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.     

The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort

Background  

Assuming a higher risk of latent tuberculosis (TB) infection in the population of Rio de Janeiro, Brazil, in October of 1998 the TB Control Program of Clementino Fraga Filho Hospital (CFFH) routinely started to recommend a two-step tuberculin skin test (TST) in contacts of pulmonary TB cases in order to distinguish a boosting reaction due to a recall of delayed hypersensitivity previously established by infection with Mycobacterium tuberculosis (M.tb) or BCG vaccination from a tuberculin conversion. The aim of this study was to assess the prevalence of boosted tuberculin skin tests among contacts of individuals with active pulmonary tuberculosis (TB).     

Tuberculin reactivity in adults after 50 years of universal bacille Calmette-Guerin vaccination in Taiwan

We aimed to assess whether tuberculin reactivity in adults is affected by bacille Calmette-Guerin (BCG) vaccination after 50 years of universal BCG vaccination with 80-95% coverage. A community-based study on tuberculin reactivity in 619 participants was conducted in February 2000 in Keelung city, Taiwan. Information on BCG vaccination policies and annual risk of infection (ARI) in the underlying population was extracted from consecutive national prevalence surveys relating to the period 1952-1997. Compared with the expected ARI estimate, the standardized morbidity ratio of positive tuberculin response for vaccination in infancy was 2.2 (95% CI 0.3-15.5) for those aged <10 years. The corresponding figures for older age groups ranged from 3.6 (95% CI 2.2-5.9) for those aged 10-12 years to 0.7 (95% CI 0.5-0.9) for those aged 57-67 years. This suggests that the effect of BCG vaccination on positive tuberculin response in adults aged >30 years is probably negligible irrespective of age at vaccination or revaccination and that the tuberculin skin test can be used to diagnose TB in control programmes in countries with moderate or high incidence of TB.     

Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage.

OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1 148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > or = 5 mm, > or = 10 mm, and > or = 15 mm) and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > or = 15 mm). We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > or = 10 mm was 14.2% (95% confidence interval (CI) = 8.0%-20.3%) for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1%) for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0%) for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > or = 5 mm and > or = 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > or = 5 mm and > or = 10 mm did not vary with age. There was no evidence for BCG effect on the results > or = 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to estimate M. tuberculosis prevalence or to assess transmission patterns as well as in tuberculin skin testing of individuals used as an auxiliary tool in diagnosing tuberculosis. Taking this information into consideration is especially important when there is increasing BCG revaccination coverage.     

Effect of oral vaccination of cattle with lipid-formulated BCG on immune responses and protection against bovine tuberculosis

Cattle were given Mycobacterium bovis bacillus Calmette-Guerin (BCG) in a lipid-based formulation via the oral route and tested for immune responses and protection against a challenge with virulent M. bovis. Calves were vaccinated by orally administering a pellet containing 10(8) colony forming units (CFU) of BCG, or 10 pellets containing a total of 10(9) CFU of BCG, whereas positive controls were injected subcutaneously with 10(6) CFU of BCG. All of the subcutaneously vaccinated calves produced positive responses in the caudal fold tuberculin skin test at 8 weeks after vaccination, whereas only 3/9 of the low dose and 6/10 of the high dose orally-vaccinated animals produced positive reactions. None of the animals produced positive reactions to the mycobacterial antigens, ESAT-6 and CFP10 in the interferon-gamma (IFN-gamma) test and only a total of four of the BCG-vaccinated animals produced positive responses in either the standard IFN-gamma or comparative cervical skin test. Oral administration of 10 pellets of lipid-formulated BCG to cattle induced a significant level of protection against bovine tuberculosis compared to that observed in non-vaccinated animals and this level was similar to that seen in the BCG subcutaneously vaccinated animals. Oral vaccination of BCG in a lipid-formulation to calves was shown to induce some positive tuberculin skin test reactions, but could also induce protection against bovine tuberculosis.     

