Table 2GRADE Summary of Findings – Role of IGRAs for evaluation of patients with pulmonary TB in low- and middle-income countries

Review question: What is the diagnostic accuracy of commercial IGRAs for pulmonary tuberculosis?

Patients/population: Adult pulmonary TB suspects and confirmed TB cases in low- and middle-income countries

Setting: Outpatients and inpatients

Index test: Commercial interferon-gamma release assays (QuantiFERON-TB Gold In-Tube [QFT-GIT], Cellestis, Australia and T-SPOT.TB [T-SPOT], Oxford Immunotec, United Kingdom)

Importance: Rapid, accurate, simple test could supplement conventional microbiology and expand testing to peripheral health centers

Reference standard: Microbiologic (culture or smear-microscopy) or clinical diagnosis of pulmonary TB

Studies: Cross-sectional or cohort

Outcomes: TP, TN, FP, FNEffect %
(95% CI)		No. of participants
(studies)		What do these results mean given 10% prevalence among suspects being screened for TB?What do these results mean given 30% prevalence among suspects being screened for TB?Quality of Evidence
Subgroups
T-SPOT.TB; HIV-infectedSensitivity 78% (56, 91)
Specificity 55% (45, 64)		549 (5)With a prevalence of 10%, 100/1000 will have TB. Of these, 78 (TP) will be identified; 22 (FN) will be missed by T-SPOT.TB. Of the 900 patients without TB, 495 (TN) will not be treated; 405 (FP) will be unnecessarily treated.With a prevalence of 30%, 300/1000 will have TB. Of these, 234 (TP) will be identified; 66 (FN) will be missed by T-SPOT.TB. Of the 700 patients without TB, 385 (TN) will not be treated; 315 (FP) will be unnecessarily treated.Low
⊕⊕○○
T-SPOT.TB; HIV-uninfectedInsufficient data for pooled estimates364 (3)------
QuantiFERON-TB Gold In-Tube; HIV-infectedSensitivity 62% (41,79)
Specificity 51% (39, 64)		469 (6)With a prevalence of 10%, 100/1000 will have TB. Of these, 62 (TP) will be identified; 38 (FN) will be missed by QFT-GIT. Of the 900 patients without TB, 459 (TN) will not be treated; 441 (FP) will be unnecessarily treated.With a prevalence of 30%, 300/1000 will have TB. Of these, 186 (TP) will be identified; 114 (FN) will be missed by QFT-GIT. Of the 700 patients without TB, 357 (TN) will not be treated; 343 (FP) will be unnecessarily treated.Low
⊕⊕○○
QuantiFERON-TB Gold In-Tube; HIV-uninfectedSensitivity 82% (76, 87)
Specificity 42% (33, 53)		1304 (5)With a prevalence of 10%, 100/1000 will have TB. Of these, 82 (TP) will be identified; 18 (FN) will be missed by QFT-GIT. Of the 900 patients without TB, 378 (TN) will not be treated; 522 (FP) will be unnecessarily treated.With a prevalence of 30%, 300/1000 will have TB. Of these, 246 (TP) will be identified; 54 (FN) will be missed by QFT-GIT. Of the 700 patients without TB, 294 (TN) will not be treated; 406 (FP) will be unnecessarily treated.Low
⊕⊕○○
OutcomeSubgroupEffect %
(95% CI)		No. of participants
(studies)		What do these findings mean?Quality of Evidence
IGRA-TST sensitivity difference*QuantiFERON-TB Gold In-Tube1% (-11 to 13%)*475 (10)This evidence suggests that QFT- GIT is no more sensitive than TST for active TB diagnosis in low- and middle-income countires.Low
⊕⊕○○
T-SPOT.TB9% (-10% to 28%)*206 (5)This evidence suggests that TSPOT is slightly more sensitive than TST for active TB diagnosis in low- and middle-income countries. This evidence should be interpreted with caution given the low number of studies available.Low
⊕⊕○○
Proportion indeterminate testsQuantiFERON-TB Gold In-Tube, HIV- uninfected Subjects4% (1-7%)1603 (11)This evidence suggests that among HIV-uninfected subjects, the proportion of indeterminate QFT- GIT test results in low- and middle- income countries will be low and similar to high-income countries.Low
⊕⊕○○
T-SPOT.TB, HIV-uninfected Subjects3% (1-4%)494 (5)This evidence suggests that among HIV-uninfected subjects, the proportion of indeterminate TSPOT test results in low- and middle- income countries will be low and similar to high-income countries.Low
⊕⊕○○
QuantiFERON-TB Gold In-Tube, HIV-infected Subjects16% (10-21%)728 (10)In low- and middle-income countries, the proportion of indeterminate QFT-GIT results among HIV-infected subjects can be expected to be high - in about 16% of the patients tested, clinicians will not be able to use the QFT results for decision making.Low
⊕⊕○○
T-SPOT.TB, HIV- infected Subjects8% (1-15%)666 (7)In low- and middle-income countries, the proportion of indeterminate TSPOT results among HIV-infected subjects can be expected to be high - in about 8% of patients tested, clinicians will not be able to use the TSPOT results for decision making.Low
⊕⊕○○
Incremental valueNeither study demonstrated significant added value over conventional tests for active TB diagnosis, as measured by change in the area under receiver operating curve (AUC).943 (2)This evidence suggests that after consideration of readily available patient data, neither commercial IGRA can be expected to be useful in diagnosing active pulmonary TB in patients living in low-and middle-income countries.Low
⊕⊕○○
*

Value is IGRA minus TST.

From: 7, GRADE tables

Cover of Use of Tuberculosis Interferon-Gamma Release Assays (IGRAs) in Low- and Middle- Income Countries
Use of Tuberculosis Interferon-Gamma Release Assays (IGRAs) in Low- and Middle- Income Countries: Policy Statement.
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