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 milder | 132 |
| Severe | Mild | 50 | ||
| Severe | Average | 39 | ||
| Mild | Mild | 30 | Both of equal severity | 72 |
| Average | Average | 22 | ||
| Severe | Severe | 20 | ||
| Mild | Average | 13 | Second more severe | 36 |
| 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.