# Tropical Diseases/Chapter 6

CHAPTER VI
MALARIA: ETIOLOGY
IN considering the etiology of malaria two things must be carefully distinguished: (1) the circumstances leading to the invasion of the human body by the malaria parasite; (2) the circumstances determining the clinical manifestation of such invasion.
CIRCUMSTANCES FAVOURING INFECTION
In the mosquito-malaria theory, now thoroughly established, we have the key to this problem. Whatever favours the presence and increase of the malaria bearing species of mosquito tends to the increase of malaria, and vice versa; whatever favours the access of these insects, and the parasites which have passed into them, to the human body favours the acquisition of malaria.
It must not be forgotten that the malaria parasite, after giving rise to fever within a few days of its original invasion of the human body, tends to pass into a latent condition from which it wakes up into clinical activity again only after longer or shorter intervals; further, that in rare instances the clinical evidence of a successful malarial invasion may be delayed for months or, perhaps, for years. Consequently, the particular circumstances in which any given malarial attack declares itself are not necessarily those which led to the acquisition of the infection originally. Therefore, in regard to the etiology of malaria, fevers of first invasion have a significance very different from that pertaining to relapses or recurrences.
Geographical range.—— The geographical range of malaria is very great; it extends in the northern hemisphere from the Arctic Circle to the Equator, and in the southern probably as widely. Malaria is not uniformly distributed throughout this vast area. It ​occurs in limited endemic foci which tend, speaking generally, to be more numerous and larger as the Equator is approached.
Influence of latitude and season.—— In colder latitudes the association of malaria with swamps is marked; in warmer latitudes this association is much less apparent. In colder latitudes the type of disease is milder; in warmer latitudes it is apt to be more severe. In certain warm countries, as the Argentine and many of the islands of the South Pacific, malaria is entirely absent, or mild and rare. In colder latitudes it is active only during the summer or early autumn; in warmer latitudes it is perennial, certain seasons—— usually, though not invariably, the warmer, or after the rains——being the more malarial.
Influence of local conditions.—— The strip of flat, waterlogged country lying along the foot of mountain ranges, the deltas of large rivers, the pool-dotted beds of dried-up streams, areas of country which have fallen out of cultivation, recently deforested lands, are, in many instances, notoriously malarial. Well-drained uplands and carefully cultivated districts, as a rule, are healthy. There are, nevertheless, instances of elevated, arid, and sandy plains which, under certain hydraulic conditions, are intensely malarial. Towns are much less malarial than villages or the open country.
Ship malaria.—— Although several instances are on record of outbreaks of what was reputed to be malaria on shipboard on the open sea, many epidemiologists refuse to accept the diagnosis as to the nature of these outbreaks, and maintain that malaria is never contracted away from the land. Mosquitoes haunt ships for some time after the latter leave port. If they are infected with the malaria parasite when they first enter the ship, or if they ingest the parasite after coming on board, they may very well communicate malaria.
Endemic and epidemic fluctuations.—— From time to time malaria extends beyond its endemic foci, spreading in epidemic form over large tracts of ​what is usually healthy country. There are a few well-authenticated instances of countries (Mauritius, Réunion) which, although previously exempt, subsequently became endemically malarial; and there are many instances of countries previously malarial which afterwards, especially under the influence of cultivation and drainage, became salubrious.
These circumstances evidently have reference to the distribution of species of malarial mosquitoes. Like other insects, mosquitoes occasionally, under specially favourable conditions, increase enormously in numbers and spread out in every direction. New species, which may belong to the malaria-bearing kinds, may be introduced into places where they formerly did not exist, just as Culex fatigans has been introduced into Australia. I believe a mosquito capable of subserving the malaria parasite was introduced in this way in the early 'sixties into Mauritius, an island whose fauna and flora had been hitherto very peculiar and special. In this way we can account for the outbreak of the great epidemic of malaria that swept over that formerly healthy island, and also for its present endemic insalubrity. A similar misfortune may very well happen to the non-malarious South Pacific islands in the near future.
