Two-step tuberculin skin test in nurse students

The tuberculin skin test (TST) was conducted in 243 nurse students (19.4 +/- 1.3 years old). The second TST were carried out in 240 students who did not show blister or necrosis in the first TST. The size of erythema was 16.5 +/- 9.4 mm in the first TST (T1) and 24.3 +/- 15.6 mm in the second TST (T2). The negative reactors, whose size of erythema was below 10 mm, were decreased from 53 to 25, whereas, the strong reactors, whose size of erythema was more than 30 mm, were increased from 11 to 71. The difference of the size of erythema (T2-T1) was 9.7 +/- 11.9 mm in the group I (190 students) who received the latest TST in junior high school, whereas, that was 0.5 +/- 9.2 mm in the group II (50 students) who received the latest TST 14 months before this study. T2-T1 in the group I was weakly correlated with T1. Twenty-four negative reactors received BCG vaccination, and 23 of them converted to positive. Seventy-one strong reactors were checked by chest X-ray, and none showed the findings of tuberculosis, and required the administration of anti-TB drug. The two-step TST is an essential means to know the baseline reactivity to TST, and to distinguish newly infected tuberculosis from booster phenomenon.     

Two-step tuberculin testing of passengers and crew on a commercial airplane

OBJECTIVES: We investigated the risk of tuberculosis transmission from a person with highly infectious pulmonary tuberculosis to fellow passengers and crew members on a 14-hour commercial flight. The 2-step tuberculin testing was used to minimize the effects of the booster phenomenon. METHODS: Passengers and flight crew members identified from airline records were contacted by letter, telephone, or both to notify them of their potential exposure to Mycobacterium tuberculosis. The subjects were advised to undergo Mantoux tuberculin skin testing within the required time period to assess a conversion. In addition, information regarding tuberculosis history and other sources of potential exposure was solicited by means of a questionnaire. RESULTS: Of the 277 passengers and crew members on the aircraft, 225 (81.2%) responded. Of these, 173 (76.9%) had positive tuberculin results on the first test (induration > 10 mm). Thirteen subjects with negative results refused further testing; 11 (28%) of the remaining 39 exhibited the booster phenomenon on the second test. Subjects who exhibited the booster phenomenon were significantly more likely to have received previous BCG vaccination. Nine contacts with negative results on the initial test had positive results on a third test administered at 12 weeks after the flight exposure Of these, 6 contacts had previous BCG vaccination, old tuberculosis, or a family member with tuberculosis; the remaining 3 reported on other risk factors for positive reactions. None of these 3 contacts had sat in the same section of the plan as the index patient. CONCLUSIONS: The 2-step tuberculin testing procedure is an effective tool for minimization of the booster effect, thus allowing accurate monitoring of subsequent tuberculin conversion rates. Moreover, the clustering of tuberculin skin test conversions among passengers in this study demonstrates the possible risk of M tuberculosis transmission during air travel.     

Analysis on the results of TB skin test in medical students

PURPOSE: To obtain baseline, medical students are recommended to make two-step tuberculin skin tests when they are in good physical health, as the baseline information to detect later tuberculosis infection. We investigated a method to obtain appropriate baseline data, because the accurate method of this test was not yet established. SUBJECTS AND METHODS: The subjects were the tuberculin skin test results of 1066 medical students who were subjected to different methods of tuberculin skin test (58% tested once, 37% tested twice, and 5% tested three times). We retrospectively made multi-dimensional analysis about these data. RESULTS: (i) In the first tuberculin skin test, 20% of the results were negative. (ii) When repeated with intervals between one to four years, the diameters of erythema gradually increased due to the effect of prior tests. (iii) The difference in size of erythema between the first tuberculin skin test and the repeated tests was less than 10 mm. (iv) When two-step tuberculin skin test was repeated, significant increase in the diameters of erythema were demonstrated in the second test (P = 0.0048). (v) Regarding booster phenomenon, it apparently lasted for one year, and it also remained after two years or over. CONSIDERATION: Thus, repeated tuberculin skin tests performed in good physical health was difficult to interpret measuring the diameters of erythema to detect tuberculosis infection. Thus, the diagnostic value of a tuberculin skin test was reduced while it requires unnecessary time and expenditure for its implementation. CONCLUSION: It seems to be appropriate for medical students to make a two-step tuberculin skin tests, soon after their enrollment, and the results should be used as a baseline to detect possible later tuberculosis infection.     

