2. Diseases which are localized in the blood are transmitted by biting flies. The biting apparatus becomes contaminated with the organisms contained in the blood, and these are directly inoculated into the blood of the next victim. The trypanosome diseases form the best example of this mode of transmission. The trypanosomes are widely distributed, exclusively parasitic, flagellated protozoa which live in the blood of a large number of animals and birds (Fig. 19). They may give rise to fatal diseases, but in most cases there is mutual adaptation of host and parasite and they seem to do no harm. One of the most dangerous diseases in man, the African sleeping sickness, is caused by a trypanosome, and the disease of domestic cattle in Africa, nagana, or tsetse fly disease, is also so produced. In certain regions of Africa where a biting fly, the Glossina morsitans, occurs in large numbers, it has long been known that cattle bitten by these flies sickened and died, and this prevented the settling and use of the land. In the blood of the sick cattle swarms of trypanosomes are found. The source from which the tsetse fly obtained the trypanosomes which it conveyed to the cattle was unknown until it was discovered that similar trypanosomes exist in the blood of the wild animals which inhabit the region, but these have acquired by long residence in the region immunity or adaptation to the parasite and no disease is produced. With the gradual extension of settlement of the country and the accompanying destruction of wild life the disease is diminishing. Some of the inter-relations of infections are interesting. The destruction of wild animals in South Africa which, by removing the sources of nagana, rendered the settlement of the country possible was due chiefly to the introduction of another infectious disease, rinderpest, which not only destroyed the wild animals but produced great destruction of the domestic cattle as well.

The sleeping sickness has many features of interest. In the old slavery days it was found that the negroes from the Congo region in the course of the voyage or after they were landed sometimes were affected with a peculiar disease. They were lethargic, took little notice of their surroundings, slept easily and finally passed into a condition of somnolence in which they took no food and gradually died. There was no extension of the disease and it was attributed to extreme homesickness and depression. A similar disease has been known for more than one hundred years on the west coast of Africa, and attracted a good deal of interest and curiosity on account of the peculiar lethargy which it produced and from which it has received the name of "sleeping sickness." Although apparently infectious in its native haunts, it lost the power of spreading from man upon removal to regions where it did not prevail. At first confined to a very small region on the Niger river, it gradually extended with the development of trade routes and the general increase of communications which trade brings, until it prevails in the entire Congo basin, in the British and German possessions in East Africa, and is extending north and south of these regions. The cause of the disease and its mode of conveyance was discovered in 1903. The fly Glossina palpalis which conveys the disease is a biting fly about the size of the common house fly and lives chiefly in the vicinity of water. When such a fly bites an individual who has sleeping sickness its bite can convey the disease to monkeys, on whom the transmission experiments were made. After biting the fly is infectious for a period of two days. After this it is harmless, unless it again obtains a supply of living trypanosomes. There is quite a period in which there are no symptoms of the disease, although trypanosomes are found in the blood and in the lymph nodes, and the individual is a source of infection. The peculiar lethargy which has given the disease its name does not appear until the nervous system is invaded by the parasites. It is impossible to compute accurately the numbers of deaths from this disease—in the region of Victoria Nyanza alone the estimates extend to hundreds of thousands.

