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The bacteriologic studies in cases of influenza described in this report fully support Pfeiffer’s claim that B. influenzæ is invariably present in the disease. It is particularly important to note that these results were obtained in early uncomplicated cases of influenza and are not dependent upon cultures made from cases complicated by pneumonia or obtained at autopsy. In view of this fact the tendency so apparent in much of the recent literature to relegate B. influenzæ to a place of secondary or minor importance in the disease seems hardly justifiable. It would seem that this tendency is largely dependent upon three factors: first, the failure of many to find B. influenzæ either during life or at autopsy in any considerable proportion of cases; second, the frequent failure to draw a clear distinction between influenza itself and the pneumonia to which it predisposes with a consequent overemphasis upon autopsy bacteriology where a considerable variety of secondary organisms have attracted particular attention; and third, an incorrect interpretation of the undoubtedly large number of B. influenzæ carriers found among normal individuals and those with other diseases during the period of the epidemic and to less extent in interepidemic times.

Since the majority of workers who are thoroughly familiar with the technic of cultivating B. influenzæ have encountered little difficulty in finding it in a large majority of cases, it is felt that the considerable number of negative reports that have appeared can depend only upon the unfamiliarity of those who have failed to find it with the proper bacteriologic methods. This is quite apparent in many of the reports that have been published, and is not surprising in the face of the excessive demand for well-trained bacteriologists occasioned by the war.

One important feature in the successful isolation of B. influenzæ from all cases that has been brought out in the course of the work here reported, is the necessity of making simultaneous cultures from all portions of the respiratory tract, since by no single culture method was it found possible to find the organism in all cases. It has been pointed out that one of the most characteristic local phenomena of the disease is the rapidly progressing attack upon the mucous membranes of the respiratory tract. It seems quite possible that B. influenzæ in predominant numbers at least may be found in many cases only at the crest of the wave, if we may speak of it as such. By way of analogy is the well-recognized fact that the successful isolation of streptococcus from cases of erysipelas often depends upon taking cultures from the margin of the advancing lesion. While definite proof is lacking for this opinion, it would seem to receive some support from the observation that B. influenzæ rapidly disappears from the throat with the onset of convalescence in a considerable proportion of cases. It is felt that these observations, establishing the predominance of B. influenzæ in the early acute stages of the disease, are of considerable significance, especially when exactly the reverse condition was found in studying the incidence of the organism in cases of measles.

In consideration of the primary cause of influenza, attention has often been focused upon the many different bacteria found in autopsy cultures. The most prominent of these are the ill-defined diplostreptococci of the European writers, the various immunologic types of pneumococci, and S. hemolyticus. Other microorganisms less frequently found are staphylococci, M. catarrhalis, nonhemolytic streptococci, and B. mucosus capsulatus. It is not within the scope of this paper to discuss their relation to the various types of pneumonia found at autopsy, but their very multiplicity would seem sufficient prima facie evidence that they bear no etiologic relationship to influenza and must be regarded only as secondary invaders. If any further support for this opinion were necessary, it may be found in the studies upon the incidence of pneumococcus and S. hemolyticus in early cases of influenza described in this report. Both were found to occur in the same proportions in which they may be found in normal individuals at any time.

Although Pfeiffer maintained that B. influenzæ was found only in true epidemic influenza, the incorrectness of this contention has been thoroughly established by many reliable investigators and it has been shown beyond question that influenza bacilli may always be found in a small proportion of normal individuals and are not infrequently found in other respiratory diseases.

The fairly extensive study that has been made of the incidence of B. influenzæ in normal men and in cases of measles has clearly demonstrated that the proportion of carriers found in any group depends upon the prevalence of influenza in the group studied and that with the progress of the epidemic the percentage of carriers has steadily increased. When one considers that the opportunity for the dissemination of B. influenzæ by contact infection is almost unlimited during an epidemic of the proportions of that which has swept over the country, this is not at all surprising. That such a large number of normal individuals became carriers of B. influenzæ during the epidemic would seem to be sufficient evidence that actual dissemination does occur and to controvert the theory that in actual cases of influenza, conditions are established in the respiratory tract whereby B. influenzæ, always present in small numbers, is enabled to “grow out” and become the predominant organism. From a consideration of all the observations made as to the incidence of B. influenzæ in various conditions it would appear that the carrier condition is quite analogous to that found with many other bacteria, and may be divided into three groups: (a) acute carriers, those having influenza, (b) contact carriers, those who during epidemic times become temporary carriers of the organism without contracting the disease, and (c) chronic carriers, the relatively small number of normal individuals or those with chronic respiratory conditions who carry B. influenzæ over long periods of time. From the facts at hand this would seem to be the most probable explanation of the conditions found. It is certainly true that the established presence of pneumococcus, B. diphtheriæ, meningococcus and many other organisms in a varying proportion of normal individuals is not regarded as sufficient evidence to exclude them as the etiologic agents of the diseases which they cause.

