Even 150 years ago, a person bitten by a rabid animal was doomed. Today, scientists are improving weapons in the war against an ancient and extremely dangerous enemy - the rabies virus.
Pasteur's legacy On the memorial plaque of the house in which Pasteur's first laboratory was located, his discoveries are listed: the enzymatic nature of fermentation, the refutation of the hypothesis of the spontaneous generation of microorganisms, the development of ideas about artificial immunity, the creation of vaccines against chicken cholera, anthrax and rabies. Pasteurization and other “little things” were not included in this list
The first, but extremely important step towards the fight against rabies was taken by the brilliant French chemist and microbiologist Louis Pasteur. He began developing a vaccine against this disease in 1880, after he had to observe the agony of a five-year-old girl bitten by a rabid dog.
Rabbits and dogs
Although rabies was first described in the 1st century BC. Roman Cornelius Celsus, almost 2000 years later, negligible little was known about this disease. It was not until 1903, eight years after Pasteur's death, that the French physician Pierre Remlenger discovered that rabies was caused by a submicroscopic life form - a filterable virus.
Pasteur, without this information, was nevertheless not going to give up: to create a vaccine, he chose a workaround - to find a container for the “poison” and turn it into an antidote. It was reliably known that something transmitted from a sick animal to another animal or person along with infected saliva infects nervous system. During the experiments, it was found that the disease had a very long incubation period, but this only spurred Pasteur and his colleagues, since it meant that doctors had the opportunity to influence the slowly developing pathological process, — the “poison” needed to reach the spinal cord and then the brain through the peripheral nerves.
Then experiments began on rabbits in order to obtain the most lethal rabies “poison” in large quantities. After dozens of transfers of brain tissue from a sick animal to the brain of a healthy one, from that to the next, etc., scientists managed to achieve that a standard extract from the brain killed a rabbit in exactly seven days instead of the usual 16-21. Now it was necessary to find a way to weaken the rabies pathogen (the method of creating vaccines - weakening the pathogen - was also Pasteur’s discovery). And they found a way: drying rabbit brain tissue soaked in the virus for two weeks over moisture-absorbing alkali.
After administering a suspension of the resulting drug, the dog infected with rabies not only recovered, but also became completely immune to rabies, no matter how much “poison” was injected into it.
Having finally made sure that vaccinated dogs were not affected by the same seven-day laboratory “poison,” the researchers conducted a cruel experiment: they introduced their rabid relatives to the vaccinated dogs. The bitten mongrels did not get sick!
40 injections in the stomach
Then it was the people's turn. But where to find volunteers? Driven to despair, Pasteur was ready to sacrifice himself for the sake of science, but, fortunately, His Majesty Chance intervened.
On July 6, 1885, a tearful woman appeared on the threshold of Pasteur’s Paris laboratory, holding the hand of her nine-year-old son, Joseph Meister. Three days earlier, the boy was bitten by a rabid dog, causing 14 open wounds. The consequences were quite predictable: at that time it was already known that death in such cases was almost inevitable. However, the boy's father had heard a lot about Pasteur's work and insisted on bringing the child from Alsace to Paris. After serious hesitation, Pasteur injected the little patient with an experimental drug, and Joseph became the first person in history to be saved from rabies.
Know the enemy by sight
The causative agent of rabies (Rabies virus) belongs to the family of rhabdoviruses (Rhabdoviridae), containing a single-stranded linear RNA molecule, the genus Lyssavirus. In shape it resembles a bullet with a length of about 180 and a diameter of 75 nm. Currently, 7 genotypes are known.
The rabies virus has tropism (affinity) for nervous tissue, just as influenza viruses have affinity for the epithelium of the respiratory tract. It penetrates the peripheral nerves and moves at a speed of approximately 3 mm/h central departments nervous system. Then, through a neurogenic route, it spreads to other organs, mainly to salivary glands.
The likelihood of the disease depends on the location and severity of the bites: when bitten by rabid animals on the face and neck, rabies develops on average in 90% of cases, in the hands - in 63%, and in the thighs and arms above the elbow - only in 23% of cases.
