It would appear to us that, as has been discussed by Dr. Holman, the case against the B. influenzæ not being the important causative agent has not been proved. The demonstration by others of a potent toxin from the B. influenzæ cannot be overlooked, and although the actual disease has not been reproduced in animals, there is evidence that this toxin will induce acute degenerations in various tissues. Furthermore, the in vitro symbiotic relation demonstrated for the B. influenzæ with other organisms, as the pneumococcus, streptococcus, staphylococcus pyogenes aureus and M. catarrhalis, gives ample support to the claim for a similar symbiosis in the human tissues. The evidence for the important primary relation of the B. influenzæ to epidemic influenza is such that we cannot disregard it—at least, not before we can produce some definite positive evidence that another demonstrable virus precedes it and produces those constitutional effects which initiate the remaining sequelæ.
We must agree with Christian in the statement that all cases dying during the acute stage of epidemic influenza have inflammatory lesions in the respiratory tract and largely in the lung (pneumonia). It is difficult to conceive of a disease comparable to the acute exanthemata, which beginning as a separate and distinct process ends fatally within 48 hours with a pneumonia which is claimed to be secondary.
Epidemic influenza is an acute infectious process of the respiratory tract, usually localizing in the upper respiratory system, but often and in a fairly constant percentage of cases extending into the lower portion of the same system and causing a type of broncho-pneumonia. Accompanying the initial invasion there is a marked systemic intoxication with lesions of degeneration arising in a variety of tissues. These lesions of degeneration are to be seen both locally in the respiratory system as well as in distant parts, as in the muscles, kidney and liver. The primary damage arising in the respiratory organs, and which we believe to be the result of infection by the B. influenzæ, facilitates attacks by such other bacteria as are available and pathogenic to man. The secondary invaders are not constant in type, but we find variations according to the localities where the epidemic takes place. Just as there is a difference in the bacterial flora which constitutes the secondary invasion, so, too, there is a variation in the picture of the inflammatory process which appears in the lungs. The occurrence of the miliary streptococcal broncho-pneumonia has been met with in certain localities much more frequently than in others; lobular and confluent pneumonia has been the prevailing type in certain regions, while a lobar purulent pneumonia with abscess and gangrene was most frequent with others. There does not appear to be an individual and constant character in the mode of distribution of the pneumonia in the lungs. That the pneumonias were not the usual type otherwise seen, is fairly agreed upon by all. The most astonishing feature presenting itself to us was the frequency of death occurring in the early stages of the inflammatory process and before the gray stage had definitely developed. The gray stage of influenza pneumonia is a purulent pneumonia which often also constitutes an acute interstitial pneumonia.
The extensive hemorrhage and inflammatory œdema of the lung are striking during the early stages of the lung involvement. The mononuclear infiltration which appears early and remains for a variable time, until the purulent process is well under way, is also unique. The hyaline deposit in the lung alveoli; the capillary thrombosis and necrosis of the alveolar walls and bronchi are important; while the tendency to abscess, infarct, gangrene and incomplete resolution with fibrosis differentiates this type of pneumonia from the common lobar variety.
As an organic evidence of the acute intoxication, none stands out more prominently than the degeneration of the voluntary muscles. These resemble the waxy degeneration of other bacterial intoxications, and particularly that of typhoid fever. The finding of these acute degenerations does not assist us in arriving at a conclusion as to the nature of the poisonous body, whether a true exotoxin. The presence, however, of such widespread degenerative lesions in cases showing no naked eye change suggests, at least, that the peculiar muscle weakness associated with pain has its origin in this definite process and not in primary nerve lesions.
Very interesting it is that the different muscular structures are not equally affected by the intoxication. This is particularly noteworthy in the heart and intestine. In neither of these structures have we met with lesions comparable to those in the voluntary muscles. Wherein this immunity resides we cannot state. In our own series, as well as in the majority of others, there was an unusual absence of evidence of myocardial weakness. In most of those dying during the acute illness, the heart muscle was found firm and the cavities not dilated. This finding was in striking contrast to that found in acute lobar pneumonia where dilatation of the right ventricle and auricle, along with muscle degeneration, is almost the rule. In but one case of the present series did we find myocardial degeneration leading to dilatation of the cavities and causing death. And in this particular case the intoxication was due to a streptococcus septicæmia arising as a late sequel from the middle ear. The heart in influenza withstands remarkably well the effects of an intoxication from the disease and carries the extra load imposed upon it by the involved lung with little evidence of fatigue.
It is also worthy of attention to note that the kidney suffers so little in this severe disease. Bacterial localization with inflammatory concomitants does not occur, and there is no lasting damage upon its structure. As in so many conditions of bacterial poisoning, tubular degeneration, varying from a cloudy swelling to a more acute damage, is to be found in a percentage of cases, but complete restoration is rapidly obtained in convalescence. It is unusual to find such severe renal damage to incapacitate function to a degree to endanger life.
Finally we can add our evidence, gained from a study of the pathology of epidemic influenza, that the primary disease induced by the invasion of the B. influenzæ opens the way for secondary infections of a variety of kinds, whose subsequent effect may be more serious than initial lesions. The many late complications which arise in this manner we have not investigated.
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