Foot And Mouth Disease

FOOT AND MOUTH DISEASE (Latin-aphthae epizooticae, French-fievre aphteuse, German-Maul- und Klauenseuche), an acute contagious epizootic disease of cloven-hoofed animals, belonging to zoonoses (see) that affect humans in the form of sporadic or group diseases. Epizootics of foot and mouth disease apparently appeared in Europe very long ago, but the first unquestionable description of it dates to the 16th century (Fracastorius). Previously, foot and mouth disease was often confused with plague of cattle and sometimes with anthrax. The occurrence of the disease was attributed to meteorological and feeding causes, only in the 18th century Sagar established its contagious nature, and in the 19th century Bollinger proved the specificity of the infection, although the infectious agent remained unknown and cannot to this day be considered fully studied. With the advent of the bacteriological era, many researchers isolated from foot and mouth disease sometimes bacteria, sometimes fungi, sometimes protozoa, which they considered the causative agents of the disease. The erroneous nature of all these assumptions became clear when in 1897 Loeffler and Frosch proved that the true causative agent of foot and mouth disease passes through Chamberland and Berkefeld filters, which do not allow bacteria to pass through. This opened a new group of infectious agents, named 'filterable viruses.' Frosch and Dahmen in 1924 claimed to have succeeded in cultivating on a solid nutrient medium a bacillus of such insignificant size (not more than 0.1 μm) that it can only be detected by photography with short-wave ultraviolet light. However, the microbe they discovered, Loeffleria nevermanni, and its etiological significance for foot and mouth disease did not find confirmation during official checks in Germany, England, and the United States. Cultivation of the foot and mouth disease virus on living nutrient media has generally not been possible to this day, and the method of propagation in living tissue cultures has not yet given sufficiently definite results in foot and mouth disease (English Commission, Hecker, C. a. W. Maitland). Therefore, the study of the foot and mouth disease virus is still carried out with the help of infectious materials from animals sick with foot and mouth disease. In the body of both naturally diseased and artificially infected animals, the foot and mouth disease virus is found in the contents and walls of primary aphthae at the site of its introduction, then during the period of generalization-in the blood, saliva, milk, and parenchymatous organs, and finally in secondary aphthae. At the same time, its virulence or rather concentration, determined by the degree of dilution in which it still proves to be infectious, varies within wide limits depending on the moment of testing and on the individuality of the sick animal. For the experimental detection of the foot and mouth disease virus, the most suitable laboratory animal is the guinea pig, which is not naturally susceptible to the disease (Hecker, Waldmann, Rabe, Hobmaier), in which after inoculation of the virus on the plantar surface of the hind paws, a typical picture of foot and mouth disease develops. Like many other causative agents of infectious diseases, the foot and mouth disease virus is not uniform. Vallée and Carre in 1922 proved the existence of two types of foot and mouth disease virus, designated by them as 'O' and 'A,' which cause completely identical pictures of the disease but do not immunize animals against each other. In 1926 Waldman and Trautwein discovered a third type 'C,' which, like the first two, can be differentiated by cross-immunization. The designations 'A' (instead of 'O') and 'B' (instead of 'A') proposed by Waldman and Trautwein did not find general recognition. The most widespread type worldwide is type 'O.' This is the only type that until 1931 in the Foot and Mouth Disease Institute on Gorodomlya Island was determined by Skomorokhov in materials received from the USSR. The question of the constancy of types, their variability, and even the transition of one into another is still in the stage of experimental development. The question of the stability of the foot and mouth disease virus against various chemical and physical agents was also studied by numerous researchers, but has not yet found a unanimous solution, which is explained by the use of virus of varying virulence, in varying quantities, from different sources (lymph of vesicles, walls of aphthae), in different media (tissue suspensions, filtrates), etc. In relation to chemical reagents, the foot and mouth disease virus was for a long time considered significantly more resistant than bacteria, especially against alcohol, ether, and chloroform, as well as against most disinfectants used, with the exception of 1-2% solution of caustic soda and 1% antiformin. However, Olitsky, Traum, and Schenning showed that this apparent extraordinary stability is explained by the fact