Rabies

RABIES (hydrophobia, lyssa, rabies canina, German Wut, Tollwut, Hundswut, Wasserscheu, French la rage, English canine madness, rabidity), an acute infectious disease characteristic of all warm-blooded animals and man, widely distributed throughout the globe from the tropics (Oceania, India) to the polar circle (Greenland). Despite its wide geographical distribution, rabies does not affect various countries equally; thus, it is absent in Australia, Great Britain, Sweden, and Norway, whereas in other countries it is endemic (USSR, Poland, Hungary) and causes epizootic outbreaks. Carnivorous animals, both wild and domestic (dog, wolf, cat, etc.), fall ill with it mainly; other animals, birds, and humans contract rabies less frequently and almost exclusively as a result of bites by diseased carnivores. The main role in the spread of rabies belongs to dogs. Statistics from all countries of the world show that of all those who underwent Pasteur treatments, 88-90% were bitten by dogs; according to the same data, out of all people who died of hydrophobia, 85-91% also fall upon those bitten by dogs. As for the transmission of rabies by herbivores, the actual degree of danger from their bites is very small, and is denied by some authors altogether. Statistics from Russian Pasteur stations over the past 40 years indicate that out of 3,522 people bitten by cows, no one died of hydrophobia; out of 2,851 individuals bitten by horses, 1 died, i.e., 0.03%. Rats and mice, although they can contract rabies and transmit this disease through a bite, have little epidemiological significance. The question of the possibility of transmitting rabies from human to human has not been resolved to this day; meager information about such cases is insufficiently substantiated; apparently, this possibility is minimal. In our climate, rabies is encountered more often in the warm season than in the cold (58.9% in spring and summer and 41.1% in winter); but the more southern the country is located, the more evenly the cases are distributed throughout the year. The breed and sex of animals have no effect on susceptibility to rabies, and the effect of age is manifested only in the fact that the incubation period in young animals is shorter. The causative agent of rabies has not been discovered to the present time; it is well known, however, that the infectious principle is contained mainly in the saliva and nervous system of the diseased animal and can pass through bacterial filters. Spontaneous disease has not been observed by anyone; the disease in natural conditions always arises as a result of a bite by a rabid animal, although cases are known where infection took place even without a bite, as a result of saliva getting onto fresh scratches and abrasions of the skin. Infection through mucous membranes, as experiments show, is also possible: a case of human death after saliva got into the eye has been described. Per os, as experience shows, infection does not occur either in animals (dogs, wolves, foxes; mice and rats are an exception) or in humans. Practically important is the fact that the saliva of a diseased animal becomes infectious several days (8-11) before the appearance of clinical signs of the disease. From the site of introduction, the infectious principle, as the majority of authors believe, spreads along the nerves; however, the possibility of spread via the lymph-hematogenous route is not excluded. The rabies virus is neurotropic and concentrates in the central nervous system upon disease. This feature of the rabies virus explains the varying duration of the incubation period. In humans, the incubation period ranges from 12 days to one year; according to some, up to several years. As clinical observations show, the duration of incubation depends on the localization and character of the bite; the closer the bite is to the central nervous system and the deeper and more extensive it is, the shorter the incubation period may be. The degree of injury and localization are not the only factors influencing the duration of incubation; here, apparently, the resistance of the infected organism, the quantity and virulence of the pathogen itself, subject to significant fluctuations in each individual case, play a role. In humans, the disease most often (59.3%) occurs 20-60 days after the bite; incubation of 12-15 days is rare (5.6%); incubations over 200 days are also rare (5.3%). Incubation of 1 year is a very rare phenomenon; incubation of more than a year and even several years has been described, but has not been scientifically verified and is therefore doubtful. In dogs, an incubation period of 14-30 days occurs in 56.3%, from 30 to 60 days in 33.3%; horses, cattle, and sheep fall ill with approximately the same incubation. Clinic. By the beginning of the disease, the rabies poison penetrates the central nervous system: first it irritates it, then depresses it. Depending on this, one distinguishes: 1) the stage of precursors (stadium prodromorum), 2) the stage of excitation (stadium irritationis), and 3) the paralytic stage (stadium paralyticum). In animals, two forms of the disease have long been distinguished: furious and quiet, or paralytic. In dogs with the furious form of rabies, the prodromal period lasts 1-2 days: the animal becomes irritable, hides, stops eating. Then excitation sets on with convulsive fits, lasting 3-4 days: the animal tends to run, bites surrounding people and animals, swallows inedible objects (rags, wood chips, stones, etc.); hydrophobia is an inconstant sign, and the animal can drink and even swim across rivers. Following these phenomena, paralysis of the lower jaw and pharynx sets in, and then of the posterior part of the body. Severe salivation appears, and with increasing paralysis on the 5th-7th day from the onset of the disease, death ensues. In the paralytic form, the period of excitation is absent, paralysis sets in earlier, the animal does not bite, responds to the owner's call, and dies in a few days. In dogs, the most characteristic sign is a change in voice and manner of barking: the sounds are somewhat hoarse, sometimes high, sometimes low compared to the norm, the bark is more like a hoarse howl. Signs of rabies in other animals are very similar to those described, but in cats rabies is characterized, in addition, by sharp excitation: they attack people and can inflict severe injuries. The disease lasts 2-4 days in them. Horses usually behave very restlessly, chew the manger, dig the ground with hooves, bite themselves, attack other