Chapter VIII
Secondary, Terminal And Mixed Infections.—The Extension Of Infection In The Individual.—Tuberculosis.—The Tubercle Bacillus.—Frequency Of The Disease.—The Primary Foci.—The Extension Of Bacilli.—The Discharge Of Bacilli From The Body.—Influence Of The Seat Of Disease On The Discharge Of Bacilli.—The Intestinal Diseases.—Modes Of Infection.—Infection By Sputum Spray.—Infection Of Water Supplies.—Extension Of Infection By Insects.—Trypanosome Diseases.—Sleeping Sickness.—Malaria.—The Part Played By Mosquitoes.—Parasitism In The Mosquito.—Infection As Influenced By Habits And Customs.—Hookworm Disease.—Inter-Relation Between Human And Animal Diseases.—Plague.—Part Played By Rats In Transmission.—The Present Epidemic Of Plague.
The infectious diseases are often complicated by secondary infections, some other organism finding opportunity for invasion in the presence of the injuries produced in the primary disease. In many diseases, such as diphtheria, scarlet fever and smallpox, death is frequently due to the secondary infection. The secondary invaders not only find local conditions favoring a successful attack, but the activity of the tissue cells on which the production of protective substances essentially depends has suffered by the primary infection, or the cells are occupied in meeting the exigencies of this. The body is in the position of a state invaded by a second power where all its forces and resources are engaged in repelling the first attack.
What are known as terminal infections occur shortly before death. No matter what the disease which causes death, in the last hours of life the body usually becomes invaded by organisms which find their opportunity in the then defenceless tissues, and the end is often hastened by this invasion.
There are also mixed infections in which two different organisms unite in attack, each in some way assisting in the action of the other. The best known example of this is in the highly infectious disease of swine known as hog cholera. It has been shown that in this disease two organisms are associated,—one an invisible and filterable organism, and the other a bacillus. It was first supposed that the bacillus was the specific organism; it was found in the lesions and certain, but not all, the features of the disease were produced by inoculating hogs with pure cultures. The disease so produced is not contagious, and the contagious element seems to be due to the filterable virus.
The modes of transmission of infectious diseases are of great importance and are the foundation of measures of public health. In the preceding chapter we have seen that in the infected individual the disease extends from one part of the body to another. There is a primary focus of disease from which the extension takes place, and the study of the modes of extension in the individual throws some light on the much more difficult subject of the transmission of disease from one individual to another. There are four ways by which extension in the individual may take place.
1. By continuity of tissue, an adjoining tissue or organ becoming infected by the extension of a focus of infection.
2. By means of lymphatics. Organisms easily enter these vessels which are in continuity with the tissue spaces and receive the exudate from the focus of infection. The organisms are carried to the lymph nodes, which, acting as filters, retain them and for a time prevent a further extension. The following illustrates the importance of the part the nodes may play in mechanically holding back a flood of infection. A physician examined after death the body of a person who died from infection with a very virulent micrococcus and in the course of the examination slightly scratched a finger. One of the organs of the body was removed, sent to a laboratory and received by a laboratory worker, a woman physician, who had slight abrasions and fissures in the skin of the hands from contact with irritating chemicals. In the course of a few hours the wound on the finger of the man became inflamed, intensely painful, and red lines extended up the arm in the course of the lymphatic vessels, showing that the organisms were in the lymphatics and causing inflammation in their course. The lymph nodes in the armpit into which these vessels empty became greatly inflamed, swollen, and an abscess formed in them which was opened. There was high fever, great prostration, a serious illness from which the man did not recover for several months. The woman only handled the organ which was sent to the laboratory in order to place it in a fluid for preservation. She also had a focus of infection of a finger with the same red lines on the arm, showing extension by the lymphatics; but there was no halt of the infection in the armpit, for all the lymph nodes there had been removed several years before in the course of an operation for a tumor of the breast. A general infection of the blood took place, there was very high fever, and death followed in a few days. The halt of the infection is important in allowing time for the body to make ready its means of defence. One cannot avoid comparing the lymph node with a strong fortress thrown in the path of a victorious invading army behind which the defenders may gather and which affords them time to renovate their strength.
3. By means of the blood. The blood vessels are universally distributed, the smaller vessels have thin walls easily ruptured and easily penetrated. It is probable that in every infection some organisms enter the blood which, under usual conditions, is peculiarly hostile to bacteria. These may, however, be carried by the blood to other organs and start foci of infection in these.
4. By means of continuous surfaces. The bacteria may either grow along such surfaces forming a continuous or more or less broken layer, or may be carried from place to place in the fluids which bathe them.
All these modes of extension are well shown in tuberculosis. This disease is caused by a small bacillus which does not produce spores, has no power of saphrophytic growth under natural conditions, and is easily destroyed. Moisture and darkness are favorable conditions for its existence, sunlight and dryness the reverse. There are three varieties or strains of the tubercle bacilli which infect respectively man, cattle and birds, and each class of animals shows considerable resistance to the varieties of the bacillus which are most infectious for the others.
