From the standpoint of general pathology, malaria is an infectious disease of man caused by protozoa, which attack the blood, or, more accurately, the red blood corpuscles. If, on the basis of our present knowledge, we were to give malaria a rational name, this would probably be " erythrocytonosis protozoica." As an infection limited to the erythrocytes, malaria occupies in human pathology a unique position. So far no second parasitic disease of the red blood corpuscles of man has been recognized. Yet the interesting discoveries of Gaule, Danilewsky, and others in the lower animals have proved that such infections are not confined to man.
Aside from the infection of special cells, malaria is of further general interest in that it is the first protozoan infection of the human organism determined with certainty.
On account of the interdependence of all cells in an organism, it could not be expected that the disease changes in the blood corpuscles would be without influence on the remaining cells. As a matter of fact, the examination of the peripheral blood itself would disprove such an idea. This shows the circulating leukocytes containing black pigment, the product of digestion of the hemoglobin in the bodies of the parasites. This pigment may be introduced into the leukocytes in three ways-namely, the leukocytes acting as phagocytes may take up pigment rests that have become free by segmentation of the parasite; second, they may take,up entire pigmented parasites, or, finally, the parasites may force their way in a hostile manner into the leukocytes.
Anatomic investigation shows further and greater effects. Pigment and parasites are found in larger and smaller mononuclear and polynuclear cells in the spleen, liver, bone marrow, and lungs, and pigment alone in the vascular endothelium of different organs and Kupffer's cells in the liver.
Even more important is the faculty manifested by the infected blood corpuscles of adhering to the vessel walls and accumulating in certain capillaries, so as occasionally to obstruct them.
The question that at once suggests itself is, How does the organism eliminate the malarial pigment?
A great part seems to be absorbed by the leukocytes, especially the macrophages; the rest is deposited by these cells in the neighborhood of perivascular lymph sheaths, and in these lymph sheaths the pigment is eventually found.
To the lymph apparently falls the work of removing it further. How it does this is not yet very clear. The lymph possibly dissolves a part, though some is undoubtedly deposited in the lymph glands, as is evident in the case of those neighboring the liver. These glands perhaps finish the work.
It is questionable if the parenchymatous cells participate at all in the absorption of the pigment. True, we sometimes find liver cells containing pigment, but whether or not they are able to transform it into bile we cannot at present say.
In addition to the black pigment, which, as the product of the parasite, is pathognomonic for malaria , there is the ocher colored pigment to account for.
In contrast to the malarial pigment which is elaborated in the peripheral blood, the ocher colored pigment takes its origin in the tissues. It is found especially in the liver cells, the spleen, the bone marrow, the kidneys, the pia, the thyroid gland, and the pancreas. It is observed only exceptionally in the vascular endothelium and circulating leukocytes.
This ocher colored pigment is a derivative of hemoglobin, and originates from the destruction of red blood corpuscles, which are not completely consumed by their parasites. This is less true of the tertian and quartan parasites than of the parasites of the second group, which segment at a time when they scarcely half fill the corpuscle, so that considerable amounts of hemoglobin or corpuscular debris are thrown into the plasma. Another source of hemolysis is probably found in the necrosis and fragmentation of non infected erythrocytes, due to the action of the toxin.
The hemoglobinuria proves that under circumstances the hemolysis may be enormous, though we are not yet in a position to explain the conditions responsible for it.
Whether the fragments of the erythrocytes are taken up as such by the parenchymatous cells and transformed into this ocher colored pigment, or whether only the hemoglobin of these fragments infiltrates the cells in a dissolved condition and is there precipitated in this form, is a question which, in our opinion, may be answered by the assertion that both probably occur. The further fate of this pigment is only partially known.
It is very probable that the liver cells elaborate their portion into bile, which would thus explain the frequently observed poly cholia.
How the other organs act toward it is not fully understood. Some of them-the spleen-seem to send it on to the liver. Whether it can be elaborated into urobilin in the places where it occurs outside the liver, as some authorities assume, must be considered questionable.
In contrast to the disturbances produced by the pigment, which, as we have seen, affect almost every cell in the body, the necrotic processes in the parenchymatous organs play a secondary role. The greater part of these are the result of capillary thromboses, though some must be attributed to the effect of toxins. The elimination of these necroses is usually brought about in the same way as in other infectious diseases.
In regard to the connective tissue overgrowth (splenic tumor, cirrhosis) that is seen as a remnant, it is impossible to say whether it is produced by "irritation" of the pigment or is the result of an equalization of equilibrium in the tissue following the necrosis of parenchymatous cells.
Up to a relatively short time ago the disease symptoms were a problem, the solution of which had occupied the minds of pathologists of all ages. But Laveran's discovery and the investigations of other observers have so thoroughly explained them that malaria may now be reckoned among these diseases, the pathogenesis of which has, to a great extent, been scientifically determined.