The exemption of certain islands from malaria, even though in the midst of an archipelago of malaria-haunted islands, is a very remarkable circumstance. Barbados is an instance in point. Low has confirmed the popular belief that malaria is unknown there as an indigenous disease, and points to the absence of Anophelinæ as the explanation. But how explain the absence of Anophelinæ, seeing that Culex abounds and all the conditions favouring mosquito life are present? The disappearance of malaria from Britain is another remarkable, and perhaps not fully explained, fact. Anophelinæ still abound in many places, yet the endemic malaria has vanished. It may be that the general use of quinine and the improved domestic hygiene have to be credited with this. Still more remarkable is the circumstance that there are villages and districts in ​India, as pointed out by Christophers and Stephens, and similar districts in Italy, as pointed out by Celli, in which, though surrounded by highly malarious country and though Anophelinæ abound, there is no malaria. The explanation of this anomaly is not apparent. Perhaps in these places there is some local substance on which the mosquitoes feed that is fatal to the parasite. Sambon ingeniously suggests that there may be special local conditions that favour hyperparasitism, that is, the attack and destruction of the malaria parasite by some other kind of parasite. Similar occurrences are common enough in nature. In support of this view he cites Ross's observation of what he designated "black spores" (Fig. 22), bodies which are now known to be protozoal organisms belonging Fig. 22.—Ruptured oöcyst containing Ross's black spores. (After Grassi.) to the genus Nosema. These "black spores" prey on the malaria oöcyst in the wall of the mosquito's stomach and destroy it, just as they prey on the larvæ of Filaria immitis encysted within the Malpighian tubes of the mosquitoes which subserve their development. Whatever the explanation of the salubrity of these mosquito-haunted plains be, it is well worth searching for; it may be that it would carry a hint of value in attempting the prevention of malaria.
Atmospheric temperature.—One of the most important conditions necessary to the sporogonic phase of the malaria germ is a sustained average temperature of at least 60° F. The malaria parasite will not develop in the mosquito at low temperatures.
Altitude.—Altitude per se has, apparently, no influence on malaria. It is the decrease in temperature, usually implied by an increase in altitude, that is the real determining circumstance in bringing about a diminution in the prevalence of malaria in uplands. In the tropics an elevation of six or seven thousand feet may not secure immunity from malaria unless there be, at the same time, a corresponding and ​sufficient lowering of temperature. In Italy there are many malarious spots high up among the hills; the same is the case in India and elsewhere in those elevated valleys which are also narrow, imperfectly ventilated, and imperfectly drained.
Moisture.—— Another important condition for the production of malaria is the .presence of water. In the Sahara there is no malaria unless in the oases; in many of these it is rife—— in Biskra, for example. A large expanse of water is not favourable to malaria. The mosquito thrives best in sluggish streams with grassy banks and many backwaters; still better, in small pools or other collections of water, as in broken bottles, empty tins, etc., where there are no fish to prey on their larvæ, and where the surface is not agitated by winds. One such puddle near a house may suffice to render that house unhealthy.
Decomposing vegetable matter.—— It is customary to add yet another condition as being necessary to the existence of malaria—— namely, the presence in the soil of a notable amount of decomposing organic matter, particularly vegetable matter. But that this is not an indispensable condition is proved by the fact that there are many almost barren spots in which malaria abounds.
Other conditions necessary.—— The concurrence of these conditions, high temperature and moisture, even though associated with abundant vegetation, is not sufficient to generate or support malaria; for there are many places in the world the Argentine and the islands of the South Pacific, for example in which high temperature, moisture, and decaying vegetable matter are present but in which malaria is almost unknown. Manifestly there are other and more complicated conditions which are equally indispensable, and which must concur with heat and moisture in order to secure the presence of malaria-bearing mosquitoes. What these conditions are it is as yet impossible to say.
Influence of subsoil moisture.—— The state of the subsoil as regards moisture appears to have considerable influence on its malaria-producing properties. ​Short of general overflow, the higher the subsoil water the greater the chance of a given locality supplying breeding-places for mosquitoes and therefore of proving malarious. Hence arises marked liability to epidemics of malaria on the subsidence of extensive floods; and hence the danger attending the raising of the level of the subsoil water by irrigation works, canals, embankments, and other engineering works.
