HEALTH DEPARTMENT, 
CRIMINAL COURT BUILDING, 
NEW YORK CITY. 
THE USE OF ANTITOXIC SERUM IN THE TREATMENT OF 
DIPHTHERIA UNDER THE SUPERVISION OF THE NEW 
YORK CITY HEALTH DEPARTMENT, WITH A 
RIiSUMB OF THE PUBLISHED REPORTS 
ON THE SUBJECT. 
BY 
HERMANN M. BIGGS, M.D., 
OF NEW YORK J 
AND 
ARTHUR R. GUERARD, M.D., 
OF NEW YORK. 
FROM 
THE MEDICAL NEWS, 
December 12, 19, and 26, 1896. | Reprinted from The Medical News, Dec. 12, 19, and 26, 1896.] 
THE USE OF ANTITOXIC SERUM IN THE TREATMENT OF DIPHTHERIA UNDER THE 
SUPERVISION OF THE NEW YORK CITY HEALTH DEPARTMENT, WITH A 
RESUME OF THE PUBLISHED REPORTS ON THIS SUBJECT. 
By HERMANN M. BIGGS, M.D. 
OF NEW YORK ; 
PATHOLOGIST AND DIRECTOR OF THE BACTERIOLOGICAL LABORATORIES, NEW YORK HEALTH DEPARTMENT, 
AND 
ARTHUR R. GUERARD, M.D., 
OF NEW YORK ; 
ASSISTANT BACTERIOLOGIST. 
On January 1, 1895, the New York City Health De- 
partment commenced the use of the diphtheria antitoxin 
prepared in the bacteriological laboratories. For about 
six weeks after this date, however, the serum at command 
was limited in amount and was not of a satisfactory 
strength. The supply of foreign preparations of anti- 
toxin at this time was very small; only a few vials could 
be obtained under any conditions, and the prices charged 
were exorbitant, averaging about 80 cents per 100 anti- 
toxin units (Behring's standard), or from $8 to $12 a 
dose. The price of similar preparations now, as fur- 
nished by the Health Department, is from 75 cents to 
$1.50, or 10 cents per 100 units. 
The serum prepared in the laboratories of the Health 
Department was first employed in the hospitals, but as 
soon as a sufficient quantity was at hand, arrangements 
were made for its administration without charge, on the 
request of the attending physician, by inspectors detailed 
for this purpose, in any case of diphtheria occurring in 
the city. During the period ending October 1, 1896, 
1352 cases regarded as diphtheria were treated in their 
homes by inspectors of the department at the request of 
the attending physicians, and 1207 persons (excluding 
inmates of public institutions), who had been exposed to 
diphtheria, were immunized by the administration of anti- 
toxin. Altogether, more than 3000 injections of anti- 
toxin have been administered and about 6000 visits 
made. This duty has been mainly performed by Medi- 
cal Inspectors Drs. H. F. Koester, W. E. Studdiford, 
J. S. Ennis, L. K. Graves and W. J. Pulley. 
The cases referred to above do not include any of those 
treated in the various institutions of the city, and were, as 
a rule, among the very poorest classes in the tenement- 
house districts. They have, generally speaking, been in 
the most unfavorable surroundings; have been severe 
cases, or regarded by the physicians in attendance as 
hopeless cases, and have usually come under observa- 
tion rather late in the course of the disease. In some of 
the later cases, however, the reverse of this may be said, 
as physicians who had seen the effects of antitoxin on the 
course of diphtheria, and had thus been convinced of its 
value, not infrequently referred comparatively mild cases 
for treatment at an early period of the disease. It will be 
noted by reference to the accompanying tables that, dur- 
ing the first year of this work, up to April i, 1896, about 
eight per cent, of the cases treated were moribund when 
first seen by the inspectors, while in the last six months 
the percentage has been reduced to about one-half of 
this number. In a large proportion of the whole num- 
ber there was practically no other treatment beside the 
administration of antitoxin. In some cases strychnia, 
whisky, and other remedies were also given. In many 
instances the physician in attendance discontinued his 
visits, after referring the case to the Health Department 
for the administration of antitoxin, as the family was un- 
able to pay for his attendance. 
There has been from the beginning a continuous and 
marked improvement in the results obtained, in conse- 
quence, it is believed, of increased experience in the use 
of this agent, the earlier application of the treatment, the 
constant improvement in the character of the serum, and 
the larger dosage employed. During the first year (see 
table No. 1) the mortality was seventeen and nine-tenths 
per cent., while during the last six months the mortality 
was only eleven and one-tenth per cent. 
For the execution of the plan adopted for the free ad- 
ministration of antitoxin among the poor the city was 
divided into districts, each district being placed in the 
charge of an inspector, who is always on duty and liable 
to call at any hour during the day or night. The re- 
quests for the administration of antitoxin are received at 
the offices of the Health Department, and immediately 
referred by police telegram, or by telephone, to the 
inspector in charge of the district in which the case oc- 
curs. In some instances during the last months, where 
several cases have been treated by the same physician, 
they have been referred by him directly to the inspector, 
in order that valuable time might thus be saved. 
There were treated up to October 1st, all included, 
1352 cases regarded as diphtheria. Of these 100 cases 
showed later on bacteriological examination no Loeffler 
bacilli-were considered as false diphtheria and excluded 
from the statistics; or were found to be true diphtheria, 
transferred to the Willard Parker Hospital, 2 
ANTITOXIC SERUM. 
Table I.-Cases of Diphtheria Treated with Antitoxin by the Health Department, January 
1, 1895, to October i, 1896. 
Total cases of true Diphtheria injected with Antitoxin by the Medical Inspectors of the Health Department, 
showing the number of cases injected, and the mortality percentage, prognosis at time of injection, extent of mem- 
brane in the throat, complications, and number of injections given: 
Cases. 
Deaths. 
Mortality, per cent. 
Prognosis. 
Extent of 
Membrane. 
Complications.3 
Number of Injections 
Given. 
i Total Injections 
Given. 
Number of 
AntitoxinUnits 
Injected. 
Good. 
£4 
Bad. 
Tonsils 
and 
Pharynx 
and 
Nose.1 
c 
U 
1 Broncho- 
, pneumonia. 
Nephritis. 
Sepsis. 
Paralysis. 
I 
2 
3 
4 
5 
January i, 1895, to 
April 1, 1896 
April i, 1896, to Oc- 
tober 1, 1896 
856 
154 
44 
17.9 
II. I 
148 
261 
148 
447 
128 
170 
114 
280 
9i 
145 
97 
261 
94 
8 
8 
35 
5 
136 
66 
7 
6 
559 
234 
230 
122 
60 
32 
8 
8 
0 
I 
1231 
611 
600 to 2500 
600 to 3000 
Totals 
1252 
15.8 
268 
409 
575 
284 
37i 
242 
355 
202 
793 
352 
92 
I 
1842 
600 to 3000 
Moribund cases, or 1 
those dying- within V 
24hrs., deducted.. ) 
80 
There remain.... 
1172 
118 
IO. 
Notes to Table I.-From January 1, 1895, to April 1, 1896, there were treated 856 cases, with 154 deaths, giving a mortality 
of 17.9 per cent. Of these 65 were moribund at the time or died within twenty-four hours after injection; deducting these, the mortality 
was 11.2 per cent. From April 1 to October 1, 1896, there were treated 396 cases, with 44 deaths, or a mortality of 11.1 per cent. Of 
these 15 were moribund, or died within twenty-four hours after injection, and deducting these, the mortality for the last six months was 
7.6 per cent. The total mortality from January 1, 1895, to October 1, 1896 (1252 cases and 198 deaths), was 15.8 per cent.; deducting 
the moribund, it was 10 per cent. 
1 In the nasal cases the pharynx and tonsils were also involved, as a rule. 
2 The larynx involved, with or without the pharynx and nose. 
3 Only the common and more important complications of diphtheria are noted here, and these notes are incomplete. Many other 
complications occurred (notably scarlet fever), and acted as contributory or determining causes of death. These fatal cases are all 
included. 
Table II.-Cases of Laryngeal Diphtheria treated with Antitoxin by the Health Department, 
January i, 1895, to October i, 1896. 
Total cases of Laryngeal Diphtheria injected with Antitoxin by the Medical Inspectors of the Health Depart- 
ment, showing the number of cases injected, and the cases, deaths, and mortality percentage in both operative and 
non-operative cases: 
Total Laryngeal Cases. 
Non-operative Cases. 
Operative Cases (Intubation). 
Cases. 
Deaths. 
M ortality, 
per cent. 
Cases. 
Deaths. 
Mortality, 
per cent. 
Cases. 
Deaths. 
Mortality, 
per cent. 
January i, 1895, to April 1, 1896. 
April 1, 1896, to October 1, 1896.. 
261 
87 
33-3 
197 
58 
29-4 
64 
29 
45-3 
94 
21 
22.2 
86 
21 
25-5 
8 
0 
0. 
Totals 
355 
108 
30.4 
283 
79 
27-9 
72 
29 
40.2 
Moribund,or dying within 24 hours, 
deducted 
38 
34 
4 
There remain .. 
3i7 
70 
22. 
249 
45 
17.9 
68 
25 
36.7 
Notes on Table II. - From January i, 1895, to April 1, 1896, there were 261 laryngeal cases injected, resultingin 87 deaths, or 
a mortality of 33.3 per cent. Of these, 25 were moribund at the time, or died within twenty-four hours after injection, and deducting 
these, the mortality was 26.2 per cent. Of the 64 cases intubated, resulting in 20 deaths, or a mortality of 45.3 per cent., 4 were mori- 
bund at the time; deducting these, the mortality of operated cases was 41.6 percent.; 197 cases, resulting in 58 deaths, were not 
operated upon, and of these the mortality was 29.4 per cent.; deducting 21 moribund at the time, or dying within twenty-four hours after 
injection, the mortality for non-operative cases was 21 per cent. From April 1 to October 1, 1896, there were 94 laryngeal cases injected, 
resulting in 21 deaths, or a mortality of 22.2 per cent.; of these, 13 were moribund, or died within twenty-four hours after injection, 
deducting which would give a mortality of 11.1 per cent. Of the 8 cases intubated, none died. There were 86 cases not operated on, 
resulting in 21 deaths, or a mortality of 25.5 per cent.; deducting the 13 moribund cases, or those dying within twenty-four hours, the 
mortality was only 9.8 per cent. According to the reports of the inspectors, many more of the laryngeal cases might have been saved 
by earlier treatment and intubation. The total mortality of laryngeal cases from January 1, 1895, to October 1, 1896 (355 cases and 108 
deaths), was 30.4 per cent.; deducting the moribund, it was 22 per cent. ANTITOXIC SERUM. 
3 
and thus passed from observation of the inspector; or 
the treatment was discontinued from some other cause. 
There remain 1252 cases, of which 1054 recovered, and 
198 died, the mortality being per cent. Of the 
whole number, 856 were treated previous to April 1, 
1896, and among these the mortality was per cent. 
Three hundred and ninety-six were treated during the 
period between April 1st and October 1st, and among 
these the mortality was 11 per cent. While the differ- 
ence in the results may be in part due to the season of 
the year, yet this does not satisfactorily account for the 
whole difference in mortality, as reference to the monthly 
mortality curve of the whole city will show that there was 
not a corresponding reduction in the general mortality 
■during the latter months. 
Of the 1252 cases, 80 were moribund at the time of the 
first injection, or died within twenty-four hours after it. 
These may be properly excluded in a consideration of the 
utility of antitoxic serum in the treatment of diphtheria. 
There remain 1172 cases with 118 deaths, or a mortality 
-of ten per cent. Five hundred and seventy-four, or nearly 
one-half of the whole number, were reported by the in- 
spectors to be in a bad condition and suffering from very 
severe or septic diphtheria at the time of the first injec- 
tion, and 268, or about twenty-one per cent., were re- 
ported as in good condition, or as apparently affected with 
a mild form of the disease, when first seen. In 355, or 
more than twenty-eight per cent, of the whole number, 
the larynx, with or without the pharynx, tonsils, and 
nares, was involved. In 242 cases, in addition to the 
pharynx and tonsils, the nares were involved. One hun- 
dred and eight deaths occurred among the 355 laryngeal 
cases, giving a mortality of per cent. Seventy-two 
of the laryngeal cases were intubated, in some instances 
by the inspectors, and in some by the attending physi- 
cians, and of these 29 died, or per cent. In 283 
laryngeal cases there was no operative interference and in 
these the mortality was per cent. Of the fatal 
laryngeal cases, 38 were moribund at the time of the 
first injection or died within twenty-four hours after it. 
If these be excluded, there remain 317 cases with 70 
deaths, or a mortality of twenty-two per cent. Other 
data as to the mortality in operative and non-operative 
-cases, and as to results in relation to the age of the 
patient, and the day of the disease on which treatment 
was begun, are shown in detail in the accompanying 
tables. (Tables Nos. 1, 2, and 3.) 
In a large majority of all cases treated-i.e., -only 
•one injection of antitoxin was administered; in 352 two 
injections were made, and in 108 three or more. In all 
severe cases the initial dose was large, varying from 1500 
to 3500 units, experience showing that the best results were 
obtained from large initial doses, and the tendency has 
been to constantly increase the size of this dose. This 
experience is in direct confirmation of the conclusions 
reached in the experimental investigations on animals. As 
a rule, the patients were seen the second time at the end 
of twenty-four hours, and where it was considered neces- 
sary a second injection was then administered. They 
were afterward seen at intervals until the disease had 
terminated either in complete convalesence or death. 
