Infection

Various degrees of virulence of microbes.

Essence of the pathogenic action of microbes.

History. I. (from Latin infectio—corruption, infection) means "introduction" into the body of a contagious principle, infect or virus (see). Contagious, or infectious principle is called the causative agent of the disease, belonging to microorganisms. The original meaning of the word I. gradually changed, and I. is now often identified with the infectious disease, i.e., it denotes not only the introduction of the contagious principle, but also the development of the disease as a result of the interaction between the body and the microbe. That the cause of I. must be considered something living, some Latin writers already suspected (Terentius Varro, Columella), applying a special term "contagium vivum", which meant the living nature of the "adhering principle". These authors explained, for example, the origin of malaria by the introduction into the human body of small living beings. The Middle Ages with their cruel plague epidemics at the extraordinary contagiousness of plague further strengthened the belief in the living nature of the causative agent of I. Therefore, even then measures were developed against "living" beings in the form of wearing special costumes, music, processions that caused noise and movement of air, which seemed to drive these beings away from people. The concept of a real living causative agent, "contagium vivum", was introduced by Kircher (A. Kircher), who in 1659 described the causative agents of plague in the form of small worms. Apparently, Kircher took the cellular elements of blood for the causative agent. The invention of the microscope at the end of the 17th century little advanced the question of the causative agents of infectious diseases, because "animalcula", living beings, were seen everywhere, but they could not be associated with a specific form of disease. Only the 19th century brought evidence that the causative agents of diseases are real living beings that transmit the disease from sick to healthy. In 1834, the scabies mite was discovered, in 1837—the fungus of silkworm disease—yeast, as the cause of wine and beer fermentation (Schwann, Cagniard-Latour). 1839 brought the discovery of the fungus of black spot and 1843—the fungus of ringworm. The famous anatomist Henle collected all these disparate facts and in 1843 already gave a coherent theory of the etiology of I., which in its main features remains correct to this day. 1850 gave victory to the microbe theory of infection, when Davaine and Payer discovered the bacillus of anthrax and Davaine's experiments (1860) on the experimental reproduction of anthrax became known. Pasteur's work on fermentation and his refutation of the doctrine of spontaneous generation put the doctrine of I. on a solid foundation. Subsequently, Lister practically showed the beneficial effect of Pasteur's doctrine in the fight against infectious diseases. Robert Koch, thanks to a special technique, gave the laws by which the specificity of the microbe as a causative agent of the disease is determined (see below—Koch's triad). The end of the 19th century and the beginning of the 20th century finally brought a series of discoveries of the causative agents of individual infections. Hansen (1878) discovered the bacillus of leprosy, Obermeier (1879)—the causative agent of relapsing fever. Neisser (1879)—the gonococcus, Pasteur (1880)—the virus of rabies, Laveran (1880)—the plasmodium of malaria, Eberth and Gaffky (1880-84)—the bacillus of typhoid fever, Fehleisen (1883)—the erysipelas streptococcus, Rosenbach (1884)—the pus-producing staphylococcus and streptococcus, Fraenkel (1888)—the diplococcus of pneumonia, Bouchard, Schütz and Löffler (1882)—the microbe of glanders, Koch (Koch)—the causative agent of cholera (1883) and tuberculosis (1884), Nicolaier (1884)—the bacillus of tetanus, Klebs and Löffler (1883)—of diphtheria, Pfeiffer (1891)—the bacillus of influenza, Bruce and Castellani (1894)—the causative agent of sleeping sickness, Kitasato and Yersin (1894)—the bacillus of plague, Schaudinn and Hoffman (1905)—the syphilitic spirochete, Bordet and Gengou (1905)—the bacillus of whooping cough, Inado and Ido (1915)—the causative agent of infectious jaundice. Characteristics of infections. Virchow for the first time combined into one group "infectious" ("contagious") diseases (see Infectious diseases), the most diverse in clinical course. The grounds on which this combination occurred are the following. Every infect, before multiplying in the body and causing disease, requires time for this, called the "latent" or "incubation" period of I. (see Incubation period). This period can be very short (several hours) and very long (many months and years). Then comes the period of precursors, the period of height of the disease and the end of the disease. All this speaks of a certain cycle of development of I. The cyclic course of I. is connected not only with the cycle of changes on the part of the infect, but also with a number of regular reactions from the body itself, expressed in the intensification of the activity of cellular elements and parenchymal organs, in general qualitative and quantitative disturbances of metabolism, phenomena of inflammation, leukocytosis, phagocytosis, the appearance of so-called antibodies, or antitoxins, etc. Furthermore, characteristic of I. is that its source will always be the environment (whether it is a living being or the external environment) containing the same living causative agent with which this I. was caused. Finally, to the characterization of I. it is necessary to add that the contagious principle, passing from the sick to those around, has a tendency to affect not only individual individuals ("sporadic" I.) and whole groups of living beings, causing mass I. ("epidemics" in humans and "epizootics" in animals). Sources of infection. Primary sources supplying the infectious material into the surrounding world should be considered man, animals, as well as plants. The sick organism is quantitatively the main supplier of I. From such an organism microbes are excreted outward by various routes (excrement, urine, sputum, opening abscesses) and contaminate the environment, the earth, water, air, animals and people. Although man is the main supplier of I., the surrounding world can also be a primary reservoir (e.g., water spirochettes in Weil's disease). Microbes are also carried outward by blood-sucking insects, which carry them to other animals and to the environment. Usually, as the body recovers from I., microbes disappear from the body. However, clinical recovery does not always coincide with bacteriological, and microbes sometimes remain in the body for a long time after recovery (convalescent excretors). Similarly, pathogenic microbes can be in persons not sick, but who had contact with the sick (bacillus carriers—see Bacillus carriage). The significance of the sick organism and the healthy carrier as sources of I. is closely connected with the amount of infectious material present in them, with the consistency of the excretions thrown out, and