.0-66.3]; P   = .002). Compared with ADA at the 30 IU/mL cut-point used in South Africa, IRISA-TB had a higher specificity (96.6% [90.3-99.3] vs 87.1% [78.6-93.2]) and a higher positive predictive value (94.7% [85.5-97.3] vs 81.8% [72.4-88.5]). The negative predictive value (NPV; rule-out value) of IRISA-TB was significantly better than that of Xpert Ultra (87.5% [83.2-93.0] vs 64.9% [61.1-68.6]; P < .001) and ADA at the 40 IU/mL cut-point (87.5% [83.2-93.0] vs 74.1% [68.7-79.0]; P < .001)., Conclusions: IRISA-TB demonstrated markedly better sensitivity and NPV than Xpert Ultra and excellent specificity for the diagnosis of TPE. These data have implications for clinical practice in TB-endemic settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Tuberculosis (TB) is a global health challenge and one of the leading causes of death worldwide. In the last decade, the TB treatment landscape has dramatically changed. After long years of stagnation, new compounds entered the market (bedaquiline, delamanid, and pretomanid) and phase III clinical trials have shown promising results towards shortening duration of treatment for both drug-susceptible (Study 31/A5349, TRUNCATE-TB, and SHINE) and drug-resistant TB (STREAM, NiX-TB, ZeNix, and TB-PRACTECAL). Dose optimization of rifamycins and repurposed drugs has also brought hopes of further development of safe and effective regimens. Consequently, international and WHO clinical guidelines have been updated multiple times in the last years to keep pace with these advances., Objectives: This narrative review aims to summarize the state-of-the-art on treatment of drug-susceptible and drug-resistant TB, as well as recent trial results and an overview of ongoing clinical trials., Sources: A non-systematic literature review was conducted in PubMed and MEDLINE, focusing on the treatment of TB. Ongoing clinical trials were listed according to the authors' knowledge and completed consulting clinicaltrials.gov and other publicly available websites (www.resisttb.org/clinical-trials-progress-report, www.newtbdrugs.org/pipeline/trials)., Content: This review summarizes the recent, major changes in the landscape for drug-susceptible and drug-resistant treatment, with a specific focus on their potential impact on patient outcomes and programmatic TB management. Moreover, insights in host-directed therapies, and advances in pharmacokinetics and pharmacogenomics are discussed. A thorough outline of ongoing therapeutic clinical trials is presented, highlighting different approaches and goals in current TB clinical research., Implications: Future research should be directed to individualize regimens and protect these recent breakthroughs by preventing and identifying the selection of drug resistance and providing widespread, affordable, patient-centred access to new treatment options for all people affected by TB., Competing Interests: Transparency declaration IM, MB, DC, KD, GG, CRH, YK, CLa, CLi, HMM, GT, ZU, RvC, GEV, RJW, and LG have nothing to declare. HRS reports honoraria in 2018 for speaking at and attending an event organized by the Latvian Society Against Tuberculosis, which was sponsored by Otsuka and Johnson and Johnson; NIP has received grant funding paid to institution from Janssen, drug donation for trials from Pfizer and Sanofi, and speaker fees from Janssen., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Tuberculous meningitis (TBM) mortality is high and current diagnostics perform suboptimally. We evaluated the diagnostic performance of a DNA-based assay (GeneXpert Ultra) against a new same-day immunodiagnostic assay that detects unstimulated interferon-gamma (IRISA-TB)., Methods: In a stage 1 evaluation, IRISA-TB was evaluated in biobanked samples from Zambia (n = 82; tuberculosis [TB] and non-TBM), and specificity in a South African biobank (n = 291; non-TBM only). Given encouraging results, a stage 2 evaluation was performed in suspected TBM patients from Zimbabwe and Malawi (n = 668). Patients were classified as having definite, probable or possible TBM, or non-TBM based on their microbiological results, cerebrospinal fluid (CSF) chemistry, and whether they received treatment., Results: In the stage 1 evaluation, sensitivity and specificity of IRISA-TB were 75% and 87% in the Zambian samples, and specificity was 100% in the South African samples. In the stage 2 validation, IRISA-TB sensitivity (95% confidence interval [CI]) was significantly higher than Xpert Ultra (76.2% [55.0%-89.4%] vs 