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CHAPTER VI.

RECENT METHODS OF DEALING WITH DIPHTHERIA AND SCARLET FEVER.

1. Introductory.-Within recent years there have been interesting developments in the control and management of diphtheria and scarlet fever. The methods employed are directed principally to the testing of susceptibility and the production of immunity, and have been for some years the subject of experiment and observation. They have now, however, been applied administratively on a considerable scale, and it will be useful to summarise the results obtained in several places in Scotland.

A. DIPHTHERIA.

2. The Schick Test of Susceptibility to Diphtheria.-The treatment of diphtheria by the injection of antitoxic serum has now been successfully practised for many years. Methods have

also been devised to concentrate antitoxic serum, and the serum in use to-day is of much greater potency than that used in the earlier years. As a result of more recent investigations it has now become possible to test the susceptibility of human beings to diphtheria, and to elaborate a method of protecting those susceptible to the disease. The method is known as the Schick test, from the name of the originator.

The function of the Schick test is to disclose the fact of the susceptibility or otherwise of an individual to diphtheria. The amount of toxin used in the test is one-fiftieth of the minimum lethal dose for a guinea-pig weighing 250 grammes, or a little over half a pound. The stock toxin is diluted as required so that one-fiftieth of the minimum dose that is fatal to the guinea-pig is contained in 0-2 c.c. This amount is the largest which can be used, without producing reactions, in persons who have sufficient antitoxin in their blood to give relative immunity. If smaller quantities be used some cases will give negative reactions, although they have too little antitoxin to render them immune from the disease.

The Schick test is carried out in the following way. An intradermal injection (i.e. an injection into the superficial layers of the skin of 0-2 c.c. of the diluted toxin) is made into the skin of one forearm, while a similar amount of toxin, which has been inactivated by heating to 75° C. for ten minutes over a water bath, and called the control, is injected into the skin of the other forearm. In the course of fourteen to forty-eight hours four distinct reactions can be distinguished as a result of this procedure.

(a) A Positive Reaction.-In the case of a positive reaction. there appears within twenty-four to forty-eight hours, on the

arm into which the unheated toxin has been injected, a circumscribed area of redness and slight swelling about half an inch to an inch in diameter. It reaches its height on the fourth day, and may persist for about a week. On fading it leaves a slight brownish pigmentation accompanied by some superficial scaling of the skin. No reaction is observed at the site of the control injection in the other arm.

(b) A Negative Reaction.-There is no reaction at the site of either the test or the control injection.

(c) A Negative Pseudo-Reaction.-The same appearances are noted at the site of the test and of the control injections, viz. a slight superficial redness which appears earlier than the true reaction, and is often at its best in twenty-four hours. It never scales, and it shews less pigmentation after fading than a true positive reaction. It is due to a hypersensitiveness of the individual to the proteins in the material injected.

(d) A Pseudo-Combined Reaction.In this condition there is a reaction in both arms, but the reaction at the site of the test injection is more pronounced than that at the site of the control.

Those that shew a positive or a pseudo-combined reaction are susceptible to diphtheria; those that shew a negative or negativepseudo-reaction are not susceptible. Schick's work has been confirmed by many workers all over the world.

3. Diphtheria Toxoid Antitoxin.-The present development of active immunisation against diphtheria is due to the work of Park and his collaborators, in particular Zingher. As stated in the Medical Research Council's Monograph on Diphtheria, precise details of the most satisfactory mixtures have been pub⚫lished, together with full details of technique employed and the results obtained in many thousands of cases.

