Rabies Lyssa rabies
Rabies it is called an infectious disease caused by a neurotropic filtering virus that is transmitted to healthy people and animals, mainly by the bites of rabies animals. The disease is expressed by extreme nervous arousal with loss of consciousness and ends with paralysis and death. People, all domestic animals and birds, as well as wild animals are susceptible to rabies.
Historical overview and prevalence. Although rabies of dogs, other animals, and humans was known long before our era, and the transmission of sick dogs through sick bites was obvious, the entities did not know it. Only relatively recently did Louis Pasteur learn from him the location of the infectious onset in the sick body, methods of experimental artificial infection and developed a method of protection against this infection. Further work, in particular, Negri’s discovery of special inclusions in the ganglion cells of the brain, facilitated the ability to recognize and differentiate rabies from other nervous diseases; finally, almost simultaneously with the discovery of Negri, the etiology of rabies was clarified. invisible pathogen. filtering virus.
In some countries, rabies is completely eliminated, in others it is minimized, in the third, on the contrary, it takes more or less significant number of victims. There have been no cases of rabies in England since 1921. In Denmark and Sweden, rabies has not been known for about 100 years. Norway is free of infection; the latter is not found in Australia either. Before the war of 1941.1945 Albania, Belgium, Luxembourg, Holland, Yugoslavia and Switzerland freed from rabies.
Etiology. The causative agent of rabies is an invisible filtering virus.
Pasteur and his students were the first to determine that the virus is found in the greatest amount in the brain and spinal cord of sick animals. It is contained (significantly less) in the peripheral nervous system. It has long been known for the presence of the virus in the saliva of patients with which it is transmitted to bitten healthy animals. The presence of the virus is proven in salivary, lacrimal, pancreas and mammary glands, adrenal glands and spleen. Some authors also found the virus in the blood of rabid animals, but in small quantities, and intermittently.
Street rabies virus and fixe virus. The work of Pasteur and his staff for the first time established the possibility of shortening the incubation period for artificial infection of rabbits with individual viruses obtained from animals and humans with their natural infection, but previously transmitted through rabbits. As the number of passages increased, the incubation period was also shortened, until the moment of fixation came at a certain period of 6. 7 days, which was no longer shortened and lengthened. The strains or viruses obtained in this way, Pasteur called fixe viruses, or passive viruses.
In Pasteur’s experiments, 100 passages through rabbits were required to produce such a constant virus. However, subsequent experiments showed that in this phenomenon there is no strict regularity; other researchers received fixed viruses after a significantly smaller number of passages; in some rare cases, natural rabies viruses showed a very short incubation period, 3.4 days or less, after very few rabbit infections.
The virus from natural cases of rabies usually causes rabies disease only after 14.21 days, unlike fixe virus with a short incubation period. The second feature of a fixed virus. its weak virulence for dogs and guinea pigs; when the latter are artificially infected, it does not cause a violent, natural form of rabies, but only a quiet, paralytic.
The fixe virus turned out to be slightly aggressive for all other animals, except rabbits, with respect to which its virulence, on the contrary, is greater. Man is also apparently insensitive to fixe virus; in the practice of pastoral laboratories all over the world, cases of infection with the fixe virus are completely unknown, while such cases were observed during manipulations with the street virus. The fixe virus serves as a protective vaccine against rabies in humans and animals.
The immersion of the brain of a rabbit containing fixe virus in bicarbonate water by 7. 12 days changes the property of this virus to cause a quiet, paralytic form of rabies in dogs: with intracerebral administration, the brain treated with the fixe virus treated in this way causes all signs of rabies rabies to appear in dogs.
Negri bodies and their nature. Negri discovered in 1903 in the protoplasm of cells of the central nervous system special inclusions found in rabies and absent in other nervous diseases.
These formations, round or oval in shape and of various sizes, were found in the protoplasm of large, ganglion cells and their processes, in a particularly large number in ammonian horns, in nerve cells of the cerebral cortex, in Purkinje cells, in the cerebellum, in oblong and spinal nerve cells the brain, as well as outside the cells, freely, in the nervous tissue. The presence of Negri bodies in these parts of the central nervous system in various animals and people who died from rabies was also established by a number of other researchers who soon confirmed the discovery of Negri, which simplified and facilitated the laboratory diagnosis of rabies.
Negri was inclined to consider the found formations as the causative agents of rabies, all the more so since they were found not only in natural, “street” (as Pasteur called it) rabies, but also in experimentally caused infections, regardless of the way the infectious material was injected into the animal.
