Background: Tuberculosis (TB) continues to be one of the major causes of illnesses and deaths worldwide. Currently, it is estimated that about one-third of the world population is infected with TB. Early effective diagnosis and treatment are crucial to reduce mortality, morbidity and transmission of TB. Tuberculin skin test (TST) has been widely used as a screening test for TB and has contributed substantially for generating valuable epidemiological information on infection trends and on the magnitude of disease. Tuberculosis low incidence countries of Western Europe and USA use TST for screening TB among migrant population from high endemic countries of Africa and Asia. For example, it is a normal procedure for students from TB endemic countries coming to Norway to undergo TST, and skin induration of ≥10mm is considered positive for infection. However, it is not well established that skin induration of ≥10mm is an indication of clinical disease, infection, or exposure to environmental mycobacteria in TB high endemic countries such as Ethiopia. Therefore, the objective of this study was to compare the size of TST indurations in individuals with active TB, their household contacts and community controls and to optimize the cut-off point for the diagnosis/ suspecting of active TB in endemic setting, Ethiopia.
Methods: In a health facility-based cross-sectional study, smear positive pulmonary TB (PTB) patients were recruited consecutively from selected health institutions, whereas their household contacts were traced back using the index cases. Community controls were also selected randomly from households neighboring index cases. Sputum was collected from all patients for AFB staining and culture. Provider initiated HIV testing and counseling was done for all participants and participants who were negative for HIV infection were included. Participants were also tested by TST and QuantiFERON®-TB Gold In Tube test (QFT-GIT). In addition, chest X-ray was done for household contacts and community controls with TST results ≥ 10mm.
Results: a total of 224 study participants, 50 smear positive PTB patients, 96 household contacts and 78 community controls were included in this study. All smear positive PTB patients who had skin test results (n= 48) had skin test induration ≥10mm, while 44(91.7%) had skin test induration ≥ 15 mm. Among 88 household contacts who had skin test results, 64 (72.2%) had skin test induration ≥10mm, while 58(65.9%) had skin induration ≥ 15 mm. Among 75 community controls who had skin test results, 35 ( 46.7%) had skin test induration ≥ 10 mm , while 26(34.7%) had skin test induration ≥ 15 mm. The mean size of TST induration was significantly higher in TB patients (18.1mm) compared to that of household contacts (13.6 mm) and community controls ( 7.9 mm) (p< 0.001).. The mean size of skin test induration was higher in individuals who had BCG scar compared to individuals without BCG scar in household contacts and community controls (p< 0, 05). Among 44 TB patients who had QFTGIT results, 36 (81.8%) had ≥ 0.35 IU/ml of IFN- level. Out of 91 household contacts and 58 community controls who were tested by QFTGIT, 64(70, 3%) and 32(55.2%) had ≥ 0.35 IU/ml of IFN level, respectively. The mean level of IFN- was 4.68 IU/ml in TB patients, 4.90 IU/ml in contacts and 2.62 IU/ml in community controls. The difference in the mean level of IFN- in TB patients and community controls as well as in household contacts and community controls were also significant (p<0.05). The mean level of IFN- did not differ by BCG status or by socio-demographic characteristics of the study participants. .
Using sputum culture as a reference test skin test induration ≥ 10 mm was found to be 100% sensitive in identifying TB patients, while the sensitivity was 91.7% at skin test induration ≥ 15 mm. Considering QFT-GIT as reference test in contacts, at skin test indurations ≥ 8mm, 10mm, 11mm and 15 mm, the sensitivities were found to be 95%, 91.7%, 83.3% and 81.7% , respectively, while the specificity was 68% in all cases. In community controls, at skin test indurations ≥ 10 mm and 15 mm, the sensitivities were found to be 81.3% and 65.6%, respectively, while the respective specificities were 80.8%, 88.5% and 100%. Among 40 household contacts who had chest X-ray results, 2(5%) were found to be active TB cases.
Conclusion: To our knowledge, this is the first study to compare TST skin induration in culture confirmed pulmonary TB patients, household contacts, and community controls in Ethiopia. The majority (91.7%) of smear positive TB patients had skin test induration ≥ 15 mm. Moreover, the specificity of the TST was found to be 100% at skin test induration ≥15 mm in community controls who had no known exposure to TB. Since, a test with high specificity is more useful in areas with a high prevalence of disease, skin test induration ≥ 15 mm seems to be optimal for suspecting active TB and recommending chest X-ray in individuals without symptoms suggestive of active TB, while skin test induration ≥ 10 mm seems optimal to suggest Mtb infection in household contacts of TB patients.