MALARIA IN HISTORY
By E. ASHWORTH UNDERWO9D
THE announcement of the result of tests on the new anti-malaria drug, " paludrine," prompts some assessment of the part which this disease has played in world history, and of the prospects which new measures extend to those who are endeavouring to bring it under control. To the average person in this country who has not -been abroad, malaria is a disease of hot clirnateS which leads to unpleasant bouts of fever, with pains, shivering and then sweating. Death does not loom large in his mental picture. He would no doubt be sur- prised if he were told that the greatest authorities have given malaria a higher importance in the history of man than any other endemic disease to which the human race is subject. Some years ago it was estimated that throughout the world Soo million persons suffer annually from acute or chronic forms of this malady, and a more recent estimate gives for India alone roo million cases, anything from one to three million deaths each year. In 'Ceylon in 1935 there' were 70,000 deaths due to malaria in a population of only 5 million. In the United States there afe probably a million cases annually with 500 deaths. Since the proportion of deaths to cases is generally small, the British layman, who does not happened to be burdened with the cares of colonial administration, is apt to make light of the cases of which he has heard, and to overlook the deaths of which he knows little or nothing. Our vast Colonial Empire merits a wider know- ledge of a disease which has given our scientists and administrators so much trouble, and which has provided our medical men with the opportunity of making fundamental contributions to the progress of medicine.
The unwelcome association between the malaria parasite and the human-race is shrouded in the mists of - antiquity. This disease is (probably) is mentioned in the book of Deuteronomy, and it has been suggested that the Maya Civilisation of Central America disappeared as the result of its ravages. From a remark of the " Father of His- tory," Herodotus, it seems probable that the disease was prevalent among the Greeks in Asia Minor in the sixth century B.C., and a reference to it occurs in Homer. The derivation of the name of the new drug, paludrine, from the Latin word for " a marsh," typifies the age-old association between malaria and marshy districts, and indeed the myth of Hercules slaying the Hydra has been construed as indi- cating the reclamation of marsh lands. In the fifth century B.C. Hippocrates, the " Father of Medicine," wrote astately that those who drink the water of marshy districts have large spleens but thin faces and shoulders, and that " long quartans " are common amongst them. Here in a nutshell is a picture of the chronic malaria patient. Of course, Hippocrates could not know that it was not the water of the marshy district, but the mosquitoes which bred in it which caused the disease. Matthew Arnold, in his poem on Empedocles, told how this early Greek philosopher was able to " cleanse to sweet airs the breath of poisonous streams "—in reference to the fact that
Empedocles was reputed to have freed the city of Selinus in Sicily from an epidemic of malaria by draining the marshes and by turning two rivers into them. This disease is mentioned not infrequently by lay-writers, such as Pindar and Aristophanes. Throughout the his- tory of the Roman Empire malaria played an important part. The Campagna and the Pontine Marshes were hot-beds of disease, and the so-called " Roman Airs " were proverbial.
As might be expected, malaria did not confine itself to the inhabi- tants of the Empire: it played havoc with the invading hosts of barbarians. Alaric the Goth died of malaria in 410 A.D. The repu- tation of the surroundings, of Rome as a hot-bed of malaria persisted throughout the Middle Ages, and one Pope after another died from it. In 1167 it decimated, the army 'of Frederic Barbarossa, and in the same year it caused ao,000 deaths in Rome itself. We have few records of what might have been true malaria in England during the Middle AgeS, but it was undoubtedly present in the fen-lands. In Tudor times there are records of " agues," some of which were true malaria. In 1557-58 there was a widespread outbreak, and although this may have been partly due to influenza, in some districts malaria was then epidemic. The frequency of the condition known as " ague- cake " (malarial enlargement of the spleen) was well-recognised, and this prevalence is found only in districts in which malaria is endemic.
