Accurate diagnosis of latent tuberculosis in children, people who are immunocompromised or at risk from immunosuppression and recent arrivals from countries with a high incidence of tuberculosis: systematic review and economic evaluation

Auguste, Peter, Tsertsvadze, Alexander, Pink, Joshua, Court, Rachel, Seedat, Farah, Gurung, Tara, Freeman, Karoline, Taylor-Phillips, Sian, Walker, Clare, Madan, Jason, Kandala, Ngianga-Bakwin, Clarke, Aileen and Sutcliffe, Paul (2016) Accurate diagnosis of latent tuberculosis in children, people who are immunocompromised or at risk from immunosuppression and recent arrivals from countries with a high incidence of tuberculosis: systematic review and economic evaluation. Health Technology Assessment, 20 (38). pp. 1-678. ISSN 1366-5278

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Abstract

Background:
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a major cause of morbidity and mortality. Nearly one-third of the world’s population is infected with MTB; TB has an annual incidence of 9 million new cases and each year causes 2 million deaths worldwide.

Objectives:
To investigate the clinical effectiveness and cost-effectiveness of screening tests [interferongamma release assays (IGRAs) and tuberculin skin tests (TSTs)] in latent tuberculosis infection (LTBI) diagnosis to support National Institute for Health and Care Excellence (NICE) guideline development for three population groups: children, immunocompromised people and those who have recently arrived in the UK from high-incidence countries. All of these groups are at higher risk of progression from LTBI to active TB.

Data sources:
Electronic databases including MEDLINE, EMBASE, The Cochrane Library and Current Controlled Trials were searched from December 2009 up to December 2014.

Review methods:
English-language studies evaluating the comparative effectiveness of commercially available tests used for identifying LTBI in children, immunocompromised people and recent arrivals to the UK were eligible. Interventions were IGRAs [QuantiFERON®-TB Gold (QFT-G), QuantiFERON®-TB Gold-In-Tube (QFT-GIT) (Cellestis/Qiagen, Carnegie, VA, Australia) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK)]. The comparator was TST 5mm or 10mm alone or with an IGRA. Two independent reviewers screened all identified records and undertook a quality assessment and data synthesis. A de novo model, structured in two stages, was developed to compare the cost effectiveness of diagnostic strategies.

Results:
In total, 6687 records were screened, of which 53 unique studies were included (a further 37 studies were identified from a previous NICE guideline). The majority of the included studies compared the strength of association for the QFT-GIT/G IGRA with the TST (5mm or 10mm) in relation to the incidence of active TB or previous TB exposure. Ten studies reported evidence on decision-analytic models to determine the cost-effectiveness of IGRAs compared with the TST for LTBI diagnosis. In children, TST (≥ 5mm) negative followed by QFT-GIT was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of £18,900 per quality-adjusted life-year (QALY) gained. In immunocompromised people, QFT-GIT negative followed by the TST (≥ 5 mm) was the most cost-effective strategy, with an ICER of approximately £18,700 per QALY gained. In those recently arrived from high TB incidence countries, the TST (≥ 5 mm) alone was less costly and more effective than TST (≥ 5mm) positive followed by QFT-GIT or T-SPOT.TB or QFT-GIT alone.

Limitations:
The limitations and scarcity of the evidence, variation in the exposure-based definitions of LTBI and heterogeneity in IGRA performance relative to TST limit the applicability of the review findings.

Conclusions:
Given the current evidence, TST (≥ 5 mm) negative followed by QFT-GIT for children, QFT-GIT negative followed by TST (≥ 5 mm) for the immunocompromised population and TST (≥5mm) for recent arrivals were the most cost-effective strategies for diagnosing LTBI that progresses to active TB. These results should be interpreted with caution given the limitations identified. The evidence available is limited and more high-quality research in this area is needed including studies on the inconsistent performance of tests in high-compared with low-incidence TB settings; the prospective assessment of progression to active TB for those at high risk; the relative benefits of two-compared with one-step testing with different tests; and improved classification of people at high and low risk for LTBI.

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