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[Koch's phenomenon after BCG vaccination and the two-step tuberculin test in elementary school children].

In Japan, BCG vaccination, which covers more than 90% of infants, has been given according to the national immunization policy. Moreover, first-grade children in elementary school are screened with tuberculin skin test, and those who show negative reaction in the Japanese standard, i.e. size of erythema less than 10 mm, are re-vaccinated with BCG according to the Tuberculosis Prevention Law. However, since the incidence of tuberculosis among children below age 14 is as low as 1.5/100,000 in Japan, it is time to reconsider the BCG vaccination policy. As the first step to assess the efficiency of the present program, we observed the occurrence of Koch's phenomenon after BCG vaccination in elementary school children in Chiba City in 1995 and 1996, and we introduced the two-step tuberculin test to elementary school children in 1997. Among 180 BCG vaccinated children in 1995 and 1996, 168 (93.3%) had been vaccinated by 4-year of age. We could follow local reaction of BCG re-vaccination and observed Koch's phenomenon in 117 (69.6%, 95% C.I. of 62.7-76.6%). Among 92 tuberculin negative children in 1997, 85 (92.4%) had been vaccinated by 4-year of age. In the two-step tuberculin test program of 85 initial negative-reactors, 63 (74.1%, 95% C.I. of 64.8-83.4%) turned to positive by the second test. Those results suggest that more than 69% of tuberculin-negative school children who were vaccinated previously maintained immunity with BCG. Our studies raised a problem of the current BCG re-vaccination policy that depends on the result of tuberculin test. Due to the discrepancy between tuberculin allergy and immunity in tuberculosis, many school children may be given BCG vaccination unnecessarily. Taking into consideration the incidence of tuberculosis in children, discontinuation of BCG re-vaccination policy at elementary school entrance should be considered.

BCG Vaccine↗

The effect of Johne's vaccination on tuberculin testing in farmed red deer (Cervus elaphus).

AIM: To assess the degree of interference with bovine tuberculin testing in farmed red deer that vaccination of young deer with an oil-adjuvanted vs aqueous formulation of live attenuated Mycobacterium paratuberculosis Strain 316F vaccines would be likely to cause, and to compare immunological responses between vaccine formulations. METHODS: Five-month-old red deer (n = 45) were randomly allocated to three treatment groups of 15 animals, which received either no vaccine, a single 2-ml dose of an oil-adjuvanted formulation or two 2-ml doses, 6 weeks apart, of an aqueous formulation of live attenuated M. paratuberculosis Strain 316F vaccine injected subcutaneously (S/C) in the neck (Control, Oil-adjuvant Ptb, and Aqueous Ptb groups, respectively). Injection- site reactions were described and measured on Weeks 3, 6 and 9. Animals were weighed and lymphocyte transformation tests (LTT) and antibody enzyme-linked immunosorbent assays (ELISA) using avian, bovine and Johnin tuberculin were conducted on blood samples collected at Weeks 0, 6, 12, 15, 24, 27, 36 and 39. A bovine mid-cervical skin test (MCT) was applied at Week 12, and comparative cervical skin tests (CCTs) at Weeks 24 and 36. At Week 42, the animals were slaughtered at a commercial deer slaughter premises and subjected to rigorous meat inspection. RESULTS: Two animals were eliminated at the start of the trial due to a positive cross-reaction with bovine tuberculin in the initial LTT. Almost all animals reacted to the MCT at Week 12, with mean skin thicknesses of 3.9, 2.9 and 1.0 mm for the Oil-adjuvant Ptb, Aqueous Ptb and Control groups, respectively. When the CCT was conducted at Week 24, 2/15 Oil-adjuvant Ptb, 2/14 Aqueous Ptb and 1/14 Control animals were classified as CCT-positive to bovine tuberculin. By Week 36, all animals were CCT-negative. The Oil-adjuvant Ptb vaccination resulted in high persistent levels of antibody that reacted with bovine tuberculin, compared with negligible levels in the Aqueous Ptb group. Overall, a single dose of the Oil-adjuvant Ptb vaccine in deer stimulated a vigorous, cross-reactive immune response, evidenced by high LTT, skin-test and antibody reactions to bovine tuberculin, with both cell-mediated and humoral characteristics. By comparison, two doses of the Aqueous Ptb vaccine produced less cross-reactivity and a bias towards a cell-mediated response. The Oil-adjuvant Ptb vaccine resulted in moderate injection site lesions that were quite persistent, whereas the Aqueous Ptb vaccine resulted in smaller nodules that regressed more quickly. CONCLUSIONS: Vaccination of farmed deer with an oil-adjuvanted Johne's vaccine has the potential to cause significant interference with routine tuberculin skin testing. The cross-reactivity should decline with time and the CCT should be able to clear MCT-positives, but there is a risk of false-positives to the blood test for tuberculosis (BTB), due to high persistent levels of antibody. The CCT could be used as a primary skin test in vaccinated deer on some farms. The Aqueous Ptb caused fewer problems with skin testing and produced significantly less bovine antibody than the Oil-adjuvant Ptb, but stimulated persistent cell-mediated immune responses that may provide some protection against Johne's disease.

