yellow fever, Leishmaniasis, and various forms of relapsing fever; but also partly due to absence of that persistent individual effort which alone is capable of solving the difficult problems of science. There has been no encouragement of such effort, and even little coordination of the slighter researches which are always being carried on in various countries. Many important questions therefore still remain unanswered; and if it had not been for the exigencies of the World War there would have been little now to add to what was available up to 1910. Certainly innumerable papers have been published; but in some cases the writers are evidently unacquainted with more than a tithe of the enormous literature; in others they mistake speculation for proof; and in nearly all they discontinue their efforts before reaching definite conclusions.
Similarly, the prevention of malaria on the large scale, which was rendered possible or even easy (in many places) by the new knowledge, has not been carried out as generally as was hoped at the beginning of the century. The classical successes obtained at Ismailia and in the Federated Malay States, in Italy, and at Havana, Hong-Kong, Khartum, and elsewhere do not seem to have encouraged the same kind of work in other localities excepting the long-continued labour of M. Watson in the Feder- ated Malay States and the brilliant sanitary victory of General Gorgas and the Americans, over both malaria and yellow fever, at Panama. The method of mosquito-reduction against malaria was first suggested and tried by a band of volunteer British workers in Freetown, Sierra Leone, in 1899, when full details of the method were published by them; but the work at Panama was on such a large scale and was so logically and thoroughly done that it set an example which we can only regret has not been more widely followed. The reasons for this are that local author- ities always dislike spending money on sanitation and that local sanitary officers seldom possess much influence or exercise it if they do possess it. For a long time also such practical efforts were much hampered by a school of writers who pleased the authorities by arguing that mosquitoes are irreducible, and that it is better to prevent malaria by quinine or by the use of mosquito- nets, and so on the truth being that local conditions must always determine the kind of prophylaxis which it is best to adopt. The history and details of all this will be found in The Prevention of Malaria (1911), by Sir Ronald Ross, with chapters by A. Celli, W. C. Gorgas, M. Watson, A. Balfour, and others.
Until the war spread to the eastern fronts British armies suffered little from tropical diseases; but then the Empire was compelled to pay dearly indeed for its neglect of investigation of these diseases in the past. In 1915 a terrible epidemic of dysentery, both bacillary and amoebic, afflicted the forces in the Dardanelles and contributed largely to the failure of that expedition. In the summer of 1916 a similar epidemic of malaria occurred among the troops on the Salonika front and continued until the end of the war. Apart from the numerous ship-loads of men invalided to Egypt, Malta, and Britain for these diseases, twenty-five thou- sand men had to be repatriated from Salonika during the height of the war for general disability caused by malaria. Both malaria and dysentery caused havoc among the forces in German East Africa and, perhaps to a less extent, among the forces in Meso- potamia. Not only did this sickness cripple the armies during the struggle, but it has left a legacy of relapses, both of malaria and of dysentery, which are now being heavily paid for by the British taxpayer in the form of pensions and medical treatment.
Towards the end of the earlier article it was remarked that " recent discoveries have done little or nothing for treatment. Quinine still remains the one specific." This was true in 1910, and it is this fact which has cost the British taxpayer so much. But our ignorance was deeper than is implied in the quotation; for, although we knew that quinine is the specific for malaria, we did not know exactjy how it should be used to the best advantage. Malaria is preeminently a disease which continues to relapse for months and years after a single infection by the mosquito, wherever the patient may be, however he may live, and in spite of quinine treatment as it is usually given. We knew that quinine in almost any doses from twenty to forty grains daily, or even less than this, was generally sufficient to control actual attacks of fever in two to four days, and to do so almost with certainty; but we did not know what dosage to use for the purpose of extirpating the infection, nor the nature of these relapses.
