A cost-effectiveness analysis of universal versus selective immunization with Mycobacterium bovis bacille Calmette-Guérin in Finland.

SETTING: Mycobacterium bovis bacille Calmette-Guerin (BCG) is provided to all infants born in Finland. OBJECTIVE: To analyze the cost-effectiveness of universal versus selective BCG immunization. DESIGN: A Markov model was developed to simulate rates of tuberculosis (TB) and non-tuberculous mycobacterial disease (NTM), and to examine the cost-effectiveness in terms of cost per case averted of three different strategies: universal BCG, selective BCG (10% of infants at higher TB risk than other infants) or no BCG immunization. RESULTS: In a cohort of 60,000 infants over 15 years, the model predicts five cases each of TB and NTM disease with universal immunization, 8-21 TB and 31 NTM cases with various strategies of selective immunization, and 25 TB and 34 NTM cases with no BCG immunization. BCG side-effects are predicted in 5, 0.5 and 0 infants, respectively. The cost per case averted for immunization strategies ranges from a cost of 38,311 US dollars to a savings of 323 dollars as selective immunization becomes more efficient at targeting infants at highest risk of TB. CONCLUSIONS: In a country with a low incidence of pediatric tuberculosis, selective BCG immunization is a more cost-effective strategy than universal BCG immunization for the prevention of tuberculosis, but results in an increase in NTM cases.

Bacillus Calmette-Guérin revaccination questionable with low tuberculosis incidence.

Bacillus Calmette-Guerin (BCG) revaccination was discontinued in Finland in 1990. The objective of this study was to assess the impact of BCG revaccination of tuberculin-negative school-children in prevention of tuberculosis. The tuberculosis cases in 1990-1995 were calculated among age cohorts born 1979-1984 and no longer covered by the BCG revaccination program. Corresponding data were collected for comparison from the period of revaccination in 1980-1985 among age cohorts born in 1969-1974. The National Tuberculosis Register was reviewed in order to observe the tuberculosis trend since 1980 in the age groups of 10-14 and 15-19 yr. Three cases of tuberculosis have been registered among non-BCG-revaccinated children during 6 yr after discontinuation of the program, i.e., 2.23 cases (95% CI 0.72 to 6.90) per million person yr. The control group revealed five cases, 3.78 (95% CI 1.57 to 9.07) per million person yr. The relative risk of tuberculosis in non-BCG-revaccinated children is 0.59 (95% CI 0.14 to 2.47) compared with the control group. The incidence of tuberculosis has continued to decline among adolescents since 1980. The follow-up data confirm that the cessation of BCG revaccination program had no effect on the continuing overall decline of tuberculosis in Finland. The efficacy of BCG revaccination seems to be low or nonexistent in countries with low tuberculosis incidence.

Pros and cons of BCG vaccination in countries with low incidence of tuberculosis.

Preventive bacille Calmette-Guérin (BCG) vaccination, together with case finding and effective chemotherapy, has formed an integral part of the tuberculosis (TB) control program in most countries. In some low-incidence countries the balance of prevention has been more on the side of chemoprophylaxis than of BCG vaccination. The time clearly has come when the strategy of mass BCG vaccination no longer is indicated medically, nor is it cost-effective. The pros and cons of the programs need to be critically evaluated against the present epidemiological background, taking into account the facts that TB, the killer disease, is recovering strength, human immunodeficiency virus infection is on the increase, and multidrug-resistant TB has changed the outcome of this previously fully curable disease. Although no longer appropriate for mass programs, BCG vaccination still should be considered for the protection of selected risk groups in low-incidence countries. The overall efficacy may be of the order 50% to 80%, but the variation is great. Therefore, further research urgently is needed on the effectiveness of BCG as an intervention in local TB programs.

Good concordance between two batches of new tuberculin in the Mantoux test.

Two batches of new tuberculin prepared from different unheated cultures of M. tuberculosis, 8 years apart, were tested for concordant skin reactions in the WHO standard Mantoux test. Both batches T1327 and T1456 were simultaneously injected (0.1 ml) into the dorsal aspects of the forearms of 123 school children, aged 11-13 years, who had been BCG vaccinated at birth. The mean size of the induration to T1327 was 10.3 (SD 4.4) mm and to T1456 it was 11.3 (SD 4.2) mm. There was a significant linear correlation between the indurations caused by both batches (r = 0.91, P < 0.0001). The discrepancies between the readings were all within the limits of a 5 mm category. The mean size of the BCG scar was 8.1 (SD 4.8) mm, and there was a trend associating smaller BCG scars with smaller tuberculin responses which did not reach statistical significance. The two different batches of new tuberculin gave remarkably concordant results in WHO standard Mantoux testing illustrating the stability of the production process and suggesting that the results obtained in studies using different batches of new tuberculin are comparable.

