IMMUNITY.
Opinions of all observers who have studied in detail the question of
immunity in influenza are remarkedly in accord. The conclusions reached
by Parkes in 1876 are valid today, and form as excellent an abstract of
our present knowledge as any produced since his time. “There is some
discrepancy of evidence, but, on the whole, it seems clear that, while
persons seldom have a second attack in the same epidemic (though even
this may occur), an attack in one does not protect against a subsequent
epidemic. Indeed, it has been supposed rather to render the body more
liable.”
In 1890, Abbott wrote: “There is but little if any evidence in support
of the protective power of one attack to confer immunity against a
second; and hence adults are not exempt, as they usually are in
epidemics of scarlet fever or other exanthemata; so that the proportion
of adults to children attacked in an epidemic is necessarily greater
than that which is observed in epidemics of other infectious diseases.”
Parsons made somewhat similar observations: “One attack of influenza
does not seem to be protective against another; the disease in this
respect resembling diphtheria, erysipelas, and cholera rather than
smallpox, measles, or whooping cough. The duration of the epidemic in a
locality is so short that it is difficult to distinguish between second
attacks properly so-called, and relapses, which are frequent enough. A
case is recorded in the ‘British Medical Journal’ of February 15, 1890,
in which a patient who had suffered from influenza in France in
December, 1889, had another attack in England in January, 1890. It was
noticed in 1837 that many persons suffered from influenza who had had
the disease during the previous epidemic in 1834. The shortness of the
interval between these two epidemics, as compared with that between 1848
and 1889, seems to show that the periodical return of the disease in an
epidemic form does not depend upon the accumulation in the interval of
susceptible individuals unprotected against the disease by a previous
attack. If one attack afforded protection against another a large
proportion of the population in 1837 must have been protected, yet an
epidemic occurred, and on the other hand for many years before 1889 a
large majority of the population must have been unprotected by a
previous attack, yet the epidemic did not recur.
“The persons now living who passed through the disease in 1847 are of
course comparatively few, but such persons have not been exempt from the
present epidemic.
“I should be inclined to attribute the short duration of the influenza
epidemic in a locality to the establishment of a tolerance for the
specific poison among the persons exposed to it, similar to the
tolerance for dust possessed by workmen in rag factories, as mentioned,
but which is soon lost on their ceasing to be exposed to it, rather than
to a true immunity being established.
“Relapses in influenza are of frequent occurrence; they occurred in 9.2
per cent. of the cases at the Morningside Asylum, Edinburgh, and in some
cases indeed a second relapse has been recorded. The time at which the
relapse occurs is usually from a week to a fortnight after the primary
attack, and it can often be distinctly traced to an exposure to cold, or
return to work before complete recovery. The symptoms of the relapse are
similar to those of the primary attack, except that they are commonly
more severe.”
In his report of 1893, Parsons goes into the subject of recurrent
attacks in individuals in greater detail. He quotes several
communications received from various physicians and health officers.
These opinions differ, some believing that the disease predisposes to
another attack; others, that there is no effect on the incidence in
recurring epidemics; and still others believing that there is a small
amount of acquired immunity. The communications are not based upon
statistical evidence. He does find, however, an opportunity for
statistical study in the industrial schools at Swinton near Manchester:
“These schools were severely affected in March, 1890, 171 out of 589
children having suffered, or 29 per cent. In the first epidemic of 1891
they were again affected, but to a less extent, only 35 cases occurring.
At that time there were in the schools 449 children who had been there
at the time of the former epidemic. Of these 150 had had influenza in
1890 and 4 of them had it again, or 2.6 per cent.; 299 had escaped
influenza in 1890 and 17 of these had it now, or 5.7 per cent. Thus, so
far as these figures go, an attack of influenza confers a degree of
protection which after the lapse of a year diminishes by one-half the
liability to contract the disease.”
