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Paul F. Russell, M.D., M.P.H., Sc. D.
But, as to public matters, it is clearly in military service that the ravages made by the diseases of malaria have been frequent, serious, and often ruinous; while if those have sometimes been inevitable, they have much too often been the results of neglect, or of what should be called ignorance * * * --MACCULLOCH, 1829.
At first, in this series on the history of preventive medicine in the U.S. Army in World War II, it was planned to include in one volume accounts of all the arthropodborne diseases that afflicted our troops throughout the world. But because of the size, scope, and attractiveness, as well as the importance of the manuscripts prepared by malariologists with wartime experience, the editors decided to devote an entire volume to malaria and a subsequent volume to be entitled "Arthropodborne Diseases Other Than Malaria." This volume will include accounts of some 15 diseases spread by mosquitoes, mites, ticks, lice, and fleas.
The following chapters tell the story of the life and death battling that went on continuously at home and overseas during World War II between the U.S. Army and the plasmodia of malaria together with certain species of Anopheles mosquitoes that spread the parasites from man to man. In many engagements, arthropodborne diseases, especially malaria., sent more soldiers to hospital beds than did the armies of the Axis with all their guns, planes, and tanks. For example, as noted in chapter V (p. 362), from 9 July to 10 September 1943, during the fierce Sicilian campaign, there were 21,482 hospital admissions for malaria compared with 17,375 battle casualties. Because most of the infections were with Plasmodium vivax, there were many incapacitating relapses during the spring of 1944, a time when every man was badly needed at Cassino and Anzio.
Naturally, malaria control became one of the main concerns of the Preventive Medicine Service of the Office of The Surgeon General. The importance in the Army's final conquest of malaria in World War II of the massive and steadily maintained primary administrative attack, initiated by Brig. Gen. James S. Simmons, and fully supported by The Surgeon General and by the Chief of Staff of the Army, can hardly be overemphasized. Details have been given by Hardenbergh 1 and by McCoy (see chapter II).
1 Hardenbergh, William A.: Control of Insects. In Medical Department, United States Army. Preventive Medicine in World War II. Volume II. Environmental Hygiene. Washington: U.S. Government Printing Office, 1955, pp. 179-232.
The power of the mosquito to knock out our soldiers was particularly manifest in the South and Southwest Pacific. I shall not forget Gen. Douglas MacArthur's statement to me in May 1943: "Doctor," he said, "this will be a long war if for every division I have facing the enemy I must count on a second division in hospital with malaria and a third division convalescing from this debilitating disease!" The general was not at all worried about defeating the Japanese, but he was greatly concerned about the failure up to that time to defeat the Anopheles mosquito. Thanks to this understanding of the power of the Plasmodium-arthropod axis and thanks to the superb attack on these enemies by American and Australian antimalaria personnel, as recounted in chapters III and X, U.S. Forces from mid-1943 onward waged a fast and successful war through some of the most malarious areas on earth.
Nearly all of the chapters that follow were written soon after the war by men who took an active part in the struggle. Place names, epidemiological facts, and authors titles appear as they existed during the period of World War II. The authors have not glossed over early mistakes and omissions which permitted malaria rates in U.S. Forces to climb, at times, to such appalling heights as 2,700 per 1,000 on Efate, in the second month of occupation; 1,781 per 1,000 on Guadalcanal, in November 1943; 4,000 per 1,000 at Mime Bay, in late 1942; and the fact (as noted in chapter IX) that malaria hastened the surrender on Bataan. Each author has attempted to give an accurate account of the difficulties and the errors--and of the ways in which these were overcome. There are valuable lessons in these chapters, published not merely for the record but in the hope that some of the pitfalls may be avoided in the future, although perhaps one is unduly optimistic to believe that the lessons of one war are ever remembered in the next. That memory is a sieve has been demonstrated over and over again with regard to military malaria control. Quoting Macculloch, 2 " * * * and still it would seem, as if fatal, that the wisdom and experience of one generation should be forgotten by the next, that peace should extirpate the knowledge that had been gained in war * * *."
