The dark color of certain organs (as the liver, spleen, brain) was recognized by the older investigators-for instance, Lancisi, Folchi, Bailly, Annesley, and others. The discovery of the pigment, microscopically, not alone in the organs, but also in the blood, was the work of Heinrich Meckel (1847); he found it in the body of an insane patient, and described in a classic way the "pigment cells" in the blood which were really the malarial parasites. The relation of this pigment to malaria was not remarked by Meckel, since he did not realize that the insane patient who had lived a long time in the asylum, and whose fatal disease had probably not been carefully studied, had died of pernicious malaria. This relation was soon after discovered by Virchow.
Almost simultaneously with Meckel, Dlauhy in Prague and Heschl in Vienna called attention to the malarial pigment. Virchow laid the site of origin in the spleen, whence it escaped into the blood. Other writers adopted his conclusions-for instance, Frerichs, who claimed the liver to be a second place of origin.
Planer hinted at the possibility of its origin in the circulating blood. Planer also seems to have been the first to observe the "pigment cells" in the living blood. Arnstein found that when death took place a long time after a paroxysm there was no melanemia, even though there might be pigmentation of the spleen, liver, and bone marrow, and that melanemia was observed only when the death occurred a short time-at most forty eight hours-after a paroxysm. He insisted, therefore, that the pigment was formed in the circulating blood, and supported his assertion with the observation that the distribution of the malarial pigment in the spleen, bone marrow, and lymph glands was exactly analogous to the distribution of pigment granules introduced experimentally. These organs were consequently to be regarded, even in malaria , as places of deposit for those granules produced in the blood.. Kelsch adopted a similar view, supported by the fact that there were cases of intense melanemia without a trace of pigment in the spleen. Kelsch assumed that in malaria a solution of hemoglobin in the blood plasma took place, which was later transformed into melanin.
C. Schwalbe, who witnessed melanosis in animals poisoned by carbon bisulphid and sulphur oxychlorid, referred the malaria to a similar poisoning, while Afanassiew looked on the pigment granules as chromo genic cocci. Marchiafava eventually determined (1879) that the pigment was formed within the red blood corpuscles.
With Laveran's discovery all these doubts were settled, yet we can only wonder at the acuteness of the earlier observers, some of whom came so near the truth. Virchow's view in regard to the origin of the pigment in the spleen was not so far wrong, since there are certain malarial infections in which the later stages of parasitic development take place, not in the circulating blood, but in the internal organs, particularly the spleen and bone marrow.
Melanemia may be found at almost any time during a malarial infection-that is, as long as the malarial parasites continue to develop and increase. The most suitable time is shortly after or during a paroxysm, when the pigment is in the largest clumps and is, therefore, most readily recognized.
Moreover, the melanemia may continue after the disease has apparently passed and no paroxysms have occurred for some days. These are cases in which crescents continue the infection without producing manifestations.
At the termination of an infection the melanin disappears from the blood in a very short time, and forty eight hours after the last paroxysm the most painstaking search usually fails to reveal it. This fact is very important, since it gives us a criterion for determining the cessation of the disease.
A positive melanemia practically assures the diagnosis of malaria . Apart from this disease, melanemia has been observed only in recurrent fever, in melanotic neoplasms, and in Addison's disease-in the first, only after a fever paroxysm; and in melanosarcoma (Nep veu) and Addison's disease, only very exceptionally.
I have frequently examined the blood of two cases of Addison's disease without finding any pigment. As regards the first two conditions I have had no personal experience.*