effectiveness of bcg vaccination in england and wales in 1983

Jercle (1987) 68, 81-92 ) Longman Group UK Ltd. 1987

EFFECTIVENESS OF BCG VACCINATION IN ENGLAND AND WALES IN 1983

Ian Sutherland*

Medical Research Council Biostatistics Unit 5 Shaftesbury Road, Cambridge CB2 2BW

V. H. Springett

67a Hampton Lane, Solihull, West Midlands B97 2QD

Summary The effectiveness of BCG vaccination, at about age 13 years, in the prevention of tuberculosis at ages 15-24 years in England and Wales in 1983, has been determined by the same method as in two previous surveys in 1973 and 1978. In 1983, the tuberculosis notification rate among those vaccinated in the schools’ scheme was 3.30 per 100 000, compared with an estimated rate of 13.20 per 100 000 among those who were tuberculin negative and not vaccinated in the scheme. The protective effectiveness of BCG vaccination at ages 15-24 years in England and Wales in 1983 is thus estimated as 75 %; the estimated efficacy in the white ethnic group is closely similar, namely 76 %.

The estimated efficacy of BCG at ages 15-19 and 20-24 years in the three surveys, both in the white ethnic group and in the entire cohort, has been compared with that found in the Medical Research Council’s controlled trial of tuberculosis vaccines which began in 1950. There is no evidence of any decrease in the protective efficacy of BCG vaccination between the four cohorts of young adults, which span a total period of 29 years. However, there were steep decreases between the cohorts in the annual notification rates for the white ethnic group; these decreases occurred in the BCG vaccinated and in the tuberculin negative unvaccinated groups, as well as among those found tuberculin positive (and not vaccinated) in the schools’ scheme.

It is concluded that the level of protective efficacy of BCG vaccination at ages 15-24 years is high, and has remained unchanged since the start of the BCG in schools’ scheme. However, as the tuberculosis notification rate in young adults has decreased steeply throughout this period, and is continuing to decrease, the benefits to be expected from the BCG in schools’ scheme will decrease equally rapidly.

L’efficacite de la vaccination BCG pratiquee a l’age de 13 ans environ, en vue de la prevention de la tuberculose chez des sujets ages de 15 a 24 ans en Angleterre et au Pays de Galles en 1983 a ete evaluee par la meme methode utilisee lors de deux etudes anterieures realisees en 1973 et 1978. En 1983, le taux de declaration de la tuberculose parmi les sujets vaccines dans le cadre du programme scolaire a ete de 3,30 pour 100.000, compare au taux de 13,20 pour 100.000 estime chez les sujets trouves negatifs au test tuberculinique et non vaccines dans le cadre de ce

*Correspondence: Dr Ian Sutherland, MRC Biostatistics Unit, 5 Shaftesbury Road, Cambridge CB2 2BW

82 Sutherland and Springett

programme. Ainsi, la protection conferee par le BCG chez les sujets ages de 15-24 ans en Angleterre et au Pays de Galles en 1983 est estimee a 75 %; I’efficacite estimee dans le groupe ethnique blanc est pratiquement le meme (76 %) que dans I’ensemble de la population etudiee.

L’efficacite estimee du BCG chez les sujets ages de 15-19 ans et de 20-24 ans dans les trois etudes, aussi bien dans le groupe ethnique blanc que dans la cohorte complete, a ete comparee a celle trouvee dans I’essai controle des vaccins antituberculeux du Medical Research Council commence en 1950. Aucune diminution de la protection conferee par la vaccination BCG n’a ete constatee dans les quatre cohortes de jeunes adultes qui couvrait au total une periode de 29 ans. Cependant, une diminution accentuee des taux annuels de declaration a ete observee dans les cohortes du groupe blanc; cette diminution a ete constatee aussi bien dans les groupes des sujets vaccines par le BCG et les groupes de sujets non vaccines tuberculino-negatifs, que dans les groupes consider&s comme tuberculino-positifs (et non vaccines) dans le programme scolaire.

Les auteurs concluent que le niveau de protection confere par la vaccination BCG a I’age de 15-24 and est eleve et qu’il se maintient sans modification depuis le debut du programme scolaire de vaccination BCG. Neanmoins, etant don& que le taux de declaration de tuberculose chez les jeunes adultes a diminue de facon marquee tout au long de cette periode, et qu’il continue a diminuer, les benefices esperes du programme de vaccination BCG dans les ecoles diminueront avec la meme rapidite.

