Part 4

One of the best descriptions of that epidemic was given by Dr. O. Leichtenstern in Nothnagel’s Encyclopedia of Practical Medicine. This contribution, among many others, describing the epidemic of 1889 and 1890 is one of the first to refer to the Pfeiffer bacillus as being etiologically associated with the disease. It differs, therefore, greatly from descriptions of previous epidemics. Leichtenstern says: “The typical influenza consists of a sudden pyrexia of from one to several days duration, commencing with a rigor, and accompanied by severe headache, generally frontal, with the pains in the back and limbs, by prostration quite out of proportion to other symptoms and marked loss of appetite.” He continues by saying that to these characteristic symptoms may be added the catarrhal phenomena arising from the affection of the respiratory tract, particularly the upper (coryza) and “occasionally” the lower, the trachea and bronchi. This description is so in accord with the symptoms of uncomplicated influenza as found in the present epidemic that very little need be added. Any difference which may occur in the description of the disease is likely to be accounted for by the peculiarity of onset, whether in the upper or lower respiratory tract, and by the different ways of interpreting complications which may have arisen. It is evident from this description that the upper respiratory tract was affected more generally than the lower in the epidemic of 1889 and 1890. In the present epidemic it can safely be said that the reverse was the usual state of affairs. It was a rather unusual occurrence when the affection was limited only to the nose, pharynx, larynx, trachea and larger bronchi. A very large number, no doubt, had a peculiar œdema, a so-called “wet lung,” which we shall discuss later; others went on to a capillary bronchitis or a bronchiolitis, and a large number had broncho-pneumonia. This sequence we shall attempt to show in the statistics at hand. In some cases the lesion in the lower respiratory tract seemed to be primary, there having been no initial coryza. At least none was observed and no history was obtained.

_Prodromal Stage and Communicability_

The length of the prodromal stage—the stage from the time of contact to the earliest onset of symptoms—has always led to interesting observations and discussion. In this epidemic we have rather definite information bearing upon this subject.

A young married farmer living in a rural community where no influenza had occurred up to the time of the present experience went to a city about 40 miles distant. On the train he sat in the same seat with a man who was apparently ill, and who was sneezing and coughing. He was in the city only a few hours, and was not in any place of congregation except the railway train. Forty-eight hours after his return to his home he noticed the first symptoms and began a mild course of influenza. About 50 hours later his wife was taken with the same symptoms, and in two days more their only child was afflicted. Other members of the household were also afflicted, and one of them died of pneumonia.

It might be interesting to quote a similar observation made by Macdonald and Lyth, of York, England, published in a recent issue of the British Medical Journal (November 2, 1918, p. 488), which corroborates this experience. They say: “We traveled from London together on Thursday, October 3, by train, leaving King’s Cross at 5.30 P. M., arriving in York at 9.30, and as we were leaving the carriage a young flying officer, who had come the whole way with us and was coughing and sneezing at intervals, informed us that he was ill and had had influenza for several days. On Saturday, October 5, we both became ill and had developed typical attacks of influenza. With both of us the illness developed suddenly with laryngitis; in both the first signs were a severe attack of coughing; and in both the time was noted fairly accurately as being between 2 and 2.30 P. M. One case was quite mild, the temperature never over 101. The other was more severe; the temperature arose to 104½ and the catarrh extended to the bronchi. His wife and two children also developed influenza, and in their case the symptoms showed suddenly, about 2 P. M., on Monday, October 7. Now we are convinced that we became infected from our traveling companion during the train journey—more likely toward the end of the journey; and if we take the time of infection as 9.30, this fixes the incubation period for both of us at a minimum of 41 hours, with a maximum margin of error of 4 hours. The three cases developing in the family of one of us point to a similar incubation period, as their illness started almost exactly 48 hours after his, and as it is likely that the infection would not take place until a few hours after the first symptom, the incubation period in these three cases must have been nearly the same as our own two.

“It can be readily understood that we were in no position to conduct extensive bacteriological examinations, but a culture taken from the posterior nares of one of us on October 10 with a guarded swab showed colonies of Pfeiffer’s bacillus and of micrococcus catarrhalis.”

This observation is so convincing, I have quoted it at length and in full.

