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Randomised Clinical Trial Investigating the Specificity of a Novel Skin Test (C-Tb) for Diagnosis of M. tuberculosis Infection
Open accessAbstract
BACKGROUND: Tuberculin skin testing is simple and relatively inexpensive, but the specificity of PPD is affected by BCG vaccination. OBJECTIVE: Determine optimal dose and specificity of recombinant ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection. METHODS: In a dose finding phase I trial 0.01 or 0.1 µg preserved and unpreserved C-Tb was injected by Mantoux technique in 38 patients with active tuberculosis and induration responses measured. In a phase II specificity trial in 151 uninfected, BCG vaccinated participants 0.1 µg C-Tb was compared to 2 TU PPD. RESULTS: 0.1 µg C-Tb gave a median induration of 15 mm after 2 days. Phenol preservation did not affect the response. The specificity of C-Tb was 99.3% (95% CI 96-100%) regarding indurations ≥5 mm as a positive outcome. This was higher than the specificity of PPD (63% using a cut-off of 5 mm or 92% using a cut-off of 15 mm to adjust for non-specific BCG responses). Local adverse reactions following C-Tb injection included transient itching and discomfort as expected components of the immune response. CONCLUSION: C-Tb offers a simple and convenient skin test to diagnose M. tuberculosis infection using a single, universal cut-off unaffected by BCG vaccination. TRIAL REGISTRATION: ClinicalTrials.gov NCT01033929 and NCT01241188.
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The C-tb test is now being mass produced by the Serum Institute of India and has sensitivity and specificity close to that of the IGRA assay at one tenth of the cost.
“The C-tb test is now being mass produced by the Serum Institute of India and has a sensitivity and specificity close to that of the IGRA assay at one tenth of the cost.54”
From Global health 2050: the path to halving premature death by mid-century (2024) · cites this paper as [54]
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Metadata
- Authors
- Aggerbeck, H., Giemza, R., Joshi, P., Tingskov, P. N., Hoff, S. T., Boyle, J., Andersen, P., & Lewis, D. J. M.
- Affiliations
- Statens Serum Institut (DK)
- St George's, University of London (GB)
- University of Surrey (GB)
- Corresponding author
- Aggerbeck, Henrik
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-05-14
- Volume
- 8
- Issue
- 5
- Pages
- e64215
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3653866
- OpenAlex
- W2029357111
- Cited by
- 52
- References
- 23
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 11 · 2015: 3 · 2014: 2 · 2013: 1
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Statens Serum Institut
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- Mycobacterium tuberculosis infection, tuberculosis diagnosis, BCG vaccination, induration, PPD, Lactococcus lactis, dose-finding, cut-off, adverse effects
- MeSH terms
- Adolescent, Adult, Antigens, Bacterial, Bacterial Proteins, Dose-Response Relationship, Immunologic, Female, Humans, Male, Middle Aged, Mycobacterium bovis, Mycobacterium tuberculosis, Sensitivity and Specificity, Tuberculin Test, Tuberculosis, Vaccination, Phenol, Young Adult
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