that researchers used in their experiments virus located in media rich in proteins, which, coagulating, protected the virus from the action of chemical poisons. Upon elimination of this factor, for example by adding caustic soda to alcohol, the foot and mouth disease virus is killed just as easily as bacteria. For practical purposes, the 1-2% solution of caustic soda is most widely used. According to the English Commission, against 50% glycerol at 5° the foot and mouth disease virus is stable for at least 400 days, and against 96%-10 months. According to experiments of the same commission, its survival is generally favored by a narrow pH zone from 7.5 to 7.6 in the medium containing it. High temperatures, starting from 50°, act destructively on the foot and mouth disease virus in periods measured in minutes, depending on the medium in which it is located. Low temperature contributes to the preservation of its activity. In its relation to the action of sunlight and artificial light, the foot and mouth disease virus does not differ from bacteria. The initially widespread opinion about the insignificant stability of the foot and mouth disease virus against drying, based on the methods used in bacteriology, proved erroneous when this question was studied under conditions approaching natural ones. Outside the organism, on objects surrounding it, the foot and mouth disease virus can withstand drying for weeks and months without damage to its viability and virulence. Inside the body of spontaneously diseased or artificially infected animals, the foot and mouth disease virus usually quickly dies (within periods from several hours to several days), but in exceptional cases it can persist for several months (carrier state). In the carcasses of animals killed during the period of generalization of the infection and kept under normal conditions, the virus disappears quickly-through 12-48 hours, as is assumed, due to the formation of meat-milk acid and other virucidal substances. With rapid cooling or freezing immediately after slaughter, it is preserved in meat for over 1 month, and in bone marrow-over 3 months. Practically important is the fact that when milk sours, the foot and mouth disease virus in it quickly dies. In epidemic form, foot and mouth disease in humans is not observed, and usually occurs in the form of sporadic cases and only rarely multiple cases during an epizootic in cloven-hoofed animals. The disease mainly affects people who have direct contact with foot and mouth diseased animals, and people, especially children, who consume raw milk or dairy products from foot and mouth diseased cows. The relatively rare at present transmission of foot and mouth disease by milk compared to other zoonoses (tuberculosis, brucellosis) is explained in part by the low susceptibility of adults to this disease, in part by the rapid death of the virus when milk sours; but mainly the infectivity of humans with foot and mouth disease is constantly decreasing due to the improvement of sanitary-prophylactic measures and sanitary-hygienic education of the masses. Transmission of foot and mouth disease from person to person has not been proven. From an epizootiological point of view, foot and mouth disease is one of the most contagious infections of animals. In former times, foot and mouth disease seized vast areas in the form of panzooties with unprecedented speed, for example passing through all of Europe, mostly from East to West, after which usually followed a period of several years free from epizootics, during which only insignificant local outbreaks appeared in some places. At present, with the development of veterinary-sanitary and prophylactic measures, such rapid spread of foot and mouth disease is no longer observed, but in most countries foot and mouth disease has become enzootic, maintained by virus carriers transmitting the infection to young animals and previously uninfected animals. In addition, the introduction of foot and mouth disease into disease-free areas can occur through live cattle (carriers) and through contaminated or polluted raw animal products. The possibility of the virus being introduced by persons who had dealings with sick cattle is also not excluded. The role of animals not susceptible to spontaneous disease (horses, dogs, cats, rats; birds), as well as flies and other insects as passive transmitters, apparently has very little epizootiological significance. Naturally susceptible to foot and mouth disease infection are almost exclusively cloven-hoofed animals: cattle, pigs, goats, sheep, northern reindeer, camels, as well as wild cloven-hoofed animals; in addition, to a lesser degree, humans. Natural foot and mouth disease in dogs, cats, odd-toed ungulates, and birds is extremely rare and occurs atypically. Artificial infection with foot and mouth disease is possible for a number of small animals: guinea pigs, rabbits, dogs, cats, white rats, field mice, hedgehogs, but in most of them infection does not always succeed.