Leichtenstern, like Parsons, recognizes the importance of distinguishing
between relapses and recurrent cases. Relapses in influenza are not
common. They usually occur after the patient is up, and about when he is
ready to leave the house. These are not recurrent cases, but in the
epidemics in the years following 1889 there were plenty of well
substantiated cases of recurrent typical influenza in the same
individual and some times even in entire families. During the 1889
epidemic, as during the 1918 epidemic it has been suggested by various
observers that the apparent immunity among the very old was due to
immunity developed as the result of previous epidemics, such as that of
1837, 1847 and 1857. Leichtenstern has collected the statistics from
five different hospitals in which 8, 32, 35, 24, and 24 per cent. of
individuals attacked in 1891–92 had already had the disease in 1889.
Allbutt in 1905 remarked that whereas he had previously believed that
immunity to influenza usually persists as long as six months, many cases
had recently been brought to his notice where such an interval seemed
improbable, where the succeeding attack was probably not a relapse but a
new infection. He has seen two attacks apparently separate occurring in
the same individual within two months. In the same year Moore wrote that
influenza shows a decided tendency to relapse, a feature to which the
indirect fatality of the disease is in great measure due. “So far from
establishing immunity, an attack of this malady seems to render an
individual more liable to contract the disease upon any future exposure
to its contagion.”
Again West, in the same year wrote, “From our present experience we must
conclude that influenza is infectious in a very high degree indeed, and
that the protection afforded by an attack is imperfect, or of very short
duration. Indeed, one attack seems actually to predispose, after a time
to another, or, to put it differently, that the positive phase of
protection is followed by a negative phase, in which the individual
seems rather more than less liable to succumb to infection if exposed to
it. It seems more likely that an individual may never have influenza at
all than that, having had it once, he should never have it again. Some,
indeed, seem to offer so little resistance that they develop it
regularly once or twice a year.”
We have previously shown that the relatively low morbidity among the
older age groups in 1918 is not satisfactorily explained by an immunity
lasting over from the epidemic of 1889–93. If such were the case the
change in mortality rate in large groups of individuals would occur at
the age of 30.
During the autumn of 1918 many observations were made, particularly in
the armies, of light incidence in those groups or communities that had
had the disease in mild form in the spring of the same year.
Parsons quotes many similar observations for the period 1890–1893.
V. C. Vaughan relates that at Camp Shelby, Mississippi, “there was in
April a division of troops numbering about 26,000. An epidemic of mild
influenza struck this camp in April, 1918, and within ten days there
were about 2,000 cases. This included not only those who were sent to
the hospitals, but also those who were cared for in barracks.
“This was the only division that remained in this country without change
of station from April until the fall of 1918.
“During the summer this camp received 20,000 recruits. In October, 1918,
the virulent form of influenza struck this camp. It confined itself
almost exclusively to the recruits of the summer and scarcely touched
the men who had lived through the epidemic of April. Not only the 2,000
who had the disease in April, but the 24,000 who apparently were not
affected escaped the fall epidemic. It appears from this that the mild
form of influenza of April gave a marked degree of immunity against the
virulent form in October. There is another observation which points the
same way. Looking over the statistics of the fall epidemic in cities in
the United States we find that certain cities had a low death rate,
while others had a relatively high rate. Among those cities which had a
low death rate we will mention Atlanta, Ga.; Kansas City, Mo.; Detroit,
Mich., and Columbus, Ohio. Going to the spring records of these cities
we find that in all of them in March and April of 1918 there was an
unusually high death rate from pneumonia and undoubtedly in these cities
at that time there was a relatively mild epidemic of influenza. In this
way I am inclined to account for the relatively low death rate in these
cities in the fall of 1918. I make no claim that this and other
instances of a similar kind prove that the mild and virulent forms of
influenza are manifestations of the same disease, but I do hold that the
evidence points that way.”
Lemierre and Raymond report the following observation in favor of the
development of a certain degree of immunity in the French troops in
April, 1918. After an intervening period of quiescence there was a
manifest recrudescence at the end of August. Many military formations
were attacked during both periods. This was true especially in three
groups of an artillery regiment under their observation. In the first of
these groups there were three cases in April, while 114 men were
attacked in August. In the third group there were 100 cases in April and
only 3 in August. In the second group there were 20 cases in April and
59 in August. Their report does not state the total number of
individuals in each of the three groups.
