Clinical Experience 
WITH 
ANTI-STREPTOCOCCUS SERUM. 
BY 
Louis Fischer, M.D., 
New York. CLINICAL EXPERIENCE WITH ANTI-STREPTOCOCCUS 
SERUM.* 
LOUIS FISCHER, M.D. 
New York. 
When the treatment of diphtheria with antitoxin became 
generalized, great hopes were entertained by the profession upon 
the announcement of a similar discovery with Marmorek’s anti- 
streptococcus serum. 
This announcement came from the Pasteur Institute at Paris. 
It was first recommended as a specific in the treatment of all 
diseases caused by the streptococcus, and therefore was urged 
as a specific in the treatment of scarlet fever. It was further- 
more recommended as a specific in erysipelas, and also in the 
treatment of puerperal septicsemia. In fact, all septic conditions 
caused by post-mortem wounds were to be similarly treated. 
Thus, we have had occasion to see what this serum can 
accomplish. 
My first experience with this Marmorek’s serum I owe to the 
courtesy of Prof. A. Baginsky. It was in the summer of 1896 
that I watched with great interest a series of cases of scarlet fever 
treated by the anti-streptococcus serum in the Scarlet Fever Pav- 
ilion, which is part of the Kaiser and Kaiser Frederich Children’s 
Hospital at Berlin. 
The treatment pursued consisted in subjecting a series of 
cases of mild, severe, and malignant scarlet fever to the thera- 
peutic influence of this serum, and by noting the results night 
and day. Owing to the large number of assistants at the dis- 
posal of Prof. Baginsky, in addition to the laboratory facilities, 
all details were handled in a masterly manner. Some cases re- 
ceived injections of 10-20, and some as much as 70-80 c.c. during 
each treatment. 
Recognizing the value of Prof. Baginsky’s advice in the treat- 
ment of diphtheria, I naturally was anxious to note his results in 
the treatment by this new therapeutic agent. He cautioned me 
not to use the serum for the present, and said to me that it is 
not a specific in the treatment of scarlet fever, in the sense that 
antitoxin is advised in the specific treatment of diphtheria. 
In his text-book on Diseases of Children, fifth edition, pub- 
lished in Berlin, 1896, in his article on scarlet fever, page 151, 
*Read before the Section on Pediatrics, New York Academy of Medicine, 
May 12, 1898. 2 
Fischer : <■Anti-Streptococcus Serum. 
speaking of Marmorek’s anti-streptococcus serum, he distinctly 
says that “ he believes that it does no harm.” 
This is now the second year since I have tried the value of 
this anti-streptococcus serum in various diseases. 
Scarlet Fever.—A. Z., three and a half years of age, had 
been sick with scarlet fever for about one week, when we took 
charge of the case on April 13, 1897. When the child was first 
seen, it had a temperature of 102.50; pulse, 140, soft, weak, and 
intermittent. The mouth and pharynx were filled with dry, grey- 
ish, fetid membranes. There was a purulent nasal discharge, an 
excoriation around the alae nasi, besides a mild bronchitis. The 
child was extremely constipated, had anorexia, was intensely 
thirsty. There had been a history of previous vomiting. The 
child was extremely restless, and the face showed a decided con- 
dition of sepsis, being pale, eyes sunken, nose pointed, furrows 
round the eyes deeply marked, and a sickening odor emanated 
from the child’s body. The child was put on calomel powders, 
which produced some very vile-smelling evacuations. Large 
quantities of brandy and milk and seltzer were also given, and 
diffusible stimulants, like carbonate of ammonia, were ordered. 
As the temperature rose, and there was evidence of delirium, 
cooling baths were ordered, which seemed to have a tonic 
effect. 
On the 17th, the child received an injection of 10 c.c. of anti- 
streptococcus serum, and noticing no distinct change in the 
child’s condition, the same dose was repeated on the 24th. The 
child showed no signs of improvement; the temperature was 
somewhat reduced, but the general condition was certainly not 
improved. 