Only guinea pigs represent a reliable object for experimental work, exhibiting typical local lesions after skin infection on the hind footpads, and sometimes generalization of the foot-and-mouth disease process. After recovering from foot-and-mouth disease infection, immunity always occurs, but only against the type of virus that served as the causative agent of this disease. The degree and duration of immunity can vary considerably. According to degree, there are "complete" and "partial" immunity, with the latter characterized by the fact that after secondary infection, pathological changes (aphthae) appear only at the site of infection. Some authors see in this not different degrees, but different types of immunity, considering partial immunity as "tissue" immunity and complete immunity as "humoral" immunity or a combination of both types. "The average duration of complete immunity in F.M.D. is from 9 to 12 months and of relative immunity up to 2 years" (Skomorokhov). In practice, significant deviations in both directions are observed, which, it is assumed, depend on the severity of the disease, its form, individual characteristics of the animal, and other, as yet unclarified factors. In the blood of sick and recovered animals, antibodies with therapeutic and protective properties appear, the presence of which can be determined only by experiment (on guinea pigs); they do not give complement fixation, precipitation, or flocculation reactions. The initiative to artificially obtain foot-and-mouth disease antibodies belongs to Löffler and Frosch. Their method consists in that piglets weighing 15-20 kg are infected with the foot-and-mouth disease virus. Lymph from the blisters that form on them is collected, filtered through bacterial candles, and injected in increasing doses intravenously into cattle, from which, after 2-3 months, an active serum is obtained accordingly. With the help of hyperimmunization, highly immune anti-foot-and-mouth disease serums can be obtained, suitable for practical purposes. Such serums were produced at special large stations—in Riemes in Germany and on Gorodomylya Island in the USSR. As numerous experiments have shown, active immunization against F.M.D. is in principle possible both with virus weakened by various methods and with virus killed but having retained its antigenicity (formalinized). However, none of the proposed methods, except simultaneous (serovaccination), has acquired practical significance. The pathogenesis of F.M.D., although not yet finally established, is increasingly clearly outlined in its details since guinea pigs were introduced into the experimental technique for this infection. The long-prevailing view that the F.M.D. virus can penetrate into the bloodstream through damaged respiratory passages and the mucous membrane of the digestive tract and then to the favorite sites for the development of typical changes has now been abandoned. The portals of entry for the F.M.D. virus are any, even microscopic, violations of the integrity of the external coverings and mucous membranes. At the site of introduction, the virus multiplies (primary aphtha), from where it enters the blood, which serves only as a passive means of its spread throughout the body. During this generalization, the F.M.D. virus exhibits its predominantly dermotropic and epitheliotropic character, expressed mainly in the formation of multiple secondary aphthae on the skin (uncovered by hair) and on mucous membranes. Even before this exanthema is clearly expressed, the virus can be excreted by some parenchymatous organs to which it was carried by the blood. These excretions (saliva, milk) have outstanding epizootiological and epidemiological significance. Focal changes in tissues of non-epidermal type are caused by virus trapped in them during generalization and are often complicated by other pathogenic microbes. The role of the reticulo-endothelial apparatus in F.M.D., as well as the supposed specific intoxication by authors, is still under study. The visible during life pathological-anatomical foot-and-mouth disease changes are located mainly on the mucous membranes of the mouth and nose and on the delicate parts of the skin of the limbs, at the coronary band, in the interdigital cleft or in the folds between the toes (therefore, in German and English, F.M.D. is called "muzzle-and-foot disease"), but they can also occur around the anus, near the vagina, on the udder, and on other parts of the skin not covered with hair. In typical form, they represent in the initial stages the so-called aphthae, i.e., separately located, sometimes merging blisters of various sizes (from the size of a pinhead in