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

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

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.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Coinfection / diagnosis*
  • Double-Blind Method
  • Female
  • HIV Infections / complications*
  • HIV Infections / diagnosis
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Sensitivity and Specificity
  • Skin Tests / methods*
  • Tuberculosis / complications*
  • Tuberculosis / diagnosis*
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT01642888

Grants and funding

This trial was sponsored by Statens Serum Institut (SSI). SSI manufactured and supplied C-Tb and PPD, led the design, data analysis, data interpretation, and writing of the clinical trial report. The funder had no role in data collection. The corresponding author had full access to all data in the trial and had the final responsibility for the decision to submit for publication.