Resumen En 1983, en lnglaterra y Gales se evaluo le eficacia de la vacunacion con BCG practicade a 10s de 13 arias de edad con fines de prevenir la tuberculosis a la edad de 15-24 arions, con el mismo metodo utilizado en 10s dos estudios anteriores realizados en 1973 y 1978. En 1983 la tasa de notification de la tuberculosis entre 10s sujetos vacunados en el programa escolar era 3.30 por 100 000 comparada con una tasa estimada de 13,20 por 100 000 en 10s sujetos que eran tuberculino-negativos y no vacunados durante la realization de este programa. Asi, la protection conferida por el BCG a la edad de 15-24 arias en lnglaterra y Gales en 1983 se estimo en 75 %; la eficacia estimada en el grupo etnico blanco fue practicamente la misma que en el total de la poblacion estudiada, es decir 76 %.

Se comparo la eficacia estimada del BCG a las edades de 15-19 y de 20-24 arias en 10s tres estudios, tanto en el grupo blanco coma en el total de la cohorte, con aquella encontrada en el estudio controlado del Medical Research Council sobre las vacunas antituberculosas que comenzo en 1950. No se constato ninguna disminucion de la protection conferida por la vacunacion con BCG en las cuatro cohortes de adultos jovenes que cubrian en total un period0 de 29 anos. Sin embargo, en las cohortes del grupo bianco se observe una disminucion acentuada de las tasas anuales de notification; esta disminmucion se constato tanto en 10s grupos de sujetos vacunados con BCG y en 10s no vacunados tuberculino-negativos coma en aquellos considerados coma tuberculino-positivos (y no vacunados) en el programa escolar.

Los autores concluyen que el nivel de protection conferido por la vacunacion con BCG a la edad de 15-24 arias es elevado y que se mantiene sin modificacibn desde el comienzo del programa escolar de vacunacion con BCG. No obstante, dado que la tasa de notification de tuberculosis en 10s adultos jbvenes ha disminuido de

Effectiveness of BCG vaccination in England and Wales in 1983 83

manera acentuada a lo largo de este period0 y que continua disaminuyendo, 10s beneficios esperados del programa de vacunacion con BCG en las escuelas disminuiran con la misma rapidez.

Introduction The effectiveness of BCG vaccination in the prevention of tuberculosis in young adults in England and Wales was demonstrated in the Medical Research Council’s controlled trial of tuberculosis vaccines [I, 21. A national scheme for BCG vaccination in schools at about age 13 years began in 1953 and about 75 % of each annual cohort of children is now vaccinated with BCG under this scheme. Two monitoring studies of the vaccine in routine use 13, 41 have shown that the efficacy of the vaccine has remained high but that there has been a steep decrease in the incidence of tuberculosis in successive cohorts of young adults who were eligible for the national scheme when they were aged 13 years.

This report presents the findings of a third monitoring study, with estimates of the effectiveness of BCG vaccination in preventing tuberculosis in young adults in 1983, and, in conjunction with the earlier findings, assessments of the current incidence of notified tuberculosis and its downward trend at age 15-24 years in England and Wales. The implications of these findings for the future control of tuberculosis in this country, and in particular for the continuation or discontinuation of the scheme for BCG vaccination of children at school, are considered in a separate report (in preparation).

Method The method used for the 1983 survey was essentially the same as that of the two previous surveys in 1973 and 1978. The starting point was the group of all patients aged 15-24 years, who were notified as cases of tuberculosis in England and Wales in 1983, and who were identified by the national survey of tuberculosis notifications in that year [5]. Information was sought, by enquiries through the notifying physicians, to determine their ethnic group, place of birth, date of first entry to the UK (for those born elsewhere) and place of residence at age 13 years. Those who were resident in the UK at age 13 years were eligible to participate in the schools’ scheme (unless they had a past history of tuberculosis, tuberculin positivity or BCG vaccination), and information was sought through local health and education authorities on their status in the scheme, that is, whether or not they participated, their tuberculin test results and details of any BCG vaccination. As a result, four groups of patients were identified among those who had been eligible for the scheme, namely those found tuberculin negative and given BCG, those found negative and not given BCG, those found tuberculin positive and not vaccinated, and those who did not participate.

