Soon after the discovery of the parasites in the blood, Gerhardt (1884) succeeded in transferring the disease to healthy individuals by inoculation of malarious blood, and thus proved that it is a true infection. This was verified by numerous experimenters and it was found that inoculation with a very minute quantity of the diseased blood would not only produce malaria but the particular type of disease.
Laveran traced out the life cycle of the malarial parasite as it occurs in man. The details as we now know them and as they are illustrated by the accompanying [figure 125], are as follows:
The infecting organism or sporozoite, is introduced into the circulation, penetrates a red blood corpuscle, and forms the amœboid schizont. This lives at the expense of the corpuscle and as it develops there are deposited in its body scattered black or reddish black particles. These are generally called melanin granules, but are much better referred to as hæmozoin, as they are not related to melanin. The hæmozoin is the most conspicuous part of the parasite, a feature of advantage in diagnosing from unstained preparations.
As the schizont matures, its nucleus breaks up into a number of daughter nuclei, each with a rounded mass of protoplasm about it, and finally the corpuscles are broken down and these rounded bodies are liberated in the plasma as merozoites. These merozoites infect new corpuscles and thus the asexual cycle is continued. The malarial paroxysm is coincident with sporulation.
As early as Laveran's time it was known that under conditions not yet determined there are to be found in the blood of malarious patients another phase of the parasite, differing in form according to the type of the disease. In the pernicious type these appear as large, crescent-shaped organisms which have commonly been called "crescents." We now know that these are sexual forms.
When the parasite became known there immediately arose speculations as to the way in which it was transferred from man to man. It was thought by some that in nature it occurred as a free-living amœba, and that it gained access to man through being taken up with impure water. However, numerous attempts to infect healthy persons by having them drink or inhale marsh water, or by injecting it into their circulation resulted in failure, and influenced by Leuckart's and Melnikoff's work on Dipylidium, that of Fedtschenko on Dracunculus, and more especially by that of Manson on Filaria, search was made for some insect which might transfer the parasite.
Laveran had early suggested that the rôle of carrier might be played by the mosquito, but Manson first clearly formulated the hypothesis, and it was largely due to his suggestions that Ross in India, undertook to solve the problem. With no knowledge of the form or of the appearance in this stage, or of the species of mosquito concerned, Ross spent almost two and a half years of the most arduous work in the search and finally in August, 1897, seventeen years after the discovery of the parasite in man, he obtained his first definite clue. In dissecting a "dappled-winged mosquito," "every cell was searched and to my intense disappointment nothing whatever was found, until I came to the insect's stomach. Here, however, just as I was about to abandon the examination, I saw a very delicate circular cell, apparently lying amongst the ordinary cells of the organ and scarcely distinguishable from them. On looking further, another and another similar object presented itself. I now focused the lens carefully on one of these, and found that it contained a few minute granules of some black substance, exactly like the pigment of the parasite of malaria. I counted altogether twelve of these cells in the insect."
Further search showed that "the contents of the mature pigment cells did not consist of clear fluid but of a multitude of delicate, thread-like bodies which on the rupture of the parent cell, were poured into the body cavity of the insect. They were evidently spores."