BCG
VACCINE
A
Symposium
PAUL W. BEAVEN, M.D., Chairman
PREVENTION OF TUBERCULOSIS AMONG CHILDREN
WITHOUT
THE
USE
OF
BCG
(Presented as an Original Article on page 793 of this issue)
J.
ARTHUR MYERS,M.D.
University of Minnesota Medical School, Minneapolis
DEFICIENCIES IN OUR KNOWLEDGE OF BCG VACCINE
MILTON I. LEVINE, M.D.
New York Cit) Health Department, New York City
STANDARDIZATION
AND
FUTURE
OF
BCG
VACCINE
SOL
Ro
ROSENTHAL,M.D.
Institution for Tuberculosis Research, University of Illinois,’ Research Foundation; Chicago Municipal Tuberculosis Sanitarium
BCG
VACCINATION
ROBERT
J.
G.
ANDERSON,M.D.
Division of Tuberculosis, U. S. Public Health Service, lVashington, D.C.
Presented at the Annual Meeting of the American Academy of Pediatrics,
862
SYMPOSIUM
ON
BCG
VACCINE
INTRODUCTION
PAUL W. BEAVEN,
M.D.
It is evident that the time has arrived when pediatricians in this country should have expert
advice on the use of BCG in the control of tuberculosis in children. Other parts of the world are now confronted with an increase in this disease. They are establishing programs to resist this infec-tion, and their respect for the value of BCG is attested to by the fact that its use forms a major kart of such programs. Physicians returning to America from these countries are advising us to accept this additional technic in our attempt to eradicate tuberculosis.
This symposium is the result of many requests from our members. In order to obtain divergent viewpoints, four speakers have been chosen whose opinions each of us respects but who have come to different conclusions.
Dr. J. A. Myers is the first speaker. He has spent his professional life in combatting tuberculosis in children and young adults. Following him, Dr. Sol Roy Rosenthal will speak. He is Director of the Tice Laboratories affiliated with the University of Illinois. This institution is one of the main distributors of BCG in this country. The next speaker is Dr. Milton Levine, Chief Consultant on
BCG
vaccination to the New York State Health Department. The concluding paper on the sym-posium will be given by Dr. Robert Anderson, Chief Medical Director, Division of Tuberculosis, of the U. S. Public Health Service.DEFICIENCIES
IN
OUR
KNOWLEDGE
OF
BCG
VACCINE
MILTON
I.
LEVINE,M.D.
Although there is today almost unanimous acceptance of the opinion that BCG vaccine is en-tirely harmless and that it confers a partial immunity against tuberculosis, considerable further knowledge is needed before this vaccine can be accepted for general use.
At the present time no method has been developed for stabilizing the potency of the vaccine. No means has been developed to assure that similar amounts of BCG from different laboratories would have equal numbers of viable organisms and equal potency. There is no knowledge of the actual degree of immunity conferred by the vaccine on the duration of this immunity. There is no agreement on the optimal dosage to be given or the best method of administering the vaccine.
Studies by Dr. Renee Dubos, of the Rockefeller Institute, demonstrated a loss of as many as 90%
of viable organisms in the first 2 hours if the vaccine is not kept under constant refrigeration. At-tempts at adequately stabilizing the potency of the fresh vaccine by lyophilization have so far been unsuccessful, cultures showing a marked decrease in the number of viable organisms immediately after preparation. However, Birkhaug has shown that the number of living elements remaining in the vaccine after drying or freezing continue unchanged for more than a year under proper conditions.
The marked variation in the potency of the same amount of vaccine from different laboratories is also open to further investigation.
Suter and Dubos, inoculating into the skin of guinea pigs a specified amount of BCG vaccine from each of 3 laboratories, found a specific difference between each vaccine not only in the size of the local lesion, but in the persistence of the lesions as well. Moreover, the cultural characteristics of the three strains varied greatly, as did their susceptibility to inhibitory substances.
Sheffer, using IICG vaccine from 5 different sources, found that the local lesions caused by the individual vaccines differed markedly even when the same number of living bacilli were inoculated.
The question is frequently asked why BCG has not been adopted for general use in the United States since it has been used so widely elsewhere. The answer is clear. In the United States, anti-tuberculous measures such as case detection, separation of contacts, hospitalization, mass x-ray studies, removal of tuberculin-positive cows and pasturization, have achieved a success surpassing that of countries where BCG has been used.
In New York City, the tuberculosis mortality for the group up to 15 years of age has dropped over 95% since 1915.
Until the necessary knowledge concerning BCG is obtained, it should not be licensed in the United States for production by commercial laboratories, and its use should be continued on an experimental basis, limiting it to the inoculation of individuals where tuberculosis exposure is likely to occur, and also in selected population areas with high tuberculosis mortality rates.
