BackgroundAccurate diagnosis and subsequent treatment of latent tuberculosis infection (LTBI) is essential for TB elimination. However, the absence of a gold standard test for diagnosing LTBI makes assessment of the true prevalence of LTBI and the accuracy of diagnostic tests challenging. Bayesian latent class models can be used to make inferences about disease prevalence and the sensitivity and specificity of diagnostic tests using data on the concordance between tests. We performed the largest meta-analysis to date aiming to evaluate the performance of tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) for LTBI diagnosis in various patient populations using Bayesian latent class modelling.MethodsSystematic search of PubMeb, Embase and African Index Medicus was conducted without date and language restrictions on September 11, 2017 to identify studies that compared the performance of TST and IGRAs for LTBI diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT-GIT) and T-SPOT.TB. Studies were included if they reported 2x2 agreement data between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed to estimate the sensitivity and specificity of TST and IGRAs in various populations, including immune-competent adults, immune-compromised adults and children. A TST cut-off value of 10 mm was used for immune-competent subjects and 5 mm for immune-compromised individuals.FindingsA total of 157 studies were included in the analysis. In immune-competent adults, the sensitivity of TST and QFT-GIT were estimated to be 84% (95% credible interval [CrI] 82–85%) and 52% (50–53%), respectively. The specificity of QFT-GIT was 97% (96–97%) in non-BCG-vaccinated and 93% (92–94%) in BCG-vaccinated immune-competent adults. The estimated figures for TST were 100% (99–100%) and 79% (76–82%), respectively. T-SPOT.TB has comparable specificity (97% for both tests) and better sensitivity (68% versus 52%) than QFT-GIT in immune-competent adults. In immune-compromised adults, both TST and QFT-GIT display low sensitivity but high specificity. QFT-GIT and TST are equally specific (98% for both tests) in non-BCG-vaccinated children; however, QFT-GIT is more specific than TST (98% versus 82%) in BCG-vaccinated group. TST is more sensitive than QFT-GIT (82% versus 73%) in children.ConclusionsThis study is the first to assess the utility of TST and IGRAs for LTBI diagnosis in different population groups using all available data with Bayesian latent class modelling. Our results challenge the current beliefs about the performance of LTBI screening tests, and have important implications for LTBI screening policy and practice. We estimated that the performance of IGRAs is not as reliable as previously measured in the general population. However, IGRAs are not or minimally affected by BCG and should be the preferred tests in this setting. Adoption of IGRAs in settings where BCG is widely administered will allow for a more accurate identification and treatment of LTBI.

IntroductionPatients with non-mucinous epithelial tubo-ovarian cancers should be referred for genetic testing because approximately 15% will carry an inherited mutation in the BRCA1 or BRCA2 cancer susceptibility genes. However, referral rates for genetic testing remain low. For patients who carry a BRCA mutation, failure to refer for genetic testing results in missed opportunities for therapy and prevention of future cancers in the patient and at-risk relatives. In Western Australia between July 2013 and June 2015, 40.6% of patients with non-mucinous epithelial tubo-ovarian cancers discussed at a statewide gynecologic oncology tumor board were referred for genetic testing. Our objective was to investigate the proportion of patients with non-mucinous epithelial tubo-ovarian cancers in Western Australia referred for BRCA1/2 testing from July 2015 to December 2017, following the introduction of mainstreaming and tele-counseling. A secondary aim was to compare the uptake of genetic testing between different genetic counseling modalities.MethodsRetrospective case series. All patients with high-grade non-mucinous epithelial tubo-ovarian cancers discussed at the weekly Western Australian gynecologic oncology tumor board meeting, between July 1, 2015 and December 31, 2017, and those referred for BRCA mutation testing, were ascertained.ResultsA total of 343 women were eligible for referral; 63 patients were excluded, leaving 280 patients for analysis. 220/280 patients were referred for genetic testing (78.6%). There were no differences in uptake of genetic testing by mode of genetic counseling.DiscussionA significant increase in referrals of eligible patients for genetic testing was observed in 2015–2017 compared with 2013–2014. Although there were no differences in uptake of genetic testing by mode of counseling, mainstreaming and tele-counseling provide alternative options for patients that may lead to higher uptake of genetic testing.