Cites W. Yorke and J.W.S. Macfie, 'Observations on Malaria made During Treatment of General Paralysis,' Transactions of the Royal Society of Tropical Medicine and Hygiene 18 (1-2) (1924), pp. 13-33.
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'After some general remarks from the Chairman the discussion was opened by --

Colonel S.P. JAMES: In opening the discussion on this important paper, I think I should approach the subject rather from the point of view of the administrative authorities, who have to decide whether, and under what regulations, this method of treatment should be applied in mental hospitals in England, than from the point of view of the malariologist. Having this in mind, the first question to be answered in connection with the treatment is whether it is really efficacious in curing general paralysis. On this point it is very important that the results of the enquiries made by the Liverpool School of Tropical Medicine, with their high reputation for critical analysis and scientific caution, confirm those of previous observers in the conclusion that the results of the new treatment are most satisfactory. One could have wished that Professor YORKE had spoken in more detail on this subject, but, in any case, the opinion expressed is helpful in deciding to what extent facilities must be provided for carrying out the treatment. A second important matter in connection with these facilities is the decision whether the arrangements should be for inducing malaria in the natural way by mosquito bites, or whether the artificial method of blood inoculation will suffice. In Professor YORKE'S series of cases, forty-one patients were given benign tertian malaria by mosquito bites and seventy or more by blood inoculation, and we [33-34] might justifiably expect a considered opinion on the relative merits of the two entirely different methods. My own more limited experience leads me to think that the therapeutic results obtained from naturally-acquired malaria are more speedy and striking than they are from malaria contracted by blood inoculation, and that the former should be, whenever possible, the method of choice. A subsidiary problem of the same subject is the relative efficacy of mild and severe attacks of induced malaria, particularly with reference to the degree of fever registered in the paroxysmal attacks. From the experimental work done in Austria on the spirochceticidal influence of high temperatures it would seem necessary that temperatures between 105°F and 106°F should be reached in most of the paroxysms. These high temperatures, and the heavy parasite infections necessary to produce them, involve considerable risk to the patient, and necessitate great care and watchfulness during the course, but I feel sure that the risk must be taken if successful results are to be obtained. Finally, of course, all the arrangements for preventing the spread of the disease have to be considered. These and other reasons have led the Board of Control, in consultation with the Ministry of Health, to arrange for special classes of instruction in malaria for medical officers of mental hospitals where the treatment is to be carried out. I am glad to be able to say that, through the good offices of Colonel ALCOCK, it has been arranged that these courses will be carried out at the London School of Tropical Medicine, and it is hoped that the first course will commence almost at once.

Now, from the point of view of the malariologist, I should like to mention very briefly one or two of the particular points in malaria which are specifically dealt with in the paper before us. The first is that our experience in regard to the certainty of infection by the bites of infected mosquitoes differs from that of the authors of the paper. On page 17 they state that the feeding of a mosquito, which on dissection immediately after the meal was found to contain sporozoites in its salivary glands, never failed to result ininfection of the patient. In our experience of infections by mosquito bites, we have had two very clear instances in which the bites of mosquitoes known to be infected failed to cause malaria in the patients bitten. In this connection also I would like to ask Professor YORKE whether, in coming to the conclusion that the bites of infected mosquitoes always have a positive result, he has taken into account the twenty-three negative results printed in Table II, on page 19. The patients in this table were treated with quinine, but I do not know how it has been decided that the negative result was due to quinine and not to a failure to infect.

The next point to which I would like to refer has reference to the so-called "virulence" of different strains of the benign tertian parasite, and as to whether a given strain can undergo an increase or deterioration of its virulence. Professor YORKE's paper contains no details bearing on the different virulence of different strains, but, as regards one of the strains which he studied, the opinion is expressed that its virulence did not increase as a result of direct passage from man to man through twenty-three generations. As I have already spoken too long, I will merely say that on this point our experience differs from that recorded by the authors of the paper, and that [34-35] I think Dr. HENSCHELL, Dr. Low and others will bear me out in the opinion that the strain which we are using has become more "virulent" than the benign tertian strains commonly encountered in the tropics. It causes almost invariably a quotidian fever, the temperature rising to 105°F or higher. In several cases we have found it necessary to commence quinine treatment earlier than we had intended to do.

Finally, I must say a word about treatment, which is very fully considered in the paper under discussion. I quite agree with the authors that the susceptibility of induced malaria to quinine treatment has something to do with the fact that we are dealing with primary infections instead of with relapses, but I cannot follow them in the theoretical explanation of the mechanism by which cure is obtained. "Susceptibility," "immunity," "tolerance to the effects of the parasite invasion," and "individual resistance" are debatable subiects which cannot be dealt with in a rapid survey of the present nature, but I take the opportunity to refer to two observations made during the procedure of treating patients suffering from general paralysis, and other nervous diseases, by infecting them with malaria by the bites of mosquitoes. The first is that two of the patients, on whom I have successfully carried out this procedure, failed to develop malaria after being bitten by mosquitoes which were proved to be infective. The second is that one patient developed, after the usual incubation period, a moderate blood infection of parasites but showed no rise of temperature, and the parasites gradually disappeared without quinine treatment. The interest of these observations is that all three patients were already anaemic, undernourished, and in a feeble state of health, and that it would be out of the question to affirm either that they already possessed some degree of "immunity," or that their general health was so good that their "resisting power" prevented the development of the infection. Indeed, what has struck us most in connection with malaria infection in the course of this work has been that the patients who are best nourished and in the best "general health," and whose blood is the least anaemic at the time of infection, are those who develop the disease most surely and in most typical form. The experience is reminiscent of the common observation in the tropics that the young and vigorous newcomer from Europe is very "susceptible" to malaria, and that, when he contracts the disease, his attack is sharper and more typical than are attacks in local residents, even when it cannot be said of the latter that they have attained a relative "immunity" or "tolerance" to the parasites or to the disease. It seems to me quite possible that, as regards the two observations I have mentioned above, the failure of the parasites to develop in the particular patients concerned is a factor of their undernourishment and feeble state of health, rather than of any natural or acquired immunity to malaria infection. If this is true, I suppose it would be necessary for Professor YORKE and Dr. MACFIE to modify completely their theory of the mechanism by which a cure is brought about. I am not prepared to discuss why a condition of anaemia and undernourishment seems to be inhibitory to malaria, but, I suppose, one might conjecture that this condition is accompanied by some chemical or other change in the blood, which causes it to be a less favourable [35-36] medium for the growth of the parasite than is the blood of quite healthy persons. Whether or not this conjecture is worthy of attention, I think it will be agreed that serious research work on the biochemistry of the blood in relation to malarial infection is of pressing importance.' (33-36)