MALARIA  , an

Italian colloquial word (from mala, bad, and aria, air), introduced into English medical literature by Macculloch (1827) as a substitute for the more restricted terms "marsh miasm" or "paludal poison." It is generally applied to the definite unhealthy condition of body known by a variety of names, such as ague, intermittent (and remittent) fever, marsh fever, jungle fever, hill fever, " fever of the country " and " fever and ague." A single paroxysm of simple ague may come upon the patient in the midst of good health or it may be preceded by some malaise . The ague-fit begins with chills proceeding as if from the lower part of the back, and gradually extending until the coldness overtakes the whole body . Tremors of the muscles more or less violent accompany the cold sensations, beginning with the muscles of the lower jaw (chattering of the teeth), and extending to the extremities and trunk . The expression has meanwhile changed: the face is pale or livid; there are dark rings under the eyes; the features are pinched and sharp, and the whole skin shrunken; the fingers are dead white, the nails blue . All those symptoms are referable to spasmodic constriction of the small surface arteries, the pulse at the wrist being itself small, hard and quick . In the interior organs there are indications of a compensating accumulation of blood, such as swelling of the spleen, engorgement (very rarely rupture) of the heart, with a feeling of oppression in the chest, and a copious flow of clear and watery urine from the congested kidneys . The body temperature will have risen suddenly from the normal to 103° or higher . This first or cold stage of the paroxysm varies much in length; in temperate climates it lasts from one to two hours, while in tropical and subtropical countries it may be shortened . It is followed by the stage of dry heat, which will be prolonged in proportion as the previous stage .is curtailed . The feeling of heat is at first an internal one, but it spreads outwards to the surface and to the extremities; the skin becomes warm and red, but remains dry; the pulse becomes softer and more full, but still quick; and the throbbings occur in exposed arteries, such as the temporal . The spleen continues to enlarge; the urine is now scanty and high-coloured; the body temperature is high, but the highest temperatures occur during the chill; there is consider-able thirst; and there is the usual intellectual unfitness, and it may be confusion, of the feverish state . This period of dry heat, having lasted three or four hours or longer, comes to an end in perspiration, at first a mere moistness of the skin, passing into sweating that may be profuse and even drenching .

Sleep may overtake the patient in the midst of the sweating stage, and he awakes, not without some feeling of what he has passed through, but on the whole well, with the temperature fallen almost or altogether to the normal, or it may be even below the normal; the pulse moderate and full; the spleen again of its ordinary size; the urine that is passed after the paroxysm deposits a thick brick-red sediment of urates . The three stages together will probably have lasted six to twelve hours . The paroxysm is followed by a definite interval in which there is not only no fever, but even a fair degree of bodily comfort and fitness; this is the intermission of the fever . Another paroxysm begins at or near the same hour next day (quotidian ague), which results from a double tertian infection, or the interval may be forty-eight hours (tertian ague), or seventy-two hours (quartan ague) . It is the general rule, with frequent exceptions, that the quotidian paroxysm comes on in the morning, the tertian about noon, and the quartan in the afternoon . Another rule is that the quartan has the longest cold stage, while its paroxysm is shortest as a whole; the quotidian has the shortest cold stage and a long hot stage, while its paroxysm is longest as a whole . The point common to the various forms of ague is that the paroxysm ceases about midnight or early morning . Quotidian intermittent is on the whole more common than tertian in hot countries; elsewhere the tertian is the usual type, and quartan is only occasional . If the first paroxysm should not cease within the twenty-four hours, the fever is not reckoned ss an intermittent, but as a remittent . Remittent is a not unusual form of the malarial process in tropical and subtropical countries, and in some localities or in some seasons it is more common than intermittent . It may be said to arise out of that type of intermittent in which the cold stage is shortened while the hot stage tends to be prolonged . A certain abatement or re-mission of the fever takes place, with or without sweating, but there is no true intermission or interval of absolute apyrexia .