By different methods of differentiated coloring of the bodies, their special structure was revealed, in which, in addition to the main homogeneous substance, they distinguish strongly refracting light and otherwise colored small round grains, or granules. The average Negri body size in the cross section reaches 6 p., BUT there are smaller and significantly larger formations, up to 27 p, and in one large ganglion cell there can be single or many formations, up to 4. 6. Checks for the discovery of Negri showed that with genuine rabies, Negri bodies can be absent only in a small percentage of cases, while they never occur in the central nervous system of healthy animals.
Negri expressed the opinion that the bodies discovered by him play the role of parasites that cause rabies, the nature of protozoa with protoplasm and the nucleus, met with serious objections from some researchers and the support of others. The debate about the nature of Negri bodies continues to the present; Negri advocates cite a number of considerations in his favor.
With rabies caused by street virus or fixe virus, even the smallest granular formations are detected by appropriate coloring. These formations are found not only in the central nervous system, but also in meningeal fluid, in the salivary glands, on the serous integuments of large body cavities. These formations are considered viral bodies. Granules lie not only freely, but also inside the cells in all these areas of the body affected by rabies. Like elemental bodies in smallpox, these viral bodies in rabies are cultivated in egg cultures, as well as in artificial nutrient media.
Coloring Negri bodies. For the detection of Negri bodies in the central nervous system of animals that died from rabies, mainly in histological sections, various authors have proposed many colorization methods.
Here we confine ourselves to a description of only a few of them, which give a clear picture of the structure of Negri bodies.
After preliminary fixation of the sections from the ammonian horns in the Cencker liquid or acetone, these sections are enclosed in paraffin and, after removal, they are stained.
Lentz Method. 1) Staining in eosin solution (Eosin B. extra hochst. 0.5; 60% ethyl alcohol 100.0). 1 minute. 2) Staining in a solution of methylene blue (Lefflerian methylene blue: saturated alcohol solution of Methylenblau B. Patenthochst. 30.0 and 0.01% potassium hydroxide 100.0). 1 minute. 3) Washing in water. 4) Dry drying with filter paper. 5) Differentiation in alkaline alcohol (absolute alcohol 30.01% solution of sodium hydroxide in absolute alcohol. 5 drops), while the drug allows you to distinguish between a weak color with eosin. 6) Differentiation in acidic alcohol (absolute alcohol 30.0; 50% acetic acid. 1 drop), while a faint blue color of a number of ganglionic strands is still noticeable. 7) Short rinse in absolute alcohol. 8) Xylene, Canadian Balm.
Glia cells are stained by this method in a delicate pinkish-red color, the protoplasm of ganglion cells. in pale blue, nuclei. somewhat darker. The nuclei of glia cells, leukocytes and cells of the walls of the capillaries are stained in black and blue, red blood cells. in cinnabar, and Negri. in bright color.
The Stucker method is simple and at the same time very demonstrative in terms of clarity of the structure of Negri bodies. For coloring, diluted Leffler’s methylene blue is used, and for differentiation. 1% solution of tannin. After the usual paraffin sections through xylene, alcohol and water, they are stained with Leffler blue diluted to complete transparency. Intensive staining is recommended. Differentiation in a 1% tannin solution is consistent with the color intensity and monitored under a microscope. As soon as the contours of the nerve cells are clearly detected, the differentiation is stopped and the preparation is washed in water, dried with filter paper, quickly passed through absolute alcohol and xylene and enclosed in Canadian balsam.
Muromtsev’s method. The coloring of Negri bodies by this method is considered by many authors to be extremely characteristic; at the same time, it is very simple and convenient for the diagnosis of rabies. Smears or preparations made from the ammonian horns of the studied brain are fixed in heated to 40. 50 ° methyl alcohol for at least 1 hour, then they are washed with water and stained for 10. 15 minutes in a 2% solution of Manson’s blue (Mansonblau). The coloring is followed by etching in a 10% aqueous solution of tannin and rinsing in water, drying and washing in a mixture of equal parts of alcohol and acetone. On a blue-green background, sharply delimited Purple formations with blue inner nucleoli appear, which show the diverse structure of Negri bodies. Although in this method the nerve cells are almost completely destroyed And the Negri bodies lie freely, due to the especially bright structure, they cannot be mixed with red blood cells and nuclei of glious cells.
