CERTAIN characteristics of BCG-induced tuberculin sensitivity

Post-vaccination tuberculin sensitivity is being used to evaluate the immediate effects of the extensive WHO/UNICEF mass BCG vaccination programmes currently in progress. During the past five years the Tuberculosis Research Office has been studying the tuberculin sensitivity produced by BCG vaccination, and the present paper discusses some of the most important characteristics of BCG-induced allergy. The material for the paper was drawn from the results in five countries of vaccinating more than 6,000 schoolchildren and retesting them at one or more intervals after vaccination.Tuberculin sensitivity produced by BCG is not the kind of response that may logically be described as "positive" or "negative". Rather, vaccination always produces, or increases, sensitivity to tuberculin, although, with some vaccines and in some persons, the degree of sensitivity produced may be low. BCG-induced allergy can best be described by the distribution of the sizes of the tuberculin reactions and summarized by the mean and standard deviation of the distribution. The common practice of classifying post-vaccination reactions as "positive" or "negative" is biologically meaningless and may be the cause of many fallacious notions about the allergy produced by BCG.The degree of post-vaccination allergy varies with the potency of the vaccine used: a potent vaccine has been shown to produce allergy about as strong as that produced by natural infection wherever carefully controlled studies have been made. No evidence was found that allergy wanes or is lost after intradermal vaccination: the impression that it does so may often have been the consequence of the practice of revaccination and of ignoring the influence of experimental error. Unless very weak vaccines are used, there is no indication that superinfection can be identified after vaccination. The diagnostic value of the tuberculin test is thus being destroyed in many places where mass campaigns are being done, particularly in those places where a high degree of tuberculin sensitivity is being produced.     

Enhancing of tuberculin allergy by previous tuberculin testing

A controlled study on the enhancing of tuberculin allergy by one or more earlier tuberculin tests was carried out in a previously untested and unvaccinated population, in an area where the prevalence of non-specific allergy was known to be high. The results have shown that a test with 1 TU of PPD RT 23 in Tween 80 diluent causes subsequent tests to elicit significantly larger reactions. This enhancing effect is more marked among those with initial reactions of 8-13 mm to 1 TU or 10 mm and more to 20 TU. There is practically no enhancement among those whose reactions to 20 TU measure 0-4 mm or even 0-9 mm. Even in the group with reactions of 10 mm and more to 20 TU only some individuals show evidence of enhancement. The enhancing of allergy increases with age.     

The effect of Tween 80 on intradermal tuberculin reactions

Since 1958, the tuberculin dilutions used in WHO-assisted tuberculosis programmes have been stabilized with the detergent Tween 80, in order to prevent adsorption of tuberculin to the inner surface of the container. However, the reactions to tuberculin with Tween 80 tend to be somewhat softer than those to ordinary tuberculin, for a given size; and, moreover, the curves for the frequency distribution, by size, of the reactions to tuberculin with Tween 80 tend to have a somewhat different shape from those of the reactions to ordinary tuberculin, intermediate-sized reactions (5-10 mm) being less frequent in a given population when Tween tuberculin is used.     

Tuberculin intradermal reaction (IDR) or tuberculin test

Tuberculinic switch is defined as an increase of the intradermal reaction diameter in two tests carried out within three months of each other. The tuberculinic skin reaction proves the presence of a delayed hypersensitivity induced by mycobacterial antigens (Mycobacterium tuberculosis, BCG, some atypical mycobacteria). However, this reaction does not always prove an effective protection against the BK. The intradermal injection of a purified Purified Protein Derivative (PPD) resulting from a culture of M. tuberculosis is the only method validated for the diagnosis of tuberculosis infection (latent infection) and screening for hypersensitivity and post-vaccine BCG (Official French decree No 96-775 of September 5, 1996 and its decree relating to vaccination by BCG and tuberculin tests). The guidelines concerning tuberculin testing are: investigating on a case of tuberculosis; tracking or surveillance of people frequently exposed to tuberculosis (examination on recruitment and follow-up of exposed professionals); prevaccine testing in children over four weeks of age.     

