IV Diphtheria
The bacillus of diphtheria, the Klebs-Loeffler bacillus, was first described by Klebs in 1875, and was first obtained in pure culture by Loeffler in 1884. Its isolation was a matter of great difficulty, and the work of many years, because of its association in the mouth with other species of bacteria. The following table, from Hewlett’s Manual of Bacteriology, is a good instance of one of many practical difficulties. Out of 353 cases of diphtheria, bacteriological examination found the diphtheria-bacillus alone in 216 cases. In the remaining 137 it was associated with the following organisms:—
| Streptococci | 6 |
| Staphylococci | 55 |
| Bacilli | 19 |
| Torulæ | 9 |
| Sarcinæ | 6 |
| Streptococci and micrococci | 2 |
| Micrococci and bacilli | 9 |
| Streptococci and bacilli | 1 |
| Torulæ and bacilli | 1 |
| Micrococci and sarcinæ | 6 |
| Micrococci and torulæ | 4 |
| Many forms present together | 19 |
| — | |
| 137 | |
| — |
In December 1890 came the news that Behring and Kitasato had at last cleared the way for the use of an antitoxin:—
“Our researches on diphtheria and on tetanus have led us to the question of immunity and cure of these two diseases; and we succeeded in curing infected animals, and in immunising healthy animals, so that they have become incapable of contracting diphtheria or tetanus.”
Aronsen, Sidney Martin, Escherich, Klemensiewicz, and many more, were working on the same lines; and in 1893, Behring and Kossel and Heubner published the first cases treated with antitoxin. Then, in 1894, came the Congress of Hygiene and Demography at Budapest, and Roux’s triumphant account of the good results already obtained. Thus the treatment is not many years old; but, if the whole world could tabulate its results, the total number of lives saved would already be somewhere above a quarter of a million. Men found it hard at first to believe the full wonder of the discovery: the medical journals of 1895 and 1896 still contain the fossils of criticism—all the may be and must be of the earlier debates on the new treatment. The finest of all these fossils is embedded in the Saturday Review of 2nd Feb. 1895—It is a pity that the English Press should continue to be made the cat’s-paw of a gang of foreign medical adventurers. To get at the truth, we must reckon in thousands: take, out of a whole mass of evidence, all just alike, the reports from London, Berlin, Munich, Vienna, Strasbourg, Cairo, Boston, and New York; these to begin with. Or the following facts, cut almost at random out of the medical journals:—
“The medical report of the French army states that since the introduction of the serum-treatment of diphtheria, the mortality among cases of that disease had fallen from 11 per cent. to 6 per cent.” (Brit. Med. Journ., 3rd September 1898.)
“Professor Krönlein (Zürich) exhibited statistical tables, showing that the prevalence of diphtheria in the canton of Zürich had been nearly uniform during the past fifteen years; and that the mortality rapidly decreased as soon as antitoxic serum was used on a somewhat larger scale. In his clinic, all the patients were examined bacteriologically, and serum was administered in every case of diphtheria without exception. Of 1336 cases treated before the serum-period, 554 = 39.4 per cent. died; whilst during the serum-period there were 55 deaths among 437 cases = 12 per cent. In cases of tracheotomy, the death-rates before and during the serum-period were 66 and 38.8 per cent. respectively.” (Lancet, 7th May 1898, Report of German Surgical Congress at Berlin.)
“Dr. Kármán was entrusted by the Hungarian Government with the task of instituting measures for preventing the spread of diphtheria in a village and its neighbourhood. As general hygienic regulations accomplished nothing, he tried preventive inoculation.... Among 114 children thus treated, there was during the next two months no case of diphtheria, although the disease was prevalent in the village up to the date at which inoculation commenced, and continued to rage in the surrounding villages afterwards. During those two months, only one case of diphtheria appeared in the village, and that was in an uninoculated child; while, in the previous five months, 18.3 per cent. of the village children had been attacked, of whom eight died, six not having been treated with serum. Considering the wretched hygienic condition of the village, the harmlessness of preventive inoculations, and the continuance of the disease in the neighbouring villages, where diphtheria-vaccination was not carried out, the extraordinary value of the inoculations, in the prophylaxis of diphtheria, can hardly be denied.” (Brit. Med. Journ., 16th January 1897.)
