Created 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.
1924

Created W. Yorke and W. Rees Wright, ‘The Mosquito Infectivity of P. Vivax After Prolonged Sojourn in the Human Host,‘ Annals of Tropical Medicine and Parasitology, 20 (3) (1926), pp. 327-328.
1926
Description:

‘In the now extensive literature relating to the malaria treatment of general paralysis, the statement is not infrequently encountered that maintenance in the human host for prolonged periods, by direct inoculation of infective blood from one individual to another, modifies the malaria parasite in certain important respects.

...

In previous papers (Yorke and Macfie, 1924, and Yorke, 1925) reference is made to the fact that a strain of Plasmodium vivax maintained by direct passage in the human host since September, 1922 -partly at Whittingham, and partly at Sheffield, mental hospitals - was still capable of infecting A. maculipennis at various passages up to the forty-first.

In March, 1926, after the strain had been maintained in the human host for three and a half years, its capacity to infect A. maculipennis was again examined. Forty-seven mosquitos were allowed to feed three times on a patient of the fifty-third passage, and once on a patient of the fifty-fourth passage. Fifteen days after the first feed, the mosquitos were divided into four groups, each of which was fed on a general paralytic; all four patients became infected [327-328] with malaria. Twenty-three of the mosquitos, which lived for longer than a week after the first feed, were dissected, and of these nineteen were found to be infected-three with oocysts only, and sixteen with sporozoites in the salivary glands.

This observation shows that the strain in question had preserved unimpaired its power to infect mosquitos after fifty-three or fifty-four direct passages through man during a period of three and a half years.’ (327-328)

Created W. Yorke, ‘Further Observations on Malaria made during Treatment of General Paralysis’, Transactions of the Royal Society of Tropical Medicine and Hygiene 19 (3) (1925), pp. 108-130.
1925

Created W. Yorke, ‘The Malaria Treatment of General Paralysis,’ Nature 114 (25th Oct. 1924), pp. 615-616.
25 Oct 1924
Description:

‘In 1919 Wagner v. Jauregg of Vienna, as the result of many years' observation of general paralysis, concluded that possibly it was the rise of temperature, which accompanied the intercurrent disease, abscess formation, or toxin inoculation, that was in some way responsible for the improvement produced in the nervous condition... Wagner v. Jauregg therefore proceeded to infect a long series of general paralytics with malaria, and during the years 1920-21 published results of a most promising nature.

It was the publication of these papers that induced Dr. Clark, the Medical Superintendent of the County Mental Hospital at Whittingham, to test the treatment at his institution; and in July 1922 a number of general paralytics were infected by inoculation of blood from patients who had contracted malaria in the tropics and had come to the hospital of the Liverpool School of Tropical Medicine for treatment... Later, the work was commenced at the other mental hospitals in the neighbourhoods, namely, Rainhill, Winwick, Belfast, and Chester.

For various reasons it was decided in a number of instances to modify the mode of infecting the patient, and, instead of producing the disease by the inoculation of malaria blood, to do so by Nature's method; i.e. by the bite of infective mosquitoes. The mosquitoes used were two commonly found in Great Britain, namely, Anopheles maculipennis and Anopheles bifurcatus, and for a constant supply of the former we are greatly indebted to Mr. Rees Wright, of the Department of Zoology, University College, Bangor, who during the winter collected the hibernating females in farm buildings in Carnarvonshire.

Up to April 1924, at the various institutions mentioned and at the Royal Infirmary in Liverpool, 139 cases of general paralysis had been infected with malaria, 98 by the method of direct inoculation of infective blood withdrawn from malaria patients, and 41 by the bites of infective Anopheles...

...

... work of this nature has enabled us to observe malaria in exceptionally favourable circumstances, and as a consequence much has been learned regarding this disease, and many hitherto unsolved problems have been answered. From this point of view the natural infections, i.e. those produced by the bites of infective Anopheline mosquitoes, have been especially valuable. They have enabled us to prove beyond all doubt that the three common malaria parasites are all true species and not merely different [615-616] stages of the same parasite, as has been so long maintained by Laveran and numerous other observers of the French school. The incubation period of simple tertian malaria - that is, the period which elapses between the bite of an infective mosquito and the development of symptoms and the appearance of parasites in the peripheral blood-has been shown to vary between 9 and 22 days; and much has been learned regarding the clinical course of the disease.’ (615-616)