WORLD
HEALTH
.... ....
ORGANIZATION
REGIONAL OFFICE FOR THE WESTERN PACIFIC BUREAU REGIONAL DU PACIFIQUE OCCIDENTAL
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ORGANISATION MONOIALE , DE LA SANTE
REGIONAL COMMITTEE Thirty-second session Seoul 22-28 September 1981 .....
WPR/RC32/l5 Corr.l 13 August 1981 ENGLISH ONLY
Provisional agenda item 20 REGIONAL POLICIES ON BCG VACCINATION Corrigenda Page 3, section 2.1, third paragraph, line 2 Before explained, insert partly. Page 4, section 2.2, fifth paragraph, (1) For the existing text substitute: (1) BCG vaccination did not protect against bacillary pulmonary tuberculosis.
Page 5, section 2.3.1, first paragraph, second line After recommended that, insert the results of the south Indian trial should not be regarded as applying automatically to other parts of the world and that ••• ,I' '.
VYORLD HEALTH ORGANIZATION
REGIONAL OFFICE FOR THE WESTERN PACIFIC BUREAU RiGIONAL DUPACIFIQUE OCCIDENTAL
•
ORGANISATION MQNDIALE , DE LA SANtE
REGIONAL COMMITTEE Thirty-second session Seoul 22-28 September 1981 Provisional agenda item 20
WPR/RC32/l5 28 July 1981
ORIGINAL:
ENGLISH
REGIONAL POLICIES ON BCG VACCINATION
In view of the recommendations of the WHO Study Group on BCG Vaccination Pol i'cies, held in Geneva in June 1980, it was fel t to be advisable to establish a study group within the Regional Office for the Western Pacific to review the recommendations of the formal WHO Study Group, review the magnitude and nature of the tuberculosis problem in th,e Region in relation to BCG vaccination, and recommend BCG vaccination policies for the Region. The WHO Study Group had been convened to cons ider whether modifications should be made in BCG .:vaccination policies in the light of current knowledge and particularly the discussions following the trial of BCG vaccines in south India, which commenced in 1968, and which had revealed a failure of BCG vaccine to protect and an unprecedented pattern of behaviour of tuberculosis in the trial area. The attached document summarizes the discussions which took place during the WHO Study Group on the south Indian and earlier trials, as well as its recommendations. It also reviews briefly the current policies in countries or areas of the Western Pacific Region and the conclus ions and recommendations of the Regional Office study group. The Regional Committee is requested to comment on the ions and re commenda t ions wi th re gard to regional policies on BCG vaccination. C onc 1 us
WPR/RC32/l5 page 2
1.
SUMMARY
A trial of BCG vaccination 1n south India pointed to its failure against bacillary pulmonary tuberculosis. However, other trials have shown its protective efficacy, while considerable differences in the epidemiology of tuberculosis and the local environment, such as in south India and in the trial areas where BCG vaccination has been shown to be effective, are cons idered to have an influence on the extent of its efficacy. Furthermore, the Indian trial was not designed to measure the effectiveness of BeG vaccination against childhood tuberculosis. There is evidence in many: count~ies or areas of the Region which suggests that BeG vaccine has been effective 1n the reduction of tuberculosis although the data hav~,c~.rt::tin deficiencies and the evidence i~ not c.mclus ive. An overwhelming majority bel ieve that it is effective. There are thus no satisfactory grounds' for recommending a change in BeG vaccination pol icies in Member States'of the Region; the same policies should be continued, particularly with regard to infants and young children. Even if the efficacy ofBCG~accination 1S assumed to be high, nat ,-onal policies, particularly' as regards '. the target age group, should continue to be adapted to clianging s'ttuations', which will take into account the epidemiological trends of tuberculosis in each country when its prevalence further declines. For that purpose, a meChanism should be est<lbl ished to collect such infortnatl.on as the incidence of tuberculosis by type of disease, age of incid~rice, relationship to history of BCG vaccination, BeG vaccination costs, and the occurrence of serious compl ications due to BCG vaccination.' Svstematic investigations among selected population groups, such as in Melanesia, are necessary to ascertain the effectiveness of BCG vaccination, wh ich should include the care of vaccine and vacc10ation techniques.
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2.
