STUDIES UPON EXPERIMENTAL MEASLES : I. THE EFFECTS OF THE VIRUS OF MEASLES UPON THE GUINEA PIG.

In general it may be said that three striking alterations occurred constantly in the animals reacting to intracardiac injections of blood from cases of measles; namely, pyrexia, leucopenia, and nephritis. The elevation in temperature usually began about the 9th day following inoculation, the rise being fairly abrupt from the normal to 104 degrees F. and above, at which height it remained with slight fluctuations for 3 or 4 days, finally subsiding by lysis. During the period of fever, particularly in the animals of first transmission, often no objective signs of illness were to be noted, the guinea pigs remaining lively and eating as usual. When the animals showed any outward signs these were manifested by a loss of appetite, lusterless and ruffled hair, and indisposition to move even when disturbed. The typical exanthematous signs of human measles were not observed in any of the animals. In some there occurred a slight coryza and watering at the eyes; however, no special account was attached to these signs as they were rather indefinite and inconstant, especially for animals of first transmission. Coincident with the rise of temperature there always appeared a fall in the total leucocytic count; in some animals the drop in white cells preceded the rise in temperature by 2 to 3 days. The leucopenia, though well defined, varied for animals of the same series. In some the count was as low as 3,600 cells per c. mm.; in no case did we fail to note at least a moderate fall in the leucocytes. The average time for the appearance of this cellular change was 9 to 10 days following inoculation; in other words, the leucocytic reaction seemed to indicate the end of the incubation period. So constant and striking was the leucopenia that we stress this as the most significant feature of the reaction of the guinea pig to the injection of measles blood, particularly since normal blood produced not the slightest change in these white elements. The greatest leucocytic depression was observed around the 12th to 14th days, which corresponded approximately to the stage of temperature peak. Following the leucopenia, the leucocytic rise was very gradual, taking on the average 8 days to attain the normal level. The animals killed at the height of the reaction, or those dying presumably from the effects of the blood containing virus, showed as the most constant lesion gross evidences of acute nephritis. The kidneys in these cases were swollen, cloudy, and congested. In certain guinea pigs there were in addition well defined petechiae and larger blood extravasations scattered throughout the cortical substance. In the animals dying after inoculation, the kidney alterations were found so constant and characteristic that we regarded them as a special index of the experimental infection. In these animals the hemorrhagic areas were not infrequently 2 to 5 mm. in extent, and when occurring on the surface of the organ produced a separation of the capsule. Occasionally free blood was noted in the pelvis, and in the absence of hemorrhage within the pelvic lining, we assumed that it came from the uriniferous orifices of the calicos. Microscopically the kidney sections revealed evidence of acute hemorrhagic nephritis, the hemorrhages for the most part being related to the capillaries of the tufts and the tubules of the pyramids. In the most pronounced cases practically all glomeruli were affected. Every stage from marked dilatation of the capillary whirl to well defined intercapillary blood extravasations that often filled the capsular space, and in consequence partially or completely obliterated the glomeruli, were found. Whether a destruction of the endothelium occurred, could not be determined. The absence of a neutrophilic reaction was of special significance, these elements of acute inflammation being nowhere found associated with the kidney lesion. The blood in relation to the tubules commonly occurred in the lumen of the collecting tubules and in the form of red blood cell casts. The spleen usually was found enlarged, particularly in the guinea pigs presumably dying as a result of the virus injections. Aside from the usual parenchymatous changes common to toxemias, the other internal organs showed nothing of special note.