On the 30th, exitns lethalis. 
The above case was attended by Emil Joel, M.D., from whom 
I received the above report, and was seen by me several times 
with him. 
Another equally interesting case is the following: 
C. G., female, six years old, and seen by me on October 17, 
1897. The mother told me that the child had been vomiting, 
and it had some diarrhoea, the latter caused by a cathartic that 
she had given. The child was covered with a rash, but had, 
according to the mother’s history, been well until yesterday. 
She complained of headache and slight pain in the throat. In- 
quiry elicited the fact that a child in the same house had had 
scarlet fever several weeks ago, and that this patient under con- 
sideration had been exposed before the character of the disease 
was defined. Physical examination showed a poor-nourished 
child, pigeon-breasted, rachitic head and limbs, an otitis puru- 
lenta dextra, which the mother told me had existed for the last 
year since the child’s attack of measles. The eruption covered Fischer: Serum. 
3 
the chest and limbs, and was not plain on the back nor on the 
face. The pharynx and fauces were congested, but showed no 
patches; the tongue was slightly coated, but did not show the 
characteristic strawberry appearance usually found in these cases. 
The temperature was 104° in the rectum at 9 a.m. ; pulse, 138. 
The urine, according to the mother’s history, was passed freely. 
The diagnosis of scarlet fever had been made. 
I requested permission to use the anti-streptococcus serum.- 
The child received ioc.c. on the evening of the same day, which 
was injected subcutaneously between the shoulder blades about 
5 p.m. The temperature at the time of the injection was 105.2° 
in the rectum; pulse, 156. At 9 p.m. the temperature was 105° 
in the rectum; pulse, 150. The child was still nauseated and 
intensely thirsty. 
The following morning, at 9 a.m. (October 18th), the tem- 
perature was 104°; pulse, 124: general condition the same, with 
the exception of diarrhoea, which had subsided, the child having 
been put on a rice, barley, and white of egg diet; no stimulants 
had been given. On the evening of the same day, at 6 p.m., 
the temperature rose to 104.8°; pulse 146; no delirium; no evi- 
dence of sepsis. 
October 19th, 9 a.m., the child’s condition seemed the same; 
eruption was more defined, covering the face, back, extremities, 
and abdomen. The temperature in the evening again rose to 
104.6°. 
October 20th, the child’s condition is bright; temperature, 
103.40; pulse, 124; the throat intensely congested; two small 
necrotic patches can be seen on the left tonsil, a culture on blood 
serum showed staphylococci and streptococci. 
October 21st, 9 a.m., the temperature being still 102.6°, an- 
other injection of 10 c.c. of serum was given. I left my ther 
mometer with instructions to take temperature. Two hours 
later (at 11 a.m.), I saw her; the temperature remained 102.6°. 
On the evening of the same day, I saw the child again, the tem- 
perature was 104°; pulse, 134. 
October 22d, temperature in the morning, 101.3°; pulse, 
118; 6 p.m., same day, temperature was 102.6°; pulse, 102. 
October 23d, temperature 9 a.m., 101°; pulse, 98; 6 p.m., 
100.6°; pulse, 90. 
October 24th, 9 a.m., temperature, 100.4°; pulse, 94; 6 p.m., 
99.4°; pulse, 96. 
The Eruption.—During the course of the disease, the erup- 
tion seemed to gradually spread, and remained at its height 
covering the whole body for three days, from the 19th until the 
22d. It then began to fade, and on the 23th appeared like small 
erythematous patches scattered over isolated areas of the body. 
It seemed to me that in this case the eruption was not influenced 
by the injections used. The urine showed slight traces of al- 
bumen during the first week of the disease. During the second Fischer : *Anti-Streptococcus Serum. 
4 
week the urine contained two pro mille of albumen, but showed 
no casts. 
The child desquamated profusely; post-scarlatinal nephritis 
continued for some time, with oedema of face, feet, and hands. 
The urine was not very scanty, however. 