The injection of diphtheria toxin in a proportion of people is not without danger, and a method has been elaborated for reducing the risk practically to the vanishing point. To effect this diphtheria toxin is exposed for about four weeks to the action of formalin of a strength of 0.1 per cent. The resulting product is found to be non-toxic and to have lost none of its immunising properties. To distinguish it from the original "toxin" it is called" toxoid," which is defined as toxin so modified that it no longer possesses poisonous properties. In practice, however, it has not been found possible to convert the last trace of toxin into toxoid, and to neutralise this trace of toxin a small amount of antitoxin (27 units) is added to 20 c.c. of toxoid. The mixture is then diluted ten times, and 1 c.c. of this diluted toxoid-antitoxin is used as the dose for producing immunity. With the toxoid-antitoxin mixtures which are now used for actively immunising against diphtheria, 3 doses of 1 c.c. each are injected at weekly intervals into susceptible individuals, the injection being made subcutaneously into the upper arm near the insertion of the deltoid muscle.

Experience of Schick testing and of immunisation against diphtheria in Scotland has been, in the main, confined to the

four principal burghs and to Aberdeen County. It will be most convenient to give a separate account of the work done in each of these areas.

4. Aberdeen.-Experience in this area has been in some respects more varied than in other areas, and it is perhaps desirable to take it first.

(a) Susceptibility to Diphtheria according to Age-Period.-Schick tests were performed in 1,500 individuals without regard to class, occupation, locality, size of dwelling, previous attack of the disease, or any other factor that apparently may have an influence on susceptibility. It was found that in the ageperiod 0-5 years, 940 per cent. gave a positive Schick reaction; in the age-period 5-10 years, 800 per cent. gave a positive reaction; in the 10-15 years age-period, 67.9 per cent., 15-20 years, 64.5 per cent., and 20-25 years, 54.2 per cent. The figures for the later age-periods are too small to have any statistical significance.

It has been found everywhere that young infants under six months of age have a considerable degree of natural immunity, but this natural immunity as measured by the Schick reaction rapidly declines, and over 90 per cent. of young children under five years, who form the majority of cases of diphtheria in our hospitals, give a positive Schick reaction. As age increases the susceptibility to diphtheria diminishes, as shewn by the smaller proportion who give a positive Schick reaction. A possible explanation of this is that in the course of years insusceptible persons have been exposed to relatively small doses of diphtheritic infection, either from carriers or actual cases, and have gradually developed sufficient antitoxin to protect them against the disease.

(b) Susceptibility to Diphtheria according to Social Condition.-In Aberdeen 708 children from west-end schools, 376 children from middle-class schools, and 404 children from eastend schools were tested. It was found that, of west-end school children, 556, or 78.5 per cent., were Schick-positive; of middleclass school children, 235, or 62.5 per cent., were Schick-positive; while of east-end school children, 126, or 31-2 per cent., were Schick-positive. A possible and probable explanation of the lessened susceptibility of the poorer classes is that the more crowded the conditions under which they live, the more likely they are to obtain minimum doses of diphtheritic infection and to develop sufficient antitoxin to prevent them from actually contracting the disease.

(c) Susceptibility to Diphtheria of Persons who gave a History of having formerly suffered from the Disease.-Some 105 persons who had previously suffered from diphtheria were also Schick-tested, and it was found that 43 of these, or 41.0 per cent., were Schick-positive. It was also observed that the Schick reaction in the majority of these positive cases was less intense than in individuals who had not suffered from diphtheria.

(d) The Schick Susceptibility Test in Cross-infected Wards. -The Schick test has also proved of the utmost value as a guide to the susceptibility to diphtheria of nurses and patients in wards in which cross-infection with diphtheria had taken place, or in wards to which cases of diphtheria had been accidentally admitted. Thus, all patients on admission to the scarlet fever wards in the City Hospital in Aberdeen are immediately Schicktested, and if a case of diphtheria has recently occurred in the ward all positive Schick reactors can be protected by a passively immunising dose of diphtheria antitoxin. As a result of experience obtained in this way, it was found that Schick-negative reactors could be left in contact with doubtful cases of diphtheria, or even with actual cases of the disease, without contracting diphtheria. Not infrequently, owing to lack of isolation accommodation, it was necessary to leave in the scarlet fever ward a scarlet fever patient who was also suffering from diphtheria or was a diphtheria carrier, and it has been found possible to prevent cross-infection by the comprehensive use of the Schick susceptibility test and passive immunisation of positive reactors.