These totals were then related to estimates of the total numbers of children from the relevant cohorts at age 13 years in the same four categories, based on the annual estimates (from the Office of Population Censuses and Surveys-OPCS) of the population of England and Wales aged 13 years [6] and the annual local authority returns (to the Department of Health and Social Security-DHSS) of tuberculin test results and BCG vaccinations in the schools’ scheme [7]. Further details of the method of derivation of the population estimates for these four groups are given below.

In the 1983 notification survey [5] it was possible to divide the patients according to their ethnic group (as distinct from their place of birth) and to relate these numbers to appropriate population estimates by ethnic group derived from the Labour Force Survey for 1983 (OPCS, unpublished findings). This allowed the efficacy of BCG vaccination to be assessed in the present report for the white ethnic group as well as for the whole population, but not for the


other smaller ethnic groups, because of the absence of information on the extent of their participation in the schools’ scheme, and uncertainties in the population estimates for these other groups.

It was possible also in retrospect to divide the patients in the two earlier surveys according to their ethnic group. Appropriate population estimates for the white ethnic group for 1978 were derived from the National Dwelling and Housing Survey, 1978 181 and for the 1973 survey by extrapolation. The opportunity was also taken during these re-analyses to incorporate the 1984 revisions, from 1961 onwards, of the national estimates of the total population by single years of age (OPCS, unpublished findings), updated totals for participants in the schools’ BCG scheme (DHSS, personal communication), and a small group of late returns for the 1978 survey, not included previously 141.

As a consequence many of the rates and other measures for the 1973 and 1978 surveys in the present report differ slightly from corresponding figures in the earlier reports. The new figures provide a more appropriate basis for comparisons with the 1983 results.

Results

Notifications of tuberculosis in persons who were eligible for the scheme

There was a total of 874 notifications of tuberculosis in England and Wales during 1983 in subjects aged 15-24 years, recorded in the national survey of tuberculosis notifications [5]; in 19 of these, the diagnosis of tuberculosis was subsequently revised. The eligibility and status of the subjects in relation to the schools’ BCG scheme is shown in Table I, according to age and ethnic group. Only 407 (47 %) of the notifications were in subjects who were eligible for the schools’ scheme, that is, who had been resident in the UK at age 13 years, and had no history of tuberculosis, tuberculin positivity, or BCG vaccination before that age.

Table I. England and Wales, 1983, persons aged 15-24 years. Notifications of tuberculosis and their status in schools’ BCG scheme, by age and ethnic group.

Total Age (years)

15-24 15-79 20-24

Ethnic group

White Indian West Other or sub- lndian mixed continent

Eligible for schools’ scheme: 407 163 244 255 94 43 15 BCG vaccinated 168 64 104 112 34 18 4 Tuberculin positive 38 22 16 14 21 2 1 Tuberculin negative, not vaccinated 4 2 2 3 1 0 0 Non-participant 149 61 88 102 24 16 7 Eligible, but no information on status 48 14 34 24 14 7 3

Not eligible for scheme: 467 130 337 49 337 9 72 Tuberculosis, tuberculin positive or

BCG vaccinated before 13 86 age years 44 42 28 51 4 3 Immigration after age 13 years 350 73 277 12 272 3 63 Not resident at 13 5 age years 1 4 0 5 0 0 Diagnosis of tuberculosis revised 19 11 8 8 5 2 4 Inadequate information on eligibility 7 1 6 1 4 0 2

Total notifications 874 293 581 304 431 52 87


Of the 407, 168 had been BCG vaccinated in the scheme, 38 were tuberculin positive (and were not vaccinated), 4 were tuberculin negative but were not vaccinated and 149 did not participate; it was not possible to determine the status in the scheme of the other 48 eligible subjects (12 %) because their school medical records could not be traced, or had been destroyed.

