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To determine the importance of the recall phenomenon ("booster effect") in chronically hospitalized patients, we performed three sequential tuberculin and Candida antigen skin tests in patients at two hospitals. Twenty of 162 patients (12.3%) demonstrated a significant reaction on the initial tuberculin test, and 9 additional patients (5.5%) showed a significant reaction (booster response) to a second tuberculin test administered 3 wk later. Five patients (3.1%) demonstrated a significant reaction only when a third tuberculin test was administered 6 wk after the initial test. Only 1 patient (0.6%) with a significant tuberculin reaction on the first 2 tests was nonreactive on the third test. Nineteen patients (11.7%) demonstrated a significant response to Candida antigen on the initial test and a booster effect was noted in 11 (6.2%) and 6 (3.7%) patients, respectively, on subsequent tests. Four patients (2.5%) appeared to lose reactivity to Candida antigen on each of the 2 repeat tests. Only 25% of patients who demonstrated a tuberculin booster response had a significant reaction to the initial Candida skin test. Serial skin tests may be necessary to reliably determine the ability of a chronically hospitalized patient to demonstrate a response to tuberculin.
SETTING: Some infants immunized with BCG in the newborn period fail to develop any measurable tuberculin reactivity despite a local reaction at the site of immunization. OBJECTIVE: We wished to determine the possibility of a genetic regulation of this phenomenon by comparing the tuberculin reactivity of BCG-immunized parents and siblings of infants who failed to respond to BCG, and of infants who developed tuberculin reactivity after immunization. DESIGN: We studied 65 parents and siblings of 33 nonresponder infants, and 35 parents and siblings of 14 infants who had developed tuberculin reactivity. Tuberculin reactivity was analyzed by multiple regression analysis considering the BCG immunization status of each individual, and the 2 groups were compared by analysis of covariance. RESULTS: 96 of these family members had one or more BCG scars. The percentages of tuberculin reactors and non-reactors among BCG-immunized family members of both index infant groups were not significantly different. CONCLUSION: These observations suggest that maturational differences among newborns, rather than genetic regulation, account for the lack of development of cellular immunity against tuberculin after BCG immunization in some infants.
We investigated reactivity to tuberculin in a group of 91 elderly subjects (65 years old and more) and in a control group of 53 younger subjects between 18 and 59 years old, by means of the tuberculin skin test (TST) and by an in vitro lymphocyte stimulation test (LST). The LST had been validated in preliminary tests to accurately reflect T cell reactivity towards tuberculin. We defined a LST with a stimulation index (SI) (ratio of the tuberculin stimulated cultures to the non-stimulated cultures) of 10 or more at a concentration of 0.4 microgram/ml as indicative for sensitisation to tuberculin. The correlation between TST and LST was r = 0.58 (p = 0.0001) in the elderly subjects and r = 0.64 (p = 0.0001) in the younger age group; age did not affect those correlations (p = 0.39). Of the subjects with initially negative TST, 44.4% (16 LST-positive and 16 LST-negative) reacted positive on TST as well as on LST after repeated testing. We conclude that (a) there is a statistically significant but rather weak correlation between in vivo and in vitro assays of cell-mediated immune response to tuberculin, (b) age did not influence this correlation, (c) the in vivo and in vitro tests give complementary information but cannot substitute for each other and (d) repeated TST can induce an immunological boosting phenomenon on TST as well as on LST.
This study confirms that repeated tuberculin testing may prevent waning of, or restore, tuberculin sensitivity in BCG-vaccinated schoolchildren, and demonstrates that tuberculin testing has this effect even if it is done relatively shortly after vaccination. Therefore the results of repeated tuberculin tests cannot reveal a possible waning of BCG-induced tuberculin sensitivity. This finding shows that a revaccination policy based on the waning of tuberculin sensitivity is not rational.
Evidence has been presented that the fever elicited by intravenous administration of old tuberculin (O.T.) in BCG-infected rabbits is a specific property of this hypersensitivity system and is probably not due to contamination of tuberculin with bacterial endotoxins. Daily injections of O.T. in sensitized animals resulted in a rapid tolerance to its pyrogenic effect. Tuberculin tolerance can be differentiated from that occurring with endotoxins and was invariably associated with the development of a negative skin test. The mechanism of this tolerance would thus appear to be desensitization. A circulating pyrogen found during tuberculin fever was indistinguishable in its biologic effects from endogenous pyrogens obtained in several other types of experimental fever. This material produced fevers in normal recipients and therefore may be clearly differentiated from O.T. itself which was pyrogenic only to sensitized animals. Since the titer of serum pyrogen was directly proportional to the degree of fever induced by injection of O.T. in the donor animals, a causal relation is suggested. On the basis of these findings, it is postulated that tuberculin fever is due to a circulating endogenous pyrogen released by a specific action of O.T. on sensitized cells of the host.
