Survey of BCG vaccination policy in Europe: 1994-96.

Survey of BCG vaccination policy in Europe: 1994-96 L. Trnka,1 D. Dankova,1 J. Zitova,1 L. Cimprichova,1 G.B. Migliori,2 L. Clancy,3 & J.P. Zellweger4 A retrospective survey, based on a standardized questionnaire sent to qualified public health experts in tuberculosis in 50 European countries, was carried out to evaluate the following: concordance between national vaccination programmes and WHO recommendations on BCG vaccination for prevention of tuber- culosis; relation between BCG vaccination and revaccination policy and the tuberculosis epidemiological situation; and differences in BCG vaccination policy between Western and Central-Eastern European countries. The results obtained (from 41 (82%) of the 50 countries) revealed that BCG vaccination programmes met WHO recommendations in 44% of European countries. Mass primary vaccination and general revaccination were extremely common in countries where the prevalence of tuberculosis was high. A highly significant difference was found between Western and Central-Eastern European countries in terms of their adhesion to WHO recommendations. Within Central-Eastern Europe no difference was found between countries that had or had not been part of the former Soviet Union. The implementation of WHO recommendations into national tuberculosis programmes must be inten- sified, based on the available body of evidence. Preventive methods whose cost-effectiveness has not been properly established should be discouraged. Introduction Bacillus Calmette-Gu6rin (BCG) vaccine has been used in Europe to prevent tuberculosis (TB) in hu- mans since 1921. At that time no other method of preventing TB in children was known (1) and as a result in virtually all European countries BCG vaccination programmes were developed with specific indications, methods, and timetables. Such programmes have never been uniform owing to disparate results from clinical trials of the vaccine's efficacy (2). Realization of the negligible impact of BCG vaccination on the community transmission of TB, the limited protection afforded to children by BCG vaccination, the doubtful efficacy of revaccinations, 1 Tuberculosis Surveillance Unit, Clinic of Pneumology and Chest Surgery, University Hospital, Prague Bulovka, Budinova 2, 18000 Prague, Czech Republic. Requests for reprints should be sent to Professor Trnka at this address. 2 Department of Pneumology, Fondazione Salvatore Maugeri, Clinica del Lavoro e della Riabilitazione, Care and Research Insti- tute, Tradate, Italy. 3 Peamont Chest Hospital, Dublin, Ireland; and International Union against Tuberculosis and Lung Disease, Paris, France. 4 Swiss Association against Lung Diseases, Berne, Switzerland; and International Union against Tuberculosis and Lung Disease, Paris, France. Reprint No. 5825 and the evidence of serious delayed postvaccination complications have raised doubts on the cost- effectiveness of BCG vaccination programmes and contributed to their subsequent modifications in European countries (3-5). In the perspective of TB control, WHO recently recommended general BCG vaccination of infants as soon after birth as possible in countries where the annual risk of tuberculosis infection is high, at the same time discouraging revaccinations, and stressing that BCG vaccination should be considered an ad- junct to national TB programmes (1). Rapid detec- tion and effective antituberculous treatment remain the highest priorities for TB control in all countries (6, 7). The European Region of the International Union against Tuberculosis and Lung Disease (IUATLD-ER) initiated the present survey to obtain an updated picture of the use of BCG vac- cination in European countries. In particular, the following issues were evaluated: - concordance of national vaccination programmes with the above-mentioned WHO recommenda- tions; - relationship between policy, including general BCG primary vaccination and/or revaccination, and the TB epidemiological situation in a given country; and Bulletin of the World Health Organization, 1998, 76 (1): 85-91 © World Health Organization 1998 85 L. Trnka et