Kelsch, who first called attention to the decrease in leukocytes (1: 2000 in comparison with the erythrocytes) during the acute infection, found that on strong faradization of the spleen the number of leukocytes in the peripheral blood increased. From this he concluded that the leukocytes had accumulated in the spleen and were forced into the circulation by the contraction of the organ. He found an increase in leukocytes only in pernicious cases (1:48).

Whether there is a causal connection between the leukocytosis and the perniciousness is uncertain. I have suggested the possibility that under normal conditions the polynuclear leukocytes collect in the spleen, where, favored by the slowing of the blood current, they are able to consume the parasites and thereby decrease the infection ; under other conditions they remain in the circulation, where they cannot exercise this activity, and the infection, as a consequence, becomes severer.

Golgi affirms a rhythm in the phagocytic activity of the leukocytes which runs parallel to the fever. In quartan and tertian fever, for instance, this phagocytosis begins with the paroxysm and continues three or four hours afterward.

This fact I can confirm, namely, that the greatest number of melaniferous leukocytes is found at the time of the paroxysm and shortly after it. Yet this is not so on account of any "cyclic function" on the part of the leukocytes, but because the segmentation of the parasites at this time sets the pigment free, and it falls to the duty of the leukocytes to carry it away. Possibly, too, chemotaxis comes into play. I regard the melaniferous leukocytes not as parasite eating phagocytes, but rather phagocytes whose duty it is to remove only the lifeless pigment.

All in all, from the investigations of Metschnikoff, Guarnieri, Bignami, Marchiafava, and others, it would appear that phagocytosis was principally an affair of the macrophages and endothelial cells; though the usefulness of the macrophages would be to a certain extent impaired, if, according to Bignami, many of them degenerate before they have digested the parasites they have taken up. The role of the circulating leukocytes appears to limit itself to the removal of the pigment, the cadavers of parasites, etc.

In addition to phagocytosis, other factors come into consideration in the spontaneous cure. We have stated in another section that by no means all the parasites reach the stage of segmentation, but that a considerable number are interrupted in their development, when they break up and die. We may recall the dropsical, distended, sterile forms of the tertian parasite, and it is to be assumed that the same thing occurs in other species.

Further, during the fever paroxysm many fragments of parasites are observed circulating in the blood. These are the remains of large parasites which have been broken up by the specific action of the blood serum, of the parasitic toxin itself, or other unknown causes.

From the standpoint of our present knowledge, therefore, we may say that spontaneous cure is the result of phagocytosis, of the sterility of numerous adult forms, and of the destruction of free parasites during the fever paroxysm.

The question now arises, Is it proper to wait for spontaneous cure and leave the patient to his fate? To this there is only one answer, namely, quinin must be administered in every case of malaria , even if spontaneous cure has already set in, unless it is excluded by very definite contraindications.

We must at the present time allow that a number of parasites may exist in the blood or in the internal organs, and even increase there, without, at least for a certain period, producing symptoms. I have seen such cases repeatedly, and Vincenzi has published interesting observations about others. This condition is usually seen in old malarial patients. The apyrexia, therefore, cannot be trusted, and for the sake of certainty quinin should be administered in order to prevent increase of the anemia and subsequent relapses. In cases of a severe character it would be decidedly injudicious to wait for spontaneous cure.