Table II summarises certain characteristics of the four groups. Confirmation of participation in the scheme was obtained from the original record in about 80 % of the participating patients, but only in 21 % of the non-participants; it is inherently more difficult to confirm a non-event than an event. The disease was bacteriologically or histologically confirmed in about half the patients in each group. About one-third of the BCG vaccinated and non-participant patients were in the non-white ethnic groups, but as many as two-thirds of the patients who had been tuberculin positive. This difference, which was also found in the 1978 survey 141 is presumably a reflection of a higher proportion of tuberculin-positive subjects in the non-white than in the white ethnic groups. About one quarter of the patients in each group had non-respiratory tuberculosis, and a few had both respiratory and non-respiratory disease.

Table II. Characteristics of notifications in the four survey groups.

Total Classification in schools’ BCG scheme

KG vaccinated

Tuberculin Tuberculin Non- positive negative participant

not vaccinated

No. % No. % No. No. X 168 100 38 700 4 149 100

Classification in scheme: Confirmed from original record Not confirmed, BCG scar present Not confirmed, no scar reading

Confirmation of tuberculosis: Bacteriology/histology positive Bacteriology negative No information

Ethnic group: White Indian subcontinent West Indian Other or mixed

Non-respiratory tuberculosis: Without respiratory tuberculosis With respiratory tuberculosis

Sex: Male Female

135 80 29 17

4 2

91 54 18 43 26 9 34 20 11

112 67 34 20 18 11

4 2

40 24 7 4 2 2

80 48 12 88 52 26

14 21

2

79 4 32 - - - - -

47 3 76 24 0 28 29 1 45

37 3 102 55 1 24

5 0 16 3 0 7

18 1 26 5 0 8

32 3 89 68 1 60

21 -

51 19 30

68 16 11

5

17 5

60 40


Population estimates

The tuberculosis notifications at ages 15-24 years, analysed in this and the earlier monitoring studies, arise from three 5-year cohorts of the population, namely those who were resident in England and Wales at age 13 years (when BCG vaccine is offered in most schools) in the periods 1967-1971 (and were thus aged 15-19 years in 1973 and 20-24years in 1978), 1972-1976 (aged 15-19 years in 1978 and 20-24 years in 1983) and 1977-1981 (aged 15-19 years in 1983). (The use of BCG vaccine in some areas at a slightly younger age than 13 is not of major importance). The required populations and sub-populations in these three cohorts at age 15-19 years were estimated as follows, and are shown in Table III.

1. Total cohort at age 75-79 years: the sum of the OPCS revised estimates of those aged 13 years at 30 June in England and Wales in each of the 5 years in the three periods. No adjustments were made for mortality or emigration between age 13 and age 15-19 years.

2. BCG vaccinated subjects: the sum of the final DHSS totals for those given BCG vaccination in the schools’ scheme in England and Wales in each of the same three periods.

3. Tuberculin positive subjects: the sum of the final DHSS totals for those found tuberculin positive in the schools’ scheme in England and Wales in each of the same three periods.

4. Tuberculin negative subjects, not given BCG vaccine: taken as 1 % of those BCG vaccinated, based on a scrutiny of local authority returns, as explained in the previous report 141.

Table III. Estimated size of the population cohorts in England and Wales aged 15-19 years in 1973, 1978 and 1983, according to their status in the schools BCG scheme at age 13 years.

Status in schools’ BCG scheme

Population aged 1519 years in: 1973 1978 1983 (thousands) (thousands) (thousands)

Total population Total eligible population

Eligible for scheme: KG vaccinated Tuberculin positive Non-participants: Estimated tuberculin positive at age 13 Estimated tuberculin negative at age 13 Tuberculin negative, not vaccinated All tuberculin negative, not vaccinated

Not eligible for scheme: Previously tuberculin positive Previously given BCG

Percentage of participants found tuberculin positive in scheme

Estimated percentage mortality in cohort from age 15-19 to age 26-24

Estimated percentage of cohort in white ethnic group

3375 3857 4071 (3127) (3656) 139161

2326 2701 3090 284 236 205

52 55 36 441 637 554

,4::, (6% ,5::,

62 50 39 186 151 116

10.55

0.33

95.0 94.3 93.6

7.91

0.30

6.18

7


5. BCG vaccinated prior to schools’ scheme: the numbers vaccinated under age 13 were taken as 75 % of those vaccinated as contacts at all ages in England and Wales in each of the three periods (DHSS final totals), this percentage being based on the findings of a national study of tuberculosis contact examinations 191, as explained in the previous report [4].