The periodicity shows itself in the form of an exacerbation of the still continuing fever, and that exacerbation may take place twenty-four hours after the first onset, or the interval may be only

half that period, or it may be double . A fever that is to be remittent will usually declare it-self from the outset: it begins with chills, but without the shivering and shaking fit of the intermittent; the hot stage soon follows, presenting the same characters as the prolonged hot stage of the quotidian, with the frequent addition of bilious symptoms, and it may be even of jaundice and of tenderness over the stomach and liver . Towards morning the fever abates; the pulse falls in frequency, but does not come down to the normal; headache and aching in the loins and limbs become less, but do not cease altogether; the body temperature falls, but does not touch the level of apyrexia . The remission or abatement lasts generally throughout the morning; and about noon there is an exacerbation, seldom ushered in by chills, which continues till the early morning following, when it remits or abates as before . A patient with remittent may get well in a week under treatment, but the fever may go on for several weeks; the return to health is often announced by the fever assuming the intermittent type, or, in other words, by the remissions touching the level of absolute apyrexia . Remittent fevers (as well as intermittents) vary considerably in intensity; some cases are intense from the outset, or pernicious, with aggravation of all the symptoms—leading to stupor, delirium, collapse, intense jaundice, blood in the stools, blood and albumen in the urine, and, it may be, suppression of urine followed by convulsions . The severe forms of intermittent are most apt to occur in the very young, or in the aged, or in debilitated persons generally . Milder cases of malarial fever are apt to become dangerous from the complications of dysentery, bronchitis or pneumonia . Severe remittents (pernicious or bilious remittents) approximate to the type of yellow fever (q.v.), which is conventiohally limited to epidemic outbreaks in western longitudes and on the west coast of Africa . Of the mortality due to malarial disease a small part only is referable to the direct attack of intermittent, and chiefly to the fever in its pernicious form . Remittent fever is much more fatal in its direct attack . But probably the greater part of the enormous total of deaths set down to malaria is due to the malarial cachexia .

The dwellers in a malarious region like the Terai (at the

foot of the Himalayas) are miserable; listless and ugly, with large heads and particularly prominent ears, flat noses, tumid bellies, slender limbs and sallow complexions; the children are impregnated with malaria from their birth, and their growth is attended with aberrations from the normal which practically amount to the disease of rickets . The malarial cachexia that follows definite attacks of ague consists in a state of ill-defined suffering, associated with a sallow skin, enlarged spleen and liver, and sometimes with dropsy . Causation.—From the time of Hippocrates onwards the malarial or periodical fevers have engaged the attention of innumerable observers, who have suggested various theories of causation, and have sometimes anticipated—vaguely, indeed, but with surprising accuracy—the results of modern research; but the true nature of the disease remained in doubt until the closing years of the 19th century . It has now been demonstrated by a series of accurate investigations, contributed by many workers, that malaria is caused by a microscopic parasite in the blood, into which it is introduced by the bites of certain species of mosquito . (See PARASITIC DISEASES and MosQuITOES.) The successive steps by which the present position has been reached form an interesting chapter in the history of scientific progress . The first substantial link in the actual History of chain of discovery was contributed in 188o by Discovery . Laveran, a French army surgeon serving in Algeria . On the 6th of November in that year he plainly saw the living parasites under the microscope in the blood of a malarial patient, and he shortly afterwards communicated his observations to the Paris Academic de Medecine . They were confirmed, but met with little acceptance in the scientific world, which was preoccupied with the claims of a subsequently discredited Bacillus malariae . In 1885 the Italian pathologists came round to Laveran's views, and began to work out the life history of his parasites . The subject has a special interest for Italy, which is devastated by malaria, and Italian science has contributed materially to the solution of the problem . The labours of Golgi, Marchiafava, Celli and others established the nature of the parasite and its behaviour in the blood; they proved the fact, guessed by Rasori so far back as 1846, that the periodical febrile paroxysm corresponds with the development of the organisms; and they showed that the different forms of malarial fever have their distinct parasites, and consequently fall into distinct groups, defined on an etiological as well as a clinical basis—namely, the mild or spring group, which includes tertian and quartan ague, and the malignant or " aestivo-autumnal " group, which includes a tertian or a semi-tertian and the true quotidian type .