finally with the virulence of the microbes. The more microbes a person has, the more people contain microbes, the greater the source of I. this person or this group of people is. The nature of the excretions with which microbes are excreted outward is also very important. Liquid excretions containing few microbes are more dangerous to others than formed ones, even with a larger number of microorganisms. The significance of the degree of virulence of the microbe is self-evident. For example, as recovery from diphtheria or epidemic cerebrospinal meningitis occurs, the virulence of the corresponding microbes quickly decreases, and such a group of sick or carriers, even with a large content of microbes, will represent less danger than one fresh sick person with a relatively small amount of microbes. Pathogenic microbes are preserved in the recovered organism or in the healthy carrier on the mucous membranes, in the lymphatic glands, gall bladder, cecum, spleen, bone marrow. Microbes de sortie as sources of I. By this name ("microbes at the exit", "ready to exit") M. Nicolle designates microbes that normally live in the bodies of humans and animals, often from birth, and under suitable conditions "coming out" onto the stage for pathogenic action. To such microbes belong two categories. One group—common microbes, found in the living organism either as saprophytes or as avirulent varieties of pathogenic microorganisms (staphylococcus, streptococcus, pneumococcus, Friedlander's bacillus, proteus, intestinal bacillus, B. perfringens, filterable viruses, spirochetes). The second group belongs to pathogenic microbes, which also colonize the organism very early, not causing disease in it upon invasion; these include the tuberculosis bacillus, catarral micrococcus, actinomycetes, tetanus microbe. Their location in the organism is the same as that of microbes remaining after an infectious disease. The causes of the "exit" of microbes and the revival of their action include on the one hand the change of the microbes themselves (see Dissociation of microbes, Variability of microbes) and on the other—all those moments that weaken the macroorganism—such as malnutrition, psychic trauma, and various diseases (see below).

Diseases with lobar pneumonia, anginas, colitis, acute rheumatism, and in some cases diseases with septicemias, postoperative pneumonias and peritonitis, encephalitides (post-vaccination),—all these are possible examples of the revival of 'microbes de sortie', as a result of which autoinfection, or endogenous infection, occurs.

* Methods of transmission of I. In the pre-bacteriological era, when microorganisms were not known, it was believed that the external environment, without human participation, could serve as a source of I., which is transmitted through the air, vapors, invisible or visible insects (malaria, typhus, typhoid fever). Such I. were called miasmic (from the Greek miasma - pollution) in contrast to contagious ones, in which the transmission of the disease from person to person was obvious (plague, cholera, diphtheria). Now, when the causative agent of I. is recognized as a microorganism, and the source is a living being and the environment as a reservoir of I., the methods of transmission are linked to the latter, and only the routes of transmission can be different. R. Koch became the founder of the doctrine of the methods of transmission of infection, emphasizing the microbe, without which there can be no disease. This viewpoint formed the basis of his so-called c o n t a g i o u s theory of I., according to which a person containing microbes or objects contaminated by them, for example drinking water, are the only transmitters of the disease to a healthy person. The latter does not get sick only when he is not susceptible, or when the microbe does not encounter the corresponding favorable conditions in the environment, or there is no contact between the person and the microbe (for example, food products, air, water, soil are not contaminated). In contrast to Koch, Pettenkofer and his school concentrated the entire center of gravity in the question of the methods of transmission of I. on the soil. The latter, in Pettenkofer's opinion, is an active agent, and only that microbe transmits the disease which has "ripened" in the soil. Pettenkofer linked this influence of the soil with the level of the groundwater (the higher it is, the less virulent the microbe) and the content of organic compounds in the soil. According to Pettenkofer and Emmerich, when the microbe multiplies in the soil, it is carried out by insects and rodents and infects man through contaminated food products. This theory of infection and the development of epidemics is called localistic. Pettenkofer considered it necessary to admit the presence in the soil of some unknown factor (named by him "x"), which is what causes the increase in virulence of the microbe. At the present time, the role of the soil in the transmission of I. and the development of epidemics is not understood in the strict sense of Pettenkofer's doctrine, but the soil is regarded as a medium which can serve as an intermediary in the transmission of infection (contaminated vegetables or the hands of workers during earthworks) and can affect the viability and virulence of the microbe. Recently, there have been attempts to return to Pettenkofer's doctrine (about the connection of the course of an epidemic with the level of the groundwater and the existence in the soil of a special factor, named by him "x", which causes the increase in virulence of the microbe). In this doctrine, the followers of Pettenkofer discard the "x's" and again return to the level of the groundwater, to the chemical transformations occurring in the soil, and emphasize the influence of soil and meteorological conditions on the development of microorganisms. The very mechanism of transmission of I. according to Koch is such that the infectious agent either passes from organism to organism directly after contact ("direct" contact) or through the medium of objects contaminated with microbes ("indirect" contact). Examples of direct contact would be infection with influenza or plague when sputum from a patient with coughing fits enters the respiratory tract of a healthy person. Examples of indirect contact can be infection with cholera or typhoid through water contaminated with excretions from the sick. The terms "direct" and "indirect" contact do not represent fundamental differences in the mechanism of transmission of I., but only the route of entry of the causative agent in indirect contact is longer. These routes are different. Sometimes the infectious agent enters the healthy organism through the air. This path was previously given great importance ("fomites"). However, it must be remembered that among the millions of microbes inhaled by living beings, very few are pathogenic, because only a few microbes can live in the air. These include spore forms (such as anthrax), tubercle bacilli, pyogenic cocci, the diphtheria microbe (Netter, Loeffler, Cornet). These resistant forms withstand drying, and when inhaled or upon contact