Joltrain and Baufle discuss the flaring up of the epidemic in October,
and relate that a troop of soldiers from Indo-China nearly all had the
disease lightly in the spring, but when the disease appeared again it
spared this troop completely, while troops and civilians around
developed it in a severe form.
Gibbon writes: “During the last three waves of the epidemic I had to
deal with the sick of 2,000 troops, and during this time we treated in
hospital over 400 cases. No cases admitted in June, July or August were
re-admitted in October, November, or December, and no cases admitted in
either of these two periods were re-admitted in February this year.
Unfortunately I am unable to trace the cases into March as the troops
were changed.”
Dopter reports recurrent epidemics of influenza in a French Army
Division in 1918. The division, of which he was surgeon, was one of the
first to contract la grippe at the time of its first appearance in the
zone of the armies at the end of April, 1918. At this time nearly the
entire body of infantry troops was attacked. The disease was mild, and
without complications. The regiment of artillery escaped nearly
entirely. This epidemic subsided very rapidly, and by the end of May it
had entirely disappeared. Early in August a group of heavy artillery was
attached to the division, bringing influenza with it. Then a few cases
appeared in the regiment of light artillery which had hitherto escaped.
By the end of August all three groups of this regiment had been
attacked. In this second epidemic the men who had come through the first
unattacked were very severely ill in the second.
With rare exceptions those sick in the first did not contract it again.
Dopter notes that in the battery the most severely affected in August,
of which the effectives were reduced almost to none, only those men were
considered well enough for duty who had had influenza in the first
period. They escaped the second in spite of the close contact with their
comrades. The infantry regiments, which were in close association with
the artillery, remained unaffected.
Finally, toward the middle of September new troops were attached to the
division, in view of an imminent attack by the enemy. These troops,
coming from neighboring and distant formations were suffering at the
time from grip, and continued to have the disease in the new sector.
Again, those attacked in May passed without damage through this new
epidemic. Among them there were only rare isolated mild cases. The
recurrences made only 1.6 per cent. of the total incidence.
Opie and his associates found that at Camp Funston after the first wave
of influenza in March and April, 1918, the succeeding waves usually
affected only new recruits, who had not been in camp during previous
waves.
In Calcutta influenza appeared as an epidemic in July, 1918, and in
November, 1918. During the first quarter of 1919, at Calcutta as
elsewhere, many cases were still recurring. Malone investigated the
incidence of the disease in three institutions of Calcutta: He found
that in the Gourepore Jute Mills where the population was practically
stationary, those individuals who were attacked in July, 1918, passed
through two later epidemics, in December, 1918, and February, 1919,
without contracting the disease a second time, in spite of intimate
contact with infected persons. The same was true according to Malone in
the Alipore Central Jail and the Presidency Jail in Calcutta. He
believes that his evidence strongly suggests an immunity lasting for at
least nine months.
Dunlop found that Glasgow had a mild epidemic in the month of May, 1918,
in which the death rate rose from 14.1 to 20.1. There is no record of
any similar outbreak in Edinburgh. In the July epidemic the Glasgow
death rate rose from 11.7 to 15.9, while the Edinburgh death rate went
from 11.3 to 18.0, a higher increase. In the October-November epidemic
the Glasgow rate rose from 11.0 to 38.4, while the Edinburgh rate went
from 10.8 to 46.2. In the February-March epidemic the Glasgow rate rose
from 14.9 to 48.3, and the Edinburgh rate from 18.9 to 52.1 In the July
and October epidemics Edinburgh showed a greater increase in death rate,
while in February, 1919, the increase in the two cities was the same.
However, in this case probably other factors play a part. Also, we must
remember that here we are dealing with death rates, not with incidence
rates.
The Inspector General of Health, in Spain, reported in January, 1918,
that those cities which had the disease in May, 1918, suffered lightly
in the autumn of that year, while others of the large cities which had
been spared in the first invasion suffered most in the second.