al. differences between Western and Central- Eastern European countries, and in the latter, between those countries that were or were not part of the former soviet Union. Methodology The study was a retrospective survey based on a standardized questionnaire sent to qualified public health staff attached to the ministries of health of European countries. A draft questionnaire was pre- pared by an IUATLD-ER task force, discussed by the IUATLD-ER Executive Committee, and ap- proved in 1994. The questionnaire, which focused on whether mass (general), selected primary or revaccination was performed, indications for individual types of vaccination, manufacturer of the BCG vaccine used, application of tuberculin tests before and after vacci- nation, and public health aspects, consisted of 11 sections and 40 single-choice questions. In 1995 an initial postal distribution of the ques- tionnaires was made to IUATLD-ER councillors. Because of the unsatisfactory high rate of non- response (23 out of 50 of those who received the form), the survey was completed by carrying out a second postal distribution of the questionnaire to WHO tuberculosis experts in the countries. The completed questionnaires were stored in a database at a coordinating centre and then analysed. The following criteria were used to evaluate adherence of countries to BCG vaccination programmes: - in countries with a high incidence of TB infection BCG vaccination is given within the first year of life; - tuberculin skin testing is not used to make deci- sions about BCG revaccination; and - general BCG revaccination is not performed. For the purposes of this analysis a country was defined to be at a high incidence of TB infection if the number of newly notified TB cases (all forms) in 1995 was >20 per 100000 population or if the number of newly notified sputum-smear-positive cases in the same period was >12.1 per 100000 popu- lation. The analysis was repeated using an alterna- tive cut-off, corresponding to 33 newly identified TB cases per 100 000 population. The first cut-off (incidence, >20 cases per 100000) was chosen by doubling the value used to define low incidence countries (8) (<10 cases per 100000 population) in order to correct for undernotification (9-12). The cut-off for the incidence of all newly notified TB cases (33 per 100000) and the cut-off for sputum- smear-positive cases (>12.1 per 100000) were based on the average rates observed in Europe (12). The incidences of newly notified cases per 100000 popu- lation (all cases and sputum-smear-positive cases) were based on WHO data (12). The relationship between policy, including mass BCG primary vaccination and/or revaccination, and the epidemiological TB situation in a given country was carried out by comparing countries after they had been stratified according to the above- mentioned cut-offs. Similarly, the differences be- tween Western and Central-Eastern European countries and in the latter group, between countries that were or were not part of the former Soviet Union, were evaluated using 2 x 2 contingency tables for general primary vaccination, revaccina- tion, and adherence to WHO guidelines. Data analysis was carried out using SPSS and Stratgraphics (version 6.0) statistical packages. Ex- pected and observed frequencies (qualitative data) were compared using a two-tailed uncorrected x2 test or Fischer's exact test, where appropriate (1 cell count <5). P values <0.05 were considered statisti- cally significant. The results of a separate survey by an IUATLD-ER Task Group, carried out using a coor- dinated questionnaire in the same countries with the same methodology that we used in our study, to investigate the current practices for preventing TB among health care workers in European hospitals (including a question on BCG vaccine), are also in- cluded in this review (13). Results Questionnaires were returned by 41 of the 50 coun- tries (82%) in the WHO European Region (Table 1). In 33 countries the BCG vaccination pro- grammes are uniform throughout the country, and in the vast majority are advised by governmental authorities. In Germany, Ireland, Spain and the United