In malaria it is the red blood corpuscles that first suffer. There is, therefore, no malaria without a decrease in erythrocytes and in the amount of the hemoglobin. To what degree this anemia may advance has been repeatedly discussed in the preceding pages; consequently we will not recur to the subject.

Progressive pernicious anemia has been repeatedly observed following malaria , and there is possibly a causal connection between the two. Fayrer and Ewart saw this sequela frequently, especially in gravid and nursing women and in children. These cases showed an especial tendency to hemorrhage and venous thrombosis. Thrombus formation in the right heart, usually with a fatal termination, was observed several times.

Whether other blood diseases, like leukemia, may be regarded as sequela? of malaria , is more than doubtful, even though a number of cases show malaria in their history. On account of the wide distribution of malaria its occurrence is probably only a coincidence, and we will omit further details.

We have already mentioned that in the course of an acute and chronic malaria , and even cachexia, hemorrhages may occur from and into the various organs. Moreover, very trustworthy writers affirm that a hemorrhagic diathesis may develop as a sequel (Mal herbe, Manson). This is characterized by hemorrhages from the nose, gums, stomach, and intestine, into the skin, etc., all of which may be intermittent; or actual hemophilia may arise.

Postmalarial Hemoglobinuria

In considering hemoglobinuria in this section, we assume that the important factor in the disease is a solution of the erythrocytes; in other words, that we have to do with a disease of the red blood corpuscles. The excretion of the dissolved hemoglobin by the kidneys is, therefore, only a symptom of the real condition; the hemoglobinemia, in the same way as jaundice, is only a symptom of obstruction of the biliary passages. Still we must not forget that some writers (Pellarin and others) locate the seat of the disease not in the blood, but in the kidneys, in that they regard renal hemorrhages (apoplexie renale) as the source of the hemoglobinuria, though we have not the slightest doubt that systematic examination will demonstrate that in the great majority of cases the solution of the erythrocytes takes place in the circulating blood.

Postmalarial hemoglobinuria may be divided into two groups, namely:

(a) Essential postmalarial hemoglobinuria.

(b) Postmalarial hemoglobinuria the result of quinin. Essential Postmalarial Hemoglobinuria.-In regard to essential postmalarial hemoglobinuria there are but few convincing observations. Murri's case is probably of most value, because accurately controlled. This was a girl who suffered a long time from malaria and who was successfully treated with quinin. One day, after the administration of quinin, a paroxysm of hemoglobinuria occurred. After this she repeatedly manifested fever with hemoglobinuria, without the slightest trace of parasites on the most careful examination and without taking quinin or any other medicament in advance. After a short time the paroxysms ceased.

In this short description the characteristics of the condition stand out clearly. We have to do here with a hemoglobinuria in a person who suffered previously from malaria that manifested itself under more or less severe general symptoms, apart from the action of medicaments, cold, etc. Much more frequent, in fact, the cause of a great part of the cases of blackwater fever is-

Quinin Hemoglobinuria

In the discussion of blackwater fever Tomaselli's observation was mentioned. According to this there are persons previously or at the time infected with malaria who manifest a paroxysm of fever with hemoglobinuria after every adminisr tration of quinin, no matter how insignificant the amount. In a small number of cases the quinin produces the paroxysm even when the malaria has existed only a short time, and occasionally one dose is sufficient. Yet the great majority of cases last months and years, during which the quinin is taken without bad results before a paroxysm is produced. On account of the rarity of the condition, in contrast to the extraordinary frequency of malaria, Tomaselli insists that an individual predisposition must be assumed. This conjecture is strengthened by the fact that several persons closely related to one another have been repeatedly found suffering from the same affection. This individual predisposition may be, therefore, congenital, possibly even hereditary. Vincenzi saw a case in which quinin, administered for the first time in early childhood on account of malaria , produced a paroxysm of hemoglobinuria and in which the idiosyncrasy against it remained unchanged. In cases like the last the malaria perhaps plays a more subordinate role, the principal factor being the individual idiosyncrasy against the drug. Yet in cases in which the malaria existed for a long time before the condition occurred it cannot be doubted that the infection or the changes produced by it are very important from an etiologic standpoint. Infections produced by the small as well as the large parasites may lead to quinin hemoglobinuria. Among the latter the quartan parasites seem especially adapted. Vincenzi and Grocco's cases were in connection with quartan affections.

According to Tomaselli's most recent publication, there have been reported 102 cases of quinin hemoglobinuria, to which he adds 12 more. Tomaselli himself saw over 30 cases. In these statistics, only the cases occurring in Italy (with Sicily and Sardinia) and Greece have been taken into consideration. The cases frequently encountered in the literature of blackwater fever, in which hemoglobinuria appeared after the administration of quinin, are not included. We have already expressed ourselves on the question whether there is a genuine blackwater fever or whether all cases are to be looked on as quinin poisoning. Here, therefore, we have only to add that those cases exclusively should be designated quinin hemoglobinuria in which, within a reasonable interval, a paroxysm breaks out every time after the administration of quinin. Cases in which a paroxysm occurs after one administration, but which a few days later bear quinin well, cannot be placed in this category, but are to be looked upon as coincidences. It must not be forgotten that blackwater fever is usually ushered in by a few mild prodromal paroxysms without hemoglobinuria. It can, therefore, readily happen that a dose of quinin is administered before the outbreak of the condition, in which case we can only say that the paroxysm took place in spite of the quinin, not that it was produced by it.