The serum employed has been generally of high grade, 
and during the last nine months has been at least twice as 
potent as Behring's No. 3; that is, it contained 300 or more 
antitoxin units in each cubic centimeter. During the past 
three months the serum employed contained from 400 to 
500 units in each c.cm. Better results have been obtained 
with the high-grade preparations, and with larger doses. 
In the earlier months, where large quantities of serum were 
administered (the serum containing proportionately less 
antitoxin), rashes were of frequent occurrence; but no re- 
liable data as to the percentage of cases in which they ap- 
peared can be obtained. There has been a considerable 
diminution in the frequency with which rashes have oc- 
curred, and in the severity of these, since the use of the 
higher grade preparations of antitoxin in which smaller 
doses of serum are employed. Joint symptoms were of 
very unusual occurrence. In five instances abscesses fol- 
lowed the administration of the serum; but in none of 
these could the abscess be properly charged to the serum 
itself. In two or three of the early cases where large im- 
munizing 'injections were employed, severe joint symp- 
toms, accompanied by prostration and pyrexia, occurred, 
and in a number, temporary (twenty-four to seventy-two 
hours) albuminuria appeared. Aside from the symptoms 
referred to, and occasionally a temporary pyrexia, no dis- 
agreeable effects in any way attributable to the antitoxin 
were observed. No case has come under observation 
where death could be ascribed to the administration of 
the serum, or where any permanent injury could be prop- 
erly regarded as having been produced by it. 
The data as regards complications are very incomplete, 
as in the class of patients treated and under the conditions 
existing, careful observations could not be made. Only the 
more common complications of diphtheria are noted; in 
many instances other serious complications existed (notably 
scarlet fever), and acted as contributing or determining 
causes of death in fatal cases. All such cases have been in- 
cluded. 
In all of the cases, with rare exceptions, in which the 
clinical features were unmistakable, the clinical diagnosis 
was confirmed by bacteriological examination. In a few 
cases the result of the bacteriological examination was in- 
decisive, while the case was evidently diphtheria, and 
these have been included. In others bacteriological exam- 
ination showed clearly that the case was false diphtheria, 
and such cases have been excluded from the list. The 
usual practice has been when a case was seen for the first 
time by the inspector (at the request of the attending 
physician) to administer an injection of antitoxin, if it 
seemed clinically to be a case of diphtheria, and at the 
same time to make a culture from the throat for bacteri- 
ological examination, if a culture had not been previously 
made. The course subsequently pursued in each case 
depended upon the results of the bacteriological examina- 
tion. 
When cases of diphtheria were seen in families in which 
there were other children, who had been exposed to the 
disease, and when the parents would allow it, an immu- 
nizing injection was administered to each of them, and trial 4 
ANTITOXIC SERUM. 
Table III.-Cases of Diphtheria Treated by the Health Department, Arranged According to 
Age and Day of Disease when Injected, January i, 1895, to October i, 1896. 
AGE. 
Mortality, per cent 
Died 
Cases 
Age 
to 
00 
to 
X 
o-i Year. 
to 
bo 
Oj 
to 
i-2 Years. 
M 
b 
GO 
to 
to 
2-3 Years. 
vb 
O 
$ 
3-4 Years. 
to 
& 
00 
to 
4-5 Years. 
o 
b 
to 
5-10 Years. 
p 
b 
0 
£ 
10-15 Years. 
00 
b 
H 
GO 
15-20 Years. 
p 
b 
0 
Go 
Over 20 years. 
bo 
to 
to 
T otals. 
Moribund, or 
dying within 
24 hours, de- 
ducted. 
O'OI 
00 
*to 
Remaining. 
DAY OF DISEASE. 
Day of Disease 
First Day. 
Second Day. 
Third Day. 
Fourth Day. 
Fifth Day, 
or later. 
Unknown. 
Total. 
Cases. 
Died. 
Cases. 
Died. 
Cases. 
Died. 
Cases. 
Died. 
Cases. 
Died. 
Cases. 
Died. 
Cases. 
I Died. 
1 
Mortality, 
per cent. 
Cases and deaths 
157 
11 
331 
30 
293 
42 
197 
39 
262 
72 
12 
4 
1252 
198 
Mortality, per cent 
7.0 
9.0 
14-3 
20.0 
27-4 
33-3 
15.8 
Moribund, or dying within 24 
hours, deducted 
5 
14 
17 
15 
25 
4 
80 
There remain 
152 
6 
217 
16 
276 
25 
182 
24 
237 
47 
8 
0 
1172 
118 
Mortality, percent 
4.0 
5-4 
9-° 
13-2 
20.0 
0.0 
10.0 
Notes to Table III.-The total mortality of those injected within the first forty-eight hours of the disease was 8.2 per cent.; 
deducting the moribund, or those dying within twenty-four hours after injection-4.3 per cent. The mortality of those injected before 
the fifth day of disease was 12.4 per cent.; deducting the moribund, 7.6 per cent. During the last six months, April to October, there 
were injected within the first forty-eight hours of disease, 178 cases, with 8 deaths, a mortality of 4.5 per cent.; deducting the moribund, 
1.6 per cent. Before the fifth day of disease there were injected 317 cases, with 22 deaths, a mortality of 6.9 per cent.; deducting the 
moribund, 3.6 per cent. 
Table IV.-Immunization with Antitoxin by the Health Department Inspectors, January i, 
1895, to October i, 1896. 
Table of cases immunized with injections of antitoxin in families where diphtheria had occurred, showing the 
number of cases immunized, the number of antitoxin units injected, the number of cases of diphtheria which occurred 
within thirty days after injection, the number of cases which occurred after thirty days and within twenty-four hours 
after injection, and the number of cases of diphtheria which occurred in the families previous to immunization: 
Number of 
Cases 
Immunized. 
Number of Anti- 
toxin Units in- 
jected. 
Number of Cases of Diphtheria within 
30 days after injection. 
Number of Cases of Diphtheria within 
24 hours and after 30 days after in- 
jection. 
Number of Cases 
of Diphtheria 
which occurred 
in families,etc., 
previous to im- 
munization. 
1207 
50 to 500 
1 on the 7th day.1 
1 " 10th day. 
5 " 19th and 20th days. 
1 " 23d day. 
1 " 30th day. 
1 severe on the 5th day recovere 
1 on the 2d day died of scarlet ai 
theria. 
■ Mild. 
d. 
rd diph- 
After 30 days. 
2 mild recovered.2 
1 on 55th day died. 
Within 24 hours. 
7 mild pharyngeal. 
5 croup, all recovered. 
One or more 
cases in 395 
families. 
1 Probably had nasal diphtheria at the time of immunization. 
2 The data as to cases occurring after.thirty days have but little value, as cases might have appeared without the knowledge of the- 
Health Department. ANTITOXIC SERUM. 
5 
Table V.-Cases Treated by Physicians with Free Antitoxin, Collated from the Reports of 
the Attending Physicians, October i, 1895, to October i, 1896. 
£ 
9 
0 
Deaths. 
Mortality, 
per cent. 
Extent of Membrane. 
Number of Injections. 
Total Injections 
given. 
T onsils. 
Pharynx. 
Nose. 
Larynx. 
I 
2 
3 
4 
-October i, 1895, to April 1, 1896 
April 1, 1896, to October 1, 1896 
86 
289 
15 
53 
17.2 
18.3 
88 
32 
58 
9 
49 
33 
94 
69 
238 
l6 
49 
0 
I 
0 
I 
IOI 
343 
Totals 
375 
68 
18.1 
IOO 
9° 
58 
127 
307 
65 
I 
I 
444 
Moribund, or dying within 24 
hours, deducted 
21 
There remain 
354 
47 
13-2 
Notes to Table V.-From October 1, 1895, to April 1, 1896, there were treated with free antitoxin 86 cases, resulting in 15 
deaths, or a mortality of 17.2 per cent. Of these 3 were moribund at the time of injection, or died within twenty-four hours after the 
first injection, deducting which would give a mortality of 14.4 per cent. In 60 cases the diagnosis was bacteriologically confirmed, and 
of these 6 died, or 10 per cent.; 56 cases were clinically diagnosed, of which 9 died, or 37.5 per cent. From April 1, 1896, to October 1, 
1896, there were treated 289 cases resulting in 53 deaths, or a mortality of 18.3 percent. Of these, 18 were moribund at the time of 
injection, or died within twenty-four hours after the first injection, deducting which would give a mortality of 12.9 per cent. In 241 
cases the diagnosis was bacteriologically confirmed (in 24 cases the examination was indecisive), and of these 35 died, or 14.5 per cent.; 
48 cases were clinically diagnosed, and of these 18 died, or 37.4 per cent. Of the 289 cases treated, 60 occurred in institutions, with 9 
deaths, or 15 per cent, mortality. 
Of the entire number of cases reported, 34 cases are excluded from the statistics on account of imperfect data in the reports, or no 
Klebs-Loeffler bacilli being found, or the cases being removed to the Willard Parker Hospital and treatment discontinued. In a total of 
375 cases treated by physicians with free antitoxin from October 1, 1895, to October 1, 1896, there were 68 deaths, or a mortality of 18.1 
per cent.; deducting 21 cases which were moribund at the time, or died within twenty-four hours after the first injection, there were 354 
cases, with 47 deaths, or a mortality of 13.2 per cent. Of the total number treated, in 100 cases the tonsils alone were involved; in 90 
cases, the pharynx alone, or tonsils and pharynx; in 58 cases, the nose alone, or nose, pharynx, and tonsils; in 127 cases the larynx was 
involved, either alone or in combination with tonsils, pharynx, and nose. In this table the prognosis at the time of treatment, and the 
complications accompanying or following the injections, are not included, because the data given in the reports were insufficient or 
incomplete. 
Table VI.-Laryngeal Cases Treated by Physicians with Free Antitoxin, October i, 1895, to 
October i, 1896. 
Total Laryngeal Cases. 
Non-operative Cases. 
Operative Cases (Intubation). 
Cases. 
Deaths. 
Mortality, 
per cent. 
Cases. 
Deaths. 
Mortality, 
per cent. 
Cases. 
Deaths. 
Mortality, 
per cent. 
October i, 1895, to April 1,1896.. 
April 1, 1896, to October 1,1896.. 
33 
12 
36-3 
23 
7 
30.4 
IO 
5 
50. 
94 
25 
26.6 
62 
16 
25-8 
32 
9 
28.1 
Totals 
127 
37 
29.1 
85 
23 
*'• 
42 
14 
33-3 
Moribund, or dying within 24 
hours, deducted 
II 
6 
5 
There remain 
116 
26 
22.4 
79 
17 
21-5 
37 
9 
24-3 
Notes to Table VI.-From October i, 1895, to April 1, 1896, there were 33 laryngeal cases treated with free antitoxin, result- 
ing in 12 deaths, or a mortality of 36.3 per cent.; 23 cases were not operated on, with 7 deaths, or a mortality of 30.4 per cent.; 10 cases 
were intubated, resulting in 5 deaths, or a mortality of 50 per cent. 
From April 1, 1896, to October 1, 1896, there were 94 laryngeal cases treated with free antitoxin, resulting in 25 deaths, or a mor- 
tality of 26.6 per cent. Of these, 10 were moribund at the time, or died within twenty-four hours, deducting which, the mortality would 
be 17.8 percent.; 62 cases were not operated on, with 16 deaths, or a mortality of 25.8 per cent.; of these, 6 were moribund at the time, 
or died within twenty-four hours, deducting which would reduce the mortality to 17.1 per cent.; 32 cases were intubated, with 9 deaths, 
or a mortality of 28.1 per cent.; of these, 4 were moribund, or died within twenty-four hours, deducting which would reduce this mor- 
tality to 17.8 per cent. In a total of 127 laryngeal cases treated by physicians with free antitoxin from October 1, 1895, to October 1, 
1896, there were 37 deaths, or a mortality of 29.1 per cent.; of these, n were moribund at the time of injection, or died within twenty- 
four hours after the first injection, and if these be deducted, there remain 116 cases, with 26 deaths, or a mortality of 22.4 per cent.; 85 
cases were not operated on, of which 23 died, a mortality of 27 per cent.; deducting 6 moribund, or dying within the first twenty-four 
hours, there remain 79 cases, with 17 deaths, or a mortality of 21.5 per cent.; 42 cases were operated on, with 14 deaths, a mortality of 
33.3 per cent.; deducting 5 moribund, or dying within the first twenty-four hours, there remain 37 cases, with 9 deaths, or a mortality of 
24.3 per cent. 6 
ANTITOXIC SERUM. 
cultures were made from their throats. In a large per- 
centage of these cases, the cultures showed the presence 
of Loeffler bacilli. 
Immunizing injections, varying from fifty to 500 units 
in amount, were administered to 1207 persons (see table 
No. 4). In five children who had been immunized, laryn- 
geal diphtheria (croup) developed within twenty-four 
hours of the time of the injection, and in seven other 
pharyngeal diphtheria appeared. All of these cases re- 
ceived further curative injections and promptly recovered. 
In nine cases diphtheria developed within thirty days of 
the time of immunization. All of these cases excepting two 
were mild and promptly recovered. In one of these two 
exceptions, scarlet fever, apparently accompanied by diph- 
theria, developed on the second day, and the child died. 