MALARIA IN PAST WARS
For centuries, it has been recognized that there must be command responsibilities if preventive measures against disease are to be successful in military forces. In 1764 for example, John Pringle noted the fact in the preface of his classical book on diseases of the army that he was writing "for the information of officers as well as physicians."3 Both in his preface and in the text, he wrote that "the prevention of diseases cannot consist in the use of medicines, nor depend upon anything a soldier shall have it in his power to neglect, but
John: Malaria; an Essay on the Production and Propagation of This Poison
and on the Nature and Localities of the Places by Which It Is Produced:
With an Enumeration of the Diseases caused by It, and of the Means of Preventing
or Diminishing Them, Both at Home and in the Naval and Military Service,
Philadelphia: Thomas Kite, 1829.
upon such orders as shall not appear unreasonable to him, and such as he must necessarily obey." In 1910, Col. C. H. Melville,4 professor of hygiene, Royal Army Medical College, London, wrote for Ronald Ross a chapter on malaria prevention in war. In this, he commented that as regards antimalaria measures: "A specially selected medical officer should be placed in charge of these operations with executive and disciplinary powers, a step that has proved to be so effective by the officers of the U.S. Army in Cuba and elsewhere."
It is a simple truth that, in an army, discipline is as important in fighting disease as in fighting the human enemy. But this seemingly obvious fact was almost completely forgotten in the early months of World War II when there was often what Macculloch referred to in 1829 as "a contempt and an incredulity respecting malaria." The attitude of all too many command officers was at first similar to that reported of a general officer in a highly malarious area who, at a time when some 40 percent of his forces were already ill with malaria, resented all suggestions of malaria prophylaxis and said that if one had to play with mosquitoes in wartime that person should go back to Washington and stop bothering him while he was so busy getting ready to fight the Japs. Unfortunately, before his forces did any fighting at all, they were ignominiously routed by anopheline mosquitoes and were all evacuated to a rear area for malaria therapy and convalescence.
Most line officers and all too many medical officers at the beginning of World War II were ignorant about malaria and its potential for disrupting military operations. This was understandable in newly recruited personnel but hard to excuse in regular officers presumably trained to fight in any part of the world. For the history books are full of examples of malaria's military power. As Melville wrote: "The history of malaria in war might almost be taken to be the history of war itself, certainly the history of war in the Christian era." He mentioned the fevers in the French and Austrian armies in the Italian campaigns of 1859 and the disastrous Walcheren Expedition a century earlier in the Low Countries when the British were conquered by malaria before a battle could be fought. Melville commented on the 1864 West African campaigns as follows: "It can scarcely be called a war, as an enemy was never seen, or a grain of powder expended; our troops were defeated by disease, much of which was preventable." Then, there was the French campaign in Madagascar in 1895 when there were 13 deaths in action and over 4,000 deaths "due almost entirely to malarial fevers and their sequelae."
Numerous other examples
could be cited, such as that of Macedonia in World War I when malaria
immobilized British, French, and German armies for 3 years. On one occasion,
when the French commanding general was ordered to attack, he replied: "Regret
that my army is in hospital with malaria." Nearly 80 percent of 120,000
French troops in this area were hospitalized with malaria. In an average
4 Melville, C. H.: The Prevention of Malaria in War. In The Prevention of Malaria by Ronald Ross. 2d edition. London: John Murray, 1910, pp. 577-599.
162,512 admissions to hospital for malaria during the years 1916 to 1918, in contrast to 23,762 killed, wounded, prisoner, and missing in action. In the spring of 1918, about 25,000 British soldiers were sent home from Macedonia with chronic malaria, and, apart from these evacuees, over 2,000,000 man-days were lost to the British Army in this area in 1918 because of malaria. 5
BASIC MALARIA EPIDEMIOLOGY
To understand why malaria can so seriously disrupt an army, one must know a few basic principles of malaria epidemiology. For example, except for occasional accidental infections, as by blood transfusion, man acquires malaria only through the bite of an anopheline mosquito. No other genera can transmit the disease, and, in practice only, about 50 of some 200 species of Anopheles are closely enough associated with man to be dangerous. Most anophelines feed on animals. There was no malaria in New Caledonia because. there were no Anopheles mosquitoes there. No malarial infections occurred on the flat coastal plain or mangrove swamp areas of the Philippines because the anophelines in those areas do not feed on man. In the Philippines, malaria is transmitted by a species of Anopheles that breeds chiefly in foothill streams
Secondly, there can be no malaria transmission if there are no malaria parasites in man available to the mosquitoes. For example, there are potent malaria vector mosquitoes in many areas of our Southern States but no malaria transmission because none of the residents has malaria parasites in his blood. When soldiers bivouac in communities where there are parasites in the blood of the residents and vector mosquitoes in the area, it is a foregone conclusion that many of the soldiers without protection will become malarious. This, in turn, will increase the parasite reservoir, and there will be an epidemic among the soldiers unless preventive measures are taken promptly. Another important fact is that anophelines are rarely effective vectors over a radius much longer than a mile and a half. Yet time and time again, troops were allowed to bivouac in highly malarious surroundings when safe locations could have been utilized a mile or two away.