Three distinct parasites, corresponding with the tertian, quartan and malignant types of fever, have been described by Italian observers, and the

classification is generally accepted; intermediate types are ascribed to mixed and multiple infections . So far, however, only half the problem, and from the practical point of view the less important half, had been solved . The origin of the parasite and its mode of introduction into the blood remained to be discovered . An old popular belief current in different countries, and derived from common observation, connected mosquitoes with malaria, and from time to time this theory found support in more scientific quarters on general grounds, but it lacked demonstration and attracted little attention . In 1894, however, Sir Patrick Manson, arguing with greater precision by analogy from his own discovery of the cause of filariasis and the part played by mosquitoes, suggested that the malarial parasite had a similar intermediate host outside the human body, and that a suctorial insect, which would probably be found to be a particular mosquito, was required for its development . Following up this line of investigation, Major Ronald Ross in 1895 found that if a mosquito sucked blood containing the parasites they soon began to throw out flagellae, which broke away and became free; and in 1897 he discovered peculiar pigmented cells, which afterwards turned out to be the parasites of aestivo-autumnal malaria in an early stage of development, within the stomach-wall of mosquitoes which had been fed on malarial blood . He further found that only mosquitoes of the genus Anopheles had these cells, and that they did not get them when fed on healthy blood . Then, turning his attention to the malaria of birds, he worked out the life-history of these cells within the body of the mosquito . " He saw that they increased in size, divided, and became full of filiform spores, then ruptured and poured out their multitudinous progeny into the body-cavity of their insect host . Finally, he saw the spores accumulate within the cells of the salivary glands, and discovered that they actually passed down the salivary ducts and along the grooved hypopharynx into the seat of puncture, thus causing infection in a fresh vertebrate host " (Sambon) . To apply these discoveries to the malaria of man was an obvious step . In working out the details the Italian school have again taken a prominent part .

Thus we get a

complete scientific demonstration of the causation of malaria in three stages: (1) the discovery of the parasite by Laveran; (2) its life-history in the human host and connexion with the fever demonstrated by the Italian observers; (3) its life-history in the alternate host, and the identification of the latter with a particular species of mosquito by Ross and Manson . The conclusions derived from the microscopical laboratory were confirmed by actual experiment . In 1898 Experiment. it was conclusively shown in Italy that if a mosquito of the Anopheles variety bites a person suffering from malaria, and is kept long enough for the parasite to develop in the salivary gland, and is then allowed to bite a healthy person, the latter will in due time develop malaria . The con- verse proposition, that persons efficiently protected from mosquito bites escape malaria, has been made the subject of several remarkable experiments . One of the most interesting was carried out in 1900 for the London School of Tropical Medicine by Dr Sambon and Dr Low, who went to reside in one of the most malarious districts in the Roman Campagna during the most dangerous season . Together with Signor Terzi and two Italian servants, they lived from the beginning of July until the 19th of October in a specially protected hut, erected near Ostia . The sole precaution taken was to confine themselves between sunset and sunrise to their mosquito- proof dwelling . All escaped malaria, which was rife in the immediate neighbourhood . Mosquitoes caught by the experi- menters, and sent to London, produced malaria in persons who submitted themselves to the bites of these insects at the London School of Tropical Medicine . Experiments in pro- tection on a larger scale, and under more ordinary conditions, have been carried out with equal success by Professor Celli and other Italian authorities . The first of these was in 1899, and the subjects were the railwaymen employed on certain lines running through highly malarious districts . Of 24 pro- tected persons, all escaped but four, and these had to be out at night or otherwise neglected precautions; of 38 unprotected persons, all contracted malaria except two, who had apparently acquired immunity .

