Previous BCG Vaccination Research Articles

Effectiveness of BCG vaccination among leprosy contacts: a cohort study

The study assessed the effectiveness of BCG vaccination against leprosy among the contacts of 1161 leprosy patients at the FIOCRUZ Leprosy Outpatient Clinic, RJ, Brazil, from June 1987 to December 2006. Following National Leprosy Program guidelines, the clinic has administered one-to-two doses to all healthy contacts since 1991. Among the 5680 contacts, 304 (5.4%) already had leprosy. Of the 5376 eligible healthy contacts, 3536 were vaccinated, 30 of whom were excluded due to previous or current tuberculosis, or HIV. In 18 years of follow up, 122 (2.15%) incident cases were diagnosed (58 vaccinated and 64 not), 28 occurring in the first year of follow up (21 vaccinated, 16 with no scar). The protection conferred by BCG was 56% and was not substantially affected by previous BCG vaccination (50% with a scar and 59% without). The risk of tuberculoid leprosy during the initial months was high among those vaccinated with no scar. However, it had substantially declined by the first year and in the following years, when the protection rate in this group reached 80%. Since Brazil is endemic for leprosy and the detection rate is not declining satisfactorily, vaccinating all contacts could be an effective means of substantially reducing the incidence of leprosy.

QuantiFERON ®-TB Gold test in the identification of latent tuberculosis infection in immigrants

The identification and treatment of latent tuberculosis infection (LTBI) among immigrants are an effective strategy for TB control in developed countries. A new test for LTBI identification that uses more specific antigens of Mycobacterium tuberculosis is now commercially available under the brand name of QuantiFERON-TB Gold test. To compare QuantiFERON-TB Gold test to tuberculin skin testing (TST) for the detection of LTBI among immigrants from high endemic TB areas. Undocumented immigrants attending a district medical center were enrolled if they originated from high endemic TB areas, the time of arrival in Italy was < or = 5 years, had neither active TB disease nor known immunodeficiency status. The TST was applied according to standards and QuantiFERON-TB Gold test was performed following the manufacturer's instructions. Hundred subjects were included in the comparative analysis. TST was positive in 44% of subjects; 15% had a positive QuantiFERON-TB Gold test result. The total agreement between TST and QuantiFERON-TB Gold test was 71%, for a kappa statistics of 0.37; agreement was 100% for TST negative results, but only 34% for TST positive ones. In the multivariate logistic regression analysis, previous BCG vaccination was independently associated with a lower chance of disagreement between the tests. The prevalence of LTBI among immigrants was lower when determined by QuantiFERON-TB Gold; this may be a consequence of more specific MTB antigens used. Our results suggest that QuantiFERON-TB Gold may be used as confirmatory test for TST positive immigrants candidate to preventive therapy.

In Vitro Gamma Interferon Tests for the Detection of Tuberculosis Infection

The QuantiFERON-TB Gold (QFT-G) is a new FDA approved test for diagnosing Mycobacterium tuberculosis infection. This test detects the release of interferon-gamma (IFNγ) in whole blood from sensitized persons when it is incubated with mixtures of synthetic peptides representing 2 proteins present in M. tuberculosis: early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). These antigens have greater specificity than tests using purified protein derivative (PPD) as the tuberculosis antigen. The CDC recommends that QFT-G may be used in all circumstances in which the TB skin test is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for health-care workers). Advantages of the QFT-G include: no false-positive reactions from previous BCG vaccination; no cross-reactivity with non-tuberculous mycobacterium infections; and, better detection of active tuberculosis.

De diagnostiek en behandeling van latente tuberculose-infectie in kinderen

More often than active tuberculosis disease children have latent tuberculosis infection (ltbi), which can occur after contact with a patient suffering from smear-positive pulmonary tuberculosis, usually an adult household member. In young children the infection is almost always recently acquired. Compared to adults, infected children, especially children with an immune disorder, have an increased risk of progression to active tuberculosis disease, and will more frequently develop severe manifestations of tuberculosis, such as tuberculous meningitis or miliary tuberculosis. Treatment of ltbi considerably reduces the risk of progression to active disease. Most infected children are identified during contact investigations or immigration screening and treated by the Department of Tuberculosis Control of the Municipal Health Service. The tuberculin skin test is not always a reliable method to diagnose ltbi, particularly in children with a previous bcg vaccination or in children with a reduced immune response. Recently developed interferon-? tests may contribute to improved diagnosis of ltbi in the future. On account of the publication of new guidelines for diagnosis and treatment of ltbi in children in the United States as well as in the Netherlands, the policies and developments in the Netherlands are discussed.