3. In the third mode of insect conveyance the insect does not play a merely passive rôle, but becomes a part of the disease, itself undergoing infection, and a period in the life cycle of the organism takes place within it. In all these cases quite a period of time must elapse before the insect is capable of transmitting the disease; in malaria, which is the best type of such a disease, this period is ten days. Malaria is due to a small protozoan, the Plasmodium malariæ, which was discovered by Lavaran, a French investigator, in 1882. The organism lives within or on the surface of the red blood corpuscles. It first appears as a very minute colorless body with active amoeboid movements, and increases in size, attacks a succession of corpuscles, and finally attains a size as large as or larger than a corpuscle. The corpuscles attacked become pale by the destruction of hæmoglobin, swell up and disintegrate, the hæmoglobin becoming converted into granules of black pigment inside the parasite. Having attained a definite size the organism forms a rosette and divides into a number of forms similar to the smallest seen inside the corpuscles; these small forms enter other corpuscles and the cycle again begins. This cycle of development takes place in forty-eight hours, and segmentation is always accompanied by a paroxysm of the disease shown in a chill followed by fever and sweating which is due to the effect of substances liberated by the organism at the time of segmentation. A patient may have two crops of the parasite developing independently in the blood, and the two periods of segmentation give a paroxysm for each, so that the paroxysms may appear at intervals of twenty-four hours instead of forty-eight (Fig. 20). This cycle of development may continue for an indefinite time, and there may be such a rapid increase in the parasites as to bring about the death of the individual; but with him the parasite would also perish, for there would be no way of extending the infection and providing a new crop. The disease has been transmitted by injecting the infected blood into a normal individual.

Fig. 20.—Part Of The Cycle Of Development Of The Organism Of Malaria, a-g, Cycle of forty-eight hour development, the period of chill coinciding with the appearance of f and g in the blood. The organisms g, which result from segmentation, attack other corpuscles and a new cycle begins. h, The male form or microgametocyte, with the protruding and actively moving spermatozoa, one of which is shown free. i and j are the macrogametes or female forms. k shows one of these in the act of being fertilized by the entering spermatozoön. The differentiation into male and female forms takes place in the blood, the further development of the sexual cycle within the mosquito.

If a mosquito of the species anopheles bites the affected person, it obtains a large amount of blood which contains many parasites. Within the mosquito the parasite undergoes a further development into male and female sexual forms, which may also form in the blood, termed respectively microgametocyte and macrogamete. From the microgametocyte small flagellate bodies, the male sexual elements microgametes or spermatozoa, develop and fertilize the macrogametes; after fertilization this develops into a large body, the oöcyst which is attached to the wall of the stomach of the mosquito. Within the oöcyst, innumerable small bodies, the sporozoites, develop, make their way into the salivary glands and are injected into the individual who becomes the prey of the mosquito, and again the cycle of development begins. The presence of the parasite within the mosquito does not constitute a disease. So far as can be determined, life goes on in the usual way, and its duration in the insect is not shortened.

The nature of the parasite which produces yellow fever is unknown, for it belongs to the filterable viruses; the infectious material, however, has been shown by inoculation to exist in the blood, and the disease is transmitted by a mosquito of another species, the stegomyia. The development cycle within this takes a period of twelve days, which time must elapse after the mosquito has bitten before it can transmit the disease. Here again the mutual interdependence of knowledge is shown. Nothing could have seemed less useful than the study of mosquitoes, the differentiation of the different species, their mode of life, etc., and yet without this knowledge discoveries so beneficial and of such far-reaching importance to the whole human race as that of the cause and mode of transmission of malaria and yellow fever would have been impossible; for it could easily have been shown that the ordinary culex mosquito played no rôle. The rôle which insects may play in the transmission of disease was first shown by Theobald Smith in this country, in the transmission by a tick of the disease of cattle known as Texas fever. The infecting organism pyrosoma bigenimum is a tiny pear-shaped parasite of the red corpuscles. Smith's investigations on the disease, published in 1893, is one of the classics in medicine, and one of the few examples of an investigation which has not been changed or added to by further work.