In 1900 further experiments gave still better results . Of 52 protected persons on one line, all escaped except two, who were careless; of 52 protected on another line, all escaped; while of 51 unprotected persons, living in alternate houses, all suffered except seven . Out of a total of 207 persons protected in these railway experiments, 197 escaped . In two peasants' cottages in the Campagna, protected with

wire netting by Professor Celli, all the inmates—ro in number —escaped, while the neighbours suffered severely; and three out of four persons living in a third hut, from which protection was removed owing to the indifference of the inmates, contracted malaria . In the malarious islet of Asinara a pond of stagnant water was treated with petroleum and all windows were protected with gauze . The result was that the houses were free from mosquitoes and no malaria occurred throughout the entire season, though there had been 40 cases in the previous year . Eight Red Cross ambulances, each with a doctor and attendant, were sent into the most malarious parts of the Campagna in 190o . By living in protected houses and wearing gloves and veils at night all the staff escaped malaria except one or two attendants . These and other experiments, de-scribed by Dr Manson in the Practitioner for March 1900, con-firming the laboratory evidence as they do, leave no doubt whatever of the correctness of the mosquito-parasitic theory of malaria . It is possible, though not probable, that malaria may also be contracted in some other way than by mosquito bite, but there are no well-authenticated facts which require any other theory for their explanation . The alleged occurrence of the disease in localities free from mosquitoes or without their agency is not well attested; its absence from other localities where they abound is accounted for by their being of an innocent species, or—as in England—free from the parasite . The old theory of paludism or of a noxious miasma exhaled from the ground is no longer necessary .

The broad facts on which it is based are sufficiently accounted for by the habits of mosquitoes . For instance, the swampy

character of malarial areas is explained by their breeding in stagnant water; the effect of drainage, and the general immunity of high-lying, dry localities, by the lack of breeding facilities; the danger of the night air, by their nocturnal habits; the comparative immunity of the upper storeys of houses, by the fact that they fly low; the confinement of malaria to well-marked areas and the diminution of danger with distance, by their habit of clinging to the breeding-grounds and not flying far . Similarly, the subsidence of malaria during cold weather and its seasonal prevalence find an adequate explanation in the conditions governing insect life . At the same time it should be remembered that many points await elucidation, and it is unwise to assume conclusions in advance of the evidence . With regard to the parasites, which are the actual cause of malaria in man, an account of them is given under the heading of PARASITIC DISEASES, and little need be said about parasites. them here . They belong to the group of Protozoa, and, as already explained, have a double cycle of existence: (r) a sexual cycle in the body of the mosquito, (2) an asexual cycle in the blood of human beings . They occupy and destroy the red corpuscles, converting the haemoglobin into melanin; they multiply in the blood by sporulation, and produce accessions of fever by the liberation of a toxin at the time of sporulation (Ross) . The number in the blood in an acute attack is reckoned by Ross to be not less than 250 millions . A more general and practical interest attaches to the insects which act as their intermediate hosts . These mosquitoes or gnats—the terms are synonymous—belong to the family Culicidae and the genus Anopheles, which was first classified by Meigen in 1818 . It has a wide geographical distribution, being found in Europe (including England), Asia Minor, Burma, Straits Settlements, Java, China, Formosa, Egypt; west, south and Central Africa; Australia, South America, West Indies, United States and Canada, but is generally confined to local centres in those countries . About fifty species are recognized at present .

It is believed that all of them may serve as hosts of the parasite . The species best known in connexion with malaria are A. maculipennis (Europe and America), A. funestus and A. costales (Africa) . In

colour Anopheles is usually brownish or slaty, but sometimes buff, and the thorax- frequently has a dark stripe on each side . The wings in nearly all species have a dappled or speckled appearance, owing to the occurrence of blotches on the front margin and to the arrangement of the scales covering the veins in alternating light and dark patches (Austen) . The genus with which Anopheles is most likely to be confounded is Culex, which is the commonest of all mosquitoes, has a world-wide distribution, and is generally a greedy blood-sucker . A distinctive feature is the position assumed in resting; Culex has a humpbacked attitude, while in Anopheles the proboscis, head and body are in a straight line, and in many species inclined at an angle to the wall, the tail sticking outwards . In the female of Culex the palpi are much shorter than the proboscis; in Anopheles they are of the same length . The wings in Culex have not the same dappled appearance . Anopheles is also a more slender insect, with a smaller head, narrower body and thinner legs . There are further differences in the other stages of life . Mosquitoes go through four phases: (i) ovum, (2) larva, (3) nympha, (4) complete insect . The ova of Anopheles are tiny black rod-shaped objects, which are deposited on the water of natural puddles, ponds, or slowly moving streams, by preference those which are well supplied with vegetation; they float, singly or attached to other objects or clustered together in patterns .