The child received some iron and decoction of cinchona 
bark, and made an uneventful recovery. 
In the London Lancet, March 19, 1896, Harold Low reports 
a case of scarlet fever complicated with acute suppurative otitis 
media, and acute hemorrhagic septicemia treated by anti-strep- 
tococcus serum. 
Low reports a case of scarlet fever in which, on the fourth 
day, pain in the ear developed, followed within twenty-four 
hours by a discharge. Two days later there was evidence of 
mastoid suppuration, and when the antrum was opened a con- 
siderable amount of pus was discharged. This was followed 
by drowsiness, irregular temperature, and some jaundice. A 
diagnosis of septicemia was made, and injections of anti-strep- 
tococcus serum were at once commenced. The patient’s con- 
dition for a time grew worse, then improved, the jaundice dis- 
appeared, and finally recovery ensued. Before this was com- 
plete, however, the patient had several attacks of epistaxis and 
a severe purpuric eruption. A bouillon-culture of the blood, 
made before the commencement of the treatment, showed the 
presence of the streptococcus. Altogether 263 c.c. of serum 
were used. 
In a series of fifty-seven cases published by Prof. A. 
Baginsky, in the Berlin Clin. Weekly of 1896, No. 16, nine cases 
must be excluded, as the treatment was not satisfactory, having 
been discontinued or otherwise; the other forty-eight cases are 
divided into several groups. 
In twenty-seven of these cases, the result was an exception- 
ally good one. In these twenty-seven there were no complica- 
tions encountered. In four of these latter cases, after the 
injections of the serum, there appeared a mild form of nephritis. 
In another case a suppurating form of otitis, and two other 
cases showed a severe angina, and a severe painful glandular 
swelling. 
A point worth noting was the fact that after the injections, 
and within the next two or three days following, the tempera- 
ture was suddenly reduced. The angina encountered term- 
inated favorably in all of his series. Fischer: zAnti-Streptococcus Serum. 
5 
Albuminuria was met but rarely, and in only one case could 
nephritis be suspected. 
The author warns against accepting too hasty deductions 
from his reported experiences with severe forms of nephritis, 
because he has found that these latter conditions occur less often 
in hospital practice than in his private cases. This he attributes 
to a strict milk diet, and better hygienic conditions. 
In another group of seven cases, the author reports the 
lethal ending of the same, owing to various complications. 
The author believes that the serum might have been used in a 
much larger dose, and that possibly some benefit could have 
been deprived from the same. 
In another series of cases, in spite of a large number of 
injections, and a sufficient quantity of the same, there was no 
appreciable benefit, although all cases recovered. 
In the other seven cases, severe complications ensued, and 
the author believes he did not have enough of the remedy to 
give it in proper doses. 
In five other cases, the serum was used to modify special 
complications. In one of these cases it did not seem to have 
any influence, and the child died. The four others recovered. 
The mortality was 14.6 per cent. The mortality in the hos- 
pital has ranged in the last year from 22.6 per cent, to 34.3 per 
cent. 
The author refers to the fact that the scarlet fever mortality is 
subject to periodical changes, and, therefore, does not show posi- 
tive deductions to be drawn from the above quoted figures. 
He does not, however, find the course of children treated 
with serum any worse than otherwise. The after-affects were 
in no wise different from those noticed during the treatment 01 
diphtheria with antitoxin. He still continues the use of the 
same Marmorek’s serum. 
In the Medical Record, March 14, 1896, Dr. Berg, speaking 
of the treatment of pneumonia as a complication of diphtheria, 
describes at length the anti-steptococcus serum, and its applica- 
tion to the various diseases known to be caused by these micro- 
organisms. 
Dr. Alexander Marmorek (Annales de Pasteur, July, 1895), 
states the belief that different forms of streptococci are varieties 
of a single microbe. Thus, Marmorek believes that Fehleisen’s 
erysipelas streptococcus cannot only produce erysipelas, but 6 
Fischer : z/Inti-Streptococcus Serum. 
when sufficiently virulent, can produce meningitis, pneumonia, 
abscess, septicaemia. It certainly depends upon the point of 
entry into the body, as to what disease shall be produced, plus 
the degree of virulence contained in this streptococcus. 