with them, infection can occur (dust method of infection, "dust" I. - Staubinfektion). Much more often, I. is transmitted through the air by the droplet method, which Fliigge defines as infection by the spraying into the air of the smallest droplets of mucus, saliva, etc., containing microbes ("droplet" I. - Tropfcheninfektion). As long as such droplets, expelled by humans and animals during breathing, coughing, float in the air, the microbes in them are still alive, but when the fluid dries up, they die. Such droplets can be carried from the sick to a distance of up to 12 m (experiments of Hubener), and the smaller the droplet, the farther the microbe can be carried. The droplet method of transmission of I. plays a greater role than the dust method, because only a few microbes can withstand drying to the degree necessary for the formation of dust. According to Gotschlich, infection with leprosy, diphtheria, influenza, whooping cough, measles, pulmonary plague, pneumonia, cerebrospinal meningitis occurs only by the "droplet" method. Only by the "dust" method are infected with the pulmonary form of anthrax, aspergillosis. By both methods are infected with tbc (more often by the dust method), smallpox, scarlet fever, chickenpox (Lange). Transmission of infection through water is a frequent route in typhoid fever, paratyphoid, cholera, and dysentery. Such water is dangerous not only as drinking water, but also when used for domestic purposes. Transmission of I. through soil is observed for microbes that are easily preserved in the earth, such as anthrax, tetanus, gas gangrene, pyogenic and putrefactive microbes. Under certain favorable conditions, cholera and typhoid microbes can also be preserved in the soil, getting into it with excretions. Of food products, milk most often transmits infection (intestinal group, Malta fever, tbc, foot-and-mouth disease). Meat can be a source of tbc, anthrax, a group of meat poisonings, putrefactive microbes. Oysters can transmit typhoid and cholera. Vegetables, fruits, kvass, mineral waters, confectionery products often serve as transmitters of diseases with cholera, typhoid, and paratyphoid. Household utensils, clothing and linen, books, toys can be contaminated with secretions and thus various pathogenic microbes, and be the cause of disease (tbc, cholera, typhoid, diphtheria, scarlet fever, influenza, etc.). Infection and animals. The source of I. can be, besides man, also an animal. If an animal suffers from the same disease as man, then transmission from animal to man occurs in the same way as from man, and the animal can be the primary source from which man receives the infection. For example, rabies has dogs as its source, glanders-horses, anthrax-cattle, foot-and-mouth disease-cows, disease sodoku (sodoku)-rats. In other cases, animals and man are equally sources of I. Man gets paratyphoid from both man and animals, which suffer from paratyphoid and are carriers of paratyphoid microbes. Tuberculous animals also serve as a source of I. for man. Animals are sources of I. for man both as carriers of microbes during their illness, and as bacillus excretors, and as healthy carriers (rats, ground squirrels, tarbagans-plague). The mechanism of transmission of I. from animals to man is the same as from man: direct communication, contamination of the environment, water, food products. To these factors must be added bites, which play an essential role in the transmission of I. from animals to man (rabies, plague, sodoku). In the transmission of I., animals can play, besides an active role, also a passive one. Without themselves being ill and not being carriers of microbes, animals can purely mechanically be sources and transmitters of I. Thus, domestic animals (dogs and cats), by becoming contaminated with human excretions in intestinal diseases, can become spreaders of infection as soon as people come into contact with them. Among the animal world, arthropods play a special role as sources and transmitters of I. Flies, bedbugs, lice, cockroaches, fleas, ticks, mosquitoes, gnats, which surround us in such enormous numbers, cannot but be involved in I. At the present time, it should be considered that arthropods as sources of infection participate in the transmission of I. in three ways. 1. Insects, having received the infectious agent from a sick animal, usually by biting and sucking blood, transmit it to a healthy individual in the same way by biting, or the infectious agent enters the healthy organism by rubbing a crushed insect; in this case, the microorganism in the insect's body undergoes no transformations. Such is the mechanism of transmission of plague by fleas and of anthrax by blood-sucking flies. 2. The insect, having sucked blood containing parasites, does not remain indifferent to the received microorganisms, but the latter undergo a certain cycle of development in its body. Arthropods are here the main or intermediate host of the parasite.

This occurs in malaria in the body of the mosquito, in typhus in the body of lice, in African relapsing fever in the body of the tick. 3. Arthropods, only mechanically receiving the infectious principle, are passive transmitters of the latter. This applies primarily to those arthropods, such as flies, beetles, cockroaches, which feed on dead and decaying plant and animal remains (excrement). The infectious principle adheres to their legs and wings and enters their intestines when food is swallowed. Such arthropods carry the infection on themselves during movement or excrete it with their feces. This occurs in tuberculosis, typhoid fever, cholera, dysentery in flies and cockroaches and probably in flies in trachoma. However, more and more facts are accumulating that dispute such a passive role of this group of arthropods. By passage through the bodies of flies, beetles and cockroaches, microbes can increase in their virulence. House flies, cockroaches (Caraffa-Corbutt) excrete typhoid bacilli and pyogenic microbes more virulent than when they were swallowed. In addition, their larvae retain the ingested microbes, and thus some forms of arthropods are carriers of microbes long captured by larvae. In the bodies of arthropods, microorganisms remain alive for many months (relapsing fever and ticks, plague and fleas), which has great epidemiological significance. Congenital I. can result from various factors: either the egg is infected and the infection passes to the fetus (I. 