Prevalence of Latent Tuberculosis Infection (LTBI) among House Hold Contacts of Sudanese Patients with Pulmonary Tuberculosis in Eastern Sudan: Revisiting the Tuberculin Skin Test
A third of the world’s population is latently infected with TB with an increased risk of developing active TB. Household contacts (HHCs) of pulmonary TB cases are at a greater risk of developing disease. Early identification and treatment of latent TB infected individuals may reduce progression to active TB. This study aimed to determine latent TB infections (LTBI) point prevalence among HHCs and community contacts (CCs) using Tuberculin Skin Test (TST) and whole blood IFN-γ release assay in an area of high TB prevalence. In a prospective, longitudinal and community-based study and following informed consent, 768 volunteers (HHCs n = 245; CCs n = 523) were enrolled. Tuberculin Skin Test (TST), whole blood stimulation with PPD and IFN-γ levels determination using ELISA were performed. Mean ages of HHCs and the CCs were not significantly different (HHCs 35.6 ± 15.7 and CCs 30.6 ± 11.7 years; p = 0.99), with a Male:Female ratio of 1:2. Mean recruitment TST indurations were 4.6 ± 5.5 mm and 2.8 ± 3 mm for HHCs and CCs respectively (p = 0.000). Follow-up (Day 614) mean TST indurations increased significantly to 9.1 ± 7.2 mm and 4.4 ± 3.2 mm for HHCs and CCs respectively (p = 0.001). Using TST indurations ≥ 10 mm, LTBI point prevalence for HHCs and CCs was significantly different (HHCs 461/1000 and 367/1000 individuals, p = 0.03). The mean IFN-γ levels for HHCs and CCs at recruitment day (Day 0) were 0.66 ± 0.17 IU/ml and 0.06 ± 0.04 respectively. The mean of IFN-γ production levels dropped significantly at Day 614 for HHCs and CCs to 0.66 ± 0.15 IU/ml and 0.02 ± 0.02 respectively (p = 0.03) (p = 0.00001). Recruitment LTBI point prevalence using IFN-γ level ≥ 0.35 IU/ml for HHCs and CCs was 440/1000 and 203/1000 respectively (p = 0.000000001). No correlations between TST indurations and IFN-γ levels were detected among HHCs or CCs (p > 0.05). TST is a simple, efficient and cheap technique for LTBI diagnosis and triaging individuals for treatment.
References
[1]
Heifets, L. (2004) Mycobacterial Infections Caused by Nontuberculous Mycobacteria. Seminars in Respiratory and Critical Care Medicine, 25, 283-295.
https://doi.org/10.1055/s-2004-829501
[2]
Shakak, A.O., Khalil, E.A., Musa, A.M., Salih, K.A., Bashir, A.E., Ahmed, A.H., Idris, F.E. and Elhassan, A.M. (2013) Prevalence of Latent Tuberculosis Infection in Sudan: A Case-Control Study Comparing Interferon-γ Release Assay and Tuberculin Skin Test. BoiMed Central Public Health Journal, 13, 1128.
https://doi.org/10.1186/1471-2458-13-1128
[3]
World Health Organization (2010) 2010/2011 Tuberculosis Global Facts. Stop TB Partnership, WHO/HTM/TB.
[4]
Palomino, J.C., Leão, S.C. and Ritacco, V. (2007) Tuberculosis 2007 from Basic Science to Patient Care. www.TuberculosisTextBook.com
[5]
Koch, R. (1890) An Address on Bacteriological Research. British Medical Journal, 2, 380-383. https://doi.org/10.1136/bmj.2.1546.380
[6]
Diel, R., Nienhaus, A., Lange, C., Meywald-Walter, K., Forssbohm, M. and Schaberg, T. (2006) Tuberculosis Contact Investigation with a New, Specific Blood Test in a Low-Incidence Population Containing a High Proportion of BCG-Vaccinated Persons. Respiratory Research Journal, 7, 77.
https://doi.org/10.1186/1465-9921-7-77
[7]
Hubner, R.E., Schein, M.F. and Bass, J.B. (1993) The Tuberculin Skin Test. Clinical Infectious Diseases, 17, 968-975. https://doi.org/10.1093/clinids/17.6.968
[8]
Van Crevel, R., Ottenhoff, T.H. and van der Meer, J.W. (2002) Innate Immunity to Mycobacterium tuberculosis. Clinical Microbiology Reviews, 15, 294-309.
https://doi.org/10.1128/CMR.15.2.294-309.2002
[9]
Tufariello, J.M., Chan, J. and Flynn, J.L. (2003) Latent Tuberculosis: Mechanisms of Host and Bacillus That Contribute to Persistent Infection. The Lancet Infectious Diseases Journal, 3, 578-590. https://doi.org/10.1016/S1473-3099(03)00741-2
[10]
Shakak, A.O., Khalil, E.A., Musa, A.M., Salih, K.A., Bashir, A.E., Ahmed, A.H., Idris, F.E. and Elhassan, A.M. (2013) Possible Risk Factors of Progression to Overt Disease among Individuals with Latent Tuberculosis Infection in Sudan. International Journal of Current Research, 5, 1107-1110.
[11]
Kunst, H. (2006) Diagnosis of Latent Tuberculosis Infection: The Potential Role of New Technologies. Respiratory Medicine Journal, 100, 2098-2106.
https://doi.org/10.1016/j.rmed.2006.02.032
[12]
Machado, A., Emodi, K., Takenami, I., Finkmoore, B.C., Barbosa, T., Carvalho, J., Cavalcanti, L., Santos, G., Tavares, M., Mota, M., Barreto, F., Reis, M.G., Arruda, S. and Riley, L.W. (2009) Analysis of Discordance between the Tuberculin Skin Test and the Interferon-Gamma Release Assay. The International Journal of Tuberculosis and Lung Disease, 13, 446-453.
[13]
Nicol, M.P., Davies, M.A., Wood, K., Hatherill, M., Workman, L., Hawkridge, A., Eley, B., Wilkinson, K.A., Wilkinson, R.J., Hanekom,W.A., Beatty, D. and Hussey, G. (2009) Comparison of T-SPOT.TB Assay and Tuberculin Skin Test for the Evaluation of Young Children at High Risk for Tuberculosis in a Community Setting. Pediatrics Journal, 123, 38-43.
[14]
Kobashi, Y., Shimizu, H., Ohue, Y., Mouri, K., Obase, Y., Miyashita, N. and Oka, M. (2010) Comparison of T-Cell Interferon-γ Release Assays for Mycobacterium tuberculosis-Specific Antigens in Patients with Active and Latent Tuberculosis. Lung Journal, 188, 283-287. https://doi.org/10.1007/s00408-010-9238-3
[15]
Katsenos, S., Nikolopoulou, M., Gartzonika, C., Manda-Stachouli, C., Gogali, A., Grypaiou, C., Mavridis, A., Constantopoulos, S.H. and Daskalopoulos, G. (2011) Use of Interferon-Gamma Release Assay for Latent Tuberculosis Infection Screening in Older Adults Exposed to Tuberculosis in a Nursing Home. The Journal American Geriatrics Society, 59, 858-862.
https://doi.org/10.1111/j.1532-5415.2011.03367.x