6. Tuberculin positivity (or tuberculosis) prior to schools’ scheme: the numbers found tuberculin positive on prior testing were taken as 25 % of all those tested as contacts under age 13 (these being taken as 75 % of those tested as contacts at all ages) in each of the three periods, these percentages being based on 191, as explained in the previous report [4].

7. Non-participants: obtained by subtracting the participants (categories 2, 3 & 4 above) and those ineligible for the scheme (categories 5 & 6) from the total (category 1); tuberculin positivity in the non-participants at age 13 was taken to be the same as in the participants (see Table Ill).

8. Cohort aged 20-24 years: the above estimates all relate to the cohort when it was aged 15-19 years. For age 20-24 years, the estimates were all reduced by the ail-causes mortality for the same cohort in England and Wales between ages 15-19 and 20-24 years (see Table Ill). No adjustment was made for emigration.

9. White ethnic cohort: the above estimates were all reduced in accordance with the estimated percentages of the population in the white ethnic group (see Table Ill). The figure for the most recent cohort was the percentage found for England at age 15-19 years in 1983, derived from the Labour Force Survey, 1983 (OPCS, unpublished findings). That for the previous cohort was the percentage found for England at age 15-19 years in 1978 in the National Dwelling and Housing Survey, 1978 [81; an extrapolated figure was used for the first cohort.

In accordance with these estimates, the population of England and Wales aged 15-24 in 1983, who had been eligible for the schools’ BCG scheme when aged 13 years, numbered 7 561 000 (3 916 000 aged 15-l 9 in 1983 and 3 645 000 survivors to age 20-24 of those aged 15-19 in 1978). The corresponding total for the white ethnic group was 7 105 000.

Table IV. Estimated tuberculosis notification rates and the protective efficacy of BCG vaccination at ages 15-24 years England and Wales, 1983-Total population.

Group Population Cases (thousands) a b

Notification rates per 100 000

c=b/axlOO d=cx407/359

BCG vaccinated Tuberculin positive Eligible non-participants

Estimated tuberculin positive Estimated tuberculin negative

Known tuberculin negative, not vaccinated All tuberculin negative, not vaccinated Eligible, but status unknown

5783 168

440 38 1280 149

91 7.86 c 1189 141.14

58 4 1247 145.14 - 48

Total eligible 7561 407

2.91 3.30

8.64 9.80

___ 8.64

11.64 13.20

Protective efficacy

75.0%


Efficacy of BCG vaccination at ages 75-24 in 7983

Thus, 407 tuberculosis notifications at ages 15-24 years in 1983 arose in an estimated population of 7 561 000. The notification rate for the BCG vaccinated group may be calculated directly from the 168 cases arising among the 5 783 000 known to have been vaccinated at school, namely 2.91 per 100 000. This is multiplied by 407/359 to allow proportionately for the 48 cases who were eligible but of unknown status, giving an adjusted notification rate of 3.30 per 100 000. The rate for the tuberculin positive group may be calculated similarly, leading to an adjusted notification rate of 9.80 per 100 000 (Table IV).

To assess the efficacy of BCG vaccination, the notification rate in the vaccinated group is to be compared with the rate among those who were tuberculin negative but were not vaccinated. This rate is estimated as follows. It is assumed that the notification rate found among tuberculin positive participants applied also among the estimated total of 91 000 tuberculin positive non-participants; thus 7.86 of the 149 cases among non-participants may be attributed to those who were tuberculin positive, leaving 141.14 cases attributable to those who were tuberculin negative, estimated at 1 189 000. To these must be added the four cases found among 58 000 tuberculin negative unvaccinated subjects, giving an estimated 145.14 cases in a population of 1 247 000. This leads to an adjusted notification rate of 13.20 per 100 000 for tuberculin negative unvaccinated subjects. The rate of 3.30 for BCG vaccinated subjects is 25 % of this figure; the estimated efficacy of BCG vaccination at ages 15-24 in 1983 is thus 75 %.

Similar calculations for the 255 notifications among the estimated 7 105 000 eligible subjects in the white ethnic group (not tabulated) lead to an estimated efficacy of BCG vaccination of 76 % in this group.