animals and even humans. Cattle roar loudly, dig the ground, tend to attack animals and people. Death occurs in 3-6 days. Rabies in humans also proceeds in the form of a neuropsychiatric disorder. The prodromal period lasts 1-2 days; in the majority, it is expressed by the fact that drawing, aching pains appear at the site of the bite or along the nerve trunks extending from this place, directed centripetally; to all this are added dyspeptic phenomena, restlessness, agonizing expectation of death with short attacks of acute anguish or confusion, restless sleep with nightmares or complete insomnia. In about two days, the temperature rises (37.2-37.3°), and the disease passes into the next stage; sometimes it is impossible to demarcate the stages. The second stage is characterized by the appearance of sharp hyperesthesia of the senses: the sight of shiny objects, a slight noise, the slightest touch to the body, even a breath in the face can cause general convulsions. An attempt to drink causes a spasm of the swallowing muscles, which makes it impossible to quench the agonizing thirst. This symptom gave rise to naming the entire disease hydrophobia, although it is not encountered in all cases of rabies; on the other hand, it is also observed in hysterical disorders and tetanus. Among other symptoms of brainstem damage, one should note: sharp disorder of respiration, circulation (pulse 150-180 per minute), rise in temperature (up to 40° and higher), dilation of pupils, disturbance of convergence, hoarseness of voice. The psychiatric picture is characterized by attacks of the strongest fear, forcing the patient to rush about in search of salvation; sometimes clouding of consciousness appears with visual and auditory hallucinations of a terrifying nature, delirium, and strong motor excitation. In the intervals between attacks, the patient retains clarity of consciousness and a correct assessment of his situation. It is considered that rabies patients are very dangerous to others, since during attacks of excitation they tend to bite; these fears are apparently greatly exaggerated and are based on convulsive twitchings of the muscles of the face, tongue, and masticatory muscles. This period of the disease lasts 2-3 days and sometimes ends in death (or the disease enters the paralytic stage): attacks of excitation subside, paralysis of the lower extremities develops, widespread convulsions, incontinence or retention of urine, speech disorder, Cheyne-Stokes respiration, decline of mental activity. This stage lasts 2-5-18 hours and ends with a short agony (15-30 minutes). The disease lasts a total of 2-5, rarely 8 days. Cases of a mild course of the disease without strong excitation are encountered. Differential diagnosis at the beginning of the disease is not easy; it is necessary to carry it out not only with organic diseases (meningitis, tetanus, acute delirium), but also with hysteria, which can give a picture of hydrophobia under the influence of fear of rabies after a bite by some animal (false rabies). Treatment is symptomatic, usually the use of narcotics (morphine).

There is still no specific treatment, and the prognosis is considered very unfavorable for humans. At present, there are data on the recovery, admittedly very rare, of dogs from rabies, and the saliva of such animals continues to be virulent 16 days after recovery, as established by animal experiments. The pathological-anatomical picture of human rabies is macroscopically characterized by hyperemia of the brain and spinal cord, some swelling of the membranes, sometimes hemorrhages in them, and small foci of softening. The spleen is not enlarged. In dogs, foreign bodies (straw, rags, pieces of wood) are found in the stomach in 65% of cases. Microscopically, the process can be characterized as non-suppurative (sometimes hemorrhagic) encephalitis. The following are usually discovered: 1) strong changes in the cells of the cerebral cortex, mainly the nuclei of the medulla oblongata and spinal cord; the shape of the cells, their size, and internal content are altered (chromatolysis, vacuolization, wrinkling of the nucleus and its displacement to the periphery); phenomena of neuronophagia; the axis-cylinder process is very uneven, swollen in places, protoplasmic processes are convoluted; 2) proliferation of glial elements is found, the formation of cellular glial nodules, so-called granulomas, especially in the dorsal part of the medulla oblongata and in the intervertebral ganglia (described by Babes as rabies nodules - nodules rabiques). Very often the most intense changes are noted in the Gasserian ganglia (Davydovsky, Dvizhkov); 3) a strong vascular reaction is also noted, expressed in the dilation of vessels, changes in their walls, perivascular infiltration, and hemorrhages (especially in the third and fourth ventricles of the brain); 4) significant changes in the autonomic nervous system, sympathetic ganglia, mainly cervical. A general remark regarding changes in the nervous system may be the indication of the absence of a definite relationship between the site of the bite and the corresponding segment of the spinal cord; 5) the presence of Negri bodies, specific for rabies, in the nerve cells of the central nervous system, especially in the cells of Ammon's horn and the cerebellum [see separate table (p. 487-488), Fig. 4]. Negri bodies are almost always found in rabies (87-91%) if the animal died from this disease. According to Dvizhkov and Bogoslovsky, Negri bodies in human material are found in 90.5%. The presence of Negri bodies always speaks in favor of rabies; conversely, their absence does not at all speak for the absence of rabies, especially in cases where the animal was killed early, since it is known that on the second day of the disease they are extremely rare. There is a solid literature on Negri bodies, with some authors seeing them as the parasite of rabies, and others as a specific cell change under the influence of the rabies virus. If the microscopic examination gave a negative result, then inoculation of the suspicious brain into a rabbit is performed. This is the most reliable method of diagnosis; however, it is not always faultless, especially if the material (brain) has rotted. In addition, the rabbit may fall ill not on the 16th-21st day after infection, as usually happens, but later (on the hundredth day); therefore, this method is of more theoretical interest than practical. Serological reactions, despite numerous attempts, are not specific and have no practical application.