Maillard and Brune report an epidemic of influenza in an epileptic
colony. There were 32 deaths among the 63 cases. None of the inmates of
the hospital who had influenza during the June epidemic contracted it
anew during the October wave.
Ovazza records that although a number of persons contracted the
influenza anew on its return in the fall after having had it in the
spring, yet the return cases were strikingly mild, and always free from
complications.
Barthélemy describes the successive waves of epidemic influenza at
Bizerte. He found that the doctors and nurses who had been through the
first epidemic did not develop influenza in the second one a few months
later, even though they came in the closest contact with the patients.
Hamilton and Leonard have studied two successive outbreaks due to lapses
in a rigid quarantine in an institution of 180 girls between 12 and 18
years of age. The girls were distributed through six cottages. In the
first epidemic November, 1918, 76 girls contracted the disease, at which
time it was entirely limited to the occupants of cottages 2, 3, and 4.
The second outbreak occurred in January, 1919, when 82 took ill. Only
five of these were located in cottages 2 and 4, the remainder being in
1, 5 and 6. No cases occurred in cottage 3 during the second spread.
Both epidemics lasted a little under two weeks. Those who had suffered
in the first spread appeared to be immune to the second. There were no
recurrences. The second epidemic was much milder in character. Twelve
per cent. of the total remained well throughout both epidemics.
Dr. Niven, in his study of 1,021 households previously described, found
that 105 families suffered in both the summer and autumn 1918 epidemics.
“They comprised a population of 565 persons, of whom 205 suffered in
summer and 360 escaped. In the autumn epidemic eighty-two (or 40 per
cent.) of the presumably ‘protected’ persons succumbed again, whereas
only 120 (or 33 per cent.) of the ‘unprotected’ suffered. Of the former,
however, only one died, while five of the latter terminated fatally.
These are interesting figures. If they are borne out by subsequent
inquiry, they are somewhat difficult of explanation. The persistent
susceptibility to the primary disease and yet comparative immunity from
the fatal sequel, would seem to suggest a dual infection, against one
element of which the body is able to produce protection, while it is
unable to do so against the other.”
Frost made a canvass of 33,776 individuals in Baltimore between November
20th and December 11th, 1918. The same population was again covered in
January, 1919, to determine the extent of the recrudescence reported in
December. Among 32,600 people, 724 cases of influenza had occurred in
the interval since the first survey. Of this number only 26 or 3.6 per
cent. were definitely cases of second attack in the same individual.
Even in these cases the diagnosis is necessarily uncertain. Frost says
that considering that 23 per cent. of the population had had influenza
prior to December 11th, the proportion of second attacks should have
been much greater if no immunity had been acquired. A second canvas in
San Francisco gave generally corresponding results.
Our own experience was quite similar. We have divided the whole period
from March, 1918 to March, 1920, into two portions separated at August
1, 1919. In the first portion we have knowledge of but four individuals
suffering from what the records would indicate to be two genuine attacks
of influenza. Similarly, five individuals appeared to have had two
attacks within the second interval. These are to be contrasted with a
total incidence in the fall and winter of 1918–1919 of 1,971 cases, and
in the winter of 1919–20, of 965 cases. Among the total nine individuals
the intervals between attacks varied from 26 days to five months. All
except one had an interval of one month or over. In two cases there was
an interval of one month, in one an interval of two months, in two an
interval of three months, in one of four months, and in one of five
months. None of the four individuals who had two attacks in the first
group of months had a subsequent attack in the second. On the contrary,
two of the five suffering two attacks in the second group of months had
one previous attack in the first. The second attack, following the first
by a relatively short interval tended to be milder than the first. In
five out of the entire nine the second attack was milder, in two it was
of the same degree of severity, and in only two was it more severe than
the first. The order of severity in the two individuals having three
attacks each was, in the first, severe, mild, severe; in the second,
severe, average, average.
Zinsser makes the following remark: “The writer himself believes that he
had three attacks during the last epidemic. The first and second were
mild ones and the third complicated and therefore severe; and
innumerable others with whom he has spoken have had similar
experiences.”