It is quite obvious that if B. influenzæ is to be regarded as the cause of epidemic influenza, it must change quite rapidly under certain circumstances from a relatively saprophytic organism to a relatively virulent pathogenic organism, and conversely return to its avirulent state following the passage of an epidemic. Animal experimentation has taught us that virulence is acquired by the rapid passage of an organism from host to host. That an opportunity for the rapid transference of B. influenzæ from man to man was provided by the assembling of large groups of individuals relatively susceptible to respiratory diseases in our camps and cantonments is by no means impossible. It has been clearly shown by Vaughn and Palmer²² that men from rural districts are very susceptible to respiratory diseases and that the camps in which such men were assembled suffered most heavily in this respect during the winter of 1917–18. This Commission has clearly demonstrated that an epidemic of influenza swept through Camp Funston²¹ in the spring of 1918 and that a similar epidemic occurred at Camp Pike. Accumulating evidence will undoubtedly show that like epidemics existed in many of our southern camps (Vaughn and Palmer,²² Soper²³). It is of considerable interest that B. influenzæ was found in almost one-half of the cases of bronchopneumonia studied by Cole and MacCallum²⁴ at Fort Sam Houston in February and March, 1918. This relation is especially noteworthy, since an epidemic of influenza was seen by one of us (Blake) among the troops at Kelly Field and Fort Sam Houston during these months. That similar conditions existed in European armies as early as 1916–17 is suggested by the reports of Hammond, Rolland, and Shore²⁵ and of Abrahams, Hallows, Eyre, and French²⁶ on epidemics of “purulent bronchitis” with bronchopneumonia in the British army. B. influenzæ was found abundantly in these cases.

Theoretically, under the conditions outlined above, ideal opportunities have been provided for B. influenzæ to build up sufficient virulence to enable it to produce the pandemic of 1918–19. While it is thoroughly recognized that these considerations are in the main hypothetical, it is felt that they are by no means beyond the bounds of possibility, and for that reason are offered as suggestions worthy of further investigation.

It is, of course, perfectly possible on the basis of the observations presented still to regard B. influenzæ as a secondary invader which makes its appearance in all cases of influenza simultaneously with the onset of clinical symptoms. Final proof of its causal relationship to the disease must depend upon the production of influenza by experimental inoculation. Results hitherto obtained in attempts to produce the disease experimentally have been contradictory. Pfeiffer⁸ claimed to have produced a disease in monkeys in some respects resembling influenza by the intratracheal injection of freshly isolated cultures of B. influenzæ. Wollstein,¹⁹ in studies upon the pathogenicity of various strains, has shown that B. influenzæ is generally pathogenic for mice and guinea-pigs without respect to source or virulence for man. Pathogenicity for rabbits and monkeys, on the other hand, was possessed only by strains that were highly virulent for man. She furthermore pointed out that for successful animal experimentation, it is imperative that inoculations be carried out immediately after the isolation of the bacilli because they rapidly lose virulence by subculture on artificial media. It is felt that failure to appreciate these facts has been responsible for the often repeated statement that B. influenzæ is not pathogenic for animals.

In a series of animal experiments carried out by this commission recorded in an appendix to this report, sixteen-hour cultures of B. influenzæ freshly isolated from early cases of influenza were demonstrated to be pathogenic for monkeys, both by inoculation of the nasal and pharyngeal mucosa and by intratracheal injection. Monkeys so inoculated developed coryza, epistaxis, tracheitis, bronchitis, and extreme prostration. Experiments with forty-eight-hour cultures of strains preserved by subculture during from ten to fifteen days failed to demonstrate pathogenicity for monkeys. Proof that these monkeys had influenza can depend only upon the demonstration that they suffered with a disease having the clinical character and pathologic lesions of influenza.

The reported failure to produce influenza in man by direct inoculation with freshly isolated cultures of B. influenzæ in experiments conducted on volunteers by the United States Public Health Service²⁷ at Gallops Island, Boston, is interesting, but would seem to lack definite significance since attempts to transmit the disease from man to man by direct contact also failed. Since all the subjects of these experiments had been previously exposed to influenza during the epidemic, 30 per cent actually having contracted the disease, it would seem probable that the remaining 70 per cent were only very slightly if at all susceptible. It is noteworthy that the attack rate of influenza in most army groups was approximately 20 to 30 per cent during the epidemic, the remaining 70 to 80 per cent failing to contract the disease though equally exposed. No other explanation presents itself except that influenza is no longer transmissible when clinical symptoms have appeared.