Numerous speculations had been advanced as to their nature. Some thought that the parasites enter upon a resting-stage some- where within the tissues during the fever-free intervals. F. Schau- dinn proposed as a hypothesis that the sexual parasites, which generally are not concerned with the patient's fever, suddenly begin to produce spores asexually when a relapse occurs ; but the evidence which he gave for this view did not bear careful examination. Sir Ronald Ross, however, had always held that the parasites continue to breed in the blood during the " rallies " just as they breed during the " relapses," except that in the former their numbers are too small to produce a febrile reaction. He had also long been much concerned regarding the defects in our knowledge of how to treat these relapses, and, in consequence, commenced researches on these subjects in collaboration with D. Thomson at Liverpool. The result was that, as he had anticipated, the parasites were found to be present in the blood in very small numbers during the rallies and to multiply greatly during the relapses. The number required to produce an attack of fever was roughly about 250 millions (a man contains about three million cubic millimetres of blood) ; but during a rally the numbers fall to a very few per cubic millimetre, while during a relapse the numbers may reach a total of many thousands of millions or may even exceed one million millions. This suggested that the proper way to extirpate the infection entirely was to give quinine constantly over a long period until the last parasite had been de- stroyed; but the material at Liverpool did not provide cases suitable for trial of this thesis so that when the war broke out we were still ignorant regarding it.
When the outbreak of malaria at Salonika occurred in 1916 Sir Alfred Keogh, the director-general, Army Medical Services, at once endeavoured to cope with the situation; and early in 1917 he appointed a special malaria hospital in each Command in the United Kingdom for the express purpose of investigating these questions, of finding a permanent cure if possible, and of treating the thousands of men who were being returned home sick with malaria from the eastern fronts, Sir Ronald Ross being also appointed Consultant in Malaria at the War Office. Many of the results will be found in the War Office publication : Observations on Malaria by the Medical Officers of the Army and Others (War Office, Dec. 1919). The fact, mentioned above, that moderate doses of quinine will control actual attacks within a few days was fully verified, and with very few exceptions; but it was quite otherwise with the complete extirpation of the infection which was so urgently required. Almost every form of treatment that had ever been suggested enormous doses of quinine reaching one hundred grains per diem, smaller doses con- tinued for three weeks or more; additional medication with arsenic and other drugs; continuous doses lasting for a month, and various kinds of interrupted dosage all proved quite uncertain. Thirty grains of quinine continued every day for three weeks proved a bad failure. Intramuscular injections and even intravenous injec- tions did no better; and the result was that men who were presumed to be cured relapsed again in a month or two after returning to duty, while those who remained apparently well even for some months relapsed later on. That is to say, a large proportion of the men who had once been infected with malaria became almost useless for further service though certainly a few cases appeared to have been finally cured. It should be added that numerous nostrums advocated for malaria proved incapable not only of checking relapses but also of influencing the number of parasites present during fever; the only exceptions being one or two arsenical preparations, which, however, certainly proved no better than ordinary quinine.
In all these attempts, be it noted, treatment had seldom been continued for more than one month and seldom or never for more than two months owing, of course, to military exigencies. But after the Armistice, when we were called upon to deal with large numbers of discharged soldiers, a longer period of treatment was decided upon. In 1918 two whole divisions, full of malaria, had been brought from Salonika to France and were there subjected to a longer course of treatment preparatory to their being sent again into the firing- line. The regiments arrived in an extremely baa condition, but were ajl placed in camps in the Dieppe region, and the men were there given 15 grains of quinine in solution once daily for a fortnight, followed by 10 grains of quinine in solution daily for two and a half months more. The course, which was designed by Col. J. Dalrymple, was carried out most strictly under his supervision, and had marvel- lous results, almost the whole of the two divisions being found fit for the front at the end of the three months. About the same time large malaria concentration-camps were established in England, where cases were given similar treatment but for shorter periods; and it was found generally that : (i) doses of less than 10 grains daily did not suffice to prevent relapses even while they were being taken; (2) doses of 10 grains daily did suffice to prevent relapses while the doses were being taken, except in about 6% of the cases, most of whom, however, relapsed during the first few days of the treatment; (3) !5 grains a day reduced the relapses still further, but only to about 4 % or 5 %.
The long-continued treatment of malaria had been advocated previously; but it was now proved to be so satisfactory that the authorities .decided to apply it to pensioners also. In Oct. 1919 the Ministry of Pensions established large clinics for tropical diseases; and the three-months' course was given as a routine to the malaria