The communicability of influenza has been observed by all, and the ease with which it passes from one individual to another noted. One observation made by us was of considerable interest. In a house where a patient lay sick with a severe attack of influenza for nearly three weeks several members of the household passed the door of the sick room a number of times daily, and yet they did not contract the disease. This is in marked contrast with the immediate contact between the two physicians and the young flying officer, who sat in the same railway carriage compartment for four hours. The same observation was made in the hospital among nurses in direct contact with patients. A large number of these contracted the disease, while those not immediately associated with influenza patients almost invariably escaped. This speaks strongly against the idea that the epidemic was a so-called “plague,” or that it passed without intermediate means through the air and pervaded all places.

From information thus far at hand it seems, therefore, that the prodromal stage, or stage of incubation, is one which covers about 48 hours, and that it is usually without symptoms unless it be a peculiar prostration which had been described by some patients. It would also appear from the experiences just narrated that it was necessary to be in rather close contact with a patient, so that there could be an exchange of respired air before infection could take place.

_Duration of the Disease_

In all descriptions of the disease the duration is spoken of as “several days, more or less,” “a three-day fever,” or “a seven-day fever.” Because of the careful supervision under which the soldiers were kept while in the barracks an excellent opportunity was afforded to note the duration of uncomplicated cases. The shortest time observed was 1 day, and the longest 10 days. The average duration of temperature among 87 soldiers without inflammation of the lungs or other certain complications was 6⅓ days. Among the civilians the shortest time of pyrexia was a few hours only, while the longest in 73 male patients was 14 days, and in 84 female patients was 16 days. The average length of pyrexia in the males was 4⅝ days, and in the females was 5¼ days.

While the very definite clinical description of the former epidemics of a so-called uncomplicated influenza seems to have served satisfactorily to the present time, the laboratory studies and the possibly more thorough clinical observations which have been carried out recently in this epidemic make it necessary to present anew the whole disease picture of influenza, with the hope of suggesting a classification more in accord with our present knowledge of the disease.

_Forms and Varieties of Influenza_

A few words as to “forms” or varieties of influenza might be helpful before suggesting a classification of symptoms. In former epidemics of influenza considerable importance was attached to the early manifestations or first symptoms as characterizing the “form” of influenza which was in evidence in the individual patient. These were reported as a “respiratory form,” a “nervous form,” a “gastro-intestinal form,” and other forms—circulatory, renal, psychic, etc. In the epidemic of 1889 and 1890 particularly these types were noted, and they have been described in the subsequent small epidemics, practically characterizing them as being of one or the other, and frequently as being without any respiratory symptoms. In the study of our group of cases in the present epidemic every effort was made to recognize the non-respiratory cases, but we were unable to find a single case which did not have definite respiratory symptoms, either early or late, in addition to any other symptoms present. Only occasionally were nausea, vomiting and diarrhea or tachycardia, or certain neuroses or psychoses, the leading symptoms. The respiratory symptoms in some cases seemed to be at the onset primarily of the lower respiratory system—that is, without the preliminary coryza. These usually ran a rapidly fatal course, characterized by marked cyanosis and confusingly irregular chest signs. We would say, therefore, in so far as our experience goes in this epidemic, we are not justified in speaking of any particular forms except the respiratory form, and whenever pronounced manifestations occurred justifying a characterization of any other form they could more easily be interpreted as a complication, or the manifestation of a coincident disease, or of a severe toxæmia.

The classification of the symptoms, therefore, takes into consideration largely those symptoms arising from the respiratory system. We are of the impression that the pathology demonstrated by Dr. Klotz and described by others justifies the following classification. Clinically we would recognize two distinct groups of epidemic cases.

The first includes those _without lung involvement_ having symptoms arising from the upper respiratory tract, including the trachea and the larger bronchi. These were practically without any chest signs except for the rather indefinite signs of an acute bronchitis, and the only symptoms referable to the respiratory tract were a coryza, soreness of the throat, hoarseness and a cough of varying degree and character. If to these symptoms are added those of Leichtenstern just mentioned, one will have a good description of a so-called simple, uncomplicated influenza.

The second includes those _with lung involvement_ and associated with physical chest signs, in some indefinite and confusing, while in others definitely conforming with the existing pathology. These symptoms and chest signs were those associated at one time with what appeared to be an acute œdema of the lungs. At another time the physical signs were those of a bronchiolitis (capillary bronchitis), or most frequently of a broncho-pneumonia, of an isolated type or of a massive type. Finally there were some forms of lobar pneumonia which at times we were unable to differentiate from a true lobar (croupous) pneumococcic pneumonia.