It is also important to know that different species of anophelines have different breeding habits. All develop only in water, but some prefer rice paddies, some pools and puddles, some foothill running streams, some swamps or ponds, some marshes, some wells, some fresh water, some brackish, some sun, and some shade. Therefore, malaria control requires the help of trained entomologists or malariologists who know or can find out the habits of the mosquitoes. For example, on Guadalcanal and in West Africa, where the vectors breed in pools, puddles, and wheel ruts, U.S. Armed Forces created
5 (1) Russell, Paul P., West Luther S., and Manwell, Reginald U.: Practical Malariology .Philadelphia: W. B. Saunders Co., 1946. (2) MacDonald, A. G.: Prevention of Malaria. In History of the Great War Based on Official Documents. Medical Services, Hygiene of the War, edited by W. G. Macpherson, W. H, Horrocks, and W. W. 0. Beveridge. London: His Majesty's Stationery Office,: 1928, vol. II, pp. 189-238.
thousands of breeding places for the local malaria vectors and thus greatly increased the numbers of malaria mosquitoes and so the eases of malaria.
The fact that most anopheline vectors feed only at night is important. In West Africa and elsewhere, U.S. Forces suffered from much preventable malaria by permitting unprotected soldiers to attend night movies where they were easy prey to the night-biting malarial mosquitoes. Air Forces personnel taking planes front the United States to the United Kingdom via South America and West Africa were often billeted in unscreened or poorly screened quarters at Eknes Field and in the Dakar-Rufisque area of French West Africa where the malaria rates among the base personnel, in the autumn of 1943, sometimes exceeded 1,500 per 1,000. Many Air Forces officers who had spent a night or two in these areas, therefore, developed malaria in nonmalarious England and so were out of action when badly needed.
The epidemiology of malaria and the technical application of control measures are basically the same in military as in civilian communities. But there are some differences. The following features, for instance, tend to make malaria control easier under wartime military conditions than in civil life: Complete authority of the commanding officer, uniformity of living habits of the personnel, and ample antimalaria funds and supplies. But other features impose handicaps; for example, troop mobility and dispersion, necessarily based on tactics and not on sanitary conditions; a great deal of vital nocturnal activity; difficult logistics, especially in combat zones; enemy action, mines, and boobytraps; and combat tension when the chief concern is not malaria control but immediate life and death. Moreover, a military force operating where malaria is endemic generally finds the malaria potential greatly increased. In jungly areas, necessary clearing opens up breeding waters for anopheline vectors that prefer sunlight, and other operations often tend to multiply breeding places. In civilized areas, war often forces the people out of cities into the malarious countryside where they live in shelters exposed to infective mosquitoes. Local health services are disrupted or abandoned so that there is no civilian malaria control. Thus troops may be exposed to malaria incidence much greater than normal for the area. Trenches, foxholes, tank traps, gun emplacements, vehicle ruts, shell, bomb and mine craters, sabotaged irrigation projects, streams ponded by bridge rubble and improvised causeways, drainage blocked by hastily built airfields and highways, all may provide additional breeding places for malaria mosquitoes. An army must depend largely on its own efforts to prevent loss of manpower due to mosquito action.6
MALARIA LESSONS FROM WORLD WAR II
The following chapters make it clear that out of World War II came certain fundamental lessons regarding military malaria control. The principal general lesson was that it is impossible to control malaria effectively in military
