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Clinical Trial
. 2018 Sep 24;13(9):e0204554.
doi: 10.1371/journal.pone.0204554. eCollection 2018.

C-Tb skin test to diagnose Mycobacterium tuberculosis infection in children and HIV-infected adults: A phase 3 trial

Henrik Aggerbeck  1 , Morten Ruhwald  2 , Søren T Hoff  2 , Bettine Borregaard  1 , Elizabeth Hellstrom  3 , Mookho Malahleha  4 , Mirna Siebert  5 , Mashra Gani  6 , Vincent Seopela  7 , Andreas Diacon  8 , Madeleine Lourens  8 , Peter Andersen  2 , Keertan Dheda  9
Affiliations
Clinical Trial

C-Tb skin test to diagnose Mycobacterium tuberculosis infection in children and HIV-infected adults: A phase 3 trial

Henrik Aggerbeck et al. PLoS One. .

Abstract

Background: C-Tb, an ESAT-6/CFP-10-based skin test, has similar sensitivity for active TB compared to tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-Tube (QFT). However, data are limited in children and HIV-infected persons.

Methods: Asymptomatic South African contacts <5 years (n = 87; HIV-uninfected), or symptomatic individuals of all ages presenting to clinics with suspected TB (n = 1003; 30% HIV-infected) were recruited from eight South African centres. C-Tb and TST were allocated to either forearm double blinded. Samples for QFT were collected in parallel, and test-positivity rates were compared.

Results: In participants with microbiologically confirmed TB (n = 75; 45% HIV-infected) sensitivity of C-Tb, TST and QFT were similar (72% versus 75% versus 73%; p>0.5). All 3 tests had similar positivity rates in HIV-infected participants with active TB, however, positivity rates were reduced when CD4 counts were <100 cells/μL. In participants where active TB was excluded (n = 920), C-Tb (41%), TST (43%), and QFT (44%) also had similar test-positivity rates. Among asymptomatic contacts aged below five, 32% (28/87) tested positive with C-Tb and 32% (28/87) with TST (concordance 89%). Overall, C-Tb and TST showed a similar safety profile.

Conclusion: C-Tb was safe and showed similar test-positivity rates, compared to TST and QFT, in children and HIV-infected persons with active or latent M. tuberculosis infection. These data inform the utility of C-Tb in clinical practice.

Trial registration: ClinicalTrials.gov NCT01642888. EudraCT 2011-005078-40.

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Conflict of interest statement

HA, MR, BBJ and PA are employed at SSI, a governmental non-profit research organization, who holds pending intellectual property rights over C-Tb. All intellectual property rights have been transferred to SSI. The other authors have declared no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Overview of the trial participants.
*These were clinic attendees that on follow-up segregated into those with microbiologically confirmed active TB and non-TB participants. Efficacy data are presented as number of test positives/n (%).
Fig 2
Fig 2. Test positivity rate according to HIV status and CD4 count.
The data shown excludes participants with unknown HIV status and healthy control group. Error bars indicate 95% CI. Cut-point for TST was 5 mm in HIV-infected and 15 mm in others. C-Tb: N = 921 (625 HIV-uninfected, 296 HIV-infected). TST: N = 923 (627 HIV-uninfected, 296 HIV-infected). QFT: N = 818 (126 indeterminate, 538 HIV-uninfected, 280 HIV-infected). Data specific to the active and non-TB groups are shown in S2–S4 Tables. *HIV-uninfected versus HIV-infected p<0.05. †CD4 counts ≥100 cells/μL versus counts <100 cells/μL in HIV-infected; p<0.05.
Fig 3
Fig 3. Test positivity rates in different subgroups of children comparing TST and C-Tb along an exposure gradient.
Healthy control group (5–11 years, n = 100), asymptomatic PTB contacts <5 years (n = 87) and active TB cases <18 years (n = 15, no HIV-infected). Error bars indicate 95% CI.
See this image and copyright information in PMC

References

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