Lack of correlation between BCG-induced tuberculin skin test sensitisation and protective immunity in cattle

Vaccination of cattle with Mycobacterium bovis Bacille Calmette-Guérin (BCG) can provide significant protection against bovine tuberculosis (TB). However, BCG vaccination sensitises animals to respond to the tuberculin skin-test. This provides a potential operational impediment to the use of BCG as a cattle vaccine since the tuberculin skin-test is the primary surveillance tool used by many countries with ‘test and slaughter’ control strategies. Currently, it is also unclear what BCG-induced skin-test conversion means in respects to BCG's protective immunity. In the current study we first investigated the duration of tuberculin skin-test sensitisation in calves neonatally vaccinated with BCG. BCG vaccination induced strong skin-test responses in calves during their first 6 months. However, a rapid decay in skin-test sensitivity was observed after this time. Between 6 and 9 months this represented a reduction from 80% to 8% of calves providing a positive response in the single intradermal comparative cervical tuberculin test at standard interpretation. We next investigated the relationship between BCG induced skin-test sensitivity and retention of protective immunity. Calves were neonatally vaccinated with BCG and subsequently divided into 2 groups based on retention or loss of tuberculin skin-test responses after 6 months. In contrast to their skin-test responsiveness, these vaccinates maintained their tuberculin specific IFN-γ blood responses. Moreover, irrespective of their pre-challenge skin-test responses, following M. bovis challenge both groups of BCG vaccinated calves demonstrated comparable levels of protection, as evidenced by reduced TB-associated pathology. Therefore, we have demonstrated that following neonatal BCG vaccination of cattle, tuberculin skin-test responder frequencies waned rapidly after 6 months but importantly, loss of skin-test sensitivity did not correlate with loss of protective immunity. These findings could have implications for the practical application of BCG based cattle vaccines.     

THE 5 TU versus the 10 TU intradermal tuberculin test

With the growing demand in practical tuberculin-testing work for an effective single-dose intradermal test to replace the serial-dose procedures, the 5 TU and 10 TU doses have both been used for single-dose tests in recent years. The present study was undertaken for the purpose of determining the difference in the effects of these two doses.The material was collected by testing large general population groups participating in the Danish mass campaign in two areas in Jutland; 5 TU and 10 TU were given to alternate persons. Results are presented for 3,764 adults, none of whom gave a history of previous BCG vaccination.With either dose, the population groups were clearly separated into two groups, reactors and non-reactors. The average diameter of reactions for 10 TU was larger by about 2-3 mm than for 5 TU, and the frequency of bullous reactions was only slightly greater with the stronger dose.The two known sources of tuberculin sensitivity in Denmark, apart from BCG, are infection with human and with bovine tubercle bacilli. As both appear to result in a degree of sensitivity demonstrated about equally well with either 5 TU or 10 TU, either dose would seem to be suitable as a single-dose test for tuberculin-testing surveys in similar general populations.     

Influence of isoniazid on naturally acquired tuberculin allergy and on induction of allergy by BCG vaccination

Previous studies on the influence of isoniazid on the size of the tuberculin reaction have given conflicting results. A controlled study in an area with high prevalence of low-grade allergy has been carried out by the administration of isoniazid or placebo tablets. For those not vaccinated with BCG, isoniazid in a single daily dose of 5 mg/kg body-weight tended to reduce somewhat the size of the tuberculin reaction among those with reactions of 12 mm or more at the initial tuberculin test.     

BCG-induced allergy and immunity in guinea-pigs during the first year after vaccination

It has been traditional practice in many countries to let revaccination with BCG depend on the outcome of periodically repeated tuberculin testing. Acquired resistance to tuberculosis and tuberculin skin sensitivity are concomitant results of BCG vaccination, and it is apparently inferred that a waning resistance will be faithfully reflected in a waning tuberculin sensitivity. However, it has been demonstrated in recent years, both in man and in animals, that the waning of tuberculin sensitivity may be prevented merely by a repetition of the tuberculin test, while data presented in this and a following report indicate that tuberculin testing has no such influence on the course of BCG-induced resistance to tuberculosis.     