“The most striking confirmation of the value of antitoxin has been afforded where the supply ran short during an epidemic. In Baginsky’s clinic, the interruption of the serum-treatment promptly raised the mortality from 15.6 to 48.4 per cent.” (Brit. Med. Journ., 20th October 1895.)
“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.
During the same period (February to June) the Trousseau Hospital, where the serum was not used, had 520 cases, with 316 deaths = 60.0.
The cases at the Hospital for Sick Children must be divided into those that required tracheotomy and those that did not require it:—
Mortality among Cases not requiring Tracheotomy.
In 1890 47.30
" 1891 46.64
" 1892 38.8
" 1893 32.02 } Average = 33.94.
During the serum-period, the mortality of these cases was 12.0. At the Trousseau Hospital, without the serum, the mortality of these cases during the same period was 32.0.
Mortality among Cases requiring Tracheotomy.
In 1890 76.35
" 1891 68.36
" 1892 74.6
" 1893 73.45 } Average = 73.49.
During the serum-period, the mortality of these cases was 49.0. At the Trousseau Hospital, without the serum, the mortality of these cases during the same period was 86.0.
Setting aside, out of the 448 children, those cases of “membranous sore throat” or “pseudo-diphtheria,” in which the Klebs-Loeffler bacillus was not found, there remain 320 cases where it was found. Of these 320 children, 20 were just dying on admission, and did not receive the serum. Of the 300 who received it, 78 died = 26.0. Before the serum-period, the mortality of these cases at the same hospital was about 50.0. The complications of diphtheria, such as paralysis, were much less frequent during the serum-period than they had been before it.
II
Report of the American Pædiatric Society’s Collective Investigation into the use of Antitoxin in the treatment of diphtheria in private practice. (Eighth Annual Meeting, Montreal, May 1896.) From the New York Medical Record, 4th July 1896.
This vast collection of cases is of special interest, because they occurred in private practice. In most of them the nature of the disease was proved by bacteriological examination; in the rest, the clinical evidence was decisive: “It is possible that among the latter we have admitted some streptococcus cases, but the number of such is certainly very small.” All other doubtful cases, 244 in number, were excluded.
Three thousand three hundred and eighty-four cases were reported by 613 physicians from 114 cities and towns, in 15 different States, the District of Columbia, and the Dominion of Canada. To these 3384 cases were added 942 cases from tenement-houses in New York, and 1468 cases from tenement-houses in Chicago. The New York and Chicago cases were, most of them, treated by a corps of inspectors of the Health Board of the city; and the municipal surveillance was very strict at Chicago:—
“There are very few hospitals in America that receive diphtheria patients.... It was the custom in Chicago to send an inspector to every tenement-house case reported, and to administer the serum unless it was refused by the parents. These cases were therefore treated much earlier, and the results were correspondingly better than were obtained in New York, although the serum used was the same in both cities, viz., that of the New York Health Board.”
The sum total of results was 5794 cases, with 713 deaths = 12.3 per cent., including every case returned; but 218 were moribund at the time of injection, or died within twenty-four hours of the first injection. “Should these be excluded, there would remain 5576 cases in which the serum may be said to have had a chance, with a mortality of 8.8 per cent.
| Of | 996 | cases injected | on the first day of the disease, | 49 | died | = | 4.9 | % |
| ″ | 1616 | ″ | on the second ″ | 120 | ″ | = | 7.4 | ″ |
| ″ | 1508 | ″ | on the third ″ | 134 | ″ | = | 8.8 | ″ |
| ″ | 758 | ″ | on the fourth ″ | 147 | ″ | = | 20.7 | ″ |
| ″ | 690 | ″ | on or after the fifth ″ | 244 | ″ | = | 35.3 | ″ |
And in 232 cases, where the day of injection was unknown, there were 19 deaths = 8.2 per cent.