The effect of bacille Calmette-Guérin vaccination at birth on tuberculin skin test reactivity in Ugandan children.

SETTING: In Uganda, bacille-Calmette Guerin (BCG) vaccination coverage at birth is between 82 and 84%. OBJECTIVE: To evaluate the effect of neonatal BCG vaccination on tuberculin skin test positivity in Ugandan children exposed to infectious cases. DESIGN: As part of an ongoing prevalence study of household contacts of new tuberculosis cases, 365 children were evaluated to determine if BCG vaccination at birth had an impact on tuberculin skin testing. The children were classified as contacts (179) and non-contacts (186) depending on the presence of a sputum acid-fast bacilli (AFB) smear-positive adult tuberculosis case in the household. RESULTS: Regardless of prior BCG vaccination, children exposed to a smear-positive adult were more likely to have a positive skin test (purified protein derivative >5mm) (68% versus 36%, P < 0.01). BCG-vaccinated children below 1 year of age without a known household contact with active tuberculosis had a lower frequency of tuberculin skin reactions (29%) compared to their counterparts in the contact households (65%, P = 0.031). CONCLUSION: BCG vaccination at birth had no important effect on the interpretation of the tuberculin skin test reactivity in this group of Ugandan children. The tuberculin skin test remains a valuable tool for the evaluation of household contacts and suspected cases of tuberculosis in BCG-vaccinated children.     

The frequency profile of tuberculin skin testing among students in nursing school]

The frequency profile of tuberculin skin testing (TST) among students in nursing school was studied. Students received a TST upon matriculation. The TST was done by the method of Mantoux, in which 0.1 ml of PPDs was administered intradermally, and the diameters of skin rash and induration were read by the medical doctor at 48 hours. When TST results are negative--that is, the diameter of skin rash is below 10 mm (in Japan, the TST results are judged by skin rash diameter rather than that of induration)-BCG vaccination is given. Those receiving the BCG vaccination are retested with a TST one year later. When the second TST was also negative both the BCG vaccination and TST were followed for two more years. Those students testing TST-negative are not permitted to take clinical training in the tuberculosis ward. Student's mean age on entrance was 18.6 +/- 2.1 years old, and all but three were female. About 70% of students entering in 1996 to 1998 had a history of previous BCG vaccination. In 14% their positive TSTs could be attributed to probable infection with tuberculosis in childhood. In the remaining 16%, details as to TST and BCG vaccination status are unknown. The frequency distribution of TST results was bimodal, showing one peak at 6 mm and another at 12 mm (skin rash diameter). The percentage of negative and positive reactors are 47.1% and 52.9%, respectively. The TST-negative students entering in 1994 to 1996 were given the BCG vaccination. Twenty-four of 134 students (17.9%) remained negative at the second TST, and 6 students (4.5%) at the third year, even after two repeated BCG vaccinations. The TST results were chronologically observed in the above 6 students after BCG vaccination. The TST results of two students showed positive in September, 1996 and June, 1997. While four students showed positive in September, 1996, all ultimately reverted to negative when retested in June, 1997. Those students had negative results for TST at the initial test in 1998 had the two step-tuberculin skin testing. All eight students with negative TST had the history of BCG vaccination. The second TST showed positive except one student whose scar after BCG vaccination was not observed on the arm. The TST is currently recommended in hospital tuberculosis-control programs. If TST-negative, medical staff and students may not work in the tuberculosis ward. However, after BCG vaccinations is given, and subsequent TST conversion is confirmed, they are then able to work or to have training in the ward. From our results, there is 4.5% non-convertors even after 2 years of repeated BCG vaccinations. However, these non-converters turned positive four months after BCG vaccination, only to revert to negative nine months later. These students are considered to have delayed hypersensitivity to PPD after BCG vaccination. However, their reactivity waned in the short period of nine months after the conversion of their TST's. Therefore, it is concluded that non converters after repeated BCG vaccinations are able to have clinical training in the tuberculosis ward as long as their BCG vaccinations are correctly administered and any immunological deficiencies are ruled out.     