No data of value are at command regarding the occur- 
rence of cases of diphtheria among those immunized after 
thirty days; but in one instance it is known that a child 
developed diphtheria on the fifty-fifth day after immuniza- 
tion, and although it received a curative injection, it never- 
theless died from the disease. The experience obtained 
from the immunization of children in various institutions 
indicates that the protective influence of the immunizing 
injections cannot be depended upon to last longer than 
about four weeks, although in many cases the period is 
apparently longer. With the high-grade preparations of 
antitoxin now employed, the amount of serum required for 
an immunizing injection is very small, varying from 3. 
to 10 or 15 minims, according to the age of the pa- 
tient and the strength of the preparation. In the earlier 
work, when young and feeble infants were immunized, 
some restlessness, accompanied by more or less pyrexia, 
occurred in many cases during the first twenty-four hours, 
and not infrequently a rash appeared later. Similar symp- 
toms appeared in a smaller proportion of instances in 
adults. In a few cases transient albuminuria occurred. 
Table VII.-Age and Day of Disease when Treatment by Physicians with Free Antitoxin was 
Commenced, October i, 1895, to October i, 1896. 
AGE. 
Mortality, per cent 
Died 
Cases 
QC 
U1 
rto 
o-i Year. 
% 
Gn 
\O 
i-2 Years. 
1) 
Cn 
b 
45 
O' 
2-3 Years. 
Ln 
£ 
8 
3-4 Years. 
& 
1) 
O' 
04 
4-5 Years. 
IO. I 
xO 
S' 
5-10 Years. 
- 
£ 
10-15 Years. 
0*0 
o 
M 
15-20 Years. 
p 
b 
0 
0 
Over 20 Years. 
00 
X 
tn 
Total. 
K) 
Moribund, or 
dying within 
24 hours, de- 
ducted. 
b 
4- 
Remaining. 
DAY OF DISEASE. 
Day of Disease 
First Day. 
Second Day. 
Third Day. 
Fourth Day. 
Fifth Day, 
or later. 
Unknown. 
Total. 
Cases. 
Died. 
Cases. 
Died. 
Cases. 
73* 
2 
Cases. 
Died. 
Cases. 
Died. 
Cases. 
Died. 
w I 
<U 73 
d - 
0 2 
Mortality, 
per cent. 
Cases and deaths 
45 
4 
IOI 
17 
77 
8 
53 
9 
67 
25 
32 
5 
375 68 
Mortality, per cent 
8.8 
16.8 
10.3 
17.0 
37-3 
i5-9 
18.1 
Moribund, or dying within 24 
hours, deducted 
I 
6 
4 
3 
5 
2 
21 
There remain 
44 
3 
95 
II 
73 
4 
50 
6 
62 
20 
30 
3 
354 47 
Mortality, per cent 
6.7 
n-5 
5-5 
12.0 
32.2 
10.0 
13-2 
Notes to Table VII.-From October i, 1895, to April 1, 1896, there were treated within the first four days of disease 61 cases, 
with 6 deaths, or a mortality of 10 per cent.; of these 3 were moribund, or died within 24 hours, deducting which the mortality would be 
5.1 per cent. From April 1, 1896, to October 1, 1896, there were treated within the first four days of disease 215 cases, with 32 deaths, 
or a mortality of 14.8 per cent.; of these, 11 were moribund, or died within twenty-four hours, deducting which the mortality would be 
10.2 per cent. In a total of 276 cases treated within the first four days of disease, there were 38 deaths, or a mortality of 13.7 per cent.; 
deducting the 14 moribund, or dying within the first twenty-four hours, the mortality would be 9.1 per cent. In a total of 138 cases 
treated within the first three years of life, 39 died, or a mortality of 28.2 per cent. From the third to the tenth year there were 212 cases 
treated, with 28 deaths, a mortality of 13.2 per cent. From the tenth to the fifteenth year the mortality was 7.1 per cent. Over fifteen 
years, none died. Two-thirds of the cases treated were under ten years of age. ANTITOXIC SERUM. 
7 
Since the employment of only very small doses of serum, 
it has been unusual to see any disturbances following the 
administration of an immunizing injection. In one group 
of about forty cases recently immunized with small doses, 
in only one instance was there a local rash near the seat of 
the injection. In another series of 130 cases, immunized 
in an infant asylum,1 in which relatively large doses were 
administered to infants varying in age from one day up, 
in only seven cases was there a mild body-rash, and in 
forty-two a local arm-rash, and in no instances were there 
other sequelae. 
On October 1, 1895, arrangements were made to ena- 
ble physicians to obtain supplies of antitoxin, free, for 
use among patients too poor to pay for the remedy, on 
condition that reports of the cases thus treated should be 
furnished to the Health Department. Druggists, act- 
ing as agents for the sale of antitoxin, were instructed to 
furnish the remedy free to any physician, upon his state- 
ment that the patient for whom it was intended was not 
in circumstances to pay for it. A blank was furnished 
upon which the history of the case could be filled out by the 
attending physician, upon the termination of the case, 
either by death or complete recovery, and then forwarded 
to the Health Department. 
This arrangement has not been very generally known, 
and has not been largely utilized by physicians until 
quite recently, and in many of the cases thus treated 
the complete report has not been obtained. Up to Octo- 
ber 1, 1896, 409 cases of this sort have been reported, 
of which 34 proved on bacteriological examination to be 
cases of false diphtheria, were transferred to Willard 
Parker Hospital, or had histories too incomplete for 
proper tabulation, and are, therefore, excluded; of the 
remaining 375, 307 recovered and 68 died, a mortality 
of i8yL per cent. 
The fuller data regarding these cases, as furnished by 
the attending physicians, will be found in the accompany- 
ing tables. (Nos. 5, 6, and 7.) 
With a view to a more complete study of the fatal cases 
of diphtheria occurring in New York during the last few 
months, a letter has been addressed to every physician 
who reported a death from diphtheria or croup, asking 
for information as to whether antitoxin was employed 
in the case, and if so, on what day of the disease it 
was administered, and what was the condition of the 
patient at the time of administration. Personal observa- 
tions on the subject were also requested. 
Information has been received, between May 7 and No- 
vember 1, 1896, from 306 physicians, with regard to 336 
fatal cases of diphtheria reported to the Board of Health- 
124, or thirty-seven per cent, of these, were reported as 
treated with antitoxin, and 212, or sixty-three per cent., 
were reported as treated without antitoxin. The total 
number of deaths from diphtheria and croup reported dur- 
ing this period was 658. There were, therefore, 322 
deaths with regard to which no information was received 
in response to the letter of inquiry. 
Of the 124 fatal cases treated with antitoxin, 41, or 
thirty-three per cent., were reported as moribund or hope- 
less at the time of injection, or as dying within twenty-four 
hours after the first injection, and hence the antitoxin 
could not have been expected to have any effect ; 33. 
cases, or twenty-six per cent., were injected on the fifth 
day of the disease, or later, when the remedy has rela- 
tively little value; 29 cases, or twenty-three per cent., 
were complicated with sepsis, scarlet fever, measles, 
bronchopneumonia-notably bad cases ; and 13 cases, 
or ten and one-half per cent., died from cardiac paralysis, 
sudden death "resulting from getting up too soon, con- 
trary to instructions." 
Of the 212 fatal cases where no antitoxin was used, 50, 
or twenty-four per cent., were moribund or hopeless when 
first seen, and hence no antitoxin was used, as stated by 
the attending physician, because of the patient's condi- 
tion; 33 cases, or sixteen per cent., were seen too late, in 
the opinion of the attending physician, for antitoxin to 
be of any use; 17 cases refused treatment with anti- 
toxin, though strongly advised; and 4 cases were not 
injected, because being complicated with scarlet fever, 
measles, etc., antitoxin was considered useless. In 94 
cases, or forty-four per cent., antitoxin was not ad- 
ministered, because the attending physician was opposed 
to its use, was doubtful of its efficacy, or no reason was 
given. A number of physicians stated that in future they 
intended to use antitoxin owing to the bad results obtained 
by other methods. A very large majority of the physi- 
cians from whom reports were received (over two-thirds), 
expressed themselves as strongly in favor of the use of 
antitoxin in diphtheria. Many of them presented records 
of previous severe cases treated with antitoxin with good 
results. 
A report is also presented which was prepared by 
Alfred L. Beebe, Ph.B., Assistant Director of the Diag- 
nosis Bacteriological Laboratory. This includes a series 
of tables and charts, showing the actual and relative 
mortality from diphtheria and croup in New York, Berlin, 
and Paris, previous to and following the introduction of 
antitoxin in these cities. Mr. Beebe's report follows: 
" In accordance with your directions the following tables 
and charts have been prepared from the official statistics 
of New York, Paris, and Berlin, with a view to show the 
effect, if any, produced by the use of diphtheria antitoxin 
on the actual and relative mortality from diphtheria and 
croup in these cities. 
Table 8 gives the annual actual mortality in New York 
from diphtheria and croup for the years 1880-1895, the 
case fatality from diphtheria, 1880-1890, and the case 
fatality from diphtheria and croup combined, 1891-1895, 
and from January to October, 1896. Croup was not 
officially classed as a contagious disease by the New York 
Health Department prior to 1891, and cases of this dis- 
ease were therefore not required to be reported to the 
1 Among injections made at this asylum were cases: No. 117, 
an infant, three weeks old, born at full term, injected with 150 
units, and weighing at the time of injection only four pounds three 
ounces; and No. 123, a premature infant, nineteen days old, born 
at seventh month, and still in an incubator, injected with 150 units, 
and weighing at the time of injection only three pounds eight 
ounces. These infants had no reaction whatever and no rash. 
Among the pregnant women: 
Ten were eight months in pregnancy. 
Two " " 
Nine " nine " " " 8 
ANTITOXIC SERUM. 
Table VIII.-New York-Diphtheria and Croup: Cases and Deaths, with Case Fatality, 1880, 
to October, 1896, Inclusive. 
oooocooooooooooooooooooooooooooooo 
XO xO XO O vo O XQ cooooooooooooooooooo 
ChCn Go to H p vp pxCn Go tO m O 
Year. 
OOxO V0 Ox A A Ox OxCn Go tO tO to Go Cn GO 
o O m O OC Go 4* 4> vO O to Q Cn h Go 
4* to Cn QxCn O Cn OOxO to Go to tOvQOvQO 
Oxen Cn 004- 0 O 0 Go Ox<l 
Diphtheria. 
Cases. 
to A Cn Cn 
4* 10 OOCn Go xQ 
0 00 O'GJ 0 O 
Croup. 
00-° \QMCnCn 
to Go Ox O M Go 
10 00 Ox 
OxGO H m 4> 4- 
T otal. 
HIHtOMMI-IHMI-ltOMHMMMlOM 
to Ox Go xO Go to OxxO H <1 GJ Q Q Cn to Go 
tO Go Cn Go Ox Ch O) m Ox tO tO xQ 0 to xQ 
4> 4* x£) 0 Ox h to O Cn 0 xO Cn xO 0 
Diphtheria. 
Deaths. 
h GJ Cn tn Cx Qstn Q\ O' OO'Q 0 M3 
O>-P> h Q to O GJ 00 e'en -S to GJ h 
0010 H 000'0 HCn'O'O OOGj 004* tO 00 0 
Croup. 
HHtOtOtOMHlOlOGOlOlOMMtOGOlO 
Go xO OOCn m \O to Cn 0 Qxh 00 Ox to to Go 
O ■<] Cn Q 00x0 Cn Cn xO QOGo Cn Cn CC Q 
to 0x0 00 Ox O Go h Go Oxen 0 00Go 0 
Total. 
m m tO GJ Go 10 tO tO 
Cn OxCn 0 0 O xO Cn xO Ox Oxen xO CO Go Go 10 
to 4* 004* '0'0 O'Otn O' 10 4* 0 h Cn GJ GJ 
Diphtheria. 
Case Fatality. 
m « to Go Go 
O"O 'OO'OC'"-;;;;;;;:; 
bo m M 4* OX<1 
Diphtheria 
and Croup. 
1 First, second, and third quarters. 
Table IX.-Paris : Deaths from Diphtheria and Croup, by Months, 1889, to July, 1896. 
Month. 
1889. 
1890. 
1891. 
1892. 
1893. 
1894. 
1895. 
1896. 
January 
214 
136 
184 
120 
164 
145 
48 
53 
February 
185 
182 
202 
135 
108 
no 
47 
61 
March 
219 
211 
I92 
162 
149 
148 
45 
59 
April 
174 
196 
183 
131 
136 
133 
36 
69 
May 
184 
169 
145 
153 
133 
122 
38 
56 
June 
148 
144 
103 
124 
115 
80 
14 
31' 
July 
128 
147 
95 
108 
83 
78 
25 
August 
125 
131 
78 
115 
80 
64 
23 
September 
135 
114 
64 
99 
63 
311 
20 
October 
116 
I25 
73 
106 
58 
27 
33a 
November 
125 
134 
97 
134 
68 
33 
38 
December 
137 
170 
115 
170 
109 
38 
73 
Totals 
1890 
1859 
I53I 
1557 
1266 
1009 
440 
Antitoxin 
not used. 
Antitoxin in 
general use. 
Largest number of deaths for any month 
219 
73 
Smallest number of deaths for any month 
58 
14 
1 Antitoxin in general use. 
2 Monthly report missing; estimated from the weekly returns. 
Table X.-Berlin : Deaths from Diphtheria and Croup, by Months, 1889 to July, 1896. 
Month. 
1889. 
1890. 
1891. 
1892. 
1893. 
1894. 
1895. 
1896. 