The dried tuberculin coatings of the tines of multiple puncture disposable tests have been found to vary in thickness and distribution. Tines which are thinly and uniformly coated at their distal 0.6-0.8 mm produce consistent responses in tuberculin positive subjects. Where the tuberculin coating is thickened and retracted from the tips, a significant number of negative responses occur in tuberculin positive subjects. Observations of tines under an electron microscope after application have shown loss of tuberculin coating from the distal 0.6-0.8 mm only. Application of tines through Indian ink placed on the skin of cadavers has confirmed that times penetrate the dermis to a maximum depth of 0.6 mm.
Tuberculin purified protein derivative (PPD) obtained from the filtrate of Mycobacterium tuberculosis was hydrolysed with proteinase, trypsin, or chymotrypsin. Each hydrolysate consisted of a tuberculin peptides mixture (TPM). From each TPM 16 fractions were obtained by ion-exchange chromatography on Dowex 50W-X8 but only one fraction was isolated from each of the 16 fractions which showed tuberculin activity in guinea pigs sensitized with M. bovis (bcg) or M. tuberculosis. This fraction was designated "purified tuberculin peptide" (PTP). The PTP fraction from the proteinase hydrolysate (PTP-proteinase) was rechromatographed on Dowex 1-X2 and two tuberculin peptide fractions having molecular weights of 3200 and 12,000 were isolated. The potency of these two fractions was assessed in guinea pigs sensitized with M. bovis (BCG) and with M. tuberculosis and they were approximately 4 to 7 times more potent than either the international standaCG and of at least equal potency to either PPD-S or Connaught PPD in guinea pigs sensitized with either M. kansasii, M. scrofulaceum, M. intracellulare, or M. avium whereas very little if any cross-reactivity was elicited by these two fractions. This lack of response indicates that either fraction could be used as an aid to differentiate between sensitization due to M. tuberculosis or M. bovis and sensitization attributed to other mycobacteria.
Multiple puncture dried tuberculin tests compare favourably with the standard Mantoux test provided the tips of the metal prongs are thinly and uniformly coated with tuberculin. Unfortunately, surface tension, varying viscosity of the acacia solutions, and deeper dipping depths lead to increased quantities of tuberculin materials adhering to the metal prongs which results in thickening and retraction of the materials on the metal. Solutions of tuberculin in buffered phosphate produce thin and uniform coatings provided adequate cleaning of the metal--especially degreasing--is carried out. In the absence of this the coating layer may fragment. However, provided the distal 0.6-0.8 mm is covered, sufficient tuberculin will be deposited intradermally.
Detection of latent tuberculosis infection is an important step in the control of tuberculosis. The tuberculin skin test is the only proven method for identifying tuberculosis infection in patients who do not have tuberculosis disease. The prevalence of tuberculosis infection among hospitalized patients in a pneumological department of an inner-city hospital was evaluated, using the intradermal tuberculin skin test (Mantoux technique). Interpretation of the Mantoux test was based on the size of induration in millimeters and the individual risk profile of the patients, according to the guidelines of the American Thoracic Society and the Centers for Disease Control, revised in 1989. Of 697 tested patients, 252 showed test results consistent with tuberculosis infection (36.2%). 55 of these 697 patients had active tuberculosis disease or a prior history of tuberculosis (7.9%). A positive tuberculin skin test was found in 197 of 642 patients (30.7%) with a diagnosis different from tuberculosis (COPD, pneumonia, cancer and others). In our study, the sensitivity of the tuberculin skin test for active tuberculosis infection was 95%. The present study revealed a high prevalence of tuberculosis infection among hospitalized patients in a pneumological department. Further studies are needed to assess the usefulness of routine tuberculin skin testing in hospitalized populations.