The primary seat of the infection in man is generally in the upper part of the lung. The organisms settle on the surface here and cause multiplication of the cells and an inflammatory exudate in a small area. With the continuous growth of the bacilli in the focus, adjoining areas of the lung become affected, and there is further extension in the immediate vicinity by means of the lymphatics. Small nodules are formed and larger areas by their coalescence. Infection with tuberculosis is so common that at least three-fourths of all individuals over forty show evidences of it. The examination of two hundred and twenty-five children of the average age of five years who had died of diphtheria showed tuberculous infection in one-fifth of the cases and the frequency of infection increases with age. The defence on the part of the body is chiefly by the formation of dense masses of cicatricial tissue which walls off the affected area and in which the bacilli do not find favorable conditions for growth. This mode of defence, which is probably combined with the production of substances antagonistic to the toxines produced by the bacilli, is so efficacious that in the great majority of cases no further extension of the process takes place. In certain cases, however, the growth of the bacilli in the focus is unchecked, the tissue about them is killed and becomes converted into a soft semi-fluid material; further extension then takes place. All parts of the enormous surface of the lungs are connected by means of the system of air tubes or bronchi, and the bacilli have favorable opportunity for distribution, which is facilitated by sudden movements of the air currents in the lung produced by coughing. The defence of the body can still keep pace with the attack, and even in an advanced stage the infection can be checked in some cases permanently; in others the check is but temporary, the process of softening continues, and large cavities are produced by the destruction of the tissue. On the inner surface of these cavities there may be a rapid growth of bacilli.
From the lungs the bacilli are carried by the lymphatics to the lymph nodes at the root of the lungs, in which a similar process takes place; this, on the whole, is favorable, because further extension by this route is for a time blocked. The extension by means of surfaces continues, the abundant sputum which is formed in the lungs and which contains large numbers of bacilli, becomes the vehicle of transportation. The windpipe and larynx may become infected, the back parts of each are more closely in contact with the sputum and are the parts most generally infected. A large part of the sputum is swallowed and infection of the intestine takes place, the lesions taking the form of large ulcers. From the intestinal ulcers there is further extension by means of the lymphatics, to the large lymph nodes in the back of the abdominal cavity (Fig. 8-25); the bacilli may also pass from the ulcers into the abdominal cavity and be distributed over the surface of the peritoneum resulting in tuberculous peritonitis. When the disease has reached an advanced stage, bacilli in small numbers continually pass into the blood and are distributed by this over the body, producing small nodules in many places. In rare cases distribution by the blood is the principal method of extension, and immense numbers of small foci of disease are produced, the form of disease being known as acute miliary tuberculosis. Although the bacilli are distributed everywhere, certain organs, as the brain and muscles, are usually exempt, because in these the conditions are not favorable to further growth of the bacilli. Tuberculosis, although frequently a very acute disease, is usually one of the best types of a chronic disease and may last for many years. The chronic form is characterized by periods of slow or rapid advance when conditions arise in the body favorable for the growth of the bacilli, and periods when the disease is checked and quiescent, the defensive forces of the body having gained the upper hand. Often the intervention of some other disease so weakens the defences of the body that the bacilli again find their opportunity. Thus typhoid fever, scarlet fever and other diseases may be followed by a rapidly fatal advance of the tuberculosis, starting from some old and quiescent focus of the disease.
Tuberculosis is also one of the best examples of what is known as latent infection. In this the infectious organisms enter the body and produce primary lesions in which the organisms persist but do not extend owing to their being enclosed in a dense and resistant tissue, or to the production of a local immunity to their action. Dr. Head has recently examined the children of households in which there was open tuberculosis in some member of the household. By open tuberculosis is understood a case from which bacilli are being discharged. He found with scarcely an exception that all the children in such families showed evidences of infection. The detection of slight degrees of tuberculous infection is now made easy by certain skin reactions on inoculation of the skin with a substance derived from the tubercle bacilli. Such latent infections may never become active and in the majority of cases do not. When, however, in consequence of some intercurrent disease or conditions of malnutrition the general defences of the body become weakened extension follows. Such latent infections explain the enormous frequency of tuberculosis in prisons. Under the general prison conditions infection in the prisons probably does not take place to any extent, and the disease is as common when the prisoners are kept in individual cells as in common prisons. It is probable that in these cases the prisoners have latent tuberculosis when entering, and the disease becomes active under the moral and physical depression which prison life entails.