goats to several centimeters on the tongue in cattle), forming in the stratum spinosum, lifting the upper layers of the epithelium and filled with transparent or yellowish fluid, which may later become turbid from leukocytes penetrating into it. In young aphthae, at the border of healthy and affected tissue, Gins found intranuclear, perfectly round acidophilic inclusions about 1.5 μ in diameter, sometimes surrounded by a basophilic rim ("Gins bodies"). Rivers and Olitsky saw similar intranuclear inclusions, but round or oval, up to 2.0 μ in size in F.M.D. and in vesicular stomatitis. The etiological significance of these bodies is disputed by Waldman and Trautwein, Skomorokhov, Akulov, and others. Ruptured aphthae represent in uncomplicated cases superficial erosions, quickly covered from the edges and below by proliferating epithelium, but when complicated by other microbes, they become suppurating ulcers. Around aphthae, edema of adjacent tissues and regional lymph glands is often encountered. Particularly strong edema is noted on the lips and tongue. At autopsies, foot-and-mouth disease changes are most often found on the mucous membrane of the digestive tract: aphthae, erosions, ulcers, edema, catarrhal condition, ecchymoses. In individual cases, they are also found in the pharynx, bronchi, and esophagus. Then specific focal lesions of the cardiac muscles and skeletal musculature are observed, with myocarditis aphthosa most often being the cause of death. Depending on the severity of uncomplicated cases of F.M.D., autopsies reveal edema of the lungs, serous effusions into the pericardium and brain sinuses, hyperemia of parenchymatous organs, petechiae, and hemorrhages. Other, deeper degenerative changes in most organs are attributed to the complication of foot-and-mouth disease infection by other pathogenic microbes capable of causing suppuration, necrosis, septicemia, and pyemia. These include in animals mainly processes occurring in the extremities leading to detachment of the horn or even to complete shedding of the hoof. Clinically, the symptoms of foot-and-mouth disease in their main features differ comparatively little in various susceptible animals and in humans. The incubation period lasts 2-7 days, rarely longer, and in artificial infection it can be reduced to 12-16 hours. The formation of the primary aphtha at the site of virus introduction occurs without fever, but from the moment the virus from it enters the bloodstream, on average after 1-2 days, a high rise in temperature occurs, which then ceases (sometimes already after 6-24 hours) when secondary aphthae appear at the favorite sites, to not return again if the course of the disease is not complicated by secondary infection. Even before the full development of the foot-and-mouth disease exanthema, animals show signs of general malaise, decreased appetite, sensitivity of the oral mucous membrane, salivation, digestive disorders (constipation or diarrhea), decreased milk yield; animals avoid movement, stand still or lie down. Depending on the species and condition of the animals, age, and the future localization of aphthae, the degree of these symptoms, as well as their further intensification or weakening, fluctuate within wide limits. To them may be added laryngitis, pharyngitis, complete loss of milk, lameness, myocarditis, and in cases complicated by secondary infection, bronchopneumonia, mastitis, loss of the hoof, and symptoms of sepsis and pyemia. There are cases when foot-and-mouth disease changes are limited to the oral cavity or digestive tract, not affecting the extremities, and vice versa. In most adult animals, F.M.D. has a favorable course: the soreness of erosions remaining after the rupture of the blisters, which occurs after 1-3 days, disappears and they are covered with epithelium, food intake and milk yield return to normal, ulcers on the extremities scar and horn formation is restored, but complete recovery sometimes requires several weeks. Young animals usually become very ill and die with signs of enteritis or myocarditis. Sometimes sporadic cases or limited epizootics of so-called "malignant foot-and-mouth disease" occur, when animals already in the stage of recovery, without signs of complications, suddenly die, or even animals without any prodromal phenomena suddenly die with symptoms of apoplexy. The clinical picture of F.M.D. in humans differs little from that described in animals. Since in the overwhelming majority of cases human infection, especially in children, occurs from consuming milk or dairy products containing the foot-and-mouth disease virus, primary aphthae form in the oral cavity or in the digestive tract.