Cultivation. The rabies virus can be cultivated in the chorion-allantois of the chicken egg. Under the influence of seeding the virus from the brain, numerous Negri bodies appear in the epithelial cells of the egg membrane. At the same time, it doesn’t matter whether the infection was caused by a street virus or fixe virus. By introducing a subdural culture from the chorion-allantois chicken embryo, rabies can be caused in a rabbit. Thus, Negri bodies must be regarded as the causative agent of rabies, and not as derivatives of cells; attach particular importance to this circumstance.
The fixe virus was cultured in tissue culture in 95 passages. It turned out to be virulent and possessing good immunogenic properties.
The cultivation of rabies virus is successful in vitro in the presence of embryonic brain tissue (brain of mice or rats). When using embryonic brain tissue and at the same time human or monkey serum (other sera are unsuitable), the virus can be cultured in passages. When cultured in eggs with embryos received up to 20 passages. The virus in chicken embryos or their brain is able to multiply when the embryos are aged 5. 14 days. Later, the amount of virus decreases and gradually completely disappears. Some chickens emerging from infected eggs behaved quite normally. The infectious onset develops more intensively in the brain. The culture virus turned out to be an effective antigen (protection experiments) both in a living state and after treatment with formalin.
Sustainability. Due to the fact that the rabies virus is found in the greatest number in the central nervous system and is closely connected with the nervous tissue, the study of its properties is very difficult; the data accumulated in this regard are small and do not completely reflect its true properties in its purest form.
In relation to elevated temperatures, the virus is unstable: it loses its virulence when heated to 45 ° C for 24 hours, at 50 ° C pathogenicity is lost within 1 hour, and at 52. 58 ° C is enough for the same purpose a half-hour action. Conversely, low temperatures (. 4 ° C. Yu. ° C. 25 ° C) do no harm to the rabies virus, but rather preserve it for periods of several months or more than a year.
Drying, as Pasteur has shown, leads to the weakening of the rabies virus and, apparently, to its gradual death. A 15-day drying of the spinal cord of a rabbit containing a virus in a jar of potassium hydroxide (Pasteur’s method) leads to its complete neutralization.
The effect of light on the virus is also detrimental: a 20-day exposure leads to a complete loss of the virulence of the brain containing the rabies virus.
Glycerin in a 50% solution preserves the rabies virus for up to 8 months and is therefore used when transporting suspicious brains to the laboratory for research on rabies, as well as when preserving viruses for laboratory purposes.
The virus is destroyed by 0.1% mercuric chloride solution in 2. 3 hours, 4% boric acid. in 15 minutes, 5% salicylic acid and 5% formalin. in 5 minutes.
The decay of the material containing the virus destroys the latter only slowly, especially at a low temperature, which delays rotting processes in general (virulence persists even after 2 months). Gastric juice weakens the virus and kills it after 20 hours. The bile is destructive to the virus. 10% ether protects the brain containing the virus from putrefactive bacteria, but does not kill rabies.
Susceptibility of various species of animals. People, all domestic animals and birds, as well as small experienced animals are susceptible to rabies: rabbits, guinea pigs, mice, rats. Cases of natural rabies were observed in deer, camels, antelopes, badgers, jackals, hyenas, martens, roe, wild goats, bear, lion, porcupine, hares, squirrels and other animals.
A reliable method of artificial experimental infection is the intra-cerebral or subdural injection of infectious material, as well as intraneural and intramuscular injections of it. The corneal, intraocular, nasal, intravenous, cutaneous and subcutaneous methods of application of rabies virus are less effective. Guinea pig and rabbit are most suitable for laboratory experiments. In these rodents, infection with the fixe virus usually leads to the so-called paralytic, or quiet, form of rabies.
Brushes of infection and ways of natural infection. Since ancient times it has been known that rabies is transmitted to healthy dogs (primarily), as well as to other animals, mainly through the bites of sick dogs. It is now generally accepted that rabies is spread predominantly by stray dogs. Their free lifestyle, constant movement, constant desire to enter into direct contact with their own kind, hostility to cats and the frequent use of teeth as a tool of defense and attack contribute to the spread of rabies if the dog is infected with it. Cats play a much smaller role in this regard, and other domestic animals take very little part in the transmission of the infection.
Wild animals, the wolf and the fox, also transmit rabies; however, compared to dogs, they have a completely secondary role. They also indicate the participation of rats in the spread of the infection, but no one has yet been able to observe the epizootic of rabies in rats.
The main route of transmission of infection. bite. Occasionally, a disease also arises as a result of contact with infectious material, for example, with the saliva of a rabid animal, especially if it gets on the integument of the skin or mucous membranes.