Berg, describing the method of producing the anti-strepto- 
coccus serum, states that the ideal serum will be that obtained 
from animals immunized against streptococci infinitely more 
virulent than any to the action of which man can by any possi- 
bility become subject. 
We have thus far succeeded in producing an anti-strepto- 
coccus serum, but not a streptococcus antitoxin, the animals 
having been immunized against the streptococcus germ, and 
not against the toxin produced by the streptococcus. 
The attempt has been made to immunize horses to the toxin 
produced by the streptococcus, but it is very difficult to obtain 
a toxin sufficiently virulent to be of any use in immunizing 
horses. 
At the time of publishing his article, Berg stated that the 
New York Health Department was engaged in the production 
of an anti-streptococcus serum, and does not, therefore, report 
any clinical results with the same. I have learned, however, 
that since that time, Dr. J. Winters Brannan and Dr. Berg have 
used this serum at the Willard Parker Hospital. 
The following three cases 1 owe to the courtsey of Dr. Sig. 
Cohn, the first of which I had the pleasure of seeing with him 
once. 
A child, Rosy, four years old, was sick three to four days 
prior to Dr. Cohn’s first visit. When he first examined the 
child he found a decided case of scarlet fever and angina nec- 
rotica. 
Culture from this case sent to the New York Health Depart- 
ment showed K.L.B. and streptococci. At the request of Dr. 
Cohn, the Inspector of the Health Department injected the child 
with antitoxin; quantity unknown. 
The temperature ranged from 104° to 105°. The throat 
symptoms increased, and as the child’s general condition did 
not improve, the doctor decided to try an injection of 10 c.c. of 
anti-streptococcus serum. 
At this time 1 saw the child with Dr. Cohn. We secured a 
nurse, and irrigated the nose with a solution of boracic acid. 
The child’s temperature went down to ioi° between two to 
three days after the injection of anti-streptococcus serum. Sev- 
eral days later the child again grew worse, the temperature Fischer: *Anti-Streplococcus Serum. 
7 
went higher, and Dr. Cohn gave another injection of 8 c.c. of 
anti-streptococcus serum. This was followed by no improve- 
ment. 
After the scarlatinal eruption faded, a new eruption resem- 
bling measles, appeared three days following the second injec- 
tion of anti-streptococcus serum. The urine, which was care- 
fully examined, did not show any traces of albumen nor casts. 
The child died of heart failure and collapse. 
The second child in this family was five years old; showed 
an eruption of scarlet fever and angina necrotica, also received 
an injection from the New York Health Department of diphthe- 
ria antitoxin. As there was no improvement following this in- 
jection, the child was also injected with io c.c. of Marmorek’s 
anti-streptococcus serum. This was followed by no reaction, 
nor any decided improvement directly attributable to the serum. 
This child recovered. 
The third child, a baby one year old, had a very mild scarla- 
tinal eruption; did not show any angina. In fact, the throat 
appeared normal. This child was not injected with anti-strep- 
tococcus serum, and the case recovered very easily with no 
complications, and no sequela. These children were attended 
about three months ago. 
A case of erysipelas attended by Dr. Sig. Cohn, and which 
was not seen by me, was between three to four years old. It 
was sick but a short time before the doctor’s first visit. The 
little patient had a typical erysipelas flush on the lower extremi- 
ties; this gradually extended to the abdomen, and then to the 
back. The doctor used lead and opium wash externally, fol 
lowed later by an ointment of ichthyol. Not finding any 
improvement, and finding that the erysipelas had spread alarm- 
ingly, the temperature at this time being 104°, the doctor 
injected at 6 p.m., 8 c.c. of anti-streptococcus serum. 
The following morning the temperature was normal; the 
erysipelas faded and gradually subsided. No other treatment 
was used, and the child recovered very rapidly. 
