GASTRO-INTESTINAL FORM.

Vomiting is one of the initial symptoms in one-fourth of all cases. Aside from vomiting, loss of appetite and other slight digestive disturbances common to the acute infectious diseases, gastro-intestinal symptoms are rarely pronounced. According to Bristow, who made an extended study of the subject, the bowel movements were normal in 72 per cent of cases. Constipation was present in 11 per cent; diarrhea, in 12 per cent. Exceptionally, however, the symptoms elsewhere may be mild or absent, and gastro-intestinal symptoms may predominate. Acute hemorrhagic gastritis and enteritis may be followed even by a peritonitis, which is usually of the fibrinous, rarely of the purulent, type. At times, gastro-intestinal influenza is characterized by vomiting and purging, approaching the severity of a cholera.

The spleen is usually not apparently enlarged in mild influenza. It is estimated that it is palpable in about 15 per cent of all cases.

FEBRILE FORM.

The febrile form of the disease, characterized by the occurrence of fever, as the only or at least the predominating manifestation of the disease, is not rare during an epidemic of influenza. The temperature may be continued, intermittent or remittent. Chills may occur. In some cases the fever is prolonged, and may resemble the curve in typhoid. It is doubtful whether an attack of real influenza occurs without fever at some time in the course of the infection, except in the very mild or abortive forms of the disease.

The disease manifestations due to the direct action of the influenza bacillus or its toxins upon the circulatory system, the urogenital tract and skin present no peculiar diagnostic features. The pulse rate usually corresponds to the temperature. It is noteworthy that a real bradycardia occurs more frequently in influenza than in any other acute infectious disease. It is probable that the slow pulse rate, when present, is due to the effect of the toxins upon the vagus center.

Herpes is present in from five to twenty five per cent of cases.

CONCLUSIONS.

1. The positive diagnosis of influenza is based upon the demonstration of the influenza bacillus in the various secretions and exudates in a given case.

2. The most important aid to the diagnosis of influenza, aside

from the bacteriological proof, is the presence of an epidemic of the disease. It is probable that sporadic influenzal infection is not rare. 3. Certain general and local manifestations of the disease have a minor value in diagnosis. Their importance, however, should not be underrated, since these general and local peculiarities cause us to suspect that influenza is present, and thus lead the way to positive bacteriological proof.

100 STATE STREET.

CONCERNING THE BACTERIOLOGY OF INFLUENZA. BY ELDRIDGE WYNEKOOP, M. S., M. D., CHICAGO.

PROFESSOR OF BIOLOGY IN THE UNIVERSITY OF ILLINOIS AND FIRST ASSISTAN1 BACTERIOLOGIST, CHICAGO HEALTH DEPARTMENT.

Of recent years influenza has worked such destruction in the human body that special interest has attended the study of its etiology. With the appearance of each epidemic, after the acceptance of the microbic theory of disease, numerous investigators sought to discover the particular organism which was believed to hold etiological relations to the disorder, but it was not until 1892 that this minute plant was recognized, and, in a measure, demonstrated to be the cause of influenza. Pfeiffer found it in the bronchial secretions, and Canon in the blood of individuals suffering with this disease. Klein verified the work of Canon and Pfeiffer, and extended our knowledge of the organism greatly by his own investigations. Others have gradually added their little, until what is known of this bacillus compares very well with what is known of other pathogenic bacteria.

MORPHOLOGY.

The Canon-Pfeiffer bacillus is a small organism-so small that fifty thousand of them placed end to end extend over but an inch of space, and when placed side by side, one hundred thousand are required to extend over the same distance. In scientific terms it is described as a minute rod, having a length of 0.54 micromillimeters, and a diameter of 0.24 micromillimeters.

In our experience, these dimensions apply only to fully developed organisms. Rapidly growing cultures often contain many bacteria which are nearly round, and which present few of the morphological characters of the adult bacillus. These forms are the daughter bacilli,

Chicago Medical Society, March, 1903.

which have been recently developed by the fission of the ancestral organisms. Frequently two of these daughter bacilli remain attached, and when division is thus incomplete, they resemble diplococci. The full grown microbes are two or three times as long as they are thick. They have round or slightly pointed ends, and are without capsules. Especial attention has been called to the segregation of the protoplasm by numerous investigators, which peculiarity sometimes gives the adult organism the appearance of a diplococcus, and when two or three of these are placed end to end they are said to resemble a chain of streptococci. This characteristic appearance has occasionally been observed when examining the bacilli, both in the bronchial secretions and in cultures which had grown eighteen or twenty four hours. When cultures of but a few hours' growth, however, were examined, the segregation of the protoplasm was seldom observed. The organism appeared as short rods, uniformly stained. This interesting fact leads to the suggestion that the segregated condition is one of the phases of cell division; that the separation of the protoplasm and its arrangement at opposite poles are changes preparatory to the fission of the entire bacillus. In support of this theory, there can also be added the fact that bacilli are met with in cultures which are longer than the average, and which show a well defined separation of protoplasm, and a slight constriction of the cell wall at the center. It seems probable that these cells are just in the act of division, and that in them we see another phase of reproduction which is completed in the formation of the young organisms.