One of the most interesting methods of extension of infection, showing on what small circumstances infection may depend, is seen in the case of the hookworm disease, which causes such devastation in the Southern States. The organism which produces the disease, the Uncinaria, belongs to the more highly developed parasites, and is a small round worm one-third of an inch long. The worms which inhabit the intestines have a sharp biting mouth by which they fasten themselves to the mucous membrane and devour the blood. The most prominent symptom of the disease is anæmia, or loss of blood, due not only to the direct eating of the parasite, but to bleeding from the small wounds caused by its bite. Large numbers of eggs are produced by the parasite which are passed out with the feces, which becomes the only infectious material. In a city provided with water-closets and a system of sewerage there would be no means of extension of infection. The eggs in the feces in conditions of warmth and moisture develop into small crawling larvæ which can penetrate the skin, producing inflammation of this, known in the region as the ground itch. The larvæ enter the circulation and are carried to the lungs, where they perforate the capillaries and reach the inner surface; from this they pass along the windpipe, and then by way of the gullet and stomach reach their habitat, the small intestine. Unfortunately, the habits and poverty of the people in every way facilitate the extension of the infection. There is no proper disposal of the feces, few of the houses have even a privy attached to them, and the feces are distributed in the vicinity of the houses. This leads to contamination of the soil over wide areas. Most of the inhabitants of the country go barefoot the greater part of the year, and this gives ready means of contact with the larvæ which crawl over the surface of the ground. The disease is necessarily associated with poverty and ignorance, the amount of blood is reduced to a low point, and industry, energy and ambition fall with the blood reduction; the schools are few and inefficient; the children are backward, for no child can learn whose brain cells receive but a small proportion of the necessary oxygen; and a general condition of apathy and hopelessness prevails in the effected communities. The control of the disease depends upon the disinfection of the feces, or at least their disposal in some hygienic method, the wearing of shoes, and the better education of the people, all of which conditions seem almost hopeless of attainment. The infection is also extended by means of the negroes who harbor the parasite, but who have acquired a high degree of immunity to its effects and whose hygienic habits are even worse than those of the whites. The organism was probably imported with the negroes from Africa and is one of the legacies of slavery.

The diseases of animals are in many ways closely linked with those of man. In the case of the larger parasites, such as the tapeworms and the trichina, there is a direct interchange of disease with animals, certain phases of the life cycle of the organisms are passed in man and others in various of the domestic animals. A small inconspicuous tapeworm inhabits the intestine of dogs and seems to produce no ill effects. The eggs are passed from the dog, taken into man, and result in the formation of large cystic tumors which not infrequently cause death. Where the companionship between dog and man is very close, as in Iceland, the cases are numerous.

Most of the diseases in animals caused by bacteria and protozoa are not transmitted to man, but there is a conspicuous exception. Plague is now recognized as essentially an animal disease affecting rats and other small rodents, and from these the disease from time to time makes excursions to the human family with dire results. The greatest epidemics of which we have any knowledge are of plague. In the time of Justinian, 542 B.C., a great epidemic of plague extended over what was then regarded as the inhabited earth. This pandemic lasted for fifty years, the disease disappeared and appeared again in many places and caused frightful destruction of life. Cities were depopulated, the land in many places reverted to a wilderness, and the works of man disappeared. The actual mortality cannot be known, but has been estimated at fifty millions. Plague played a large part in the epidemics of the Middle Ages. An epidemic started in 1346 and had as great an extension as the Justinian plague, destroying a fourth of the inhabitants of the places attacked; and during the fifteenth and sixteenth and seventeenth centuries the disease repeatedly raised its head, producing smaller and greater epidemics, the best known of which, from the wonderful description of De Foe, is that of London in 1665, and called the Black Death. Little was heard of the disease in the nineteenth century, although its existence in Asia was known. In 1894 it appeared in Hong Kong, extended to Canton, thence to India, Japan, San Francisco, Mexico, and, in fact, few parts of the tropics or temperate regions of the earth have been free from it. Mortality has varied greatly, being greatest in China and in India; in the last the estimate since 1900 is seven million five hundred thousand deaths. The disease is caused by a small bacillus discovered in 1894 which forms no spores and is easily destroyed by sunlight, but in the dark is capable of living with undiminished virulence for an indefinite time. The disease in man appears in two forms, the most common known as bubonic plague, from the great enlargement of the lymph nodes, those of the groin being most frequently affected. The more fatal form is known as pneumonic plague, and in this the lungs are the seat of the disease.