The main wild animals - sources of infection - are wolves, foxes, jackals, raccoon dogs, badgers, skunks, and bats. Among domestic animals, cats and dogs are dangerous, and it is the latter that account for the maximum number of confirmed cases of rabies transmission to humans. Most sick animals die within 7-10 days, the only exception described is the yellow fox-shaped mongoose Cynictis penicillata, which is capable of carrying the virus without developing a clinical picture of infection for several years.
The most characteristic and reliable sign The presence of a virus in a human or animal body is the detection of so-called Negri bodies, specific inclusions in the cytoplasm of neurons with a diameter of about 10 nm. However, in 20% of patients Negri bodies cannot be found, so their absence does not exclude the diagnosis of rabies.
The photo shows the rabies virus under an electron microscope.
People from all over the world flocked to Paris - Algerians, Australians, Americans, Russians, and often they knew only one word in French: “Pasteur”. Despite such success, the discoverer of a vaccine against a deadly disease had to hear the word “killer” addressed to him. The fact is that not all those bitten survived after vaccination. In vain Pasteur tried to explain that they contacted too late - some two weeks after the animal attack, and some even a month and a half later. In 1887, at a meeting of the Academy of Medicine, colleagues directly accused Pasteur of simply killing people with pieces of rabbit brains. The scientist, who devoted all his strength to science, could not stand it - on October 23 he suffered a second stroke, from which he never recovered until his death in 1895.
But they supported him ordinary people. By subscription, over a year and a half, residents of many countries around the world collected 2.5 million francs, with which the Pasteur Institute was created, officially opened on November 14, 1888. On its territory there is a museum and tomb of a researcher who saved humanity from death. dangerous infection. The date of Pasteur's death, September 28, was chosen by the World Health Organization (WHO) for its annual world day fight against rabies.
For a long time the vaccine was injected under the skin of the anterior abdominal wall, and up to 40 injections were required to complete the full course. A modern immunotherapy drug is administered intramuscularly into the shoulder; six visits to the emergency room are sufficient.
Milwaukee Miracle
During the 20th century, the situation with rabies was clear: if the victim was not vaccinated on time or did not receive the vaccine at all, the matter ended tragically. According to WHO estimates, 50-55 thousand people die every year in the world after attacks by rabid animals, 95% of them occur in Africa and Asia.
The possibility of fully treating the infection was only discussed in the 21st century. This was connected with the case of American Gina Gies, who for the first time in the history of medicine did not receive a vaccine, but survived after the onset of rabies symptoms. On September 12, 2004, 15-year-old Gina caught a bat that bit her on the finger. The parents did not consult a doctor, considering the wound to be trivial, but after 37 days the girl developed a clinical picture of infection: a rise in temperature to 39 °C, tremors, double vision, difficulty speaking - all signs of damage to the central nervous system. Gina was sent to Children's Hospital of Wisconsin, and rabies was confirmed at the Centers for Disease Control and Prevention (CDC) labs in Atlanta.
Viruses and bacteria
WITH bacterial infections humanity is fighting relatively successfully. Antibiotics and vaccines are doing their job, and sanitation and epidemiology are excellent. With viruses everything is much more complicated. Suffice it to recall the flu, which the world's population suffers from with enviable regularity, despite all the achievements of science and the availability of vaccines and antiviral drugs.
This is primarily due to the ability of viruses to change in the most unpredictable ways. Some, like influenza pathogens, change the proteins of their shell, like gloves, so it is still not possible to develop high-precision weapons against them.
In the fight against diseases, success came when a weak double was discovered in the virus, which did not kill a person, but left behind powerful cross-immunity. Deliberate infection with a weaker strain made it possible to protect against a deadly one. The classic case from which the history of vaccination began is natural and cowpox, then a similar story was repeated with polio. In the summer of 2012, there was hope that a similar scenario would help control rabies.
The parents were offered to try an experimental treatment method on the girl. Having received consent, doctors used ketamine and midazolam to put the patient into an artificial coma, essentially turning off her brain. She also received antiviral therapy with a combination of ribavirin and amantadine. Doctors kept her in this condition until her immune system began to produce enough antibodies to cope with the virus. This took six days.
