A 2013 study by Al Jahdali et al. (2013) explored the screening utility of a novel laboratory test for Tuberculosis. The Interferon-Gamma Release Assay (IGRA) is antigen-specific for Mycobacterium tuberculosis, and has some advantages over the traditionally-used Tuberculin Skin Test (TST). Some of these advantages include less tendency to report false positives due to anergy, as well as less cross-reactivity with the Bacille-Camille-Guerin (BCG) immunization and infection by other species of Mycobacterium (Al Jahdali et al., 2013).
In this study, the researchers screened a total of 200 dyalisis patients using both tests: the Tuberculin Skin Test (TST) and the Interferon-Gamma Release Assay (IGRA). The rationale behind the choice of the study population is that dyalisis patients are 10-25 times more likely to develop active tuberculosis (TB) when compared with immunocompetent people (Al Jahdali et al., 2013). Confirmed diagnosis of tuberculosis was not an excluding criterion. Demographic information was obtained along with the blood samples and the application of the TST. On one hand, the threshold for considering the TST positive was induration of 10mm or more in transverse diameter (Al Jahdali et al., 2013). On the other hand, in case of the IGRA, a value of 0.35 UI/ml was considered positive. Both tests were measured in a binary way: either positive or negative. The negative results were obtained when below the threshold for each test. Additionally, a recent chest X-ray (< 3 months) was used as a diagnosis confirmation, and thus a gold standard against TST and IGRA.
Results showed that of the 200 screened patients, 26 (13%) were positive for for TST, while 65 (32.5%) were positive for IGRA (Al Jahdali et al., 2013). Within this sample, the concordance between the two tests was 75.5% with a kappa value of 0.34. A subsample of only confirmed TB patients was also screened. Within this subsample (n=15), the TST was not able to identify any of the TB patients, while the IGRA correctly identified 10 out of the 15 TB patients (66.7%). Regarding the prediction of the confirmed TB cases, Al Jahdali et al. (2013) also report that the IGRA was more sensitive and less specific than the TST, and the Areas Under the Curve (AUC) of these tests were significantly different (p = 0.0003) (Al Jahdali et al., 2013). The degree of concordance between these two tests in the aforementioned TB subsample was 33.3% with a kappa value of 0.00 (Al Jahdali et al., 2013).
As Porsa et al. (2006) comment, the kappa statistics provides the interobserver level of agreement adjusted according to the amount of agreement that could be expected by chance alone (Porsa el al., 2006). The strength of the agreement that the kappa statistic measures depends on the underlying study population. Therefore, it is not uncommon to find similar overall agreements with different kappa values, which hinders its comparison across several studies (Porsa et al., 2006). The high variation of the kappa statistic among studies relies on the difference in prevalence of the outcome.
It is worth the mention that although this study by Al Jahdali et al. (2013) includes the word ‘diagnosis’ instead of ‘screening’ in the title, the terminology is not exactly accurate, and at some point misleading. Screening procedures do not diagnose illnesses, but classify asymptomatic patients according to their likelihood of having a particular disease (Hennekens & Buring, 1987). In fact, diagnostic procedures for tuberculosis include Acid-Fast Bacillus (AFB) microscopy, mycobacterial culture, nucleic acid amplification, drug susceptibility testing, radiographic procedures, and there is currently no gold standard for the diagnosis of latent tuberculosis infection (LTBI) (Longo et al., 2011).
Studies like the one reported in this review by Al Jahdali et al. (2013) contribute into finding a laboratory gold standard for the diagnosis of latent tuberculosis infection, especially in immunocompromised patients.
References
Al Jahdali, H., Ahmed, A. E., Balkhy, H. H., Baharoon, S., Al Hejaili, F. F., Hajeer, A., & Al Sayyari, A. A. (2013). Comparison of the tuberculin skin test and Quanti-FERON-TB Gold In-Tube (QFT-G) test for the diagnosis of latent tuberculosis infection in dialysis patients. Journal of Infection and Public Health, 6(3), 166-172.
Hennekens, C. H. & Buring, J. E (1987). Epidemiology in medicine. S. L. Mayrent (Ed.). Boston: Little, Brown.
Longo, D. L., Fauci, A., Kasper, D. L., Hauser, S. L., Jameson, J. L., & Loscalzo, J. (2011). Harrison’s Principles of Internal Medicine, 18th. New York: Mc Graw Hill Professional.
Porsa, E., Cheng, L., Seale, M. M., Delclos, G. L., Ma, X., Reich, R., & Graviss, E. A. (2006). Comparison of a new ESAT-6/CFP-10 peptide-based gamma interferon assay and a tuberculin skin test for tuberculosis screening in a moderate-risk population. Clinical and Vaccine Immunology, 13(1), 53-58.