25% [8.9%-53.3%]; P = .0048) when trace readouts were considered negative. Specificity (95% CI) was similar for both assays (91.4% [88.8%-93.4%] vs 86.9% [83.4%-89.8%]). When the Xpert Ultra polymerase chain reaction product was verified by sequencing, the positive predictive value of trace readouts in CSF was 27.8%. Sensitivity of IRISA-TB was higher in human immunodeficiency virus (HIV)-infected versus uninfected participants (85.8% vs 66.7%)., Conclusions: As a same-day rule-in test, IRISA-TB had significantly better sensitivity than Xpert Ultra in a TB/HIV-endemic setting. An immunodiagnostic approach to TBM is promising, and further studies are warranted., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Tools to evaluate and accelerate tuberculosis (TB) vaccine development are needed to advance global TB control strategies. Validated human infection studies for TB have the potential to facilitate breakthroughs in understanding disease pathogenesis, identify correlates of protection, develop diagnostic tools, and accelerate and de-risk vaccine and drug development. However, key challenges remain for realizing the clinical utility of these models, which require further discussion and alignment among key stakeholders. In March 2023, the Wellcome Trust and the International AIDS Vaccine Initiative convened international experts involved in developing both TB and bacillus Calmette-Guérin (BCG) human infection studies (including mucosal and intradermal challenge routes) to discuss the status of each of the models and the key enablers to move the field forward. This report provides a summary of the presentations and discussion from the meeting. Discussions identified key issues, including demonstrating model validity, to provide confidence for vaccine developers, which may be addressed through demonstration of known vaccine effects (eg, BCG vaccination in specific populations), and by comparing results from field efficacy and human infection studies. The workshop underscored the importance of establishing safe and acceptable studies in high-burden settings, and the need to validate >1 model to allow for different scientific questions to be addressed as well as to provide confidence to vaccine developers and regulators around use of human infection study data in vaccine development and licensure pathways., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. C. L. W., S. B., N. R. S., and C. N. L. are employees of Wellcome Trust. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To evaluate diagnostic yield and feasibility of integrating testing for TB and COVID-19 using molecular and radiological screening tools during community-based active case-finding (ACF)., Methods: Community-based participants with presumed TB and/or COVID-19 were recruited using a mobile clinic. Participants underwent simultaneous point-of-care (POC) testing for TB (sputum; Xpert Ultra) and COVID-19 (nasopharyngeal swabs; Xpert SARS-CoV-2). Sputum culture and SARS-CoV-2 RT-PCR served as reference standards. Participants underwent ultra-portable POC chest radiography with computer-aided detection (CAD). TB infectiousness was evaluated using smear microscopy, cough aerosol sampling studies (CASS), and chest radiographic cavity detection. Feasibility of POC testing was evaluated via user-appraisals., Results: Six hundred and one participants were enrolled, with 144/601 (24.0%) reporting symptoms suggestive of TB and/or COVID-19. 16/144 (11.1%) participants tested positive for TB, while 10/144 (6.9%) tested positive for COVID-19 (2/144 [1.4%] had concurrent TB/COVID-19). Seven (7/16 [43.8%]) individuals with TB were probably infectious. Test-specific sensitivity and specificity (95% CI) were: Xpert Ultra 75.0% (42.8-94.5) and 96.9% (92.4-99.2); Xpert SARS-CoV-2 66.7% (22.3-95.7) and 97.1% (92.7-99.2). Area under the curve (AUC) for CAD4TB was 0.90 (0.82-0.97). User appraisals indicated POC Xpert to have 'good' user-friendliness., Conclusions: Integrating TB/COVID-19 screening during community-based ACF using POC molecular and radiological tools is feasible, has a high diagnostic yield, and can identity probably infectious persons., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Simpler, shorter, safer and more effective treatments for tuberculosis that are easily accessible to all people with tuberculosis are desperately needed. In 2016, the World Health Organization (WHO) developed target regimen profiles for the treatment of tuberculosis to make drug developers