They can live in brackish and even in

sea water . The larva has no breathing-tube, and floats horizontally at the surface, except when feeding; it does not frequent sewage or foul water . The ova of Culex, on the other hand, are deposited in any stagnant water, including cesspools, drains, cisterns, or water collected in any vessel; they float in boat-shaped masses on the surface . The larva has a breathing-tube, and floats head downwards; when disturbed it wriggles to the bottom (Christy) . Some observers maintain that Anopheles does not " sing," like the common mosquito, and its bite is much less irritating . Only the females suck blood; the act is believed to be necessary for fertilization and reproduction . Anopheles rarely bites by day, and then only in dark places . In the daytime " the gorged females rest motionless on the walls and ceilings of rooms, choosing always the darkest situations for this purpose " (Austen) . In temperate climates the impregnated females hibernate during the winter in houses, cellars, stables, the trunks of trees, &c., coming out to lay their eggs in the spring . The four phases are passed in thirty days in a favourable season, and consequently there are ordinarily four or five generations from April to September (Celli) . The most important question raised by the mosquito-parasitic theory of malaria is that of prevention . This may be considered under two heads: (1) individual prophylaxis; (2) administrative prevention on a large scale .

(i) In the first place, common sense suggests the avoidance, in malarious countries, of unhealthy situations, and particu- larly the neighbourhood of stagnant water . Among Pro- phylaxis. elements of unhealthiness is next to be reckoned the proximity of native villages, the inhabitants of which are infected . In the tropics " no

European house should be located nearer to a native village than half a mile " (Manson), and, since children are almost universally infected, " the presence of young natives in the house should be abso- lutely interdicted " (Manson) . When unhealthy situations cannot be avoided, they may be rendered more healthy by destroying the breeding-grounds of mosquitoes in the neigh- bourhood . All puddles and collections of water should be filled in or drained; as a temporary expedient they may be treated with petroleum, which prevents the development of the larvae . When a place cannot be kept free from mos- quitoes the house may be protected, as in the experiments in Italy, by wire gauze at the doors and windows . The arrange- ment used for the entrance is a wire cage with double doors . Failing such protection mosquito curtains should be used . Mosquitoes in the house may be destroyed by the fumes of burning sulphur or tobacco smoke . According to the experi- ments of Celli and Casagrandi, these are the most effective culicides; when used in sufficient quantity they kill mosquitoes in one minute . The same authorities recommend a powder, composed of larvicide (an aniline substance), chrysanthemum flowers, and valerian root, to be burnt in bedrooms . Anointing the skin with strong-smelling substances is of little use in the open air, but more effective in the house; turpentine appears to be the best .

Exposure at night should be avoided . All these prophylactic

measures are directed against mosquitoes . There remains the question of protection against the parasite . Chills are recognized as predisposing both to primary infection and to relapses, and malnutrition is also believed to increase susceptibility; both should therefore be avoided . Then a certain amount of immunity may be acquired by the systematic use of quinine . Manson recommends five to ten grains once or twice a week; Ross recommends the same quantity every day before breakfast . There is some evidence that arsenic has a prophylactic effect . An experiment made on the railway staff at Bovino, a highly malarious district on the Adriatic, gave a striking result . The number of persons was 78, and they were divided into two equal groups of 39 each . One group was treated with arsenic, and of these 36 escaped altogether, while three had mild attacks; the remaining 39 who were not treated, all had fever . In a more extended experiment on 657 railway-men 402 escaped . This was in 1889; but in spite of the encouraging results the use of arsenic does not appear to have made any further progress .

