The diagnostic performance of novel skin-based in-vivo tests for tuberculosis infection compared with purified protein derivative tuberculin skin tests and blood-based in vitro interferon-γ release assays: a systematic review and meta-analysis

• Published in: The Lancet infectious diseases 2022-02, Vol.22 (2), p.250-264
• Main Authors: Krutikov, Maria, Faust, Lena, Nikolayevskyy, Vladyslav, Hamada, Yohhei, Gupta, Rishi K, Cirillo, Daniela, Matteelli, Alberto, Korobitsyn, Alexei, Denkinger, Claudia M, Rangaka, Molebogeng X
• Format: Article
• Language: English
• Subjects: Algorithms; Antigens; BCG Vaccine; Biomedical materials; Child; Diagnostic systems; Diagnostic tests; Disease prevention; HIV; HIV Infections - epidemiology; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Interferon; Interferon-gamma Release Tests; Latent Tuberculosis - diagnosis; Medical diagnosis; Meta-analysis; Performance evaluation; Population studies; Populations; Proteins; Qualitative analysis; Quality assessment; Russian language; Sensitivity; Sensitivity and Specificity; Skin; Skin tests; Systematic review; Translations; Tuberculin; Tuberculin Test; Tuberculosis; Tuberculosis - diagnosis; Tuberculosis - prevention & control; γ-Interferon
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(21)00261-9

Novel skin-based tests for tuberculosis infection might present suitable alternatives to current tests; however, diagnostic performance of new tests compared with the purified protein derivative-tuberculin skin test (TST) or interferon-γ release assays (IGRA) needs systematic assessment. In this systematic review and meta-analysis, we searched English (Medline OVID), Chinese (Chinese Biomedical Literature Database and the China National Knowledge Infrastructure), and Russian (e-library) databases from the inception of each database to May 15, 2019, (with updated search of the Russian and English databases on Oct, 20 2020) using terms “ESAT6” OR “CFP10” AND “skin test” AND “Tuberculosis” OR “C-Tb” OR “Diaskintest”. We included studies reporting on the performance of index tests alone or compared with a comparator. Inclusion criteria varied according to review objectives and performance outcome, but reporting of test cut-offs for positivity applied to study population was required from all studies. We used a hierarchy of reference standards for tuberculosis infection consistent with the 2020 WHO framework to evaluate diagnostic performance. Two authors independently reviewed the titles and abstracts for English and Chinese (LF and MK) and Russian studies (MK and VN). Study quality was assessed with QUADAS-2. Pooled random-effects estimates are presented when appropriate for total agreement proportion, sensitivity in microbiologically confirmed tuberculosis and specificity in cohorts with low risk of tuberculosis infection. This study is registered with PROSPERO, CRD42019135572. We identified 1466 original articles, of which 37 (2·5%) studies, including 10 915 individuals (7111 Diaskintest, 2744 C-Tb, 887 EC, 173 DPPD), were included in the qualitative analysis (29 [78%] studies of Diaskintest, five [15%] studies of C-Tb, two [5%] studies of EC-skintest, and one [3%] study of DPPD). 22 (1·5%) studies including 5810 individuals (3143 Diaskintest, 2129 C-Tb, 538 EC-skintest) were included in the quantitative analysis: 15 (68%) of Diaskintest, five (23%) of C-Tb, and two (9%) of EC-skintest. Tested sub-populations included individuals with HIV, children (0–18 years), and individuals exposed to tuberculosis. Studies were heterogeneous with moderate to high risk of bias. Nine head-to-head studies of index test versus TST and IGRA permitted direct comparisons and pooling. In a mixed cohort of people with and without tuberculosis, Diaskintest pooled agreement with I