A month later, tests confirmed that there was no virus in the girl’s body. Moreover, brain functions were minimally impaired - she graduated from school, and a year later received a driver's license. Currently, Gina has graduated from college and intends to continue her studies at the university. It is not surprising that she sees biology or veterinary medicine as her future profession, and plans to specialize in the field of rabies.
To enter a cell, the rabies virus uses the endosomal transport system: the cell itself must capture it and draw in the resulting cell membrane vesicle - endosome, “inner body” - into the cytoplasm. Activation of this process occurs after the virus binds to special receptor proteins on cell membrane. The resulting endosome disintegrates over time, the viral particle releases RNA, and then everything goes according to the standard scenario.
The treatment protocol that was used on the girl was called the “Milwaukee” or “Wisconsin” protocol. They have repeatedly tried to reproduce it in other medical institutions... but, alas, without much success. The first version of the protocol was tested on 25 patients, of which only two survived. The second version, which removed ribavirin but added drugs to prevent vasospasm, was used in ten patients and prevented the death of two of them.
During epidemiological investigations, it turned out that patients who were cured using the Milwaukee Protocol were bitten by bats. It is this fact that has allowed some scientists to suggest that in fact the treatment method has nothing to do with it, but the point is precisely these mammals, or rather, the fact that they are infected with a different strain of the virus, less dangerous to humans.
The Bat Riddle
In 2012, this assumption received the first confirmation. An article by a group of CDC experts, American military virologists and epidemiologists from the Peruvian Ministry of Health appeared in the American Journal of Tropical Medicine and Hygiene. The results of their research produced the effect of a bomb exploding: in the Peruvian jungle they were able to discover people who had antibodies to the rabies virus in their blood. These people have never been given any vaccines, moreover, they don’t even remember being sick with anything serious. This means that rabies is not 100% fatal!
“From this area of the Peruvian Amazon jungle, there have been numerous reports of exposure to vampire bats and cases of rabies in humans and domestic animals over the past 20 years,” lead study author Dr. Amy Gilbert, who works in the CDC's Rabies Research Program, explains to PM. . “The villages and farms that we examined are located in very remote places from civilization - the nearest hospital, for example, is two days away, and in some areas movement is only possible by boats on water.”
In a survey of residents, 63 out of 92 people reported bat bites to scientists. Blood samples were taken from these people, as well as from local vampire bats. The test results were unexpected: seven samples contained antibodies that neutralize the rabies virus.
The presence of antibodies could be explained by the administration of an anti-rabies (Latin rabies - rabies) vaccine, but, as it turned out, only one out of seven people received such a vaccine. The rest suffered from rabies not only without death, but even without any serious symptoms. In two Peruvian villages, more survivors of this infection were found than described in the entire medical literature! Not surprisingly, Gilbert's group spent two years rechecking their findings before deciding to publish them.
“It is likely that there is a unique set of circumstances where the local population is regularly exposed to a particular non-lethal strain of the rabies virus,” Dr. Gilbert said. “In this case, natural vaccination occurs, which is confirmed by fairly high titers of antibodies. However, this still requires additional confirmation and clarification.”
From a laboratory diary, 1885
“The death of this child seemed inevitable, so I decided, not without serious doubts and anxiety, which is well understandable, to try on Joseph Meister the method which I had found successful in the treatment of dogs. As a result, 60 hours after the bites, in the presence of doctors Villepeau and Granchet, young Meister was vaccinated with half a syringe of extract from spinal cord a rabbit that died of rabies, previously treated with dry air for 15 days. I made a total of 13 injections, one every day, gradually introducing an increasingly lethal dose. Three months later I examined the boy and found him completely healthy.”