“No one feature of the cases of diphtheria treated by antitoxin has excited more surprise among the physicians who have reported them than the prompt arrest, by the timely administration of the serum, of membrane which was rapidly spreading downward below the larynx. Such expressions abound in the reports as ‘wonderful,’ ‘marvellous,’ ‘in all my experience with diphtheria, have never seen anything like it before,’ etc.
“Turning now to the operative cases, we find the same remarkable effects of the antitoxin noticeable. Operations were done in 565 cases, or in 16.7 per cent. of the entire number reported. Intubation was performed 533 times, with 138 deaths, or a mortality of 25.9 per cent. In the above are included 9 cases in which a secondary tracheotomy was done, with 7 deaths. In 32, tracheotomy only was done, with 12 deaths, a mortality of 37.4 per cent. Of the 565 operative cases, 66 were either moribund at the time of operation or died within twenty-four hours after injection. Should these be deducted, there remain 499 cases operated upon, by intubation or tracheotomy, with 84 deaths, a mortality of 16.9 per cent.
“Let us compare the results of intubation, in cases in which the serum was used, with those obtained with this operation before the serum was introduced. Of 5546 intubation cases in the practice of 242 physicians, collected by M’Naughton and Maddren (1892), the mortality was 69.5 per cent. Since that time, statistics have improved materially by the general use (in and about New York, at least) of calomel fumigations. With this addition, the best results published (those of Brown) showed in 279 cases a mortality of 51.6 per cent.
“But even these figures do not adequately express the benefit of antitoxin in laryngeal cases. Witness the fact that over one-half the laryngeal cases did not require operation at all. Formerly, 10 per cent. of recoveries was the record for laryngeal cases not operated upon. Surely, if it does nothing else, the serum saves at least double the number of cases of laryngeal diphtheria that has been saved by any other method of treatment.”
III
In 1898, the Clinical Society published the Report of their Special Committee, based on 633 cases (Trans. Clin. Soc., xxxi., 1898, pp. 1-50). The whole report should be read carefully; but there is room here for nothing more than the latter part of it. This is given at length.
A
Table showing the General Mortality of cases treated, on the same
day of the disease, with and without Antitoxin.
| Antitoxin Committee: 633 Cases treated with Antitoxin. | Metropolitan Asylums Board 1894: 3042 Cases treated without Antitoxin. | Difference of Percentage. | ||||||
|---|---|---|---|---|---|---|---|---|
| Day of the | C | D | M | Day of | C | D | M | |
| Disease on | a | e | o | Admission | a | e | o | |
| which | s | a | r | to | s | a | r | |
| Treatment | e | t | t | Hospital | e | t | t | |
| was begun. | s. | h | i | s. | h | a | ||
| s. | l | s. | l | |||||
| i | i | |||||||
| t | t | |||||||
| y. | y. | |||||||
| % | % | |||||||
| 1st | 20 | 2 | 10.0 | 1st | 133 | 30 | 22.5 | 12.5 |
| 2nd | 92 | 10 | 10.8 | 2nd | 539 | 146 | 27.0 | 16.2 |
| 3rd | 133 | 20 | 15.0 | 3rd | 652 | 192 | 29.4 | 14.4 |
| 4th | 130 | 26 | 20.0 | 4th | 566 | 179 | 31.6 | 11.6 |
| 5th | 258 | 66 | 25.5 | 5th | 1,152 | 355 | 30.8 | 5.3 |
| and after. | ||||||||
| Totals | 633 | 124 | 19.5 | Totals | 3,042 | 902 | 29.6 | 10.1 |
B
Summary and Conclusions of the Committee’s Report
“The material for the investigation of the clinical value of the antitoxin serum in the treatment of diphtheria was not obtained from selected, but from consecutive, cases, reported from the general hospitals and the fever hospitals of the Metropolitan Asylums Board; all were made use of which fulfilled the requirements of the Committee.
“The Committee rejected all cases in which satisfactory proof of the existence of true diphtheria was not shown, either by the presence of the Bacillus diphtheriæ upon bacteriological examination, or by the occurrence of paralysis in the course of the illness. All were also rejected in which the amount of antitoxin administered was stated in cubic centimetres and not in normal units, the Committee having no means by which the strength of the antitoxin could in these cases be determined.
