survey of bcg vaccination policy europe -...

Survey of BCG vaccination policy in Europe:1994-96L. 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 intuberculosis in 50 European countries, was carried out to evaluate the following: concordance betweennational vaccination programmes and WHO recommendations on BCG vaccination for prevention of tuber-culosis; relation between BCG vaccination and revaccination policy and the tuberculosis epidemiologicalsituation; and differences in BCG vaccination policy between Western and Central-Eastern Europeancountries.

The results obtained (from 41 (82%) of the 50 countries) revealed that BCG vaccination programmesmet WHO recommendations in 44% of European countries. Mass primary vaccination and generalrevaccination were extremely common in countries where the prevalence of tuberculosis was high. A highlysignificant difference was found between Western and Central-Eastern European countries in terms of theiradhesion to WHO recommendations. Within Central-Eastern Europe no difference was found betweencountries 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 beenproperly established should be discouraged.

IntroductionBacillus Calmette-Gu6rin (BCG) vaccine has beenused in Europe to prevent tuberculosis (TB) in hu-mans since 1921. At that time no other method ofpreventing TB in children was known (1) and asa result in virtually all European countries BCGvaccination programmes were developed withspecific indications, methods, and timetables. Suchprogrammes have never been uniform owing todisparate results from clinical trials of the vaccine'sefficacy (2).

Realization of the negligible impact of BCGvaccination on the community transmission of TB,the limited protection afforded to children by BCGvaccination, the doubtful efficacy of revaccinations,

1 Tuberculosis Surveillance Unit, Clinic of Pneumology and ChestSurgery, University Hospital, Prague Bulovka, Budinova 2, 18000Prague, Czech Republic. Requests for reprints should be sent toProfessor 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 Unionagainst 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 postvaccinationcomplications have raised doubts on the cost-effectiveness of BCG vaccination programmes andcontributed to their subsequent modifications inEuropean countries (3-5).

In the perspective of TB control, WHO recentlyrecommended general BCG vaccination of infants assoon after birth as possible in countries where theannual risk of tuberculosis infection is high, at thesame time discouraging revaccinations, and stressingthat BCG vaccination should be considered an ad-junct to national TB programmes (1). Rapid detec-tion and effective antituberculous treatment remainthe highest priorities for TB control in all countries(6, 7).

The European Region of the InternationalUnion against Tuberculosis and Lung Disease(IUATLD-ER) initiated the present survey toobtain an updated picture of the use of BCG vac-cination in European countries. In particular, thefollowing issues were evaluated:- concordance of national vaccination programmes

with the above-mentioned WHO recommenda-tions;

- relationship between policy, including generalBCG primary vaccination and/or revaccination,and the TB epidemiological situation in a givencountry; 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 notpart of the former soviet Union.

MethodologyThe study was a retrospective survey based on astandardized questionnaire sent to qualified publichealth staff attached to the ministries of health ofEuropean countries. A draft questionnaire was pre-pared by an IUATLD-ER task force, discussed bythe IUATLD-ER Executive Committee, and ap-proved in 1994.

The questionnaire, which focused on whethermass (general), selected primary or revaccinationwas performed, indications for individual types ofvaccination, manufacturer of the BCG vaccine used,application of tuberculin tests before and after vacci-nation, and public health aspects, consisted of 11sections 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 theform), the survey was completed by carrying out asecond postal distribution of the questionnaire toWHO tuberculosis experts in the countries. Thecompleted questionnaires were stored in a databaseat a coordinating centre and then analysed.

The following criteria were used to evaluateadherence of countries to BCG vaccinationprogrammes:- in countries with a high incidence of TB infection

BCG vaccination is given within the first year oflife;

- 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 ifthe number of newly notified TB cases (all forms) in1995 was >20 per 100000 population or if thenumber of newly notified sputum-smear-positivecases 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 TBcases per 100 000 population. The first cut-off(incidence, >20 cases per 100000) was chosen bydoubling the value used to define low incidencecountries (8) (<10 cases per 100000 population) inorder to correct for undernotification (9-12). Thecut-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 basedon the average rates observed in Europe (12). Theincidences 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 massBCG primary vaccination and/or revaccination, andthe epidemiological TB situation in a given countrywas carried out by comparing countries after theyhad been stratified according to the above-mentioned cut-offs. Similarly, the differences be-tween Western and Central-Eastern Europeancountries and in the latter group, between countriesthat were or were not part of the former SovietUnion, were evaluated using 2 x 2 contingencytables for general primary vaccination, revaccina-tion, and adherence to WHO guidelines.