Her point of view is shared by her Russian colleagues. Virologist Alexander Ivanov from the Laboratory of Molecular Bases of Action of Physiologically Active Compounds, Institute of Molecular Biology named after. V.A. Engelhardt, whom PM asked to comment on the discovery of CDC experts, emphasized that these strange at first glance results may have a completely scientific explanation: “Based on the available data, it can be assumed that local residents were infected with virus variants that, for a number of reasons, had low replicative activity (ability to reproduce) and low pathogenicity (“toxicity”). In my opinion, this may be due to several factors. First, each virus has a huge number of variants due to its relatively high variability. Infectious disease experts suggest that even for a successful transition from bats to other species, the rabies virus must undergo several specific mutations. If this is true, then many strains of the virus carried by bats may be of little danger to humans. Secondly, mutations in the virus genome affect its recognition immune system, as well as the ability of the virus to block the immune response to infection. At the same time, it is those variants of the rabies virus that are able to evade the innate immune system that have increased pathogenicity. Thus, these facts really suggest the existence in the bat population of such strains of the rabies virus that are promptly recognized and destroyed by the human immune system without causing fatal consequences.”
But in no case - this is emphasized by all experts, including the authors of the study - should one refuse to administer an anti-rabies vaccine when bitten by wild animals. Firstly, it may indeed turn out that in bats There is another version of the virus, a weaker one, and the luck of Peruvian peasants does not extend to strains transmitted by dog or raccoon bites. Secondly, results and conclusions this study may turn out to be wrong, so there is no point in taking another risk.
By the early 1870s, Louis Pasteur had already made the lion's share of his medical discoveries. Over the past 30 years, he has made significant contributions to the discovery of germ theory with his work in fermentation, pasteurization, saving the silk industry, and ultimately debunking the theory of spontaneous generation of life.
But at the end of the 1870s, Pasteur had another epoch-making discovery, the reason for which was this time a rather ominous gift: a chicken head. No, it was not a threat or a cruel joke. Chicken died from fowl cholera - serious infectious disease, the rampant of which destroyed up to 90% of the chicken population in the country.
The veterinarian who sent Pasteur the chicken head believed that the disease was caused by a specific microbe. The scientist soon confirmed his theory: taking a sample from a dead chicken head, he grew a similar microbial culture in the laboratory and injected it into healthy chickens. They soon died of bird cholera. This served as further confirmation of the validity of the germ theory, but the pathogenic culture grown by Pasteur soon played a much more important role in history. The scientist’s absent-mindedness and a happy accident helped her in this.
In the summer of 1879, Pasteur went on a long trip, completely forgetting about the culture of avian cholera left in an open test tube in the laboratory. Returning from a trip, he introduced this culture to several chickens and discovered that the virus had largely lost its deadly properties: birds injected with weakened, or attenuated, bacteria became ill but did not die .
However, after this, Pasteur had an even more important discovery. He waited until the chickens had recovered from their illness, injected them with the deadly avian cholera bacteria, and found that they were now completely immune to the disease.
Pasteur immediately realized that he had discovered new way making vaccines: the introduction of weakened bacteria gave the body the ability to fight and with active fatal forms.
Discussing this discovery in 1881 in an article published in The British Medical Journal, Pasteur wrote:
“We have touched on the basic principle of vaccination. Having contracted the virus in a weakened form, the birds then did not suffer even after being infected with a virulent virus, and were reliably protected from avian cholera.”
Inspired by this discovery, Pasteur began to explore the possibility of using the new approach in making vaccines against other diseases. His next success came with anthrax.
This disease caused serious damage to agriculture, killing 10-20% of the sheep population. Previously, Robert Koch had already proven that anthrax is caused by bacteria. Pasteur wanted to find out whether it was possible to weaken them, make them harmless, but in such a way that they would retain the ability to stimulate the defenses of the body into which they would be introduced as a vaccine.
He achieved the desired result by growing bacteria at elevated temperature. When some contemporaries doubted his findings, Pasteur decided to prove he was right by conducting a very spectacular public experiment.
On May 5, 1881, Pasteur injected 25 sheep with his vaccine - a new weakened virus anthrax. On May 17, he again injected them with a more virulent, but still weakened, virus. Finally, on May 31, he injected the deadly anthrax bacteria into 25 vaccinated sheep and another 25 unvaccinated ones. Two days later, a crowd of spectators, including members of parliament, scientists and reporters, gathered to see how the experiment would end. The result spoke for itself: from the vaccinated group, only one pregnant sheep died, while from the unvaccinated group, 23 died and two were close to death.