Since ancient times to the present day, a large number of diverse remedies have been used to prevent rabies, but all of them have survived only because they give an apparent success. Man, fortunately, is little susceptible to rabies: most authors acknowledge that out of those bitten by undoubtedly rabid animals, only about half fall ill without treatment (Leblanc 16.6%, Tarde 30-50%, Renault 64%, Pitet 58%, Proust 49.4%). The only rational method protecting against rabies is vaccination according to Pasteur's method, proposed by him in 1885. The essence of the method is as follows. Pasteur, Roux, Chamberland, and Thuillier, experimenting with rabies, found that a rabbit inoculated under the dura mater with a suspension of ground brain of a rabid dog (the so-called "poison of street rabies") falls ill on the 16th-21st day. If the brain of such a rabbit that died from rabies is inoculated in a similar way to another, and then from it to a third, and so on, upon transfer from rabbit to rabbit, the incubation period is shortened. At the 133rd passage, it turned out that the incubation period was reduced to 6-7 days and did not change further with subsequent passages. Consequently, the rabies poison began to possess constant properties, which is why it was named by Pasteur the "fixed" virus (virus fixe). It turned out that, having reached the limit of virulence for the rabbit, such passage virus (otherwise virus fixe, or laboratory virus) weakened in relation to other animals. Pasteur, taking the spinal cord of such a rabbit and suspending it in a jar with caustic potassium, subjected it to drying for 14 days. It turned out that the brain completely lost its virulent properties and, ground with broth, when injected into a rabbit and a dog in any quantity, did not cause them to fall ill. By successively injecting dogs under the skin with a suspension of such a brain dried for 14 days, then 13, 12, etc., down to 0 days of drying, i.e., fresh virulent brain, Pasteur achieved complete immunity to rabies in them. Such an immunized dog did not fall ill with rabies even after inoculation of street poison sub duram. These experiments formed the basis of anti-rabies vaccination of humans, used at present all over the world at so-called Pasteur stations (see). The laboratory rabies poison (or virus fixe) is available at every Pasteur station, where it is maintained by inoculation under the dura mater from rabbit to rabbit. But Pasteur's method is not used everywhere now. The principle, of course, remained the same (the starting material for the vaccine is everywhere virus fixe, i.e., the brain of a rabbit that died from passage rabies), only the method of its attenuation changed. Pasteur's original method has also been modified. In Paris, vaccination is currently started with a brain dried for five days; Pasteur stations in the USSR use the brain starting from 4- or 3-day drying. Vaccination schedules have also changed. Some institutes use the Högyes method - attenuation of the fresh virus by diluting a ground thin brain suspension several thousand times with physiological saline solution. Some use carbolic acid for attenuation, adding it to the ground fresh brain, as suggested by Fermi. Sometimes the virus is attenuated by heating from 50 to 80°. Recently Alevisatos proposed a method of attenuation with ether, etc. Calmette showed that glycerin is a good agent for preserving the virus; therefore, stations with a small number of vaccinees have long used the preservation of pieces of virulent brain in glycerin to prepare the vaccine. Kraus applied this method to send material to the field, and the Berlin R. Koch Institute prepares an emulsion from the brain with glycerin in a ratio of 1:9 and uses it to prepare the vaccine, diluting it ex tempore 25 times with physiological saline solution. Many institutes both in the USSR and in Germany use this method of brain processing for sending out for the purpose of vaccinating those bitten in the field. With all methods of brain processing, vaccinations for therapeutic purposes are given subcutaneously. The course of treatment with all vaccination methods varies depending on the nature and location of the bite and usually lasts from 10 to 22-30 days. For severe bites to the head, almost everywhere since the time of Pasteur, a repeated course of treatment of varying duration has been used. Pasteur vaccination usually produces no reaction, neither local nor general; there are generally no contraindications to it, but it must be borne in mind that in chronic malaria it provokes an attack, and nervous phenomena in malaria are exacerbated. The same can be said about tuberculosis. In rare cases (on average, 1 per 10,000 vaccinated), vaccinees develop neurological complications, expressed either as monoplegias of individual nerves, most often the facial nerve, or paraplegias of greater or lesser severity. Usually, such complications end in recovery; however, fatal cases have also been described. The cause of such complications is not entirely clear. Some speak of atypical, weakened (under the influence of vaccinations) forms of street rabies; others about the effect of only the rabies toxin; finally, others (and this is apparently more probable) connect the indicated phenomena with infection by virus fixe; the latter was discovered by Kotzervalov and others "in the brain substance of people who died from vaccination paralyses.