Influence of rainfall.—— As regards the relation of the prevalence of malaria to rainfall there have been too many generalizations based on the limited experience of one or two districts. Thus, it is often said that the most malarious time of the year is at the end of the rains, when the soil is beginning to dry up. A wider view of the subject shows that, though applying to some places, this statement does not apply to all. There are localities where the fever curve is highest before the setting in of the rains. In some places, particularly in those that are low-lying, flat, and swampy, fevers of first invasion disappear almost entirely when the country becomes flooded. This apparent want of a universal and definite relationship of fever curve to rainfall indicates that the conditions determining the prevalence of malaria are highly complex, and that they are not by any means merely a matter of heat, moisture, and vegetation. In some places much rain will scour out the mosquito pools; in other places it will just fill them. The key to the explanation of the varying relation of malaria to rainfall is to be found in the influence of the latter on the local mosquito pools.
Influence of winds and atmospheric diffusion.—— It has been said that the wind can carry the malaria germ great distances, roll it along the ground like thistledown, and even force it to ascend high mountains. It is very doubtful, however, if the malarial mosquito can be transported, in this way, very far from its native pool. The mosquito does not ascend more than a few feet from the ground, and in high winds, or even in draughts of air, such as that from a ​punkah, immediately seeks shelter. It is certain that some thousand or fifteen hundred yards of water between a ship and a malarious coast may suffice to secure immunity to the crew. The experience of the notorious Walcheren Expedition proves this. A similar distance on land from a malaria source is probably approximately as effective. The diffusion of malaria by winds is generally extremely restricted. Inside, a city may be quite healthy, whilst outside the walls the country may be pestilential. One village may be sickly, whilst a neighbouring village may be healthy. Surely, if winds transport the malarial germ for any distance from its source, there would not be so great a difference in the relative salubrity of urban and suburban localities, nor of neighbouring houses and villages. Neither does the malaria germ ascend to any great height above the ground. Acting on the empirical observation of this fact, the peasants in many unhealthy spots in Italy and Greece are said to secure a remarkable degree of immunity by passing the night, during the fever season, on platforms raised on poles a few yards above the ground. It seems safe, therefore, to conclude that the horizontal and vertical diffusion of the malaria germ that is to say, of the mosquito is, as a rule, very restricted.
Influence of trees, houses, and lodging:—— The intervention of a belt of trees between a malarial swamp and a village is said to protect from malaria the houses on the leeward side of the trees. The trees may filter out the mosquitoes by affording them protection from winds. Open windows and doors, by giving ready access to mosquitoes, are sources of danger in malarial countries; for this and similar reasons sleeping on the ground, on the ground floor, or unprotected by a mosquito curtain, is dangerous.
Time of day in relation to infection.——Evidently in conformity with the habits of the mosquito, the time just before sunrise and just after sunset, and the night, have the reputation of being the most dangerous as regards liability to contract the infection. Although mosquitoes are most active during twilight and night, they bite readily enough during the daytime ​in shady and windless places, as in thick jungle or in a dark room. A very few species are diurnal in habit.