“Six hundred and thirty-three cases form the basis on which the report is drawn up; 549 were treated with antitoxin obtained from the laboratory of the Royal Colleges of Physicians and Surgeons; the remainder, 84 in number, were injected with antitoxin obtained from other sources. In nine instances, antitoxin from two different sources was injected into the same patient.
“Statistics of the disease before the use of antitoxin are introduced as control series; these were obtained from the fever hospitals of the Metropolitan Asylums Board, and from the general hospitals; and, like the antitoxin series, are compiled from consecutive and not from selected cases.
“The general mortality, under the antitoxin treatment, was 19.5 per cent.; a reduction of 10 on the percentage mortality of the cases treated in the hospitals of the Metropolitan Asylums Board in 1894. If 15 fatal cases, in which death took place within twenty-four hours of the first injection, be deducted, the mortality falls to 15.6 per cent.; which is very little more than half the mortality during 1894 under other forms of treatment.
“The lessened mortality is especially noticeable in the earlier years of life, the percentage mortality of children under five being 26.3, as opposed to 47.4. In the next period of five years, the percentage of mortality is 16.0, as opposed to 26.0; whilst after ten years of age the difference in the mortality is slight.21
“Laryngeal diphtheria is admittedly the most dangerous form. The laryngeal cases have a percentage mortality of 23.6 in the antitoxin, as compared with 66.0 in the non-antitoxin series. In the cases in which laryngeal symptoms are so severe as to necessitate tracheotomy, the saving of life by the use of antitoxin is very marked, the mortality being reduced one-half, to 36.0 as opposed to 71.6 per cent.
“The strongest evidence of the value of the antitoxin treatment is that, in addition to reducing the general mortality by one-third, the duration of life in the fatal cases is decidedly prolonged. These two facts taken together conclusively prove the beneficial effects of the antitoxin treatment.
“The incidence of paralysis is greater in the antitoxin than in the control series. This increased number is partly explained by the lessened mortality, and partly by the longer duration of life in the fatal cases affording time for the development of paralytic symptoms. The percentage mortality of those who had some form or other of paralysis is lower in the antitoxin than in the control series; so that, notwithstanding the apparent greater risk of paralysis supervening, the probability of final recovery is greater.
“No definite conclusion can be drawn, for the reasons stated in the body of the report, as to the advantage of administering the whole of the antitoxin within forty-eight hours of the first injection, or continuing it for a longer period; but evidence is afforded of the importance of its administration as early as possible in the course of the disease; the percentage mortality in cases injected on the first and second days of the disease being 10.7, as compared with 25.5 for those first receiving the injection on the fifth or some subsequent day.
“No conclusion can be drawn, from the cases reported on, as to the amount of antitoxin which should be used to produce the best effects; but they show that the administration of very large doses is followed by no pronounced ill effects.
“The injection of antitoxin is responsible for the production of rashes, joint-pains, and possibly for the occurrence of late pyrexia. In 34.7 per cent. the injections were followed by rashes. Some amount of fever accompanied the rash in 60 per cent. In only 9.4 per cent. of those in whom rashes were observed did death ensue.
“Joint-pains were observed in 40, or 6.3 per cent. of the whole number, and all but five of them had a rash as well.
“In 26, or 65 per cent. of the joint-pains, some rise of temperature accompanied the pain. A rise of temperature during convalescence, accompanied by either rash or joint-pain, occurred in 27, or 4.2 per cent. of the whole number.
“No connection could be traced between the amount of antitoxin administered and the occurrence of rashes or late pyrexia, but the pain in and about the joints appears to have a relationship to the amount of antitoxin used.
“The results of the Committee’s investigation tend to show that by the use of antitoxin—
1. The general mortality is reduced by one-third.
2. The mortality in tracheotomy falls by one-half.
3. Extension of membrane to the larynx very rarely occurs after the administration of antitoxin.
4. The duration of life in the fatal cases is decidedly prolonged.
5. The number of fatal cases is less when antitoxin is used early in the illness than in those which do not receive it until a later period.
