Pneumococci, Types I (10 per cent.), II (14 per cent.) and
III (6 per cent.) 30 per cent.
Pneumococci Group IV and the allied
green-producingdiplostreptococci described 30 per cent.
Hemolytic Streptococci 20 per cent.
Staphylococcus Aureus 10 per cent.
Influenza bacillus 10 per cent.
Most of the vaccine was distributed within a radius of 200 miles of
Rochester, Minn., but samples were furnished to physicians all over the
country, who agreed to return statistics on its use. No evidence was
found that this vaccine caused a temporary break in the resistance of
the user. Out of a total of 20,972 persons vaccinated, 14.6 cases of
influenza, 1.8 cases of pneumonia, with 1.8 mortality, occurred per
thousand in the six weeks following vaccination. As controls, he took
“such persons in institutions, colleges, factories and communities where
vaccine was used, and included only those reports which contained
accurate data as to the incidence and mortality among them.” Among
61,753 such controls he found 229 cases of influenza, 15.7 cases of
pneumonia and 3.4 deaths per thousand. He concluded from his results
that “it appears possible to afford a definite degree of immunity by
prophylactic inoculations to persons against the more serious
respiratory infections during the present epidemic.” It is quite
difficult to agree with Rosenow in his interpretation of the figures as
presented by him, inasmuch as he made no allowance for the stage of the
epidemic at which vaccination was carried out, either among the
vaccinated or the non-vaccinated. Such a comparison would be well nigh
impossible where the vaccine was sent in varying quantities to such a
large number of places.
4. League Island Report (22). Vaccines were used as a preventive in 50
persons, most of whom were hospital apprentices and in the wards 12 to
15 hours a day. Other precautions were used, such as masks, but not a
single case developed in the group. The vaccine was used as a curative
agent in 50 uncomplicated cases; none of the patients injected early
developed pneumonia.
5. Puget Sound Navy Yards Report (23). The vaccine used at this station
was made from hæmolytic streptococci, no other organisms being used;
4,212 men were vaccinated, and not one died from influenza. Among 111
Philippinos isolated and vaccinated there occurred only 2 cases. Among
361 marines vaccinated early there occurred 2 cases. Among 62 marines at
the ammunition depot who were vaccinated early there occurred 3 cases,
only 1 of which occurred after completion of vaccination. Among 662
bluejackets at Seattle Training Camp only 10 men developed the disease.
Among 83 at the aviation corps there were 32 cases—31 of them developed
the disease within a few hours after the first injection. There were no
deaths in any of the above groups. The period of observation was closed
on October 21, and so few cases of influenza appeared subsequent to that
date that it seemed that the epidemic was practically over at the time
the data was obtained.
6. Kitano (24) used a vaccine for prophylaxis containing 0.2 m.g. of
Pfeiffer bacilli per c.c. on 10,300 persons with encouraging results. He
used vaccine for treatment on 87 patients, without any deaths. In the
same group were 270 cases treated in the usual way, with 23 per cent.
mortality. The vaccine lessened the severity, shortened the period of
illness, and lowered the mortality.
7. Wynn (25) used mixed vaccines in the treatment of influenza, and
believed they aborted the disease if given early.
8. Norman White (26) states that vaccination in India would be
impractical, because the disease is so brief and severe that it would be
over before innumerable doctors could complete inoculations.
9. Whitingham and Sims (27) reported the use of a mixed vaccine in an
institution where 156 were inoculated and 149 were not. The case
incidence was 5 per cent. among the vaccinated and 12 per cent. among
the controls. No statement of the stage of the epidemic at which
vaccination was done is mentioned in the report.
10. Cadham (28) reported on inoculations in a military hospital and in
the civilian population near Winnipeg. Of 282 vaccinated soldiers
admitted to the hospital, 17 had pneumonia and 5 died. Of 238 not
vaccinated, 41 had pneumonia and 17 died. Among 24,184 civilians given
two doses, 9.7 per cent. had influenza and 0.5 per cent. had pneumonia
and 0.09 per cent. died. Among 85,941 controls, 24.8 per cent. had
influenza, 2.2 per cent. pneumonia and 0.66 per cent. died. Cadham
states that most of the inoculations were made early in the epidemic,
but no accurate statistics were kept on the point.
11. A conference was held at the British War Office on October 14, 1918
(30), to discuss prophylactic vaccination and vaccines for treatment of
influenza. Elaborate plans regarding dosage and gathering of statistics
were made.
NOTANDA.—For reasons already given, the reports in Series III fail to
give very reliable data on which to base a knowledge of the value of
preventive vaccination against epidemic influenza.
_The Attempt to Prevent Pneumonia as a Complication of Influenza Through
the Use of Lipovaccine_
Whitmore, Fennel and Peterson (31) developed a method of preparing an
oily suspension of killed bacteria which they called “lipovaccine.” The
method was used at first in making typhoid and dysentery vaccines. The
advantages of lipovaccines (32) over salt suspensions are: the
prevention of autolysis of the bacteria, thus increasing the length of
time during which the vaccine remains active; the slow absorption of the
dose, allowing the patient to continue to absorb immunity-producing
substances over a period of days or weeks; the administration of a
single massive dose, which does away with the three doses necessary when
salt suspensions are used; and perhaps, also, the direct reduction in
the toxicity of the dose by the lipoid material.
Based upon the classification of pneumococci by Dochez and Gillespie
(33) in this country, and by Lister (34), (35), (36) in South Africa,
and upon the latter’s successful use of anti-pneumonia vaccine on the
Rand, an anti-pneumonia lipovaccine was prepared at the Army Medical
School which contained approximately 10,000,000,000 each of types I, II
and III pneumococci. The vaccine was made by growing the pneumococci in
dextrose broth, centrifuging them out of the broth with a sharpless milk
centrifuge, drying the sediment at 55° C., weighing it out so that each
cubic centimeter of the finished vaccine contains 0.83 m.g. of each
type, and making a suspension of them in olive oil. More recently
cotton-seed oil has been used.
