Grocco reports a case in which, while parasites were present in the blood, a dose of 0.40 gram quinin per os called forth a severe paroxysm of hemoglobinuria, with a temperature of 40°, while after the disappearance of the parasites a dose of 1.50 gram quinin subcutaneously produced only a mild paroxysm. From this Grocco draws the logical conclusion that it is not the quinin itself which destroys the corpuscles in malarial cases, but a toxin produced by the parasites under the irritation of the quinin. This theory, though, fails to take into consideration that genuine parasitic reactions, as mentioned above, usually yield to quinin without the production of other symptoms.

Moreover, these cases can be, least of all, regarded as examples of the toxic effect of quinin, in which, after the administration of the drug, the paroxysm of hemoglobinuria appears, but the disease is cured. Without considering the treatment of blackwater fever, we must insist that that primary dose of quinin, whether or not it caused hemoglobinuria, surely affected the parasites and eventually brought about recovery.

As far as the etiologic role of quinin in blackwater fever is concerned, our own opinion is that there are undoubted cases of acute malarial infection in which hemoglobinuria is caused by the quinin; yet in the criticism of cases which show a paroxysm a short time after the first dose, none at all after subsequent doses, we must be especially careful, since there is no proof that quinin acted poison ously in these cases. In the section on Complications and Sequela? we will return to quinin hemoglobinuria.

From the preceding it is clear what importance can be attached to the blood examination in these cases. Only by a parasitologic diagnosis is it possible to decide whether we have to do with a post malarial hemoglobinuria produced by quinin or a paroxysm in the course of a malarial infection. The therapeutic indication in these cases can be grasped only from the positive or negative finding, and without this the patient may be injured or even his life placed in danger. (Further details in the section on Therapy.)

The frequency of blackwater fever varies with the geographic location and the season. In general we may state, with Berenger-Feraud, that the disease is most frequent in those tropical regions which show the most extensive foci of malaria . [Further, we must take into account, in comparing different regions, not only whether the type of fever there is especially virulent; we cannot compare, for instance, the fever of tropical Africa with that of northern Italy, even if the parasite is the same, but also whether there is a susceptible population present, living under the unfavorable conditions of climate and danger of infection, such as we find in tropical Africa. -Ed.] According to his statistics, based on a large amount of material, there occur in the French West African colonies 0.28 to 53.05 cases of blackwater fever among 100 people a year, depending on the locality. The worst places are Gabun, with 53.05 per cent. ; the gold coast, with 37.7 per cent.; Upper Senegal, with 21.31 per cent., etc. According to his estimation, the average shows a morbidity of 17.81 per cent, a year. According to Davidson, there were reported in Nossi Be, among 2600 malarial cases, 185 cases of black water fever, a proportion of 1:14. In Kamerun Friedrich Plehn observed a proportion of 1:11 or 12; Albert Plehn, 1:8.05. Dor ing had, from May 1, 1896, to February 1, 1897, in Kamerun, among 169 malarial cases, 40 (!) of blackwater fever. [Against the malarial origin of blackwater fever is generally quoted the fact that black water fever is unknown in India; this is, as we have seen, not true. And, again, though India is rightly designated a malarial country, it is not so in the sense that tropical Africa is. For, on the whole, it is the simple tertian parasite that predominates in India, while this parasite is exceedingly rare in tropical Africa, where the malignant tertian parasite almost exclusively prevails. Then in India we do not often have a European population living under the wretched conditions still so widely prevalent in Africa, and we see comparatively few of these malarial "wrecks" so common in tropical Africa. That this is a very important difference, we strongly believe.-Ed.] As to the season of the year during which cases are most frequent, Berenger-Feraud found that a much smaller number of cases occurred in Senegal from January to June than from July to December, while on the gold coast and in Gabun the distribution over the whole year was more uniform. It is almost the unanimous opinion of writers that the transition periods between rainy and dry weather are the most dangerous.

All authorities agree as to the difference in race predisposition. Negroes show the greatest immunity, though even among them isolated cases have been reported (Berenger-Feraud, Borius, Corre). Mulattoes too are rarely attacked. Hindus and the Chinese coolies suffer more frequently, and most frequently of all, the Europeans and the white Creoles. From this has arisen the French name, "Fievre jaune des Creoles ou cles acclimates." According to Blanc, who collected his observations in Tongking, the Annamese are immune, while Europeans are not infrequently victims.

The principal symptoms of blackwater fever consist in hemoglobinuria, icterus, and fever. The fever may be intermittent (quotidian or tertian), remittent, or continued, though we may add that the less inclination the fever shows to intermit or remit, the more severe the attack.

Since the urine contains the principal symptoms, it is naturally of the greatest importance in the recognition of the condition. The red or black urine is usually discharged for the first time several hours after the beginning of the attack. It is rarer to find the bloody urine appear first, and the other symptoms, fever and icterus, later. Its color varies between a clear brownish red and the translucent color of venous blood. In most descriptions it is compared with port wine, Malaga wine, or black coffee.