Animals↗

[Tuberculin test in diabetic patients in a health center].

OBJECTIVES: To determine the frequency of Tuberculin positives in the diabetic population attending our Health Centre, with readings at three and seven days. Of less importance, to assess how often patients present conversion after a second Tuberculin test, seven days after the first; and to determine the frequency of Tuberculin positives in diabetics in relation to whether they are over or under 65. DESIGN: A transversal observational study. SETTING: Pío XII Health Centre, Ciudad Real. PARTICIPANTS: Patients registered as diabetic in the eight General Medicine clinics and who attended for the customary check-ups. MEASUREMENTS AND RESULTS: PPD was administered to 163 diabetics and the test was read at three and seven days; if this last reading was negative, a second test was carried out and evaluated at three days. At three days 42.2% were positive; at seven, there was an increase of 6.5% of the total. A second test was performed on 78 patients, which provided an increase in patients with tuberculous infection of 7.14% of the total. There was a statistically significant relationship (p < 0.001) between the positive responses of the first Mantoux and age. CONCLUSIONS: There is a high prevalence of Tuberculin positive patients, which increases when another reading is done seven days after the Mantoux; as it does after a second test, by which a retreat in these patients' response to Tuberculin was observed.

Adult↗

Two-step tuberculin testing in a veterans domiciliary population.

Seven hundred ninety-six veterans were scheduled for tuberculin testing during a hospital/domiciliary employee health program in southern Ohio. The Mantoux test, using 5 TU of commercial purified protein derivative (PPD) was used. Nonsignificant reactors were retested at one week to detect and quantitate the "booster phenomenon," following Centers for Disease Control (CDC) recommendations. Cost data were recorded. The initial frequency of 39.3% reactions greater than 10 mm in 740 tested subjects increased to 46.7% on two-step testing. Fifty-five of 414 subjects exhibited the booster effect, a rate intermediate between that reported in Alabama and no boosting reported in Rochester, New York. Costs of two-step testing exceeded, by a small margin, estimated costs of isoniazid preventive therapy for apparent converters detected by two-step testing.

Adult↗

[Observation of the effect of PSTF oral liquor on the positive tuberculin test reaction].

The transfer factor is a medicine used for immunotherapy. It is mainly administered by injection. In this paper, the effect of PSTF oral liquor on immunity has been examined. Persons who have negative TB reaction were selected as the test sample. PSTF was taken orally for 4 weeks. Then the tuberculin test was done again. The test results indicated that in the test group the number of people who had a positive reaction and the size of the scleroma were obviously higher than those in the control group (P < 0.01, P < 0.001). In the test group with or without BCG vaccine scar, the ratio of positive reaction was higher than that in the control group (P < 0.05, P < 0.1). Within the test group the ratio of positive reaction in those with no scar did not differ from that in subjects without such scars (P > 0.05), so patients who have negative tuberculin reaction will have a higher ratio of positive reaction after taking PSTF orally for 4 weeks. This increased ratio can reach 53.33%. Thus, we conclude that the oral liquor is convenient and easily acceptable especially for the aged and children.

Administration, Oral↗

Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society.

This statement provides new recommendations for targeted tuberculin testing and treatment regimens for persons with latent tuberculosis infection (LTBI) and updates previously published guidelines (1,2). This statement is issued in recognition of the importance of these activities as an essential component of the TB Elimination Strategy promoted by the U.S. Public Health Service Advisory Council on the Elimination of Tuberculosis, and reports the deliberations of expert consultants convened by the American Thoracic Society (ATS) and Centers for Disease Control and Prevention (CDC). Isoniazid for 6-12 mo has been the mainstay of treatment for LTBI in the United States for more than 30 yr. However, the application of isoniazid for LTBI has been limited because of poor adherence, due to the relatively long duration of treatment required, and because of concerns about toxicity. Therefore, there has been interest in the development of shorter, rifampin-based regimens as alternatives to isoniazid for the treatment of LTBI. During the past decade, a series of studies of "short-course" treatment of LTBI in persons with human immunodeficiency virus (HIV) infection has been undertaken. The results of these trials have recently become available, and the in-depth analyses of these and prior studies of isoniazid form the scientific basis of the treatment guidelines presented in this report. In addition, many changes to previous recommendations regarding testing for and treatment of LTBI are presented (Table 1).

