The segmentation of the parasites occurs immediately before and during the fever paroxysm. Ordinarily we see that the first sporulation forms about three hours before the outbreak of the chill, at which time there may already be considerable elevation of temperature.
The sporulation forms may vary more or less in their shape and size. For instance, it sometimes happens that sporulation may occur at a time when the parasite has not yet reached the size of the red blood corpuscles. Under these circumstances the number of spores is usually less-about four to six. Canalis described an interesting sporulation form of fan shape, produced by the clumping of the pigment eccentrically. The nucleolus may be invisible. Jancso and Rosenberger assert that they have observed flagella on the spores, by the aid of which they moved about.
The infected red blood corpuscles remain unaltered in shape and size, or become somewhat smaller without change of form. The color of these shrunken, though round corpuscles is darker than that of the non infected. The infected corpuscles are not at all or only slightly decolorized-in fact, as already mentioned, they may become somewhat darker. In this they are especially differentiated from the corpuscles infected with tertian parasites.
The following findings in quartan fever show the different stages of the parasites corresponding to the different stages of a fever cycle:
Twelve hours after the paroxysm: Small parasites, showing sluggish ameboid motion or immotile, containing but little pigment, or non pigmented, and situated on or within the red blood corpuscle.
Twenty four hours after the paroxysm: Isolated organisms show at the periphery a few pigment granules, others none at all. Their size is about one sixth to one fifth that of the red blood corpuscle.
Forty eight hours after the paroxysm (twenty four hours before the subsequent paroxysm): The parasites take up half or two thirds of the red blood corpuscle; they are markedly pigmented, usually round, and immotile. The pigment likewise shows no motion.
Sixty hours after the paroxysm (twelve hours before the paroxysm) : The parasites fill the red blood corpuscle so completely that only a small margin recognizable by its color remains.
Sixty six hours after the paroxysm (six hours before the paroxysm) : In many instances nothing more can be seen of the margin of the red blood corpuscle. The pigment is radially arranged, and in some corpuscles, loosely clumped. In isolated parasites signs of beginning sporulation may be perceived.
Sixty nine hours after the paroxysm (three hours before the paroxysm): Individual organisms are in the act of sporulation; many others show clumped pigment and the signs of beginning sporulation.
As an example of the connection between the stages in the fever and the development of the parasite I give here, in an abridged form, an instance of simple quartan:
R. G., aged twenty two, was admitted on January 26, 1893, to the first Medical Clinic (Prof. Nothnagel). He first manifested quotidian intermittent in September, 1892; he had a relapse in November of the same year. He had now been suffering since December 28 with a new relapse, the paroxysm of which occurred every second or, more frequently, every third day.
Blood examination-January 26, 11 a. m. : Temperature, 37°. Large numbers of parasites filling completely the red blood corpuscles. In many the pigment was clumped and their substance divided into four to six segments. Many of these segments showed a clear speck. The infected blood corpuscles were not swollen. Simple quartan was diagnosticated, and the paroxysm was announced as immediately at hand. As a matter of fact, at 2.45 p. m. there was a violent chill and the temperature at 4 p. m. was 39.6°. In the blood taken during the paroxysm large numbers of organisms in the act of sporulation were found.
January 27: Normal temperature. The blood showed quite a number of small pigmented parasites, from about one sixth to one fifth the size of a blood corpuscle.
January 28: Normal temperature. In every twentieth microscopic field an infected blood corpuscle. The parasites contained considerable pigment, lying immotile at the periphery. The size of the parasites was three fifths to four fifths that of a blood corpuscle. The blood corpuscles were neither enlarged nor decolorized.
January 29: Day of paroxysm. 10 a. m. : Temperature, 36.8°. A parasite was found in about every twentieth microscopic field, taking up almost the whole of a corpuscle. The majority contained pigment clumped at the center and showed beginning sporulation; in a few the sporulation was almost complete. Number of spores, nine.
12 m. : Temperature, 37.5°.
2 p. m. : Temperature, 39.6°. Beginning of the chill.
4 p. m. : Temperature, 40.5°. A small number of sporulation forms, some of which were in the act of breaking up, and a few quite young parasites with scanty pigment.
We observe sometimes a lively activity of the pigment in large free spheric organisms that probably remain sterile.
The protrusion of flagella is seldom seen. The course of development is more regular than in the other species, both in relation to the duration of development and the progress in growth of the single individuals. Moreover, sporulation forms are more frequently found in the peripheral blood, since the whole cycle of development usually takes place within the vascular system.
Finally, the development of the parasites belonging to one generation or series pari passu makes it relatively easy to recognize the presence of several generations and judge of their age.
Its duration of development requires forty eight hours. When seen first in the corpuscle, it appears as a small (1 to 2 micro in diameter), somewhat clear spot. In this stage it is non pigmented or contains only extremely fine pigment dust. It possesses a lively ameboid movement, readily visible at the room temperature for a long time (about an hour) after the removal of the blood. This consists not in a slight change of form, but in the actual protrusion of pseudopodia in different directions, which are soon drawn in to make room for another formation. The parasite remains at this stage (Golgi's first phase), growing gradually for about twenty four hours. More and more pigment in the form of fine granules and lines collects, particularly at the periphery of the plasma, where it usually manifests a lively swarming movement. The greater the amount of pigment, the older the parasite and the less its ameboid movement. Still we frequently see, on apy retic days, pigmented organisms (often curiously branched on account of their pseudopodia) which continue to change their form actively, at a time when they are more than half the size of the corpuscle.