But perhaps Pasteur's most famous achievement in this field was the discovery of the rabies vaccine, his first vaccine intended for use in humans. At that time there was rabies terrible disease and invariably ended in death.
The cause of the disease was usually the bite of a rabid dog, and the treatment methods were more terrible than the other: the patient was asked to insert a long hot needle into the wound or sprinkle gunpowder on the bite site and set it on fire. No one knew what exactly caused rabies: the pathogenic virus was too small for the microscopes of the time, and it could not be grown as a separate culture.
But Pasteur was still convinced that the disease was caused by some microorganism that affected the central nervous system. To create the vaccine, Pasteur cultured an unknown pathogen in the brain of a rabbit, weakened it by drying tissue fragments, and used them to make the vaccine.
Initially, Pasteur did not intend to test the experimental vaccine on humans, but on July 6, 1885, he had to change his mind. On that day, nine-year-old Joseph Meister was brought to him with traces of 14 rabid dog bites on his body. The boy's mother begged Pasteur for help, and, giving in to her pressure, he agreed to administer a new vaccine to the child. The course of treatment (13 injections over 10 days) was successful, the boy survived.
After this, although the introduction of a lethal agent to humans caused protests in society, within 15 months another 1,500 people received the rabies vaccine.
So, in just eight years Louis Pasteur not only made the first major breakthrough in the history of vaccination since Jenner, discovering ways to attenuate viruses, But and created effective vaccine against avian cholera, anthrax and rabies.
However, there was another unexpected twist hidden in his pioneering work: it was not just about reducing the virulence of viruses.
As Pasteur later realized, the viruses that made up his rabies vaccine were not just weakened, but dead .
Louis Pasteur born on September 18, 1822 in the small French town of Doyle. His father, a veteran of the Napoleonic Wars, made a living by running a small tannery. The head of the family never finished school and barely knew how to read and write, but he wanted a different future for his son. The tanner spared no expense, and after graduating from school, young Louis was sent to college, where he continued his education. They say it would be difficult to find a more diligent student in all of France. Pasteur showed unprecedented persistence, and in letters to his sisters he talked about how much success in science depends on “desire and work.” No one was surprised when, after graduating from college, Louis decided to take the exam for the Ecole Normale Supérieure in Paris.
Successfully passing entrance examinations, Pasteur became a student. The money that the tannery brought in was not enough for education, so the young man had to work as a teacher. But neither work nor passion for painting (Pasteur received a Bachelor of Arts degree, painted many portraits that were highly appreciated by artists of that time) could distract the young man from his passion for the natural sciences.
Vaccination of a boy bitten by a rabid dog. Photo: www.globallookpress.com
Already at the age of 26, Louis Pasteur received the title of professor of physics for his discoveries in the field of the structure of tartaric acid crystals. However, in the process of studying organic matter the young scientist realized that his calling was not physics at all, but chemistry and biology.
In 1826, Louis Pasteur received an invitation to work at the University of Strasbourg. While visiting rector Laurent, Pasteur met his daughter Marie. And just a week after they met, the rector received a letter in which the young professor asked for his daughter’s hand in marriage. Pasteur saw Marie only once, but was completely confident in his choice. In the letter, he honestly informed the bride’s father that “except good health and a kind heart” he has nothing to offer Marie. However, for some reason Mr. Laurent believed in a happy future for his daughter and gave permission for the wedding. Intuition did not disappoint - the Pasteur couple lived in harmony for many years, and in Marie the scientist found not only his beloved wife, but also a faithful assistant.
Wine and chickens
One of the first works that brought Pasteur fame was a work devoted to fermentation processes. In 1854 Louis Pasteur was appointed dean of the faculty natural sciences at the University of Lille. There he continued his study of tartaric acids, which he had begun at the École Normale Supérieure. Once upon a time, a wealthy winemaker knocked on Pasteur’s house and asked the scientist to help him. Local winemakers could not understand why wine and beer spoiled. Pasteur enthusiastically set about solving an unusual problem. Having examined the wort under a microscope, Pasteur discovered that in addition to yeast fungi, the wine also contained microorganisms in the form of rods. In vessels containing sticks, the wine turned sour. And if fungi were responsible for the process of alcoholic fermentation itself, then the sticks were responsible for the spoilage of wine and beer. This is how one of the greatest discoveries was made - Pasteur explained not only the nature of fermentation, but also made the assumption that microbes do not arise by themselves, but enter the body from the outside. Pasteur began to solve the problem of wine spoilage by creating an environment free of bacteria. The scientist heated the wort to a temperature of 60 degrees so that all microorganisms would die, and based on this wort they prepared wine and beer. This technique is still used in industry and is called pasteurization in honor of its creator.