For the practical physician, the scheme of Panisset and Verge can serve as a reference point when a person is bitten by an animal: Biting animal Bitten 1. Died earlier than 15 days after the bite 2. Killed before 15 days

» 4. It remained unknown 5. Alive and placed j a) fell ill with rabies b) died from rabies c) died from other diseases a) fell ill and shows suspicious clinical signs e) fell ill, but on the 15th day did not die, there are no suspicious clinical signs D) alive and healthy after 15 days of observation under observation for 15 days. During the 15 days of observation: connection with the danger and material losses that a sick animal can cause; 2) prohibition of keeping dogs off the leash; 3) obligation to put muzzles on dogs. In England, moreover, the import of dogs from the continent is prohibited, and in other countries (Sweden, Norway, Finland) a dog can be imported only after a 6-month quarantine. Recently, a large number of reports have appeared (Japan, America) on the use of anti-rabies vaccination according to the Umeno method for prophylactic purposes in healthy dogs. It is pointed out that this method has yielded excellent results. In Tokyo and Yokohama, out of 104,629 vaccinated dogs, 49 fell ill with rabies, while among the unvaccinated, which Must receive anti-rabies vaccinations Continue observation Vaccinations are not needed Immunity sets in no earlier than 15 days after the end of vaccinations; therefore, a favorable outcome can be counted on only in those cases when the incubation period can be assumed to be about a month. It is clear that vaccination must be started as early as possible after the bite. The duration of immunity for humans (by analogy with animals) can be considered about 6 months. The mortality rate from rabies treated with Pasteur vaccination in different institutes varies, which depends mainly on the diversity of statistical accounting and the accuracy of collecting information about the dead. The significance of individual vaccination methods at the present time cannot be assessed, since there are no equivalent numerical data that could be compared. On average, across all institutes, total mortality ranges from 1.23% to 0.25%, and reduced mortality, i.e., where only deaths occurring 14 days after the end of vaccination are taken into account, ranges from 0.83 to 0.16%. If we assume the percentage of mortality among those bitten by rabid animals without treatment to be equal to only ten, then mortality after Pasteur vaccinations decreases, approximately, tenfold. Although Pasteur vaccinations are of great help in the prevention of rabies in humans, they are nevertheless not a measure that reduces the possibility of human and animal infection. Since the main carriers of infection are dogs, to stop rabies, the necessary measures are directed mainly at the carriers. Laws and regulations of governments of various countries regarding the fight against rabies are generally similar; the difference concerns only details. Schematically, these measures boil down to the following: 1) restriction of the number of dogs, which can be carried out by: a) a tax on dogs, b) control over dogs (extermination of stray dogs), c) civil and criminal liability of owners for losses caused by their dog, both healthy and rabid, d) health education, acquainting the population which number about 7% of the vaccinated, there were 1,699 cases of rabies. At the present time, mass experiments of this kind are being carried out in several countries (e.g., in America). Laboratory-type experiments are also being carried out in the USSR (Moscow, Leningrad, Rostov-on-Don), but do not yet have practical application. As for anti-epizootic rather than prophylactic measures, schematically they boil down to the following: 1) the sick animal must be killed immediately; 2) all dogs and cats bitten by this animal must also be killed; 3) valuable and large domestic animals bitten by rabid animals must be isolated and kept under the supervision of a veterinarian for at least three months; 4) all stray dogs in the area where there were cases of rabies must be killed; 5) all other dogs of the locality where a case of rabies has been detected must be immediately tied up and kept as such for three months; 6) people bitten by rabid animals must be immediately sent to the nearest Pasteur station to undergo preventive vaccinations.