Determining the prevalence of tuberculosis infection in populations with non-specific tuberculin sensitivity

In tropical countries, where there is generally a high prevalence of non-specific sensitivity, the tuberculin test is inadequate for detecting tuberculosis infection. A method is proposed by which the prevalence of infection in the population can be determined under such circumstances thus making possible meaningful epidemiological surveillance of the disease. This method compares levels of tuberculin sensitivity in individuals before and after BCG vaccination. If BCG vaccination fails to produce an increase in tuberculin sensitivity, the individual must have been infected with human or bovine tubercle bacilli.     

Relationship between Bacille Calmette-Guérin vaccination, Mantoux test positivity, and geohelminth infection

To investigate the potential protective effects of Bacille Calmette-Guérin (BCG) vaccination scar and sensitization to tuberculin against geohelminth infections, we conducted a cross-sectional study among school age children in rural communities in Pichincha Province in Ecuador where BCG vaccination is routinely given at birth. A total of 944 children aged 8-14 years were evaluated for the presence of BCG scars and sensitization to tuberculin, and underwent faecal examination for geohelminth parasites. BCG scars were present in 88.2% of children and positive Mantoux tests were observed in 19.1% of children. Geohelminth prevalence was high with 70.3% infected with any parasite, 52.1 % with Ascaris lumbricoides, 52.3% with Trichuris trichiura, 7.6% with Ancylostoma duodenale, and 3.0% with Strongyloides stercoralis. In multivariate analyses, the presence of BCG vaccine scars was not significantly associated with infections with any geohelminth parasite (adjusted odds ratio [AOR] = 0.74, 95% CI 0.43-1.28, P = 0.28), but an inverse association was observed for infections with S. stercoralis that was of borderline statistical significance (AOR = 0.38, 95% CI 0.15-1.00, P = 0.05). There were no associations between sensitization to tuberculin and infection with geohelminth parasites. The data provide little support for an important protective role of neonatal BCG vaccination or current mycobacterial sensitization against geohelminth infections.     

Trial of BCG vaccines in south India for tuberculosis prevention: first report: Tuberculosis Prevention Trial*1

The protective effect of BCG vaccination is being evaluated in a controlled community trial near Madras in south India. After tuberculin and sensitin testing and radiographic and bacteriological examinations, BCG vaccines and placebo were allocated randomly to about 260 000 individuals, of whom 115 000 were definitely tuberculin negative at the time of vaccination. Intensive efforts are being made, by means of regular follow-up surveys, to identify all new cases of tuberculosis occurring in the community. This report presents the findings of the first 7½ years of follow-up. Incidence of infection was high in the study population. However, incidence of bacillary disease was more frequent among initial tuberculin reactors, especially among the older persons, than among non-reactors of whom the majority were in the younger age groups. The distribution of new cases of bacillary tuberculosis among those not infected at intake did not show any evidence of a protective effect of the BCG vaccines.     

Relationship between bacille Calmette-Guérin vaccination, Mantoux test positivity, and geohelminth infection

To investigate the potential protective effects of Bacille Calmette-Guerin (BCG) vaccination scar and sensitization to tuberculin against geohelminth infections, we conducted a cross-sectional study among school age children in rural communities in Pichincha Province in Ecuador where BCG vaccination is routinely given at birth. A total of 944 children aged 8-14 years were evaluated for the presence of BCG scars and sensitization to tuberculin, and underwent faecal examination for geohelminth parasites. BCG scars were present in 88.2% of children and positive Mantoux tests were observed in 19.1% of children. Geohelminth prevalence was high with 70.3% infected with any parasite, 52.1% with Ascaris lumbricoides, 52.3% with Trichuris trichiura, 7.6% with Ancylostoma duodenale, and 3.0% with Strongyloides stercoralis. In multivariate analyses, the presence of BCG vaccine scars was not significantly associated with infections with any geohelminth parasite (adjusted odds ratio [AOR] = 0.74, 95% CI 0.43-1.28, P = 0.28), but an inverse association was observed for infections with S. stercoralis that was of borderline statistical significance (AOR = 0.38, 95% CI 0.15-1.00, P = 0.05). There were no associations between sensitization to tuberculin and infection with geohelminth parasites. The data provide little support for an important protective role of neonatal BCG vaccination or current mycobacterial sensitization against geohelminth infections.     