Louis Pasteur in his laboratory. Photo: www.globallookpress.com
Despite the fact that this discovery brought recognition to Pasteur, those times were difficult for the scientist - three of Pasteur’s five daughters died from typhoid fever. This tragedy prompted the professor to study infectious diseases. By examining the contents of ulcers, wounds and ulcers, Pasteur discovered many infectious agents, including staphylococcus and streptococcus.
Pasteur's laboratory in those days resembled a chicken farm - the scientist identified the causative agent of chicken cholera and tried to find a way to counteract this disease. The professor was helped by an accident. The culture with cholera microbes was forgotten in the thermostat. After the dried virus was injected into the chickens, to the scientist’s surprise, they did not die, but only suffered light form diseases. And when the scientist infected them again with a fresh culture, the chickens did not show a single symptom of cholera. Pasteur realized that introducing weakened microbes into the body could prevent future infections. Thus vaccination was born. Pasteur named his discovery in memory of the scientist Edward Jenner, who, to prevent smallpox, injected patients with the blood of cows infected with a form of this disease that was safe for humans (the word “vaccine” comes from the Latin vacca - “cow”).
After a successful experiment with chickens, Pasteur developed a vaccine against anthrax. Preventing this disease in livestock saved the French government huge amounts of money. Pasteur was given a lifetime pension and was elected to the French Academy of Sciences.
Reservoir Dogs
In 1881, the scientist witnessed the death of a five-year-old girl, bitten by a rabid dog. What he saw amazed Pasteur so much that he began to create a vaccine against this disease with great zeal. Unlike most microorganisms with which the scientist had to deal before, the rabies virus could not exist on its own - the pathogen lived only in brain cells. How to obtain a weakened form of the virus - this question worried the scientist. Pasteur spent days and nights in the laboratory, infecting rabbits with rabies and then dissecting their brains. He personally collected the saliva of sick animals directly from the mouth.
The professor personally collected the saliva of rabid animals directly from the mouth Photo: www.globallookpress.com
Relatives seriously feared for the professor’s health - even without the unbearable loads it left much to be desired. 13 years earlier, when Pasteur was only 45, he suffered a severe stroke, which turned the scientist into an invalid. He never recovered from the illness - his arm remained paralyzed and his leg dragged. But this did not stop Pasteur from making the greatest discovery of his life. He created a vaccine against rabies from dried rabbit brains.
The scientist did not risk conducting tests on humans until the mother of a boy who had been severely bitten by a rabid dog contacted him. The child had no chance to survive, and then the scientist decided to inject him with a vaccine. The child recovered. Then, thanks to Pasteur's vaccine, 16 peasants who were bitten by a rabid wolf were saved. Since then, the effectiveness of rabies vaccinations has no longer been questioned.
Pasteur died in 1895 at the age of 72. For his services he received about 200 orders. Pasteur received awards from almost all countries of the world.
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Rabies(hydrophobia) - acute zoonotic viral infectious disease with a contact mechanism of pathogen transmission, characterized by damage to the central nervous system with attacks of hydrophobia and death.
History and distribution
Rabies was known to the doctors of the East 3000 BC. First detailed description disease (hydrophobia) belongs to Celsus (1st century AD), who recommended cauterizing bite wounds. In 1801, the possibility of transmission of the disease through the saliva of a sick animal was proven. In 1885, L. Pasteur and his employees E. Roux and Chamberlain used the rabies vaccine they developed to prevent the disease in a person bitten by a sick dog.
Already in 1886, for the first time in the world, in Odessa, I.I. Mechnikov and N.F. Gamaleya organized a Pasteur station. In 1892, V. Babes, and in 1903, A. Negri, described specific intracellular inclusions in the neurocytes of animals that died from rabies (Babes-Negri bodies), but the morphology of the virus was first described by F. Almeida in 1962.