'germinative' in syphilis), or the sick mother transmits the infection to the fetus through the placenta (the child's disease with measles, smallpox; 'intrauterine infection'), or finally the child becomes infected from the mother at the moment of birth (e.g., gonorrhea). All these basic assumptions have received experimental confirmation. Thus, the experiments of Malvoz showed that a placenta damaged by septic and hemorrhagic microbes freely passes microbes, while a healthy placenta is a strong barrier to microbes. Experiments on animals have proven that an infected mother transmits microbes to the fetus through the placenta in babesiosis, anthrax, symptomatic carbuncle, rabbit septicemia, chicken cholera, pneumococcemia, glanders, rabies, tuberculosis [in the latter case (Calmette) filterable forms easily pass through the placenta]. In humans, such transmission has been proven in streptococcal diseases, pneumonias, typhoid fever, cholera, relapsing fever, rabies, malaria, tuberculosis, measles, and foot-and-mouth disease. Regarding transmission through male and female elements, there is experimental material dating back to Pasteur, who first proved that the disease of silkworms is transmitted through infected eggs from generation to generation; Levaditi and Sauvage found spirochetes in eggs in syphilis. All the listed cases of congenital I. are often incorrectly interpreted as phenomena of heredity. However, it is not difficult to understand that these phenomena have nothing in common with changes in the genotype. -Only those microorganisms can cause disease that have the ability to multiply in a living organism and harm it either directly by destroying its tissue elements or by their toxic products. The degree of pathogenic action of the microbe depends on both the properties of the macroorganism and the nature of the microbe. Different degrees of virulence of microbes. In those cases where microbes can live only in the living body of an animal and are not adapted to life in the external environment, they are called 'obligate' or 'absolute' parasites. In other cases, the pathogenic microbe is able to live not only in a living organism but also outside it. At present, it is essentially no longer possible to speak of absolute parasites, as was previously thought of the causative agents of relapsing fever, syphilis, the bacillus of leprosy, since all these microorganisms have been obtained on artificial nutrient media; perhaps only relative parasites are meant. However, as a basic principle, it can be accepted that the less demanding the microorganism is in relation to the living body, the more easily it multiplies on artificial nutrient media and the sooner it passes from a parasitic state to a saprophytic one. The virulence of the microbe also shows large fluctuations. The same microbe depending on different conditions is sometimes weakly and sometimes highly virulent. Virulence manifests differently in microbes in relation to different animals. The virulent properties of microbes in different species represent different degrees of stability. While the plague microbe stubbornly retains its virulence under all conditions, the gonococcus or pneumococcus quickly loses its virulence outside the body. In those cases where the virulence of the microbe represents a constant quantity, usually artificially obtained, such a microbe is called virus fixe (Pasteur-rabies). The degree of virulence is determined by the minimum lethal dose, i.e., that minimum amount of culture which is still capable of causing a fatal disease. Strengthening and weakening of virulence. The virulence of microorganisms can be artificially strengthened in various ways. The oldest and effective method, first used by Pasteur, is the passage of the microbe through a susceptible organism (passage). Such strengthening can be extremely long, for example with the plague microbe. In other cases, 'passage' has its limits, and one has to pass from one species of animal to another. Strengthening of virulence is also obtained when introducing to the animal along with the main microorganism some other microorganism (mixed infection with streptococcus). An organism previously weakened by another microorganism also provides a favorable soil for passage (the course of tuberculosis in those who have had measles). Furthermore, strengthening of virulence is obtained when preserving microorganisms in immune and normal sera. In this case, it is obviously a matter of the 'habituation' of the microbe to an unfavorable environment, with the stronger individuals surviving. A number of authors (Mechnikov, Sanarelli, Roux) used the method of collodion sacs to strengthen virulence. The latter, filled with culture, are introduced into the abdominal cavity of the animal, and the microbes, thus protected from the harmful action of the cellular elements of the organism, more easily become accustomed to it. By various methods, it is possible to strengthen and maintain the virulence of the microbe outside the organism (in vitro). Addition of protein to the nutrient medium (Merezhkovsky), ascitic fluid (Marmorek), glycerin (Roux and Calmette), preservation on ice - all this contributes to the strengthening and maintenance of virulence. Weakening of virulence is usually the result of the action of factors harmful to the life of the microbe: light, high temperature, drying and various physical factors and chemical substances. Preservation of a pathogenic microbe on an artificial nutrient medium also weakens its virulence. The most reliable method of weakening virulence is heating at a certain temperature; thus, for the anthrax microbe, 43° (Pasteur) or 55° (Toussaint) is needed. Drying (in rabies), especially together with aeration, as well as sunlight, has long been used to reduce virulence. Some chemical substances, such as carbolic acid, iodine, bile, added to nutrient media, sharply change virulence (BCG culture in Calmette's experiments with bile). Virulence can also be weakened by passing the microorganism through non-susceptible or slightly susceptible animals or when another infectious process develops simultaneously (erysipelas and lupus, progressive paralysis and malaria). Types of I. Natural and artificial infections are distinguished. Any infection occurring under the influence of the environment outside our intervention will be 'natural'. In the case when for the purpose of experiment the infectious principle is forcibly introduced into the body, the infection will be 'artificial'. The latter is used in experiments on animals, as well as in humans for therapeutic purposes, e.g., in the treatment of progressive paralysis, the patient is infected with spirochetes of relapsing fever or malaria. If the disease is caused by one type of microorganism, such an infection is called simple, if several types are involved, then we speak of a mixed infection. Mixed infection, depending on the nature of the microbes, can be either more severe than each simple one (e.g., diphtheria microbe + streptococcus), or milder (typhoid infection + B. rosanoff). If one infection follows another, we speak of secondary or 'sequential' infection. In this case, it is not always certain that the secondary infection actually penetrated the body after the primary one. Often several infections penetrate the body simultaneously, but some of them have their effect later than others. Secondary infections often have as their source endogenous microbes ('microbes de sortie'). Such secondary, or sequential infections are sometimes also called 'para-infections'. According to the sources from which infections arise, they are also divided into exogenous ('heterogeneous') and endogenous ('auto-infections'). Exogenous have as their source microbes coming from outside the body, and most epidemic diseases belong to this group of infections.