6. The frequency of the occurrence of paralysis is not diminished, but the percentage of recoveries in cases with paralysis is slightly increased.22
7. Rashes are produced in about one-third of the cases, and are attributable to the antitoxin.
8. Pain, and occasionally swelling about the joints, are produced in a number of cases.
9. Even when used in large doses, no serious ill effects have followed the injection of antitoxin.”
The foregoing reports belong to ancient history. Let us leave them, and study the record of the hospitals of the Metropolitan Asylums Board. They serve a city of 121 square miles, and 4-1/2 millions of inhabitants.
The use of the antitoxin in the hospitals of the Metropolitan Asylums Board began in 1895. It had been used in 1894 on a few cases only, during the latter part of the year, and had been procured with much difficulty from various sources, chiefly from the Institute of Preventive Medicine. On 9th November 1894, the Board applied to the Laboratories’ Committee of the Royal Colleges of Physicians and of Surgeons, asking them to undertake the supply. Arrangements were made for this purpose; and the sum of £1000 was given by the Goldsmiths’ Company. Dr. Sims Woodhead, then Director of the Laboratories of the Conjoint Colleges, now Professor of Pathology at Cambridge, was put in charge of the bacteriological work and the preparation of the serum, with a host of expert colleagues: the administration of the treatment was the work of the medical officers of the hospitals of the Metropolitan Asylums Board. The experiences of 1895 are given in the following passages from the joint report to the Board from the medical superintendents:—
“The period covered by the report extends from 1st January 1895 to 31st December of the same year. During this time—with the exception of an interval of three months at the Eastern Hospital, when its use was suspended; of three months at the Fountain, and to a considerable extent throughout the year at the South-Eastern Hospital, when all cases were consecutively treated, irrespective of their severity—the serum was administered only to cases which at the time of admission were severe, or which threatened to become so. In a certain number, the patients being moribund at the time of their arrival, and beyond the reach of any treatment, no antitoxin was given. No change has taken place during the year in the local treatment of the cases, nor has there been any new factor in the treatment other than the injection of antitoxin.
“It must be clearly understood that, with the exceptions previously stated, it has been the practice at each of the hospitals to administer serum to those cases only in which the symptoms on admission were sufficiently pronounced to give rise to anxiety, the mild cases not receiving any.
“No less than 46.4 per cent. of the antitoxin cases were under five years of age, against 32.5 per cent. in the non-antitoxin group; and only 16.1 per cent. in the former class were over ten years of age, against 33.8 per cent. in the latter. The high fatality of diphtheria in the earlier years of life is notorious.
“It is obvious, therefore, that to compare the mortality of those treated with antitoxin with that of those which during the same period were not so treated, would be to institute a comparison between the severe cases and those of which a large proportion were mild. This would clearly be misleading.
“The only method by which an accurate estimate can be obtained as to the merits of any particular form of treatment, is by comparing a series of cases in which the remedy has been employed with another series not so treated, but which are similar, so far as can be, in other respects. This, in the present instance, is impossible; but, having regard to the fact that 61.8 of the 1895 cases were treated with serum, an approximately accurate conclusion can be drawn by contrasting all cases of diphtheria completed during 1895, the antitoxin period, with all cases completed during 1894.
“The year 1894 has been selected for the purpose of comparison, not only because it is the year immediately preceding the antitoxin period, but because the average severity of the cases has been, in our opinion, about equal. Moreover, the death-rate in 1894 was slightly lower than it had been in any previous year.
“... Of 3042 patients of all ages treated during 1894, 902 died—a mortality of 29.6 per cent.; whereas, of 3529 cases treated during 1895, 796 died—a mortality of 22.6 per cent.; the difference in percentage between the two rates being therefore 7.1. This, assuming that the former rate would otherwise have been maintained, represents a saving of 250 lives during the past year.
Influence of Age.