January 
119 
154 
102 
119 
165 
138 
791 
72 
February 
109 
108 
IO3 
103 
145 
137 
64 
55 
March 
98 
134 
86 
113 
115 
140 
88 
46 
April 
94 
167 
73 
94 
120 
133 
68 
49 
May 
75 
126 
73 
93 
106 
134 
56 
45 
June 
82 
119 
67 
81 
101 
96 
74 
27 
July 
70 
9° 
49 
88 
116 
71 
77 
August 
91 
106 
64 
9° 
92 
92 
57 
September 
113 
146 
96 
100 
162 
134 
88 
October 
119 
137 
112 
140 
174 
119 
120 
November 
131 
161 
127 
182 
182 
118 
115 
December 
183 
136 
126 
193 
163 
118 
no 
T otals 
1284 
1584 
1078 
1406 
1643 
1430 
996 
294' 
1 Antitoxin largely used. 
2 Mortality for first half of 1896. ANTITOXIC SERUM. 
9 
Department. It will be noticed that in the first two years 
after the reporting of croup is required, the mortality 
from diphtheria is raised nearly 10 per cent, by the 
croup deaths (27.9 per cent, to 36.7 per cent., and 30.9 
per cent, to 40.6 per cent.). After this the influence of 
the croup deaths becomes less, as in 1893 the Health De- 
partment declared that membranous croup was in the vast 
majority of cases laryngeal diphtheria, and would be so 
regarded by the Department. After this announcement 
the relative proportion of deaths ascribed to croup gradu- 
ally diminishes, until in 1895 the croup deaths equaled only 
about one-fifth of the diphtheria deaths, while in 1891, and 
before, they equaled from two-fifths to one-half or more 
the number of diphtheria deaths. In no single year until 
1895 did the number of cases of croup reported equal the 
number of deaths. Owing to the rapidly fatal termina- 
tion of the majority of cases of croup, the report of death 
was either the first report received by the Department, or 
that for the earliest years for which figures are given, the 
case fatalities for diphtheria alone are somewhat too high; 
that for the years immediately preceding 1891 they are too 
low; while for the immediate years they are more nearly 
correct. 
Before considering these figures, and those in other 
tables relating to New York, it should be stated that anti- 
toxin was first introduced to a very limited extent from 
abroad in November, 1894. In January, 1895, the dis- 
tribution and use of the antitoxin produced by the New 
York Health Department was begun, the amounts used 
and distributed, of both the foreign and domestic products, 
increasing gradually until the fall, when a very rapid ex- 
pansion in the use of antitoxin took place, as indicated by 
the large increase in its sale, its free distribution to the 
physicians of the city, and its free administration by the 
medical inspectors of this Department. 
Proceeding now to the consideration of the figures in 
Chart No. i. 
New York. Diphtheria and Croup. Case fatality, periods of four weeks. November, 1893, to October, 1896. 
the report of the case and of the death arrived almost 
simultaneously." 
Bearing the above in mind, it is evident that the figures 
for case fatality from diphtheria, 1880-1890, are not 
comparable with those showing the combined fatality 
from diphtheria and croup, 1891-1895. The figures 
for case fatality from diphtheria alone are relatively lower 
from 1891-1895 than before, as is shown by the table, 
and as the figures for case fatality from diphtheria and 
croup combined undoubtedly show the true mortality in 
diphtheria, they are absolutely, as well as relatively, too 
low for these years. On the other hand, progressing 
backward in the scale of years, an increasing percentage 
of cases of diphtheria were not reported, and the case 
fatalities for these years are therefore higher than the truth, 
especially in the earlier years for which figures are given. 
Taking all the facts into consideration, it seems probable 
table 8, we note that the percentage of mortality from 
diphtheria and croup in 1895 (19.1 percent.) is much 
lower than that for any previous year, even when com- 
pared with the percentage of mortality from diphtheria 
alone. The lowest rate prior to 1895 is that for 1889, 
25.9 percent., which, for reasons previously given, is cer- 
tainly too low. It is also to be noted that the decrease in 
mortality from 1894 to 1895 is considerable, amounting 
to over thirty-five per cent, of the rate for 1894. In 
the sixteen years for which the figures are given, the 
greatest previous increase or decrease in case fatality for 
any year as compared with that preceding it, is in 1887, 
when the decrease amounted to twenty-five per cent, of 
the rate for 1886, or twelve percent, less than the per- 
centage decrease, 1894 to 1895. But in this year (1887) 
the decrease in death-rate is accompanied by an increase 
of 361 in the number of deaths, while in 1895 there is a 10 
ANTITOXIC SERUM. 
decrease of 894 in the absolute mortality as compared 
with that of 1894. This large actual and relative de- 
crease in case fatality in 1895 points to the introduction 
in this year of some previously non-existent factor. 
Proceeding next to a comparison of total cases with 
total deaths, there is indicated an apparent tendency 
toward correspondence of deaths and cases as to increase 
or decrease. To this there are several exceptions, as will 
be seen by an examination of the figures. From 1890 to 
1894, however, with the exception of a small decrease in 
the number of cases in 1892 as compared with the pre- 
vious year, there is a steady and rapid increase in both 
cases and deaths until 1895, when this correspondence is 
abruptly destroyed, a very large decrease in deaths taking 
place, while the number of cases is increased by 712, 
making the total of cases for 1895 the largest ever recorded 
in the city. The introduction of some disturbing factor, 
previously non-existent, is thus again strongly indicated. 
Chart No. 1 1 gives the case fatality from diphtheria and 
croup in New York for periods of four weeks, the figures for 
cases and deaths on which it is based being taken from the 
weekly reports of the Health Department. The method 
of bacteriological examination in the diagnosis of diph- 
theria was inaugurated by the Department in May, 
1893, and by the autumn of that year had been very gen- 
erally adopted by the medical profession, and entirely so 
by this Department through its medical inspectors, as an 
efficient adjunct to clinical diagnosis. It has been claimed 
that a considerable increase in reported cases of mild 
diphtheria, with a consequent decrease in case fatality, 
results from the extended use of bacteriological examina- 
tions in this disease. This claim is not substantiated by 
a careful comparison, recently made in this office, of the 
clinical diagnosis with the results of bacteriological ex- 
amination in cases of suspected diphtheria; but supposing it 
to be true, any variation in case fatality so produced 
would in all probability have been relatively the same in 
the period selected for comparison, previous to the intro- 
duction of antitoxin (Z. e., November, 1893, to November, 
1894), as in the corresponding periods after its use had 
been begun. The influence of this factor may therefore 
be almost entirely disregarded. Considering the chart 
we note, in the year previous to the introduction of anti- 
toxin, an increase of case fatality from 32.3 per cent, in 
November to a maximum of 43.3 per cent, in January, 
followed by a decrease to a minimum of 27.1 percent, in 
July. With the exception of a slight decrease in October, 
1894, the case fatality increases from July to November. 
At this point, coincident with the introduction of antitoxin, 
a decrease begins, continuing steadily, with the exception 
of a slight rise in January, to March, 1895. This is in 
sharp contrast with the figures for the corresponding 
period of the previous year. From March to June, 1895, 
the rate remains practically constant, declining to a mini- 
mum of 17.2 per cent, in July. The usual seasonal in- 
crease in case fatality then begins, but in October, at 
which period began the rapid extension in the use of anti- 
toxin previously noted, a decrease begins, which, with the 
exception of comparatively small increases in November, 
1895, and March, 1896, and a somewhat marked rise in 
August, 1896, has continued to date of writing (Novem- 
ber, 1896). The case fatality for October (12.8 per cent.) 
is the lowest ever recorded for a corresponding period in 
New York. The rise in August (from 14.4 per cent, for 
July to 20.6 per cent.) is undoubtedly due, in large 
measure, to the protracted period of extreme heat, which 
occurred in the early part of this month, and which pro- 
duced the highest general mortality recorded in this city 
Chart No. 2. 
Berlin, Paris, New York. Diphtheria and Croup. Number of 
deaths per 100,000 of population, 1886-1895. 
for many years. It is interesting to note that the usual 
seasonal decrease in actual cases and deaths during the 
late summer and early autumn, followed by an increase 
on the advent of colder weather, and the opening of the 
public schools, occurred both before and after the intro- 
duction of antitoxin, being apparently uninfluenced by 
this, and bearing, as a rule, no direct relation to the 
changes in case fatality recorded. 
Chart No. 2 gives the case fatality in diphtheria and 
1 The tables containing'the data from which this and subsequent 
charts presented have been constructed, are omitted for the sake 
of brevity. ANTITOXIC SERUM. 
11 
croup for periods of four weeks in New#York and Paris, and 
for diphtheria only (croup not separately reported) in Berlin. 
Cases of croup are not separately reported in the statistics 
of the latter city. The figures for cases and deaths are 
taken from weekly reports of the three cities, and for 
New York correspond with those presented in a portion 
of chart No. 1. In Paris, antitoxin was in general use 
in January, 1895, the beginning of the period tabulated, 
and was largely used in Berlin, while in New York it had 
just been introduced. The gradual approximation of the 
case fatality in New York to that in Paris and Berlin is 
well shown in the chart, and coincides with the increasing 
use of antitoxin in the former city. In Berlin, climatic 
influences appear to have but little, if any, effect in in- 
creasing or diminishing the number of actual cases and 
deaths. The effect on case fatality is, however, more 
apparent, as the lowest rate for 1895 (12.1 per cent.) oc- 
curs in July. In Paris, the seasonal variations coincide 
quite closely with those in New York for 1894, the lowest 
case fatality and smallest number of deaths occurring in 
July, and the smallest number of cases in October. The 
Tables 9 and 10 give the deaths from diphtheria and 
croup, in Paris and Berlin respectively, from January, 1889, 
to June, 1895, inclusive, by months. The remarkable 
decrease in mortality in Paris, coincident with the intro- 
duction of antitoxin, is well shown, the number of deaths 
per month falling off rapidly from June, 1894, while the 
annual mortality for 1895 exhibits a large decrease from 
previous years, being but forty-four per cent, of that in 
1894, which is itself lower than that for any previous year, 
back to 1886, the figures before this date not being at 
command. In the week ending September 19, 1896, 
with eighty-five cases reported during this and the pre- 
vious week, not a single death occurred from diphtheria 
or croup in the city of Paris. 
Table 11 gives the case fatality from diphtheria and 
croup in the Paris hospitals by months, quarters, and 
years, 1893 to 1895, inclusive, with a portion of 1896. 
Antitoxin was introduced into some of the hospitals some 
time in advance of its employment in the city at large (it 
having been used somewhat during June, July, and 
August, 1894, and generally, after September). The re- 
Chart No. 3. 
New York, Paris. Diphtheria and Croup. Berlin. Diphtheria, only. Case fatality, periods of four weeks. 1895-1896. 
remarkably low case fatality in Paris is of special interest. 
In July, 1895, it reached the extraordinarily low figure of 
4.8 per cent., while the highest record-rate (May, 1896) 
is but 15.9 per cent. 
Chart No. 3 gives the number of deaths from diphtheria 
and croup, per 100,000 of population, in Berlin, Paris, 
and New York, from 1886 to 1895. In all three cities 
the ratio of deaths to population is lower in 1895, and the 
decrease from the ratio of the preceding year greater, than 
for any previous year, with the exception of Berlin, where 
the decrease of ratio from 1890 to 1891 is greater than 
that from 1894 to 1895. In Paris and Berlin, the actual 
number of deaths, independent of the population, is lower 
than for any previous year-in Paris most markedly so, 
less than one-half that of the lowest previous annual mor- 
tality (that of 1894), when antitoxin was already in use. 
In New York the decrease from the ratio of 1894 is in ex- 
cess of any change in previous years, the decrease being 
thirty-three per cent, of the ratio of 1894, as compared 
with a decrease from 188910 18900! twenty-four percent, 
of the ratio of 1889, the largest previous change. 
duction in case fatality subsequent to its introduction is 
extraordinary. The lowest rate recorded in 1893 is for 
October (thirty-seven per cent.), while in 1894, prior to 
the introduction of antitoxin, the lowest rate is that for 
February (forty-seven per cent.). As compared with 
these, the highest rate in 1895 and 1896 is that for De- 
cember, 1895 (19.7 per cent.). The quarterly and yearly 
statistics are equally striking. The lowest rate for 1893 
and 1894, before the general use of antitoxin, is that for 
the third quarter of 1894 (forty per cent.), at which time 
antitoxin was already in use to a considerable extent, 
while the highest subsequent rate is that for the second 
quarter of 1896 (seventeen per cent.). For the year 1895, 
the rate reaches the extraordinarily low figure of 13.6 per 
cent., as compared with 51.4 per cent, for 1893, 50.3 
per cent, for the first three quarters of 1894, and 35.5 
per cent, for the year (one-quarter year, antitoxin in 
use). 
Here, as in all other tables presented, the case fatality 
rapidly decreases with the introduction and increasing use 
of antitoxin, although in each of the three cities, this took 12 
ANTITOXIC SERUM. 
place at a time when the case fatality is normally on the 
increase with the advent of cold weather. 
Table 12 presents statistics for the Berlin hospitals 
similar to those given for Paris in table 7. They are un- 
fortunately incomplete, no figures for 1894 being at com- 
mand, and for 1893 the annual figures only. A com- 
parison of the case fatality for 1893 with that for 1895 *s> 
however, entirely confirmatory of the figures previously 
considered. The rate for 1893 is forty-four per cent.; 
that for 1895, 15.7 per cent. 
Considering as a whole the facts and figures presented 
above, we observe that a large and rapid decrease in the 
absolute number of deaths from diphtheria and croup has 
taken place at certain times in three cities, of varying 
Table XI.-Paris Hospitals : Diphtheria and Croup; Cases and Deaths, with Case Fatality, 
by Months. 
January 
February 
March 
April 
May 
June 
July 
August 
September 
October 
November 
December 
Totals 
Month. 
oo 
00 
H H H H H H H H 10 to H tc 
'oo £ §0 H §0 0 OOM SO 'w OJ & 
Cases. 