Experiments in immunizing by sero-therapeutic methods have not as yet met with success . (2) Much attention has been directed in scientific circles to the possibility of " stamping out " epidemic malaria by administrative measures . The problem is one Adminlsof

great practical importance, especially to the trative British Empire . There are no data for estimating Measures. the damage inflicted by malaria in the British colonies . It is, indeed, quite incalculable . In Italy the annual mortality from this cause averages 15,000, which is estimated to represent two million cases of sickness and a consequent loss of several million francs . In British tropical possessions the bill is incomparably heavier . There is not only the heavy toll in life and health exacted from Europeans, but the virtual closing of enormous tracts of productive country which would otherwise afford scope for British enterprise . The " deadly " climates, to which so much dread attaches, generally mean malaria, and the mastery of this disease would be equivalent to the addition of vast and valuable areas to the empire . The problem, therefore, is eminently one for the statesman and administrator . A solution may be sought in several directions, suggested by the facts already explained . The existence of the parasite is maintained by a vicious inter-change between its alternate hosts, mosquitoes and man, each infecting the other .

If the cycle be broken at any point the parasite must

die out, assuming that it has no other origin or mode of existence . The most effective step would obviously be the extermination of the Anopheles mosquito . A great deal may be done towards this end by suppressing their breeding-places, which means the drying of the ground . It is a question for the engineer, and may require different methods in different circumstances . Put comprehensively, it involves the control of the subsoil and surface waters by drainage, the regulation of rivers and floods, suitable agriculture, the clearing of forests or jungles, which tend to increase the rainfall and keep the ground swampy . The city of Rome is an example of what can be done by drainage; situated in the midst of malaria, it is itself quite healthy . Recent reports also show us how much may be done in infected districts . At Ismailia malaria was reduced from 1551 cases in 1902 to 37 cases in 1905 . The cost of operations amounted to an initial expenditure of 6.25 francs, and an annual expenditure of about 2.3 francs per head of the population . " The results are due to mosquito reduction together with cinchonization." The following' is a tabulated list of the cases . The population of Ismailia is about 6000 . Year .

1900 1901 1902' 1903 1904 1905 Cases of Malaria . 2250 1990 1548 214 90 37 2 Kiang and

Port Swettenham are contiguous towns in the Federated Malay States, having a population of 4000 and a rainfall of roo in. a year . At Kiang the expenditure has been £3100, with an annual expenditure of £270, devoted to clearing and draining 332 acres . At Port Swettenham £7000, with an annual upkeep of £240, has been devoted to treating rro acres . In Hong-Kong similar measures were carried out, with the result that the hospital admissions for malaria diminished from 1294 in 1901, the year when operations were begun, to 419 in 1905 . Kiang and Port Swettenham . A few other points may be noted . The pathological changes in malaria are due to the deposition of melanin and the detritus of red corpuscles and haemoglobin, and to the congregation of parasites in certain sites (Ross) . In chronic cases the eventual effects are anaemia, melanosis, enlargement of the spleen and liver, and general cachexia . Apparently the parasites may remain quiescent in the blood for years and may cause relapses by fresh sporulation . Recent discoveries have done little or nothing for treatment . Quinine still remains the one specific .

In serious cases it should not be given in solid form, but in solution by the stomach, rectum, or—better—hypodermically (Manson) . According to Ross, it should be given promptly, in sufficient doses (up to 30 grains), and should be continued for months . Euquinine is by some preferred to quinine, but it is more expensive . Nucleogen and Aristochin have also been recommended instead of quinine . The nature of immunity is not known . Some persons are naturally absolutely immune (Celli), but this is rare; immunity is also some-times acquired by infection, but as a rule persons once infected are more predisposed than others . Races inhabiting malarious districts acquire a certain degree of resistance, no doubt through natural selection . Children are much more susceptible than adults . Malaria in the Lower Vertebrates.—Birds are subject to malaria, which is caused by blood parasites akin to those in man and having a similar life-history . Two species, affecting different kinds of birds, have been identified . Their alternate hosts are mosquitoes of the Culex genus . Oxen,

sheep, dogs, monkeys, bats, and probably horses also suffer from similar parasitic diseases .

In the

case of oxen the alternate host of the parasite is a special tick (Smith and Kilborne) . In the other animals several parasites have been described by different observers, but the alternate hosts are not known .