_Influenza Without Lung Involvement_

Of the group without lung involvement nothing further would seem necessary to be said in addition to what one finds in standard text-books describing the disease picture of former epidemics. The incidence of influenza of this type among our group was as follows: Of 153 soldiers 93, or about 60 per cent., had a so-called simple, uncomplicated influenza, and of the 394 civilians 185, or about 52 per cent., had no lung involvement. There are a few points in which the symptoms of the present epidemic seem to be so peculiar that they merit special consideration.

_The Temperature_

This can be described as showing a sudden rise to 102–104, at which point it is maintained for a few days, and subsides by lysis in a few days more. A typical chart is as follows:

Or the temperature might fall one or two degrees for a day or so after the first rise, and then go up again for one or two more days, and subside by lysis as is shown in Chart II.

This would occur without our being able to find any lung lesion unless we accept the acute œdema or wet lung as a complication, and this we were rarely able to recognize by any definite physical signs in the chest. Cyanosis frequently accompanied this second rise of temperature, and was later interpreted as being associated with the so-called wet lung. When the temperature remained up longer than five days it could safely be concluded that lung involvement must be present.

_The Pulse and Respirations_

The pulse was invariably slow, or rather out of proportion to the temperature. Even when the patient seemed very ill the pulse remained from 84 to 96, and of surprisingly good quality. This was noted also when some of the more severe pulmonary involvements or some complications arose. The pulse frequently did not become rapid until shortly before death. The respirations in an uncomplicated case also remained about normal. The rate was not accelerated until lung complications arose, and then a gradually increasing rate was often the first herald of oncoming danger and a sign of grave prognostic import. The relation of the pulse phenomena toward the end of a fatal case was most remarkable. The respiratory rate was accelerated, as has been noted above, but the pulse rate frequently remained unchanged, being characteristically slow. In a patient seen in consultation with Dr. Lester H. Botkin, of Duquesne, Pa., death took place while we were in the sick room. It was a case of apparently uncomplicated influenza of seven days’ duration. The respirations were rapid and the pulse was only 96. In the last five minutes of life the heart beats as observed with the stethoscope never varied, until they suddenly ceased; during the same time the respiratory efforts were only three agonal ones, the last being a minute or so before the last heart beat. There were no physical signs of consolidation at any time recognized in this case, but we feel that the lung, had we seen it at autopsy, would in all likelihood have shown the peculiar hemorrhagic and œdematous character so often observed in the fatal cases.

There were, of course, marked exceptions to the description of slow pulse and later rapid respirations observed. In some the pulse rate and respirations increased, together with or without definite signs of a grave complication.

_Cyanosis_

This was recognized early in the epidemic. It was sometimes preceded by a peculiar flushing of the face, such as accompanies belladonna poisoning. It might be noticed in the very first days of the attack. The cyanosis was looked upon as being a very early symptom of lung involvement. With our later knowledge from autopsies, and especially as shown by Dr. Klotz, we feel it was surely an accompaniment of, or may even have preceded, the changes in the lung which have been designated as œdematous, “wet” or cyanotic. At the earliest appearance of the cyanosis we were frequently unable to find any change in the physical signs of the chest. Of course, the indefinite signs of an acute bronchitis were present, and in some cases an additional “impaired resonance” was noted over one or both lower lobes, but when this was definitely present other more definite signs soon followed, and our case was shifted suddenly from Group I, i. e., without apparent lung involvement, to Group II, i. e., with definite lung involvement. This cyanosis was noticed first in the face, and frequently was marked on the dorsal surface of the hands. It was not unlike the cyanosis which may sometimes be seen when large doses of certain coal tar derivatives are taken. In fact, the question arose whether in the epidemic of 1889 and 1890, when the coal tar derivatives were prescribed with such freedom and with accompanying cyanosis and apparently such deleterious effects, the cyanosis may not after all have been due more largely to the infection than to the medication. After that epidemic it was said: “Influenza has slain its thousands, but the coal tar products have slain their tens of thousands.” There was no gross hæmaturia or hæmoglobinuria present in these cases, although a few red blood cells were seen microscopically. There was, however, epistaxis, sometimes early in the disease or later associated with the cyanosis. In a few cases there was hæmoptysis, which we regard as always arising in cases where the wet or hemorrhagic lung was present. Cyanosis in disease of the lungs, and especially in the terminal stage of lobar pneumonia, is a familiar and common occurrence, but the cyanosis observed in this epidemic seemed quite different from the ordinary. The points of difference were these: (a) it came early in the disease; (b) it seemed to be more generally present when very little lung involvement could be demonstrated physically, and was just as likely to disappear when more definite chest signs were demonstrable; (c) it was not associated with embarrassment of respiration; (d) it had no relation with a demonstrable circulatory disturbance. The pulse did not become rapid; the quality of the pulse did not change; _the right heart was not dilated_, as is so frequently the case in the terminal stage of a lobar pneumonia when cyanosis appears; (e) and finally there was no associated œdema of the lungs, or at least that œdema of the lungs which occurs in the later stage of lobar pneumonia, when the pulse becomes rapid, when there is rapid and labored respiration, when the right heart dilates, when there is cold perspiration, and when the signs of impending death are plainly evident. The cyanosis of influenzal pneumonia seemed to be due to an entirely different cause or combination of conditions from those present in lobar or pneumococcic pneumonia. The cyanosis of influenzal pneumonia was, therefore, most confusing, and became all the more so when it was recognized that it did not yield to the respiratory and circulatory stimulants usually employed when cyanosis is present. The inhalation of oxygen was resorted to rather routinely early in the epidemic. It seemed to temporarily influence the cyanosis, but the results were not permanent, and the outcome of the cases did not seem to be different from those in which oxygen inhalations were not used.

