The more rapid development may depend either on an increased virulence of the parasites or a lessened resisting power on the part of the individual. Postponement is almost always the result of a retarded evolution produced by medication. The occurrence of the paroxysm at a later time is frequently observed after the first administration of quinin.
Relapses occur when some micro organisms fail to fall victims to the quinin, and later develop into sufficient numbers to produce paroxysms. It cannot be doubted that in the great majority of cases relapses are attributable to insufficient treatment, just as is the case in acute articular rheumatism.
We need only call attention to the similar duration of the intervals after which the majority of relapses occur and those which ordinarily constitute the period of incubation. The connection between these two facts need scarcely be mentioned. Still it sometimes happens that relapses occur in spite of sufficient and proper treatment. This would seem to indicate that there are parasites which possess a very high power of resistance to quinin. This conclusion is especially true of the crescents, which are absolutely refractory to quinin. The obstinate relapsing of estivo autumnal fever is thereby explained.
In fevers of the first group, not omitting quartan, we have no knowledge of refractory forms. Nevertheless it is possible that there are such forms, and likewise possible that Bignami's view may be the correct one.
Bignami assumes that the spores contained in the macrophages may become again capable of development after degeneration of their hosts. The inclosed spores are, therefore, to be regarded as latent parasites, capable, under circumstances, of reproduction.
It is possible, too, that, like certain bacteria, the malarial parasites are protected in the spleen. It is only necessary to recall cases in which trauma, electrization, or massage of the spleen called forth paroxysms. In those cases it may be that the latent parasites are forced from the spleen into the circulation, when paroxysms result as a consequence.
Though the relapses occurring within several weeks may be so explained, the problem remains unsolved how paroxysms can occur months and years after a single infection. Still we must say that further investigations are wanting to prove absolutely that there are such relapses without a renewal of infection.
The acute enlargement of the spleen which constitutes an almost constant symptom of malaria is attributable to different factors, as intense hyperemia, the deposition of large amounts of black and ocher colored pigment and of necrotic blood corpuscles, the invasion of parasites in all stages of development, in macrophages, in endothelial cells, and free in the pulp, etc. Moreover, a large number of the infected erythrocytes from the circulation are retained in the spleen, and it is probable that a further increase in parasites takes place there. Finally, the occlusion of the portal capillaries in the liver by pigmented macrophages, first observed by Frerichs, may exercise an influence by the consequent stasis (Bignami).
The phenomena coming into consideration in chronic tumor of the spleen have been sufficiently discussed in the section on Pathologic Anatomy.
Whether the spleen plays a more inimical or protective role toward the parasites is uncertain. It is undoubtedly true that it frequently constitutes a center of location for them; in fact, there are cases in which the peripheral blood is very poor in parasites, when puncture of the spleen shows the presence of numbers. The numerous macrophages filled with parasites would speak for the inimical role; the occurrence of enormous numbers of actively developing parasites, for the protective one.
The fact seems to be determined that malaria does not, at least, run a severer course after removal of the spleen than before (Tizzoni, Massopust).
The obstruction of the capillar circulation constitutes the important cause of the functional disturbances in the central nervous system. Planer made the pigment thromboses of the brain capillaries responsible for the different symptoms of cerebral pernicious fever. Frerichs agreed in part with Planer's conclusion, but introduced other considerations. Though he frequently observed pigment thromboses of the brain capillaries, as well as occlusion by white thrombi, he insisted that too much stress should not be laid on them, on account of the rich collateral circulation. He likewise affirmed that he had more than once seen markedly pigmented brains without cerebral symptoms during life, and that among 28 cases of cerebral pernicious fever, the pigmentation was entirely lacking in 6. On the whole, Frerichs seemed more inclined to think that it was chemic products resulting from the destruction of the red blood corpuscles that produced the cerebral symptoms.
The older observers recognized not only the thromboses of the vessels, but also the capillary hemorrhages, the result of them (Meckel, Planer), and Frerichs has even reported a large meningeal hemorrhage. Our views to day in regard to the origin of the cerebral disturbances differ in but few points from those of previous authorities.
Laveran, Marchiafava, and Celli demonstrated that we have not to do with pigment thromboses, but with obstruction of the vessels by infected erythrocytes. The tendency of these erythrocytes to adhere to the walls of the smaller vessels has already been spoken of, and the obstruction is aided by swelling of the capillary endothelium.
In the majority of cases, therefore, the thrombosis is produced not by a dead mass, like pigment, but by living parasites inclosed in blood corpuscles. Only occasionally do we meet true pigment thrombi or ones that are made up of melaniferous leukocytes, free parasites, or free spores (Marchiafava and Bignami). This origin of the thrombi makes it intelligible how severe cerebral disturbances may come and go with surprising rapidity. The obstruction to the circulation is of such a kind that it may be removed even as quickly as it develops.