Comparative study of skin testing with PPD and new tuberculins by the WHO Mantoux test.

PPD RT 23 tuberculin and two batches of new tuberculin (NT) were tested for concordant skin indurations in the WHO standard Mantoux test in 11- to 13-year-old Finnish school children BCG vaccinated at birth. All were double tested with RT 23 and with either batch T1327 (614 children) or with batch T1456 (312 children) of NT. The results were compared with data available from an earlier study employing RT 23 and T1327 in Ethiopian children, 50/134 of whom had a BCG scar. The mean induration to RT 23 after 72 h was slightly smaller than to the NTs. The individual readings for RT 23 had significant linear correlations with T1327 in Finland (r = 0.77) and in Ethiopia (r = 0.89), and for T1456 (r = 0.83; P < 0.001 for all three). Zero reactions were much fewer to NTs (5.5% to T1327 and 0.3% to T1456) than to RT 23 in Finland (18.2% and 9.3% respectively for the two groups). The results were similar in Ethiopian children. Our results indicate that RT 23 and the two NTs give concordant results, but NTs seem to be more specific, perhaps because they retain more species-specific antigens. Analysis of our results suggests that different peaks in the distribution of reaction sizes were due to responses to different antigens or combinations of antigens, and in the case of the largest reactions, to a different type of immunological response.

Sensitivity to PPD tuberculin and M. scrofulaceum sensitin in schoolchildren BCG vaccinated at birth.

OBJECTIVE: To determine the degree of and variation in sensitivity to PPD RT 23 tuberculin and M. scrofulaceum sensitin RS 95 at school age in children BCG vaccinated at birth. DESIGN: Double-testing by applying standard WHO Mantoux tests and inspecting BCG scars. SETTING AND PARTICIPANTS: Urban and rural schools in Southwest Finland, 1091 children aged 11-13 years. MAIN OUTCOME MEASURES: Size of tuberculin and sensitin indurations and BCG scar (mm). RESULTS: The mean size of tuberculin indurations was 7.2 mm, sensitin indurations 8.1 mm and BCG scars 7.9 mm. The reaction to sensitin was significantly larger than to tuberculin (95% confidence interval 0.58-1.10 mm) and the zero reactions to sensitin were fewer. Correlation between tuberculin and sensitin indurations was significant (r = 0.75, 95% confidence interval 0.72-0.77). There were induration greater than or equal to 15 mm to tuberculin in 16% and to sensitin in 14%. Sensitin indurations exceeded those of tuberculin by 4 mm or more in 14% of the children with at least 5 mm tuberculin indurations. CONCLUSIONS: High tuberculin sensitivity in healthy schoolchildren may be partially maintained by contact with environmental mycobacteria. Our data do not prove but very probably indicate that children have protective immunity. In view of the current incidence of tuberculosis in Finland and the likelihood that lymph node infections and sensitivity to environmental mycobacteria will increase, continued BCG vaccination at birth is recommended.

Evaluation of the BCG revaccination programme of schoolchildren in Finland.

OBJECTIVE: To evaluate the need for the BCG revaccination programme of schoolchildren in Finland. DESIGN: Investigating tuberculin sensitivity using the standard WHO Mantoux test and developing a model to estimate the risk of discontinuation, assuming that the annual incidence of tuberculosis within ten years after revaccination will remain at its present level; that the revaccination rate will be 2, 6 or 20%; and that the degree of protection will be 10, 20, 40 or 80%. SETTING AND PARTICIPANTS: Urban and rural schoolchildren--3,346 vaccinated with Copenhagen and 655 with Glaxo BCG vaccine at birth. RESULTS OF DATA ANALYSIS: The annual incidence of tuberculosis was 4.2 per 100,000 in the age-group 15-24 years. BCG revaccination was given formerly to 20% of the age cohort but nowadays only 6% or 2% meet the criteria after receiving either Copenhagen or Glaxo BCG at birth. After discontinuation the expected increase of tuberculosis in the age-group 15-24 years is predicted to fall within the limits of 0.1-24 cases per year. If 2% are left without revaccination the increase will be 0.1-2.4 cases. CONCLUSIONS: Due to the low annual incidence of tuberculosis in adolescents and to the small risk of increase the BCG revaccination programme has been discontinued from 1990 onwards.