WHO STUDY GROUP ON BCG VACCINATION POLICIES l
The WHO Study Group on BCG Vaccination Policies met l.n Geneva 1n June 1QSO to cons ider whether modi fications should be made 1n current BCG vaccination policies in the light of existing knowledge and particularly the discuss ions following the trial of BeG vaccines i.n south India which started in 1'168 [\nd which was followed up for 7-1/2 years.
1 WHO p.0l~~ies:
Technical Report Series, No. report of a WHO Study Group).
652,
1980
(BeG
vacc i nation
2.1 Review of earlier trials
WPR/RC32/l5 page 3
The discuss ions which took place during the Study Group are summarized below.
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Reviewing the evidence availab Ie, the Study Group recalled the early observation 1n Europe that tuberculin-negative students often developed tuberculosis shortly after contact with patients, whereas tuberculinpositive students did not. This observation has never been challenged. The rather simplistic reasoning that, by rendering students tuberculinpositive by means of BCG vaccination, they could be protected against tuberculosis was confirmed quite convincingly. 1 Furthermore, 1.n an epidemic among schoolgirls exposed to massive infection, prevention of primary tuberculos is in the vaccinated was complete. 2 Tn other small epidemics in schools, a marked reduction of tuberculosis was observed 1n the vaccinated children. Eight controlled trials of BCG vaccination had been conducted before the 1968 trial in south India. 3 Studies conducted among north American Indians from 1935 to 1938, Chicago infants from 1937 to 1948, and 1n Great Britain from 1950 to 1952 showed an 80% protective efficacy. Studies in Georgia in 1947, Illinois from 1947 to 1948, and Georgia and Alabama in 1950 showed no effect; while those in Puerto Rico from 1949 to 1951 and earlier, from 1950 to 1955, in south India showed a 30% protective efficacy. The differences in the protective effect observed between the trial in Great Britain and the Georgia" and Alabama trial could be explained by di fferences in the prevalence of sensitization by atypical mycobacteria. In most tropical areas, low-grade tuberculin sensitivity, considered to be caused by atypical mycobacterial sens1t1zation, is prevalent. This is assumed to produce some immunity against tuberculosis in man, thus reducing the efficacy of BCG vaccination. In studies in laboratory animals, several atypical mycobacterial species were found to immunize against tuberculosis in varying degrees. However, the protective effect connected with sensitization by atypical mycobacteria is always less than the effect of BCG vaccination, and BeG vaccination increases the protection in animals sensitized by atypical mycobacteria up to the maximum level provided by BeG vacc inat ion alone. Thus, sensitization by atypical mycobacteria alone could not ex:plain the lack of protection in the Georgia and Alabama trial. The vaccine used for th is and the other two tria Is wh ich showed no protective effect came from the same laboratory and was suspected to be 0f low potency.
I He imbeck, J.
Annales de l'Institut Pasteur, 43: 1229 (1929).
2Hyge, T. 3Dam, H.G. 54: 255(1976).
Acta tuberculosea sc~ndinavica, ~: 1 (1947). et ale
Bulletin
of
the
World
Health
Organiz~tiQn,
WPR /RC32/l5 page 4
2.2
The BCG vaccines trial in south India t
The trial area, located to the west of Madras City, included a total population of about 360 000 persons. The entire population over 1 month old was eligible for inclusion in the trial. Persons aged 1 year and above were tested with PPD-S and PPD-B. At the same time, an injection of one of two BCG vaccines or a placebo, allocated according to a random procedure, was given to all the eligible population. The vaccines were prepared from two seed lots, the French strain and the Danish strain. Intensive follow-up efforts were made by means of regular surveys every 2-1/2 years; selective case-Hnding among suspects, initially every 7-1/2 months and later every 10 months; and the maintenance of permanent diagnostic services for persons with symptoms, to identify all new cases of tuberculosis occurring in the community. There were two significant findings: (1) the failure of BCG vaccine to protect; and
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(2) an unprecedented pattern of behaviour of tuberculosis 1n the trial area: (a) a very low incidence of disease among those newly infected; (b) considerable prolongation of the period between infection and the development of pulmonary disease; although the infection rate was high, most of the cases developed among those whose tuberculin reaction wa~; already positive at the start of the study; (c) a high prevalencf> of low grade sensitivity, presumably caused by atypical mycobacterial infection; and (d) low virulence of strains of M. tuberculosis isolated in the Madras area. The study was not designed vaccination among infants. to measure the effectiveness of BCG
Based on the above findings, the following conclusions were reached: (1) The resul ts of the trial, showing that BeG did not protect against bacillary pulmonary tuberculosis, ought to be regarded as applying automatically to other parts of the world.