Techniques diagnostiques de la tuberculose et des autres mycobactérioses

Every 10 seconds, one person in the world dies of tuberculosis (TB). It is estimated that one third of the world's population is latently infected with Mycobacterium tuberculosis. The proportion of multidrug-resistant strains of M. tuberculosis is increasing at an alarming rate in some parts of the world linked in part with the human immunodeficiency virus epidemic. For these reasons, TB remains a major public health problem, both in less-developed countries and in many industrialized countries, with 8–10 million new cases and 2 million deaths yearly in the world. Clinical, radiological and histological signs are not specific for tuberculosis or for other mycobacteriosis and allow only a presumptive diagnosis. In the same way, the tuberculin skin test is useful if the reaction is strong or phlyctenular because this test depends on various factors as previous BCG vaccination, contact or primary infection and host immune responses. The diagnosis of mycobacterial infection is proved only when bacilli are present in biological samples. Nevertheless, only 50% of cases in adults and 30% in infants have a positive bacteriological result. It seems necessary to develop new methods for a rapid and efficient diagnosis to optimize the therapy and the control of the epidemic. Laboratory testing in the mycobacteriology field is experiencing more changes today than ever before. Determining what assays will be most useful to the clinician is a challenge, and acceptance of the new technology is under discussion. Progress in future will be linked probably to the progress of the genomic area. However the incidence rate is higher in less-developed countries, it is also important to develop now techniques possible to use in these countries. This review focuses on the current state-of-the-art resources useful for accurate and rapid laboratory diagnosis of mycobacterial infections.

The influence of BCG immunisation on tuberculin reactivity and booster effect in adults in a country with a high prevalence of tuberculosis

The relationship of age and previous BCG vaccination with tuberculin skin test (TST) reactivity was investigated to assess the interpretation of TST results in the adult population of Turkey, where there is a high prevalence of tuberculosis and a routine BCG vaccination programme. The influences of age and BCG vaccine status on booster reaction were also evaluated. TST was applied (5 tuberculin units of purified protein derivative intradermally) to two healthy adult groups, namely 98 medical students and 187 elderly people in a retirement home. The TST was considered positive if an induration > or = 10 mm in diameter was produced. Subjects (41 elderly people and 39 students) with a reaction < 10 mm in diameter were retested 1 week later. There was no significant difference between the students (59.1%) and elderly subjects (58.8%) with respect to positive TST response. No influence of BCG scars on TST reactivity was observed in either group. The booster effect was seen more commonly in the elderly, but the presence of a BCG scar did not influence the booster effect in either group. It was concluded that a positive TST response and booster reaction in adults in high-prevalence countries may be caused by latent tuberculosis rather than previous vaccination.

Estudio de la infección tuberculosa en adultos

Tuberculous infection in adults is not a well known entity in our country, despite its epidemiological importance. We have designed an observational study in a homogeneous group of adult civil servants of Catalonia (n = 8,202) from 20 to 54 years old that were submitted to a health examination which included a tuberculin test, in order to study the tuberculous infection in these people and to evaluate the factors associated with this infection. The global prevalence of reactivity in tuberculin test was 22.36% and the prevalence of the tuberculous infection was 14.76%. The factors related to the tuberculous infection were the following: age, male sex, background of exposure to sources of contagion, and previous BCG vaccination. The prevalence of tuberculous infection in adults has declined, and is currently greater in men than women, among patients who recognize previous contact with a tuberculous patient, and among patients with previous BCG vaccination.