If infection through the digestive tract with contaminated feed takes place, then only as an exceptional rarity. Not. reasons to attach any importance to the mediation of parasites (fleas or lice) or stinging insects. The transmission of infection with milk can hardly play any serious role, although the possibility of finding the virus has been proven in milk. Intrauterine infection with rabies of the fetus was established experimentally; it occurs, obviously, through the placental circle of blood circulation. Such cases were observed only in experiments with small laboratory animals.
Infectiousness of saliva. Researchers paid much attention to the question of how long after infection a bitten animal can secrete an active virus and spread the infection. It turned out that animals a few days before the manifestation of clinical signs of rabies in them contain the virus in their saliva. The bites of such animals cause disease to injured people or animals.
The maximum period of saliva infectivity observed in the literature in the pre-clinical period of rabies is 15 days. often, saliva infectivity is noted 3. 3. 10. 10. 12 days before the onset of clinical signs of rabies.
Along with these extremely important data for practice, showing how seriously it is necessary to approach every bite of even a healthy looking dog, there were also fears of a different order: could dogs artificially protected against rabies or naturally resistant to infection become carriers of infection in cases of bite by their rabid animals? The established fact is the recovery of individual animals after undoubtedly manifested clinical symptoms, or the so-called abortive rabies. However, healthy dogs that have not had a history of abortion rabies cannot be considered virus carriers; no cases of rabies have been reported in humans or animals after being bitten by long-term healthy dogs.
Pathogenesis. Already modern Pasteur is known that the favorite location of the virus in the infected body. central nervous system. The gateway for the introduction of the virus is, as a rule, almost the place of the bite. The question of how the virus penetrates the brain required serious and lengthy research. On the one hand, experiments and observations showed that the virus spreads along the nerves from the periphery to the center, on the other. Naturally, suggestions arose whether blood and lymph vessels were also involved in the transport of the virus.
Against the latter assumption were the experiments of infection of animals in the tail and anterior chamber of the eye. If the tail was amputated after 12 hours or the optic nerve was removed after 24 hours, infection did not occur. Virus infection tests through the lymph nodes were also unsuccessful. Finally, infection was made into the sciatic nerve, while cutting the spinal cord in the lumbar region, or infected animals were infected into the blood, cutting above the nerve and cauterizing it; rabies did not come. It was also possible to cause the effects of lesions only of those nerves that were included in the infected area, and to show that where the pathway for the virus was blocked by nerve transection, there were no clinical symptoms of damage to this area. When an infection was introduced into the subcutaneous tissue or peritoneum, where nerves were absent, rabies also did not occur.
In addition, many other experiments have been performed that show with sufficient convincing evidence that the rabies virus reaches the central nervous system only along the nerve paths. If it was found occasionally and in small quantities in the blood and lymphatic passages, then in order to get to the center of gravity, multiply there and create a picture of a typical disease, it must first penetrate the nerves.
In the central nervous system, the virus spreads centrifugally along the nerve pathways. With the rapid course of the vaccinated disease, the virus is found only in the nerve that is associated with the vaccination site, as well as in the brain and spinal cord; on the contrary, in a slow course, the virus disappears after some time from the nerves of the infected members, so that later they appear on the other side of the body, obviously, after passing through the corresponding segment of the spinal cord. Similarly, moving forward in a centrifugal direction, the virus penetrates the salivary glands and their secret. in saliva.
In the central nervous system, the virus damages nerve cells and blood vessels. Irritation of nerve cells initially leads to a state of excitement, impaired awareness, increased reflexes due to diseases of the medulla oblongata, to an increase in temperature, polyuria and the appearance of sugar in the urine. However, after some time, degeneration of nerve cells occurs; paralysis develops on this soil, among which there is paralysis of the respiratory muscles and ultimately determines the immediate cause of death. Due to vascular wall disease, perivascular small cell infiltrates occur. The pathogenic effect of rabies virus is presumably explained by the influence of toxic chemical products, the nature of which, however, is not yet known.
The incubation period. The latent period from the moment of infection to the onset of the first clinical symptoms of the disease with rabies varies widely.
The most important distributors of rabies. dogs. fall ill most often during the first 28 days after infection; over the next 30 days, the disease is almost also frequent, in the third month of incubation, cases of rabies are much less common, and in the future the percentage of diseases drops to units. In the first week after a bite, diseases are as rare as in the 5th and 7th month of incubation. In some cases, dogs became ill one year or more after infection. In general, the incubation period for rabies is rarely shorter than three weeks and longer than six. Period of 4. 5 months. a record, and the one-year incubation period should be approached with skepticism.