控制抗菌药物皮内过敏试验假阳性的方法研究

目的分析抗菌药物皮内过敏试验假阳性率高的原因,探索解决方法。方法细化抗菌药物皮内过敏试验操作流程和结果判断方法,对护士进行集中理论培训、操作示教和跟班带教,严格控制判断抗菌药物阳性的标准和权限,总结分析应用此方法1年青霉素类和头孢类抗菌药物皮内过敏试验结果。结果 2008年2月-2009年2月头孢类抗菌药物皮内过敏试验阳性率为0.37%、青霉素类为0.11%,所有抗菌药物皮内过敏试验阴性患者均按规定用药,未发生急性药物过敏现象。结论应用该方法能有效控制抗菌药物皮内过敏试验假阳性率。     

REPEATED tuberculin tests in the same site

When the tuberculin-testing technique for the Tuberculosis Research Office field studies became so standardized that successive tests were being placed in about the same site on the forearm, there was a sudden and pronounced increase in the frequency of bullous reactions.Preliminary trials pointed to repeated testing in the same site as the most likely cause of this altered response to tuberculin. To obtain further information, a study was carried out on 356 mental patients, each receiving an initial test with 5 TU in one forearm and 3 months later two follow-up tests with 5 TU-one in the same site as the initial test and one in the corresponding site on the other forearm.This study shows that among tuberculin-sensitive persons the response to tuberculin injected into the site of a previous test differs both in size and in character from the response to tuberculin injected into an unused site. In the previously used sites the tuberculin reactions appear sooner and fade sooner than reactions in new sites; they attain greater maximum size and present a much higher frequency of bullae. Thus, the "used-site" phenomenon may cause practical problems in the interpretation of reactions in programmes involving periodic tuberculin-testing.     

Disposable tuberculin tests: available and needed. A review

The literature relating to the value of imotest and the tine test in comparison with the Mantoux test and the Heaf test is reviewed. The reports on the concordance of the results of Heaf and Mantoux tests are also considered. It is concluded that the tine test and the imotest have significant advantages in terms of safety so far as cross-infection risks are concerned. Large-scale multicentre trials to attain consensus on the interpretation of results from all four tests are suggested.     

The accuracy of tuberculin skin tests: self-assessment by adult outpatients

Tuberculin skin testing is an accurate, inexpensive screening procedure for detecting tuberculosis infection. The return visit needed to interpret the reaction is inconvenient, costly, and may contribute to under-utilization of the test. Although some clinicians ask patients to read their own purified protein derivative (PPD) test results, patient accuracy and the degree of teaching needed to learn this skill are unclear. This study evaluated the accuracy with which 145 outpatients read their own Mantoux skin test (PPD) reactions and reported by postcard after brief training by nurse practitioners. A total of 89 instructed patients returned postcards and also returned for clinician readings; 46 submitted postcards without returning; 7 returned but did not complete postcards; and 3 neither returned postcards nor returned for readings. Ten of 135 postcards were uninterpretable. For 81 subjects with both interpretable tuberculin self-assessment postcards and clinician readings, overall PPD classification agreement was 88 percent; Kappaw = +0.905 (P less than .001). Compared to clinician readings, 1 of 53 patients falsely reported a positive reaction (greater than or equal to 10 mm) and 2 of 25 patients falsely reported negative PPD readings (0-4 mm). There was 100 percent agreement between postcard readings and clinician classifications in a subgroup of patients (N = 26), prospectively identified by nurse practitioners as capable of accurate tuberculin self-assessment. Inter-clinician reading agreement (N = 37) was 89 percent; Kappaw = +0.943 (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)