In bronchial secretions, the influenza bacilli are usually solitary; sometimes in pairs, or arranged in chains of a few elements. Some observers claim that they are occasionally found in masses, especially in severe cases. They have been met with, also, inside of the leucocytes of the sputum. While this arrangement is seen when the bacilli are examined in expectoration, yet when observed in preparations made from cultures, they are, in the majority of instances, collected into groups or masses, seemingly held together by an intercellular

substance.

The organism stains best with carbol-fuchsin prepared according to Ziehl's method, using, however, but one-half of the prescribed amount of fuchsin. Before applying the stain it is well to immerse the cover slip or slide on which the material is dried in water, and thus prevent a precipitation of the fuchsin, which often occurs when this solution is used on a preparation that is dry, and especially one that is yet hot, after being passed through the flame, in order to

secure fixation of the material to the slide. Other staining solutions can be used, but are not satisfactory, in that they fail to make apparent all the morphological characters.

BIOLOGY.

These bacilli, we are told, are nonmobile, and so far as is known, do not produce spores. Their resistive powers are limited. They die quickly when dry, and are killed within five minutes when exposed to a temperature of 60° C. They will not grow at a temperature below 26° C., nor above 35° C., when developed on artificial media.

Cultivation.-Very few materials can be used for their cultivation. The best has been found to be blood serum, which contains a little hemoglobin. Human blood serum was at first used by us, but finding that the serum of beef's blood answered every purpose, it was decided to use it altogether. The blood should be collected in sterilized jars, and after standing a few minutes transferred to the laboratory and placed in an ice box. It is not necessary to use any special care in the handling; in fact, the opposite procedure is better, as by this means "bloody serum" is obtained, which will contain a sufficient amount of hemoglobin to make it a suitable medium for the development of the organism. In the further preparation of this culture material, Loeffler's method can be followed.

Upon such a medium the organism grows in a very characteristic After a few hours' incubation, "colorless, transparent, drop like colonies" appear, which resemble "condensed moisture." Upon serum which is somewhat old and dry the growth is scant, and the colonies are small and have a tendency to become opaque. When a smear culture is made, the growth is a moist, transparent layer. The organism does not develop well upon other media.

Pure cultures can, in most instances, be easily secured in the manner described in the Bulletin of the Chicago Department of Health for January, 1899, from which I take the following:

"Upon this medium," that is, blood serum, "cultures were made from the mucous membranes of the tonsils, pharynx, and from the bronchial secretions of persons ill with influenza. In many of these cultures the small bacillus was found, and in a few instances in a state which was almost pure. From the cultures which were comparatively free from other bacteria, transplantations were made to bouillon, a drop of which was immediately transferred to the surface of blood serum. Three tubes or boxes of serum were inoculated with the same drop, and by this means isolated colonies were usually obtained in the second or third tube."

According to Klein and other observers, the life cycle of the influenza bacillus is very short; unless a transmission is carried on within two or three days the the subculture will remain sterile. In substance, these observations have been found correct. A comparatively rapid death of the bacteria occurs when developed within the incubator. It has been noticed, however, that cultures, although there may be but infrequent transmissions, will live a number of weeks, provided they are left at room temperature.

Distribution. The bacillus seems pretty completely distributed within and without the body. In the course of our studies, it has been found on the nasal, pharyngeal, laryngeal mucous membranes; in pus from the pleural cavity, from the middle ear, and from the eyes; in discharges from the bladder and from the intestines; and in secretions from the bronchial mucous membrane. Canon found it in the blood, and other observers have met with it upon the meninges.

Galliard reports a case of influenza in which the symptoms proceeded successively from the intestines, the lungs, and the heart, and by bacteriological examination it was demonstrated that the invasion was gastro-intestinal primarily, the lungs and the heart being involved secondarily.

PANTHOGENESIS.

The bacillus is pathogenic for some of the laboratory animals. Pfeiffer found rabbits and apes susceptible to the disease, while rats, pigeons and mice were not affected. Guinea pigs are said to be especially subject to fatal infection.

Kruse, Huber, Richter and Borchardt demonstrated the presence of the organism in numerous influenza patients, and confirmed the results reported by Pfeiffer.

Mixed Infections.-That this minute fungus may complicate almost every disorder to which the flesh is liable seems probable. In the examination of several thousand cultures during the past five years, I have found it many times inhabiting various parts of the body, during varied disease conditions. It has been met with in tonsillitis, quinsy, diphtheria, whooping cough, measles, scarlet fever, mumps, pneumonia, typhoid fever, and disorders of the nervous system.

Of 2,460 cultures, made from various throat affections, but largely from suspected cases of diphtheria, within the last few months, and sent to the city laboratory for diagnosis, 677 contained the influenza bacillus. At no time since the winter of 1898 and 1899, when the board of health began the study of the bacteriology of influenza,