Cases of rabies in animals are recorded throughout the world, excluding the UK and some other island countries. Frequency of disease in people (always with fatal) annually amounts to several tens of thousands. On the territory of Russia, there are natural foci of rabies and cases of disease in wild and domestic animals are recorded, as well as isolated cases of rabies in humans every year.
Etiology of rabies
The causative agent of the disease contains single-stranded RNA and belongs to the family Rhabdoviridae, genus Lyssavirus. IN environment the virus is unstable, heat labile, is inactivated within 2 minutes when boiled, and can be stored for a long time in frozen and dried form.
Epidemiology
The main reservoir of rabies in nature are wild mammals, different in different regions of the world (fox, arctic fox, wolf, jackal, raccoon and raccoon dog, mongoose, vampire bats), in whose populations the virus circulates. Infection occurs through the bite of sick animals. In addition to natural foci, secondary anthropurgic foci are formed in which the virus circulates between dogs, cats and farm animals. The source of rabies for humans in the Russian Federation most often are dogs (especially stray ones), foxes, cats, wolves, and in the North - arctic foxes. Although the saliva of a sick person may contain the virus, it does not pose an epidemiological danger.
Infection is possible not only through a bite from a sick animal, but also through salivation of the skin and mucous membranes, since the virus can penetrate through microtraumas. It is important to emphasize that the pathogen is detected in the saliva of animals 3-10 days before the appearance of obvious signs diseases (aggressiveness, salivation, eating inedible objects). Latent virus carriage is possible in bats.
In cases of a bite from a known sick animal, the probability of developing the disease is about 30-40% and depends on the location and extent of the bite. It is greater when bitten on the head, neck, less when biting distal sections limbs; more for extensive (wolf bite), less for minor injuries. Cases of rabies are more often recorded among rural residents, especially in the summer-autumn period.
Pathogenesis
After the virus penetrates through damage to the skin or mucous membranes, its primary replication occurs in myocytes, then the virus moves centripetally along afferent nerve fibers and enters the central nervous system, causing lesions and death nerve cells brain and spinal cord. From the central nervous system, the pathogen spreads centrifugally along efferent fibers to almost all organs, including the salivary glands, which explains the presence of the virus in saliva already at the end of the incubation period. Damage to neurocytes is accompanied by an inflammatory reaction.
Thus, the basis of the clinical manifestations of the disease is encephalomyelitis. Clinical manifestations rabies are associated with the predominant localization of the process in the cerebral and cerebellar cortex, in the thalamus and hypothalamus, subcortical ganglia, nuclei cranial nerves, pons (pons), midbrain, in life support centers in the area of the bottom of the IV ventricle. Along with the neurological symptoms caused by these lesions, an important place is occupied by the development of dehydration due to hypersalivation, sweating, increased perspiration losses while simultaneously reducing fluid intake as a result of hydrophobia and the inability to swallow. All these processes, as well as hyperthermia and hypoxemia, contribute to the development of cerebral edema.
Pathomorphology of rabies
During a pathological examination, attention is drawn to the swelling and plethora of the brain substance, and the smoothness of the convolutions. Microscopically, perivascular lymphoid infiltrates, focal proliferation of glial elements, dystrophic changes and necrosis of neurocytes are detected. A pathognomonic sign of rabies is the presence of Babes-Negri bodies - oxyphilic cytoplasmic inclusions consisting of a fibrillar matrix and viral particles.
Rabies is a fatal disease. Death occurs due to damage to vital centers - respiratory and vasomotor, as well as paralysis of the respiratory muscles.
Clinical picture
The incubation period is from 10 days to 1 year, usually 1-2 months. Its duration depends on the location and extent of the bites: with bites to the head and neck (especially extensive ones) it is shorter than with single bites to the distal extremities. The disease occurs cyclically. There is a prodromal period, a period of excitation (encephalitis) and a paralytic period, each of which lasts 1-3 days. The total duration of the disease is 6-8 days, with resuscitation measures - sometimes up to 20 days.