Efficacy of BCG vaccination in four cohorts at 15-79 and 20-24 years

When assessing the present findings in conjunction with those of the earlier studies, it is preferable to study the experience at ages 15-19 and 20-24 years for each of the three 5-year population cohorts, rather than to compare the findings by calendar year. Table V shows the estimated efficacy of BCG vaccination at ages 15-19 and 20-24 years for each cohort, together with its initial size and the total notifications contributing to each estimate. Estimates are given both for the entire cohort and for the white ethnic group. Corresponding information is also given for the MRC tuberculosis vaccines trial cohort, 19 years earlier than the first of the three national cohorts. (The white ethnic group was not separately identified in this trial, but comprised virtually the whole cohort.)

There is no evidence of any decrease in the protective efficacy of BCG vaccination in young adults between these four cohorts, which span a total period of 29 years. The protective efficacy at ages 15-19 years is about 80 %, and rather less at 20-24 years, about 75 %.

Annual tuberculosis notification rates in three cohorts at 75-79 and 20-24 years

The annual notification rates are presented for each of the three national cohorts at ages 15-19 and 20-24 years in Table VI for the white ethnic group only. The notification rates for the entire cohort are affected by the much higher notification rates in the principal non- white ethnic groups [5]; they have not been included in Table VI because the non-white contribution to the total rate differs between the cohorts. The incidence rates in the MRC tuberculosis vaccines trial have been omitted from this Table because they depended on positive case-finding procedures as well as on notifications.

There were steep decreases in the notification rates in the BCG vaccinated, tuberculin


Table VI. Estimated annual tuberculosis notification rates per 100 000 in BCG vaccinated and unvaccinated cohorts at ages 15-19 and 20-24 years in England and Wales, for the white ethnic group.

Period during which the cohort was aged 13 years

KG vaccinated

1!%19 Z&24

Tuberculin positive Tuberculin negative unvaccinated unvaccinated Is-19 Z&24 15-79 26-24

1967-71 2.57 4.46 19.98 7.21 22.58 20.06 1972-76 2.70 3.12 14.34 3.02 10.81 11.42 1977-81 1.53 4.50 - 7.59

Annual percentage decrease* 5 7 14 16 10 11

-Cohort not yet old enough. *Between first and third cohorts for ages 15-19, between first and second cohorts for ages 20-24.

positive and tuberculin negative unvaccinated groups between the cohorts, both at ages 15-19 and 20-24 years. These rates are based on relatively small totals of cases and estimated populations, and the decreases in rate between the cohorts range from 5-16 % annually. The decreases are consistent with a continuation of the steep general decrease in tuberculosis notification rates in white adults aged 15-24 years which has been taking place since about 1950. The annual decrease at ages 15-24 years during this period is of the order of 9 % [IO; and report in preparation].

Discussion This is the third of a series of surveys to monitor the effectiveness of BCG vaccination against tuberculosis given at school in the national scheme at about 13 years. The basic approach has been the same in all three surveys, though the methods of data collection and analysis have differed in detail. The proportion of children in the minority ethnic groups who are born in Britain is increasing and country of birth no longer provides an adequate criterion for identifying the various ethnic groups in the population. Direct information on ethnic group has now been obtained and used instead and this is the main new feature in this report. This has made it possible to assess the efficacy of BCG for the white ethnic group separately from that for the total population, which is of particular importance when considering the future of the schools’ BCG scheme. The data for the two earlier surveys have been re-analysed for this report on the same basis: the opportunity was taken to incorporate revised population estimates and totals vaccinated, and a small amount of supplementary data from the 1978 survey.

These studies have asessed the effects of BCG vaccination in practice. Although they are not randomly controlled trials of its efficacy, estimates have been made of the notification rates in vaccinated participants and in tuberculin-negative unvaccinated subjects (mainly non-participants) and hence of the efficacy of BCG. Thus the estimated efficacy may have been affected by differences between the groups other than the vaccination, as well as by any biases in the estimation process.

