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. 2015 Mar 1;191(5):584-91.
doi: 10.1164/rccm.201409-1704OC.

The dynamics of QuantiFERON-TB gold in-tube conversion and reversion in a cohort of South African adolescents

Jason R Andrews  1 , Mark Hatherill, Hassan Mahomed, Willem A Hanekom, Monica Campo, Thomas R Hawn, Robin Wood, Thomas J Scriba
Affiliations

The dynamics of QuantiFERON-TB gold in-tube conversion and reversion in a cohort of South African adolescents

Jason R Andrews et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Interferon-γ release assays are used to diagnose tuberculosis infection. In developed countries, high rates of reversion following conversion have been described.

Objectives: To assess QuantiFERON TB Gold In-Tube test (QFT) conversion and reversion dynamics in a tuberculosis-endemic setting.

Methods: Adolescents aged 12-18 years residing near Cape Town were recruited. Tuberculin skin tests (TSTs) and QFTs were performed at baseline and after 2 years of follow up. Half of the participants had TST and QFT performed at additional time points. Participants were observed for incident tuberculosis disease for up to 5 years.

Measurements and main results: Among 5,357 participants, 2,751 (51.4%) and 2,987 (55.8%) had positive QFT and TST results, respectively, at baseline. Annualized QFT and TST conversion risks were 14.0 and 13.0%, respectively, and reversion risks were 5.1 and 4.1%, respectively. Concordance was excellent for conversions (κ = 0.74), but poor for reversions (κ = 0.12). Among recent QFT converters, the magnitude of the QFT value was strongly inversely associated with risk of reversion (P < 0.0001). When longitudinal QFT data were analyzed in a cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion of reversions in the analysis showed that the actual risk of infection was 14.0%. Incident tuberculosis was 8-fold higher among QFT reverters than in participants with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, P = 0.011).

Conclusions: In this tuberculosis-endemic setting, annual risk of infection was extremely high, whereas QFT and TST conversion concordance was higher and QFT reversion rates were lower than reported in low-burden settings.

Keywords: adolescents; epidemiology; interferon-γ release assays; tuberculin skin tests; tuberculosis.

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Figures

Figure 1.
Figure 1.
Distribution of baseline tuberculin skin test (TST) results (A) and QuantiFERON TB Gold In-Tube test (QFT) results (B) (histograms, right vertical axis) and proportion with a positive test result (black line, left vertical axis) as threshold varies. Vertical dashed lines indicate the positivity criteria used in this study (TST ≥ 5 mm; QFT ≥ 0.35 IU/ml).
Figure 2.
Figure 2.
Annual QuantiFERON TB Gold In-Tube test (QFT) conversion and reversion rates according to QFT threshold. Vertical dashed line reflects the manufacturer’s recommended threshold (≥0.35 IU/ml). At values of less than 0.35 IU/ml, conversions decreased precipitously as QFT threshold increased; however, this sensitivity leveled off at values of more than 0.35 IU/ml. By contrast, reversion rates gradually increased with increasing QFT threshold.
Figure 3.
Figure 3.
Probability of reversion at 720 days among participants with QuantiFERON TB Gold In-Tube test (QFT) conversion at 360 days, according to QFT quartile at 360 days. The probability of reversion decreased from 52% in the lowest QFT quartile to 0% in the highest quartile (P < 0.0001).
Figure 4.
Figure 4.
QuantiFERON TB Gold In-Tube test (QFT) conversions by time and baseline tuberculin skin test (TST) status (left y-axis), along with the cross-sectional and cumulative prevalence of positive QFT (right y-axis), among participants with data available for all five time points. TSTs (arrows) were administered at baseline, Day 90, and Day 180; only participants with negative baseline TST had a TST performed at Day 90, as indicated by the asterisk. QFT conversions were much higher in the 180 days following TST conversion (Days 0 and 540) but only in the TST-positive group. The high rates of reversions led to divergence of the cross-sectional prevalence and cumulative positivity of QFT.
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References

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