Single-step QuantiFERON screening of adult contacts: a prospective cohort study of tuberculosis risk

Abstract

BackgroundThe efffectiveness of tuberculosis (TB) contact screening programmes using interferon γ release assays remains uncertain as prospective contact TB risk is not well characterised. Objectives To quantify 2-year TB risk and evaluate screening performance with single-step QuantiFERON TB Gold-In Tube (QFT) in adult contacts. To compare TB risk between QFT tested subgroups stratified by exposure type (smear positive pulmonary (SP) versus non-smear positive (NSP) TB) and age (younger (16-35 years) versus older (≥36 years)). Methods Screening involved QFT testing in older contacts of SP and all younger contacts, 8-12 weeks after index notification. Chemoprevention (3RH) was offered to QFT positive (+) younger adults. TB risk was determined in a prospective cohort study. Results 43 TB events occurred in 1769 adult contacts observed for median 717 days (2-year rate (95% CI) =2·5% (1.7 to 3.2)). Index-contact strain matching was demonstrable for 18 of 22 (82%) paired samples. No contacts (0/98) receiving 3RH developed TB. 215 of 817 appropriately tested adults (26.3%) were QFT+. 14 of 112 untreated QFT+ adults developed TB (2-year rate (95% CI)=13·4% (7.7 to 21.1)). The model required 35 contacts screened with QFT to identify one contact developing TB at 2 years. TB rates were comparable in QFT+ contacts of SP and NSP (rate ratio (RR)=0.98, p=0·962). For QFT+ older contacts, the disease rate was lower (8.9% (3.3 to 19

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

“…In a German study, Geis and colleagues 22 reported that five (83%) of six contacts with disease had interferon-γ values higher than 10 IU/mL, and suggested that raising the QFT test threshold could improve the positive predictive value and reduce the number needed to treat. By contrast, Haldar and colleagues 23 did not find an association between QFT conversion interferon-γ value and progression to tuberculosis disease among adult contacts in the UK, and Zellweger and colleagues 19 found minimal variability in risk by interferon-γ value in a cohort of contacts in a large European network. Notably, these studies measured interferon-γ values in primarily adult tuberculosis contacts in low endemicity areas, whereas our study enrolled young children in a high transmission area who were known to be QFT negative and were then followed prospectively for QFT conversion and subsequent disease.…”

“…16 Whether higher interferon-γ values represent more recent M tuberculosis exposure, greater aerosolised inoculum, or sustained infection-or simply reflect heterogeneity in human immune responses to M tuberculosis-is unclear. Importantly, evidence for whether higher QFT conversion interferon-γ values are associated with increased risk of progression to active disease is conflicting, 19,[21][22][23] and current management algorithms do not distinguish between interferon-γ values above the QFT manufacturer's recommended test threshold of 0·35 IU/mL.…”

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

“…Since the publication of the aforementioned review, five new longitudinal studies have been published (122)(123)(124)(125)(126). Table 3 presents the characteristics of all 20 longitudinal studies.…”

How can we achieve better prevention of progression to tuberculosis among contacts?

“…However, three out of 19 contacts who developed active TB had IFN-c levels ,1.0 IU?mL -1 . HALDAR et al [12] did not find a difference when comparing the magnitude of IFN-c levels and disease progression.…”