Yet it may be regarded as settled that, ceteris paribus, an infection with a large number of malignant parasites is more severe than one with a smaller number.
There are apparent individual exceptions to this rule-for instance, Baccelli has reported cases of pernicious fever where the number of parasites was small. But in these cases only the peripheral blood was examined, which, as mentioned above, cannot be regarded as a criterion. In other cases where there are no parasites or their number is small and yet the pernicious symptoms continue, we must consider the possibility that the parasites may have been killed by the quinin, but that the organic changes produced by them or their toxin (for instance, degeneration of the endothelium of cerebral or renal vessels, or small hemorrhages in the brain substance) are so advanced as to be able to continue the symptoms of the disease.
The toxicity of the malarial parasite is an assumption, though, according to our way of thinking, a justifiable one. Moreover, it is not without reason that we attribute a greater toxicity to the malignant parasites than to those of the first group. As we have shown, the difference in numbers is not sufficient, therefore we must bring into question the toxicity. This is not necessary in all cases, for there is no doubt that a great number of the pernicious symptoms may be explained on purely mechanical grounds, yet there always remain certain symptoms which cannot be explained in this way-for instance, the malarial or postmalarial hemoglobinuria and the necrotic changes in the renal epithelium found by Bignami. These, for the present, must be attributed to the action of the toxin.
The effect of quinin on the parasites varies, probably because the vitality of the parasites is not always the same. In one series of cases the small parasites disappear on relatively small doses of quinin as promptly as or even more so than benign parasites ordinarily do; in others they manifest an especial obstinacy to treatment. True, certain forms-the crescents and their spheres-are absolutely indifferent to quinin, but this is of little importance since the crescents usually have nothing to do with the acute symptoms.
The histologic findings are usually sufficient to explain the majority of the pernicious symptoms. These histologic lesions consist principally in the occlusion of vessels by infected erythrocytes (Frerichs, Laveran, Guarnieri, Bignami, Marchiafava), and depending on the organ in which the capillaries are occluded, one or another symptom may be manifested. Additional details in relation to these findings will be given in the section on Pathologic Anatomy. Here we only desire to call attention to the fact that it is exactly the cases of infection with the malignant parasites that show these accumulations in the smallest vessels. The reasons for this can only be conjectured, not proved. It cannot be, for instance, that the blood corpuscle is carried less freely by the blood stream on account of the increase in weight produced by the parasite, because in this regard there is no difference between the benign and malignant parasites, and if there were a difference, it would be in favor of the former, which are much larger and therefore probably heavier. Further, the blood corpuscles infected by malignant parasites are usually somewhat shrunken, and should consequently pass through the capillaries more readily. Possibly it may be a sort of agglutination, either as a result of roughness or adhesiveness, that holds the infected erythrocytes to the vessel walls. As a matter of fact, we have more than once observed in unstained preparations under the microscope that the infected blood corpuscles do not swim in and out of the field division like the non infected-in other words, they appear to adhere more to the glass.
In addition to the occlusion of vessels in the brain we find punctate hemorrhages as a direct result of this occlusion, which may produce and continue the pernicious symptoms.
A much discussed question is, whether the fever itself may produce the perniciousness; in other words, is there any type which eo ipso necessitates perniciousness ?
In answer to this we may say, first, that pernicious symptoms occur in strictly intermittent as well as continued fevers. More than this, they may occur, even though seldom, without any fever (latent pernicious). These facts are already sufficient to prove that at least perniciousness is not associated with any definite type of fever, though experience shows that the majority of pernicious cases manifest a subcontinued fever. Baccelli saw, among 356 pernicious cases, 193 with subcontinued fever, and not without reason drew the conclusion that the subcontinued pernicious fever is pernicious on account of its type.
In spite of the frequency of the subcontinued type in pernicious fevers the endeavor to make this a basis of classification has not met with success.
It is readily conceivable that pernicious symptoms accompanying an intermittent fever would usually show a different character to those accompanying a continued fever. In the former, so called culminating symptoms (coma, eclampsia, hemiplegia, aphasia, hemoglobinuria, etc.) occur, which may be truly pernicious or indifferent, depending on whether they proceed from a very important or less important organ (these are the comitatse of Torti). In the latter, these culminating symptoms may also appear, but this is not the rule; on the contrary, the fevers extending over several days usually give rise to a symptom complex which includes the whole organism and frequently imitates that of other diseases (solitarise of Torti).
Baccelli correctly points out that an individual personal factor participates in the culminating symptoms of the comitatae, which is not the case in the solitariae.
Yet, all in all, it may be considered settled that the perniciousness is associated with no definite elevation of temperature and no particular type of fever.