Data analysis was carried out using SPSS andStratgraphics (version 6.0) statistical packages. Ex-pected and observed frequencies (qualitative data)were compared using a two-tailed uncorrected x2 testor Fischer's exact test, where appropriate (1 cellcount <5). P values <0.05 were considered statisti-cally significant.

The results of a separate survey by anIUATLD-ER Task Group, carried out using a coor-dinated questionnaire in the same countries with thesame methodology that we used in our study, toinvestigate the current practices for preventing TBamong health care workers in European hospitals(including a question on BCG vaccine), are also in-cluded in this review (13).

ResultsQuestionnaires were returned by 41 of the 50 coun-tries (82%) in the WHO European Region (Table1).

In 33 countries the BCG vaccination pro-grammes are uniform throughout the country, andin the vast majority are advised by governmentalauthorities. In Germany, Ireland, Spain and theUnited Kingdom some areas have adopted modifiedprogrammes.

In 29 European countries (71% of respondents)general (mass) BCG vaccination of either neonatesor older children is carried out. The distribution ofcountries that perform mass primary vaccination ofneonates is shown in Fig. 1.

Mass vaccination of older children is advised inFrance upon entering a nursery or primary school),Greece (at 6 years of age), Malta (at 12-13 years ofage), Norway, and United Kingdom (at 13-14 yearsof age).

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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 revaccinationNo. revacc:d (years)

PPDCountry Proga Apprb afterc 1 2 3 5-8 10-15 >15

Westem EuropeAustriaBelgiumDenmarkEngland and WalesFinlandFranceGermanyIcelandIrelandItalyLuxembourgMaltaMonacoNetherlandsNorwayPortugalScotlandSpainSan MarinoSwedenSwitzerland

NNyNyyNNNy

y

NyyyN

N

Ny

yyyyNyyyy

yNNyy

y

Central-Eastem Europe, group 1Albania Y NBosnia-HerzegovinaBulgaria Y NCroatia Y NCzech Republic Y NGreece Y Y

Hungary Y NIsrael Y Y

The former YugoslavRepublic of Macedonia Y N

Poland Y NRomania Y NSlovakia Y NSlovenia Y NTurkey Y ?Yugoslavia

Central-Eastern Europe, group 2Armenia Y NAzerbaijan Y NBelarus Y NEstonia Y NGeorgia Y NKazakhstan Y NKyrgyzstanLatvia Y NLithuania Y NRepublic of Moldova Y NRussian Federation Y Y

TajikistanTurkmenistanUkraineUzbekistan

NNN

NyyNNNy

N

NN

y

N

yyyNN

yyyN

yyyy

yNy

?

NNNNNyNNNNyN

N

N

N

yy

y

y

NNNNN

NNNN

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

12-1411

10-11

7 or 14

7

7

6-78

5-66-7

77

6-7

12

13

10

1417

14-15

11-12

14-15

14-15

18

2116-17

18

16

15

25

17

21-22


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 ispractised.

General BCG pnmary vaccinaton of neonates

In total, 12 of 41 countries prefer selective BCGvaccination, with the following policy options:

- perform the vaccination only if asked for byparents;

- the vaccination is performed rather exclusively;and

- vaccinate predominantly children in contact withbacillary index cases, immigrants from highprevalence countries, asylum seekers, travellersto high prevalence countries, and medical andparamedical staff in hospitals where bacillary TBpatients 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-careworkers is not recommended at all (13).

In 18 countries (see Table 1) parents must givetheir consent before BCG vaccination is carried out,while in others parental approval is not necessarysince vaccination is compulsory.

Tuberculin skin tests are performed beforevaccination of older children only. In 15 countriesskin tests are performed after primary vaccina-tion, while a further 15 countries do not insist ontuberculin skin tests as a proof of prior vaccination.Rather exceptionally, observation of BCG scars isrecommended.

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 andapplies to certain age groups. The number ofrevaccinations and age when they are performed areshown in Table 1. In a few other countries selectiverevaccinations are performed on the basis of nega-tive tuberculin skin tests.

Primary vaccinations and revaccinations areperformed in Europe exclusively by the intradermalroute. Table 2 reviews the manufacturers of theBCG vaccines used in Europe. Two commercialproducers cover 14 European countries and localBCG production is limited to a few countriesonly.

BCG vaccination programmes met WHO rec-ommendations in 18 of the 41 respondent countries(44%). In Western Europe, France and Portugal donot meet the criterion for general BCG revac-cination, and Ireland the criterion for generalprimary vaccination. Within Central and EasternEurope, Slovenia was the only country to meet thethree WHO criteria. Mass primary vaccination andgeneral revaccination are very common in coun-tries where TB has a high prevalence, without takinginto consideration differences in the two incidencecut-offs proposed (P < 0.0001 for each one of thecriteria and for both values of cut-off). A highlysignificant difference was found between Westernand Central-Eastern European countries in terms of



Fig. 2. Study countries with no general BCG revaccination policy.