Table showing variations in reduction of mortality obtained with
Antitoxin at different ages.
| Ages. | Antitoxin Cases, 1895 | All Cases, 1895 | All Cases, 1894 | Diff. in Mortalities, 1894 and 1895. | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Cases. | Deaths. | Mortality per cent. | Cases. | Deaths. | Mortality per cent. | Cases. | Deaths. | Mortality per cent. | ||
| Under 5 | 1013 | 379 | 37.4 | 1453 | 497 | 34.2 | 1171 | 556 | 47.4 | 13.2 |
| ″ 10 | 1829 | 575 | 31.4 | 2720 | 744 | 27.3 | 2246 | 836 | 37.2 | 9.9 |
| ″ 15 | 2056 | 606 | 29.4 | 3144 | 779 | 24.7 | 2609 | 877 | 33.6 | 8.9 |
| All ages | 2182 | 615 | 28.1 | 3529 | 796 | 22.5 | 3042 | 902 | 29.6 | 7.1 |
For every age-group, with the single exception of that comprising the years 15 to 20 (the numbers of which are small), the percentage mortality was less in the 1895 than in the 1894 cases. The reduction in mortality was greatest in early life.
Influence of Time of coming under Treatment.
Table showing percentage mortality in relation to day of disease
on which cases came under treatment.
| Day of Disease. | 1894. | 1895. | Difference. |
|---|---|---|---|
| 1st | 22.5 | 11.7 | 10.8 |
| 2nd | 27.0 | 12.5 | 14.5 |
| 3rd | 29.4 | 22.0 | 7.4 |
| 4th | 31.6 | 25.1 | 6.5 |
| 5th and over | 30.8 | 27.1 | 3.7 |
| Total | 29.6 | 22.5 | 7.1 |
“It will be seen that the percentage mortality of cases admitted on the same day of disease is less in every instance in the year 1895. The difference is most marked in the case of those patients who were admitted on the first and second day of illness, viz., 10.8 and 14.5 respectively.
“Both in 1894 and 1895, no less than over 37 per cent. of the patients were admitted on, or after, the fifth day of disease. And, moreover, while in 1894 as many as 59.2 per cent. of the fatal cases were not brought under treatment until the fourth day, or later, in 1895, the antitoxin year, the proportion was even higher, viz., 67.7 per cent.
Laryngeal Cases
“The tracheotomy results at each hospital are more favourable in the year 1895 than in 1894, the mortality ranging in the latter year at the different hospitals between 90 per cent. and 59.4 per cent., whereas in 1895 the range was from 56.2 to 40.5.
“The combined tracheotomy mortality for all the hospitals, which in 1894 was 70.4 per cent., has fallen to 49.4 per cent. in 1895. This is a lower death-rate than has ever been recorded in any single hospital of the Board for a year’s consecutive tracheotomies. In other words, rather more than 50 per cent. of children on whom the operation has been performed have been saved since the employment of antitoxin. In one of the hospitals no less than a fraction under 60 per cent. survived, although the recoveries in that hospital in any previous year did not exceed 25 per cent., and in the preceding year—viz., 1894—were as low as 10 per cent.
“The improved results in the tracheotomy cases of 1895 have also been shared by analogous cases in which the operation was not performed. The percentage mortality of all laryngeal cases has fallen from 62 in 1894 to 42.3 in 1895.
“Moreover, the number of laryngeal cases which required tracheotomy has fallen in 1895 to 45.3 per cent., whereas in 1894 it was 56 per cent.
“The following tables briefly summarise the foregoing results. As no returns for 1894 were furnished by the Fountain Hospital by reason of the smallness of the numbers, the Fountain cases have also been omitted from the 1895 figures, in order that the two series may be rendered strictly comparable:—
1. Comparative Mortality of Laryngeal Cases at all Hospitals,
except the Fountain.
| Year. | Cases. | Deaths. | Percentage Mortality. |
|---|---|---|---|
| 1894 | 466 | 289 | 62.0 |
| 1895 | 468 | 196 | 41.8 |
2. Comparative Results in Tracheotomy Cases at all Hospitals,
except the Fountain.
| Year. | Cases. | Deaths. | Percentage Mortality. |
|---|---|---|---|
| 1894 | 261 | 184 | 70.4 |
| 1895 | 219 | 108 | 49.3 |
3. Comparative Number of Laryngeal Cases which required
Tracheotomy at all Hospitals, except the Fountain.
| Year. | Cases. | Tracheotomies. | Percentage of Tracheotomies. |
|---|---|---|---|
| 1894 | 466 | 261 | 56.0 |
| 1895 | 468 | 219 | 46.8 |
“On these tables further comment seems unnecessary.