The effect of BCG vaccination on tuberculin reactivity and the booster effect among hospital employees

BACKGROUND: We estimated the effect of remote BCG vaccination on tuberculin reactivity and the booster effect among hospital employees. METHODS: Cross-sectional survey at a university hospital. All personnel employed during a 24-month period were included in the study. Employees were administered 2-step tuberculin testing, and BCG vaccination scars were verified. RESULTS: Of 665 hospital employees studied, 239 (36%) had been vaccinated with BCG in childhood. Significant tuberculin reactions (> or =5 mm) were more frequent among BCG-vaccinated (60%) than among nonvaccinated (29%) employees (odds ratio [OR], 3.6; 95% confidence interval [CI], 2.6-5.2). The predictive value of tuberculosis infection increased with increasing reaction size and greater age (from 37% in subjects 30 years or younger with indurations > or =5 mm to 100% in subjects 50 years or older with indurations > or =15 mm). Among 374 employees with a negative tuberculin test reaction who underwent a second test, 39 (43%) of 91 vaccinated subjects had a positive booster reaction in contrast to 51 (22%) of 232 nonvaccinated subjects (OR, 3.4; 95% CI, 2-5.7). Neither different size criteria nor different definitions of the booster effect had an impact on the predictive value of tuberculosis infection. CONCLUSIONS: Remote BCG vaccination largely influences the tuberculin reaction and the boosting phenomenon among hospital employees. The interpretation of the results of 2-step tuberculin testing in a BCG-vaccinated subject must take into account age, size of the reaction, and local prevalence of tuberculosis infection. No single criterion, however, can accurately separate reactions caused by true infection from those caused by BCG vaccination.     

Prevalence and factors associated with tuberculosis infection among new school entrants, New York City, 1991-1993.

SETTING: New York City public (or state-run) and private schools-elementary and secondary. OBJECTIVE: To describe the prevalence and determine factors associated with positive tuberculin skin tests (TSTs) in school children. DESIGN: Mandatory TST surveys among cohorts of new school entrants for the 1991, 1992 and 1993 school years, of whom birthplace was known for 81%. A positive tuberculin skin test defined as > or =10 mm induration. RESULTS: Of the 298506 new school entrants, 2.1% (6326) were tuberculin test positive. The proportion that was tuberculin test positive was 0.5% (931/199 728) among US-born and 9.2% (3794/41 346) among foreign-born students. Foreign-born (FB) students with a history of BCG vaccination were much more likely to have a positive tuberculin test than US-born students (13.6% vs. 0.5%, odds ratio [OR] = 33.6, 95% confidence interval [CI] 31.7, 35.6), and were more likely to have a positive tuberculin test than FB students with no history of BCG (13.6% vs. 4.4%, OR = 3.4, 95% CI 2.5, 4.6). Older age was independently associated with tuberculin test positivity, except among foreign-born BCG-vaccinated children, in whom the youngest were more likely to have a positive tuberculin test. CONCLUSIONS: Even in the midst of a tuberculosis resurgence such as that experienced by New York City, where tuberculosis cases nearly tripled from 1978 to 1992, the risk of tuberculosis infection among school children remained quite low. Given the reduced predictive value of the tuberculin test among low risk children and the effects of BCG vaccination, many children (especially younger children) with positive tuberculin test results are probably not infected with Mycobacterium tuberculosis. To reduce unnecessary evaluation and treatment, routine tuberculin tests should be administered only to high risk groups such as older children from countries with high rates of tuberculosis.     

Safety and immunogenicity of Bacillus Calmette-Guerin vaccine in children born to HIV-1 infected women