Kingdom some areas have adopted modified programmes. In 29 European countries (71% of respondents) general (mass) BCG vaccination of either neonates or older children is carried out. The distribution of countries that perform mass primary vaccination of neonates is shown in Fig. 1. Mass vaccination of older children is advised in France upon entering a nursery or primary school), Greece (at 6 years of age), Malta (at 12-13 years of age), Norway, and United Kingdom (at 13-14 years of age). WHO Bulletin OMS. Vol 76 199886 BCG vaccination policy in Europe: 1994-96 Table 1: Summary of the results of the questionnaire survey on BCG vaccination policy in European countries, 1994-96 Age group at revaccination No. revacc:d (years) PPD Country Proga Apprb afterc 1 2 3 5-8 10-15 >15 Westem Europe Austria Belgium Denmark England and Wales Finland France Germany Iceland Ireland Italy Luxembourg Malta Monaco Netherlands Norway Portugal Scotland Spain San Marino Sweden Switzerland N N y N y y N N N y y N y y y N N N y y y y y N y y y y y N N y y y Central-Eastem Europe, group 1 Albania Y N Bosnia-Herzegovina Bulgaria Y N Croatia Y N Czech Republic Y N Greece Y Y Hungary Y N Israel Y Y The former Yugoslav Republic of Macedonia Y N Poland Y N Romania Y N Slovakia Y N Slovenia Y N Turkey Y ? Yugoslavia Central-Eastern Europe, group 2 Armenia Y N Azerbaijan Y N Belarus Y N Estonia Y N Georgia Y N Kazakhstan Y N Kyrgyzstan Latvia Y N Lithuania Y N Republic of Moldova Y N Russian Federation Y Y Tajikistan Turkmenistan Ukraine Uzbekistan N N N N y y N N N y N N N y N y y y N N y y y N y y y y y N y ? N N N N N y N N N N y N N N N y y y y N N N N N N N N N N 5 6 1.7 7 6 Y Y Y Y Y Y N Y Y N Y N Y Y Y Y 18-25 18-2011 12 12-14 11 10-11 7 or 14 7 7 6-7 8 5-6 6-7 7 7 6-7 12 13 10 14 17 14-15 11-12 14-15 14-15 18 21 16-17 18 16 15 25 17 21-22 WHO Bulletin OMS. Vol 76 1998 a Prog = BCG programme countrywide identical (Y) or with regional differences (N). b Appr = approval of parents necessary (Y) or unnecessary (N). c PPD after = tuberculin skin test after BCG vaccination routinely performed (Y) or not performed (N). d No. revacc = No. of BCG revaccinations. 87 L. Trnka et al. Fig. 1. Study countries where general BCG primary vaccination of neonates is practised. General BCG pnmary vaccinaton of neonates In total, 12 of 41 countries prefer selective BCG vaccination, with the following policy options: - perform the vaccination only if asked for by parents; - the vaccination is performed rather exclusively; and - vaccinate predominantly children in contact with bacillary index cases, immigrants from high prevalence countries, asylum seekers, travellers to high prevalence countries, and medical and paramedical staff in hospitals where bacillary TB patients are hospitalized. In 12 countries all tuberculin-negative health- care workers receive BCG vaccine. In four, only se- lected groups of health-care workers are vaccinated, and in six countries BCG vaccination of health-care workers is not recommended at all (13). In 18 countries (see Table 1) parents must give their consent before BCG vaccination is carried out, while in others parental approval is not necessary since vaccination is compulsory. Tuberculin skin tests are performed before vaccination of older children only. In 15 countries skin tests are performed after primary vaccina- tion, while a further 15 countries do not insist on tuberculin skin tests as a proof of prior vaccination. Rather exceptionally, observation of BCG scars is recommended. In 15 of 41 respondent countries BCG re- vaccination is not permitted (Fig. 2). In 24 countries (in Central-Eastern Europe and in France and Por- tugal) the revaccination policy is fixed by law and applies to certain age groups. The number of revaccinations and age when they are performed are shown in Table 1. In a few other countries selective revaccinations are performed on the basis of nega- tive tuberculin skin tests. Primary vaccinations and revaccinations are performed in Europe exclusively by the intradermal route. Table 2 reviews the manufacturers of the BCG vaccines used in Europe. Two commercial producers cover 14 