"In an analysis of the ratio of mortality in 266 German cities of about 15,000 inhabitants, it was found that the ratio of mortality per 100,000 of the living, before antitoxin was used, varied from 130 to 84 from 1886 to 1893, while the ratio from 1894 to 1897 varied from 101 to 35. It is a significant fact that during 1894, when, although antitoxin was used to a certain extent, it was not in general use, the ratio was 101; that when antitoxin was used more extensively, in 1895, the ratio was 53; that in 1896 it was 43; that in 1897, when antitoxin was very generally used, the rate fell to 35." (Trans. Massachusetts Med. Soc., 1898.)

"Dr. Gabritchefski points out that in recent years the number of persons (in Russia) attacked by the disease has increased, the figures for the whole of Russia rising from about 100,000 or 120,000, ten years ago, to considerably over 200,000 in 1897. The introduction of the serum treatment has, however, had a marked effect on the mortality of the disease; and the actual number of deaths from diphtheria has either not increased at all, or has slightly diminished." (Lancet, 5th Aug. 1899.)

Of course there will still be bad diphtheria years and good diphtheria years: for example, the death-rate of the population of England, from diphtheria, was higher during the years 1893-1899 than during the years 1889-1892. Antitoxin can no more prevent a bad diphtheria year than an umbrella can prevent a wet day. But in limited outbreaks of diphtheria, such as occur in a village, an asylum, a school, or a large family of young children, it can be used, and is used, as a prophylactic, and with admirable results. The example of Dr. Kármán, just quoted, is one of the earliest instances of this preventive use of antitoxin: other instances, of equal importance, are given in the Boston Medical and Surgical Journal, December 1897 and March 1898; and in the Lancet, 2nd April 1898, and 28th January 1899. A summary of later experiences of this preventive use of antitoxin in different countries is given by Dr. Wilcox of New York, and Dr. Stevens of Philadelphia, in Gould's Year-Book for 1902:—

"At a meeting of the Société de Pédiatrie (Paris), held June 1901, a resolution was adopted affirming that preventive inoculations present no serious dangers, and confer immunity in the great majority of cases for some weeks, and recommending their employment in children's institutions and in families in which scientific surveillance cannot be exercised. Netter stated that he had collected 32,484 observations (cases) of prophylactic injections, and after eliminating cases in which the disease developed in less than twenty-four hours after injection, or more than thirty days after, there were 6 per cent. of failures. On the other hand, the author stated that he had recently made ninety preventive injections with but 2.17 per cent. of failures. Potter reports a series of twenty-four families in which preventive injections were used. Only one case of diphtheria occurred. In another series of cases, in which no prophylactic injections were given, the disease occurred secondarily in one-third of the houses, and one-sixth of the inmates contracted the disease, in spite of the fact that a large number of the primary cases were removed to the hospital. Blake reports a series of thirty-five prophylactic injections. The treatment was instituted after three cases of diphtheria had developed in a children's home. No secondary cases developed. Voisin and Guinon describe an epidemic of diphtheria in the Salpetrière Hospital among idiots and epileptics. Prophylactic injections were given to all those exposed to the contagion. After that, but four cases appeared, all mild in character. One severe case developed, however, two weeks later, ending fatally in twenty-four hours, showing that the prophylactic action of the antitoxin, while efficacious, is not of very long duration."

It would be easy to prolong ad infinitum the proofs of the curative and preventive efficacy of the antitoxin: it would be impossible to find any evidence to be weighed for one moment against these proofs. There are three early records that ought to be quoted more fully: the 1894 report from the Hospital for Sick Children, Paris; the 1896 report of the American Pædiatric Society; and the 1898 report of the Clinical Society of London.

I

The report from the Hospital for Sick Children, Paris, is contained in a memoir, Sérum-Thérapie de la Diphtérie, the joint work of MM. Roux, Martin, and Chaillon (Annales de l'Institut Pasteur, September 1894). It gives the results of the serum-treatment during February to July 1894. The cases were not selected: the antitoxin was given in every case that was proved, by bacteriological examination, to be diphtheria—with the exception of 20 cases where the children were just dying when they were brought to the hospital. No change was made either in the general treatment or in the local applications to the throat; these were the same that had been used in former years: le sérum est le seul élément nouveau introduit.

In 1890-1893, before the serum-treatment, 3971 children were admitted to the diphtheria wards, and 2029 of them died. The percentage of these deaths was—

In 1890 55.88
" 1891 52.45
" 1892 47.64
" 1893 48.47		}Average = 51.71.

The serum was used from 1st February to 24th July 1894. During this period 448 children were admitted, of whom 109 died = 24.5.