One possibly relevant difference between the participants and the non-participants is their past exposure to tuberculosis. The estimation process, summarised in Table IV, assumes a similar proportion of tuberculin positives, and a similar notification rate in those tuberculin positives, among non-participants as are found among participants. However, even if these


assumptions are not wholly justified, they are not of critical importance to the final estimate of protective efficacy, as they involve such a small adjustment to the figures, namely the transfer of only about 8 of the 149 cases among eligible non-participants (5 %) to the tuberculin-positive group. On the other hand, the size of the BCG vaccinated cohort, and the proportion it represents of the total cohort, are major determinants of the estimated efficacy and both these population estimates are well established; the size of the BCG vaccinated cohort is taken directly from the totals of the local authority returns of vaccinations made in the schools’ scheme, and the total population directly from the revised OPCS estimates at age 13.

The other important determinants of the estimated efficacy are the numbers of cases assigned to the BCG vaccinated and the negative unvaccinated groups. The reliability of these assignments is probably much greater than the disparity in documentary confirmation of the status of patients in the BCG vaccinated and non-participant groups (Table II) might suggest. It should be noted that if there were a tendency (because of more frequent documentary confirmation) for the total of cases assigned to the vaccinated group to be more nearly complete than the total assigned to the negative unvaccinated group, the effect would be to reduce the estimate of efficacy below the true level, not to exaggerate it. Thus, although it is not possible to claim that the estimates of protective efficacy are unbiased, there seems no reason to suspect major bias, nor is it clear in which direction any bias might be.

A similar high level of estimated efficacy was found in all three surveys, and this was in agreement with the level of efficacy found in the Medical Research Council trial 20-30 years previously in a cohort vaccinated at a similar age [I, 21, but subject at that time to a much greater exposure to, and incidence of, the disease. Thus there is no evidence of any change in the protective efficacy of BCG since the start of the schools’ scheme. As a corollary, it may be concluded that the high efficacy of BCG, given at school age in England and Wales, does not depend on the intensity of exposure to the disease. The tendency for efficacy to appear less at age 20-24 years, 7-l 1 years after vaccination, than at age 15-l 9 years, 2-6 years after vaccination, was also found in the Medical Research Council trial, and is discussed [I]. A closely similar survey of tuberculosis notifications in Edinburgh from 1970-1983, in Caucasian children who attained age 13 years during this period, showed an estimated efficacy of 63 % for BCG [II].

In contrast to this constancy in the efficacy of BCG, the estimated notification rates show that there was a steep decrease in the incidence of the disease among young white adults between 1973 and 1983. The findings in Table VI suggest that the decreases may have been particularly steep among those who were tuberculin positive at age 13, and less steep among those who were vaccinated than in the tuberculin negative unvaccinated group, but these apparent differences in trend should be regarded with some reservation. The main conclusion from these studies, namely, that there has been no apparent calendar trend in the efficacy of BCG over a 30-year period, implies that there has been the same annual percentage decrease in notification rate throughout the whole period in those tuberculin negative and unvaccinated, as in those given BCG. In general, the estimates of efficacy within each survey must be regarded as more trustworthy than the comparisons of notification rates in the separate subgroups between surveys. The latter will have been affected by the relatively small numbers of notifications, particularly in the tuberculin positive subgroups, and by the appropriateness of applying a uniform correction factor to all subgroups to allow for incomplete information on status. Also, comparisons of the rates in 1983 with those in 1978 and 1973 may have been affected by the less satisfactory basis for the correction factors in the earlier surveys.

A full assessment of the changes in tuberculosis notification rates in the white ethnic


group in England and Wales during the past 30 years, at these and other ages, will be the subject of a separate report (in preparation). It may be noted that between 1971 and 1978/1979 the notification rate in England among white subjects born in the UK decreased by 8.9 % annually at ages 15-24 and by 9.7 % annually at ages 25-34 [IO].

The findings in this report, taken in conjunction with the decline in notification rates, have implications for future tuberculosis control policy in this country, which will be considered in a separate report (in preparation).

Acknowledgements

We thank the very many chest physicians and local health and education staff, who supplied information on status in the schools’ BCG scheme. Special tabulations were supplied by the Office of Population Censuses and Surveys and the Department of Health and Social Security. The administration of the survey, which was undertaken by Mr Marc Coghlan of the MRC Biostatistics Unit, was assisted by information from the national survey of tuberculosis notifications, made available by the MRC Tuberculosis and Chest Diseases Unit.

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