THE DIVISION OF PREVENTIVE MEDICINE.

Lieut. Commander J. R. PHELPS, Medical Corps, United States Navy, in charge.

Notes on Preventive Medicine for Medical Officers, United States Navy.

REPORT OF WORK CARRIED ON DURING 1922 BY THE BUREAU OF LABORATORIES, DEPARTMENT OF HEALTH, NEW YORK CITY, UNDER THE DIRECTION OF DR. WILLIAM H. PARK,1

The valuable work with diphtheria accomplished by the Health Department of New York City is well known in the public health world. The official report of the continuation of that work during 1922 is interesting as well as the report of progress in laboratory investigations of whooping cough and likewise the results of miscellaneous activities of the bureau during the year, quoted below:

DIPHTHERIA PREVENTION WORK.

Work in the schools. We have continued the work in the public schools during the spring and fall terms of 1922 and have finished in nearly all. In the fall we also started to carry out the Schick test actively in the parochial schools and expect to finish these schools during the coming spring term.

Each child in the Boroughs of Manhattan and Bronx received not only the Schick test, but also the control test. In the other boroughs the Schick test alone was used. We hope to come to a final decision as to whether there is a sufficient number of pseudoreactors among school children to justify the control test. It is invariably used for obtaining scientific data or in retests when we wish to make final decision as to the presence or absence of immunity.

We have made repeated efforts to have the technique of the test and the interpretation of the reaction witnessed by practicing physicians in this city, so that they in turn can apply the test to the children in their private practice.

During the spring of 1922 we used mixtures of toxin-antitoxin containing from 3 to 6 L plus doses of toxin to each cubic centimeter. During the fall mixtures of toxin-antitoxin were used containing one-tenth L plus per cubic centimeter.

1 From the Monthly Bulletin of the Department of Health, city of New York, May, 1923.

Many of the children in the public schools tested and injected in the spring were retested in the fall. The different mixtures used gave different immunity results. In a general way the immunity response seemed not to depend upon the L plus content in each dose but upon the unneutralized or partly neutralized portion of toxin in the toxin-antitoxin mixture. The results of the injection into guinea pigs of the two mixtures confirmed the results obtained in children. The new mixtures of toxin-antitoxin containing one-tenth L plus toxin per cubic centimeter gave much less local and constitutional disturbance than the previous mixture with the larger protein content. The efficiency of these mixtures will be determined further during the coming months in additional schools and institutions in which they were used.

New public and parochial schools tested and children injected during 1922.

In the city we retested the pupils of 111 public schools. At the same time that we retested the children that had been previously injected with toxin-antitoxin we also Schick tested for the first time the newly admitted children to the kindergarten and 1-A classes. From 60 to 80 per cent of the children in these classes showed positive reactions.

We gave two additional injections of toxin-antitoxin to the children who had been previously injected with toxin-antitoxin and who still showed the positive Schick reaction at the retest. For this purpose we obtained additional consent from the parents.

Preschool work.-Work among children at preschool age was a logical sequence to the Schick work in the schools, through which nearly 800,000 homes had already been reached with the literature on diphtheria prevention.

The preliminary circularization of the homes consisted of distributing through the public schools, just before they closed in June, 200,000 copies of a special circular printed in English, Italian, and Jewish. Another important and effective method of reaching many parents was through 50,000 special mailing cards sent to all parents whose babies had been registered at the stations during the years 1920 and 1921.

The preschool diphtheria work was started on July 1 and continued until September 15. The injections were given in the ma

jority of the baby health stations of the department of health, of the Diet Kitchen Association, and of the American Red Cross; also in a majority of the mothers' and babies' vacation playgrounds in the public schools. Each child received not only the Schick test but was also given three injections of toxin-antitoxin. A temporary diphtheria vaccination certificate was issued to each child. Nearly 8,000 children were injected. The work with preschool children has inherent difficulties in that the individual family has to be reached. This is in striking contrast to the work in the schools, where thousands of children, and through the children the parents, can be reached in a short time.

A circular letter was sent to 6,000 physicians urging them to cooperate with the department of health in distributing literature and giving the injections of toxin-antitoxin to the young children in their private practices. Each physician also received a list of the stations in which the Schick outfits and supplies of toxin-antitoxin are obtainable free of charge in New York City. Sample copies of the special circular in different languages were also inclosed. Two hundred physicians sent in requests for literature.

In institutions.-The Schick work and toxin-antitoxin immunization was started in 10 new institutions.

Preparations of toxin-antitoxin.-Toxin-antitoxin mixtures act most effectively when slightly underneutralized. If too much underneutralized, the injections produce a local inflammatory reaction.