This prospective cohort study was conducted to determine the complication of Bacillus Calmette-Guerin (BCG) vaccination given to newborn infants born to HIV-1 seropositive mothers and to compare the tuberculin reaction 9 months after BCG vaccination between HIV-1 infected and non infected children. Two hundred and twenty-three infants with BCG immunization at birth were examined. No BCG complication was noted. Tuberculin skin tests were performed on 126 children (56.5%). Eleven of them were excluded because of failure to have skin tests read at 48 hours. Of the 115 infants enrolled to this study, 15 (13%) had no BCG scar and 50 (43.5%) had no tuberculin reaction. Twenty-six children were classified as group 1 or HIV-1 infected children and 89 children were group 2 or HIV-1 non infected. Group 1 children had a smaller tuberculin skin response (X+SD) than group 2 (1.15 +/- 2.82 vs 4.64 +/- 4.29 mm; p < 0.0001). Mean weight + SD of group 1 children was also significantly less than those in group 2 (8,013 +/- 741 vs 8,540 +/- 984 g; p < 0.05). The proportion of children with non reactivity to the tuberculin test, a negative tuberculin test and no BCG scar in group 1 was significantly higher than that in group 2 (76.9% vs 33.7%, 92.3% vs 52.8% and 36.4% vs 6.7% respectively; p < 0.0001 for all). But, the proportion of non reactivity to the tuberculin test in children with or without BCG scar of each group was not different (p > 0.05). Positive tuberculin tests were 7.7% and 47.2% in group 1 and 2 respectively. None of the children with positive tuberculin tests had clinical evidence of tuberculosis. The findings of this study indicate that BCG vaccine given to newborn infants of HIV-1 seropositive mothers is safe. Although tuberculin skin responses of HIV-1 infected children are less than those of HIV-1 non-infected children, it is possible that BCG vaccine might protect these children from developing severe tuberculosis.     

Tuberculin reactivity in a chest clinic: the effects of age and prior BCG vaccination

Heaf tests were performed in 834 adults and children seen during one year in a tuberculosis contact clinic in Edinburgh. All subjects with a past history of tuberculosis, or who subsequently developed evidence of tuberculous infection and 63 subjects of Asian origin were excluded to leave 749 'healthy' adults and children broadly representative of the local caucasian population. All Heaf tests in 178 children without BCG vaccination were negative or grade I whereas 16 (73%) of the 22 children with a history of previous BCG vaccination were positive grade I or II. A strongly positive Heaf test (grade III-IV) in any child with or without previous BCG vaccination seen as a tuberculosis contact implies recent infection and merits consideration for chemoprophylaxis or prolonged follow-up. Two hundred and seventy adults without previous BCG vaccination showed an increasing incidence of strongly positive Heaf tests (grade III or IV) with age reaching a peak of 55% in the 45-65 age group; beyond the age of 65 this fell to 37%. Two hundred and eighty-one adults with previous BCG vaccination showed significantly more Heaf grades I and II, fewer negatives and fewer strong positives than the unvaccinated group. A strongly positive Heaf test (III-IV) is a frequent finding in a healthy adult and has little discriminatory value in the diagnosis of active tuberculosis infection in Edinburgh, and by implication elsewhere in the United Kingdom. Positive tuberculin tests should be viewed in the context of the tuberculin profile of the local population.     

Tuberculin skin testing in students of school of nursing]

Tuberculin skin testing in students of the School of Nursing Attached to National Hiroshima Hospital was analyzed. On initial test using 0.05 microgram of PPDs, diameter of erythema in 26.7% of 300 new students were less than 9 mm. Twelve of 24 who were tested by two-step method reacted more than 10 mm on the second test. Twenty-seven non-reactors who were vaccinated with BCG all reacted more than 10 mm after 9 to 16 weeks after vaccination. They might be vaccinated in the past by insufficient technique and better be revaccinated. Thirty-one of 49 students who graduated in 1998 were tested and their reactions were compared with those on entrance or after BCG vaccination. The two tests were spaced 31 to 34 months apart. The reactions were weakened in the cases after BCG vaccination, and in those who were not vaccinated on entrance, only a little booster effect were observed, except in 3 graduates whose reactions were significantly boosted and thought to be infected while in school. As there is considerable variation in tuberculin reactivity after BCG vaccination, diameter of reaction should be kept on personal health record as base line reaction to diagnose tuberculous infection henceforce.     

The influence of Calmette-Guérin bacillus immunization on the booster effect of tuberculin testing in healthy young adults

