Borius found in Senegal that the majority of pernicious cases occurred in new arrivals and individuals who were in the tropics over thirty six months. He stated that, among 100 malaria cases, 4.1 per cent, were pernicious, and these were divided so that in the month of June there occurred 0.9 per cent.; in September, 6.3 per cent. In the years 1863-1872 there occurred, among the 16,366 men in the garrison, 600 pernicious cases.

Pernicious fever occurs in all malarial regions only in the hot season, and especially between the rainy and the dry season. In southern Europe, as well as in Algiers, it is the months July to November that show the most cases.

The different pernicious symptoms occur with varying frequency. In the majority of malarial regions the severe general and the nervous symptoms are the most common. In certain places, like, for instance, tropical Africa, the hemoglobinuric form predominates.

Different factors, sometimes acting alone, sometimes together, seem to be necessary for the origin of the pernicious symptoms, though we must insist that many of these factors are unknown and that in individual cases it is often impossible to say how the severe symptoms originated.

The factors which are at present considered as especially responsible for perniciousness are the following: (a) Individual predisposition; (6) peculiarity of the parasite; (c) anatomic lesions.

Individual Predisposition

The majority of writers are unanimous in affirming that certain individuals or that an individual at a certain time manifests an especial susceptibility to pernicious malaria . There are people who, as often as they are attacked with malaria, show every time a severe form (sometimes the same, again a different one). It may be that these people, as a result of organic peculiarities of a chemic or anatomic nature not yet recognized, possess something that assists the development of the parasite or its toxin, or that permits the local accumulation of infected blood corpuscles in certain important capillary regions.

There are others who show a temporary-therefore, acquired- predisposition-for instance, alcoholics, convalescents, or persons enfeebled by heat, overwork, or insufficient nourishment.

It has been observed that an extra effort on the part of a certain organ immediately preceding the outbreak of the malaria leads to a pernicious case manifesting symptoms from this organ; or that a local susceptibility is grounded in an organ weakened by previous disease and transformed into a locus minoris resistentice.

Baccelli observes that farmers working in the heat of the sun and alcoholics suffer uncommonly frequently from forms associated with coma or delirium, while people with intestinal catarrh are attacked by the choleraic form.

It has been further recognized that strangers not accustomed to the climate suffer relatively more frequently from pernicious fever than the native inhabitants. According to Borius, the native adult blacks in Senegal seldom manifest it. Some writers (Rho) observed that at the beginning of a hot season persons who never before had malaria are attacked by severe symptoms, even when the blood examination shows a comparatively small number of parasites. This would seem to indicate a special susceptibility. Finally those cases are also attributable to individual predisposition which begin mildly but take on a pernicious character as a result of improper treatment.*

As to the peculiarities of the infecting parasite, only the small parasites come into consideration in the genesis of pernicious fever. Infections with parasites of the first group run always a mild course. This alone is very significant of the possession by the parasites of the second group of certain specific properties.

* The fact that the small parasites cause pernicious fever much more frequently in the tropics than in the temperate zone is probably due to the enfeeblement of the organism by the climatic conditions, by which a temporary individual susceptibility is created. Otherwise we would be obliged to assume that the small parasites were endowed with different toxic and pathogenic properties in different parts of the world, and for this assumption we have no foundation.

Moreover, of this group it is especially the malignant tertian parasites that, according to Marchiafava and Bignami, produce pernicious fever.

When we consider the factors that may be responsible for this tendency to malignancy, the following present themselves: (1) Their number; (2) their toxicity; (3) their power of resistance against medicaments. Besides these three factors there are others which we will take up later.

The number of parasites in pernicious cases is usually extraordinary. In an unstained preparation from the blood of the finger we frequently see a very large number of infected erythrocytes, but when we make sections of the internal organs, especially the brain, the spleen, etc., this number is discounted. Moreover, it sometimes happens that the peripheral blood is very poor in parasites, when that of the internal organs swarms with them. In cases of infection with crescent forming parasites, therefore, nothing can be concluded from the ordinary blood examination as to the numbers that may be present. Whether the number of parasites in the pernicious cases is much larger than that of the parasites of the first group in high grades of infection with them is a question which at the present time can be answered only approximately, since, as far as I know, no actual counts have been made. From the general impression which I have obtained, naturally only from the peripheral blood, the number in malignant fevers is perhaps larger, yet the difference scarcely seems so decided as to make this factor alone responsible for the perniciousness.

Why in one person the malignant parasites should increase but little, in fact, occasionally even disappear spontaneously, while in another they increase to extraordinary numbers, is a problem that must be referred to the causes of perniciousness in general, namely, the personal susceptibility of the affected individual and the proliferative activity of the parasites.