(2) The lack of protective effect of BCG vaccine might have been relateo to the interaction between the epidemiological, environmental and immunological characteristics of the population of the trial area.
ITuberculosis Prevention Trial, Madras Indian J. Med. Res., 72 (Suppl.), July 1980, pp. 1-74. An abridged version of the repor-twas pllb1 ished 10 the Bulletin of the World Heal th OrganizCltiQn, 57: 819-827 (1979).
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WPR/RC32/l5 page 5
2.3
Reconnnendations of the WHO Study
_.Gr~~p
2.3.1 On the basis of an extended review of BCG vaccination, including the results of the south Indian trial, the Study Group recommended that the use of BCG as an antituberculosis measure should be continued. Thus the Study Group found itself in substantial agreement with current BCG vaccination policies. The lack of protective effect of BCG, coupled with the unexpectedly low incidence of tuberculosis among the recently infected in the Indian study area, served to highlight the fact - established by the differing results in the previous large BCG trials - that there were situations in wh ich the effectiveness of BCG could not be predicted with certainty. It was reconnnended that every effort should be made to identify the local factors that apparently might modify the outcome of BCG vaccination. Pending the acquisition of such new knowledge, and in view of the safety of BCG vaccination and the fact that, with the scarce resources availab Ie, it might be the only instrument available for a connnunity attack on tuberculosis, the Study Group was convinced that it would be wise to go on using it. This was particularly the case for infants and children, avai lab Ie evidence being favourable and not contradicted by the Indian tr ial.
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2.3.2 The Study Group noted that the worldwide tuberculosis problem presented differing patterns in different countries, so that a single reconnnendation for all situations would be unwise. It believed that the kind of BCG progrannne chosen (e. g. as regards the age group for initial vaccination) must be based on the epidemiological situation in each country: (a) in countries with a high prevalence of tuberculosis, BCG . vaccination should be administered as early in life as possible, since there was evidence that it could playa valuable role in the prevention of the severe· forms of ch ildhood tuberculos is, e.g. meningitis and miliary tuberculosis; in countries with a low prevalence of tuberculosis, current BeG pol iciesshould continue to be adapted to the changing situation, taking into account both local and global epidemiological trends. including such factors as migration.
(b)
2.3.3 As far as possible. BeG vaccination should not be considered in isolation as a means of tuberculosis control, but should form part of a comprehens ive control programme that included case-detection and trjitatment. Due attention should continue to be paid to the quality of BeG vaccine. its handl ing, techniques of application, the training of personnel, and coverage of the eligible popUlation.
2.3.'+
WPR!RC32/15 page 6
2.3.5 The need for proper evaluation and monitoring of the BCG vaccination programme was of paramount importance. 2.3.6 In addition to research, examples of which were listed in the report of an ICMR/WHO scientific group on vaccination against tuberculosis held in . New Delhi in early 1980, I the Study Group recommended the organization of operational research activities in order to yield information that could be used for improving the effectiveness of BeG programmes. One important object of such research might be to devise simple and only crudely quantitative methods for detecting and defining local factors of possible epidemiological relevance in situations in which scarce resources prevented more precise epidemiological surveillance. 2.3.7 In view of the high calibre of the south Indian tuberculosis prevention trial, the careful design and objective analysis of the data, and particularly the long-term importance of the study, the Study Group s trong1 y r.ecommended that, on its completion, all the accumulated data should be preserved.
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3.
REGIONAL POLICIES ON BCG VACCINATION
In the light of the recommendat ions made by the above-mentioned Study Group, a regional office study group, composed of nine staff members, was established, with the following terms of reference; (l)
to review the recommendations made by the WHO Study Group on BCG Vaccination Policies, held in Geneva in June 1980; to review the magnitude and nature of the (tuberculosis epidemiology) 1n the Region vaccination ~ tuberculosis in relation problem to BCG
(2)
(3)
to recommend BCG vaccination policies in the Region, particularly with respect to the epidemiological situation of tuberculosis 1n the commun ity.
