“The transmission of the disease occurs equally whether the blood is taken during the apyretic [aguish] period or during a febrile [feverish] paroxysm, whether it contains young parasites or those in process of development, or whether it contains sporulation [minute spore-like] forms. Only the crescent forms, when injected alone, do not transmit the infection, as has been demonstrated by Bastianelli, Bignami and Thayer, and as can be readily understood when we remember the biological significance of these forms.
“In order that the disease be reproduced in the inoculated subject it is not necessary to inject the malarial blood into a vein of the recipient, as has been done in most of the experiments; a subcutaneous injection is all-sufficient. Nor is it necessary to inject several cubic centimeters, as was done especially in the earlier experiments; a fraction of a cubic centimeter will suffice, and even less than one drop, as Bignami has shown.”
After the inoculation of a healthy individual with blood containing the parasite a period varying from four to twenty-one days elapses before the occurrence of a febrile paroxysm. This is the so-called period of incubation, during which, no doubt, the parasite is undergoing multiplication in the blood of the inoculated individual. The duration of this period depends to some extent upon the quantity of blood used for the inoculation and its richness in parasites. It also depends upon the particular variety of the parasite present, for it has been ascertained that there are at least three distinct varieties of the malarial parasite—one which produces the quartan type of fever, in which there is a paroxysm every third day and in which, in experimental inoculations made, the period of incubation has varied from eleven to eighteen days; in the tertian type, or second day fever, the period of incubation noted has been from nine to twelve days; and in the æstivo-autumnal type the duration has usually not exceeded five days. The parasite associated with each of these types of fever may be recognized by an expert, and there is no longer any doubt that the difference in type is due to the fact that different varieties or “species” of the malarial parasite exist, each having a different period of development. Blood drawn during a febrile paroxysm shows the parasite in its different stages of intra-corpuscular development. The final result of this development is a segmenting body, having pigment granules at its center, which occupies the greater part of the interior of the red corpuscle. The number of segments into which this body divides differs in the different types of fever, and there are other points of difference by which the several varieties may be distinguished one from the other, but which it is not necessary to mention at the present time. The important point is that the result of the segmentation of the adult parasites contained in the red corpuscles is the formation of a large number of spore-like bodies, which are set free by the disintegration of the remains of the blood corpuscles and which constitute a new brood of reproductive elements, which in their turn invade healthy blood corpuscles and effect their destruction. This cycle of development without doubt accounts for the periodicity of the characteristic febrile paroxysms; and, as stated, the different varieties complete their cycle of development in different period of time, thus accounting for the recurrence of the paroxysms at intervals of forty-eight hours, in one type of fever, and of three days in another type. When a daily paroxysm occurs, this is believed to be due to the alternate development of two groups of parasites of the tertian variety, as it has not been possible to distinguish the parasite found in the blood of persons suffering from a quotidian form of intermittent fever from that of the tertian form. Very often, also, the daily paroxysm occurs on succeeding days at a different hour, while the paroxysm every alternate day at the same hour is a fact which sustains the view that we have to deal, in such cases, with two broods of the tertian parasite which mature on alternate days. In other cases there may be two distinct paroxysms on the same day, and none on the following day, indicating the presence of two broods of tertian parasites maturing at different hours every second day.
The hypothesis that malarial infection results from the bites of mosquitoes was advanced and ably supported by Dr. A. F. A. King, of Washington, D. C., in a paper read before the Philosophical Society on February 10, 1883, and published in the Popular Science Monthly in September of the same year. In 1894, Manson supported the same hypothesis in a paper published in the British Medical Journal (December 8), and the following year (1895) Ross made the important discovery that when blood containing the crescentic bodies was ingested by the mosquito, these crescents rapidly underwent changes similar to those heretofore described, resulting in the formation of motile [spontaneously moving] filaments, which become detached from the parent body and continue to exhibit active movements. In 1897, Ross ascertained, further, that when blood containing crescents was fed to a particular species of mosquito, living pigmented parasites could be found in the stomach walls of the insect. Continuing his researches with a parasite of the same class which is found in birds, and in which the mosquito also serves as an intermediate host, Ross found that this parasite enters the stomach wall of the insect, and, as a result of its development in that locality, forms reproductive bodies (sporozoites), which subsequently find their way to the venenosalivary [poisonous salivary] glands of the insect which is now capable of infecting other birds of the same species as that from which the blood was obtained in the first instance. Ross further showed that the mosquito which served as an intermediate host for this parasite could not transmit the malarial parasite of man or another similar parasite of birds (halteridium). These discoveries of Ross have been confirmed by Grassi, Koch and others, and it has been shown that the mosquitoes which serve as intermediate host for the malarial parasites of man belong to the genus Anopheles, and especially to the species known as Anopheles claviger.