Quinine was for long regarded not only as a specific for treatment, but also as a means of warding off malarial infection, if taken in the correct doses for a sufficient period. Something of a romance sur- rounded the introduction of this drug from Peru to Europe. The legend has it that either the first or the second wife of Don Luis Geronimo Fernandez de Cabrera, Count of Chinchon, the Viceroy of Peru, was suffering from a tertian ague, and that she was cured by the powdered bark of the quina-quina tree, administered to her by the Count's physician, Juan del Vego. She returned to Spain about 1640, bringing with her supplies of the bark for the use of the fever-stricken patients in her native land. A century later the qui'na- quina tree was given the name Cinchona by Linnaeus, but in the meantime it had been known as "Countess' bark," or, alternatively, as " Jesuit's bark," because of the large quantities which were sent to Rome by Jesuit missionaries in 1670. Unfortunately for the pretty story, the Countess' official diary was discovered a few years ago and did not confirm it. The whole question was recently investigated by the late A. W. Haggis, who showed that the bark which was originally used in Peru was Peruvian Balsam, a drug of general use in fevers. Cinchona, which was much more a specific remedy for malaria, was given the name of " quitah-quina " by European merchants at the time when it was being illicitly used as a substitute for Peruvian Balsam bark. The truth appears to be that the bark was introduced to Europe about the year 1633 by persons unknown. The bark had various vicissitudes in the treatment of malaria, the most astonishing being its utter eclipse, which was encompassed by the advocacy of James Johnson, who had a very wide influence, and who by,• the heroic purging and bleeding which he first recommended in 1813 as a substitute increased the' mortality from malaria ten-fold. His influence unfortunately lasted for over forty years.
The story of malaria could hardly be told-without even the briefest mention of the discovery ot the malaria parasite and the manner of its transmission. Pigmented bodies in the cells of the blood were noticed by Meckel in 1847, and later by other observers. It was not until 1880, however, that Laveran, a French Army surgeon, recog- nised that they • were living parasites, and observed the whiplike motion of the male elements. He was therefore the " discoverer " of the malaria parasite. How was it transmitted from patient to healthy individual? In classical times the Rothan architects Varro and Columella had independently suggested that insects might spread the disease. Sir Richard Burton, the explorer, in a work published in 1856, told of a tribe in Somaliland among whom the superstition was current that mosquito bites caused fatal fevers, and the native superstition proved forty yeartlater to be correct. The true sponsor of this line of investigation was Sir Patrick Manson, who inspired the work of Major (later Sir) Ronald Ross, of the Indian Medical Service. On August zoth,' 1897, Ross found pigmented cells in the stomach of a mosquito, and this insect was thereby proved to be the " vector " of malaria. On the analogy of certain observations made
at that time by MacCallum in the United States, Manson built up the theory that there was a special " sexual " cycle of reproduction of the malaria parasite in the mosquito. It is a sad reflection on the administrative obtuseness of official medicine that Ross, just after he had made his great observation, was allocated other duties which pre- vented him from working on human malaria. However, he took up Manson's suggestions and proved their correctness in the malaria of birds. During the following year (1898) the Italian malariologists Grassi, Bastianelli and Bignami—without question great observers— proved the theory for human malaria, and worked out the life cycle of the parasite. As Ross remarked : " I put the key in the door, and the Italians had only to turn it! "
In the half-century which has elapsed since these events much has been done, bfit malaria is still a major problem of humanity. With- out the anopheline mosquito there would be no malaria—yet the mosquito, despite " assisted efforts," is an unconscionable time in dying. Treatment and prevention still leave much to be desired. Quinine, one of the alkaloids of cinchona bark, was isolated by two famous French pharmacologists in 182o, and the others by 1853. During the last fifteen years the synthetic drugs atebrin and plas- mochin have been much used, and they compensated nobly for the loss of Java, which provided over 90 per cent. of the world's supply of quinine. However, neither the cinchona alkaloids nor these new drugs are true " prophylactics " in the sense that they prevent infec- tion. When given in preventive doses they merely damp down the symptoms when the individual is infected. More than a thousand synthetic compounds were tested in the search for the new drug, paludrine. There is already evidence that it is excellent, not only for treatment but also for prevention, and, combined with D.D.T. in combating the mosquito, it should provide a sound basis for rich hopes for the future.
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