Risk factors for positive tuberculin skin test in Guinea-Bissau

BACKGROUND: The tuberculin skin test is used for tracing of tuberculosis transmission and identifying individuals in need of prophylactic treatment. METHODS: Using a case-control study design, we recruited 220 smear-positive tuberculosis cases and 223 randomly selected healthy community controls in Bissau, Guinea-Bissau, during 1999-2000. Tuberculin skin tests were performed on family members of cases and controls (n = 1059 and n = 921, respectively). Induration of 10 mm or greater was considered positive. Risk factors were calculated for children (<15 years) and adults separately in multivariate logistic regression analysis. RESULTS: The prevalence of positive tuberculin skin test was 41% in case-contacts compared with 22% in control-contacts, resulting in a prevalence ratio of 1.48 (95% confidence interval = 1.37-1.60). Positive skin tests among case-contacts increased with age for children, as well as with proximity to a case during the night, for both children and adults. A Bacille Calmette Guerin scar increased the likelihood of having a positive tuberculin skin test for adults in case households, but not in other categories of contacts. Among control-contacts the prevalence of positive skin test was associated with older age in children, history of tuberculosis in the family, and a positive tuberculin skin test of the control person. CONCLUSIONS: Risk factors for a positive tuberculin skin test among case- and control-contacts are closely related to tuberculosis exposure. Having a BCG scar did not increase the risk of positive skin test in unexposed individuals. Tuberculin skin testing remains a useful tool for diagnosing tuberculosis infection.     

HAS evaluation: interferon gamma detection test for the diagnosis of tuberculous infections

Infection with Mycobacterium tuberculosis is limited by the host immune defenses in most individuals, and the infection remains latent. In 10% of patients, the latent tuberculosis infection can be reactivated and cause active disease. The tuberculin skin test is the established screening method for diagnosing latent tuberculosis infection, but it poses many problems such as cross reactivity due to prior BCG vaccination. A new type of in vitro Tcell based assay, for the detection of tuberculosis infection, was recently developed. This interferon gamma (IFNgamma) blood assay is based on the measure of IFNgamma production by previously sensitized lymphocytes in response to the M. tuberculosis specific proteins. The French National Authority for Health assessed the two commercial IFNgamma assays. Assessment was based on the critical review of scientific literature and the opinion of experts in the field.The diagnostic tool of IFNgamma detection test was considered indicates in four situations: diagnosis of latent tuberculosis infection in adults; before health care worker recruitment; diagnosis of extrapulmonary form of tuberculosis disease; before starting anti-TNFalpha treatment. This report states that IFNgamma assays may be used instead of a tuberculin skin test in these four situations.     

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.     

The effect of Bacille Calmette-Guérin vaccine on tuberculin reactivity in indigenous children from communities with high prevalence of tuberculosis

The Bacille Calmette-Guérin (BCG) vaccine is the most widely used vaccine in the world, however it may cause problems for the appropriate interpretation of the tuberculin skin test (TST). We assessed the diagnostic value of latent infection in vaccinated and unvaccinated indigenous children from communities that have a very high prevalence of adult tuberculosis (TB). A total of 997 children under 15 years old and classified in age groups (0-1.9, 2-5, 6-9 and 10-15 years old) were randomly selected and given TSTs using the Mantoux technique. TST induration values of vaccinated children (n=724) were compared with those of children unvaccinated (n=273). BCG vaccination was not an important cause of false-positive TST, except in communities with a low prevalence of active TB. In conclusion, the results suggested that a history of BCG vaccination on TST+ response after 10 years of vaccination was statistically insignificant but whether at earlier age TST+ reflects most probably the degree of exposure to TB cases than BCG vaccination should be clarified in the future.     