Antitubercular Agents↗

Tuberculin testing in residential homes for the elderly.

BACKGROUND: Evidence from the United States has shown that tuberculin sensitivity increases with length of stay among residents in homes for the elderly, implying an increasing risk of infection. There is no evidence as to whether or not residents in homes in the United Kingdom have a similar risk. METHODS: A study was undertaken to determine whether residence in a home for the elderly increases the risk of tuberculosis infection. Over a six month period all residents in homes for the elderly in Liverpool received a tuberculin test. A health questionnaire was completed by the field team for each resident. A total of 2665 residents in homes for the elderly were surveyed. RESULTS: Heaf test grade positivity declined with age, the odds ratio being 0.71 for each 10 year period. Adjusting for age, there was no change in Heaf test grade with length of stay in the home. Heaf test positivity was stronger in smokers (odds ratio 1.59) than ex-smokers (odds ratio 1.20) and non-smokers. Heaf test grade positivity was directly related to pack years. Allowing for age and smoking, the odds ratio for men compared with women for a positive test was 1.62 (95% confidence interval 1.32 to 1.99). CONCLUSIONS: Heaf test positivity declines with age. Residence in a home for the elderly is not associated with increased rate of tuberculosis sensitivity. Smoking and male gender is associated with increased Heaf test positivity.

Adult↗

Comparison of Mantoux, tine, and 'Imotest' tuberculin tests.

In a study designed to compare the Mantoux with the tine and 'Imotest' multiple-puncture tuberculin tests 200 subjects underwent a Mantoux test (10 IU PPD-Weybridge) and, simultaneously, either a tine test or an imotest. All tests were read after 72 h by two observers independently. The false-negative rate for the Mantoux was estimated by immediate repetition of the Mantoux in subjects with an initially negative Mantoux but positive multiple-puncture test. When the criterion for a positive reaction was at least 5 mm of induration for the Mantoux and at least 2 mm of induration for the multiple-puncture tests, the false-negative rate of 27% for the imotest was significantly higher than the 4% for the tine and 5% for the Mantoux (p less than 0.001 in each case). Positive multiple-puncture tests were always associated with a Mantoux test that was positive on either the first or second application. Observers agreed in their interpretation of 98% of all tests, and there were no significant differences between testers in frequency of false-negative results for any test. The tine test, when carefully applied and correctly interpreted, gives results which correlate well with those given by the standard Mantoux test. The imotest is less reliable and has no advantages over the tine test.

Clinical Trials as Topic↗

[Indications for, and the significance of, the tuberculin test in the Netherlands].

The almost 100-year-old tuberculin skin test still is the gold standard for diagnosing Mycobacterium tuberculosis infection. The sensitivity of this test with the usual cut-off values is high, but may be decreased with impaired cellular immunity and at older age. The specificity is primarily determined by cross-reactivity to atypical mycobacterial infections and vaccination with Bacillus Calmette-Guérin (BCG). Positivity of the skin test after BCG vaccination decreases with time after vaccination and depends on the age when vaccinated. The tuberculin reaction can be boosted by repeated tuberculin skin tests over a short time period, whereby the anamnestic immune response is stimulated. This boosting phenomenon occurs mostly with atypical mycobacterial infections, after BCG vaccination and at older age. Interpretation of the tuberculin skin test depends on the indication for the test, the expected risk of latent tuberculosis infection, higher prevalence of 'old' tuberculosis in elderly Dutch people and immigrants, BCG vaccination status and, if a baseline value is available, the boosting phenomenon. Its role in the diagnosis of tuberculosis is limited.

BCG Vaccine↗

EVIDENCE IN FAVOUR OF A LOW DOSE FOR THE TUBERCULIN TEST.

In an attempt to solve the problem of whether a high or a low dose should be used for tuberculin testing a new method of statistical analysis is presented. It consists in tabulating the frequency of tuberculin "positive" children in households where the adults are tuberculin "positive" and tuberculin "negative" respectively; these frequencies are compiled for a wide range of arbitrarily chosen limits between "positive" and "negative" reactions. Values for these statistics have been obtained from data collected in Kenya; they strongly suggest that the reactors to the low-dose test are those infected with tubercle bacilli and the non-reactors to this test are the uninfected. However, a more detailed analysis is possible and this paper demonstrates that statistics of the type described may be used for testing the plausibility of a specific hypothesis about the patterns of tuberculin reactions among infected and uninfected persons. By testing a number of different hypotheses, the most plausible was found to be that the tuberculin sensitivities of infected and uninfected persons correspond to those of the reactors and the non-reactors to the low-dose test respectively. On the basis of the data presented it thus appears that the low-dose test is better suited than the high-dose test for distinguishing between infected and uninfected persons.

Adult↗