Summary
“The improved results in the diphtheria cases treated during the year 1895, which are indicated by the foregoing statistics and clinical observations, are—
1. A great reduction in the mortality of cases brought under treatment on the first and second day of illness.
2. The lowering of the combined general mortality to a point below that of any former year.
3. The still more remarkable reduction in the mortality of the laryngeal cases.
4. The uniform improvement in the results of tracheotomy at each separate hospital.
5. The beneficial effect produced on the clinical course of the disease.
Conclusions
“A consideration of the foregoing statistical tables and clinical observations, covering a period of twelve months, and embracing a large number of cases, in our opinion sufficiently demonstrates the value of antitoxin in the treatment of diphtheria.
“It must be clearly understood, however, that to obtain the largest measure of success with antitoxin it is essential that the patient be brought under its influence at a comparatively early date—if possible, not later than the second day of disease. From this time onwards, the chance of a successful issue will diminish in proportion to the length of time which has elapsed before the treatment is commenced. This, though doubtless true of other methods, is of still greater moment in the case of treatment by antitoxin.
“Certain secondary effects not unfrequently arise as a direct result of the injection of antitoxin in the form in which it has at present to be administered, and even assuming that the incidence of the normal complications of diphtheria is greater than can be accounted for by the increased number of recoveries, we have no hesitation in expressing the opinion that these drawbacks are insignificant when taken in conjunction with the lessened fatality which has been associated with the use of this remedy.
“We are further of the opinion that in antitoxic serum we possess a remedy of distinctly greater value in the treatment of diphtheria than any other with which we are acquainted.”
Now let us take the whole record of all the hospitals together. The disease was first admitted in 1888; this year is therefore to be reckoned as incomplete.
| Year. | Percentage Mortality. | Year. | Percentage Mortality. |
|---|---|---|---|
| 1888 | 59.35 | 1897 | 17.69 |
| 1889 | 40.74 | 1898 | 15.37 |
| 1890 | 33.55 | 1899 | 13.95 |
| 1891 | 30.63 | 1900 | 12.27 |
| 1892 | 29.35 | 1901 | 11.15 |
| 1893 | 30.42 | 1902 | 11.04 |
| 1894 | 29.29 | 1903 | 9.69 |
| 1895, first antitoxin year | 22.85 | 1904 | 10.08 |
| 1896 | 21.20 | 1905 | 8.3 |
These results, of course, are but one instance of what has happened, since 1895, in every country all over the civilised world. Securus judicat orbis terrarum. We have Siegert’s tables (1900), based on no less than 40,038 cases admitted in nine years to sixty-nine hospitals in Germany, Austria, Switzerland, and Paris. He divides these nine years into a “pre-serum period,” an “introduction year,” and a “serum period.” In the pre-serum period the general mortality was 41.5, and the mortality of cases requiring operation was 60; in the serum period, the general mortality was 16.5, and the mortality of cases requiring operation was 37.5.
Any bad results that have been recorded from the use of the antitoxin are so rare, in comparison with the hundreds of thousands of injections made, that they do not come to be considered here. And, even though a few have occurred, we may be sure that some of them were due, not to the antitoxin, but to the natural course of the disease.23 The lesser drawbacks, the occurrence of joint pains and of rashes, are transient and in no way serious.
It has been supposed, and said, that the use of the antitoxin increases the complications of the disease. On this point, the best authority is Professor Woodhead’s monumental Report (1901), dealing with the Metropolitan Asylums Board cases for 1895 and 1896. He sums up the matter thus:—
“The free use of antitoxin does not raise the percentage of cases of albuminuria. As regards vomiting, the statistics give little information, as vomiting is usually met with only in the very severe cases. This also holds good of anuria. The number of cases of adenitis appears to be distinctly reduced by the use of antitoxin, as the percentage of cases falls as the injections of antitoxin are pushed. The use of antitoxin has also had a perceptible effect in diminishing the cases of nephritis, and it certainly has not aggravated the kidney complications of diphtheria. There can be no doubt that in cases treated with antitoxin there is a greater percentage of cases in which joint-pains occur than in cases not so treated; these, however, are transitory, and are probably the result of some slight change in the blood set up by the action of the serum itself, and not by the antitoxic substance in the serum. The number of primary abscesses has undoubtedly been reduced by the use of antitoxin. It may also be accepted that antitoxic serum has some effect in temporarily raising the temperature, but only during the periods of joint-pains and serum rashes; all these, however, are of comparatively slight importance as compared with the effect the antitoxin has in diminishing the percentage mortality and alleviating the more severe symptoms.