The result of the use of a salt suspension pneumococcus vaccine at Camp
Upton was published by Cecil and Austin (37). A study of the
agglutination and protective power of the serum of 42 persons vaccinated
against pneumococcus types I, II and III demonstrated that a definite
immune response could be secured to types I and II but not to type III.
Twelve thousand five hundred and nineteen men were vaccinated at the
camp, and most of the men received three or four inoculations at
intervals of from five to seven days. The men were under observation for
ten weeks, and during that time no cases of pneumonia of the three fixed
types occurred among those who had received two or more injections. In a
control of approximately 20,000 men there were 26 cases of pneumonia of
types I, II and III. The incidence of pneumococcus type IV pneumonia was
less among the vaccinated than among the unvaccinated groups. There
were, however, 17 cases of pneumonia among the vaccinated men, compared
to 173 cases of pneumonia among the controls. The annual pneumonia death
rate for vaccinated groups in the army was 0.83 per one thousand, and
for unvaccinated groups was 12.8.
Fennell reported the use of pneumo-lipovaccine in Washington during the
influenza epidemic, but the number of cases cited by him were too small
to permit of definite conclusions. His results appeared favorable.
Cecil and Vaughan (37a) reported on the results of vaccination with
pneumo-lipovaccine at Camp Wheeler; 13,460 men, comprising 80 per cent.
of the camp, were inoculated. Most of these men were under observation
for 2 or 3 months after vaccination, and there occurred among them 32
cases of pneumococcus types I, II and III pneumonia. In one-fifth of the
camp which was not vaccinated there occurred 43 cases of pneumonia. They
observed that influenza caused a marked reduction in the resistance to
pneumonia among vaccinated as well as non-vaccinated men. Of 155 cases
of pneumonia of all types, which developed one week or more after
vaccination, 133 were secondary to influenza. The death rate among
vaccinated men one week or more after vaccination was 12.2 per cent.,
whereas the death rate for 327 cases of all types of pneumonia which
occurred among unvaccinated groups was 22.3 per cent. The death rate for
primary pneumonia among vaccinated groups was 11.9 per cent., and among
unvaccinated 31.8 per cent. It was found that protective bodies do not
begin to appear in the serum after lipovaccines are given until the
eighth day after the injection. Twenty-four cases of pneumonia occurred
in the first week after vaccination. In their conclusions Cecil and
Vaughan state that there was no evidence whatever that pneumococcus
vaccine predisposed the individual, even temporarily, toward either
pneumococcus or streptococcus pneumonia. Most of the reactions after
vaccination were mild, but one disagreeable feature was that in a
certain percentage there persisted a small fluctuating mass at the site
of the injection. Lacy saw a number of these cysts aspirated, and the
contents were found to be a sterile, oily fluid, with many leucocytes
present. In one instance the primary reaction disappeared within a few
days after vaccination, but recurred after four months and persisted for
several weeks.
NOTANDA.—The army lipovaccine apparently offers a certain definite
amount of protection against pneumonia, which was the most dangerous
complication of influenza. The protective substances do not appear in
the serum until eight days have elapsed after the vaccination, and while
no definite evidence has appeared to show that there is a temporary
increase in susceptibility immediately after vaccination, the best
results would undoubtedly be obtained where the dose is given something
more than eight days before the appearance of the epidemic. The
indications are that the vaccine will not protect against influenza, but
that the complication of pneumonia is less likely to occur in the
vaccinated than in the unvaccinated individual.
_Summary_
Records of attempts to confer immunity to influenza by the use of
vaccines have been separated into related groups and studied. Those
where pure Pfeiffer strains were used have been considered in one group.
Those where mixed vaccines were used have been analyzed in three
sub-groups or series, depending on the relation between the times of
vaccination and of the advent of the epidemic, upon whether or not a
week-by-week comparison of the occurrence of influenza among vaccinated
and unvaccinated groups was made, and upon whether or not statistics for
total comparison alone were available. The third group included the
reports of the use of army pneumo-lipovaccines for the prevention of the
secondary pneumonia complications of influenza.
_Conclusions_
From our statistics we conclude that:
1. There is as yet no evidence that vaccines composed purely of strains
of Pfeiffer bacilli will confer immunity to epidemic influenza.
2. The only data which can be used as a basis for estimating the value
of mixed vaccines as a preventive for epidemic influenza must be
obtained from experiments in which vaccination was either completed
before the epidemic appeared, or in which week-by-week comparisons
between the number of cases occurring in the vaccinated and unvaccinated
groups can be made.
3. Data obtained from experiments conducted under the above
qualifications is inconclusive, but presents little evidence of the
value of mixed vaccines in protecting against influenza. There is,
however, an indication that mixed vaccines used prior to the arrival of
the epidemic will lessen the number and the severity of secondary
pneumonias, and will probably lower the death rate to a small degree.
4. The army pneumo-lipovaccine apparently offers some protection against
primary infections with types I, II and III pneumococci, and a somewhat
lesser amount of protection against secondary pneumococcic infections
with these strains following influenza.
5. While it is impossible to say that the large number of influenza
cases developing almost immediately after vaccination would not have
occurred anyway, it is at least suggestive that a temporary break occurs
in the resistance after the inoculation, and that unusual care should be
taken by persons who have been recently vaccinated, particularly when
they are in the midst of an epidemic disease.