The question whether mosquitoes infected with the malarial parasite invariably become infected as a result of the ingestion [taking in] of human blood containing this parasite has not been settled in a definite manner, but certain facts indicate that this is not the case. Thus there are localities noted for being extremely dangerous on account of the malarial fevers contracted by those who visit them, which on this very account are rarely visited by man. Yet there must be a great abundance of infected mosquitoes in these localities, and especially in low swampy regions in the tropics. If man and the mosquitoes are alone concerned in the propagation of this parasite, how shall we account for the abundance of infected mosquitoes in uninhabited marshes? It appears probable that some other vertebrate animal serves in place of man to maintain the life cycle of the parasite, or that it may be propagated through successive generations of mosquitoes.
It is well known that persons engaged in digging canals, railroad cuts, etc., in malarious regions are especially liable to be attacked with one or the other of the forms of malarial fever. This may be due to the fact that the digging operations result in the formation of little pools suitable for the development of the eggs of Anopheles, but another explanation has been offered. Ross and others have found in infected mosquitoes certain bodies, described by Ross as “black spores,” which resist decomposition and which may be resting spores capable of retaining their vitality for a long time. The suggestion is that these “black spores” or other incysted [enclosed in a small vessel] reproductive bodies may have been deposited in the soil by mosquitoes long since defunct, “and that in moving the soil these dormant parasites are set at liberty, and so, in air, in water or otherwise, gain access to the workmen engaged” (Manson). This hypothesis is not supported by recent observations, which indicate that infection in man occurs only as a result of inoculation through the bite of an infected mosquito. The question is whether malarial fevers can be contracted in marshy localities independently of the mosquito, which has been demonstrated to be an intermediate host of the malarial parasite? Is this parasite present in the air or water in such localities as well as in the bodies of infected mosquitoes? Its presence has never been demonstrated by the microscope; but this fact has little value in view of the great variety of micro-organisms present in marsh water or suspended in the air everywhere near the surface of the ground, and the difficulty of recognizing the elementary reproductive bodies by which the various species are maintained through successive generations. It would appear that a crucial experiment for the determination of this question would be to expose healthy individuals in a malarious region and to exclude the mosquito by some appropriate means. This experiment has been made during the past summer, and the result up to the present time has been reported by Manson in the London Lancet of September 29, 1900. Five healthy individuals have lived in a hut on the Roman Campagna since early in the month of July. They have been protected against mosquito bites by mosquito-netting screens in the doors and windows and by mosquito bars over the beds. They go about freely during the daytime, but remain in their protected hut from sunset to sunrise. At the time Manson made his report all these individuals remained in perfect health. It has long been known that labourers could come from the villages in the mountainous region near the Roman Campagna and work during the day, returning to their homes at night, without great danger of contracting the fever, while those who remained on the Campagna at night ran great risk of falling sick with fever, as a result of “exposure to the night air.” What has already been said makes it appear extremely probable that the “night air,” by itself, is no more dangerous than the day air, but that the real danger consists in the presence of infected mosquitoes of a species which seeks its food at night. As pointed out by King, in his paper already referred to, it has repeatedly been claimed by travelers in malarious regions that sleeping under a mosquito bar is an effectual method of prophylaxis [prevention] against intermittent fevers.
That malarial fevers may be transmitted by mosquitoes of the genus Anopheles was first demonstrated by the Italian physician Bignami, whose experiments were made in the Santo Spirito Hospital in Rome. The subjects of the experiment, with their full consent, were placed in a suitable room and exposed to the bites of mosquitoes brought from Maccarese, “a marshy place with an evil but deserved reputation for the intensity of its fevers.” It has been objected to these experiments that they were made in Rome, at a season of the year when malarial fevers prevail to a greater or less extent in that city, but Marchiafava and Bignami say:
“It is well known to all physicians here that, although there are some centers of malaria in certain portions of the suburbs, the city proper is entirely free from malaria, as long experience has demonstrated, and at no season of the year does one acquire the disease in Rome.”
In view of the objection made, a crucial experiment has recently been made in the city of London. The result is reported by Manson, as follows:
“Mosquitoes infected with the parasite of benign tertian malarial fever were sent from Rome to England, and were allowed to feed upon the blood of a perfectly healthy individual (Dr. Manson's son, who had never had malarial disease). Forty mosquitoes, in all, were allowed to bite him between August 29 and September 12. On September 14 he had a rise of temperature, with headache and slight chilliness, but no organisms were found in his blood. A febrile paroxysm occurred daily thereafter, but the parasites did not appear in the blood until September 17, when large numbers of typical tertian parasites were found. They soon disappeared under the influence of quinine.”