For the extension of infection from one individual to another the infecting organisms must in some way be transferred. The most important of the conditions influencing this are the localization of the disease and the character of the infectious organisms, particularly with regard to their resistance to the conditions met with outside of the body. The seat of disease influences the discharge of organisms; thus, if the disease involve any of the surfaces the organisms become mingled with the secretions of the surface and are discharged with these. If the seat of disease be in the lungs, the throat or the mouth, the sputum forms the medium of extension, which can take place in many ways. The sputum may become dried, forms part of the dust and the organisms enter with the inspired air. The organisms which cause most of the diseases in which the sputum becomes infectious are quickly destroyed by conditions in the open, such as the sunlight and drying; street dust does not play so prominent a part in extension as is generally supposed. Organisms find much more favorable conditions within houses. It is now generally recognized that infection with tuberculosis does not take place in the open, but in houses in which the bacilli on being discharged are not destroyed. The hands, the clothing and surroundings even with the exercise of the greatest care may become soiled with the saliva.
It has been shown that in coughing and speaking very fine particles of spray are formed by the intermingling of air and saliva, which may be projected a considerable distance and remain floating in the air for some time. These particles are so fine as to be invisible; they may be inspired, and their presence in the air forms an area of indeterminate extent around the infected person within which such infection is possible. Such spray formation is also an important means of the extension of infection in the sick individual, for it is continually formed and inspired. It is in this way that the extreme prevalence of broncho-pneumonia in infants and young children is to be explained. No matter what the essential disease, an almost constant finding in young children after death is small areas of inflammation in the lungs in and around the terminations of the air tubes. The situation renders it evident that the organisms which caused the lesions entered the lung by the air tubes. The mouth of the child is unclean and harbors numbers of the same sort of organisms as those causing the lung inflammation; but in the absence of such a mode of infection as is given by spray formation it is difficult to see how the extension from the mouth to the lungs could take place. The weakened condition of the body in these cases favors the secondary infection.
If the disease be located in the intestines, as in typhoid fever and dysentery, the organisms are contained in the fecal discharges, and by means of these the infection is extended. In typhoid fever, dysentery and cholera massive infections of the populace may take place from the contamination of a water supply and the disease be extended over an entire city. One of the most striking instances of this mode of extension was in the epidemic of cholera in Hamburg in 1892. There were two sources of water supply, one of which was infected, and the cases were distributed in the city in the track of the infected supply. Many such instances have been seen in typhoid fever. Certain articles of food, particularly milk, serve as sources of infection. This is more apt to happen when the organism causing the infection grows easily outside of the body. A few such organisms entering into the milk can multiply enormously in a few hours and increase the amount of infectious material. In all these cases the sick individual remains a source of infection, for it is almost impossible to avoid some contamination of the body and the immediate surroundings with the organisms contained in the discharges.
Transmission by air plays but little part in the extension of infection. In such a disease as smallpox, where the localization is on the surface of the body, the organisms are contained in or on the thin epithelial scales which are constantly given off. These are light, and may remain floating in the air and carried by air currents just as is the pollen of plants. There seem to have been cases of smallpox where other modes of more direct transmission could be excluded and in which the organisms were carried in the air over a considerable space. All sorts of intermediate objects, both living and inanimate, such as persons, domestic animals, toys, books, money, etc., can serve as conveyors of infection.
Insects play a most important part in the transmission of disease, and in certain cases, as when a disease is localized in the blood, this is the only means of transmission. There are three ways in which the insect plays the rôle of conveyor.
1. The insect may play a purely passive part in that its exterior surface becomes contaminated with the discharges of the sick person, and in this way the organisms of disease may be conveyed to articles of food, etc. The ordinary house fly conveys in this way the organisms of typhoid and dysentery. Flies seek the discharges not only for food, but for the purpose of depositing their eggs, and the hairy and irregular surface of their feet facilitates contamination and conveyance. When flies eat such discharges the organisms may pass through the alimentary canal unchanged and be deposited with their feces; they also often vomit or regurgitate food, and in this way also contaminate objects. Flies very greedily devour the sputum of tuberculous patients, and the tubercle bacilli contained in this pass through them unchanged and are deposited in their feces.
Fig. 19.—Trypanosomes From Birds. All the trypanosomes are very much alike. They contain a nucleus represented by the dark area in the centre and a fur-like membrane terminating in a long whip-like flagellum. They have the power of very active motion within the blood.
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.
In the old descriptions of the disease it was frequently mentioned that large numbers of dead rats were found when it was prevalent, and the most striking fact of the recent investigations is the demonstration that the infection in man is due to transference of the bacillus from infected rats. There are endemic foci of the disease where it exists in animals, the present epidemic having started from such a focus in Northern China, in which region the Tarabagan, a small fur-bearing animal of the squirrel species, was infected. Rats are easily infected, the close social habits of the animal, the vermin which they harbor, and the habits of devouring their dead fellows favor the extension of infection. The disease extends from the rat to man chiefly by means of the fleas which contain the bacilli, and in cases of pneumonic plague from man to man by means of sputum infection. The disease once established in animals tends to remain, the virus being kept alive by transmission from animal to animal, and the persistence of the infection is favored by mild and chronic cases.