Dataset Information

Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis.

ABSTRACT:

Background

Interferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear.

Methods

We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood for the diagnosis of active TB in HIV-infected patients.

Results

The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6-80.5%) and 77.4% (95%CI, 71.4-82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0-78.0%) and 63.1% (95%CI, 57.6-68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8-11.3%) and 13.2% (95%CI, 10.6-16.0%) for QFT-GIT and T-SPOT, respectively.

Conclusion

IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy.

SUBMITTER: Chen J

PROVIDER: S-EPMC3206065 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis.

Chen Jun J Zhang Renfang R Wang Jiangrong J Liu Li L Zheng Yufang Y Shen Yinzhong Y Qi Tangkai T Lu Hongzhou H

PloS one 20111101 11

<h4>Background</h4>Interferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear.<h4>Methods</h4>We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood ...[more]

PMID: 22069472

Similar Datasets

Project description:OBJECTIVE:To determine whether interferon-gamma release assays (IGRAs) improve the identification of HIV-infected individuals who could benefit from latent tuberculosis infection therapy. DESIGN:Systematic review and meta-analysis. METHODS:We searched multiple databases through May 2010 for studies evaluating the performance of the newest commercial IGRAs (QuantiFERON-TB Gold In-Tube [QFT-GIT] and T-SPOT.TB [TSPOT]) in HIV-infected individuals. We assessed the quality of all studies included in the review, summarized results in prespecified subgroups using forest plots, and where appropriate, calculated pooled estimates using random effects models. RESULTS:The search identified 37 studies that included 5736 HIV-infected individuals. In three longitudinal studies, the risk of active tuberculosis was higher in HIV-infected individuals with positive versus negative IGRA results. However, the risk difference was not statistically significant in the two studies that reported IGRA results according to manufacturer-recommended criteria. In persons with active tuberculosis (a surrogate reference standard for latent tuberculosis infection), pooled sensitivity estimates were heterogeneous but higher for TSPOT (72%; 95% confidence interval [CI], 62-81%) than for QFT-GIT (61%; 95% CI, 47-75%) in low-/middle-income countries. However, neither IGRA was consistently more sensitive than the tuberculin skin test in head-to-head comparisons. Although TSPOT appeared to be less affected by immunosuppression than QFT-GIT and the tuberculin skin test, overall, differences among the three tests were small or inconclusive. CONCLUSIONS:Current evidence suggests that IGRAs perform similarly to the tuberculin skin test at identifying HIV-infected individuals with latent tuberculosis infection. Given that both tests have modest predictive value and suboptimal sensitivity, the decision to use either test should be based on country guidelines and resource and logistic considerations.

Project description:BackgroundWe aimed to assess whether interferon-γ release assays (IGRAs) can predict the development of active tuberculosis and whether the predictive ability of these tests is better than that of the tuberculin skin test (TST).MethodsLongitudinal studies of the predictive value for active tuberculosis of in-house or commercial IGRAs were identified through searches of PubMed, Embase, Biosis, and Web of Science and complementary manual searches up to June 30, 2011. Eligible studies included adults or children, with or without HIV, who were free of active tuberculosis at study baseline. We summarised incidence rates in forest plots and pooled data with random-effects models when appropriate. We calculated incidence rate ratios (IRR) for rates of disease progression in IGRA-positive versus IGRA-negative individuals.Findings15 studies had a combined sample size of 26 680 participants. Incidence of tuberculosis during a median follow-up of 4 years (IQR 2-6), even in IGRA-positive individuals, was 4-48 cases per 1000 person-years. Seven studies with no possibility of incorporation bias and reporting baseline stratification on the basis of IGRA results showed a moderate association between positive results and subsequent tuberculosis (pooled unadjusted IRR 2·10, 95% CI 1·42-3·08). Compared with test-negative results, IGRA-positive and TST-positive results were much the same with regard to the risk of tuberculosis (pooled IRR in the five studies that used both was 2·11 [95% CI 1·29-3·46] for IGRA vs 1·60 [0·94-2·72] for TST at the 10 mm cutoff). However, the proportion of IGRA-positive individuals in seven of 11 studies that assessed both IGRAs and TST was generally lower than TST-positive individuals.InterpretationNeither IGRAs nor the TST have high accuracy for the prediction of active tuberculosis, although use of IGRAs in some populations might reduce the number of people considered for preventive treatment. Until more predictive biomarkers are identified, existing tests for latent tuberculosis infection should be chosen on the basis of relative specificity in different populations, logistics, cost, and patients' preferences rather than on predictive ability alone.FundingSpecial Programme for Research and Training in Tropical Diseases (WHO), Wellcome Trust, Canadian Institutes of Health Research, UK Medical Research Council, and the European and Developing Countries Clinical Trials Partnership.