Of the 32 countries or areas of the Region, information on BCG polici.es is available only for twenty-one. Of these, 17 have BeG programmes covering the population nationwide, one performs BCG vaccination only for selected population groups such as migrants and workers engaged i.n medical services, and three do not have systematic BCG programmes. All of the 17 with nationwide BCG programmes vaccinate newborns (less than one month), infants or preschool children, and in addition, revaccinate children at school entrance or school-leaving age or on both occasions.
lWHO Technical Report Series, No. 651, 1980 (Report Sclentifi.c Group on vaccination against tuberculosis).
of an
ICMR/WHO
WPR!RC32/15 page 7
... In Hong Kong and Singapore, newborns .'Ire maternity wards and the coverage is around 95%. 3.2 vaccinated at birth in
Review of tuberculosis epidemiology in relation to BCG vaccination in selected countries or areas
In Hong Kong, Malaysia, Republic of Korea and Singapore, morbidity and mortality from tuberculosis, particularly among children, have been declining conspicuously. over the last decade or so. In August 1980, they were visited in order to collect information on tuberculos is epidemiology related to BeG vaccination, to ascertain, at the major hospitals, the availability of hospital statistics on tuberculous meningitis, and to identi fy hospitals t;hat would cooperate in the collect ion of information on the disease. These four countries or areas, as well as Samoa and Tonga, have enough data to suggest that BeG vaccination has been effective in the reduction of tuberculosis, although all data have certain deficiencies if they are critically reviewed. An overwhelming majority believe that the decline in childhood tuberculosis has been due to BeG vaccination. The consensus in the countries or areas visited and within the regional study group is that the epidemiological information available in any country does not provide a satisfactory basis for modifying the present BeG policy. A degree of pragmatism is inevitable in the course of policy making .. There are data suggesting a •. mycobacteria in Hong Kong and the Singapore there is evidence of atypical mycobacteria, which is tropical countries. low prevalence of infection with atypical Republic of Korea, while in Malaysia and a higher prevalence of infection with also most probably prevalent in other
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for the Information on tuberculous meningitis, which is useful evaluation of BCG vaccination, was not readily available in most of the hospitals visited. However, many expressed willingness to cooperate in the future collection of such information. In the Melanesian population of the Region, there is a relativelY high proportion of children under 15 years among tuberculosis patients and also a relatively high proportion of extra-pulmonary tuberculosis, including meningitis. More than 80% of children with childhood tuberculosis have a BOG scar. Many health workers doubt the effectiveness of BCG vaccination. However, the care of vaccine and vaccination techniques need to be improved.
WPR/RC32/15 page 8
4. SUMMARY OF THE CONCLUSIONS AND RECOMMENDATIONS OF THE STUDY GROUP ON REGIONAL POLICIES ON BCG VACCINATION
(1) Most of the developing countries or areas of the Region have nationwide BCG vaccination prograllDlles and vaccinate newborns, infants, and preschool children; many of them revaccinate schoolchildren at school entry/or school leaving age. (2) There is evidence in many countries which suggests that BCG vaccination has been effective in the reduction of tuberculosis, although the data have certain deficiencies and the evidence is not conclusive. An overwhelming majority believe that BCG vaccination is effective. (3) There is, thus, no satisfactory evidence to recommend a change in the policy of Member States of the Region, and hence the same policies should be continued, except with regard to tubercul in testing every year for revaccination.
(4) Even if the efficacy of BeG vaccination is assumed to be high, national policies, particularly as regards target age groups, need to be periodically adjus ted, to take into account the epidemiological situation as the prevalence of tuberculosis declines further. For this purpose, a mechanism should be established to enable the collection of such necessary information as tuberculosis incidence, by type of disease, age of incidence, relationship to BeG scar, vaccination cos ts, and the occurrence of seri.ous complications due to BCG vaccination. (5) Systematic investigations among selected population groups, such as in Melanes ia, are necessary, to ascertain the effectiveness of BCG vaccination, including the care of vaccine and vaccination techniques.
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5.
OTHER ACTIVITIES
The Phil ippine National Institute of Tuberculos is has commenced a retrospective study on the effectiveness of BCG vaccination, comparing the history of previous BCG vaccination as between tuberculosis patients and other patients admitted in selected hospitals in Manila. The Tuberculos is and Leprosy Control Section, Department of Health, Papua New Guinea, in collaboration with WHO, is planning to conduct a retrospective study on BCG vaccination among infants.
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