Endogenous infections have as their source the body's own microbes, which acquire pathogenic properties under the influence of various factors activating them or weakening the macroorganism. Such endogenous infections include lobar and postoperative pneumonias, anginas, furunculosis in diabetics, some colitis, apparently post-vaccinal encephalitides, partly tuberculosis, for example after injuries, after infectious diseases, typhoid abscesses many years after having typhoid. The latter examples, when the infectious agent, while in the body for a certain time, does not manifest itself in any way, and then under the influence of various factors the disease arises, can serve as examples of hidden, or latent, or dormant infections. To these can be added examples of endocarditis lenta, aggravated joint rheumatism. French authors single out a special type of 'unmanifested' infections ('infections inapparentes') when the organism, containing microbes, always retains the ability to infect others, but remains itself immune and clinically completely healthy. Nicolle and Lebailly (Ch. Nicolle, Lebailly) called by this name acute and septicemic diseases which can be detected only by infecting animals. Such facts were first discovered in experimental typhus, then in syphilis (Kolle, Prigge), Malta fever, measles. Kolle called such infections asymptomatic; they are also called silent, dumb ('stumme'). Friedemann includes among hidden infections also abortive and mild forms, with which one cannot agree. Reiter separates 'dumb' infections from 'hidden' ones, considering the former only those states when the animal is clinically absolutely healthy. Both hidden infections and purely dumb ones, in particular bacillemia, in a number of cases can lead to immunization of the organism (meningococcus, measles and scarlet fever infections, diphtheria). American authors call 'focal' infections those infections which have as their source foci of microbes which may not manifest their presence in any way. But from these foci microbes spread throughout the organism, causing general and local diseases, such as endocarditis, arthritis, nephritis, etc. Such foci are teeth (pulpitis, apical granulomas, etc.), tonsils, accessory nasal cavities, gall bladder, prostate gland, genitourinary organs. Most often the causative agents of such focal infections are streptococci, both hemolytic and green (Rosenow). According to Rosenau, such microbes in 'foci' possess selective affinity for organs and tissues, which explains the lesions of certain organs. In experiments on animals, extremely demonstrative facts of selective lesions of various organs by streptococci isolated from corresponding diseases are obtained; thus, with the streptococcus isolated from patients with appendicitis, out of 71 (intravenously) infected animals, appendicitis was obtained 70 times (Rosenau). Out of 168 animals infected with the streptococcus isolated from patients with stomach ulcers, 68 times lesions of the stomach and duodenum were obtained. 'Cryptogenic' infection is such a disease when the microorganism penetrates the body without giving local phenomena and without stopping at the gates of infection. As an example of such an infection one can cite cases of septic anthrax without local phenomena, cases of sepsis without visible local foci. Under 'primary' infection is meant the first infection with the virus; e.g. one speaks of primary tuberculosis. By reinfection is meant a new endo- or exogenous infection of an organism that has already had the corresponding disease at some time (e.g. one says: tuberculous reinfection); such reinfections can sometimes be several. If the organism has not acquired immunity, a new disease is possible (syphilis, relapsing fever), but only on the condition that no microbes from the previous disease remain in the body. Otherwise, the new disease will be the result of the revival of the remaining microbes, i.e. a 'relapse' of the disease occurs. In some cases it is possible for microbes to enter an organism already infected with the same microbes, and a new disease occurs, which is called superinfection (superinfectio). Such phenomena are observed, for example, in syphilis. The essence of the pathogenic action of microbes can be considered from two sides. First of all, the microbe multiplies and feeds at the expense of the living macroorganism, exhausting the latter and burdening it with its metabolic products and enzymes which digest the nutritional material present in the cells and juices of the organism. On the other hand, it must be assumed that pathogenic microbes produce substances that are poisonous to the cells of the organism. However, when studying various microbes and their action on the organism, it can be clearly seen that this action is different. In some cases the microbe does not go beyond the place of entry into the organism, and the organs and tissues of the latter suffer from the poisons produced by the microbe and absorbed by the rest of the organism through the lymphatic and blood vessels; such microbes are called toxic, and the disease they cause is characterized by 'toxemia', or toxemia. These include the diphtheria, tetanus microbes, the sausage poison microbe, dysentery, cholera, malignant edema, streptococcus in scarlet fever. In other cases, microbes spread throughout the organism; such microbes are called septic, and the disease they cause is characterized by septic phenomena (septicemia), or 'sepsis'; these include the microbes of anthrax, plague, pyogenic, partly typhoid fever and others. The poisonous products causing the action of microbes on the organism belong to substances different in composition and physiological effect. Some of them have a characteristic action for a given infection, i.e. 'specific' action. These include toxins. Other substances, also poisonous, do not have a specific action. These are primarily bacterial proteins, protein substances associated with the microbial molecule. They were first obtained by Buchner by treating microbial cultures with alkali. If the alkali-dissolved microbial bodies are acidified, a precipitate falls out, giving protein reactions. Such a precipitate, when injected under the skin of an animal, causes suppuration and elevation of temperature, and a similar effect is obtained from different microbes, both pathogenic and saprophytes. Next come ptomaines, protein cleavage products from the amine group, having a poisonous effect on protoplasm. Microbial enzymes should also have a certain destructive effect on cells. All these substances, acting specifically and non-specifically, constitute the sum of influences that explains to us the essence of the pathogenic action of microbes on the organism. Depending on which tissues the toxins act on, 'neurotoxins' (affecting the nervous system), 'hemotoxins' (destroying erythrocytes) and 'leukotoxins' (destroying leukocytes) are known. The mechanism of action of toxins on tissues is different. While neurotoxins (e.g. tetanus and sausage) cause hydrolysis of the protein and lipoid parts of the nervous system, snake and dysentery toxins first cause coagulation of the protoplasm of cells, then dissolution, and leukotoxins (staphylococci, septic vibrio) clump leukocytes, then dissolve them. Some microbes possess multifaceted toxins; thus, tetanus has both neurotoxin