In horses, the incubation period is an average of 15. 60 days and lasts up to 4 months or more.
In cattle and other animals, fluctuations in the incubation period are also noted, with most diseases occurring in the first 2 months, and some cases were observed later, up to 1. 2 and even 3 years (Linier notes one case of a three-year incubation period in cattle )
Such is the incubation period in humans: 3. 15 months.
Such fluctuations in the incubation time depend in part on a greater or lesser dose of the infectious onset and on its virgosity, as well as on the strength of the wounds inflicted and their localization in the sense of proximity to the central nervous system; however, some cases of particularly long latent periods of infection are difficult to explain. The degree of individual susceptibility, as well as factors predisposing and weakening the body, can play an undoubted role here.
The long-term persistence of the virus at the site of its introduction has been experimentally proven.
The incidence rate of animals infected through animal bites is not easy to establish because of the difficulty in selecting statistical material.
In Austria for the period 1877. 1887 40% of bitten horses got rabies, among cattle and sheep. 50% goats. 20% of pigs. 36% Lyon Veterinary School establishes 20%, Alforta. 33% of rabies in bitten animals.
It can be considered on average that only about 30% of those bitten by really rabid animals get sick.
Forms and clinical picture. Distinguish atypical, or consumptive (consumptio. Exhaustion, exhaustion), abortive, paralytic and violent form of rabies.
Cases of atypical rabies in dogs occur subacute and are characterized by depletion and muscular atrophy, which is why this form is also called atrophic. Vaccinations of parts of the central nervous system, in particular, the medulla oblongata from dogs suffering from this form of rabies, in some cases manage to cause a typical picture of the disease in vaccinated animals. Atypical forms of rabies were often observed, especially during epizootics. Gastroenteritis in patients with rabies dogs should be considered as one of the most important symptoms.
The abortive form is understood to mean cases with typical phenomena, but ending in recovery.
Recovery of dogs from rabies was noted by Pasteur and confirmed by others. Recovery in experimental rabbits was recorded by Koch et al.
Despite the predominantly fatal outcome, rabies sometimes nevertheless goes into recovery, and the existence of abortive forms of rabies is beyond doubt.
A paralytic, or silent, form of rabies in dogs and other animals is observed in vivo, in approximately 15.20% of cases. In rabbits experimentally infected with the passage virus, it develops almost as a rule.
At the onset of the disease, the symptoms are the same as in violent rabies, but they are less pronounced. Masseters paralyze very quickly, as a result of which the mouth of the animal remains open all the time; from it hangs a violet tongue covered in dust. Often saliva flows out of the mouth with long, viscous strings. Usually the dog is motionless; her look is sullen, dull; eyes sunken into orbits. She has no tendency to bite if this form does not turn violent.
Quiet rabies usually ends in death in 2. 3 days. But there are atypical forms. For example, a dog rides on three legs. In the study of the fourth, sore legs do not find anything. The dog is locked in a cage, and after 2. 3 days lameness passes to the limb of the same name. it turns out paraplegia. Such paralytic events are sufficient to suspect rabies.
If the animal is not touched, it is not dangerous. And, conversely, when he is hurt, he defends himself and bites.
A case of hemorrhagic gastroenteritis in a dog that has been cured by copper-cement treatment is described. The dog was taken under observation because of a bite of its owner when giving medicine. Suddenly, on the 4th day, the dog was found dead. Negri bodies were found in her brain, and a rabbit infected with the brain fell due to rabies.
Similar forms of rabies are common in Greece.
With this form, the phenomena of arousal and extreme irritability are absent or very weakly expressed. In dogs with this form, after very short and slightly expressed symptoms of arousal, paralysis of the hind limbs and lower jaw (sagging) is observed. Typical manifestations of rabies, in the form of a sharply increased desire to bite:, salivation, cramps when swallowing, are absent or are only outlined. Paralysis of the lower jaw and back, sometimes occurring independently of each other, is very characteristic of a quiet form.
According to Pasteur, violent form of rabies is associated with a primary lesion of the head, and a quiet form. with a predominant spinal cord lesion. In general, mixed forms are also observed in various transitions in the manifestation of the disease in individual individuals.
The clinical presentation of the disease in individual animal species in its classical, or dominant, form of violent rabies is given in the further presentation.