Tuberculin reactivity: prevalence and predictors in BCG-vaccinated young Norwegian adults

We studied tuberculin reactivity in young Norwegian adults and its possible dependency on age, gender, previous BCG vaccination, smoking habits, occupational exposure, diet as well as years of education as a measure of socio-economic status. Responders of a random sample of men and women aged 20–44 years living in Bergen, Norway were interviewed and tested with the adrenaline-Pirquet test with Norwegian-produced synthetic medium tuberculin at the out-patient chest clinic in the city of Bergen in 1992–1993. Nine hundred and three subjects out of 1200 met for the clinical examination (75%). Five hundred and eighty-eight subjects were tuberculin-tested and read, whereof 95% were BCG vaccinated by age 14. Mean tuberculin reactivity was 4.8 mm (SD: 3.0 mm). A positive reaction (⩾4 mm) was found in 64%, whereof 7% had a strongly positive reaction (⩾10 mm). A negative reaction (<4 mm) occurred in 36%, whereof 10% had no reaction (0 mm). Only 30% of the females and 36% of the males aged 21–25 years were tuberculin positive 7–12 years after BCG vaccination. Linear regression analysis demonstrated tuberculin reactivity to increase with increasing age, male gender with an increasing sex effect by age, and current smoking. Occupational dust or gas exposure, a diet rich in vitamin C or years of education did not influence tuberculin reactivity significantly.

A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements

Background: The accurate diagnosis of latent tuberculosis infection (LTBI) is an important component of any tuberculosis control programme and depends largely on tuberculin skin testing. The appropriate interpretation of skin...

Purified protein derivative anergy in Kawasaki disease.

It was previously reported from Italy that all patients with Kawasaki disease had a positive tuberculin intradermal test. In this study from Seattle, WA, nine patients with Kawasaki disease showed no reaction to intradermal tuberculin. The difference in results might be caused by the different tuberculin products.

Prevalencia de tuberculosis en una población procedente de Kosovo acogida en Cataluña

Prevalence of tubeculosis (TB) among refugees is high. The goal was to detect TB active cases in a group of refugees from Kosovo and to describe the prevalence of TB infection. 222 people sheltered in Catalonia, Spain, were tested for TB using the Mantoux method and a chest x-ray. The odds ratio (OR) was adjusted by the age of presenting a positive PPD test for different diameters of induration according to the previous BCG vaccination history. No cases of active TB were detected and 82% of the population was found to be vaccinated with BCG. The OR of presenting a positive PPD was higher, and statistically significant, in vaccinated subjects compared to non-vaccinated ones for indurations >= 5 mm and >= 10 mm (OR: 4.5 and 3.6 respectively). BCG-vaccinated subjects from this population can be considered to be infected by Mycobacterium tuberculosis as long as the induration is higher than 15 mm.

Antituberculosis chemoprophylaxis in a public hospital - study of 100 children

OBJECTIVE: To evaluate recommendations for antituberculosis chemoprophylaxis in children according to the guidelines of the National Tuberculosis Control Program, and in special situations, as very young children, BCG vaccinated children with positive tuberculin skin test and recent or current exposure to infected cases. METHODS: A retrospective cross-section study has been made of 100 children who underwent chemoprophylaxis at a public hospital in Rio de Janeiro. Variables analyzed were sex, age, BCG vaccination, nutritional status, tuberculin skin test, recent tuberculosis converters, infection source for tuberculosis, adherence to prevention, monotherapy failure and isoniazid side effects. RESULTS: The case history was made up of 57 males and 43 females, 62% were younger than five years of age, there was reference to previous BCG vaccination in 92%, malnutrition in 28% and recent tuberculosis converters in 9% of the cases. Parents represented 60% of infection source known, there was adherence to prevention in 73%, monotherapy failure in 1% and isoniazid side effects in 1% of the cases. CONCLUSIONS: It has been concluded that 15% followed the Health Department guidelines thoroughly, which included the 9 cases of recent tuberculosis converters; 85% of the recommended chemoprophylaxis were due to the coverage of high-risk groups to develop the disease.

Routine two-step skin testing for tuberculosis in the staff of a geriatric hospital in Israel: booster and conversion rates