_ Countries wiUh no genera BCG rvaccinatlon

their adhesion to WHO guidelines (P < 0.0001) andrevaccination (P < 0.0001). In Central-EasternEurope there was no difference between countriesthat were or were not part of the former SovietUnion (adherence: P = 1; general primary vaccina-tion: P = 0.48; general revaccination: P = 0.48).

Table 2: Source of BCG vaccines used in the studycountries

SSI Copenhagen

Pasteur-Merieux

Glaxo-Evans-Berua

Boehring-Hoechst

Gamalea, RussianFederation

RIVM Bilthoven

Institut Pasteur

Moreau, WSS Lublin

Local manufacturer

Different vaccinesdonated by WHO orUNICEF

Not specified

8 Denmark, Estonia, Iceland, Latvia,Lithuania, Malta, Norway, Sweden

6 Austria, Greece, Ireland, Italy,Slovenia, former YugoslavRepublic 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 ofMoldova

8 Azerbaijan, Croatia, France,Israel, Kazakhstan, Portugal,Spain, Turkey

DiscussionThe aim of the study was to update information on

BCG vaccination programmes in Europe and toevaluate the correspondence between national vacci-nation programmes and WHO recommendations,the relationship between policy (including generalBCG primary vaccination and/or revaccination) andthe epidemiological situation in the country, and thedifferences between Western and Central-EasternEuropean countries and within the latter group, be-tween those that were or were not part of the formerSoviet Union.

The results confirm that general primary vac-

cination is performed mainly in Central-EasternEurope 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 inWestern Europe with the exception of France andPortugal.

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 fromapplication of the two cut-off values proposed. Asignificant difference was found between West andCentral-Eastern European countries in terms oftheir adhesion to WHO-recommended BCG vac-

cination guidelines, adoption of mass primaryvaccination, 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 ofthe former Soviet Union.

There are various reasons for this situation, butthe most important is the epidemiological situationregarding tuberculosis. Countries with a highprevalence of TB in Europe choose mass primaryvaccination of children and attempt to extend theprotection for as long as possible through repeatedrevaccinations. Some pneumologists and paedia-tricians in these countries are reluctant to acceptthe available body of evidence on the role of BCGvaccination and prefer to adhere to traditionalconcepts on the dominant position of preventivemethods in TB control. These individuals fear thatif BCG vaccinations and revaccinations are notoffered the TB situation in their countries willdeteriorate; however, it is to be hoped that theiropinions will change. National TB programmes needto reflect the available body of scientific evidence,promote better treatment of contagious cases, andmust be intensified in order to limit the spread of TBinfection.

The tradition of carrying out repeated revac-cinations stems also from the use ofBCG vaccines oflow but undefined protective capacity.

Mass BCG primary vaccination and revac-cination programmes carried out within a centralizedhealth system are easier to perform than selectiveprimary vaccination of risk groups, passive casefinding, or directly observed ambulatory treatment.

Although BCG vaccine is relatively cheap, vac-cination after the first year of life or revaccinationsmay represent a significant economic burden forhealth care systems, particularly in Eastern Europe.Postponed mass primary vaccinations and repeatedrevaccinations are probably not cost-effective evenin high-prevalence European countries, since massprimary vaccination is not cost-effective in countrieswhere the prevalence of TB is low (1). In a periodof limited economic resources, where differentprogrammes are competing for financial support,health policy decisions should be based on cost-effectiveness.

Unfortunately, the cost-effectiveness of BCGvaccination is difficult to study because of the vari-ability in vaccine efficacy, BCG preparations, vacci-nation schedules, and the TB epidemiologicalsituation in different countries. Properly designedstudies of the cost-effectiveness of TB controlprojects are a priority in most European countries.

Until the effectiveness of revaccination andpostponed vaccination in countries where the preva-lence of TB is high or where economic resources arelimited are clearly demonstrated, such preventivemeasures should be discouraged, in agreement withWHO recommendations (1), to permit mobilization

of resources to be redirected to TB control activitiesof proven efficacy.

The results of our study show that in 23 of 41European countries WHO recommendations are notbeing met (1). Several comments can be made in thisrespect, as outlined below.* In France and Portugal BCG revaccination shouldbe 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 BCGrevaccination of children aged more than 7 years isrecommended.* Countries that carry out BCG revaccination atschool entrance should reconsider this policy.* Tuberculin skin testing should not be used beforeor after BCG vaccination, except in small studies tocheck the quality of vaccination and vaccines.

