Interferon gamma release assays for diagnosis of osteoarticular tuberculosis: A systematic review and meta-analysis

Abstract

Background: Although the Interferon Gamma Release Assays (IGRA) is often used to identify latent tuberculosis, it also plays a crucial role in diagnosing active extrapulmonary tuberculosis. Some studies have assessed the use of IGRA as a biomarker for osteoarticular tuberculosis (OATB), which is elevated following TB infection. Still, conclusive results about its effectiveness have not been reported.

Method: We searched PubMed, Embase, and Cochran databases. We obtained literature related to the diagnosis of OATB by IGRA, and the retrieval period was from the establishment of the database to June 2021. The bivariate random effect model was used to summarize the sensitivity, specificity, and accuracy of other indicators in diagnosing OATB by IGRA, and the forest plot and receiver operating characteristic (ROC) curve were used for testing.

Results: We included seven studies involving 643 subjects in diagnosing OATB by IGRA. The comprehensive sensitivity and specificity were 0.84 (95% CI, 0.70-0.92) and 0.78 (95% CI, 0.66-0.87), respectively. The area under the curve (AUC) was 0.87.

Conclusion: In blood samples, the diagnostic accuracy of IGRAS is poor in patients with suspected OAT. We conclude that IGRA may not be appropriate for patients with OATB.

Fig 1. Flow chart of the study selection process.

The flowchart shows the procedure used to select the articles for the qualitative and quantitative synthesis.

Fig 2. Risk of bias assessment of the included studies.

According to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2), the summary of the methodological quality of studies.

Fig 3. Evaluation of the sensitivity and specificity of interferon-γ release assay in the diagnosis of OATB: A study forest plot.

Filled squares represent sensitivity/specificity estimates from studies done using. interferon-γ release assay. See references 24 to 30 for details. Thresholds for the interpretation of I2 are as follows: 0% to 40%: might not be essential; 30% to 60%: may represent moderate heterogeneity; 50% to 90%: may represent substantial heterogeneity; 75% to 100%: considerable heterogeneity.

Fig 4. Summarize the receiver operating characteristic (SROC) curve and summarize the performance of interferon-gamma release assay in the diagnosis of OATB.

Each study is represented by an open circle whose size is proportional to the inverse standard error of sensitivity and specificity. The filled square represents the summary estimate of the test accuracy, with the surrounding dashed zone outline denoting the 95% confidence region around this estimate.

Fig 5. Deeks’ funnel plots for publication bias.

Deeks funnel plot assessment test evaluates the potential publication bias for interferon-gamma release assays on OATB. The plot shows the symmetric distribution of the log of diagnostic odds ratios against the inverse root of effective sample sizes (ESS), indicating the absence of any publication bias.