The blood pressure in those cases in which cyanosis was observed was invariably low. This seemed to be due to the infection, for in several private patients not belonging to this group of patients with previously known high blood pressures the blood pressure was observed as much lower throughout the course of the infection.

_Leucopenia_

The peculiar behavior of the white blood corpuscles will be discussed more fully in another paper of this series. Our remarks will deal more particularly with the clinical observations and interpretations. The leucocytes fell below the normal from the very onset of the disease; they varied very little regardless of great changes in temperature; they did not always increase, or if they did increase at all it was comparatively little, even in an extensive invasion of the lungs or in severe complications. Concerning the leucopenia we have no explanation to suggest, save that it is a clinical characteristic of the disease. Our first thought was that the infection came on so suddenly and profoundly there was no time for a leucocyte reaction. But when we recall other diseases associated with a leucopenia, notably typhoid fever, which does not come on with such suddenness, our explanation for the leucopenia of influenza does not seem to hold. The leucopenia must be simply a peculiar toxic blood reaction characteristic of the Pfeiffer bacillus invasion. Such an explanation has long been accepted in the Eberth bacillus infection.

_Asthenia_

A condition which was frequently noted by the patient was an indescribable weakness and prostration which appeared early, sometimes before any other symptoms were noted or before any elevation of temperature. The young soldier was in apparent perfect condition when he arose in the early morning. During the “setting up” exercises he did not feel so fit, and a few hours later appeared extremely weak. When his condition was called to the attention of the medical officers he was found to have a slight elevation of temperature and was sent to his bed.

In former epidemics, as also in this one, marked prostration was recognized as coming at the height of the disease and remaining persistently during convalescence. But it does not seem to be recorded as among the first symptoms.

_Influenza with Lung Involvement_

Of the group with lung involvement much may be written from a clinical standpoint, and much confusion may be brought about. Especially is this so if one has no definite idea of the pathology present, or if one enters into a discussion of the character of the infection—a point upon which there is as yet no unanimity of opinion. From the many reports which have been put forth from the base hospitals of the various cantonments, and also from the reports coming from civilian practice, it is evident that scarcely any two groups of laboratory men or any two individuals of those separate groups have the same idea as to the bacteriology and the pathology peculiar to this epidemic.

As long as there is this confusion and element of doubt in the minds of those to whom we are accustomed to look, the clinician must necessarily speak with considerable hesitancy, especially when he attempts to interpret the physical signs observed. In our own group the observations of Klotz, Guthrie, Holman and others have given us an interpretation of our clinical findings which, at present at least, is more or less satisfactory. We shall definitely keep in mind their observations and conclusions as we go on with the description of the physical signs of the chest in cases having lung involvement.

In the description of this group it will readily be seen that the lower respiratory tract stood the brunt of the infection. Of the 153 soldiers under our care, 60, or about 40 per cent., were recognized as having pneumonia. Of these, 34 had undoubted demonstrable signs, while 26 were questionable, and yet from the temperature and other symptoms we concluded there was a pneumonia. Of the 394 civilians, 189, or about 50 per cent., had pneumonia. Of this group there were again some 28 or 30 in which the diagnosis was doubtful, according to the ordinary way of making a diagnosis, but we felt sure from the temperature course that more than a simple influenza was present. In the description of the physical findings of the chest in these influenzas with lung involvement it will be readily seen why the diagnosis must sometimes be in doubt.