(e) Result of active immunisation of City Hospital Staff.-In Aberdeen active immunisation of the nurses and maids at the City Hospital, who number about 125, was begun in January, 1922. In the four years 1922-5, 126 nurses and 30 maids were Schick-tested, and of these 50 nurses and 11 maids gave a positive reaction and were not put on duty in diphtheria wards until they had been protected. Among those so protected seven have contracted diphtheria in the four years. Prior to the institution of active immunisation in 1922 an average of 11 per cent. of the staff suffered annually from diphtheria; since 1922 this average has been reduced to 1.6 per cent. The result of the procedure has therefore been very satisfactory in diminishing the occurrence of diphtheria among the staff.

(f) Result of active immunisation of School Children.-In all 734 school children in Aberdeen over seven years of age have to the end of September, 1926, received a first series of immunising injections of the diphtheria prophylactic. Of these 201 were retested at the end of six months, when 164 or 81.6 per cent. were found to be protected as indicated by a negative Schick reaction. None of these 164 school children thus protected has contracted diphtheria, although three of the children who had received a first series of injections and who had not yet been retested developed diphtheria within five months of receiving the injections.

(g) Prevention of Return Cases and Control of Epidemic Prevalence.-Immunity to diphtheria takes from six weeks to six months to develop after injection, and the delay in the development of antitoxin in the blood of individuals who have received the immunising injections makes the active immunisation procedure useless for immediately controlling the spread of the disease. It is obvious that several years must elapse before reliable statistical evidence is obtained of the value of the present

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intensive community immunising campaign in the City of Aberdeen.

5. Glasgow.-Dr. Macgregor, Medical Officer of Health of the City, states that the Schick test is offered in all the City's. Fever Hospitals to all probationer nurses, most of whom accept it, and those found susceptible are immunised. No systematic Schick testing of patients is carried out in the City's Fever Hospitals, but it is the practice in Belvidere Hospital to apply the Schick test to all patients in wards that have been exposed to infection with diphtheria.

In the country homes under the Glasgow Child Welfare Scheme, and in institutions, such as the Deaf and Dumb Institute, Langside, where cases of diphtheria have occurred, it has become the practice to apply the Schick test and to immunise with toxin-antitoxin those children who shew a positive reaction, consent having first been obtained from the parent or guardian. No organised attempt has yet been made to apply the Schick test to the general population.

6. Edinburgh.-Dr. Robertson, Medical Officer of Health of the City, has supplied the following information on the testing and immunising of persons found susceptible in Edinburgh.

Schick testing and active immunisation were begun in January, 1924, and are still being actively carried out in schools and institutions in Edinburgh. The better the class of school the more readily is consent obtained from parents to have the procedure carried out. Immunisation without preliminary Schick testing is the rule in the case of pre-school children. Up to December, 1926, Schick testing and immunisation of positive reactors have been carried out in 33 schools and 12 institutions. In 18 schools and 8 institutions retests have been performed, and those children who shewed some remaining slight susceptibility have had further immunising injections. In all 5,976 children have, till December, 1926, been immunised against diphtheria in schools and institutions in Edinburgh, of whom 1,254 were under five years, 4,542 between five and ten years of age, and 180 were eleven years of age and over.

At the City Hospital 650 persons, including 224 of the staff, have been immunised against diphtheria.

7. Dundee.-Dr. Burgess, Medical Officer of Health of the City, has supplied the following information as to the testing and immunisation of persons found to be susceptible.

(a) Diphtheria Prophylaxis.—(1) All patients (except cases of diphtheria) admitted to King's Cross Hospital are Schicktested and, if positive, immunised.

(2) The staff at King's Cross Hospital are all Schick-tested and, if positive, immunised.

(3) A special out-patient clinic has been established at King's Cross Hospital where Schick testing and immunisation of those giving a positive reaction are practised. Children over

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