and hemotoxin. Hemotoxin is most common among microbes: besides streptococcus, it is possessed by cholera vibrios, anthrax microbe, pneumococcus, plague microbe, blue pus bacillus, B. perfringens, hay bacillus, etc. In addition to the above data on the causes of the pathogenic action of microbes, it is necessary to mention the aggressins of Bail and the antiphagins of Chistovich and Yurevich ('virulins' of Rosenau). In relation to the so-called 'septic' microbes, where the mechanism of action is not sufficiently clear due to the absence of pronounced toxins, the doctrine of aggressins (see) and antiphagins (see) helps to understand this mechanism. A number of microbes, such as pneumococci, staphylococci, chicken cholera bacillus, Metchnikoff's vibrio, blue pus bacillus, are associated with special substances, antiphagins or virulins, which act on the cells of the organism, as if protecting themselves from the harmful influence of the latter. These substances are easily obtained from highly virulent cultures; by washing the microbes are freed from them and become accessible to phagocytosis. Koch's Triad. By Koch's triad are meant the three basic propositions first put forward by Robert Koch as conditioning the recognition of the etiological role of the given microorganism in a given infection. 1. The microbe must always be found in the given disease and not be found in healthy individuals or in other diseases as the causative agent of the latter. 2. The microbe must be obtained in pure culture. 3. The pure culture of the microbe must cause in an experiment on an animal or in a person that very disease, the causative agent of which it must be recognized. These propositions establish the concept of the 'specificity' of the microbe. This triad at one time played an enormous role in the search for various causative agents, putting the entire question of the etiological role of this or that microorganism in strict framework. On the example of the Koch's tubercle bacillus Koch brilliantly confirmed the significance of his triad.

However, over time, various amendments were introduced to the triad, softening the strictness of its requirements and somewhat changing its provisions. As for the first point, since the appearance of the doctrine of microbe carriers, the finding of microbes in healthy individuals no longer contradicts the specificity of the microbe. The same must be said regarding the finding of the microbe in other diseases. Besides the possibility of simultaneous carriage of microbes by patients with another contagious disease, e.g., diphtheria bacilli in scarlatinal patients, the microbe may possess various pathogenic properties, causing different diseases under different conditions. Thus, the plague microbe causes bubonic and pulmonary plague, streptococci - phlegmon, erysipelas, and sepsis. The second point - the requirement of pure cultures - also has relative significance. In a number of infections where pure cultures have not been obtained, as in leprosy and syphilis, there was no doubt about the etiological role of the corresponding microbes, since the material containing the microbes satisfied the third provision, i.e., it caused corresponding diseases in artificial infection of animals and humans. The third point of the triad, which is particularly important, cannot be fulfilled in many cases, because it is far from always possible to reproduce the actual human disease in animals with a culture (measles, scarlet fever, epidemic parotitis). Furthermore, experiments on humans, even positive ones, cannot always be considered convincing, because it is rarely possible to avoid the objection that the experiment was conducted during the incubation period of the disease. It is necessary to introduce another amendment to Koch's triad due to the modern view on specificity: one microbe not only can cause various diseases, but the same clinical disease can be caused by different microbes (e.g., dysentery, pneumonia, sepsis). Conditions facilitating the development of infection. For the manifestation of pathogenic action on the organism, the microbe must possess a certain virulence; however, the further course of infection depends on the conditions that the microbe encounters in the organism. General weakness of the organism after a disease, local predisposition of individual organs, prior artificial introduction of live or killed cultures of other microbes (e.g., B. prodigiosus makes a rabbit susceptible to the microbe of symptomatic anthrax) are well-known factors making the organism susceptible to infection. Furthermore, it is necessary to point out insufficient nutrition, excessive physical and mental work. The influence of the nervous system, emotions on the course of infection has been experimentally proven by Gabrichevsky, Fere, Massart and Bordet (Fere, Massart, Bordet). 21 Trauma, cold, cooling or overheating of the body, various poisonings (alcohol, morphine, cocaine) also favor the development of infection. Age has an influence on infection (infancy poorly tolerates intestinal infections, senility - pneumonias). Sex also does not remain without influence on the course of infection. The menstrual period, pregnancy, childbirth make the woman's organism particularly susceptible to streptococcal infections. The state of the endocrine system is also connected with the course of infection: the influence on tuberculosis of hypo- or hyperfunction of the thyroid gland. The path by which the microbe penetrates the organism and the place of its entry also have great significance for the course of infection. It is necessary to consider the microbe's affinity for certain organs and the length of the path traversed. Thus, in rabies, the disease manifests more quickly when the virus is introduced under the brain, meninges, than under the skin, and moreover, bites in the head always proceed more severely than bites in the leg. The significance of the place of entry of the infectant is illustrated by the example of bovine peripneumonia: the virus introduced into the skin of the tail does not cause disease, and only when introduced under the skin of another area of the body can disease be obtained. This difference can be explained by the difference in local anat. and physiol. conditions, hindering or aiding absorption. Mixed infections can also play a role as conditions facilitating the development of infection. In this respect, streptococcus is in the first place, then B. proteus, B. perfringens, filterable viruses. The paths of penetration of pathogenic microbes into the organism are extremely diverse. All open cavities of the body", such as the cavity of the mouth, nose, external opening of the auditory canal, conjunctiva of the eye, external opening of the urethra and sexual organs, serve as gates for the entry of microbes ('gates of infection'). Upon entering such cavities, microorganisms either remain here, causing local diseases, or cause general diseases, penetrating through the lymphatic and circulatory systems into internal organs. In those cases where internal organs are affected by microbes that have entered there via the bloodstream, in the absence of local lesions in the mucous membranes through which the microbes penetrated, the infections are called 'hematogenous'. Such are considered abdominal typhus, lobar pneumonia, pulmonary