AcknowledgementsThe IUATLD-Europe Region Task Group thanks theindividuals and health authorities in European countrieslisted below for answering the questionnaires and forthe 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).

ResumeEnquete sur la politique de vaccinationpar le BCG en Europe: 1994-1996Une enquete r6trospective basee sur un question-naire standardise adress6 a des experts de sant6



publique dans le domaine de la tuberculose a 6ter6alisee dans 50 pays de la R6gion europeenne del'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 consistanten une vaccination et/ou revaccination demasse par le BCG et la situation 6pidemio-logique de la tuberculose dans le pays;

- d6terminer les diff6rences entre les paysd'Europe de l'Ouest et ceux d'Europe centrale etorientale et, dans ce dernier groupe, entre lespays 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 etorientale, la vaccination gen6ralis6e (= de masse)par le BCG est pratiqu6e soit chez les nouveau-n6ssoit plus tardivement chez l'enfant. Douze pays,pour la plupart en Europe de l'Ouest, pratiquent unevaccination s6lective des groupes a risque.

Dans 21 pays, pour la plupart d'Europe cen-trale et orientale, la vaccination de masse par leBCG est pratiqu6e par voie intradermique. Aucunproducteur en particulier ne domine le march6, maisdeux fabricants assurent la fourniture du vaccindans 14 pays.

Les programmes nationaux de vaccination parle BCG suivent les recommandations de l'OMSdans 44% des pays. La primovaccination de masseet les revaccinations g6n6ralis6es sont courantesdans les pays a forte pr6valence de la tuberculose.Une diff6rence nettement significative entre lespays d'Europe de l'Ouest et ceux d'Europe centraleet 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 ledeuxieme groupe de pays, aucune difference n'a6te 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 desrecommandations de l'OMS par les programmesnationaux de lutte contre la tuberculose doit etrerenforce afin de limiter la propagation de la maladie.Comme apres l'age d'un an les vaccinations etrevaccinations par le BCG repr6sentent un fardeaupour le systeme de soins, il convient de promouvoir

des 6tudes de cout-efficacite et de deconseillerI'adoption de mesures pr6ventives dont l'efficaciten'est pas demontree.

References1. Global Tuberculosis Programme and Global

Programme on Vaccines. Statement on BCGrevaccination for the prevention of tuberculosis.Weekly epidemiological record, 1995, 70(32): 229-236.

2. Colditz GA et al. Efficiacy of BCG vaccine in theprevention of tuberculosis: meta-analysis of the pub-lished literature. Journal of the American Medical As-sociation, 1994, 271: 698-702.

3. Romanus V. The impact of BCG vaccination onmycobacterial disease among children born inSweden between 1969 and 1993. Stockholm,Smittsdkyddsinstituted, 1995.

4. Lotte A et al. BCG complications. Advances in tuber-culosis research, 1984, 21: 107-193.

5. Trnka L, Dankova D, Svandova E. Six years experi-ence with the discontinuation of BCG vaccination. 1.Risk of tuberculosis infection and disease. Tuberculo-sis and lung disease, 1993; 74: 167-172.

6. WHO tuberculosis programme: framework for effec-tive tuberculosis control. Geneva, World Health Or-ganization, 1994. Unpublished document WHO/TB/94.179: 1-13 (available upon request from GlobalTuberculosis Programme, World Health Organization,1211 Geneva 27, Switzerland).

7. Clancy L et al. 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 inWestern Europe. Bulletin of the World Health Organi-zation, 1993, 71: 297-306.

9. Raviglione MC et al. Tuberculosis trends in EasternEurope and the former USSR. Tuberculosis and lungdisease, 1994, 75: 400-416.

10. Migliori GB et al. Validation of the surveillance sys-tem for new cases of tuberculosis in a province ofnorthern Italy. European respiratory journal, 1995, 8:1252-1258.

11. Sheldon CD et al. Notification of tuberculosis: howmany cases are never reported? Thorax, 1992, 47:1015-1018.

12. Tuberculosis - a global emergency: case notificationupdate. Geneva, World Health Organization, 1996.Unpublished document WHO/TB/96.197: 18-20(available upon request from Global TuberculosisProgramme, World Health Organization, 1211Geneva 27, Switzerland).

13. Zellweger JP et al. Prevention of tuberculosis amonghealth-care workers in European hospitals. Tubercu-losis and lung disease, 1996, 77(Suppl. 2): 108-109.

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