£ 
O Cn 4- O"0 00 5 h Ln 10 
00 00 0 Ln to KI Ln M to v£> 4- O' 
Deaths. 
J"1 
■£*■ O>GJ O' 
O 00 hi GJ kO Cn ri 0 
Cn GJ 10 Cn O' 
Case 
F atality. 
gj 
GJ to to M m( h< H< to to to to to 
Cn -0 0 Cn Gj Cn - 0 GJ Gj 0 m 
Cases. 
00 
f 
00 
Go GJ to to Cn Go Q h to O to 
Cn vO O O O'-P* Cn Cn 00 
Deaths. 
35-5 
m hi hi GJ GO to Cn Cn Cn O' 
O K 4 O vi O"O tO 0 G- h 
MO K> N 4* O'O'OO'O 0 0 
Case 
Fatality. 
to 
GJtOtOHMHIHItOtOtOtOtO 
Q Go tO O'GJ m O OO 
vO Cn m tO 00 0 GJ tO 4- OA O 
Cases. 
00 
s 
to 
•-< O (>Cn 10 OCCn Cn 0 Go 0 
Deaths. 
O' 
"O GJ 00GJ O to Cn 004- to to H 
Case 
Fatality. 
■ 
to to to to to 
0 to to 00 O' 
Cases. 
: : : : : : : 
Deaths. 
00 
$ 
Cn OCGJ Cn Go 
0 O' to \0 o 
Case 
Fatality. 
1 Monthly reports not available; figures are taken from the weekly reports. 
First quarter 
Second quarter 
Third quarter 
Fourth quarter 
Year 
Quarter. 
00 4- Oj Cn C/1 
1 O C A C 
00 M OJ 00 v.. 
tO to 
00 
to m gj to 
Deaths. 
Gn 4- 4. (ji (jt 
- \O ChCn m 
i. <) i 
Case 
Fatality. 
to 1 
GJ OCGo Ch Os 
Cn to GJ -U 
Cn vj di£4- 
Cases. 
<? 
\© c5 <R 
00 
Deaths. 
ui h "o "<> A 
cn bo b oo b 
Case 
Fatality. 
-J Ch 00 
<S?S\5 8 
Cases. 
h Cn tO 
ChCn 0 tO 
Deaths. 
Ch 
Cn tO m -5 
GJ 0 tO sO 
Case 
Fatality. 
• • 00 
. . 00 H 
• • Ch 
Cases. 
• • 00 H 
• • to. <1 
Deaths. 
00 
'S' 
• • 0 Go 
Case 
Fatality. 
THE SAME, BY QUARTERS AND YEARS. 
1 April and May only. 
Table XII.-Berlin Hospitals : Diphtheria and Croup; Cases and Deaths, with Case Fatality, 
by Quarters and Years. 
Quarter. 
1893- 
1895- 
1896. 
Cases. 
Deaths. 
1 
Case 
Fatality. 
Cases. 
Deaths. 
Case 
Fatality. 
Cases. 
Deaths. 
Case 
Fatality. 
First quarter 
Second quarter 
Third quarter 
Fourth quarter 
Year 
Monthly 
not 
figures for 
reported. 
1893 are 
737 
712 
845 
850 
141 
73 
125 
>54 
19.1 
10.3 
14.8 
18.1 
628 
472 
80 
71 
12.7 
15.0 
2570 
1132 
44-o 
3144 
493 
!5-7 
(The Berlin hospital statistics for 1894 are not available.) 
Note.-The case fatalities for both Berlin and Paris hospitals are calculated on the sum of the total cases discharged by death or 
recovery during each month, quarter, or year. The number of cases admitted during and remaining in hospital at the end of each 
month, quarter or year is not given in the statistics. ANTITOXIC SERUM. 
13 
climatic conditions and different nationalities, in which 
these diseases are endemic. An extraordinary decrease 
in the case fatality from these diseases has also occurred, 
and this fatality has not subsequently risen to any extent 
in a period of some twenty-two months, and is now, in 
New York, far lower than at any period in the previous 
twenty-two years. This decrease did not take place at 
the same time in each of these cities. It occurred in New 
York some months later than in Berlin, and in Berlin some 
months later than in Paris. It has, however, occurred 
in all three cities at a period of the year when, from the 
history of former years, an increase in the mortality would 
be expected. The reduction in mortality has occurred in 
hospital practice as well as throughout the cities at large. 
It seems evident that some influence, hitherto inoperative, 
must have come into action to produce the results out- 
lined above. Upon investigation, it appears that all of 
the results described have followed closely upon the intro- 
duction of diphtheria antitoxin, and have become more 
marked in close coincidence with its increasing use as a 
remedy for the treatment of diphtheria. The conclusion 
seems therefore inevitable that we owe to antitoxin the 
remarkable decrease noted in the mortality from diph- 
theria and croup. 
The following resume of the statistics and reports on 
the antitoxin treatment of diphtheria begins with the first 
extensive application of the new remedy in the early part 
of 1894, and brings the subject as nearly as possible up 
to date (October 1, 1896). 
In reviewing the reports which have been published in 
the various medical journals of the Continent of Europe, 
Great Britain, and the United States, such a mass of 
material has been found that it has been no easy matter 
to sift and condense it in such a way as to make it avail- 
able for the purpose desired. 
Several collective investigations of the antitoxin treat- 
ment of diphtheria have already been published in Ger- 
many and this country by Heubner, Monti, Eulenberg, 
Crandall, Foster, Welch, the Kaiserliches Gesundheitsamt 
in Berlin and others; and though in making these investiga- 
tions the whole field has been carefully gone over, there 
has been no hesitation in following the paths which 
others have marked out. Special acknowledgment of 
obligation for assistance, however, is due to Welch's most 
admirable article on the subject. 
It is hoped that such a compilation of the results ob- 
tained by a large number of the best scientific and clinical 
observers in all parts of the world, from a thorough trial 
of antitoxin for a period extending over two years, may 
be of use and interest, not only in demonstrating the value 
of the remedy, but also in inducing a still more extended 
application of what may now be confidently affirmed to be 
a specific against one of the most terrible diseases with 
which we have to deal. 
The first report of experiments made with the blood 
serum of immunized animals was communicated by Behr- 
ing and Wernicke to the Seventh International Congress 
of Hygiene and Demography, held in London, August, 
1891. In 1892 these authors published a second article 
describing more fully the principles of serum-therapy as 
applied to diphtheria. The earliest report of cases treated 
with antitoxin was in 1893, and consisted of thirty cases of 
diphtheria treated by Behring in the Institute for Infectious 
Diseases in Berlin. At this time the serum employed was 
very weak in antitoxin, but later, Behring and Ehrlich suc- 
ceeded in obtaining a stronger serum (though for some 
time the serum did not have the strength which is now 
considered to be necessary for curative purposes). In 
April, 1894, 233 cases of diphtheria treated in the Berlin 
Hospitals, with a mortality of twenty-three per cent., were 
reported by Ehrlich, Kossel, and Wassermann. Dr. Otto 
Katz reported to the Berlin Medical Society on June 27, 
1894, the results of the antitoxin treatment of 128 cases 
from March 14, 1894, in Professor Baginsky's service in 
the Kaiser und Kaiser in FriederichKinder-Krankenhaus 
in Berlin. The serum used in these cases was Aronsons' 
serum obtained from horses. A few weeks later Baginsky 
reported 163 cases in all with a mortality of 12.9 percent. 
Several reports now appeared of similar results obtained 
during the latter part of 1893 and the first part of 1894. 
It remained, however, for Roux to arouse the interest 
of the world in the discovery which Behring had an- 
nounced three years before. His masterly address de- 
livered at the Eighth International Congress of Hygiene 
and Demography held in Budapest, September, 1894. 
in which he gave a clear and forcible description of his ex- 
periments and results in the treatment of 300 cases of 
diphtheria with antitoxin in the Hopital des Enfants 
Malades in Paris, really directed the attention of the 
whole medical profession to this subject, and with this 
may be said to have begun the first extensive application 
of the new treatment for diphtheria. 
In reviewing the subject of the antitoxin treatment of 
diphtheria it will be found that its value has been tested 
chiefly in two ways: the first is by a study of statistics 
which show the absolute mortality in cities and hospitals 
before and since the introduction of antitoxin and the 
comparative mortality of series of cases treated by antitoxin 
with that of similar series treated previously, or simul- 
taneously, in other ways; the other is by the clinical 
method, the observation of the effect of antitoxin upon the 
course of the disease. 
All statistics are open to fallacies owing to varying fac- 
tors and conditions. The age of the patient is a most 
important factor in determining the mortality in diph- 
theria, either with or without the use of antitoxin, and 
unless the age is stated, the statistics are of little value. 
Different methods of diagnosis may also lead to errors 
in the conclusions. The diagnosis of the cases treated by 
antitoxin has been usually verified by bacteriological ex- 
amination, whereas in former times the diagnosis was 
mostly clinical. A bacteriological examination enables us 
now to exclude from our statistics many cases of angina 
which would formerly have been included. These cases 
are less severe than cases of true diphtheria, and on this 
account the statistics of mortality in the older reports are 
lower than they should be. On the other hand, a bac- 
teriological examination often enables us to recognize as 
diphtheria mild cases of angina, which in former days 
would not have been included in diphtheria statistics. It 14 
ANTITOXIC SERUM. 
is not likely, however, that among hospital patients the 
number in this class is as large as in the other. Experi- 
ence, moreover, has shown that the cases, which on bac- 
teriological examination have proved to be true diphtheria, 
when subjected to the former methods of treatment have 
given the highest mortality. 
Another question to be considered is the severity of the 
epidemic. This not infrequently varies in different times 
and places. The only way to avoid the fallacy thus aris- 
ing is to take a large number of cases for comparison oc- 
curring in widely separated places and over an extended 
period of time, and to compare cases treated with and 
without antitoxin at the same time and in the same place. 
Again, it is maintained by some that the low rate of 
mortality in diphtheria, which has been ascribed by its 
advocates to the antitoxin treatment, is due to a large in- 
crease in the number of cases, a milder type of the disease 
being now received into the hospitals, owing to the early 
treatment recommended under the new method, while 
formerly only the severest cases were brought for treat- 
ment. This is possibly true to a certain extent in some 
hospitals, but it does not account for the great difference 
in the total mortality between the old and the new treat- 
ment; then, too, many cases are now excluded, as all 
cases admitted into the hospitals are bacteriologically 
diagnosed and treated only with antitoxin when found to 
be true diphtheria, and the remaining cases if not brought 
for early treatment would frequently have developed into 
severe or fatal cases. 
Regarding the value of the evidence as to the efficacy 
of the remedy based on clinical study, this, of course, de- 
pends upon the confidence we place in the opinions formed 
by the individual observers. But when the opinions, ex- 
pressed by many of the best clinical observers in Ger- 
many, Austria, France, England, and America, etc., are 
almost unanimously in favor of it ; and when we con- 
sider that the majority of these men, if not absolutely 
opposed to the new treatment, were very timid and cau- 
tious in adopting it, and have reached their conclusions 
only after the most convincing proofs based on practical 
results, it would seem that there were no longer any rea- 
sonable grounds for refusing to accept the opinion of the 
vast majority. 
It remains now to present a series of statistical tables 
showing the results of the antitoxin treatment up to the 
present time. The statistics contain all the larger series 
of cases which have been reported up to date (omitting 
the statistics of the New York Board of Health, which are 
given separately), which it has been possible to find in the 
library of the Academy of Medicine. The list is not com- 
plete, as no single or isolated cases have been taken, only 
series of cases of ten and over. There has been no se- 
lection of cases, and no reduplication so far as known, 
certainly none that could be avoided. 
The results obtained by different observers naturally 
vary somewhat, taken as they are from so many different 
sources treated under such varying conditions, and with 
such different preparations of antitoxin, and yet, on the 
whole, the apparent unanimity is all the more remarkable 
on this very account, and proves that the total results arrived 
at are reasonably true and conclusive. Admitting all 
possible accidental errors which may have arisen-and it 
is simply preposterous to assume that intentional errors 
have been committed by scientific observers in every part 
of the world-the fact remains that in over 24,000 cases 
of diphtheria treated with antitoxin, which have been re- 
ported, the mortality has been apparently reduced by fully 
fifty per cent. 
Summaries of the various tables, prepared from the col- 
lected reports follow: 
TABLE I.-MORTALITY OF CASES OF DIPHTHERIA 
TREATED WITH ANTITOXIN AND PREVIOUS OR 
SIMULTANEOUS PERCENTAGE OF MORTALITY WITH- 
OUT ANTITOXIN. 
This table gives the number of cases treated with anti- 
toxin, the number and percentage of deaths, and the pre- 
vious or simultaneous percentage of mortality without anti- 
toxin, contained in 158 reports of larger series of cases, in 
hospital and private practice. These cases include not only 
those which, in the early use of antitoxin, were given in- 
sufficient doses, but also the cases which were moribund 
at the time of the first injection or died within twenty-four 
hours after it. 
In a total of 24,768 cases treated with antitoxin, there 
were 4004 deaths, or an average mortality of sixteen per 
cent. The following is a summary of the results obtained 
in hospital and private practice : 
SUMMARY OF TABLE I. 
Cases. 
Deaths. 
Mortality, 
per cent. 
Previous 
Mortality, 
per cent. 
In 109 reports from hospital 
practice 
15,560 
9208 
3009 
995 
19.0 
io. 1 
30 to 40 
In 49 reports from private prac- 
tice 
Total in 158 reports 
24,768 
4004 
16.0 
30 to 40.0 
In 109 reports from hospitals, there were 15,560cases, 
with 3009 deaths, or a mortality of 19 per cent, with the 
antitoxin treatment; in 49 reports from private practice, 
there were 9208 cases, with 995 deaths, or a mortality of 
10.1 per cent., or, in a total of 24,768 cases, there were 
4004 deaths, a mortality of 16 per cent., as against a 
previous or simultaneous mortality of 30 to 40 per cent, 
(taking the lowest figures in the reports) without anti- 
toxin. 
