Guozhong Zhou1, Qingyi Luo2, Shiqi Luo1, Zhaowei Teng3, Zhenhua Ji1, Jiaru Yang1, Feng Wang1, Shiyuan Wen1, Zhe Ding1, Lianbao Li1, Taigui Chen1, Manzama-Esso Abi1, Miaomiao Jian4, Lisha Luo4, Aihua Liu5, Fukai Bao6. 1. Department of Microbiology and Immunology, Kunming Medical University, Kunming, Yunnan Province, China. 2. School of Basic Medical Sciences, Department of Medical Imaging, Affiliated Yanan Hospital, Kunming Medical University, Kunming, Yunnan Province, China. 3. Department of Orthopedic Surgery, The 6th Affiliated Hospital, Kunming Medical University, Kunming, Yunnan Province, China. 4. Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, Yunnan Province, China. 5. Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, Yunnan Province, China; Yunnan Province Key Laboratory for Tropical Infectious Diseases in Universities, Kunming Medical University, Kunming, Yunnan Province, China; The Institute for Tropical Medicine, Kunming Medical University, Kunming, Yunnan Province, China. Electronic address: liuaihua@kmmu.edu.cn. 6. Department of Microbiology and Immunology, Kunming Medical University, Kunming, Yunnan Province, China; Yunnan Province Key Laboratory for Tropical Infectious Diseases in Universities, Kunming Medical University, Kunming, Yunnan Province, China; The Institute for Tropical Medicine, Kunming Medical University, Kunming, Yunnan Province, China. Electronic address: baofukai@kmmu.edu.cn.
Abstract
BACKGROUND: Use of an interferon-γ (IFN-γ) release assay or tuberculin skin test for detection and management of latent tuberculosis infection is controversial. For both types of test, we assessed their predictive value for the progression of latent infection to active tuberculosis disease, the targeting value of preventive treatment, and the necessity of dual testing. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions, on Oct 18, 2019, using the keywords ("latent tuberculosis" OR "latent tuberculosis infection" OR "LTBI") AND ("interferon gamma release assays" OR "Interferon-gamma Release Test" OR "IGRA" OR "QuantiFERON®-TB in tube" OR "QFT" OR "T-SPOT.TB") AND ("tuberculin skin test" OR "tuberculin test" OR "Mantoux test" OR "TST"). We included articles that used a cohort study design; included information that individuals with latent tuberculosis infection detected by IFN-γ release assay, tuberculin skin test, or both, progressed to active tuberculosis; reported information about treatment; and were limited to high-risk populations. We excluded studies that included patients with active or suspected tuberculosis at baseline, evaluated a non-commercial IFN-γ release assay, and had follow-up of less than 1 year. We extracted study details (study design, population investigated, tests used, follow-up period) and the number of individuals observed at baseline, who progressed to active tuberculosis, and who were treated. We then calculated the pooled risk ratio (RR) for disease progression, positive predictive value (PPV), and negative predictive value (NPV) of IFN-γ release assay versus tuberculin skin test. FINDINGS: We identified 1823 potentially eligible studies after exclusion of duplicates, of which 256 were eligible for full-text screening. From this screening, 40 studies (50 592 individuals in 41 cohorts) were identified as eligible and included in our meta-analysis. Pooled RR for the rate of disease progression in untreated individuals who were positive by IFN-γ release assay versus those were negative was 9·35 (95% CI 6·48-13·49) compared with 4·24 (3·30-5·46) for tuberculin skin test. Pooled PPV for IFN-γ release assay was 4·5% (95% CI 3·3-5·8) compared with 2·3% (1·5-3·1) for tuberculin skin test. Pooled NPV for IFN-γ release assay was 99·7% (99·5-99·8) compared with 99·3% (99·0-99·5) for tuberculin skin test. Pooled RR for rates of disease progression in individuals positive by IFN-γ release assay who were untreated versus those who were treated was 3·09 (95% CI 2·08-4·60) compared with 1·11 (0·69-1·79) for the same populations who were positive by tuberculin skin test. Pooled proportion of disease progression for individuals who were positive by IFN-γ release assay and tuberculin skin test was 6·1 (95% CI 2·3-11·5). Pooled RR for rates of disease progression in individuals who were positive by IFN-γ release assay and tuberculin skin test who were untreated versus those who were treated was 7·84 (95% CI 4·44-13·83). INTERPRETATION: IFN-γ release assays have a better predictive ability than tuberculin skin tests. Individuals who are positive by IFN-γ release assay might benefit from preventive treatment, but those who are positive by tuberculin skin test probably will not. Dual testing might improve detection, but further confirmation is needed. FUNDING: National Natural Science Foundation of China and Natural Foundation of Yunnan Province.