The objective of this study was to determine the prevalence of positive skin tests amongst the staff of a 200 bed geriatric hospital in Haifa, Israel. By comparing the findings with those of a study performed five years previously, we hoped to ascertain the number of conversions which had occurred in the period studied. This was undertaken in order to assess a new policy from the Israel Ministry of Health regarding skin testing for health care workers. We also hoped to decide upon the frequency of skin testing required and to compare data from recent immigrants from countries with a high prevalence of TB. In 1997, we performed two-step skin testing (TSST) on 318 health care workers. We ascertained the number of positive reactions on the first and second testing and calculated the number of subjects who showed significant boosting. We also compared the results to those obtained in a study in 1992 and calculated the rate of conversion. We used multivariate analysis to examine the effects of age, gender, country of origin, years in Israel, previous BCG vaccination, previous exposure to contagious TB, work site and area of residence in the city, on the response to TSST. Between 1990 and 1996, 655 000 immigrants from the former USSR arrived; ‘recent immigration’ was defined from that date onward. The final number of positive reactions out of 282 subjects, who were either positive or negative on step 1 and presented for step 2, was 171 (60%).Booster effect was not significantly associated with any of the variables examined. The size of reaction in TSST was related to country of origin and recent immigration. The 83 recent immigrants from the former USSR had more frequent (61%) and larger reactions (mean (sd): 9.0 (6.46) mm) than the 114 native-born Israelis with 39% positive reactions (6.2 (5.89) P= 0.009). Comparison with 1992 revealed 26 (31%) of previous negatives as positive. Conversion was associated with age. All conversions save one were in individuals younger than 50 years (P= 0.07). In conclusion, TSST, performed to enable detection of recent infection after exposure to contagious TB, was relevant for 40% of health care workers (HCWs). Second step testing contributed an additional 23% positive reactions. New immigrants had larger initial reactions. Conversion occurred mostly in younger workers and could be either due to unrecognized TB in the hospital or to exposure in the community.

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. (AJIC Am J Infect Control 2000;28:233-8)

Lichen scrofulosorum–like eruption localized to multipuncture BCG vaccination site

Lichen scrofulosorum is a rare complication of BCG vaccine. We describe a patient with an unusual lichen scrofulosorum–like eruption localized to a previous multipuncture BCG vaccination site. (J Am Acad Dermatol 1999;41:262-4.)

Prevalence of allergy in children in relation to prior BCG vaccination and infection with atypical mycobacteria.

By influence on the Th1/Th2 cell balance, infectious agents may affect the development of atopic allergy. In this study, we investigated whether previous BCG vaccination or infection with atypical mycobacteria might be related to the development of atopic disease. The study, which involved skin testing with mycobacteria and answers to a questionnaire for more than 6000 children in Sweden, revealed a low prevalence of allergy among BCG-vaccinated children who were immigrants or adopted from other countries. Vaccinated children born in Sweden, however, did not have significantly lower allergy prevalence than age-matched, unvaccinated children. Furthermore, the overall frequencies of skin-test reactivity to the atypical mycobacteria M. avium and M. scrofulaceum were higher rather than lower in allergic than in nonallergic children. By contrast, there was a tendency toward a lower frequency of more strongly positive skin reactions (> or = 10 mm) to mycobacteria in allergic than in nonallergic children. These findings do not support the hypothesis that early mycobacterial infections have a suppressive effect on the development of atopic disease. Earlier findings of an apparent association between atopy and lack of previous mycobacterial infection may possibly be explained by a relatively decreased ability of atopic patients to mount strong Th1 cell-mediated immune responses.

Gamma/delta T lymphocytes in the blood of patients with sarcoidosis.

Gamma/delta T lymphocytes are thought to have a role in granulomatous immune responses at peripheral sites of antigen contact such as the gut, skin and lung. The aim of this study was to determine if gamma/delta T lymphocytes are increased in the peripheral blood of patients with active sarcoidosis. Peripheral blood from 21 untreated patients with a new presentation of sarcoidosis (12M, 9F), 20 normal volunteers (12M, 8F), and 12 patients with cavitary pulmonary tuberculosis were subjected to Ficoll Hypaque separation and flow cytometry analysis using monoclonal antibodies to CD3, 4, 8, 25, HLA-DR and gamma/delta T cell receptor. All patients with sarcoidosis had compatible chest radiographs and all were Mantoux negative in spite of previous BCG vaccination. In all but one patient histological examination showed non-caseating granuloma. There was no difference in the mean percentage or absolute numbers of gamma/delta positive peripheral blood lymphocytes between the three populations. Thirteen patients with sarcoidosis had an absolute lymphopenia and the mean percentage of CD3 positive peripheral blood lymphocytes in the group with sarcoidosis was lower than the other two groups. The percentage of CD25 and HLA-DR positive cells was higher in the group with sarcoidosis, supporting the fact that these patients had active disease. Gamma/delta T lymphocytes are not increased in the peripheral blood of patients with sarcoidosis and are unlikely to have a role in the pathogenesis of this disease.