European countries and local BCG production is limited to a few countries only. BCG vaccination programmes met WHO rec- ommendations in 18 of the 41 respondent countries (44%). In Western Europe, France and Portugal do not meet the criterion for general BCG revac- cination, and Ireland the criterion for general primary vaccination. Within Central and Eastern Europe, Slovenia was the only country to meet the three WHO criteria. Mass primary vaccination and general revaccination are very common in coun- tries where TB has a high prevalence, without taking into consideration differences in the two incidence cut-offs proposed (P < 0.0001 for each one of the criteria and for both values of cut-off). A highly significant difference was found between Western and Central-Eastern European countries in terms of WHO Bulletin OMS. Vol 76 199888 BCG vaccination policy in Europe: 1994-96 Fig. 2. Study countries with no general BCG revaccination policy. _ Countries wiUh no genera BCG rvaccinatlon their adhesion to WHO guidelines (P < 0.0001) and revaccination (P < 0.0001). In Central-Eastern Europe there was no difference between countries that were or were not part of the former Soviet Union (adherence: P = 1; general primary vaccina- tion: P = 0.48; general revaccination: P = 0.48). Table 2: Source of BCG vaccines used in the study countries SSI Copenhagen Pasteur-Merieux Glaxo-Evans-Berua Boehring-Hoechst Gamalea, Russian Federation RIVM Bilthoven Institut Pasteur Moreau, WSS Lublin Local manufacturer Different vaccines donated by WHO or UNICEF Not specified 8 Denmark, Estonia, Iceland, Latvia, Lithuania, Malta, Norway, Sweden 6 Austria, Greece, Ireland, Italy, Slovenia, former Yugoslav Republic of Macedonia 4 Albania, Finland, Switzerland, United Kingdom 3 Czech Republic, Germany, Slovakia 2 Belarus, Russian Federation 2 3 3 Belgium, Netherlands Luxembourg Poland Bulgaria, Hungary, Romania Armenia, Georgia, Republic of Moldova 8 Azerbaijan, Croatia, France, Israel, Kazakhstan, Portugal, Spain, Turkey Discussion The aim of the study was to update information on BCG vaccination programmes in Europe and to evaluate the correspondence between national vacci- nation programmes and WHO recommendations, the relationship between policy (including general BCG primary vaccination and/or revaccination) and the epidemiological situation in the country, and the differences between Western and Central-Eastern European countries and within the latter group, be- tween those that were or were not part of the former Soviet Union. The results confirm that general primary vac- cination is performed mainly in Central-Eastern Europe and in some countries of Southern Europe. Similarly, revaccination is performed predomi- nantly in Central-Eastern Europe, with the excep- tion of Slovenia and Israel, and is not carried out in Western Europe with the exception of France and Portugal. BCG vaccination programmes met WHO rec- ommendations in 18 of 41 European countries (44%). Mass primary vaccination and revaccina- tion are very common in countries where the preva- lence of TB is high, with no difference arising from application of the two cut-off values proposed. A significant difference was found between West and Central-Eastern European countries in terms of their adhesion to WHO-recommended BCG vac- cination guidelines, adoption of mass primary vaccination, and revaccination; however, in Central- Eastern Europe in this respect there was no differ- WHO Bulletin OMS. Vol 76 1998 89 L. Trnka et al. ence between countries that were or were not part of the former Soviet Union. There are various reasons for this situation, but the most important is the epidemiological situation regarding tuberculosis. Countries with a high prevalence of TB in Europe choose mass primary vaccination of children and attempt to extend the protection for as long as possible through repeated revaccinations. Some pneumologists and paedia- tricians in these countries are reluctant to accept the available body of evidence on the role of BCG vaccination and prefer to adhere to traditional concepts on the dominant position of preventive methods in TB control. These