REPORT 
of 
Dr. F. A. Coward 
Director of Laboratory 
State Board of Health 
On Anti-Typhoid Vaccine , 
Lot 67. 
1916 
J. T. McCaw 
Columbia, S. C. REPORT OF DR. F. A. COWARD, DIRECTOR OF 
LABORATORY, STATE BOARD OF HEALTH, 
ON ANTI-TYPHOID VACCINE, LOT 67. 
Dr. James A. Hayne, State Health Officer and Secretary, 
State Board of Health, Columbia, S. C. 
Dear Sir: 
I herewith submit the following report of investigation 
into the circumstances surrounding the recent deaths of 
children, following the administration of typhoid vaccine. 
Summary of Cases. 
Four cases have been reported to this laboratory as fol- 
lows-the full statement of attending physicians being 
attached to this report: 
Case No. 1.-Age 2^ yrs. Quantity given 2 minims (?) 
Summary of Symptoms: Inoculated at 11 A. M. 
Fever during night, after IIP. M. At 6 A. M. began 
to have nausea, vomiting, and marked cyanosis and 
intestinal paresis. Gradually grew worse, coma and 
convulsions supervened death in 31 hours after inoc- 
ulation. 
Case No. 2.-Age 4(4 yrs. Quantity given, 3 minims (?) 
Summary of Symptoms.-Inoculated at 11 A. M. At 
6 P. M. became nauseated, vomited, cyanosed. Coma- 
tose at 4 A. M. Convulsions, marked cyanosis, and 
intestinal paresis. Death in 19 hours after inocula- 
tion. 
Case No. 3.-Age 9 months. Quantity given, 10 minims. 
Summary of Symptoms: Inoculated at 4 P. M. Cyan- 
otic on morning after inoculation, when first seen. 
"Gradually grew worse and died at 4 P. M., 23 hours 
after inoculation." Case No. 4.-Age 4^ yrs- Qauntity given, 3 or 4 minims. 
Summary of Symptoms: Awoke nauseated at 1 A. 
M., fever 104, vomiting and diarrhea. Improved after 
above discharges, and slept until morning. Came 
down stairs and seemed better. Drank milk at this 
time. Later became mere nervous, diarrhea returned 
at noon. Cyanotic at 2 P. M., pulse 160, unconscious. 
Convulsions at 4:30 P. M. Died at 5 P. M. 
No autopsies were obtained. 
The family history was without interest in cases No. 1 
and No. 2. No history was given for case No. 3. Father 
of case No. 4 died of "Interstitial Nephrites and arterio 
sclerosis, probably luetic." No history suggesting asth- 
ma, enlarged thymus, status lymphaticus, urticaria, pro- 
tein idiosyncrasy was given in any case. 
Vaccine Used. 
The vaccine was in each case from the same lot, pre- 
pared by the method which has been in use in this labo- 
ratory since August, 1911. It was found sterile by all 
the usual tests, up to the time of bottling, and was stored 
in the refrigerator while in the laboratory. It was not 
tested on guinea pigs. As will be seen later in the report 
this test would not have given warning of the trouble. 
Practically all of this lot of vaccine had been used when 
the trouble was reported, but unused portions were ob- 
tained from two physicians, one being the physician in 
charge of cases No. 1 and No. 2. 
The parents of these children were inoculated from the 
same lot at the same time, by the same physician. They 
had moderate reactions. Two other children were inocu- 
lated at the same time as case No. 3. They •'had severe 
symptoms, high temperatures, swelling of extremities 
and mucous membranes, convulsions and a dark red rash. 
Two other children under five, and three over five, also 
several adults were inoculated from the same lot by the. 
3 physician in charge of Case No. 4. None of them had 
severe reactions. 
A report was requested from every physician who had 
used any of this lot of vaccine. A summary of their re- 
ports, received to date is attached. They may be con- 
densed as follows: 
Number of persons inoculated 322 
Under 5 years of age 37 
No reaction 10 3.1% 
Usual reaction 244 75.7% 
Severe reaction 68 21.1% 
Abscesses 26 
Deaths 4 
All deaths were in children under 5 years of age, but 
several physicians reporting severe reactions state that 
adults were more affected than children. 
Tests of Vaccine. 
The unused portions of vaccine used in cases No. 1 and 
No. 2 was tested by aerobic and anaerobic culture. There 
was not sufficient material for animal test. Five ampuls 
of vaccine from the same box were also cultured as above, 
and portions also used for animal inoculation. All cul- 
tures showed the presence of staphylococcus pyogenes. 