The disease begins with the appearance discomfort and pain at the site of the bite. The scar after the bite becomes inflamed and painful. At the same time, irritability, depressed mood, feelings of fear, and melancholy appear. Sleep is disturbed and headache, malaise, low-grade fever, increased sensitivity to visual and auditory stimuli, and skin hyperesthesia. Then comes a feeling of tightness in the chest, lack of air, and sweating. Body temperature reaches febrile levels.
Against this background, suddenly, under the influence of an external stimulus, a first significant attack of illness(“paroxysm of rabies”) caused by painful cramps muscles of the pharynx, larynx, diaphragm. It is accompanied by breathing and swallowing disorders, severe psychomotor agitation and aggression. Most often, attacks are provoked by an attempt to drink (hydrophobia), air movement (aerophobia), bright light (photophobia) or loud sound(acousticophobia).
The frequency of attacks, which last several seconds, increases. Confusion, delirium, and hallucinations appear. Patients scream, try to run, tear clothes, break surrounding objects. During this period, salivation and sweating sharply increase, vomiting is often observed, which is accompanied by dehydration and rapid loss of body weight. Body temperature rises to 30-40 °C, pronounced tachycardia is noted, up to 150-160 contractions per minute. It is possible to develop paresis of the cranial nerves and muscles of the limbs. During this period there may be death from respiratory arrest or the disease progresses to a paralytic period.
Paralytic period characterized by the cessation of convulsive attacks and agitation, easier breathing, and clearing of consciousness. This imaginary improvement is accompanied by an increase in lethargy, adynamia, hyperthermia, and hemodynamic instability. At the same time, paralysis of various muscle groups appears and progresses. Death occurs suddenly from paralysis of the respiratory or vasomotor centers.
Possible various options course of the disease. So, prodromal period may be absent and attacks of rabies appear suddenly; “silent” rabies is possible, especially after bat bites, in which the disease is characterized by a rapid increase in paralysis.
Diagnosis and differential diagnosis
The diagnosis of rabies is established on the basis of clinical and epidemiological data. To confirm the diagnosis, the detection of the virus antigen by the IF method in corneal prints, skin and brain biopsies, and isolation of a virus culture from saliva, cerebrospinal fluid and tear fluid using a bioassay on newborn mice are used. Postmortem diagnosis is confirmed histologically by the detection of Babes-Negri bodies, most often in the cells of the ammon's horn or hippocampus, as well as by identifying the virus antigen using the above method.
Differential diagnosis is carried out with encephalitis, polio, tetanus, botulism, polyradiculoneuritis, atropine poisoning, hysteria (“lyssophobia”).
Treatment of rabies
Patients are hospitalized, as a rule, in individual boxes. Attempts to use specific immunoglobulin, antiviral drugs, and resuscitation methods have so far been ineffective, so treatment is mainly aimed at reducing the patient’s suffering. They use sleeping pills, sedatives and anticonvulsants, antipyretics and analgesics. Correction of water and electrolyte balance, oxygen therapy, and mechanical ventilation are carried out.
Forecast. Mortality 100%. The isolated cases of recovery described are not well documented.
Prevention is aimed at combating rabies in animals by regulating the population of foxes, wolves and other animals that are reservoirs of the virus, registering and vaccinating dogs, using muzzles, and catching stray dogs and cats. Persons professionally associated with the risk of infection (dog catchers, hunters) are subject to vaccination. Persons bitten or salivated by unknown sick animals or animals suspected of rabies are treated with wound treatment, rabies vaccination, and a specific immunoglobulin is administered.
Those bitten by healthy known animals are given a conditional course of vaccine prophylaxis (2-4 injections of rabies vaccine), and the animals are monitored for 10 days. If during this period they show signs of rabies, the animals are slaughtered and histological examination brain for the presence of Babes-Negri bodies, and those bitten are given a full course of vaccine prophylaxis. Antirabies drugs are administered in trauma centers or surgical rooms. Efficiency specific prevention is 96-99%, adverse reactions, including post-vaccination encephalitis, are observed in 0.02-0.03% of cases.
Yushchuk N.D., Vengerov Yu.Ya.