From a consideration of these reports by divers authorities it is
reasonable to conclude that for a period of a few months at least, one
attack of influenza protects against a second. As is to be expected,
this relative immunity is not of constant duration in all individuals.
If there were no lessened susceptibility following an attack we would be
faced with the phenomenon of individuals succumbing time and again to
rapidly successive attacks of the disease. Such a circumstance is very
rare.
It is difficult to determine how long even on an average this relative
protection or insusceptibility lasts. Evidence is fairly uniform in
indicating a protection of at least three months. Usually it is longer.
There seems to be some basis for the supposition that a group of
individuals exposed to an attack of influenza displays within the
succeeding three months, or slightly longer, a relative general group
immunity. If the group be considered as a whole those even who did not
develop the disease previously appear to have become less susceptible.
Whether we can ascribe this to the individual as a unit, or whether we
must explain it by some assumption with the community as a unit, is
uncertain. Is it because the exposed individuals in the group who did
not contract the disease have individually received some of the virus
into their systems and developed a certain immunity, or is it a much
more complex phenomenon depending on greater relative dispersion of
susceptibles and other communal factors?
We may place the minimum period of “immunity” at from three to five
months, rarely less. There is additional evidence by which we may
delimit fairly closely the other extreme, that time at which individuals
considered as a group no longer manifest increased resistance to the
disease.
The author found that 19.17 per cent. of his population contracted
influenza in 1918, and 9.55 per cent. contracted the disease in 1920.
Two hundred and forty individuals, or 2.4 per cent. of the entire
population developed the disease in both epidemics. Out of 1,971
individuals having the disease in the 1918 spread, 240, or 12.1 per
cent. recurred in 1920. This is to be compared with the total 1920
incidence of 9.55 per cent. More correctly we should separate the 1920
cases into two groups, those who had and who had not had influenza
previously. The former group, 240 individuals, constitute as just
stated, 12.1 per cent. of all who had had the disease previously. The
second group, 715 individuals, constitute 8.9 per cent. of the 8,034 who
had not had the disease in 1918–19.
From these results we must conclude that _a previous attack contracted
on an average of from 10 to 17 months before, conferred no protection
whatever against a second attack. On the contrary, the attack rate was
slightly higher in this group than in those who had not previously had
the disease._
Yet another evidence of the insignificant part played by any immunity in
the occurrence of influenza in individuals in 1920 is indicated by our
series of 319 infants living in 1920 but who had not been born during
the 1918 spread and who were presumably not immune to the disease. We
have not investigated whether the mothers had had the disease in 1918.
From among these 319 infants, thirty or 10 per cent., developed the
disease in 1920. This is practically the same percentage as for the
population at large.
These findings also correspond with our previously recorded conclusion
made after studying the disease incidence with three increasing degrees
of exposure, _sleep_, _room_ and _family_ (page 198).
TABLE IX.
_Comparison of the severity of the first and second attacks in
individuals contracting influenza in 1918–19 and again in 1920._
═════════════════════════════╤═════════════╤═════════════╤═════════════
Severity. │No. of cases.│ Comparison. │No. of cases.
──────────────┬──────────────┼─────────────┼─────────────┼─────────────
1918–19. │ 1920. │ „ │ „ │ „
──────────────┼──────────────┼─────────────┼─────────────┼─────────────
Average │Mild │ 43│Second attack│ 132
│ │ │ milder │
Severe │Mild │ 50│ „ │ „
Severe │Average │ 39│ „ │ „
──────────────┼──────────────┼─────────────┼─────────────┼─────────────
Mild │Mild │ 30│Both of equal│ 72
│ │ │ severity │
Average │Average │ 22│ „ │ „
Severe │Severe │ 20│ „ │ „
──────────────┼──────────────┼─────────────┼─────────────┼─────────────
Mild │Average │ 13│ Second more │ 36
│ │ │ severe │
Mild │Severe │ 5│ „ │ „
Average │Severe │ 18│ „ │ „
──────────────┴──────────────┴─────────────┴─────────────┴─────────────
Altho we find no conclusive evidence of protection against recurrent
attacks, we do find (Table IX) that the second attack in the same
individual was usually milder. However, the 1920 epidemic as a whole was
milder, (Chart XVIII).