aware of both the important features of treatment regimens, and patient and programmatic needs at the country level. In view of recent ground-breaking advances in tuberculosis treatment, WHO has revised and updated these regimen profiles. We used a similar process as for the 2016 profiles, including a baseline treatment landscape analysis, an initial stakeholder survey, modelling studies estimating the impact and cost-effectiveness of novel tuberculosis treatment regimens, and an extensive stakeholder consultation. We developed target regimen profiles for the treatment of rifampicin-susceptible and rifampicin-resistant tuberculosis, as well as a pan-tuberculosis regimen that would be appropriate for patients with any type of tuberculosis. We describe the revised target regimen profile characteristics, with specific minimal and optimal targets to be met, rationale and justification, and aspects relevant to all target regimen profiles (drug susceptibility testing, adherence and forgiveness, treatment strategies, post-tuberculosis lung disease, and cost and access considerations). We discuss the trade-offs of proposed characteristics for decision-making at developmental or operational levels. We expect that, following these target regimen profile revisions, tuberculosis treatment developers will produce regimens that are quality-assured, affordable and widely available, and that meet the needs of affected populations., ((c) 2024 The authors; licensee World Health Organization.)

Background: South Africa has high tobacco-attributable mortality and a smoking prevalence of 32.5% in males and 25.6% in females. There are limited data on smoking prevalence and desire to quit in hospitalised patients, who have limited access to smoking cessation services., Objectives: To determine smoking prevalence and the extent of nicotine withdrawal symptoms, using a hospital-wide inpatient survey., Methods: A 1-day point prevalence survey was conducted at Groote Schuur Hospital, Cape Town. All wards except the haematology isolation, active labour and psychiatry lock-up wards were evaluated. Smoking status, withdrawal symptoms and desire to quit were established., Results: Smoking status was confirmed in 85.8% of inpatients (n=501/584), of whom 31.9% (n=160) were current smokers; 43.5% (n=101/232) of male and 21.9% (n=59/269) of female inpatients were smokers. Documentation and confirmation of smoking status was highest in the maternity wards (100%) and lowest in the surgical wards (79.6%) and intensive care units (70.0%). Smoking prevalence ranged from 47.6% in male surgical patients to 15.2% in maternity patients. Of the smokers, 54.5% reported being motivated to quit, with a median (interquartile range) Fagerström test for nicotine dependence score of 4 (2 - 6), and 31.4% reported moderate to severe cravings to smoke, highest in the surgical wards., Conclusion: Smoking prevalence was higher in hospitalised patients than in the local general population. Many inpatients were not interested in quitting; however, a third had significant nicotine withdrawal symptoms. All inpatients who are active smokers should be identified and given universal brief smoking cessation advice. Patients with severe withdrawal symptoms should be allowed to smoke outside, and nicotine withdrawal pharmacotherapy should be provided to those who are bedbound or express a desire to stop smoking during the current admission., Study Synopsis: What the study adds. A single data point prevalence study of active smokers at Groote Schuur Hospital, Cape Town, was conducted. The prevalence of smoking was higher in the hospitalised patients than in the general community, but not all smokers were identified by the clinicians. Although symptoms of nicotine withdrawal were severe in some patients, motivation to quit smoking was not related to the degree of withdrawal being experienced. Many patients were not motivated to quit smoking. Implications of the findings. Better identification of inpatient smokers is required, and all should be given smoking cessation advice. Withdrawal symptoms can be severe in some patients, and those who are not interested in stopping smoking should allowed to smoke outside or be provided with nicotine withdrawal pharmacotherapy while in hospital. Those who are willing to quit should be supported as well as possible, including provision of nicotine replacement therapy or varenicline, and followed up after discharge as best practice., (Copyright © 2024, Soin et al.)