It would appear, therefore, according to these re- 
ports, that there has been a reduction of mortality in 
diphtheria, in both hospital and private practice, of at 
least fifty per cent., as the result of the antitoxin treat- 
ment. The lower percentage of mortality in private 
practice is probably due to the fact that the patients 
usually come under treatment in an earlier stage of the 
disease, and are generally more favorable cases. ANTITOXIC SERUM. 
15 
TABLE II. MORTALITY OF CASES OF DIPHTHERIA 
TREATED WITH AND WITHOUT ANTITOXIN. 
TABLE III. 
This table gives the number of cases (taking the reports 
which show these data) treated with and without anti- 
toxin, and the percentage of mortality. These cases were 
treated simultaneously or during intervals of forced inter- 
ruption of the antitoxin treatment, or in the periods imme- 
diately before and after the antitoxin treatment. 
With 
Antitoxin. 
Without Antitoxin. 
43 
d 
d 
d 
d 
0 
o 
a 
a 
u 
a 
a 
- 
- 
- 
- 
- 
I. 
Hospital d. Enfants 
Maladies, Paris.... 
300 
78 
26.0 
2. 
Hospital T rousseau, 
Paris 
520 
316 
60.0 
3- 
Hospital Franz Jo- 
seph 
no 
14 
12.7 
144 
62 
43-° 
4- 
Unterholzner 
37 
8 
25.8 
36 
24 
66.0 
5- 
Epidemic, Triest... 
321 
56 
17.1 
427 
213 
50.0 
6. 
Kaiser and Kaiserin 
Friederich Hospital, 
Baginsky 
3°3 
39 
R3-2 
230 
70 
47-8 
7- 
Vucetig 
30 
2 
6.6 
30 
6 
20.0 
8. 
Austrian statistics.. 
1128 
149 
13.2 
1849 
704 
38.1 
9- 
Rauchfuss (Russia). 
34 
7 
21 .O 
30 
16 
52.0 
IO. 
V. Engel 
39 
IO 
25-5 
62 
31 
50.0 
II. 
Charite Hos., Berlin 
299 
53 
16.7 
12. 
Bethany Hos., B'rlin 
249 
12 
43-1 
13- 
Blumenfeld 
229 
20 
8.7 
48 
II 
23.6 
- 
- 
- 
- 
- 
Totals 
2930 
436 
14.9 
3625 
1455 
40.0 
SUMMARY OF TABLE II. 
Cases. 
Deaths. 
.VI ortality, 
per cent. 
Hospital cases with antitoxin 
7986 
9°39 
3161 
4255 
1754 
3309 
412 
>7i7 
Hospital cases, without antitoxin 
36-4 
i3-° 
40.0 
Private cases, with antitoxin 
Private cases, without antitoxin 
Total in 45 reports, with antitoxin. ... 
11,147 
2169 
19-1 
Total in 45 reports, without antitoxin.. 
13.294 
5026 
37-8 
From 45 reports in which these cases were recorded 
it appears that there were 11,147 cases treated with anti- 
toxin, resulting in 2169 deaths, or a mortality of 19.1 
per cent.; while at the same time, or during the period 
immediately before or after the antitoxin treatment, there 
were 13,294 cases treated without antitoxin, with 5026 
deaths, or a mortality of 37.8 per cent. 
Separating the hospital and private cases there were 
treated in hospital 7986 cases with antitoxin, with a mor- 
tality of 21 per cent., as against 9039 cases treated with- 
out antitoxin, with a mortality of 36.4 per cent. In pri- 
vate practice there were 3161 cases treated with anti- 
toxin, resulting in a mortality of 13 per cent., as against 
4255 cases treated without antitoxin, with a mortality of 
40 per cent. 
Thus put to the severest test, selecting only the worst 
cases, as was often done intentionally for purposes of con- 
trol, and to determine the value of the new remedy 
(though occasionally it was an unfortunate necessity, 
owing to the lack of antitoxin, as some reports show, 
which compelled a forced interruption of the antitoxin 
treatment) there is still a difference of 50 per cent, in 
favor of the antitoxin treatment. Surely no effect of 
climate, or season, or "genius epidemicus," or any of 
the various theories brought forward by the opponents of 
antitoxin, can explain the difference in these results. 
Some other and more powerful factor than any or all 
of these was evidently at work to produce such a 
striking contrast in the practical results from two modes 
of treatment applied at the same time, or under identically 
the same conditions, by so many different observers. 
Some of the details of the most striking of these groups of 
cases which were treated with and without antitoxin at the 
same time, or during intervals of forced interruption, may 
be tabulated as follows (the full table will be published 
elsewhere): 
In a total of 2930 cases treated with antitoxin, 436 
died, giving a mortality of 14.9 per cent., while of 3625 
cases treated without antitoxin at the same time, or dur- 
ing intervals of forced interruption (owing to lack of anti- 
toxin) 1455 died, a mortality of 40 per cent. 
EXPLANATORY NOTES REGARDING THE STATISTICS IN 
TABLE NO. III. 
Roux reports 300 cases treated with antitoxin in the 
Hop it al des Enfants Malades (1) in Paris with a mortal- 
ity of 26 per cent, at the same time that 520 cases 
were treated without antitoxin in the Hopital Trousseau 
(2) with a mortality of 60 per cent. The previous mortal- 
ity in these hospitals had been about the same; the time, 
the type of the disease, every condition was the same, ex- 
cept the mode of treatment, and the resulting mortality. 
Ganghofner reports no cases treated with antitoxin in 
the Franz [osef Clinic (3) in Prague with a mortality of 
12.7 per cent, while during an interval of forced interrup- 
tion in the same hospital, owing to the supply of antitoxin 
having run out, 144 cases were treated without antitoxin 
with a mortality of 43 per cent. 
Unterholzner (4) in the Leopoldstadt Hospital in Vienna 
records the results in 37 cases with antitoxin in which 
the mortality was 25.8 per cent., and 36 cases without 
antitoxin during an interruption of the antitoxin treatment, 
in which the mortality was 66 per cent. 
During an epidemic of malignant diphtheria in the dis- 
tricts of Triest (5) and Bukowina, the Austrian Health 
Department sent out a supply of antitoxin to be used 
among the people. Before the antitoxin arrived the mor- 
tality had been fearful in these districts. Three hundred 
and twenty-one cases were treated with antitoxin with a 
mortality of 17 per cent. The supply of antitoxin sent 
was insufficient to furnish the whole section in which the 
epidemic was raging. Four hundred and twenty-seven 16 
ANTITOXIC SERUM. 
cases were treated without antitoxin, and the mortality 
among these was 50 per cent. 
Baginsky (6) records a most striking illustration of the 
effects of antitoxin in the Kaiser und Kaiserin Friedrich 
Kinder-Krankenhaus in Berlin-a result so striking that 
it converted Professor Virchow, who, up to that time, 
had been an opponent of the new treatment. In eight 
weeks in this hospital 63 cases had been treated with 
antitoxin with a mortality of less than 13 per cent. Sud- 
denly the supply of serum gave out, as unfortunately the 
horse from which the serum had been taken died. The 
old methods were resorted to, and during the next seven 
weeks, 109 cases were treated without antitoxin with 55 
deaths, or a mortality of over 50 per cent. This increase 
in the mortality induced the hospital authorities to return 
to the use of the serum. Immediately there was a change. 
In the next six weeks 84 cases were treated with a mor- 
tality of less than 15 per cent. The total figures are 
given in the table. 
In speaking of this remarkable experience Professor 
Virchow said "All theoretical considerations must give 
way to the brute force of these figures, and I consider it 
the duty of every physician to use a remedy giving such 
clinical results." 
Baginsky, in commenting on this circumstance, says : 
" It is all the more remarkable, as the ratio of mortality 
of those treated with the serum, before and after the 
period of interruption varied within very small limits. 
If one will permit figures to speak at all, there has 
scarcely been made on human beings a more demon- 
strative test of the curative power of a therapeutic agent. 
It was an experiment forced upon us, but it proved to us 
how terrible was the form of disease which we were treat- 
ing, and how numerous would have been the victims 
without the use of the healing serum." 
Professor Virchow again reiterated his opinion in a re- 
port which was read on the antitoxin treatment of diph- 
theria in the same hospital, on December 25, 1895, when 
he said, that from April to November of that year 303 
cases out of 335 treated had recovered, the mortality 
which had formerly been 43 per cent, having decreased 
to 9X per cent. 
Vucetig (7) reports two groups of cases of 30 each, one 
treated with antitoxin and the other with Loeffler's solu- 
tion; the antitoxin cases gave a mortality of 6.6 percent., 
the others a mortality of 20 per cent. 
According to the official records of the Austrian Health 
Department, (8) there were treated during the month of 
February (1896) in all Austria 1128 cases with antitoxin 
with a mortality of 13.2 per cent., whereas 1849 cases 
which were treated without antitoxin at the same time 
gave a mortality of 38 per cent. 
Rauchfuss (9) reports 34 cases treated in hospital with 
a mortality of 21 per cent., and 30 control cases treated at 
the same time without antitoxin with a mortality of 52 
per cent. 
Von Engel (10) in Bohemia reports 39 cases treated with 
antitoxin with a mortality of 25.5 per cent., and 62 cases 
treated at the same time without antitoxin with a mortality 
of 50 per cent. The antitoxin cases, in these reports, are 
said to have been unusually severe and therefore taken as 
a test of the new remedy. 
Heubner (11) reports 299 cases treated with antitoxin 
in the Hopital Charite in Berlin with a mortality of 16.7 
per cent., and 249 cases treated in the Bethany Hospital 
(12) at the same time under the same conditions of age, sea- 
son, etc., without antitoxin with a mortality of 43 per 
cent. 
Blumenfeld (13) reports 229 cases treated in private prac- 
tice with antitoxin with a mortality of 8.7 per cent., and 
48 cases not treated with antitoxin, because they were 
considered to be too mild ; the mortality among the " mild 
cases" was 23.6 per cent, as against 8.7 per cent, among 
the apparently severer cases treated with antitoxin. 
Many examples of the same kind might be cited from 
the published reports, fuller details of which will be found 
in the Bulletin of the Health Department, but from these 
it may be seen that the antitoxin treatment has stood the 
test of comparison with other approved methods of treat- 
ment, whenever the contrast has been decidedly drawn. 
kossel's statistics of reduction in the abso- 
lute MORTALITY FROM DIPHTHERIA AND CROUP. 
It has been maintained by some in criticizing the statis- 
tics of the antitoxin treatment, that the reduction of the 
death-rate, as shown by the mortality percentage, proves 
nothing, if at the same time there has been an increase in 
the number of cases reported, as the reduced mortality 
rate may have been due to the milder character of the 
cases treated ; and that the only convincing figures are 
those which show, not a reduction of percentage mortal- 
ity, but of absolute mortality. 
Kossel has undertaken to satisfy this desideratum in 
the following statistics: 
I.-In the Hopital Charitem Berlin there were admitted 
during the years 1886 to 1893-94, an annual average of 146 
diphtheria patients, of whom 78, on the average, died; in 
1894-95 and 1895-96, 285 were admitted, of whom 40 
died. The absolute mortality, therefore, during the se- 
rum period (1894-95 and 1895-96) was reduced to one- 
half of the average for the previous eight years, though 
the number of cases admitted had increased two-fold. 
II. THERE WERE REPORTED IN ALL THE BERLIN 
HOSPITALS THE FOLLOWING CASES AND DEATHS 
FROM DIPHTHERIA DURING THE ELEVEN YEARS. 
1885-1896: 
OOOOOOCOOCOOOOOOOOCOCO 
O O O O O O 00 00 CO CO 00 
Cfi +• Go to m O VO 00<1 pxczi 
Year. 
GObOtOtOHHMMWMW 
Q CO-P> o I O O 
Ch\O tn ChMD M Go Go to 
1-1 0 to OJ O Ch 00 00 
Cases. 
COO 00 Ch Q\Cn Cn tn 
00 0 tn Go to COO QP 
M M GO CnGo Go O O O 
Deaths. 
It appears from these statistics that in the Berlin 
hospitals, as a whole, the deaths have been reduced one- ANTITOXIC SERUM. 
17 
half since the introduction of antitoxin, though the num- 
ber of cases reported has steadily increased. The sta- 
tistics for 1896 show a still larger reduction in the absolute 
and case mortality. 
diminution at the rate of 65.6 per cent. The rate of 
diminution, month by month, went on almost uniformly 
from one of 56.2 per cent, for the month of January, to 75 
per cent, for the month of June. 
III.-THE FOLLOWING TABLE GIVES THE CASES AND 
DEATHS REPORTED IN BERLIN AND THE DEATHS IN 
PARIS (CASES NOT REPORTED PREVIOUS TO 1894) 
FROM 1886 TO 1896 : 
V.-M0N0D, THE DIRECTOR OF THE PUBLIC HEALTH 
DEPARTMENT OF FRANCE, HAS GIVEN THE AVERAGE 
ABSOLUTE MORTALITY FROM DIPHTHERIA PER 
MONTH FOR THE FIRST SIX MONTHS OF EACH YEAR 
FROM 1888 TO 1895, AND FOR 1895, IN ALL FRENCH 
CITIES OF OVER 20,000 POPULATION : 
Berlin. Paris. 
Year. 