Schenk (Central Blatt filr Barter iologie, page 170, Band 
xxiii., Part 111.), treated in the State Institute, and reported in 
the Vienna Klin. IVochen, 28th of October, 1898, four animals 
(three horses and one mule), according to Marmorek. They 
received increased doses of streptococcus serum. The animals 
had previously received injections of diphtheria toxin. The 
animals all tolerated the poison well, and were able to with- 
stand the poisonous effects of living cultures. 
One animal withstood 200 c.c. without any after-effects. 
After ten months’ treatment, the serum of these animals was 
tested for their therapeutic value. 8 
Fischer: Serum. 
Sixty rabbits were injected with 0.1-5 c.c.m., and twenty 
hours later injected with one hundred times the usual poisonous 
dose of toxin. 
Although the animals so previously injected showed a simi- 
lar mortality, 36 per cent, against 11 per cent, of controlled 
animals, still this author could not arrive at any positive deduc- 
tions from the amount of poison injected or the amount of 
prophylactic serum used to control or neutralize the poison. 
His results are the same as those of Petruschky, and ques- 
tions the value of the serum made according to the method 
of Marmorek. Still poorer were the healing results with this 
same serum, for out of twenty-one rabbits thus treated, nine- 
teen died. 
The following case of a baby, K., one year old, female, was 
feverish and restless for about two days, when Dr. Aronson was 
called. According to the family the doctor did not make a diag- 
nosis, as the disease was not properly developed. 
On the third day of the child’s illness, Dr. Berger was called 
and diagnosed the case as erysipelas. On the fourth day of the dis- 
ease the child grew worse. The disease spread very rapidly, and 
there was a marked rise in the temperature. The doctor had 
used ichthyol ointment locally with no apparent benefit. 
On the fifth day of the child’s illness, Dr. Henry M. Groehl 
was called in, and found a very well marked case of erysipelas, 
involving the both lower extremities, and spread from there to 
the back, covering the same, and over the abdomen. The tem- 
perature at the time of his first visit was 104.20; the child was 
very restless. He ordered locally lead and opium wash to cool 
the surface, and internally he gave calomel and phenacetine with 
sparteine. 
The following day, the sixth day of the child’s illness, Dr. 
Groehl found the child much improved. The mother stated that 
it had rested well; the child would sit up and play. The tem- 
perature had fallen to 990; the pulse was good. 
The erysipelas flush was not spreading; the color was not 
so red, and some areas of the skin had lost the hard and elevated 
thickened induration. The child was in every way greatly im- 
proved, and was nursed by its mother, taking the breast with 
evident relish. 
The seventh day of the child’s illness, there was a marked 
change for the worse. The temperature still remaining at 990; 
the pulse was rapid and feeble; there was continuous vomiting. 
The inflammation had suddenly spread from the abdomen to the 
chest, almost completely covering the child. The child’s ap- 
pearance was decidedly septic. The child vomited long after all Fischer: zAnti-Streptococcus Serum. 
9 
drinks; the mouth had been stopped. In fact, long after rectal 
feeding had been commenced, the vomiting persisted. 
On the eighth day of the child’s illness, Dr. Louis Fischer was 
called in consultation, and after going over the history of the case 
and the treatment pursued, recommended injections of io c.c. of 
anti-streptococcus serum. This was injected in the usual aseptic 
manner, just as we inject antitoxin, on the morning of the 
eighth day of the child’s illness. On the evening of the same day 
that the injection was given there was no reaction. The child 
continued the same. 
The following day, about three hours before the exitus le- 
ihalis, the body was covered with ecchymotic spots. The var- 
ious parts of the body were covered with discolorations; some 
of them resembled the colors of the rainbow. 
Two very instructive cases are the following: 
A child seven years old, complained of nausea and vomiting 
quite freely. The mother, believing the child had a disordered 
stomach, gave her some citrate of magnesia, which had quite a 
marked laxative effect. 