individuals fear that if BCG vaccinations and revaccinations are not offered the TB situation in their countries will deteriorate; however, it is to be hoped that their opinions will change. National TB programmes need to reflect the available body of scientific evidence, promote better treatment of contagious cases, and must be intensified in order to limit the spread of TB infection. The tradition of carrying out repeated revac- cinations stems also from the use ofBCG vaccines of low but undefined protective capacity. Mass BCG primary vaccination and revac- cination programmes carried out within a centralized health system are easier to perform than selective primary vaccination of risk groups, passive case finding, or directly observed ambulatory treatment. Although BCG vaccine is relatively cheap, vac- cination after the first year of life or revaccinations may represent a significant economic burden for health care systems, particularly in Eastern Europe. Postponed mass primary vaccinations and repeated revaccinations are probably not cost-effective even in high-prevalence European countries, since mass primary vaccination is not cost-effective in countries where the prevalence of TB is low (1). In a period of limited economic resources, where different programmes are competing for financial support, health policy decisions should be based on cost- effectiveness. Unfortunately, the cost-effectiveness of BCG vaccination is difficult to study because of the vari- ability in vaccine efficacy, BCG preparations, vacci- nation schedules, and the TB epidemiological situation in different countries. Properly designed studies of the cost-effectiveness of TB control projects are a priority in most European countries. Until the effectiveness of revaccination and postponed vaccination in countries where the preva- lence of TB is high or where economic resources are limited are clearly demonstrated, such preventive measures should be discouraged, in agreement with WHO recommendations (1), to permit mobilization of resources to be redirected to TB control activities of proven efficacy. The results of our study show that in 23 of 41 European countries WHO recommendations are not being met (1). Several comments can be made in this respect, as outlined below. * In France and Portugal BCG revaccination should be stopped and the laws in this respect changed. * In 18 countries (Luxembourg, Portugal; Albania, Bulgaria, Czech Republic, Greece, Hungary, Poland, Romania, Slovakia, Turkey; Armenia, Azerbaijan, Belarus, Kazakhstan, Latvia, Lithuania, and the Russian Federation) stopping the BCG revaccination of children aged more than 7 years is recommended. * Countries that carry out BCG revaccination at school entrance should reconsider this policy. * Tuberculin skin testing should not be used before or after BCG vaccination, except in small studies to check the quality of vaccination and vaccines. Acknowledgements The IUATLD-Europe Region Task Group thanks the individuals and health authorities in European countries listed below for answering the questionnaires and for the fruitful collaboration. H. Cocoli, 1. Mino (Albania); E. Matevosian (Armenia); E. Junker (Austria); F. Abdullager, A. Meherremov (Azerbaijan); L. Gorbach (Belarus); J.M. Verstraeten (Belgium); S. Popova (Bulgaria); R. Pardon (Croatia); S. Kos (Czech Republic); G. Pallisgaard (Den- mark); J. Leese (England and Wales); H. Sillastu (Estonia); E. Tala, K. Liipoo (Finland); M. Lequellec-Nathan (France); R. Urushadse (Georgia); R. Ferlinz, M. Forssbohm, F. Schweissinger (Germany); N.E. Yatromanolakis (Greece); D. Kozma (Hungary); T. Bloendal (Ireland); L. Clancy (Ireland); A. Eliraz (Israel); L. Casali, G.B. Migliori (Italy); A. Pjunusbekov (Kazakhstan); D. Pakule (Latvia); D. Schlapkauskaticz (Lithuania); G. Molitor (Luxembourg); S. Talevski (the former Yugoslav Republic of Macedonia); R. Busuttil (Malta); C. lavorski (Republic of Moldova); C.S.B. Lambregts van Weezenbeek (Netherlands); T. Ruigdal (Norway); 1. Szczuka (Poland); M.L. Antunes (Portugal); E. Corlan, D. Stavir (Romania); A.G. Khomenko, L.A. Mitinskaya (Russian Federation); A. Thores, P. Christie (Scotland); A. Bajan (Slovakia); J. Schorli (Slovenia); R. Rey (Spain); V. Romanus, G. Boman (Sweden); J.P. Zellweger (Switzerland); and E. Kibaroglu (Turkey). Resume Enquete sur la politique de vaccination par le BCG en Europe: 1994-1996 Une enquete r6trospective basee sur un question- naire standardise adress6 a des experts de sant6 WHO Bulletin OMS. Vol 76 199890 BCG vaccination policy in Europe: 1994-96 publique dans le domaine de la tuberculose a 6te r6alisee dans 50 pays de la R6gion europeenne de l'OMS, avec pour objectifs: - d6terminer la concordance entre les programmes de vaccination antituberculeuse et les recom- mandations de l'OMS; - identifier la relation entre la politique consistant en une vaccination et/ou revaccination de masse par le BCG et la situation 6pidemio- logique de la tuberculose dans le pays; - d6terminer les diff6rences entre les pays d'Europe de l'Ouest et ceux d'Europe centrale et orientale et, dans ce dernier groupe, entre les pays de l'ex-Union sovi6tique et les autres. Sur 50 pays, 41 (82%) ont envoye une reponse. Dans 29 pays, pour la plupart d'Europe centrale et orientale, la vaccination gen6ralis6e (= de masse) par le BCG est pratiqu6e soit chez les nouveau-n6s soit plus tardivement chez l'enfant. Douze pays, pour la plupart en Europe de l'Ouest, pratiquent une vaccination s6lective des groupes a risque. Dans 21 pays, pour la plupart d'Europe cen- trale et orientale, la vaccination de masse par le BCG est pratiqu6e par voie intradermique. Aucun producteur en particulier ne domine le march6, mais deux fabricants assurent la fourniture du vaccin dans 14 pays. Les programmes nationaux de vaccination par le BCG suivent les recommandations de l'OMS dans 44% des pays. La primovaccination de masse et les revaccinations g6n6ralis6es sont courantes dans les pays a forte pr6valence de la tuberculose. Une diff6rence nettement significative entre les pays d'Europe de l'Ouest et ceux d'Europe centrale et orientale est apparue en ce qui concerne le re- spect des recommandations de l'OMS (p < 0,001), I'adoption de la primovaccination de masse (p < 0,0001) et la revaccination (p < 0,001). Dans le deuxieme groupe de pays, aucune difference n'a 6te observ6e entre les pays de 1'ex-Union sovi6- tique et les autres (respect des recommandations: p = 1; primovaccination gen6ralisee: p = 0,48; revaccination: p = 0,48). D'apres nos observations, le respect des recommandations de l'OMS par les programmes nationaux de lutte contre la tuberculose doit etre renforce afin de limiter la propagation de la maladie. Comme apres l'age d'un an les vaccinations et revaccinations par le BCG repr6sentent un fardeau pour le systeme de soins, il convient de promouvoir des 6tudes de cout-efficacite et de deconseiller I'adoption de mesures pr6ventives dont l'efficacite n'est pas demontree. References 1. Global Tuberculosis Programme and Global Programme on Vaccines. Statement on BCG revaccination for the prevention of tuberculosis. Weekly epidemiological record, 1995, 70(32): 229- 236. 2. Colditz GA et al. 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Tuberculosis elimination in the coun- tries of Europe and other industrialized countries. Eu- ropean respiratory journal, 1991, 4: 1288-1295. 8. Raviglione MC et al. Secular trends of tuberculosis in Western Europe. Bulletin of the World Health Organi- zation, 1993, 71: 297-306. 9. Raviglione MC et al. Tuberculosis trends in Eastern Europe and the former USSR. Tuberculosis and lung disease, 1994, 75: 400-416. 10. Migliori GB et al. Validation of the surveillance sys- tem for new cases of tuberculosis in a province of northern Italy. European respiratory journal, 1995, 8: 1252-1258. 11. Sheldon CD et al. Notification of tuberculosis: how many cases are never reported? Thorax, 1992, 47: 1015-1018. 12. Tuberculosis - a global emergency: case notification update. Geneva, World Health Organization, 1996. Unpublished document WHO/TB/96.197: 18-20 (available upon request from Global Tuberculosis Programme, World Health Organization, 1211 Geneva 27, Switzerland). 13. Zellweger JP et al. 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