Cases. Deaths. Deaths. 
1886 6968 1662 1524 
1887 5438 1392 1564 
1888 4190 1195 1718 
1889 4220 1210 1706 
1890 4586 1601 1639 
!89i 3504 1342 1363 
1892 3683 1637 1398 
1893 4315 1416 1262 
1894 5220 1321 993 
1895 6106 987 411 
Month. 
1888-1895. 
1895. 
January 
469 
205 
February 
466 
187 
March 
499 
155 
April 
442 
160 
May 
417 
113 
June 
334 
84 
Totals 
2,627 
904 
The use of antitoxin began in Paris and Berlin in the 
latter part of 1894, and was general in 1895; in New 
York antitoxin was introduced by the health department 
in 1895, and is only now becoming generally used. 
Taking all these figures together it would seem to have 
been conclusively proved that, whether we estimate the 
percentage mortality, or whether we consider the abso- 
lute death-rates reported in hospitals or cities as a whole, 
there has been a marked and sudden reduction in mor- 
tality from diphtheria since the introduction of antitoxin. 
To what else should this be attributed if not to the effects 
According to these figures the mortality from diph- 
theria rose and fell in Berlin, corresponding more or less 
closely to the number of cases reported up to the year 
1894. In 1894 and 1895 the cases increase in number, 
while the absolute mortality declines, and in Paris, in 
1895, it decreases to less than one-third of the previous 
average. The statistics for Berlin for 1896 (see previous 
tables) show an equal reduction. Antitoxin was more 
lowly introduced there than in Paris. 
IV. THE ABSOLUTE MORTALITY AND DEATHS PER 
100,000 POPULATION IN ALL GERMAN CITIES OF 
OVER 15,000 INHABITANTS, FROM 1886-1895: 
VI.-FROM STATISTICS TAKEN FROM THE OFFICIAL 
RECORDS OF BERLIN, PARIS, AND NEW YORK, ON 
FILE IN THE OFFICES OF THE NEW YORK HEALTH 
DEPARTMENT, THE FOLLOWING DEATH-RATES FROM 
DIPHTHERIA AND CROUP, ESTIMATED PER 100,000 
POPULATION, ARE GIVEN: 
ABSOLUTE DEATH-RATE PER 100,000 POPULATION. 
OOOOQOQOOOOOOOCOOOOO 
Year. 
- 
£ 
(A 
O, 
£> P'P p p p p p 
S 
U1 C/0 4- \0 '»O M sQ tO 
HtvQCn 0\OOM hi 
h 0 v] tO O nr 
Mortality. 
Death 
Cn OWO CO O 0 5 
w H o -4 Cn w 0\*J 
(/) 
Average from 1886 
to 1894, 106. 
100,000. 
cooooooooooooooooooooo 
xO o o o o xQ KQ 00 00 00 00 
OxGi 4* Go to H o O COO Ox 
Year. 
GO Cn 00 Q x£) Ox 0 00O Q tO 
OxO Ox 0 10 O tO Cn Ox 0 Cn 
xQ O O 00x0 Cn O Ox h o 
Berlin. 
h h Cn O' Oxo O COO o 
OO 0 H OJ OJ O X0 Ca) OxCa) 
O'OCn'OMvO K> 
Paris. 
HHHMMHHHItOl-l 
xO tO H M Ox Q 00 
M Cn 00Cn U 00 0 Oxo OxO 
Co to Cn tn Go O OxtOO OxCn 
New York. 
This table shows a steady rise in absolute mortality up 
to 1894, when there was a moderate reduction, followed 
by a very great reduction in 1895, when antitoxin was 
generally used in the German cities. The sudden fall in 
the absolute mortality from diphtheria amounts to one- 
half the average of the previous nine years. 
The Pasteur Institute in Paris began the distribution of 
antitoxin in November, 1894. Early in 1895 arrange- 
ments were made to furnish antitoxin free to those who were 
unable to pay for it. In 108 cities of over 20,000 inhab- 
itants, with an aggregate population of 8,150,000, the 
average number of deaths from diphtheria during the first 
six months of the seven years, 1888-1895, was 2,627. 
In the first six months of 1895 the absolute mortality 
from diphtheria in the same 108 cities was only 904, or a 
of the antitoxin treatment? It would be a strange coinci- 
dence, indeed, which produced by natural causes such 
a diminution in the death-rate of a disease that had 
continued unchanged, within slight variation, for many 
successive years, and then dropped to one-half during 
the period corresponding to the use of antitoxin, if it were 
not due to the improved method of treatment. 
TABLE IV.-COLLECTIVE INVESTIGATIONS. 
This table has been prepared in order to compare the 
results noted in the present report, with the collective in- 18 
ANTITOXIC SERUM. 
vestigations of other observers. It gives the total results 
reported of the antitoxin treatment, and the previous 
mortality without antitoxin, in twelve collective investiga- 
tions, published in Germany, Austria, Japan, and the 
United States. It is seen, by a comparison of these re- 
ports, that each and all of them record almost exactly the 
same results, viz., that the mortality from diphtheria has 
apparently been reduced. 
This table gives the cases, deaths, and percentage of 
mortality in operative and non-operative cases of diph- 
theria treated with antitoxin as compared with the pre- 
vious or simultaneous mortality in operative cases without 
antitoxin. 
SUMMARY OF TABLE V. 
Total in 72 ) 
reports.. J 
ix 
Cases. 
Total Cases 
Treated. 
& 
Ch 
Deaths. 
Mortality, 
per cent. 
JO 
Cases. 
Non-operative 
Cases. 
Deaths. 
Go 
Mortality, 
per cent. 
u 
to 
Cases. 
Operative 
Cases. 
M 
Deaths. 
O' 
Mortality, 
per cent. 
0 
9 
Previous Mortality, 
per cent. 
TABLE IV.-COLLECTIVE INVESTIGATIONS OF OTHER 
OBSERVERS OF THE SAME OR SIMILAR CASES 
TREATED WITH ANTITOXIN, AND PREVIOUSLY, 
WITHOUT ANTITOXIN. 
Reporter. 
Treated with Antitoxin 
T reated pre- 
viously or 
without Anti- 
toxin : Mortal- 
ity, per cent. 
Cases. 
Deaths. 
Mortality, 
per cent. 
Heubner, Berlin 
3036 
625 
20.6 
38 to 40.0 
Monti, Vienna 
3888 
716 
18.4 
Crandall, St. Louis 
2632 
442 
16.8 
42.0 
Forster, Washington 
2740 
509 
18.5 
45-3 
Eulenburg and Schwalbe, Berlin 
5833 
559 
9.6 
14-7 
Welch, Baltimore 
7166 
1239 
T7-3 
42.0 
Kaiserl.Gesundh. Amt.(Berlin): 
First quarter 1895 
2228 
386 
i7-3 
Second quarter 1895 
2130 
306 
i4-3 
26.7 
Hilbert, Konigsberg 
7663 
1282 
16.6 
38 to 40.0 
Paltauf, Vienna 
Loddo, Japan 
1207 
138 
11.3 
38 to 40.0 
10,000 
1800 
18.0 
44-0 
American Ped. Society 
5794 
7i3 
12.3 
Totals 
54,317 
8715 
16.1 
30 to 40.0 
Present report to October, 1896. 
24,768 
4004 
16.0 
30 to 40.0 
Of the 3082 operative cases 1355 were tracheotomized,. 
resulting in 569 deaths, or a mortality of 42 per cent. 
1173 cases were intubated with 361 deaths, or a mortality 
of 30.8 per cent.; 52 cases intubated required secondary 
tracheotomy, of which 37 died, or 71 per cent.; 502 cases 
required tracheotomy or intubation (it was not stated 
which) with 168 deaths, or a mortality of 33.2 per cent. 
According to a report of 12,736 cases up to 1887 pub- 
lished by Monti, the mortality in tracheotomy previously 
was 73.3 per cent. Hirsch gives from statistics collected 
in von Bergmann's clinic the average previous mortality in. 
tracheotomy cases for the last ten years up to July, 1894, 
at 68.5 per cent. Of 5546 intubation cases collected by 
McNaughton and Maddren 1 (1892) the previous mortality 
was 69.5 per cent. Brown has shown since somewhat 
better results in intubation, viz., a mortality of 51.6 per 
cent. 
In a total of 15,148 cases treated with antitoxin in this 
table taken from 72 reports, there were 2626 deaths, or a 
mortality of 16.6 per cent.; of these 12,066 cases were 
not operated on, (80 per cent.) of which 1491 died, 
giving a mortality of 13.5 per cent.; 3082 were oper- 
ated on, intubation or tracheotomy, of which 1135 
died, or 36.7 per cent. Before the antitoxin treatment 40- 
per cent, of all cases are reported generally as having re- 
quired operation, and the previous mortality was 70 per 
cent, for all operated cases, according to the average fig- 
ures recorded in these reports. 
But taking the lowest average recorded at all in any 
reports, viz., 68.5 per cent, as the previous mortality in 
tracheotomy cases, and 51.6 per cent as the previous mor- 
tality in intubated cases, and the contrast in these figures, 
and those obtained under the antitoxin treatment is suffi- 
ciently evident. Here again, in operative cases of the 
severest forms of the disease the mortality seems to have 
been reduced by nearly fifty per cent, as the result of the 
antitoxin treatment; while at the same time the number 
of cases requiring operative interference has decreased to 
one-half. This last effect of the serum treatment is due 
to the fact that many cases of beginning laryngeal steno- 
sis are relieved after injection, without having recourse to 
operation, few or no cases, which were free of laryngeal 
It would thus appear from this table that twelve differ- 
ent observers, analyzing the same or similar cases treated 
with antitoxin, have arrived at identically the same result, 
viz., that the mortality of diphtheria, according to the pub- 
lished reports, has been reduced at least one-half as the 
effect of the antitoxin treatment; the average mortality for 
the antitoxin cases being sixteen per cent., including hos- 
pital and private practice, and thirty to forty per cent, for 
the cases treated previously or without antitoxin. There 
is naturally in this table, in many instances, a reduplica- 
tion of cases; they are put together merely to show the 
uniformity of the results of the collective investigations. 
There is a reduction of at least one-half, as the effect 
of the antitoxin treatment, the average mortality for the 
antitoxin cases being sixteen per cent., including hospital 
and private practice, and thirty to forty per cent, for the 
cases treated previously or without antitoxin. 
TABLE V.-MORTALITY OF OPERATIVE AND NON- 
OPERATIVE CASES OF DIPHTHERIA TREATED WITH 
ANTITOXIN. 
One of the most significant effects of the antitoxin treat- 
ment of diphtheria, and that which affords the best proof 
of its value, is shown in the remarkable results, which have 
been obtained in cases of laryngeal diphtheria with stenosis, 
which include the severest and most fatal forms of the dis- 
ease. 
1 Collective Investigation of the American Ped. Soc., July, 1896. ANTITOXIC SERUM. 
19 
obstruction when the antitoxin was injected, being reported 
as having developed such symptoms later. 
mortality of cases treated with antitoxin, arranged accord- 
ing to the day of the disease on which the treatment was- 
begun. It is to be understood, as stated in all the re- 
ports, that these statistics are based in most cases upon 
the statements of parents or friends of the patients and 
may not be absolutely correct as to the exact day of the dis- 
ease on which the antitoxin was administered, but they 
give nevertheless an average of the results obtained. 
Or, taking only those reports in which the day of dis- 
ease on which treatment was commenced is more specifi- 
cally stated, we have: 
TABLE VI.-MORTALITY OF CASES TREATED WITH 
ANTITOXIN ARRANGED ACCORDING TO AGE. 
As age is an important factor in estimating the value of 
any treatment of diphtheria, these statistics have been col- 
lected from all the reports in which the age was mentioned, 
and arranged in the form of a table. The reports of age 
mortality, however, have not been uniformly or systemat- 
ically recorded; but the main features of the table may be 
summarized as follows : 
Age. 
Cases. 
Deaths. 
Mortality, 
per cent. 
0-2 Years 
1494 
469 
3i.4 
2-5 " 
3678 
762 
20.7 
5-io " 
3184 
473 
14.8 
Over io Years 
1444 
99 
6.9 
SUMMARY OF TABLE VI. 
Cases. 
Deaths. 
Mortality, 
per cent. 
First day of disease 
Second day of disease.... 
2640 
213 
O • 
8.0 
Third " " .... 
2340 
300 
12. S' 
Fourth " " .... 
1458 
346 
23-6 
Fifth day and after 
1912 
671 
35-o 
Totals 
9765 
1581 
16.1 
Comparing these results with those obtained previously 
or without antitoxin the following have been reported: 
Herz: Mortality, 
per cent. 
Hirsch: Mortality, 
per cent. 
Baginsky: Mortality, 
per cent. 
o-i Year 80.0 
i-3 " 45-0 
3-5 " 4o.o 
5-io " 17.0 
Over io Years. ..17.0 
0-1 Year 88.3 
1-3 " 82.5 
3- " 63.9 
4- " 46.9 
6-7 " 43-2 
Over 7 Years. .22.2 
0-2 Years 63.3 
2-4 " 52.8 
4-6 " 37-9 
6-10 " 24.6 
10-15 " 14.6 
According to these statistics it is apparent that by far 
the best results are obtained when treatment is com- 
menced early in the disease, if possible within the first 
forty-eight hours, and not later than the third day; that 
after the third day the mortality increases rapidly, and 
that after the fifth day comparatively little benefit is de- 
rived from the use of antitoxin, though it should always 
be administered. 
