STUDIES ON MEASLES (1921)

By the intratracheal injection into monkeys of unfiltered nasopharyngeal washings from cases of measles in the preeruptive and early eruptive stages of the disease a relatively constant group of symptoms was induced which closely resemble those of measles in man. Of seven monkeys inoculated intratracheally with unfiltered nasopharyngeal washings from seven cases of measles, five developed the symptoms. The same group of symptoms was induced in one monkey by inoculation of the mucous membrane of the nose and mouth with unfiltered nasopharyngeal washings from a case of measles. In these experiments a variety of organisms, largely saprophytic inhabitants of the nasopharynx and mouth, were present in the material inoculated. There is sufficient evidence, however, that these organisms were in no way responsible for the reaction, since the same group of symptoms was induced in two monkeys by the intratracheal injection of nasopharyngeal washings from three cases of measles after the washings had been freed from ordinary organisms of the mouth flora by filtration through Berkefeld N filters. The characteristic group of symptoms which follows the inoculation of monkeys with the nasopharyngeal washings from patients with measles has been. successfully carried through six passages by intratracheal injection of saline emulsions of the skin and buccal mucous membranes of monkeys killed from 2 to 6 days after the onset of the reaction. From the fourth passage monkey the reaction was also successfully induced in three monkeys by means of citrated whole blood injected intravenously. This experiment showed the blood to be capable of inciting the reaction from at least the 7th to 13th days after intratracheal inoculation of the donor monkey, but incapable of inducing it from the 2nd to 4th days. Cultures of the blood showed no growth. The group of symptoms induced has been constant and definite in character. After an incubation period of 6 to 10 days the animal becomes listless and drowsy, the conjunctivae become injected, and small, discrete, hyperemic macules appear on the labial mucous membrane. These spots increase in number and may eventually coalesce in the course of 2 to 4 days to form a diffuse, red, granular rash. This rash is usually limited to the labial mucous membrane but may extend to the inside of the cheeks. The individual macules may or may not show the minute bluish white center characteristic of Koplik spots. From one to several days after onset an eruption of small, discrete, red maculopapules appears on the skin, usually coming out first on the face. The rash progressively increases in the number and size of the individual lesions and may in the course of 2 to 3 days extend to the skin of the neck, shoulders, upper arms, chest, abdomen, and thighs. It is constant in character but varies considerably in extent in different animals. By the time the exanthem is fully developed, the rash on the mucous membranes has begun to fade and soon disappears. The exanthem in turn progressively fades, sometimes with a branny desquamation, sometimes without. There may be moderate pigmentation. By the 6th to the 10th day after onset all symptoms have disappeared and the animal again appears well. Coincident with this group of symptoms there is a constant and definite reduction in the total leucocyte count, frequently constituting a true leucopenia. Other symptoms of irregular occurrence are photophobia, diarrhea, and fever. Symptoms of rhinitis and bronchitis have not been noted. Histological sections of the lesions of the skin show an exudative and proliferative lesion about the capillaries of the corium in which endothelial leucocytes are the predominating cells. Mitotic cells are not infrequently present in these areas. The endothelial leucocytes may be seen migrating toward and occasionally invading the epithelial layers of the hair follicles, sebaceous glands, and epidermis. In places the epithelial cells appear edematous and vacuolated, and there is evidence of minute vesicle formation. The lesions of the labial mucous membrane are similar in character. Minute vesicle formation in the epithelium is more frequent and the vesicles occasionally assume a more pustular appearance. Similar lesions are found in histological sections of the tongue. Cultures of the blood made both during the incubation period and during the course of the reaction in a variety of media, aerobic and anaerobic, have consistently shown no growth. The close similarity of the symptoms and pathological lesions of the reaction to the symptoms and pathological lesions of measles, the successful transmission of the reaction from monkey to monkey, and the elimination of ordinary bacteria as a possible source of error in the interpretation of the results, warrant the belief that the reaction is caused by the inciting organism of measles.