STANDARDIZATION
AND
FUTURE
OF
BCG
VACCINE
SOL Ro ROSENTHAL,
M.D.
On July 7, 1950, the Federal Security Agency licensed the BCG Laboratory of the University
of Illinois and Research Foundation to produce, sell and distribute BCG vaccine. This implies, in the opinion of the United States Government, that the vaccine is safe for human inoculation. Since 50 million persons have thus far been vaccinated with BCG and in some countries it is mandatory to be vaccinated, the safety of
BCG
is unequivocable.For the past 16 years the vaccine has given consistent results in the following method of standardization:
1. Viability
2. Conversion of tuberculin reaction in animal and man 3. Immunity in animal and man
4. Avirulence for animal and man 5. Morphology
6. Sterility
These consistent results indicate that the vaccine is well standardized and consistent in the results it
produces.
In some 3,418 children vaccinated at birth, half of whom were controls, there was a 71% de-crease in morbidity and 83% decrease in mortality, as compared with the controls. In children vac-cinated in a Federal Housing Project (all Negro), where the open cases of tuberculosis were re-moved, there has not been a single case of tuberculosis in 8 years of study among the vaccinated (745 children). In 1,086 controls, there were 9 cases of tuberculosis, which included 2 deaths. No tuberculosis developed in a group of 1,622 children vaccinated in orphanages and followed for 6 years. In 987 controls, there were 4 cases of tuberculosis during the same period. These results mdi-cate that using the accepted methods of tuberculosis control, such as mass x-ray, isolation of the
active case, and improvement of social conditions, plus BCG vaccination, the possibility of
eliminat-ing tuberculosis completely is great.
A new method has been developed for the production of a vaccine which is stable for periods
up to one year. The conversions in both animal and man have compared very well with the freshly prepared material, and experimentally in animals immunity produced is equal to that produced by the fresh vaccine.
BCG
VACCINATION
ROBERT
J.
G.
ANDERSON,M.D.
BCG
vaccination for all children is a widespread practice in some countries, and it is justified where tuberculosis morbidity and mortality rates are high and where many shortages make usual methods of tuberculosis control impossible. But in the United States, most children are not constantly threatened with tuberculosis as they are in other countries, and as long as the efficacy of BCG is sub-ject to many questions, its use as a part of the pediatrician’s routine of preventive measures is not indicated. BCG vaccination of children, furthermore, would contribute little to total tuberculosis control at present, because tuberculosis prevalence and mortality are low among children, and much higher in older age groups. In 1948, only 3.7% of the tuberculosis deaths in the United States occurred among children under 15, whereas 54.9% were among persons of 45 years and over. There will be circumstances, however, where physicians, concerned about children under their care who are exposed to the risk of infection, may want to consider giving BCG.864 SYMPOSIUM ON BCG VACCINE
resistance and how long it lasts are matters on which we have little information. In time, careful observation of tuberculosis morbidity and mortality in terms of BCG vaccinations performed will give us knowledge about the vaccine’s effectiveness. Continued studies in the laboratory and the field will ultimately clear up the unanswered questions about standardization of the product, the duration of its potency, about dosage, technics of vaccinating, and criteria for determining tuberculin conversions.
In the meantime, however, the private physician and the public health officer must decide how BCG is to be used now, while there are still many uncertainties about it.
Experts are agreed that mass application of BCG would not be wise in this country, but that
vaccination here should be limited to persons who by occupation or situation are exposed continually
to tuberculosis. Whatever protection BCG offers should perhaps be given to physicians, nurses, laboratory workers and hospital employees, whose work implies a certain risk of infection, and to the patients, inmates and employees of institutions such as mental hospitals and prisons, where the mci-dence of tuberculosis is known to be high.
In any use that is made of BCG, the interests of all concerned can be served best through plans
worked out mutually by physicians and public health authorities. Pediatricians, who are accustomed
to working with health departments in the practice of preventive medicine, will have an established pattern for such cooperative planning.
Many health departments will want to set up rosters of persons vaccinated with
BCG.
Such a list should be readily available to the physician, so that he can check against it the results of his patients’ tuberculin tests, since the test is an important tool in differential diagnosis.In many communities, the practical arrangement will be the sponsorship of
BCG
vaccination clinics by the health department. Because the life of the organisms in BCG is a matter of days,administration of the vaccine presents exceptional difficulties to the private practitioner. The health
department, however, can have routine procedures for obtaining BCG and administering it under
the necessary conditions. Arrangements should be made to have these facilities available to physicians so that they could refer to the clinic those patients for whom they recommend BCG vaccination.
