Safety and efficacy of the C-Tb skin test to diagnose TB
Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial
Summary
Background
Targeted screening and
treatment of Mycobacterium tuberculosis infection substantially
reduces the risk of developing active tuberculosis. C-Tb
(Statens Serum Institute, Copenhagen, Denmark) is a novel
specific skin test based on ESAT-6 and CFP10 antigens. We
investigated the safety and diagnostic potential of C-Tb
compared with established tests in the contact-tracing setting.
Methods
Negative controls, close
contacts, occasional contacts, and patients with active
pulmonary tuberculosis were enrolled at 13 centres in Spain. We
compared C-Tb with the QuantiFERON-TB Gold In-Tube ([QFT]
Qiagen, Hilden, Germany) interferon γ release assay (IGRA)
and the purified protein derivative (PPD) RT 23 tuberculin skin
test ([TST] Statens Serum Institute). All participants older
than 5 years were tested with QFT. Some participants in the
negative control group received C-Tb without the TST to test for
potential interactions between C-Tb and PPD RT 23. The rest were
randomly assigned in blocks of ten and tested with both C-Tb and
TST, with five in each block receiving injection of C-Tb in the
right arm and the TST in the left arm and five vice versa. The
primary and safety analyses were done in all participants
randomly assigned to a group who received any test. This trial
is registered with ClinicalTrials.gov, number NCT01631266, and
with EudraCT, number 2011-005617-36.
Findings
From July 24, 2012, to Oct
2, 2014, 979 participants were enrolled, of whom 263 were
negative controls, 299 were occasional contacts, 316 were close
contacts, and 101 were patients with tuberculosis. 970 (99%)
participants completed the trial. Induration sizes were similar
for C-Tb and TST, but TST positivity was affected by BCG
vaccination status. We found a strong positive trend towards
C-Tb test positivity with increasing risk of infection, from 3%
in negative controls to 16% in occasional contacts, to 43% in
close contacts. C-Tb and QFT results were concordant in 785
(94%) of 834 participants aged 5 years and older, and results
did not differ significantly between exposure groups. The safety
profile of C-Tb was similar to that for the TST.
Interpretation
C-Tb delivered
IGRA-like results in a field-friendly format. Being unaffected
by BCG vaccination status, the C-Tb skin test might provide more
accurate treatment guidance in settings where the TST is
commonly used.
To download the full article, click
here.
Source:
The Lancet Respiratory Medicine
