Rabies

What is Rabies?

Rabies (outdated – hydrophobia) – an acute infectious disease that occurs after the bite of an infected animal, occurs with a heavy lesion of the nervous system and ends, as a rule, fatal.

Rabies was known to people long before our era and described in various ancient books. Already in the Egyptian papyrus, the Indian sacred books of the Vedas, Greek and Roman written sources, and then the Bible told about the frenzy, which is transmitted to people from the enraged animals (wild and domestic). The danger of this disease was written in the Middle Ages, the Renaissance and later.

All sorts of recommendations for the prevention and treatment of rabies – the destruction of enraged animals, cauterization of people’s bite with a hot iron – did not give an effect. Almost every man bitten by a rabid animal was doomed to death. Until the 80s of the nineteenth century, people did not have a reliable means of protection against this terrible disease.

The great French scientist Louis Pasteur is honored to create a rabies vaccine (rabies vaccine, from the word rabies), which was successfully used for the first time on July 6, 1885. Then, thanks to vaccination, a boy was bitten by a rabid dog. And some time later, in a French village, a mad dog attacked the playing children. Protecting them, fifteen-year-old shepherd Jean Jupil made a real feat. He managed to tie the dog’s face with a belt whip and kill it with its wooden shoe. But the whole body of the boy was covered with wounds. Jean, barely alive, was brought to Paris. Pasteur saved the hero.

Causes of Rabies

The causative agent of rabies – the virus Neuroiyctes rabid, belongs to the group of myxoviruses of the genus Lyssavirus of the Rhabdovtridae family. It has the form of a rifle bullet, sizes from 90-170 to 110-200 nm, contains single-stranded RNA.

The virus is resistant to phenol, freezing, antibiotics. It is destroyed by acids, alkalis, heating (at 56 ° C is inactivated for 15 minutes, boiled for 2 minutes. Sensitive to ultraviolet and direct sunlight, to ethanol to drying. Quickly inactivated by sublimate (1: 1000), lysol (1- 2%), carbolic acid (3-5%), chloramine (2-3%).

The virus is pathogenic for most warm-blooded animals and birds. There is a street (circulating in nature) and a fixed rabies virus that is supported in laboratories. The fixed virus is not secreted with saliva and cannot be transmitted during a bite. It propagates in various tissue cultures (primarily trypsinized and transplanted, in cultures of human diploid cells or hamster embryo fibroblasts), and after adaptation, on chicken and duck embryos, which is used to obtain rabies vaccines. The mechanism of viral persistence in cell cultures is associated with the formation and accumulation of di-particles. Virus penetration into cells occurs through adsorption endocytosis – virions are detected as inclusions surrounded by a membrane, adsorbed on microtubules and in the composition of lysosomes.

The sources of infection for 60% of those with rabies are dogs, 24% for foxes, 10% for cats, 3% for wolves and 3% for other animals. The animal becomes infectious 3-10 days before the onset of signs of the disease and remains infectious during the entire period of the disease. Rabies occurs in almost all countries of the world, with the exception of island states (Great Britain, Japan, Cyprus, Australia, etc.}, as well as a number of states in the north (Norway, Sweden) and southern Europe (Spain, Portugal).

Infection occurs when a animal is bitten or salted by rabies. The rabies virus is transmitted with saliva. Bites to the head and hands are especially dangerous.

Diseases of people are mainly associated with the late treatment of those bitten for medical care, with a violation of the regime during vaccinations or incompleteness of their course. Most of the patients after contact with sick animals did not go to medical institutions. Among the cases, a quarter of cases are children aged 4-14 years. Sick, as a rule, had contact with sick animals in the countryside in the spring-summer months.

Pathogenesis During Rabies

After penetration through the damaged skin, the rabies virus spreads along the nerve trunks centripetally, reaches the central nervous system, and then again, along the nerve trunks, centrifugally goes to the periphery, affecting almost the entire nervous system. In the same perineural way, the virus enters the salivary glands, standing out with the patient’s saliva.