plague. This passage of microbes through mucous membranes is possible not only with their damage, but also with their complete integrity. The latter is known for glanders, relapsing fever, and plague, for which a number of studies (Nocard, Ficker, Bazarov and Kulesha) have proven the permeability of the intestinal mucosa, oral and nasal cavities. Microbes can penetrate through lymphatic spaces of mucous membranes or enter deep layers with the help of migrating leukocytes. Through the skin, microbes pass with its damage - scratches, bites of insects. Under natural conditions, microbes enter the blood through the lymphatic system. Directly into the blood, microbes can enter; in artificial infection or in bites of insects, animals. The same microbe in different cases can have different gates of infection; thus, in plague, bubonic forms have damaged skin as their gate, pulmonary - the respiratory tract. Usually each infection has its permanent gates. Such are for abdominal typhus and cholera - the cavity of the mouth, for anthrax carbuncle - the skin. The question of the gates of infection and the primary affection should be distinguished: they do not always coincide, i.e., the infection can pass through the given gates without leaving visible changes here; for example, plague lymphadenitis is observed with completely unnoticeable, only presumed damage to the skin; the same is observed in some cases of tuberculosis, syphilis, sepsis and many other infectious diseases. But even in those cases where, seemingly, the gates of infection undoubtedly coincide with the primary affection, it is not always possible to assert that this is indeed so: e.g., cases of scarlatina-like and vulgar type angina are observed in the course of gynecological sepsis as its manifestation; in other words, not only the gates of entry, but also the gates of exit of infection can be marked by characteristic anatomical processes. The organism's struggle with infection. The organism has a number of protective adaptations against infection of a physical, chemical, and biol. nature (see Immunity). First of all, on the path of invasion into the organism, microbes encounter purely mechanical obstacles: the integrity of the skin and mucous membranes to a certain degree serves as a barrier to microbes. Settling on mucous membranes, microbes here encounter secretions of mucous membranes (saliva, mucus, tears), which mechanically remove them; microbes reflexly irritate the mucous membranes, the result of which are cough, sneezing, vomiting, and diarrhea, also contributing to the removal of microbes. Urine, bile, and milk excrete microbes and their toxins from the body. The chemical reaction of the environment (acidic gastric juice), alkalinity of the blood, content of O and finally body temperature - all this in many cases hinders the development of microbes. The most significant factors in the struggle with microbes are the work of cellular elements, their ability to phagocytosis and to produce protective substances of the nature of antibodies. Only by the action of such factors can the final death of microbes within the organism be explained. (See also Infectious diseases, Epidemiology, Disinfection, etc.)

S. Zlatogor. Protozoan and spirochetal infections differ from bacterial infections in certain features, which impart a number of characteristic peculiarities to their pathogenesis. - Pathological changes in the organism caused by parasitic protozoa as well as spirochetes and fungi are expressed a) in the form of direct primary damage to infected cells and tissues up to their destruction and b) in the form of reactive, resp. inflammatory changes in the cells and tissues of the organism, arising in connection with the introduction e-t» and multiplication of parasites and expressed in the formation of infiltrates, abscesses, in the proliferation of connective tissue, in changes in the permeability of the walls of blood capillaries, in necroses, etc. All changes that arise in the order of the organism's reaction can be designated as secondary changes. - The direct action of parasites on a cell, uncomplicated by reactive phenomena from other cells, is encountered in the infection of protozoa themselves by parasites (resp. super parasites)-in the case of parasitic protozoa. Thus, infection of amebae by nuclear parasites (Nucleo-phaga) initially leads to hypertrophy of the nucleus, then to hypertrophy of the body and finally to its destruction. Similar phenomena are also observed in the infection of cellular elements in higher organisms. Thus, infection of plant tissues by myxomycetes (Plasmodiophora brassicae) is also the cause of their hypertrophy and destruction. Infection by malarial plasmodia leads to the direct death of the corresponding erythrocytes. The same is observed in the infection of endothelial cells by leishmanias in penden ulcer, tropical splenomegaly, etc. or muscle cells by leishmanial forms of Tr. Cruzi in Chagas' disease, etc. In the examples cited, we observe destruction of cells under the influence of the direct penetration of the parasite into their body. However, in the process of cell destruction, the biochemical action of parasites also plays a role. In other cases, destruction of cells occurs already upon their mere contact with parasites, apparently under the influence of toxic substances, enzymes, etc., secreted by the latter. Thus, in infection of the intestinal wall by the infusorian Balantidium coli, these parasites do not penetrate into the cells; however, as they pass between the epithelial and connective tissue cells of the intestinal wall, the latter undergo necrosis, apparently under the influence of proteolytic secretions of the mentioned infusorians. In other cases, toxic substances secreted by parasites can apparently spread in the organism through the bloodstream, and in these cases the action of toxins can manifest itself even in distant parts of the organism that have no direct contact with the parasites. The secondary changes arising in the organism under the influence of protozoan infections consist, firstly, of the direct results of cell destruction. This includes, for example, anemia developing in connection with malaria. In this case, it would be erroneous to reduce the said process exclusively to the destruction of the affected erythrocytes, since undoubtedly the toxic action of plasmodia on the hematopoietic organs also plays a significant role. One of the most complex biochemical phenomena associated with malarial intoxication is apparently hemoglobinuric fever. Similar phenomena we also encounter in the infection of cattle and other animals by piroplasms, also leading to hemoglobinuria. Toxic phenomena undoubtedly underlie the anemia in trypanosomiasis (sleeping sickness, disease 'nagana'), where there is no primary destruction of erythrocytes by parasites. This also applies to the hemorrhagic and icteric processes developing in malaria and in some spirochetoses (typhus fever, Weil's disease, syphilis). - Secondly, the secondary consequences of protozoan infections include inflammatory cellular reactions arising in response to the penetration and multiplication of parasites. These changes show in various infections a varying degree of complexity depending on the peculiarities of the parasites on the one hand, and on the other hand on the