Project description:National guidelines recommend screening for latent tuberculosis infection (LTBI) in all HIV-infected patients. Thus, the objective of this study was to measure protocol adherence to national guidelines regarding LTBI screening for HIV-infected patients entering care at an urban primary care clinic specializing in HIV care, identify clinical and other characteristics associated with adherence, and determine whether transitioning from the tuberculin skin test (TST) to the interferon-gamma release assay (IGRA) improved adherence. We conducted a retrospective study using protocol adherence to LTBI screening guidelines within twelve months of entering care at an HIV clinic as the primary outcome. Successful protocol adherence was defined as the placement and reading of a TST, performance of an IGRA, or a note in study clinic records documenting prior testing or treatment for tuberculosis in an outside setting. Multivariable modified Poisson regression models were used in analyses. Overall, 32% (n?=?118/372) of patients received LTBI screening within twelve months of entering care. Protocol adherence to LTBI screening guidelines increased from 28% to 37% following the transition from TST to IGRA screening. IGRA screening [adjusted prevalence ratio: 1.45, 95% confidence limits: (1.07, 1.96)], male sex [1.47 (1.05, 2.07)], transfer patient status [1.51 (1.05, 2.18)], and greater than one year of clinic attendance [1.62 (1.06, 2.48)] were independently associated with protocol adherence. Among patients without prior LTBI screening or treatment, patients entering the clinic in 2013 under the IGRA screening protocol were more likely to be screened for LTBI compared to patients entering under the TST screening protocol (34.3% vs. 9.7%, p?<?0.001). In conclusion, transitioning from TST to IGRA-based screening improved adherence to screening guidelines. However, further work on improving adherence to LTBI screening guidelines among HIV-infected patients is needed.

Project description:BackgroundThere is growing concern that interferon-? release assays (IGRAs) are being used off-label for the diagnosis of active tuberculosis (TB) disease in many high-burden settings, including India, where the background prevalence of latent TB infection is high. We analyzed the costs and consequences of using IGRAs for the diagnosis of active TB in India from the perspective of the Indian TB control sector.Methods and findingsWe constructed a decision analytic model to estimate the incremental cost and effectiveness of IGRAs for the diagnosis of active TB in India. We compared a reference scenario of clinical examination and non-microbiological tests against scenarios in which clinical diagnosis was augmented by the addition of either sputum smear microscopy, IGRA, or Xpert MTB/RIF. We examined costs (in 2013 US dollars) and consequences from the perspective of the Indian healthcare sector. Relative to sputum smear microscopy, use of IGRA for active TB resulted in 23,700 (95% uncertainty range, UR: 3,800 - 38,300) additional true-positive diagnoses, but at the expense of 315,700 (95% UR: 118,300 - 388,400) additional false-positive diagnoses and an incremental cost of US$49.3 million (95% UR: $34.9 - $58.0 million) (2.9 billion Indian Rupees). Relative to Xpert MTB/RIF (including the cost of treatment for drug resistant TB), use of IGRA led to 400 additional TB cases treated (95% UR: [-8,000] - 16,200), 370,600 (95% UR: 252,200 - 441,700) more false-positive diagnoses, 70,400 (95% UR: [-7,900] - 247,200) fewer disability-adjusted life years averted, and US$14.6 million (95%UR: [-$7.2] - $28.7 million) (854 million Indian Rupees) in additional costs.ConclusionUsing IGRAs for diagnosis of active TB in a setting like India results in tremendous overtreatment of people without TB, and substantial incremental cost with little gain in health. These results support the policies by WHO and Standards for TB Care in India, which discourage the use of IGRAs for the diagnosis of active TB in India and similar settings.

Dataset Information

Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis.

Background

Methods

Results

Conclusion

Publications

Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis.

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