BACKGROUND: Use of an interferon-γ (IFN-γ) release assay or tuberculin skin test for detection and management of latent tuberculosis infection is controversial. For both types of test, we assessed their predictive value for the progression of latent infection to active tuberculosis disease, the targeting value of preventive treatment, and the necessity of dual testing. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions, on Oct 18, 2019, using the keywords ("latent tuberculosis" OR "latent tuberculosis infection" OR "LTBI") AND ("interferon gamma release assays" OR "Interferon-gamma Release Test" OR "IGRA" OR "QuantiFERON®-TB in tube" OR "QFT" OR "T-SPOT.TB") AND ("tuberculin skin test" OR "tuberculin test" OR "Mantoux test" OR "TST"). We included articles that used a cohort study design; included information that individuals with latent tuberculosis infection detected by IFN-γ release assay, tuberculin skin test, or both, progressed to active tuberculosis; reported information about treatment; and were limited to high-risk populations. We excluded studies that included patients with active or suspected tuberculosis at baseline, evaluated a non-commercial IFN-γ release assay, and had follow-up of less than 1 year. We extracted study details (study design, population investigated, tests used, follow-up period) and the number of individuals observed at baseline, who progressed to active tuberculosis, and who were treated. We then calculated the pooled risk ratio (RR) for disease progression, positive predictive value (PPV), and negative predictive value (NPV) of IFN-γ release assay versus tuberculin skin test. FINDINGS: We identified 1823 potentially eligible studies after exclusion of duplicates, of which 256 were eligible for full-text screening. From this screening, 40 studies (50 592 individuals in 41 cohorts) were identified as eligible and included in our meta-analysis. Pooled RR for the rate of disease progression in untreated individuals who were positive by IFN-γ release assay versus those were negative was 9·35 (95% CI 6·48-13·49) compared with 4·24 (3·30-5·46) for tuberculin skin test. Pooled PPV for IFN-γ release assay was 4·5% (95% CI 3·3-5·8) compared with 2·3% (1·5-3·1) for tuberculin skin test. Pooled NPV for IFN-γ release assay was 99·7% (99·5-99·8) compared with 99·3% (99·0-99·5) for tuberculin skin test. Pooled RR for rates of disease progression in individuals positive by IFN-γ release assay who were untreated versus those who were treated was 3·09 (95% CI 2·08-4·60) compared with 1·11 (0·69-1·79) for the same populations who were positive by tuberculin skin test. Pooled proportion of disease progression for individuals who were positive by IFN-γ release assay and tuberculin skin test was 6·1 (95% CI 2·3-11·5). Pooled RR for rates of disease progression in individuals who were positive by IFN-γ release assay and tuberculin skin test who were untreated versus those who were treated was 7·84 (95% CI 4·44-13·83). INTERPRETATION: IFN-γ release assays have a better predictive ability than tuberculin skin tests. Individuals who are positive by IFN-γ release assay might benefit from preventive treatment, but those who are positive by tuberculin skin test probably will not. Dual testing might improve detection, but further confirmation is needed. FUNDING: National Natural Science Foundation of China and Natural Foundation of Yunnan Province.
Authors: Andreas Törnell; Hanna Grauers Wiktorin; Johan Ringlander; Mohammad Arabpour; Malin R Nilsson; Staffan Nilsson; Roberta Kiffin; Magnus Lindh; Martin Lagging; Kristoffer Hellstrand; Anna Martner Journal: J Infect Dis Date: 2022-08-24 Impact factor: 7.759
Authors: G B Migliori; S J Wu; A Matteelli; D Zenner; D Goletti; S Ahmedov; S Al-Abri; D M Allen; M E Balcells; A L Garcia-Basteiro; E Cambau; R E Chaisson; C B E Chee; M P Dalcolmo; J T Denholm; C Erkens; S Esposito; P Farnia; J S Friedland; S Graham; Y Hamada; A D Harries; A W Kay; A Kritski; S Manga; B J Marais; D Menzies; D Ng; L Petrone; A Rendon; D R Silva; H S Schaaf; A Skrahina; G Sotgiu; G Thwaites; S Tiberi; N Tukvadze; J-P Zellweger; L D Ambrosio; R Centis; C W M Ong Journal: Int J Tuberc Lung Dis Date: 2022-03-01 Impact factor: 3.427