“It is of importance to observe that amongst the cases of paralysis following diphtheria the death-rate (32 per cent.) was actually higher amongst those not injected with antitoxin than amongst those where antitoxin was used (30.5 per cent.), although the former paralyses must be looked upon as being the result of a comparatively mild attack of the disease. From this it is evident that, when once paralysis supervenes in these cases, it is quite as fatal in its effects as in the cases (usually those of a more severe type) where antitoxin has been given. Antitoxin cannot cure the degeneration of the nerve, but it can neutralise the diphtheria toxin, and so put a stop to the advance of the degenerative changes due to its action. In 1896, when, of course, antitoxin was given much more freely, the percentage of deaths in the non-injected cases where paralysis had come on fell to 18.4.
“Antitoxin rashes occur at a comparatively late stage of the disease. They cannot be looked upon as in any way dangerous, although the secondary rise of temperature, and the irritation of the skin which usually accompany their presence are very undesirable complications, and may retard somewhat the convalescence of nervous and irritable patients.
“Antitoxin appears to diminish the liability of the lungs to inflammatory change in severe attacks of diphtheria.”
Now let us take another point of view. If anybody really doubts whether the antitoxin did really save these lives in the hospitals of the Metropolitan Asylums Board, what answer has he got to the following table? It is published in the Board’s Report for 1904, and was drawn up by Dr. MacCombie, Medical Superintendent of the Brook Hospital. It shows the supreme importance of giving the antitoxin at the very beginning of the disease. The figures in brackets are the total numbers of the cases in the eight years:—
Percentage Mortality according to Time of coming under
Treatment.
| Day of Disease. | 1897. | 1898. | 1899. | 1900. | 1901. | 1902. | 1903. | 1904. |
|---|---|---|---|---|---|---|---|---|
| (204) 1st | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| (1278) 2nd | 5.4 | 5.0 | 3.8 | 3.6 | 4.1 | 4.6 | 4.2 | 5.43 |
| (1374) 3rd | 11.5 | 14.3 | 12.2 | 6.7 | 11.9 | 10.5 | 17.6 | 10.63 |
| (1086) 4th | 19.0 | 18.1 | 20.0 | 14.9 | 12.4 | 19.8 | 16.7 | 19.51 |
| (1382) 5th and after | 21.0 | 22.5 | 20.4 | 21.2 | 16.6 | 19.4 | 17.3 | 13.11 |
Here we see that in 1482 patients, who got the antitoxin within forty-eight hours of the onset of the disease, the mortality was 2-1/4 per cent. In 1278 patients, who did not get the antitoxin till the third day, the mortality was 11-3/4 per cent. That is the result of one day’s delay over sending the child into hospital.
Again, it is not only lives that are saved, but suffering that is avoided. Just lately, at a meeting of the Chelsea Clinical Society (May 1906), reference was made to this point by Dr. Foord Caiger, Medical Superintendent of the South-Western Hospital. “The number of tracheotomies is less than half what it used to be;” and again, “Instead of the spectacle of a number of patients in great distress, with swollen necks and stuffed-up noses, fretful and crying, such cases are now quite the exception, and, in the few one does come across, the condition lasts for a comparatively short time.” And again, “It was quite unusual (before 1895) for a nurse to care to stay very long in charge of one of the diphtheria wards, because she found the work so depressing. But nowadays the diphtheria wards are perhaps the most popular in the hospital, a fact which is mainly owing to the change in the general aspect of the patients and the greatly reduced mortality.” (Clinical Journal, May 23, 1906.)