6 See footnote 5 (1), p. 4.
forces in highly malarious areas unless commanding officers from highest to lowest echelons are malaria conscious. Training and education of both medical and line officers in regard to malaria and its control are essential. Malaria control in the army is a military problem. A malaria policy must not only be formulated: it must be enforced. Malaria discipline is absolutely necessary to an army's success in fighting the Plasmodium-mosquito axis. This malaria discipline is a part of what Sir Neil Cantlie, Director General of British Army Medical Services, called "Health Discipline" and which he defined as "measures that concern the preservation of health and the prevention of disease which are enforced by disciplinary means."7 Cantlie tells of one commander who, when he had grasped the importance of Brig. N. H. Fairley's proof that clinical malaria could be prevented by taking a tablet of Atabrine (quinacrine hydrochloride or mepacrine hydrochloride) a day, said: "You doctors think you can prevent malaria, but you can't. I can and I'm going to." This lay officer's declaration that he was going to prevent malaria signified a vital turning point that made victory possible. Again quoting Cantlie: "When for the first time in history a combatant officer was considered unfit to command a unit on the grounds that he had allowed his men to become ineffective through disease, a new day in military medicine dawned. The clouds of forgetfulness must not be allowed to overshadow the brightness of that day."
The second general lesson was that it is scarcely possible to control malaria successfully in any but lightly endemic areas, or in small units, unless there is a special military malaria control organization to survey, plan, execute, supervise, amid maintain the numerous and technical measures that must be carried out continuously if malaria is to be defeated. Personnel charged with all manner of sanitary duties cannot give the time and care to malaria that is required for its control. Full and undivided attention by a specially trained malaria control organization is absolutely essential.
A third lesson was that malaria supplies and personnel require priority of movement commensurate with their importance. For example, in some areas of New Guinea, malaria supplies and personnel were more important to the success of the fighting than was much of the materiel being sent forward. Yet early in 1943, malaria supplies for use in the Southwest Pacific were mostly piled up on the piers of the west coast of the United States. The few supplies that went to Australia stayed there and were not moved on to New Guinea because malaria supplies were about tenth down the list of priority of movement. In wartime, everything moves from the rear toward the front on strict priorities set by the theater command. When the need became obvious in May 1943, the priorities for malaria supplies and personnel were raised to first place, and thereafter no serious shortages occurred. This action, together with the enforcement of malaria discipline and the provision of specialist malaria control and survey units, turned the scales, and malaria was thoroughly defeated. These were the fundamentals: (1) Malaria discipline, (2) special-
7 Cantlie, N.: Health Discipline. U.S. Armed Forces Med. J. 1: 232-287, February 1950.
ized malaria control organization, and (3) high priorities for movement of malaria personnel and supplies. The military experience taught once again that the prevention of malaria is neither automatic nor simple but is compounded of law and persuasion, organization and training, supplies and technical application. Once the fundamental lessons were learned, the military malaria problem was solved.
ADVANCES IN MALARIOLOGY IN WORLD WAR II
Certain advances in malariology during World War II should be briefly mentioned. The greatest were in the development and use of (1) synthetic antimalarial drugs and (2) residual insecticides.
Antimalarial drugs.-- As regards antimalarial drugs, World War II liberated us from quinine, taught us how to use Atabrine, and led us to such powerful new antimalarials as chloroquine and amodiaquin, primaquine, proquanil, and pyrimethamine. Quinine and its source, cinchona bark, had been the only effective medicament in malaria therapy and prophylaxis for over 300 years. Then, when the Germans were unable to obtain quinine during World War I, they began to experiment with synthetic substitutes, producing Plasmochin naphthoate (pamaquine naphthoate),in 1925; Atabrine, in 1930; Resochin or Aralen (chloroquine diphosphate),in 1943; and Sontochin or Sontoquine, a little later. 8 Resochin, strange to say, was discarded by them as apparently too toxic.