In the latter case, they may remain clinically unnoticed. - In less frequent infections of persons having contact with sick animals, primary aphthae appear on the skin areas that served as portals of entry for the virus, i.e., on the hands or feet (in barefoot herders). The duration of the incubation period is 3-6 days. With the onset of virus generalization, the following are observed: elevated temperature, general malaise, headache, dryness in the mouth, sometimes constipation, vomiting, and aching in the limbs. Then the fever ceases with the appearance of secondary aphthae in the oral cavity and around the mouth, in the nasolabial folds, on the flexor side of the fingers, at the base of the nails, on the palms and soles, sometimes on the genital organs, and in rare cases on the conjunctiva of the eyes. In the mouth, the vesicles are usually the size of a pea and surrounded by a red rim. After 2-3 days, the aphthae rupture, exposing superficial, very sensitive erosions, which after several more days are covered with young epithelium. In uncomplicated cases, foot and mouth disease in adults usually runs relatively mildly and ends in complete recovery within 1-2 weeks. On the contrary, in children, who contract the disease more often than adults, foot and mouth disease often takes a severe gastrointestinal form, which is accompanied by abdominal pain, vomiting, diarrhea with blood admixture, and ends fatally. The diagnosis of F.M.D. usually presents no difficulties, especially in mass outbreaks, and is made on the basis of the existing symptom complex. In sporadic cases among animals and always in humans, anamnestic data are collected about the possible source of infection. In doubtful cases, diagnostic inoculation of guinea pigs on the scarified foot of the hind legs with lymph from the vesicles or tissue from the edge of ruptured aphthae is recommended. No reliable serodiagnostic methods for F.M.D. have yet been developed. From the point of view of differential diagnosis, it is necessary to exclude in animals mainly vesicular stomatitis, aphthous stomatitis of calves, stomatitis of various non-infectious origin, purulent lesions of the coronary band and interdigital cleft, localized on the udder vesicles, and in cases of lightning-fast course - anthrax, rinderpest, hemorrhagic septicemia. In humans, F.M.D. can be mistaken for herpes and vice versa. - Therapy for F.M.D. consists of symptomatic treatment of local manifestations with the help of antiseptic, astringent, and analgesic agents. There are no specific remedies for F.M.D., except for the blood or serum of convalescent animals or hyperimmune polyvalent serum, which, however, are used with some success only in animals in the very earliest stages of the disease (before the appearance of secondary aphthae). The fight against foot and mouth disease has not only anti-epizootic and livestock but also significant economic importance. This fight is almost exclusively of a preventive nature. To localize outbreaks of F.M.D. in places where it appears, a quarantine is established for all kinds of animals, feed, and animal products, as well as for people having contact with sick animals. In addition, around epizootic foci, a 'preventive ring zone' is established, in which quarantine restrictions on the movement of livestock also apply. To eliminate F.M.D. in epizootic foci, therapeutic injections of convalescent serum or, if possible, 'hyperimmune' serum are administered to animals in the very earliest stages of the disease; to other animals susceptible to F.M.D., except pigs, in affected or threatened farms, simultaneous inoculations with serum and virus obtained locally from sick individuals are performed. For pigs, passive immunization with serum alone is limited. The same passive method, which provides short-term protection (8-10 days), is used when necessary in the ring zone, on transport, at agricultural exhibitions, markets, etc. Purely active vaccinations with only live virus are still practiced at the present time where the simultaneous method cannot be carried out due to the lack of sera. The practical significance of active immunization with virus killed by formalin or carbolic acid is still in the study stage. In farms infected with F.M.D., it is necessary to carry out current and final disinfection (with 2% NaOH or 1% formalin) and decontamination of manure by the thermophilic method. Compliance with zoohygienic requirements contributes to a milder course of the disease and a shorter duration of the epizootic. Veterinary-sanitary supervision is not limited to the unfavorable farm but extends also to the communication routes serving it, to slaughterhouses and factories processing animal raw materials, to which material suspected of being infected with F.M.D. may be delivered. - Personal prevention for people dealing with foot and mouth disease animals and their products requires extreme cleanliness and disinfection of exposed skin areas. To avoid infection per os, milk from suspicious sources should be consumed only well-boiled or in sour form no earlier than 24-48 hours after souring.

A-Vladimirov.