About the best preparation is a mixture which in 1 cubic centimeter (the human dose) produces paralysis in guinea pigs with considerable proportion of deaths. This mixture produces a good immunization and but little local reaction. A mixture a little more toxic is safe and somewhat more effective but produces more local reaction. A mixture more neutralized is less effective. Toxin (without mixture of antitoxin) in safe doses produces less antitoxin response than suitable toxin-antitoxin mixtures.

The antitoxin response to three injections of different mixtures of either one-fifth cubic centimeter or one-tenth cubic centimeter is shown in several hundred guinea pigs.

The relation between the toxicity of toxin-antitoxin and the immunity response in guinea pigs; also between toxin-antitoxin and unmodi fied toxin.

The results obtained from three injections of toxin-antitoxin solution in several groups of guinea pigs.

The antitoxic response was tested by means of the Schick test:

Immunity results following three infections of unmodified toxin (dose 0.066 or 0.1 or 0.2 M. L. D.).—One hundred and nineteen guinea pigs were tested 11 weeks after treatment; all gave the positive Schick reaction, proving that there had been no immunty re

sponse.

Diphtheria toxin production.-Eight comparative tests of the Research No. 8 and Pasteur cultures of B. diphtheria cultivated upon different peptone broths were made at different periods throughout the year 1922. The results may be summarized as follows:

(a) The Pasteur culture cultivated on Parke-Davis peptone broth is still capable of producing a potent toxin.

(b) The Pasteur culture which has been kept exclusively on Löffler serum produced the most potent toxin of any of the cultures tested, except in one test when it was equaled by the toxin produced by Pasteur culture kept in Parke-Davis broth.

(c) The Pasteur culture which had been subcultured from ParkeDavis peptone broth to Witte peptone broth has lost to a slight degree its toxigenic property; that is, it now produces toxin 1 to 800 instead of 1 to 1,000.

(d) The Pasteur culture subcultured from Witte peptone broth to Parke-Davis peptone broth has not as yet recovered its toxigenic property.

(e) The Research No. 8 cultures which had been cultivated exclusively in Witte peptone broth since 1895 have not as yet recovered their toxigenic property.

PERTUSSIS WORK.

Improved methods for the isolation and cultivation of B. pertussis. The need of more strains of B. pertussis for inquiry as to the presence of types and the possibility of making a more effective vaccine was the starting point of this work.

Although it is comparatively easy for an experienced worker under favorable conditions to isolate B. pertussis in the first 10 days of the disease, it becomes more difficult to do so as the disease advances. The greatest obstacle is the accompanying growth of B. influenza. The latter appear in increasing numbers as the disease progresses, and because they grow much faster, they outgrow B. pertussis.

In the search for a more favorable medium for the isolation of B. pertussis, the chief object was to find a substance which would inhibit in a measure the development of B. influenza and at the same time be favorable for the growth of B. pertussis.

It was found that a definitely acid reaction (Ph 5) in a BordetGengou medium is favorable for the isolation and growth of B. pertussis, and at the same time such a reaction inhibits the growth of B. influenza and a number of other organisms.

The superiority of an acid Bordet-Gengou medium over a "neutral" (Ph 7.2 to 7.4) one used heretofore, was demonstrated in the second series of whooping-cough cases in which 43.5 per cent of isolation were obtained as compared with 22.8 per cent isolations in the first series of analogous cases in which a "neutral" BordetGengou medium (Ph 7.2 to 7.4) was used.

It was also found that B. pertussis grows very profusely immediately after isolation on a glycerin veal potato agar of an acid reaction (Ph 5.8 to 6.1) to which blood in the proportion of 1 to 4 is added. This fact is important when large quantities of freshly isolated cultures of B. pertussis are desired for antigens or vaccines; at present chocolate veal agar is used for this purpose, but B. pertussis grows on this medium only after many weeks of continuous cultivation.

To determine the length of time B. pertussis is harbored by the patient. Repeated cultures were taken from pertussis patients; but in no case was the organism isolated after the fourth week of the whoop. This work is still in progress.

Attempts to isolate B. Pertussis from diseases other than whooping cough.-Cultures from fresh "colds," measles, scarlet fever, croup, and diphtheria have thus far proved negative for B. Pertussis. This work is also still in progress.

Potency of stored pertussis vaccine.-The problem was to determine whether stored vaccines retained their potency for any length of time, or deteriorate soon after preparation, as claimed recently by some clinicians and laboratory workers. Vaccines were prepared in 1921 and kept in the ice box. Tests were made after storing 1, 2, 3, 4, 6, 12, and 18 months. Rabbits were immunized with each preparation and their sera were tested for agglutinin and complement-fixing antibodies.