The pathologic findings in long continued cases of malaria are variable and numerous.

It is necessary to differentiate between organic lesions the direct result of the infection, and ones due to complications. We intend to discuss especially the former, but so far as the limits of the work allow, we will not ignore the latter.

It is necessary to differentiate again between the organic changes observed after a long continuous, but not yet terminated, infection, and those which persist after the disease has passed. Since these differ from one another only in the presence and absence of parasites in the circulating blood and organs, a separate discussion is not called for.

The most important alterations in chronic malaria are found in the spleen, liver, and bone marrow.

Spleen

The spleen is always considerably enlarged, and usually exceeds a kilometer in weight. Kelsch and Kiener observed, as a maximum in one case, 2625 gm.; Pantioukoff, 3342 gm. According to the latter, chronic splenic tumors are found in 69 per cent, of autopsies in the Caucasus.

The capsule is thickened and in places indurated. This thickening is not uniform, but is irregularly distributed over small areas. In one case I observed the whole capsule calcified. Adhesions to the diaphragm and other neighboring organs are frequent.

By the enlargement the normal form is lost; the consistence is increased; the color becomes a reddish, that sometimes recalls muscle tissue, though while the infection continues it is more grayish brown.

On section, numerous grayish white lines corresponding to the thickening of the connective tissue stroma and the vascular sheaths are found. The veins are dilated, sometimes to such an extent that they give the appearance of an angioma. The Malpighian bodies are scarcely or not at all recognizable.

The microscopic picture varies according to the interval which has elapsed since the first infection, for changes are continually occurring which gradually produce, from the soft pigmented, relatively small, acute tumor, the immense hard ague cake. It is impossible for us to follow the gradual phases of this highly interesting process, and we can only refer to the thorough work of Bignami, to which we have had frequent recourse in the following.

Shortly after the cessation of the infection, the most important histologic factors are: A marked diminution in the hyperemia; miliary necrotic areas and intense hyperplastic processes in the pulp and sometimes in the follicles. The arrangement of the pigment changes, in that it collects in heaps in the pulp, concentrating itself about the vessels, and in the connective tissue septa.

In later stages the pigment is found only in the perivascular lymph spaces, and gradually a larger portion of it is resorbed by the spleen. The macrophages, which, in the acute enlargement, were the carriers of the pigment, have disappeared, probably as the result of degeneration, and the pigment is now extracellular. Later on the pigment disappears entirely.

The necrotic areas are gradually resorbed, while the hypertrophy of the septa, the dilatation of the vessels, and the lessening of the pulp become more and more conspicuous. The follicles undergo fibroid degeneration and become eventually unrecognizable. The final ague cake is made up principally of thickened stroma and dilated vessels; the pulp cells and follicles are reduced to a minimum, and the physiologic function has almost disappeared.

Liver

The liver is enlarged and may reach a weight of three or four kilos. Its surface is smooth; its consistence, increased. The capsule is frequently thickened. The cut section varies according to the time that has elapsed since the infection. Regularly pigmented during the acute infection, we see, in the course of time, the pigment lines becomes arranged perilobularly, with the production of a very pretty network.

Shortly after the infection we find microscopically the following (Bignami): The capillaries are devoid of parasites, the endovascular macrophages have disappeared, and the pigment is exclusively in the endothelial and Kupffer's cells. The necrotic parts of the lobules atrophy, and the vessels dilate in consequence.

Later on the lobules get rid of the pigment by means of mononuclear and polymorphonuclear leukocytes, which carry it to the periphery. At the same time regenerative changes are occurring in the liver cells.

As a result of the atrophy and regeneration we find here false angiomata and lymph cysts, there, enormously large lobules. The pigment is carried from the vessels by leukocytes and deposited in the perivascular lymph spaces. The perilobular connective tissue becomes hyperplastic.

Eventually, therefore, we have a large hard liver of reddish color, which, on section, shows conspicuously the granular looking lobules surrounded by their connective tissue stroma. The vessels are dilated ; the amount of blood in the organ is increased, and the pigment is no longer visible.

According to Kelsch and Kiener, a few months after the termination of an infection no pigment can be found in the organs. Bignami likewise observed that after three to four months the greatest portion of the pigment had disappeared.

In addition to the three forms of parenchymatous nodular hepatitis (with hyperemia, with cirrhosis, and with adenoma) Kelsch and Kiener differentiate an insular cirrhosis with nodular hepatitis, an insular cirrhosis with diffuse parenchymatous hepatitis, and an annular cirrhosis with parenchymatous hepatitis. Though these cirrhoses have been carefully described by Kelsch and Kiener, we refrain from further details, since they have not, as yet, been generally accepted.

Marchiafava and, according to him, Bignami deny, as we have previously stated, that cirrhosis develops as a result of malaria . They admit a perilobular increase of connective tissue about the individual lobules, but assert, at the same time, that the branches of the portal vein are not only not destroyed, but further developed, while in Laennec's cirrhosis the connective tissue surrounds several lobules at a time and produces strangulation of the portal vessels. Moreover, the liver cells themselves show differences.