Immune responses to hepatitis B virus and tuberculosis infections in Southeast Asian refugees

Both Mycobacterium tuberculosis and hepatitis B virus infections are common in the Philadelphia Southeast Asian refugee population. Among 224 hepatitis B carriers identified between January 1, 1982 and March 31, 1984, there was a statistically significant association between a negative tuberculin skin test (purified protein derivative (PPD)) and viral replication (hepatitis B e antigen positivity (HBeAg)). This finding suggests that bacille Calmette Guérin (BCG) vaccination might reduce the prevalence of infectious carriers, thereby ultimately reducing the incidence of hepatitis B infection.     

Performance of an interferon-gamma release assay for diagnosing latent tuberculosis infection in children

Newly developed interferon-gamma release assays have become commercially available to detect tuberculosis (TB) infection in adults. However, little is known about their performance in children. We compared test results between the QuantiFERON-TB Gold test (QFT) and tuberculin skin test (TST) in young children living with pulmonary TB patients in Cambodia. Of 195 children tested with both QFT and TST, the TST-positive rate of 24% was significantly higher than the QFT-positive rate of 17%. The agreement between the test results was considerable (kappa-coefficient 0.63). Positive rates increased from 6% to 32% for QFT and from 15% to 43% for TST, according to the sputum smear grades of the index cases. The presence of Bacille Calmette-Guérin (BCG) scars did not significantly affect the results of TST or QFT in a logistic regression analysis. In conclusion, QFT can be a substitute for TST in detecting latent TB infection in childhood contacts aged 相似文献   

EXPERIMENTAL studies of vaccination,allergy, and immunity in tuberculosis. II. Effect of varying the dose of BCG

Results are given for one of a series of projects designed to investigate the relation between observable post-vaccination responses and acquired resistance to tuberculosis. Controlled variations in the dose of BCG vaccine have previously been shown to cause systematic variations in the degree of skin sensitivity to tuberculin and the size of vaccinal lesions in human beings: the purpose of the present project was to see if similar variations would be produced in guinea-pigs and then, by infecting the animals with virulent tubercle bacilli, to see how survival time correlates with tuberculin allergy and vaccinal lesions.Four doses of freshly prepared BCG vaccine, ranging from 1/100 to 10 times the dose ordinarily used for intradermal vaccination of humans, and one dose of heat-killed BCG 100 times that strength, were used to vaccinate five groups of guinea-pigs, each containing 120 animals. A sixth group of 120 animals was not vaccinated. All animals were tuberculin-tested just before and five weeks after vaccination, challenged with a strong dose of H-37 Rv, and then allowed to die, so that survival time could be used as a measure of resistance.As the dose of living BCG was increased, groups of guinea-pigs showed a progressive increase in the average degree of post-vaccination tuberculin allergy, size of vaccinal lesion, and length of survival after virulent infection. The heat-killed BCG resulted in weak allergy and a short survival time, yet the vaccinal lesions averaged about as large as would be expected from a corresponding dose of living BCG. These results (excluding studies of survival time) correspond closely to those found in human studies.The implications of the results with respect to practical BCG vaccination programmes, while no more than speculative at present, point toward possible advantages in inducing high degrees of tuberculin allergy and toward the dubious significance of the vaccinal lesion as an index of a vaccine's immunizing potency.     

