| Efficacy of preventive therapy based on IGRA results | No studies | | | | Critical
(7-9) |
| Prospective predictive value of IGRA for the development of active incident TB? (Do IGRA positive results have a stronger association with subsequent development of active TB compared to IGRA negative results?) | 7,392 (3) |
IGRA positives results appear to have a moderate but higher statistical association with incident TB compared to IGRA negatives, pooled IRR=3.2 (95% CI 0.74-5.64), I2=0%, p=0.91. This estimate is not statistically significant- the confidence interval includes the null. Furthermore, the small number of studies, the heterogeneity of populations studied all warrants caution when interpreting the pooled results. Despite the lack of evidence for statistical heterogeneity. IGRA positives results appear to have higher rates of incident TB than IGRA negatives. A pooled IR (IGRA+)=16.5 (95% CI 11.24-21.7), I2=98%, p<0.0001 and
IR (IGRA-)=2.85 (95% CI 0.86-4.84), I2=35%, p=0.217. The 95% CI do not overlap suggesting the difference may be significant. However, this is based on just three studies with different populations. The pooled results should be interpreted with caution; there is low-high statistical heterogeneity. | Moderate increase in incidence rates of TB in IGRA positives compared to IGRA negatives. This translates to moderate risk of progression. There are too few studies to conclude this with certainty.
However, even in those with positive IGRA results, the vast majority of individuals did not progress to TB disease during follow- up. | Very low
⊕○○○ | Critical
(7-9) |
| Predictive value of IGRA for the development of active incident TB compared to the TST (Do IGRAs (positive vs. negative) have a stronger statistical association with subsequent active TB than the TST (positive vs. negative)? | 7,392 (3) |
IGRA+: Pooled IRR=3.24 (0.62-4.69); I2=0%, p=0.90 TST+: Pooled IRR=2.3 (0.83-3.73); I2=0%, p=0.38
The derived estimates are not statistically significant; the confidence intervals include the null. The pooled estimates should also be interpreted cautiously: there are only three studies; heterogeneous populations and study methods | IGRA+ and TST+ may have a similar strength of association with subsequent TB compared to test negative individuals. | Very low
⊕○○○ | Critical
(7-9) |
| Predictive value of IGRA for subsequent TB when IGRA are evaluated as part of a multivariable clinical algorithm for predicting TB (Additive value of IGRA) | No studies | | | | Important
(4-6) |
| Quantitative IGRA levels and subsequent rates of TB | 721 (1) | No pooled estimates: there is only one study
It suggests no exposure-gradient relationship between quantitative IGRA levels and rates of subsequent TB. Rates appeared highest in the lowest IGRA quartile, 0.35-0.64 IU/ml at 73.8/1000PY (23.8-228.94), and not at subsequent higher strata, 0.65-3.94 IU/ml at 30.1 (12.5-72.4), 3.95-10 IU/ml at 0 rate per/1000PY and the highest IGRA quartile of >10 IU/ml at 50/1000PY (18.8-133.1). However, comparisons across the strata are not statistically significant, as confidence intervals overlap and results should be interpreted with caution. | Inconclusive results.
Number of studies assessed is too small. | Very low
⊕○○○ | Important
(4-6) |
| Immunological phenotypes of discordant-concordant TST/IGRA pairs and subsequent rates of TB | 5,861 (2) | No pooled estimates.
Rates of TB during follow-up may be higher in those with double positive TST+/IGRA+ results than in those with double negative results.
The Zambia study reported higher rates in the discordant pair where IGRA was the positive tests compared to when TST was the positive tests, 29.7/1000PY (13.4 – 66.2) and 0 for IGRA+/TST- and IGRA-/TST+, respectively. By contrast the South African study reported marginally higher rates in IGRA-/TST+ of 3.3/1000PY (0.4-12.0) than in IGRA+/TST- of 1.8/1000PY (0.4-5.4). However, these differences are not significant as the confidence intervals are wide and overlap. | Inconclusive results. Numbers of studies is too small and/or the rate of TB observed per strata too low. | Very low
⊕○○○ | Important
(4-6) |
| Sensitivity, Specificity, False positive rates etc for active TB (as surrogates of patient relevant outcomes) | 7,392 (3) | No pooled results.
IGRA sensitivity for incident TB was 88% (64-99), 75% (48- 93) and 75% (61-86) for the China (T-SPOT.TB), Zambia (QFT-GIT) and South Africa (QFT-GIT) studies, respectively. Specificity was low across the studies at 35% (30-41), 50% (46-54) and 49% (48-51). That means, the false positive rate (100-specificity) for the studies will be 65% (59-70), 50% (46-54) and 51% (49-52). Based on a positive IGRA alone, all these individuals would unnecessarily receive IPT.
TST sensitivity for incident TB was similar at 76% (50-93) and 73% (59-84) for the China and South Africa studies, respectively. Specificity for those studies was 35% (29-41) and 58% (57-58). The proportions that would unnecessarily receive IPT based on IPT alone would be 65% (59-71) and 42% (41-42) for the China and South Africa studies, respectively. By contrast sensitivity for subsequent TB disease was poorest for the Zambia study at 44% (20-70) with a specificity of 67% (64-71). The Zambia study acknowledged logistical issues at the clinical sites that possibly affected TST results. | IGRA have moderate sensitivity for subsequent TB in keeping with observed moderate rates. This is not different from the TST.
False positive rate is similar for both tests.
The proportions scored positive by IGRA and TST are similar for the China and South Africa studies. By contrast, the proportion IGRA+ is higher than TST+ for the Zambia study. However, lower TST results may have resulted from logistical issues. | Very low
⊕○○○ | Important
(4-6) |
| Utility of repeated or serial IGRA results for predicting subsequent incident active TB | No studies | | | | Important
(4-6) |