Delayed-type hypersensitivity, mycobacterial vaccines and protective immunity

SummaryThere is a longstanding debate over the implications of natural and vaccine-induced delayed type hypertensivity for protective immunity to mycobacterial infections. The identification of correlates of vaccine-induced protective immunity should help explain the inconsistent behaviour of BCG vaccines in different populations and assist in efforts to devise improved vaccines.More than 70000 subjects in Karonga District, northern Malawi were skin tested with soluble antigens of the tubercle and leprosy bacilli, and then followed up for five years for tuberculosis and leprosy incidence. Incidence rate ratios were calculated to compare subjects with different levels of prior skin test sensitivity, after controlling for the effects of age, sex and previous BCG vaccination. BCG vaccination protected against leprosy without persistent delayed-type hypersensitivity to tuberculin or to soluble antigens of the leprosy bacillus. In subjects who had not received BCG, hypersensitivity to tuberculin or to antigens of the leprosy bacillus was associated with strong protection against leprosy. In BCG-vaccinated and unvaccinated subjects, there was a J-shaped relation between hypersensitivity to tuberculin and subsequent rates of tuberculosis, with lowest rates associated with low grade sensitivity (induration 1-10 mm).This study shows that delayed-type hypersensitivity to mycobacterial antigens has different implications for tuberculosis and leprosy: low-level hypersensitivity (probably attributable to environmental mycobacteria) is associated with protection, but persistent vaccine-associated hypersensitivity to mycobacterial antigens is not a correlate of vaccine-derived protection against mycobacterial diseases.

Use of the 1 tuberculin unit (TU) Mantoux test in the assessment of tuberculous infection in children following neonatal BCG vaccination.

BCG vaccination alters the response to tuberculin testing and influences the potential validity of the Heaf test in the diagnosis of tuberculosis. This study used a purified protein derivative 1 tuberculin unit (TU) Mantoux test with a cut off of 5 mm induration as an indicator of tuberculous infection in high risk children to determine whether this would distinguish infection from previous neonatal BCG vaccination. Children at high risk of tuberculosis on chest radiography, Heaf test, or contact history who had been screened in the contact tracing clinic and referred for further assessment were included in the study. After clinical examination, chest radiography, and Mantoux testing they were assigned to three groups (tuberculous disease, chemoprophylaxis, or no treatment) and followed up for 6-24 months in the outpatient clinic and subsequently by postal questionnaire. Comparison of the Heaf and Mantoux tests showed a difference in the results with 82% of cases positive by the Heaf test and 59% positive by the Mantoux test. Using the Mantoux test result in combination with clinical and radiographic findings 194 children were allocated to the three groups as follows: primary tuberculosis (5), chemoprophylaxis (101), no treatment (88). During follow up for a mean (range) time of 46 (11-102) months four additional cases received treatment for primary tuberculosis, two in the chemoprophylaxis group and two in the untreated group. The use of the 1 TU Mantoux test after neonatal BCG vaccination reduced the number of children receiving treatment from 129 to 93-that is, by 36%. Although the numbers are small, there was no increase in the later development of tuberculosis.

Is the BCG test of diagnostic value in tuberculosis?

Setting: In developing countries including Turkey, tuberculosis is still a major problem. Rapid diagnosis and early medical intervention are the two most important considerations in preventing the spread of the disease. Objective: This study was carried out to determine the diagnostic value of BCG test in childhood tuberculosis and compare it with tuberculin test in this regard. Design: 50 patients and 20 healthy children without any evidence of previous BCG vaccination and aged 80 days-15 years were simultaneously tested with purified protein derivative (PPD) and BCG vaccine. Results: In pulmonary tuberculosis BCG test was positive in 100% of cases and the PPD test in 44.5%. Similarly, BCG test was positive in 100% of miliary tuberculosis and tuberculous meningitis cases but PPD test was negative in all of them. Out of 22 patients with malnutrition 18 (82%) had positive BCG test and 4 had positive PPD test. BCG test showed uniformly high positivity in all grades of malnutrition. Conclusion: BCG is more reliable and sensitive than the tuberculin test in the diagnosis of tuberculosis. It is still valuable in the diagnosis of tuberculosis especially in developing countries where the disease is still a major public health problem and where sophisticated methods such as rapid culture with BACTEC and demonstration of bacilli with DNA probes are not widely available.