Disturbance of the soil.—— It has often been observed that in malarious countries, so long as the soil remains undisturbed, agues and the severer forms of fever are comparatively rare; but so soon as building, road-making, and other operations implying soil disturbance commence, then severe malarial fevers appear. After a time when, in the progress of events, these operations have concluded, and the broken surface of the soil has, so to speak, skinned over again, the place becomes once more comparatively healthy. The medical history of Hong Kong may be cited in illustration of this fact. At the commencement of the occupation of this island by the British, for a short time it was healthy enough. Then, on its cession being completed, and when barracks and houses were being built and roads laid out, it became excessively unhealthy, the soldiers dying by the hundred of pernicious fevers. In time the sickness and mortality gradually decreased; and now, so far as malaria is concerned, the city of Victoria is healthy. But, even at the present day, wherever in the outskirts, in the course of the construction of houses, roads, forts, and similar works, soil is turned up, fever—— often of a most pernicious type—— is nearly sure to break out among those engaged in the works. I cite the case of Hong Kong; but there are dozens of other instances which might be quoted, and which are quite as apposite and convincing, as to the danger of carelessly disturbing the soil in malarious localities, particularly during the warm season. Soil disturbance usually implies the formation of holes. Holes imply puddles, and puddles imply mosquitoes. Workmen from many districts, some of them malarious, are assembled in crowded lodgings; one infected workman suffices to start the epidemic. In the present state of knowledge this seems to be adequate explanation of the recognized danger of earth-cutting in malarious dis-
CIRCUMSTANCES FAVOURING THE CLINICAL
MANIFESTATION OF MALARIAL INVASION
As a rule, a successful malarial infection declares itself within a week or ten days. As with other infections, certain individuals resist the pathogenic influences of the malaria parasite for a longer period. A very few appear to be permanently immune. Everything tending to cause physiological depression favours susceptibility and acute manifestations.
Influence of meteorological conditions on relapse.—— A malarial subject while in the mild climate of the tropics may keep in fair health; but when, as is so often the case with sailors and others returning to Europe, he is plunged into the stormy winter of the North, is exposed to cold, and has long watches and fatiguing work, very probably latent malaria will become active and ague follow. This is a common experience with malarials from the tropics. It is almost the rule with people coming from the West Coast of Africa. Stanley remarks that so long as he and his companions were ascending the Congo, the wind being with them and therefore not much felt, they did not have fever ; but that on descending the stream, a strong breeze blowing in their faces and chilling them, they constantly had attacks. The physiological depression and disturbances caused by the cold wind paralysed the self -protecting power of the body, and permitted the hitherto latent parasite to get the upper hand. And so it is found, in the highly malarial districts of tropical Africa, that houses perched on elevated and windy situations are not so healthy as those on lower and, therefore, less exposed and more sheltered ground. This must not be interpreted as showing that wind causes or carries malaria. The wind merely acts as a cause of physiological strain, of chills; it acts just in the same way as fatigue, hunger, a wetting, disease, fear, excesses, or depressing emotions are found to do.
Sex, age, occupation—— Sex per se seems to have no particular influence as regards liability to or severity of malarial attacks. Neither has occupation; ​although, of course, those engaged in tilling and working the soil are more exposed to mosquito bite, and therefore more subject to malaria, than the townsman or the sailor. Malarial attacks are more severe, more common, and much more dangerous in young children than in adults.
Malaria a commmunicable disease.—— Malaria is certainly not directly communicable, in the same way that such diseases as smallpox or measles are. It can be communicated directly only by injection of malarial blood. But there can now no longer be any doubt that a malarial patient introduced into a community, provided suitable mosquitoes are present, is a source of danger. If mosquitoes of the proper species bite such a patient say in the wards of a hospital, in a gaol, a house, or a camp and a week later bite someone else, that second individual may become infected, and ten days later may be seized with malarial fever.
Study of the mosquito indispensable.——Full knowledge of all that concerns the etiology of the disease will only be attained when we have full knowledge of the various species of mosquito capable of subserving the germ, of certain vertebrates which may be capable of taking the place of man in the malarial cycle, of their geographical distribution, of their habits, and of their enemies. As yet this knowledge is but beginning. When we have said that the alaria parasite is subserved by several species of Anophelinse and that these species are mainly of nocturnal habit, we have enumerated the principal items of existing knowledge on the subject. Whether certain species of Culex, Stegomyia and other Culicinæ are efficient hosts for the parasite, as some of them certainly are for Plasmodium danilewskyi and Filaria bancrofti, can as yet neither be affirmed nor denied. Studies in this field are being actively carried on, and important advances may be looked for.