Zinsser quotes a letter from Frost in which the latter states that in
Baltimore those persons who were attacked during the 1918–19 epidemic
showed no relative immunity during the epidemic of 1920. This is not a
contradiction to the earlier Baltimore studies, since in that case the
interval between the epidemic waves was not more than about three
months.
Jordan and Sharp have obtained statistics regarding approximately 4,000
men at the Great Lakes Naval Training Station. The men’s statement
regarding previous influenza was accepted whenever the attack was said
to have occurred during the influenza period of 1918–1919, _i.e._, in
September, October, November, December, January, February and March. The
great majority were reported for the period of September to December.
Only a few cases were reported as occurring in March, and perhaps these
actually occurred somewhat earlier than the men recalled. A few cases
were accepted as influenza when reported as occurring in Europe during
July and August, 1918.
They found that 28.5 per cent. of 3,905 men had had the disease in 1918,
and that 22.6 per cent. were attacked in 1920. Of those who had the
disease in 1918–19, 21.2 per cent. had a repeated attack in 1920, while
of those who had not had a previous attack, 23.1 per cent. were attacked
in 1920.
A similar study among 2,472 men at Camp Grant showed that 15.8 per cent.
had had influenza in 1918–19, and 11.7 per cent. in 1920. Of those with
previous influenza history 15.6 per cent. had a repeated attack, while
of the remainder without previous history of influenza 10.9 per cent.
were attacked in 1920. They conclude that no marked immunity to
influenza exists 12 to 15 months after a previous attack, but that the
results do not show that some degree of immunity may not obtain at an
earlier period.
It is interesting while considering the subject of immunity to pay
particular attention to those who _did not_ develop the disease as well
as to those who did. In our series 70 per cent. of all individuals
escaped the disease in both epidemics. With some variation this figure
will hold for all communities. Or, again, among those who had the
disease in 1920, 75 per cent. _had not had it_ in the preceding waves.
Hall states that in Copenhagen at the Bispebjaerg Hospital, among the
500 patients with influenza in the four weeks early in 1920, 91.8 per
cent. _had not had_ the influenza during the 1918–19 epidemic. H. F.
Vaughan found in a review of 2,500 cases occurring in Detroit in
January, 1920, that _84 per cent. had never had_ the influenza before.
The true significance of these figures cannot be recognized, because we
are not informed as to the per cent. of these populations attacked in
1918–19.
We observed such a universal distribution of influenza during the
epidemic period that it is frequently assumed that all individuals are
exposed to the disease, that the virus must enter the body of all or
nearly all, and that it is due chiefly to a relative natural immunity
that some do not fall victims. Is this the actual state, or is it true
that the distribution of the virus is limited to about one-third of the
population and that practically all of those who are actually exposed
develop the disease? These are the two extremes; more probably the
actual state is somewhere between.
This question cannot be definitely answered, and yet it is one of
extreme importance, particularly with regard to prevention and combat of
the disease. How universally is the influenza virus distributed during
pandemics? What proportion of the population is actually exposed by
invasion with the virus? What proportion of actually exposed individuals
develops the disease? We will refer to this again when comparing
influenza with other infectious diseases, but it is of particular
interest now to review our individuals who were exposed by sleeping with
cases of influenza. Fifty-five per cent. of all individuals sleeping in
the same bed with cases of influenza in 1918 _did not_ contract clinical
influenza. Seventy per cent. of all individuals sleeping with influenza
cases in 1920 _did not_ contract the disease, in recognizable form.
Sixty-nine per cent. of all individuals in 1920 who had not had the
disease previously and who slept with cases _did not_ develop evidences
of the disease.
It is difficult to conceive of a degree of exposure much closer than
that of sleeping in the same bed with a sick individual. And yet it is
equally conceivable that many individuals sleeping in the same bed with
a patient were not penetrated by the virus of influenza. This does not
aid us in answering our question. We do not know whether the more
important factor is that of a natural immunity or that of absence of
actual invasion by the virus.