character of the general or local immunity inherent in this infection, and the course of the process also depends on the specific peculiarities of the host. Usually the character of the cellular and tissue reaction is for each given infection more or less typical. Thus, infection with pathogenic amebae Ent. histolytica leads to the formation of necrotic ulcers in the intestinal wall, as well as to metastases in other organs with the formation of necrotic abscesses in them. The changes in malaria, sleeping sickness and syphilis are expressed in the formation of cellular infiltrates along the course of blood capillaries and small arteries in various organs, including the brain, and this in connection with the toxic action of the parasites can explain the origin of various neuropsychic phenomena arising in connection with the said infections (coma, drowsiness, excitement, psychoses, etc.). - In some cases, e.g. in amebiasis and malaria, the tissue reaction of the organism has a relatively simple character. In other cases, tissue, histological changes in the organism show a complex cyclic sequence, which stands in an undeniable connection with the peculiarities of immunity in these infections. In the most obvious form these relations are expressed under natural conditions in syphilis, where, as is known, the entire process in typical cases consists of three phases: 1) penetration of the infection with the formation of a chancre; 2) its generalization with the formation of exanthems and 3) a period characterized by destructive-gummatous processes. In addition to the direct toxic action, the action of toxins has also been proven by their influence on the general metabolism. According to the latest research, when rats are infected with trypanosomes, the content of lactic acid in their blood increases 3-4 times, which leads to a decrease in the alkaline reserve of the blood and reduces the oxidative processes due to the influence of lactic acid on Hb. In this connection, the introduction of bicarbonates proves capable of neutralizing to a certain extent the pathological process (Kligler, Heider, Komaroff; 1929). - Thus, the general course of protozoan infections is determined both by the biological properties of the corresponding parasites and by the biological peculiarities of the host and in particular by the character and degree of its immunity.

G. Epsteyan. Infection in plants. One can distinguish between proper infection and the introduction of a parasite. The former is characterized by the fact that the plant exhibits a certain active reaction to the penetration of the parasite, expressed in changes in structure and function and culminating in a set of phenomena of disease. In contrast to this, introduction does not lead to sharply expressed active reactions. Between these two concepts, it is impossible to draw a sharp line, since in essence some active reaction is always observed when a foreign body is introduced, even with simple minor injuries. Therefore, the difference here is essentially quantitative and conditional. The most typical are fungal and mycotic infections, which are generally most common in plants. Bacterial infections are less typical and less common. As for the damage to plants by floral parasites (e.g., our dodder and dodder or tropical Rafflesiaceae), some Protozoa (mainly Flagellata), and especially insects and some worms, here one usually has to speak not of proper infection, but precisely of introduction; although it often leads to the death of the entire plant (mostly from exhaustion), the plant's active reaction in this case is little expressed. (It should be noted that in many cases of damage by insects, a very typical reaction of the plant is observed, for example in the formation of galls.) Infection in plants is usually local, i.e., the parasite does not spread far from the place of initial penetration and affects only the tissues nearest to it, while other parts remain completely healthy. Only when there is a very large number of individual foci of infection or when infection occurs in particularly important places, e.g., when it causes a break in the conducting pathways in the main stem or root, does the death of the entire plant occur. In relatively few cases, a wider spread of toxic substances secreted by parasites throughout the plant body is observed, which leads to death, so to speak, from general poisoning. This is the case, for example, partly in the damage to many plants by Bact. tumefaciens, which causes them to exhibit cancer phenomena. Sometimes general infection occurs, when the parasite penetrates the entire plant body. This is characteristic, for example, of the damage to cereal grains by smut fungi. With infection by unicellular parasites (bacteria, Protozoa), the latter multiply immediately in the plant body, while with other infections, especially the most typical fungal infections, there is initially only growth of the parasite, and only later does its multiplication begin. At this time, special organs that emerge to the outside form spores, which can only re-enter the plant through new infection. This moment of the beginning of parasite multiplication usually manifests itself as the appearance of the infectious disease, until which the incubation period lasts. In most fungal infections, it measures a few days, but sometimes it is much longer, especially in cases of general infection (almost an entire growing season, sometimes even several years). The parasite penetrates the plant body either through ready-made openings in its covering tissues (mainly stomata) or by boring through the coverings themselves. Finally, in a number of cases, the parasite itself is unable to penetrate the plant, and the gates of infection here are various accidental damages that violate the integrity of the outer coverings. Such so-called wound infection is very typical, for example, for most bracket fungi that attack tree trunks. In many cases, wounds are inflicted by insects, and sometimes specific relationships are observed between the parasitic fungus and insects that facilitate its spread (for example, the fungus Monilia and the fruit moths and especially codling moths on apples and plums).- In plants, true hereditary infections, i.e., those that would be transmitted through the sex cells, have not been noted, although on the other hand there are cases of transmission of infection through seeds, which become infected from the maternal organism. Sometimes such an infection is obligatory for a given plant species and turns into a special symbiosis. Such are, for example, our heather (Calluna) or the intoxicating darnel (Lolium temulentum), which are constantly infected with a fungus, or the tropical Ardisia, which carries a constant bacterial infection. Close to the above-mentioned parasitic infections in character are viral infections. So-called viral diseases are quite widespread in some, especially cultivated plants (potato, tobacco, tomatoes, etc.). Experimentally, infection is mostly easily achieved here by injecting the sap of a diseased plant into a healthy one. In nature, it is mainly carried out through the agency of piercing and sucking insects, especially aphids. In some cases (beet mosaic disease), aphids seem to be obligatory carriers of infection, and without their mediation it does not occur.

L. Kurganov