After the entry of Japan into World War II, the Allies were quickly cut off from Indonesia, the principal source of quinine, and so they began an extensive program of research on antimalarials both in the United Kingdom and in the United States. The secrets of Atabrine manufacture had been kept in Germany but were soon solved by Allied chemists, and the drug was put into large production in the United States. Atabrine immediately gained widespread recognition as an excellent therapeutic agent, but there was some confusion about its use as a prophylactic until the classic experiments of Brigadier N. Hamilton Fairley in Australia in l943. 9 These proved beyond doubt that one tablet of Atabrine (100 mg.) a day would prevent overt attacks of malaria, curing those due to Plasmodium falciparum. and postponing clinical manifestations of P. vivax infections until the drug was withheld. With relatively few exceptions, this suppressive Atabrine could be administered for many days without serious toxic effect. The evidence is clear that the taking of suppressive Atabrine, when strictly enforced by suitable malaria discipline, enabled our forces to fight in highly malarious surroundings without being hampered by clinical malaria.
8 (1) Covell,
Gordon, Coatney, G. Robert, Field, John W., and Singh, Jaswant: Chemotherapy
of Malaria. Monograph Series No. 27. Geneva: World Health Organization,
1955. (2) Most, Harry: Clinical Trials of Antimalarial Drugs. In
Medical Department, United States Army. Internal Medicine in World War II.
Volume II. Infectious Diseases. Washington : U.S. Government Printing Office,
After the Allied occupation of North Africa, the Allies learned that the French had found Sontoquine to have high antimalaria value. This led to the exploration of a large series of 4-aminoquinolines by investigators in the United States. They determined that Camoquin (amodiaquin) and Resochin or Aralen were excellent antimalarial drugs comparable to Atabrine. Neither drug became available to the Army in any quantity before the end of the war.
Other wartime studies were directed to the 8-aminoquinolines and led to the discovery of primaquine in 1945. In the overall U.S. wartime program up to 1946, more than 15,000 compounds were studied for antimalaria values.
British investigators also carried out extensive studies on malaria drugs, and these led to the synthesis of quite different but highly effective compounds, proguanil or Paludrine (chlorguanide hydrochloride) in 1944 and Daraprim or malocide (pyrimethamine) in 1952, reported by Covell and others.
DDT.-- Dichlorodiphenyltrichloroethane (DDT) was first synthesized in 1874 by a Viennese pharmacist, Othmar Zeidler, who at the time was a chemistry student in Strasbourg interested in the then new phenomena of organic synthesis.10 He did not investigate the properties of the new substance but simply published his synthesis. Then in 1939 in Switzerland, Paul Müller of the Geigy Company, searching for a toxicant that would kill clothes moths, resynthesized this compound and made his Nobel Prize-winning discovery that it was an insecticide of remarkable versatility. The Geigy Company began in 1940-41 to market the substance in two forms: (1) A 5-percent dust called Gesarol spray insecticide, at the time principally for use against potato beetles, and (2) a 3-percent dust called Neocid dust insecticide, for use as a lousicide.
Due in large measure to the U.S. Military Attaché at Berne, Maj. A. R. W. de Jonge, samples of these products were sent to the Geigy Company's New York branch and to London, in the autumn of 1942. Studies at the Orlando, Fla., laboratory of the Bureau of Entomology and Plant Quarantine demonstrated beyond question that this new insecticide had tremendous possibilities not only against lice but also against several other noxious insects, such as mosquitoes and houseflies. 11 With the help of the War Production Board, the new insecticide was put into large production as soon as possible. The now universally used name, DDT, was first applied by the British Ministry of Supply in 1943. 12 DDT was first added to U.S. Army supply lists in May 1943. 13
Gahan and colleagues, in August 1943, appear to have made the first practical tests of DDT as a residual insecticide against adult vector mosquitoes.14
Paul F.: Man's Mastery of Malaria. New York: Oxford University Press,
They sprayed the interior surfaces of various types of houses and found the procedure to be quite effective against Anopheles quadrimaculatus. The first field test in which residual DDT was applied to the interior surfaces of all habitations and outbuildings of a community to test its effect on Anopheles vectors and malaria incidence was begun in Italy in the spring of 1944. This experiment was carried out in the town of Castel Volturno at the mouth of the Volturno River, north of Naples, by the Malaria Control Demonstration Unit of the Malaria Control Branch of the Public Health Sub-Commission, Allied Control Commission, Italy. Spraying began on 17 May 1944, and this experiment, together with a second one started later in the Tiber Delta area, lasted 2 years. 15 The Malaria Control Demonstration Unit, under the direction of Dr. F. L. Soper, consisted largely of members of the Rockefeller Foundation Health Commission who had brilliantly carried out their first assignment--that of assisting in typhus control in Naples.
