In regard to the melanemia, we have nothing to add to what has already been said in the previous sections. The origin of the pigment in the bodies of the parasites as an end procluct of the hemoglobin digested by the protozoa, has been absolutely determined and needs no further proof.
The second symptom, the anemia, may also be regarded as explained.
The degree of the anemia depends, on the one hand, on the number of the parasites and the rapidity with which they increase; on the other, on the activity of the blood making organs. The latter is never sufficient to make good the loss with the rapidity of its occurrence; a certain degree of anemia, therefore, is never lacking. The high degree that may occasionally be reached has been repeatedly discussed in the clinical description.
The third principal symptom-the fever or the fever paroxysm in its typical and atypical forms-has likewise been explained and satisfactorily, even though not so clearly and simply as the melanemia and anemia.
Golgi's demonstration of the coincidence of the fever paroxysm with the segmentation of the quartan and tertian parasites; Marchiafava and Celli's demonstration of the same for the quotidian parasites; and Marchiafava and Bignami's for the malignant tertian parasites, have divested the intermittent fever paroxysm, with its periodic recurrence, of the mysticism surrounding it, by referring it to a simple biologic fact. This biologic fact is the cycle of development of the parasites occurring at the time in the blood.
Turning to the fever paroxysm itself, with its three separate stages, we find that it sets in with the segmentation of a generation of parasites.
The association of this segmentation with the fever paroxysm in the way of cause and effect was neither an unjustifiable nor too bold an employment of the usually condemned argument post hoc ergo propter hoc.
Golgi described the process as follows: As a result of the sporulation an enormous number of spores, together with substances elaborated in the parasites and probably poisonous to the organism, are thrown into the blood and produce the paroxysm.
That, exceptionally, isolated segmentation forms may be found in the blood apart from a paroxysm is no argument against this standpoint, for undoubtedly a certain quantity of the injurious agent is necessary to produce symptoms.
The fact that the parasites exist in the blood in generations which show individual members of almost exactly the same age makes this theory of the paroxysm probable.
How it happens that such an innumerable number of parasites as are often present in the blood are of the same age is unknown, though we have a hypothesis that probably approaches the truth.
It is assumed that infection results only when the organisms are in a very definite stage of development. Let us suppose, for the moment, that spores introduced either by mosquitos or by aspiration into the lungs produce the infection. If a certain number of these gain entrance, a basis is at once formed for the evolution of a generation, all the members of which will be of the same age. It is somewhat similar to several human beings of the same age marrying and begetting children simultaneously. It is evident that in the continuation of this parallelism in the reproduction a large number of individuals of the same age will eventually result. Moreover, in the case of the malarial parasites it is much more sure, since their time of evolution is very definite, namely, the quotidian parasite twenty four, the tertian two times twenty four, and the quartan three times twenty four, hours. Within a short time, therefore, large numbers of families of the same age will be produced from a relatively small number of micro organisms.
Still, we must insist again that this similarity in age of the different individuals is not absolute. If all the parasites which we reckon as belonging to the one generation were the same age to the minute, and if this entire host would segmentate at a given moment and throw off their spores, then the blood picture would correspond exactly with the outline, but, as a matter of fact, the parasites of the same generation show differences of one to several hours. The struggle for existence is evidently a factor capable of influencing the duration of evolution. In spite of the slight differences in age it is necessary to reckon all these individuals to one generation.
The fact that the individuals of one generation do not sporulate at the same moment, but after one another at short intervals, produces its own clinical feature in that the paroxysm does not ordinarily last only a few moments, but several hours-even half a day and more. In relation to this, we previously wrote: "If the innumerable sporulation forms, similarly to a volley of a large number of guns, would burst in a moment and throw their contents into the blood stream, it is very likely that a much shorter but also much more violent paroxysm would be the result, but, as it actually is, the sporulation takes place after the manner of a rapid fire, and continues the fever paroxysm through a series of hours." That toxic substances are set free at the time of the rupture has not yet been fully demonstrated, though the assumption can scarcely be wrong. True, Roque and Lemoine found that the toxicity of the urine excreted after a paroxysm was higher than normally, and Queirolo showed that the sweat of malarial patients, similarly to that of other acute infectious diseases, was poisonous to rabbits; yet these experiments are by no means convincing.