Considering the fact that in all these statistics are in- 
cluded the cases which were moribund at the time of 
the first injection, or which died within twenty-four hours 
after, there would seem to be very good reason to be- 
lieve with Behring, Kosse 1, Roux, and other observers, 
that every fresh case of true pharyngeal diphtheria can be 
cured by the timely administration of an adequate dose 
of antitoxin, and that the claim, that only five per cent, of 
the cases injected within the first forty-eight hours of the 
disease would die, has actually been substantiated. 
The contrast here shown of the results of treatment 
'with or without antitoxin, arranged according to age, is 
sufficiently evident and needs no further comment. 
TABLE VII.-MORTALITY OF CASES TREATED WITH 
ANTITOXIN ARRANGED ACCORDING TO THE DAY 
OF DISEASE ON WHICH TREATMENT WAS COM- 
MENCED. 
Behring claims that the specific curative effect of anti- 
toxin will be the more certainly produced the sooner the 
treatment is commenced; and that out of 100 cases of 
true diphtheria, which are injected with a curative dose 
of antitoxin within forty-eight hours from the beginning of 
the disease, not more than five will die. 
TABLE VIII.-IMMUNIZATION BY ANTITOXIN. 
The question of immunization now comes up for con- 
sideration, and though but comparatively few complete 
statistics on this subject have been published, yet the 
prophylactive treatment of diphtheria is a matter of so 
great importance that this table has been prepared to 
show in how far (according to the reports already pub- 
lished) the administration of immunizing doses of anti- 
toxin has resulted in protecting those exposed to infection. 
The data are incomplete and unsatisfactory, not only 
from the fact that many cases immunized have not been 
reported, but also because many reported as immunized 
have received insufficient doses of antitoxin; but such as 
they are the results are interesting as showing the com- 
plete protection apparently afforded to many persons ex- 
posed to the disease. 
According to thirty-five published reports, of which this 
is a summary, there are 17,516 persons, children and adults, 
to whom immunizing injections of antitoxin have been 
given, with the result that, though exposed to infection 
to 
Go 
to 
Cases. 
First and Sec- 
ond Day of 
Disease. 
Deaths. 
Go 
Mortality, 
per cent. 
Go 
00 
0 
Cases. 
Third and 
Fourth Day of 
Disease. 
Deaths. 
to 
Mortality, 
per cent. 
I 
Cases. 
After the 
Fourth Day. 
Deaths. 
£ 
Mortality, 
per cent. 
§ 
Cases. 
Day Unknown. 
Deaths. 
Go 
b 
Mortality, 
per cent. 
SUMMARY OF TABLE VII. 
In order to test the truth of this statement, and to de- 
termine what has actually been effected by the use of the 
remedy, this table has been prepared, which gives the 20 
ANTITOXIC SERUM. 
from diphtheria in families and institutions, and during 
epidemics when the disease was raging, only 131 of 
those immunized were attacked later, and of these 129 
were mildly affected (109 within thirty days, and 20 after 
a month), and recovered; while only 2 died of the disease, 
■one within and the other after thirty days from the time of 
injection. The two fatal cases probably received far too 
small doses to produce immunity, or the diphtheria was 
■complicated with other diseases not mentioned. The 
■mild cases all recovered, in some a repetition of the injec- 
tion being given. Only some slight and temporary ill 
■effects are described as having occasionally resulted from 
the immunizing injections, though in the Hopital des 
Enfants Malades and the Hopital Trousseau in Paris, 
and in Lohr's experiments, full curative doses were often 
given to healthy subjects. Rashes, joint-pains, and other 
transient effects of the antitoxin serum were occasionally 
observed, but no serious after effects which could be 
ascribed to the action of the antitoxin, or which would 
contra-indicate its use. 
may probably be considered as the average duration. 
Note.-The complete tables, of which these are only 
the summaries, will shortly be published, with a full report 
of the cases, in a scientific bulletin of the New York 
Health Department. They are omitted here, as they are 
too bulky for such an article. 
From an examination of these statistics, it appears that 
the most marked reduction in the death-rate from diph- 
theria and croup in the period from 1894 to 1895 and 
1896, has occurred in France and Germany, and in those 
countries which are more directly under their influence, 
viz., Austria, Belgium, Switzerland, Denmark and Swe- 
den. This is exactly what we would have expected to 
find, if the mortality-reduction be the result of the anti- 
toxin treatment. There has also been a considerable, but 
less conspicuous, fall in the death-rates in Russia and 
Italy. In Great Britain, Holland, and Egypt, the mor- 
tality has been but little affected. But in none of the great 
cities of the civilized world has there been an increase in 
the death-rate from diphtheria since the introduction of 
antitoxin, and in all the countries where antitoxin has been 
most and longest used the mortality has been distinctly 
reduced. The reduction, which began in the latter part 
of 1894, is conspicuous in 1895, and is continued into 
1896 with apparently a still further reduction of mor- 
tality. 
In the United States the effects of antitoxin are now 
just beginning to be felt, for which reason it was not 
thought necessary to add these to the list of comparative 
statistics. 
The statistics given have been collected from reports of 
series of cases of diphtheria treated with antitoxin, published 
upto October 1, 1896, in the various medical journals of 
the world-Germany, France, England, Austria, Italy, 
Russia, Switzerland, Denmark, Australia, Japan, etc., 
and America,-accessible in the Library of the New York 
Academy of Medicine. 
SUMMARY OF TABLE VIII. 
Number of 
Cases 
Immunized. 
Number of Anti- 
toxin Units 
Injected. 
Number of those 
Immunized 
Attacked Within 
30 Days. 
Number of 
those Immun- 
ized Attacked 
After 30 Days. 
i7> 516 
50 to 1000 
(Average, 150 
to 200). 
109 mild, 
1 fatal. 
20 mild, 
1 fatal. 
The prophylactive dose of antitoxin is now thought by 
most observers to be from 150 to 500 antitoxin units. 
The duration of immunity after injection has not been 
definitely determined, and undoubtedly varies. Some hold 
the opinion that it lasts only one or two weeks, others 
that it extends over thirty days and more. Four weeks 
Aggregate Population, Deaths, and Ratio per 100,000 from Diphtheria and Croup in Cities 
Over 100,000 Inhabitants, for the Years 1894, 1895, and 1896, in Great Britain, France, 
Belgium, Holland, Germany, Austria, Switzerland, Denmark and Sweden, Russia, Italy' 
and Egypt, Compiled from the Official Records on File in the Registrar's Office of 
the New York Health Department: 
1894. 
1895- 
18Q6.1 
Population. 
Deaths. 
Ratio. 
Population. 
Deaths. 
Ratio. 
Population. 
Deaths. 
Ratio. 
Great Britain 
9,721,631 
4150 
42.7 
9.843,854 
3603 
36.6 
10,077,760 
3854 
36.0 
F rance 
3,655,203 
1562 
42.4 
3,655,203 
782 
21.3 
3,655,203 
685 
18.7 
Belgium 
1,058,535 
378 
35-7 
1,081,199 
215 
19.8 
1,081,199 
154 
14.2 
Holland 
849,264 
264 
31.0 
903,990 
152 
16.8 
903,990 
252 
27.2 
Germany 
6,237,751 
5680 
9i-5 
6,403,159 
3362 
52.5 
6,387,080 
2301 
36.0 
Austria 
2,633,692 
2750 
104.4 
2,684,377 
1327 
5i.7 
2,736,046 
1186 
43-3 
Switzerland 
103,271 
85 
82.3 
126,497 
24 
18.9 
126,497 
18 
14.2 
Denmark and Sweden 
755,078 
672 
89.0 
760,606 
218 
28.6 
760,606 
209 
27,4 
Russia 
2,533,300 
2721 
108.0 
2,548,023 
1692 
66.4 
2,576,523 
1729 
66.7 
Italy 
1,086,244 
373 
34-3 
1,120,948 
221 
19.7 
1,120,948 
216 
19.2 
Egypt ; 
534,891 
97 
18.1 
534,891 
152 
28.4 
534,891 
96 
18.0 
Totals 
29,168,860 
18,732 
64.2 
29,662,747 
11,748 
39-6 
29,960,743 
10,700 
35-7 
i The deaths for the year 1896 are taken from the weekly reports of the first 39 weeks, and from these the average for the 52 weeks 
has been estimated. For 1894 and 1895 the annual reports are given. ANTITOXIC SERUM. 
21 
CONCLUSIONS. 
We desire to bring out strongly and clearly the fact 
that it matters not from what point of view the subject is 
regarded, if the evidence now at command is properly 
weighed, but one conclusion is, or can be reached, whether 
we consider the percentage of mortality from diphtheria 
and croup in cities as a whole, or in hospitals, or in private 
practice; or whether we take the absolute mortality for all 
the cities of Germany whose population is over 15,000, 
and all the cities of France whose population is over 
20,000 (in France and Germany antitoxin has been more 
generally employed than elsewhere); or the absolute mor- 
tality f or N ew YorkCity, orforthe great hospitals in F rance, 
Germany, and Austria; or whether we consider only the 
most fatal cases of diphtheria-the laryngeal and opera- 
tive cases; or whether we study the question with relation 
to the day of the disease on which treatment is commenced, 
or the age of the patient treated; it matters not how the 
subject is regarded or how it is turned for the purpose of 
comparison with previous results, the conclusion reached 
is always the same, namely, there has been an average 
reduction of mortality from the use of antitoxin in the 
treatment of diphtheria of not less than fifty per cent., 
and under the most favorable conditions a reduction to 
one-quarter, or even less, of the previous death-rate. 
This has occurred not in one city at one particular time, 
but in many cities, in different countries, at different sea- 
sons of the year, and always in conjunction with the intro- 
duction of antitoxic serum, and proportionate to the extent 
of its use. 
Then, finally, there is to be added not only the experi- 
mental proof of the specific action of antitoxin in neutraliz- 
ing the toxin of diphtheria, but also the overwhelming mass 
of evidence derived from the personal observations of the 
most distinguished practitioners of medicine of every 
country. There are to-day, in the whole civilized world 
not more than three or four active opponents of the anti- 
toxin treatment of diphtheria, whose names were known to 
the medical profession before the introduction of antitoxin. 
It is well to bear in mind the fact, that what is called 
conservatism in medicine is often only a cloak assumed to 
cover up indolence. The acceptance of a new principle, 
or a new fact, involves the expenditure of a certain amount 
of mental energy. Old ideas and conceptions must be 
discarded or readjusted to the new information acquired. 
This involves labor and effort, which some are not willing 
to expend. They are not willing to go over the data 
at hand and form conclusions for themselves, but shake 
their heads wisely, predict a reaction, and plead for con- 
servatism. It is not possible now for any unprejudiced 
person to master the evidence available regarding the 
value of antitoxin in the treatment of diphtheria, and reach 
anything but a positive conclusion. 
The deductions to be drawn from a review of these sta- 
tistics and reports presented would seem to be self-evident 
and conclusive. The value of antitoxin in diphtheria is 
no longer a question of opinion or theory, but an estab- 
lished fact. ' ' Proberin geht ueber studerin, " those who 
have had the largest experience with the remedy, and 
have most thoroughly tested its merits, are most in favor 
of it. The few who oppose it have proved nothing in 
comparison with the enormous mass of evidence as to its 
specific value, 
It may, therefore, be affirmed that the following facts 
have been demonstrated: 
1. That diphtheria antitoxin, where generally employed, 
has reduced the mortality from diphtheria at least one- 
half. 
2. That it has a distinctly favorable effect on the clini- 
cal course of the disease, shortening it and lessening its 
severity. 
3. That the earlier the treatment is commenced the 
better the results obtained; the mortality, when adequate 
doses of antitoxin have been given with the first forty- 
eight hours of the disease, not exceeding five per cent. 
4. That antitoxin is a specific against true diphtheria, 
(z. <?., where the symptoms are due solely to the Klebs- 
Loeffler bacillus) and is less efficacious in mixed infec- 
tious, but even in these forms of diphtheria is of decided 
benefit. 
5. That it is not necessary to wait for a confirmatory 
bacteriological diagnosis, but that in every clinically sus- 
picious case of membranous angina, especially in children, 
a medium dose of antitoxin should immediately be given, 
and repeated if required by the further developments of 
the case. 
6. That antitoxic serum is a remedy without serious 
after-effects in the doses which have ordinarily been em- 
ployed (the after-effects, such as rashes, etc., being in- 
significant in comparison with the danger of the disease) ; 
that it has no injurious action on the kidneys, the heart, 
or the nervous system; that it does not entirely prevent 
albuminuria, heart failure, and post-diphtheritic paralysis, 
because the effects of the diphtheritic toxin which has 
already entered the system before the administration of 
the remedy, no matter how soon the treatment is begun, 
are not always completely counteracted by the antitoxin, 
though there is every reason to believe that in sufficient 
doses it does prevent any farther extension of the toxic 
action after its affects have been produced. 
7. That the protection conferred by immunizing doses 
of antitoxin is almost absolute for a short period of time, 
e.g., three or four weeks, when a sufficient number of 
antitoxin units is administered, and that with a high grade 
preparation, where only small quantities of serum are re- 
quired, the remedy is absolutely harmless even with the 
youngest infants. 
8. That antitoxin, if not a specific cure for all forms of 
diphtheria occurring in the human subject, is by far the 
best remedy for the treatment of the disease. 
To the critics of the antitoxin treatment I may repeat 
the words of a famous German poet, quoted by Professor 
Soltman: 
" Das ist die richtigste Kritik von der Welt, 
Wenn neben das was ihm missfallt, 
Einer etwas Ergens and Besseres stellt." 
Or, in other words: 
1 ' The best critics in the world are they 
Who along with that which they gainsay, 
Suggest another and a better way." The Medical News. 
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