Tuberculin reaction, BCG scar, and lower female mortality

BACKGROUND: Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in response to BCG immunization were related to better overall survival in Guinea-Bissau and, if so, whether the effect was sex-specific. METHODS: Skin tests and BCG scarring were monitored at ages 2 months (n = 2332) and 6 months (n = 1817) in children born from March 2000 to July 2002. A tuberculosis (TB) surveillance system allowed us to exclude from the analysis children with likely TB exposure. The children were followed for survival until 18 months of age. RESULTS: Among children with a tuberculin skin test at 2 and 6 months of age, the mortality rate ratio for skin test reactors (>1 mm) versus nonreactors (0-1 mm) was 0.54 (95% confidence interval = 0.30-0.99). Comparing children with and without a BCG scar, the ratio was 0.55 (0.31-0.96). The effect of a skin test reaction or a BCG scar seemed stronger among girls; for those with positive reaction, the mortality ratio was 0.31 (0.11-0.88) among girls and 0.84 (0.39-1.82) among boys; and for BCG scar, the results were 0.41 (0.21-0.82) and 0.88 (0.34-2.30), respectively. CONCLUSIONS: A good response to BCG vaccination is related to lower child mortality. The effect seems most pronounced among girls. The findings may have implications for future vaccine trials and policy.     

BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?

Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.     

Tuberculin skin reactivity after neonatal BCG vaccination in preterm infants in Minas Gerais, Brazil, 2001-2002.

OBJECTIVES: The efficacy of BCG vaccination in preterm babies is unknown, and available data on conversion rates to tuberculin in this age group are scarce and controversial. This study assessed the tuberculin response in preterm infants after BCG vaccination.METHODS: This randomized cohort study was carried out at the Neonatal Department, University Hospital, Federal University of Minas Gerais in Brazil during 2001 and 2002. The BCG vaccine was administered at birth to 65 full-term (control) and 40 preterm newborns. All of them were tested with 5 tuberculin units of purified protein derivative-S approximately 3 months after vaccination.RESULTS: A typical BCG scar was verified in 96.9% of the control group and in 90.0% of the preterm infants (P = 0.19). Indurations > 5 mm in diameter were recorded in 87.7% of the full-term and 67.5% of the preterm infants (P = 0.02). Indurations > 10 mm were recorded in 70.8% of the full-term and 42.5% of the preterm infants (P = 0.007). For indurations > 5 mm the upper and the lower limits of the 95% confidence interval for the difference between proportions were 8.5% to 31.8%, and for indurations > 10 mm these limits were 18.0% to 38.4%. No adverse reactions were observed in the study population.CONCLUSION: BCG vaccination could be recommended for preterm infants upon discharge from the neonatal unit to reduce morbidity and mortality in infants at risk for tuberculous infection, and to increase BCG vaccination coverage rates, especially in countries with high prevalence rates of tuberculosis.     

Is tuberculin skin testing useful to diagnose latent tuberculosis in BCG-vaccinated children?

BACKGROUND: The tuberculin skin test (TST) is the most commonly used tool to detect infection with Mycobacterium tuberculosis. We sought to determine whether tuberculin skin testing is useful to detect latent infection by M. tuberculosis in a population that was vaccinated with the Bacille Calmette Guérin (BCG) vaccine. METHODS: We performed a cross-sectional study during October 2000-February 2001, enrolling first and sixth graders from a random, stratified sample of public elementary schools in Orizaba, Veracruz, Mexico. We assessed the relationship between sociodemographic and epidemiological information, BCG scars, and TST reactivity. RESULTS: There were 858 children enrolled in the study with a completed questionnaire and TST result. The prevalence of a positive TST result (> or =10 mm) was 12.4%. Controlling for BCG scar, age, and other characteristics, close contact with pulmonary tuberculosis patients (odds ratio 6.56, 95% confidence interval 2.05-21.07, P = 0.001) was independently associated with TST reactivity. CONCLUSIONS: TST results helped identify children in a BCG-vaccinated population who had recent exposure to persons with pulmonary tuberculosis, were probably infected with M. tuberculosis, and could benefit from treatment for their latent tuberculosis infection.