Four guinea pigs were inoculated with vaccine from this 
box, receiving .5 c.c., 1.0 c.c,, 1.5 c.c. and 2.0 c.c. respec- 
tively. None showed any symptoms except the pig re- 
ceiving 2.0 c.c. which became sick and drowsy at the end 
of 72 hours and died during the night of the fourth day. 
Autopsy showed nothing abnormal except marked con- 
gestion in the region of the subcutaneous inoculations. 
Cultures from lung, liver, kidney and spleen were nega- 
tive except for organisms of the B. Coli type; this owing 
to unavoidable delay of over 15 hours before autopsy 
could be performed. As the dose of vaccine received by 
this pig is equivalent to more than one pint for an adult 
man, the death of this pig is not conclusive. 
4 Five ampuls of the same lot of vaccine, (but which had 
given no severe reactions), were obtained from another 
physician, and tested by culture. All tubes remained 
sterile. Stained smears and hanging drop frcm the ques- 
tionable vaccine showed bacilli corresponding to B. ty- 
phosus ,and cocci in pairs and groups. Several vials and 
stoppers, taken at random from containers in which they 
had been sterilized by the usual process, were cultured by 
aerebic and anaerebic method. All were found sterile. 
Conclusions. 
The entire lot of vaccine No. 67 was not contaminated, 
therefore contamination must have occurred in the bot- 
tling. The usual habitat of staphylococcus pyogenes 
points to the hands of someone as the source of infection. 
The rubber stoppered vials were adopted in the hope of 
making the vaccine more easily opened by the physicians, 
but the filling and stoppering of such vials offers too 
many chances for hand contamination, and must be aban- 
doned. 
The cause of death in the four cases is obscure. The 
staphylococcus should be expected to produce local abs- 
cesses, and did so in many cases, but the rapid and vio- 
lent symptoms, cyanosis, dilated heart, etc., are not those 
of a progressive local or general infection. It is my opin- 
ion that death was due to protein poison. 
Two explanations might be suggested. 
First, The growth of staphylococcus in the vaccine, 
aided by the high temperature prevailing at the time, and 
the inability of the physicians to keep the vaccine on ice, 
caused too high a total bacterial content, so that the re- 
sult was that of an overdose of pure vaccine. 
or Second, Growth of staphylcoccus produced lysis < f 
the dead typhoid bacilli, with consequent protein splitting, 
the results being that the entire mass of typhosus endotox- 
in was ready for immediate absorption when injected, in- 
5 stead of being prepared by the gradual process of paren- 
teral digestion. The fact that the symptoms came on at 
the usual time for the normal reaction, however, inclines 
me to accept the first theory. 
A copy of the instructions sent out with the vaccine 
is attached to this report. Several of the physicians' re- 
ports indicate that our splendid results in the past have 
caused some relaxation from a strict observance of these 
rules. As no previous ill effects have been reported from 
these men it is not likely that this was a factor in the re- 
cent catastrophe, but it seems wise to emphasize the point 
at this time. In each case where death occurred there 
may be noted circumstances which might possibly be con- 
sidered contributory causes. Cases No. 1 and No. 2 were 
well during the afternoon and went a mile or more to a 
village, where they are said to have eaten fruit or ice 
cream. Case No. 3, a child nine months of age, was given 
ten minims of vaccine-the proper dose for 100 pounds 
of body weight. 
Case No. 4 was a delicate child who had a bowel infec- 
tion at the time of inoculation. 
Other physicians have been retaining unused portions 
of vaccine for future use, by replacing the stoppers in 
vials. A return to the sealed ampuls will, of course, 
make this impossible. 
It has been reported to this office that some physicians 
have been giving the three doses of vaccine all in one 
week, but this has not been personally verified by me. 
These criticisms are not intended in any way as an ef- 
fort to shift the blame from the laboratory, or to ob- 
scure the facts that only this contaminated vaccine had 
ever caused trouble, while the above errors have been 
possibly habitual and without bad results, but the pres- 
ent seems an opportune time to call attention to them. 
We were unaware of many of them up to this time. 
6 Inoculation of guinea pigs with ordinary doses is not 
sufficient to prove the safety of the vaccine. The proper 
lethal dose will be worked out by us. This, together with 
the results of further investigation, will be reported sub- 
sequently, but we feel that this report should not longer 
be delayed. 
Finally, it is evident that the principle and practice of 
protective inoculations is in no way discredited by the 
deplorable accident. 
Whatever can be said by criticism can only be directed 
at the failure of technic to produce and administer a pure 
vaccine; the first such failure during four years of the 
work. Pure vaccine, properly administered, has proved 
its value in our State as it has elsewhere, wherever it has 
been used. 
Respectfully submitted, 
F. A. COWARD, M. D., 
Director of Laboratory. 
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