The following day the child complained of intense headache, 
and being very feverish and thirsty, was put to bed, and a phy- 
sician sent for. On examining the child he found the body 
covered with a distinct scarlatinal eruption. He ordered spir. 
mindereri; a teaspoonful every two hours, and a liquid diet. 
The next day he injected io c.c. of anti-streptococcus serum. 
The temperature was between 103° and 104°; the exact meas- 
urement not noted. 
The next day, finding the child’s headache still persisted, and 
the general condition not improved, he again injected 10 c.c., 
and continued to inject every day for seven successive days 10 
c.c., until 70 c.c. had been used. 
The temperature ranged from 105° to 106° in the evening 
during the second week of the child’s illness, and from 103° to 
104° every morning. 
When I saw the child, at the request of the family, I found a 
condition of general furunculosis on the back, and in the axillae 
on the shoulders, over the left patella. The family objected most 
strenuously to incising the furunculosis, and thus these furuncles 
were allowed to open spontaneously. 
The urine was very turbid, high colored and loaded with al- 
bumen. On boiling the same it almost coagulated in the test 
tubes. There were also casts found on microscopic examina- 
tion. The child suffered from a continuous diarrhoea, which bis- 
muth and injections of laudanum with starch would not control. 
The throat showed small areas of necrotic scarlatinal pseudo 
membrane, and there was quite some discharge from the nose. 
There was also a purulent ophthalmia, the eyes being glued to- 
gether when the child dozed. There was a constant stupor, 10 
Fischer: <•.Anti-Streptococcus Serum. 
and the child seemed to be drowsy. The nose was pinched; 
there was an intense thirst all the time, and continuous cough, 
which had appeared when I first saw the child, and which we 
first thought resembled pertussis, proved later, on careful physi- 
cal examination to be an empyema. The child died in a condi- 
tion of most profound sepsis several days after the aspiration of 
the purulent effusion. 
The family objected to the operation of empyema. During 
the course of this child’s treatment, an older child (nine years) 
which had been exposed and was now isolated, contracted the 
disease, the mother calling our attention to the persistent vomit- 
ing and sore throat. In this case 1 used quite some diplomacy 
in order to convince the attendant that 1 did not believe anti- 
streptococcus serum could do any good. In fact 1 advised him 
that if he would again inject the second child, that I would with- 
draw from the case. As the family insisted on my continuing to 
attend the child with the attending physician, we used carbo- 
lated vaseline inunction, and the usual expectant plan of treat- 
ment, treating symptoms as they arose, giving an iron and glyc- 
erine gargle, and although this child suffered with a nephritis for 
six weeks, it made an uneventful recovery. 
In an elaborate paper on pneumonia complicating diphtheria, 
H. W. Berg (lMedical Record, March 14, 1896), suggests the 
practicability of using anti-streptococcus serum in this disease. 
W. H. Park (The W. M. Carpenter Lecture, 1897), states that 
the rapid deterioration of serum in vials may account for the ab- 
sence of curative powers in the serum. He further says, that the 
preparations of anti-streptococcus serum now on the market are 
either quite weak or entirely wanting in curative substances. 
Van de Belde, (‘Pediatrics, Vol. 4, Nos. 9 and 10, 1897, 
Arch, de (Med. Exper.) studied the question as to the protective 
value of the anti-streptococcus serum prepared from one variety 
of streptococcus, and to see whether it was equally protective 
against other streptococci. Selecting two varieties, one obtained 
from a sore throat, the other from a case of puerperal septicaemia, 
he tested the effects of their respective sera. His conclusions were, 
that the serum of one variety was only curative against that same 
variety of streptococcus. Thus, a serum made from a strep- 
tococcus in puerperal septicaemia was only protective against 
this same disease. 
Steele (‘British (Med. Journal, Oct. 3, 1897), reports twenty- 
six cases of puerperal septicaemia where serum was used. 
There were sixteen recoveries; ten died. He says there are so 
many other causes for transatory rise of temperature during the Pages 11-12 missing FROM 
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