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Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance. https://bit.ly/3i43wb6

Background We compared 6 new interferon-γ release assays (IGRAs; hereafter index tests: QFT-Plus, QFT-Plus CLIA, QIAreach, Wantai TB-IGRA, Standard E TB-Feron, and T-SPOT.TB/T-Cell Select) with World Health Organization (WHO)–endorsed tests for tuberculosis infection (hereafter reference tests). Methods Data sources (1 January 2007–18 August 2021) were Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, and manufacturers' data. Cross-sectional and cohort studies comparing the diagnostic performance of index and reference tests were selected. The primary outcomes of interest were the pooled differences in sensitivity and specificity between index and reference tests. The certainty of evidence (CoE) was summarized using the GRADE approach. Results Eighty-seven studies were included (44 evaluated the QFT-Plus, 4 QFT-Plus CLIA, 3 QIAreach, 26 TB-IGRA, 10 TB-Feron [1 assessing the QFT-Plus], and 1 T-SPOT.TB/T-Cell Select). Compared to the QFT-GIT, QFT Plus's sensitivity was 0.1 percentage points lower (95% confidence interval [CI], −2.8 to 2.6; CoE: moderate), and its specificity 0.9 percentage points lower (95% CI, −1.0 to −.9; CoE: moderate). Compared to QFT-GIT, TB-IGRA's sensitivity was 3.0 percentage points higher (95% CI, −.2 to 6.2; CoE: very low), and its specificity 2.6 percentage points lower (95% CI, −4.2 to −1.0; CoE: low). Agreement between the QFT-Plus CLIA and QIAreach with QFT-Plus was excellent (pooled κ statistics of 0.86 [95% CI,.78 to.94; CoE: low]; and 0.96 [95% CI,.92 to 1.00; CoE: low], respectively). The pooled κ statistic comparing the TB-Feron and the QFT-Plus or QFT-GIT was 0.85 (95% CI,.79 to.92; CoE: low). Conclusions The QFT-Plus and the TB-IGRA have very similar sensitivity and specificity as WHO-approved IGRAs. [ABSTRACT FROM AUTHOR]

Background A systematic review showed that the accuracy of Mycobacterium tuberculosis antigen–based skin tests (TBSTs) for tuberculosis is similar to that of interferon γ release assay, but the safety of TBSTs has not been systematically reviewed. Methods We searched for studies reporting injection site reactions (ISRs) and systemic adverse events associated with TBSTs. We searched Medline, Embase, e-library, the Chinese Biomedical Literature Database, and the China National Knowledge Infrastructure database for studies through 30 July 2021, and the database search was updated until 22 November 2022. Results We identified 7 studies for Cy-Tb (Serum Institute of India), 7 (including 2 found through the updated search) for C-TST (Anhui Zhifei Longcom), and 11 for Diaskintest (Generium). The pooled risk of any injection site reactions (ISRs) due to Cy-Tb (n = 2931; 5 studies) did not differ significantly from that for tuberculin skin tests (TSTs; risk ratio, 1.05 [95% confidence interval,.70–1.58]). More than 95% of ISRs were reported as mild or moderate; common ISRs included pain, itching, and rash. In 1 randomized controlled study, 49 of 153 participants (37.6%) given Cy-Tb experience any systemic adverse event (eg, fever and headache), compared with 56 of 149 participants (37.6%) given TST (risk ratio, 0.85 [95% confidence interval,.6–1.2]). In a randomized controlled study in China (n = 14 579), the frequency of systemic adverse events in participants given C-TST was similar to that for TST, and the frequency of ISRs was similar to or lower than that for TST. Reporting of the safety data on Diaskintest was not standardized, precluding meta-analysis. Conclusion The safety profile of TBSTs appears similar to that of TSTs and is associated with mostly mild ISRs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To conduct a comprehensive assessment of the case-mix of patients admitted to tuberculosis hospitals and the reasons for their admission in four Russian regions: Ivanovo, Orel, Samara and Vladimir. We also sought to quantify the extent to which efficiency could be improved by reducing hospitalization rates and re-profiling hospital beds available in the tuberculosis-control system. METHODS: We used a standard questionnaire to determine how beds were being used and who was using the beds in tuberculosis facilities in four Russian regions. Data were collected to determine how 4306 tuberculosis beds were utilized as well as on the socioeconomic and demographic indicators, clinical parameters and reasons for hospitalization for 3352 patients. FINDINGS: Of the 3352 patients surveyed about 70% were male; the average age was 40; and rates of unemployment, disability and alcohol misuse were high. About one-third of beds were occupied by smear-positive or culture-positive tuberculosis patients; 20% were occupied by tuberculosis patients who were smear-negative and/or culture-negative; 20% were occupied by patients who no longer had tuberculosis; and 20% were unoccupied. If clinical and public health admission criteria were applied then < 50% of admissions would be justified and < 50% of the current number of beds would be required. Up to 85% of admissions and beds were deemed to be necessary when social problems and poor access to outpatient care were considered along with clinical and public health admission criteria. CONCLUSION: Much of the Russian Federation's large tuberculosis hospital infrastructure is unnecessary when clinical and public health criteria are used, but the large hospital infrastructure within the tuberculosis-control system has an important social support function. Improving the efficiency of the system will require the reform of health-system norms and regulations as they relate to resource allocation and clinical care and implementation of lower-cost approaches to case management for patients with social problems. Additionally, closer attention will need to be paid to the management of staff numbers in the tuberculosis system.