The booster or enhancement effect of repeated tuberculin skin testing in Calmette-Guérin bacillus (BCG)-vaccinated young adults was studied in 208 first-year medical, nursing, and medical technology students in Santiago, Chile, where BCG vaccine is usually administered at birth and at 6 and 14 yr of age. Thirty-three students had no BCG scar, 62 had one scar, 71 had two scars, and 42 had three scars. The mean age for each group was 19 yr. All students were healthy and had no known exposure to tuberculosis or history of tuberculosis or other mycobacterioses. The size in millimeters of induration of the first tuberculin reaction (PPD1) was clearly correlated with the number of BCG scars: 2.3 +/- 4.6 for no scars; 6.7 +/- 6.7 for one scar; 10.9 +/- 5.9 for two scars, and 13.2 +/- 5.3 for three scars. The second tuberculin reaction (PPD2), performed 2 wk later on the contralateral forearm, showed a marked increase in reactivity. The increase in reaction size was most evident in students who had BCG scars but who were initially PPD negative (less than 10 mm). Smaller increases were observed in students without BCG scars, and also in those who had BCG scars but who were initially tuberculin positive (greater than or equal to 10 mm). The persistence of the booster effect was evaluated by performing PPD3 1 yr later. PPD1-negative students with BCG scars maintained the increased level of reactivity to PPD2 after 1 yr. An immunizing effect of tuberculin testing was suggested in 11 nonimmunized students who were initially PPD negative.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristics of children with positive tuberculin skin test

The aim of the study was to define the characteristics of children with latent tuberculosis diagnosed with positive tuberculin skin test (TST) and evaluate potential risk factors in children with positive TST. Children followed with the diagnosis of latent tuberculosis infection were included in the study retrospectively. Demographic characteristics of patients including history of atopy, respiratory infections, family history of tuberculosis and atopy, number of BCG vaccinations, findings of physical examination and laboratory data were extracted from patient's file. Eighty-one children (51 male, 30 female) who had positive TST were retrospectively evaluated in the study. Mean age of the patients was 8.00 ± 4.00 years. Only 13 (16%) of the children had contact with a case who had active tuberculosis. It was shown that the age of the patients, number of BCG scars and BCG vaccination significantly affected TST reaction size. TST size was not affected with time passed after last dose of BCG vaccination, family history of tuberculosis, presence of TST positive case in the family, exposure to cigarette smoke, number of household family members and presence of respiratory allergic disease. The patient's age, numbers of BCG vaccination and BCG scars significantly affect TST results in childhood. This may cause difficulty in diagnosing latent tuberculosis infection and in decision of initiating prophylactic treatment. The results of this study may show that recently developed, more accurate and convenient in vitro tests that they have higher costs and require sophisticated laboratory, can be used to diagnose latent tuberculosis.     

Comparison of tuberculin skin testing and QuantiFERON-TB Gold-In Tube test in health care workers

The purpose of this prospective, cross-sectional observational study was to compare the tuberculin skin testing (TST) with QuantiFERON-TB Gold-In Tube (QTF-GIT) for the detection of latent tuberculosis infection in healthcare workers (HCWs). The study included 78 volunteers who are HCWs at the same tertiary care teaching hospital for chest diseases and tuberculosis. Participants with active tuberculosis, immunodefficiency or malnutrition were not included. The TST was administered by the Mantoux method. Peptides representing ESAT-6, CFP-10 and TB7-7 were used as TB-specific antigens in the whole-blood Interferon-gamma (IFN-g) assay (QTF-GIT). There was a statistically significant relation between the number of Bacillus Calmette-Guerin (BCG) scars and the diameter of TST (p< 0.01). QTF results according to previous BCG vaccinations did not significantly differ (p> 0.05). There was an intermediate concordance between two tests (k: 0.346). QTF-GIT has a sensitivity of 56.14% (both TST and QTF-GIT are positive), specificity of 90.48% (both TST and QTF-GIT are negative); positive predictive value of 94.12% and negative predictive value of 43.18% and accuracy is 65.38%. There was a statistically significant relation between TST diameter and QTF result (p< 0.01). Latent tuberculosis infection prevalance of our study population was 43% according to QTF-GIT test, 73% according to TST and BCG vaccination rate was 87%. In conclusion, TST is affected by previous BCG vaccinations, QTF-GIT is not. We can recommend QTF-GIT test for the detection of latent tuberculosis infection as an alternative to TST in populations with routine BCG vaccination programme.     