BACKGROUND AND AIM: To study the pattern of tuberculin sensitivity and its interpretation to diagnose sarcoidosis in the presence of a high prevalence of Mantoux positivity in the general population in India. METHODS: Tuberculin sensitivity was examined in two groups of subjects: Group I included 50 newly diagnosed patients with pulmonary sarcoidosis and two control subjects with pulmonary ailments other than sarcoidosis or tuberculosis for each case; Group II included 62 new patients with sarcoidosis and 130 healthy volunteers as control subjects. Mantoux test was performed using 1 TU tuberculin. The test was repeated with 5 TU tuberculin for those cases and controls who were anergic to 1 TU among the group II subjects. Sensitivity and specificity for a "negative Mantoux test" in sarcoidosis were calculated at different cutoff points. The influence of prior BCG vaccination status on the performance of Mantoux test was also studied. MEASUREMENTS AND RESULTS: Forty-six (92%) of the 50 patients with sarcoidosis in Group I and 55 of the 62 (88.7%) in Group II did not show any reaction to Mantoux test, compared to 32 (32%) and 21 (16.2%) controls, respectively in groups I and II (P < 0.001). Thirty-nine (70.9%) of the 55 patients and 6 (28.6%) of the 21 controls from the group II subjects who were tested again with 5 TU did not show any reaction. A negative Mantoux test had a high sensitivity value at all the cut off points for the diagnosis of sarcoidosis. BCG vaccination administered during childhood had no correlation with a negative Mantoux reaction. CONCLUSIONS: Tuberculin anergy in sarcoidosis is not influenced by the rate of Mantoux positivity in the general population. A positive Mantoux test (irrespective of the size of reaction) in a suspected case of sarcoidosis should arouse strong suspicion of an alternate or an additional diagnosis of tuberculosis.
By means of dual-testing with tuberculin (2 TU PPD RT 23 and 2 TE PPD Dessau) and sensitin Scrophulaceum (5 TU PPD scroph.) evidence and degree of specific and non-specific tuberculin sensitivity in schoolchildren aged 7-14 years was examined under the conditions of preceding BCG-vaccination as newborns in the counties of Cottbus, Erfurt and Neubrandenburg. In a cohort of 2,792 children sensitivity to tuberculin was found in 5.98% considering positive reactions with greater than or equal to 6 mm induration and in 1.50% considering reactions with greater than or equal to 10 mm only. Reactions with induration of 6 mm and more comprehend remaining allergy caused by BCG while the limit greater than or equal to 10 mm seems to be suitable to define tuberculosis infection prevalence. Tuberculin sensitivity shows frequencies corresponding with the epidemiology of tuberculosis. Sensitivity to PPD scroph. increases from north to south with significant difference between the counties of Neubrandenburg and Erfurt. Nonspecific tuberculin sensitivity is partly prevalent in the counties of Cottbus and Erfurt.
The administration of triton WR-1339 (300 mg./kg. subcutaneously) to tuberculin-sensitive guinea pigs 2 hours before the intradermal injection of PPD depresses slightly their skin sensitivity to tuberculin and essentially obliterates the lytic effect of tuberculin on their circulating leucocytes. When leucocytes from tuberculin-sensitive guinea pigs are exposed to triton in vitro at a concentration level attainable in vivo the cells are partially protected against lysis by PPD.
BACKGROUND: Historically, 10 TU has been employed in Australia and the United Kingdom to perform the tuberculin skin test (TST). However, this makes it difficult to compare the rates of TST positivity with other countries such as the USA who use 5 TU. To assess the impact of the dose of tuberculin on the TST a comparison was made of TST responses in health care workers given a TST with both 5 and 10 TU. METHODS: Two TSTs were performed simultaneously in each health care worker using 5 and 10 TU. Each dose was randomly assigned in a blinded manner to the right or left forearm and read at 48-72 hours by a single nurse who was blinded to the assignment of the 5 and 10 TU doses. RESULTS: A total of 128 health care workers were enrolled, 119 (93%) of whom had a past history of BCG vaccination. The overall mean difference in paired reaction sizes for the two doses was 1.5 mm with 95% limits of agreement of -3.6 to 6.5 mm. CONCLUSION: A slightly larger TST reading was seen with 10 TU than with 5 TU. The mean difference of 1.5 mm between the two doses should be considered when comparing rates of TST positivity between countries who use different doses of tuberculin to perform the tuberculin skin 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.