These highly significant experiments, the first to prove the practical usefulness of residual DDT in malaria control, were possible only because of the support given to them by the ranking U.S. medical officer in the theater, Maj. Gen. Morrison C. Stayer, and his preventive medicine officer, Col. William S. Stone, MC, and by the commanding officer of the Public Health Sub-Commission, Brigadier George Parkinson.
As DDT supplies became more abundant many other trials under military and civilian auspices were carried out in 1944 and 1945 in various parts of the world. They led directly to the concept of "nationwide malaria eradication" now being applied practically in so many countries. DDT no doubt would eventually have found its place in malaria control, but the war needs and experiments greatly accelerated its acceptance and use and led to the discovery and application of similar insecticides such as benzene hexachloride and dieldrin.
Allied malaria control units demonstrated the value of malaria control by modern methods all over the world with such striking success that civilian authorities were willing after the war to budget large funds for antimalaria programs. There can be no doubt that antimalaria activities of World War II constituted a prime factor in the development of the present move for worldwide malaria eradication.
Other advances .--Besides the major advances in preparation and use of synthetic antimalarials and insecticides just described, there were certain others as, for example, the improvement in repellents represented by dimethyl phthalate; the increased scope of airplane larvicidal dusting with paris green, due to wartime research which raised the prewar maximum load of 700 to 3,000 pounds, applied from the air with great efficiency; the development of pressure cylinders using liquid Freon-12 as a propellant for pyrethrum insecti-
15 Soper, F. L., Knipe, F. W., Casini, G., Riehl, L. A., and Rubino, A.: Reduction of Anopheles Density Effected by the Pre-Season Spraying of Building Interiors with DDT in Kerosene, at Castel Volturno, Italy, in 1944-45 and in the Tiber Delta in 1945. Am. J. Trop. Med. 27: 177-200, March 1947.
cide expelled as an Aerosol mist; the broadening of taxonomic and biologic knowledge of the genus Anopheles around the world; and increased understanding of the Plasmodium and its growth in vivo, in vitro, and in tissue culture.16
The devising, manufacturing, and distributing of antimalaria. supplies and equipment was notable in World War II from mid-1943 onward. Unusually effective cooperation from the beginning of the war was maintained among the Army, Navy, U.S. Public Health Service, National Research Council, Bureau of Entomology and Plant Quarantine of the U.S. Department of Agriculture, War Production Board, Institute of Inter-American Affairs, industrial firms, medical schools, research institutes, and foundations. Information was freely exchanged between the United States, United Kingdom, and Australia; moreover, the three Governments effectively supported vital laboratory and field experiments. Seldom, if ever, have research and practical application in preventive medicine come closer together. 17
Man's net losses from World War II were so enormous that these lessons and advances can hardly be called dividends or be pointed to with pride. The progress in malariology, such as it was, constituted a sort of salvage, undoubtedly of considerable value.
But we can very definitely point with pride to the skill, courage, and devotion to duty of the personnel, officers and men, of the malaria organizations of the Army in World War II. Tribute is best expressed in the following message which Brig. Gen. (later Ma]. Gen.) Guy B. Denit,18 Chief Surgeon, Southwest Pacific Area, published at his headquarters in December 1944:
The reduction of the malaria attack rate in this theater to a point at which it no longer constitutes a dangerous handicap to our military effort is an achievement of historical importance in preventive medicine. It has been the result of a joint effort which is to the great credit of all who have participated. In this accomplishment the malariologists and the malaria survey and malaria control units have played the major role. Despite hardships and often danger, their achievements have been notable. The Medical Department is proud of your initiative and perseverance, of your professional contributions, and of the striking success of your efforts.
The following 18th century quotation from Pringle (p. 2) seems appropriate in closing this introduction: "Yet, however, imperfect these sheets may be, I hope they may serve as a foundation for others to build upon; who, by making improvements on this subject, will concur with me, in attempting to draw from the calamities of war some benefit to mankind."
P. P.: Lessons in Malariology from World War II. Am. J. Trop. Med. 26:
5-13, January 1946.