The last stage in the development of the parasite is that of multiplication. This is ushered in, as a rule, by the pigment which was previously irregularly distributed, concentrating itself centrally or eccentrically. Though this is the rule, it must not be forgotten that exceptions are very numerous, and that multiplication may take place while the pigment is scattered.

The principal feature in multiplication consists in the breaking up of the mother parasite into a number of small bodies, every one of which is complete in structure and possesses the power of independent existence. We designate these new organisms as spores, and their process of origin as sporulation.

Arrived at a certain stage of development, the parasite, therefore, sporulates. With this its existence ceases, and in its place several young organisms appear and continue its parasitic activity.

Besides these newly formed spores there remains a remnant of the mother parasite, consisting principally of pigment. These pigment rests are inanimate and are quickly taken up by leukocytes and vascular endothelium and so removed from the circulation.

At the time of their formation the spores lie within the motherparasite, which, on its part, is within the remaining shell of the infected red blood corpuscle. Rupture of this double shell is, therefore, necessary before the spores are free. This rupture may be observed not infrequently under the microscope.

The size and number as well as the other characteristics of the spores differ with the different varieties of parasites, but we will return to this when treating of the special peculiarities of the organisms.

In addition to sporulation, there is another very remarkable metamorphosis in the mature parasite, which, differing from sporulation, does not take place within the blood vessels, but only after the blood has been exposed to external influences. It is observed when the microscopic preparation is studied some time (ten to twenty minutes) after the removal of the blood. This process consists in the sending out of flagella.

These flagella are developed from large sexual (male) forms of the parasites. This highly interesting process is best studied in the spheric bodies of the crescent group (see below), and occurs as follows : The round parasite, which up to this time has lain immovable, except for the lively to and fro motion of the pigment within it, begins suddenly to show marked movements of contraction, associated with drawing in and bulging out of its margin. Soon after, glove finger like pseudopoclia protrude from different places on the surface. These are limited by the membrane of the organism. This membrane resists the outward pressure of the flagella for some time (often entirely), yet eventually, they break through, and while the plump pseudopoclia sink back, their long, thin flagella shoot out and whirl around so rapidly that their contour is visible only now and then. The violence with which the flagella strike the red blood corpuscles lying about, causing deep furrows in their substance (though these furrows quickly disappear), has been frequently described.

Small nodules which seem to change their place are often found on the flagella, and their free end is usually knobbed. Here and there fine pigment granules are seen within them.

The number and arrangement of the flagella vary. From one to five may be observed on one organism, though they are often difficult to count on account of their rapid vibration.

Their movement continues about fifteen to thirty minutes, becoming gradually weaker, more intermittent, and finally ceasing. The motionless flagella may then be seen attached to the organism.

Frequently the flagella become separated from the organism and swim about in the plasma with a liveliness resembling that of an eel. These free flagella constitute the only form of malarial parasites which have to any degree the power of changing their location.

What is the signification of these flagella? Since he first observed them, Laveran has claimed that they represent the highest stage of development of the parasite, because they develop in the cell body and escape at the time of maturity. They may be considered, therefore, as significant of the multiplication of the parasite. Up to the time when Laveran stated this he had not recognized the sporulation of the organism.

But little attention was bestowed by the Italian investigators on the flagella. Their occurrence was represented as exceptional, and the whole phenomenon of their origin was described by Grassi and Feletti as an agonic symptom of the parasite. This view was adopted at the time by many Italians, but in the light of recent discoveries has been universally abandoned.

In the course of my investigations I paid especial attention to the flagella, and came to the following conclusions: Flagella occur in connection with all varieties of malarial parasites. They are most frequently observed on the spheres that belong to the crescent group, almost as frequently on the tertian parasites, and more seldom on the quartan ones. From their frequency (which can be confirmed only by repeated and careful examinations of the blood) I concluded that the flagella are to be regarded as necessary attributes of the parasite in a certain stage of its existence.

In connection with some varieties of parasites, as, for instance, the common tertian, flagella may be found regularly, and often in large numbers, a few moments after the removal of the blood; a longer time-about ten to thirty minutes-is necessary before they appear on the crescents. I have been able to find flagella in most cases of malaria that showed numerous parasites, especially when the duration of the disease permitted several examinations.

In my opinion these forms were by no means the products of the agonic period, for in this case it would be inconceivable why so relatively small a number should occur at a time when all the organisms in the preparation are in the act of dying, and why they are not seen, at least here and there, in the circulating blood at the time of the paroxysm, or after the administration of quinin, when so many organisms are succumbing. Finally, the extraordinary activity of the flagella could scarcely be said to indicate that they are an expression of death.