I220 



THE TROPICAL HEMOGLOBINURIAS 



He considers that the causation of blackwater fever is threefold 



(i) Injury to the stroma of the red cell by the malarial parasite. (2) The 

 action of the malarial haemolysin. (3) The administration of sulphates. 



He thinks that, though the first and second causes may bring about the 

 disease, still quinine sulphate or any other sulphate, by its action on the plasma, 

 is the exciting cause if the former are ineffectual. On the other hand, he finds 

 that chlorides cause an increase of the resisting power of the erythrocytes to 

 haemolysis. Quinine hydrochloride, especially when combined with sodium 

 chloride and dilute hydrochloric acid, causes usually a marked rise in the 

 resistance. Therefore, according to him, it is not the quinine, but the sulphuric 

 acid in the form of quinine sulphate, which produces the haemolytic action. 

 In addition to sulphates, McCay found that alkaline carbonates, compounds 

 of alkalis with vegetal acids and potassium salts, diminished the inorganic 

 molecules of the plasma, thus tending to help haemolysis. We have, however, 

 seen haemoglobinuria following the administration of euquinine, the hydro- 

 chloride, and even the tannate of quinine. We have already referred to 

 Barratt and Yorke's experiments on this subject (see p. 1215). 



Malaria, Quinine, or Depressing Influence. — Decks and James maintain, 

 from the study of 230 cases of blackwater fever in Panama, that it is a mani- 

 festation of malarial toxicity usually induced by repeated attacks, but also 

 appearing coincidentally with an acute attack, and may be determined by any 

 depressing influence or quinine. 



This is really a malarial toxicity and other factor theory. In order to 

 produce the requisite conditions, they maintain that there must be a popula- 

 tion non-immune to malaria, of which infection there must be a large portion 

 due to L. malaricB, and malaria must be in such quantity as to produce an 

 almost continuous infection, and this must be associated with a neglect of 

 a thorough administration of quinine, especially in primary attacks. 



Against the view that it is caused by malaria treated with insufficient dosage 

 of quinine, followed by a large dose of quinine, we may quote the fact that we 

 are personally acquainted with a case of malaria associated with depressing 

 influences in which the infection was L. malaricB, which had remained latent 

 for a considerable period, and which for some weeks was treated by quite 

 inadequate doses taken by the mouth, and after severe fever varying from 

 104° to io5'8° F., and lasting for two days, i gramme of the bihydrochloride of 

 quinine was administered by the mouth, and 2 grammes given at the same time 

 by intramuscular injection, with the result of a quick and lasting cure of the 

 malaria without any signs of blackwater fever. This case appears to us to 

 answer every point required by the supporters of the malaria quinine theory of 

 blackwater fever, and it may further be stated that the original infection with 

 L. malaricB was in West Africa in one of the endemic regions of blackwater fever. 



Matko gives great importance to a disturbance in the phosphate meta- 

 bolism as an aetiological factor. According to his researches the secondary 

 and tertiary phosphates, whether of sodium or potassium, protect against 

 quinine haemolysis, while the primary salts do not. 



3. Anaphylaxis. — In 1909 Cleland advanced the theory that the disease 

 might be an expression of anaphylaxis to the malarial parasite brought about 

 by the presence in the serum of a foreign protein in the shape of disintegrated 

 merozoites. But this is open to serious objections, though recently supported 

 by Cardamatis, who considers that quinine might be able, when converted into 

 the albuminate, in certain unknown conditions to act as an antigen, which, 

 when combined with the malarial toxin, might produce antibodies, which 

 might provoke a sensitiveness to quinine in the person suffering from malaria, 

 when a further dose of the drug would produce anaphylaxis, perhaps because 

 it combines with the antibodies, or perhaps by its transformation into a 

 hypertoxic substance, 



4. Unknown Agent. — Sir Patrick Manson, in 1893, first promul- 

 gated the theory that blackwater fever was a disease distinct from 

 malaria, and supported this by the peculiar distribution of the 

 disease, which is widespread in tropical Africa, and very local in India. 