These results with sleeping contacts form an interesting link in the
chain of evidence started during 1918 by the U. S. Navy and Public
Health Service, and reported by Rosenau and by McCoy and others. These
experimenters working in Boston and in San Francisco carried out
inoculation experiments on human volunteers. The work in Boston, as
reported by Rosenau, was carried on with 100 volunteers from the Navy
between the ages of eighteen and thirty, most of them between eighteen
and twenty-five; all of them entirely well, and with the exception of a
few controls, none having experienced known attacks of influenza
previously. First, suspensions of thirteen different strains of
influenza bacilli, all from cases of influenza during the epidemic, were
sprayed into the nose, eyes and throat of nineteen volunteers. None of
them took sick. Next, secretions from the mouth, nose and throat and
bronchi of acute cases of influenza were collected, pooled, and without
filtration sprayed into each nostril, into the throat during
inspiration, and onto the conjunctiva of each of ten volunteers. None of
them took sick. Some of this same material was filtered through a
porcelain filter and administered in the same manner, with similar
results. One cubic centimeter of each type was administered to each
individual. The interval between the time of collection and time of
inoculation was then decreased to one hour and forty minutes, the
minimum time in which the material could be transferred from hospital to
experiment station. The same results were obtained. This time six cubic
centimeters were administered to each individual. Finally, transfer was
made directly with swabs from the nose, throat and nasopharynx of one
individual to another in nineteen cases. None developed the disease.
The next series of experiments consisted in an attempt to inoculate
volunteers with influenza by injecting into them 10 cc. of citrated
blood, which was the pooled collection from five cases of acute
influenza. Ten volunteers were inoculated. None took sick. Next, the
secretions from the upper respiratory tract of acute cases were injected
subcutaneously into ten volunteers, each receiving 3.5 cc. This material
was first put through a porcelain filter. None took ill. In an attempt
to reproduce the disease in imitation of nature, ten individuals were
exposed to cases of acute influenza in hospital wards. Each volunteer
was placed very near to the patient, shook hands with him, talked and
chatted with him, for five minutes, after which he received the
patient’s breath full in his face five times while he inhaled, and
finally the patient coughed five times directly into the subject’s face.
Each volunteer did this with each of ten different patients, all of them
acutely ill, none more than three days sick. No volunteers developed the
disease. All cases of influenza used throughout the period of these
experiments were typical acute cases selected from a distinct focus or
outbreak of the disease. Sometimes, for example, they would select four
or five typical cases from an epidemic in a school with a hundred cases.
In February, 1919, the experiments were continued at Portsmouth, where
the secretions were transferred direct from individual to individual. In
about thirty-six hours half of the number came down with streptococcus
sore throat, but not with influenza. One of the medical officers,
however, who had been very active in the experiments, and who had come
into intimate contact with the disease since early in October, but who
had not been inoculated, developed, during this experiment, typical
influenza. The explanation for these failures is not certain. The
experiments were started rather late after the onset of the epidemic,
and the volunteers may have developed some immunity, although they had
not developed the disease. Or, they may never have been susceptible.
McCoy made a similar series of experiments in San Francisco, using
volunteers who so far as known had not even been exposed to the
outbreak, also with negative results. However, many of these latter had
been “vaccinated against influenza” with a mixed vaccine.
Wahl and his co-workers found that the nasal application of a filtrate
from the pneumonic lung of an individual dead with typical
influenza-bronchopneumonia failed to call forth any abnormal symptoms in
human subjects. The application to the mucous membrane of the nares and
nasopharynx of five healthy men, who had been inoculated from four to
six weeks previously against influenza with a polyvalent influenza
vaccine, and of one uninoculated, of freshly prepared suspensions of
four different live strains of Bacillus influenzae, even in massive
doses failed to produce any abnormal symptoms. The implantation of
living suspensions of Bacillus influenzae produced no material
alteration besides the addition of the influenza bacillus itself. When
experimentally introduced into the nasopharynx of men the influenza
bacillus exists and multiplies for a considerable length of time, two
weeks or more. It apparently shows much resistance to the action of
dichloramin T.