Competing Interests: We declare no competing interests.

Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for ∼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung). Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group. Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry. Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection ( P  < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity. Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).

Tuberculosis (TB) remains the foremost cause of death by an infectious disease globally. Multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB; resistance to rifampicin and isoniazid, or rifampicin alone) is a burgeoning public health challenge in several parts of the world, and especially Eastern Europe, Russia, Asia and sub-Saharan Africa. Pre-extensively drug-resistant TB (pre-XDR-TB) refers to MDR/RR-TB that is also resistant to a fluoroquinolone, and extensively drug-resistant TB (XDR-TB) isolates are additionally resistant to other key drugs such as bedaquiline and/or linezolid. Collectively, these subgroups are referred to as drug-resistant TB (DR-TB). All forms of DR-TB can be as transmissible as rifampicin-susceptible TB; however, it is more difficult to diagnose, is associated with higher mortality and morbidity, and higher rates of post-TB lung damage. The various forms of DR-TB often consume >50% of national TB budgets despite comprising <5-10% of the total TB case-load. The past decade has seen a dramatic change in the DR-TB treatment landscape with the introduction of new diagnostics and therapeutic agents. However, there is limited guidance on understanding and managing various aspects of this complex entity, including the pathogenesis, transmission, diagnosis, management and prevention of MDR-TB and XDR-TB, especially at the primary care physician level., (© 2024. Springer Nature Limited.)

Background: Tuberculous pericarditis (TBP) is a paucibacillary disease, where host biomarkers such as unstimulated interferon γ (IRISA-TB) have high diagnostic accuracy. However, DNA-based diagnostic tests (GeneXpert Ultra), more sensitive than an earlier versions, have recently become available. Given that the diagnosis of TBP is challenging, we performed a comparative diagnostic accuracy study comparing both assays., Methods: We recruited 99 consecutive patients with suspected TBP in Cape Town, South Africa. Definite TBP was defined by microbiological confirmation of tuberculosis (TB) on pericardial fluid culture or an alternative polymerase chain reaction-based test (GeneXpert MTB/RIF) or by use of sputum (polymerase chain reaction or culture). Probable TBP was defined as a high clinical suspicion of TB accompanied by anti-TB treatment, while non-TBP was defined as negative microbiological test results for TB without initiation of TB treatment and/or the presence of an alternative diagnosis., Results: There were 39 patients with definite TBP, 35 with probable TBP, and 23 with non-TBP. Approximately 70% of participants who received TB treatment were HIV coinfected. Overall, IRISA-TB was more sensitive than Xpert Ultra (88.6% [95% CI, 74.1%-95.5%] vs 71.5% [55.0%-83.7%], n = 53) and significantly more sensitive in participants who were HIV uninfected (100% [95% CI, 72.3%-100.0%] vs 60% [31.3%-83.2%], P = .03). In patients with definite and probable TBP combined (n = 84), sensitivity was significantly higher with IRISA-TB (77.3% [95% CI, 65.9%-85.8%] vs 37.9 [27.2%-50.0%], P < .0001). A similar pattern was seen in persons who were HIV uninfected (88.3% vs 35.3%, P = .002). Specificity was high for both assays (>95%)., Conclusions: Unstimulated interferon γ (IRISA-TB) was significantly more sensitive than Xpert Ultra for the diagnosis of TB pericarditis in a TB-endemic resource-poor setting., Competing Interests: Potential conflicts of interest. P. R. is an employee of Antrum Biotech, the company that developed the IRISA-TB test and donated the kits. She provided training to laboratory technicians who performed the assay for this project and assisted with the performance of quality checks on the kits. The company-affiliated first author and all laboratory personnel were blinded to the patients’ clinical diagnoses. Furthermore, the first author was not involved in any aspects related to the recruitment of participants, classification of patients, or analysis of the data. Thus, the inclusion of an industry-affiliated first author has not influenced the results of this research in anyway. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