ACCLIMATIZATION AND IMMUNITY
Personal acclimatization.—— Is there such a thing as acquired immunity as regards malaria? The ​answer to this is, " Yes and No." As regards the European, it would seem that those who have resided many years in a malarious district are less liable than recent arrivals to severe remittents, but more liable to mild agues. As already mentioned, the first attack of malarial fever is generally remittent and severe in character; subsequent attacks are generally frankly intermittent. Old febricitants are more liable to pernicious attacks of an adynamic type than the recently infected. Trifling causes, such as do not provoke fever in the fresh arrival, are often sufficient to bring on an ague fit in the old resident. The new arrival in the tropics does not think much of exposing himself to the sun, the rain, and the wind; but the old resident is very chary about going out without his sun-hat and white umbrella. The latter wears flannel, and changes his clothes after exercise; he is careful not to cool off too rapidly by sitting in a draught; he will not sit down in wet clothes. The new-comer may look on these precautions against chill as signs of effeminacy. They are not so, however; experience has taught the old resident that neglect of them means an attack of fever and a week off work. The new-comer takes a cold bath; the old resident takes a warm one. The new-comer sits up late, eats and drinks and smokes as in Europe; the old resident goes to bed betimes, and eats and drinks and smokes in moderation. By and by, sharp lessons teach the new-comer to respect the sun and the rain and the wind, to clothe with a view to avoiding chill, and to live temperately. This is an education all pass through in malarial countries. "Acclimatization," to a great extent, though not entirely, means experience, education; not simply an unconscious adaptation of the physiology of the individual, but an intelligent adaptation of his habits.
Racial and individual differences of susceptibility.—— Nevertheless, there can be no doubt that, for some occult reason, certain races and certain individuals are less susceptible to malarial influences than others. A very few individuals are absolutely immune and can live in intensely malarial places with impunity. It is a ​well-established fact that the negro in Africa, although he does get fever, does not get it so frequently nor so severely as the European; even although the latter, from his hygienic ways of living, is of the two much the less exposed to infection. The Chinese, the Malays, and some other dark-skinned races also appear to enjoy a comparative immunity—— an immunity considerably less pronounced, however, than that enjoyed by the African and West Indian negro. There is some evidence to show that even the individual European, if he survive the process, may after many years, through frequent infection, attain immunity; this, however, does not appear to be transmitted. The inhabitants of the malarious districts of Italy, Corsica, Greece, Turkey, and other South European countries have inherited no marked immunity from malaria in virtue of the thousands of years during which their ancestors lived in malarious districts. But they have inherited experience, and many of them know how to keep clear of the infection they cannot overcome; this probably is, in great measure, the extent of their acclimatization and apparent acquired immunity.
We are indebted to Koch for an important observation, with manifest practical bearings, on this subject; an observation which throws light on the apparent immunity of negroes, Melanesians, and other dark-skinned races living in highly malarious countries. He has shown, and his statements have been abundantly confirmed, that the natives of such districts acquire their immunity from repeated and persistent infection in childhood. In such places the blood of practically every child up to three or four years of age contains malaria parasites. The proportion of infected children gradually becomes smaller with each additional year, until adolescence is approached, when the blood becomes practically parasite-free, and immunity is established. Daniels had already shown, by a comparative study of the prevalence of malarial pigmentation in the cadavers of natives of British Guiana, that such was probably the case; Koch's more direct observations on the ​parasite in Melanesia, confirmed as they have been by English observers in India and Africa, have definitely settled the matter.
The mortality in native children from malaria is very great; but it would appear that a relative tolerance is soon acquired, for although the negro child may have a rich infection of parasites in its blood, possibly in consequence partly of increasing immunity, partly of some racial and inherited quality, it may exhibit a remarkable tolerance of the malaria toxins. It has often been remarked that these dark-skinned children, with enormous spleens and a rich stock of malaria parasites in the blood, run about fever-free, and apparently in rude health. It would seem that certain races of men react to the malaria parasite much in the same way as the Texan cattle react to Babesia, or as the large game animals of Africa react to Trypanosoma brucei; repeated infection in early youth, if it does not quickly prove fatal, creates immunity. Race may have something to do with the tolerance of the infection; but it is not everything, for the negro from a non-malarial country on becoming infected in a malarial country suffers almost as severely as the European.