The Purified Protein Derivative tuberculin skin tests (TST) and blood-based Mycobacterium tuberculosis (M.tb) specific interferon-gamma release assays (IGRA) are the currently used tests for identifying individuals with TB infection for preventive treatment. However, challenges around access and implementation have limited their use. Novel M.tb specific skin tests (TBST) such as Diaskintest, ESAT6-CFP10 (C-TST), C-Tb (also known as Cy-Tb), and DPPD may provide accurate and scalable options but evidence synthesis on their economic impact is lacking. We conducted two separate systematic reviews to compare the costs and cost-effectiveness of (1) the novel skin tests TBST (primary), and (2) TST and IGRA tests (secondary), to support WHO guideline development. We searched for articles presenting economic evaluations of the diagnostic tests using a health provider perspective and related to TB infection in humans. We considered papers written in English, Chinese or Russian. In the primary review, eight studies for novel TBST were found. One study in Brazil assessed cost-effectiveness of C-TST and Diaskintest and seven in Russia assessed the Diaskintest, while none evaluated C-Tb or DPPD. The review showed on average, Diaskintest kit costs (in 2021 USD) $1.60 (1.50 - 1.70), while full unit costs were estimated at $5.07. C-TST unit cost was $9.96. The second review found 32 articles on IGRA and/or the TST. These presented an average TST full unit cost of $37.88, and $87.81 for IGRA. Studies' quality for TBST was limited while high-quality studies were found for TST and IGRA tests. In conclusion, there is limited evidence regarding the costs and cost-effectiveness of novel TBST. Conversely, there is substantial evidence for TST and IGRA tests, but most studies were performed in high-income and low-TB burden settings and their cost-effectiveness varied between and within risk groups without clear economic consensus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Goscé 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.)

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests. Unfortunately, such studies often have limitations in design, execution, and reporting, leading to low certainty of the evidence about true test performance, which can delay or impede policy and scale-up decisions. This introductory paper outlines the following: (1) the purpose of this series of papers on study guidance; (2) WHO evidence needs and process for the development of policy guidelines for new TB diagnostic tests; and (3) study design considerations, ie, general diagnostic study considerations, intended use of test and role in the clinical pathway, choice of population and setting, index-test specific issues, suitable reference standard and comparators, study flow and specimen issues, and finally key issues beyond accuracy that should be considered. The other 4 papers in this series will provide more detailed guidance for each of the 4 WHO high-priority TPPs. By increasing the clarity around the clinical evaluation needs for tests that have the potential to meet the TPP specifications, we hope to support harmonized evidence generation and enable the WHO review process towards meeting the WHO End TB Strategy targets for reducing the incidence and mortality associated with TB., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)