COVID-19 self-testing strategy (COVIDST) can rapidly identify symptomatic and asymptomatic SARS-CoV-2-infected individuals and their contacts, potentially reducing transmission. In this living systematic review, we evaluated the evidence for real-world COVIDST performance. Two independent reviewers searched six databases (PubMed, Embase, Web of Science, World Health Organization database, Cochrane COVID-19 registry, Europe PMC) for the period April 1st, 2020, to January 18th, 2023. Data on studies evaluating COVIDST against laboratory-based conventional testing and reported on diagnostic accuracy, feasibility, acceptability, impact, and qualitative outcomes were abstracted. Bivariate random effects meta-analyses of COVIDST accuracy were performed (n = 14). Subgroup analyses (by sampling site, symptomatic/asymptomatic infection, supervised/unsupervised strategy, with/without digital supports) were conducted. Data from 70 included studies, conducted across 25 countries with a median sample size of 817 (range: 28-784,707) were pooled. Specificity and DOR was high overall, irrespective of subgroups (98.37-99.71%). Highest sensitivities were reported for: a) symptomatic individuals (73.91%, 95%CI: 68.41-78.75%; n = 9), b) mid-turbinate nasal samples (77.79%, 95%CI: 56.03-90.59%; n = 14), c) supervised strategy (86.67%, 95%CI: 59.64-96.62%; n = 13), and d) use of digital interventions (70.15%, 95%CI: 50.18-84.63%; n = 14). Lower sensitivity was attributed to absence of symptoms, errors in test conduct and absence of supervision or a digital support. We found no difference in COVIDST sensitivity between delta and omicron pre-dominant period. Digital supports increased confidence in COVIDST reporting and interpretation (n = 16). Overall acceptability was 91.0-98.7% (n = 2) with lower acceptability reported for daily self-testing (39.5-51.1%). Overall feasibility was 69.0-100.0% (n = 5) with lower feasibility (35.9-64.6%) for serial self-testing. COVIDST decreased closures in school, workplace, and social events (n = 4). COVIDST is an effective rapid screening strategy for home-, workplace- or school-based screening, for symptomatic persons, and for preventing transmission during outbreaks. These data will guide COVIDST policy. Our review demonstrates that COVIDST has paved the way for self-testing in pandemics worldwide., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NPP reports an open access application for COVID self-testing: “COVIDSmart CARE!”, McGill University Copyright 2022-002. This digital innovation was supported by the CIHR grant no FRN 174921., (Copyright: © 2024 Anand 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.)

Background: Computer-aided detection (CAD) may be a useful screening tool for tuberculosis (TB). However, there are limited data about its utility in active case finding (ACF) in a community-based setting, and particularly in an HIV-endemic setting where performance may be compromised., Methods: We performed a systematic review and evaluated articles published between January 2012 and February 2023 that included CAD as a screening tool to detect pulmonary TB against a microbiological reference standard (sputum culture and/or nucleic acid amplification test [NAAT]). We collected and summarized data on study characteristics and diagnostic accuracy measures. Two reviewers independently extracted data and assessed methodological quality against Quality Assessment of Diagnostic Accuracy Studies-2 criteria. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines were followed., Results: Of 1748 articles reviewed, 5 met with the eligibility criteria and were included in this review. A meta-analysis revealed pooled sensitivity of 0.87 (95% CI, 0.78-0.96) and specificity of 0.74 (95% CI, 0.55-0.93), just below the World Health Organization (WHO)-recommended target product profile (TPP) for a screening test (sensitivity ≥0.90 and specificity ≥0.70). We found a high risk of bias and applicability concerns across all studies. Subgroup analyses, including the impact of HIV and previous TB, were not possible due to the nature of the reporting within the included studies., Conclusions: This review provides evidence, specifically in the context of ACF, for CAD as a potentially useful and cost-effective screening tool for TB in a resource-poor HIV-endemic African setting. However, given methodological concerns, caution is required with regards to applicability and generalizability., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)