Analysis of tuberculin reaction of tuberculous children below 4 years of age]

To clarify whether the size of tuberculin reaction could be used as an useful index of the severity of tuberculosis, we analyzed the sizes of tuberculin reaction (TR) of 60 children below 4 years of age with active tuberculosis at the time of diagnosis. Of 60 patients, 53 (88.9%) had positive reactions to tuberculin. The mean size of TR of 60 patients was 24.0 +/- 13.9 mm and maximum size was 60 mm. Seven patients who had no reaction to the tuberculin skin test consisted of three primary complex and four serious tuberculosis (two miliary tuberculosis and two tuberculous meningitis). The patients without BCG vaccination showed significantly smaller TR than the patients with BCG vaccination (p < 0.05). The patients less than 1 year of age showed significantly smaller TR than the patients of 4 years of age (p < 0.05). The patients with serious tuberculosis showed significantly smaller TR than the patients with primary complex (p < 0.05). Of patients with primary complex, there were no difference of the size of TR between the patients with pulmonary tuberculosis (III) and hilar lymphadenopathy (H). Together with, it did not necessarily mean that negative TR showed no infection with tuberculosis and the sizes of TR depended on the severity of tuberculosis in infantis and young children.     

The tuberculin skin test in relation to immunological in vitro reactions in BCG-vaccinated healthcare workers.

The aim was to study the tuberculin skin test in relation to immunological in vitro reactions in bacille Calmette-Guerin (BCG)-vaccinated healthcare workers. The present study was performed in Sweden, a country with a low incidence of tuberculosis, a high BCG vaccination efficacy and high tuberculin conversion rates. BCG-vaccinated healthcare workers (n=381) were tuberculin skin tested. From these, 11 subjects with negative tuberculin reactions (<6 mm) were matched for age and sex with 11 subjects with large positive reactions (> or = 15 mm). Lymphocyte transformation and the production of interferon-gamma (IFN-gamma) were analysed after stimulation in vitro of peripheral blood mononuclear cells with tuberculin purified protein derivative, heat-killed tubercle bacilli and a culture filtrate from tubercle bacilli. In the tuberculin-positive group the lymphocyte transformation response was 2-3 times larger, and IFN-gamma production was 7-10 times larger, than in the tuberculin-negative group (p<0.001). The present results suggest that a positive tuberculin skin test in bacille Calmette-Guerin-vaccinated subjects indicates a stronger immune response of the protective T-helper 1-type than does a negative test. In similar settings, the study supports the traditional practice of regarding the tuberculin skin test in bacille Calmette-Guerin-vaccinated subjects as an indicator of a protective immune response against tuberculosis.     

Contact tracing using a new T-cell-based test: better correlation with tuberculosis exposure than the tuberculin skin test.

SETTING: Residential institution for alcoholics in Switzerland. OBJECTIVE: To compare the results of the tuberculin skin test (TST) and the new T-cell-based test for tuberculosis infection (T-SPOT.TB) in subjects exposed to a case of smear-positive pulmonary TB (PTB). DESIGN: After the notification of smear-positive PTB in a resident of an institution for alcoholics, contacts underwent TST and determination of Mycobacterium tuberculosis specific T-cells in blood by T-SPOT.TB. Results were analysed according to age, history of BCG vaccination, and level of exposure to the index case. RESULTS: There was no correlation between the level of exposure and the TST results, but the T-SPOT.TB results were significantly correlated with the level of exposure (P = 0.029, OR 5.00, 95%CI 1.05-23.86). Contacts who had been previously BCG-vaccinated were significantly more likely to have a positive TST than unvaccinated contacts (52% vs. 0%, P = 0.0003), but there was no influence of prior BCG vaccination on T-SPOT.TB results. CONCLUSIONS: T-SPOT.TB test results correlated better than TST with level of exposure to M. tuberculosis and were not confounded by prior BCG vaccination. This test allows better selection of contacts who should receive treatment for latent TB infection.     

Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test.

Bacille Calmette-Guérin (BCG) vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection (LTBI). The TST was compared with a Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot (ELISPOT) assay during an outbreak of MTB infection at a police academy in Germany. Participants were grouped according to their risk of LTBI in close (n = 36) or occasional (n = 333) contacts to the index case. For the TST, the positive response rate was 53% (19 out of 36) among close and 16% (52 out of 333) among occasional contacts. In total, 56 TST-positive contacts (56 out of 71 = 78.9%) and 27 TST-negative controls (27 out of 298 = 9.1%) underwent ELISPOT testing. The odds ratio (OR) of a positive test result across the two groups was 29.2 (95% confidence interval (CI) 3.5-245.0) for the ELISPOT and 19.7 (95% CI 2.0-190.2) for the TST with a 5 mm cut-off. Of 369 contacts, 158 (42.8%) had previously received BCG vaccination. The overall agreement between the TST and the ELISPOT was low, and positive TST reactions were confounded by BCG vaccination (OR 4.8 (95% CI 1.3-18.0)). In contrast, use of a 10-mm induration cut-off for the TST among occasional contacts showed strong agreement between TST and ELISPOT in nonvaccinated persons. In bacille Calmette-Guérin-vaccinated individuals, the Mycobacterium tuberculosis-specific enzyme-linked immunospot assay is a better indicator for the risk of latent tuberculosis infection than the tuberculin skin test.     

Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts

The tuberculin skin test used to detect latent Mycobacterium tuberculosis infection has many drawbacks, and a new diagnostic test for latent tuberculosis (QuantiFERON-TB [QTF-TB]) has recently been introduced. This test measures the production of IFN-gamma in whole blood upon stimulation with purified protein derivative (PPD). The QTF-TB test addresses the operational problems with the tuberculin skin test, but, as the test is based on PPD, it still has a low specificity in populations vaccinated with the Bacille Calmette-Guérin (BCG) vaccine. We have modified the test to include the antigens ESAT-6 and CFP-10, which are not present in BCG vaccine strains or the vast majority of nontuberculous mycobacteria. This test was used to detect infection in contacts in a tuberculosis outbreak at a Danish high school. The majority of the contacts were BCG-unvaccinated, which allowed a direct comparison of the skin test and the novel blood test in individuals whose skin test was not confounded by vaccination. An excellent agreement between the two tests was found (94%, kappa value 0.866), and in contrast to the blood test based on PPD, the novel blood test was not influenced by the vaccination status of the subjects tested.     

Two-step tuberculin skin testing in our hospital employees

To evaluate the baseline values of tuberculin reaction, two-step tuberculin skin testing was carried out in 365 employees of our hospital. We defined strongly response group when the size of erythema showed more than 30 mm or who showed strongly positive reaction. Two-step tuberculin skin testing was carried out in 165 hospital employees excluding those who were defined as the strongly response group in the first testing. 80 hospital employees (48.5%) became strongly response group by the second tuberculin skin testing. Altogether, 76.7% of all employees were strongly response group either by the first time or the second tuberculin skin testing. The size of erythema and that of induration showed 13.2 +/- 12.6 mm (mean +/- SD), 6.9 +/- 9.2 mm increase, respectively, in the two-step tuberculin skin testing, so-called Booster phenomenon. We could not know the true tuberculin reaction status by the single tuberculin skin testing. Therefore, two-step tuberculin skin testing is important as one of an infection prevention countermeasures in the hospital workers.     

Tuberculosis vaccination versus isoniazid preventive therapy: a decision analysis to determine the preferred strategy of tuberculosis prevention in HIV-infected adults in the developing world.

SETTING: The developing world. OBJECTIVE: To compare the strategy of TB vaccination with that of tuberculin skin-testing in conjunction with isoniazid (INH) in preventing tuberculosis in HIV-infected persons. For any clinical scenarios in which immunization would be more effective than INH preventive therapy, to determine the minimum necessary vaccine safety and effectiveness required. DESIGN: Decision analysis. A hypothetical cohort of 10000 HIV-infected persons, 65% of whom were tuberculin positive, living in the developing world, was studied. Probability estimates were based on BCG vaccine for the baseline analysis, and it was assumed that the vaccine cannot protect if given after infection. RESULTS: Under the probability estimates and assumptions of the analysis, tuberculin skin testing/INH preventive therapy would prevent 458 more cases of TB and 45 more deaths due to TB than TB vaccination. One- and two-way sensitivity analyses revealed no thresholds at which TB vaccination would be the preferred strategy. Vaccine safety did not impact the outcome of the analysis. Three-way sensitivity analysis revealed that if the prevalence of anergy were 35% and the risk of progression to active TB among anergic persons 12.2 cases per 100 person-years, a vaccine would have to be at least 87% effective to be preferred over INH preventive therapy. CONCLUSIONS: Under the conditions of the analysis, which did not account for cost or logistics, tuberculin skin testing/INH preventive therapy would be more effective than TB vaccination in preventing TB among HIV-infected persons. The hypothesized TB vaccine would prevent more TB than INH preventive therapy only in areas where the prevalence of anergy and risk of active TB if anergic were high, and vaccine effectiveness exceeded 87%.