Neurogenic spread of the virus is proved by experiments with ligation of the nerve trunks, which prevents the development of the disease. The same method proves centrifugal spread of the virus in the second phase of the disease. The rate of spread of the virus along the nerve trunks is about 3 mm / h.

One hypothesis explains the spread of rabies virus through the axoplasm of peripheral nerves to the central nervous system by the influence of the electromagnetic field of the body on negatively charged virions [Anna N., 1984]. In experiments on mice, it is possible to achieve a therapeutic effect by exposing animals to an electric field created by fixing a negative electrode on the head, and a positive one on the foot. With the reverse arrangement of the electrodes, infection is stimulated.

The role of the hematogenous and lymphogenous pathways of the virus in the body cannot be denied either. Interestingly, the amino acid sequence of the rabies virus glycoprotein is similar to snake venom neurotoxin, which binds selectively to acetylcholine receptors. Perhaps this is due to the neutrotropic nature of the rabies virus, and by linking it with specific neurotransmitter receptors or other neuron molecules, the development of autoimmune reactions and the selective defeat of certain groups of neurons are explained.

Multiplying in the nervous tissue (brain and spinal cord, sympathetic ganglia, nerve glands of the adrenal glands and salivary glands), the virus causes characteristic changes in it (edema, hemorrhage, degenerative and necrotic changes in nerve cells). The destruction of neurons is observed in the cortex of the cerebrum and cerebellum, in the optic tubercle, the hypogastric region, in the black substance, the nuclei of the cranial nerves, in the midbrain, in the basal ganglia, and in the brain bridge. However, there are maximum changes in the medulla oblongata, especially in the region of the bottom of the fourth ventricle. Lymphocytic infiltrates (slave nodules) appear around the areas of the affected cells. In the cytoplasm of the cells of the affected brain (most commonly in the ammonium horn neurons), oxyphilic inclusions (Babesh-Negri bodies) are formed, representing the sites of production and accumulation of rabies virions.

Symptoms of Rabies

The incubation period lasts on average from 1 to 3 months (variations from 12 days to 1 year or more are possible). The duration of the incubation period is affected by the localization of the bite. The shortest incubation is observed with a bite of the face, head, then upper limbs and the longest – with a bite in the lower limbs.

There are 3 stages of the disease: I – initial (depression), II – arousal, III – paralysis.

Stage I rabies. The disease begins with the appearance of unpleasant sensations in the area of ​​the bite (burning, pulling pains radiating to the center, itching, hyperesthesia of the skin), although the wound can already heal completely. Sometimes local inflammations reappear, the scar becomes red and swells. With bites in the face, olfactory and visual hallucinations are observed. Body temperature becomes subfebrile – usually 37.2-37.3 ° C. At the same time, the first symptoms of mental disorder occur: unexplained fear, melancholy, anxiety, depression, less often – increased irritability. The patient is closed, apathetic, refuses to eat, does not sleep well, his sleep is accompanied by frightening dreams. The initial stage lasts 1-3 days. Then apathy and depression join in with anxiety, pulse and breathing become more frequent, there is a feeling of tightness in the chest.

Stage II rabies – excitement is characterized by increased reflex excitability and sharp sympathicotonia. The most prominent clinical symptom of rabies is hydrophobia: when you try to drink, painful spastic contractions of the swallowing muscles and auxiliary respiratory muscles occur. These phenomena increase in intensity, so that a single reminder of water or the sound of flowing fluid causes muscle spasms of the pharynx and larynx. Breathing becomes noisy in the form of short, convulsive breaths.

At this time, reactions to any stimuli are sharply exacerbated. An attack of seizures can be triggered by a blow in the face of a jet of air (aerophobia), a bright light (photophobia), or a loud sound (acoustical phobia). Pupils of the patient are strongly expanded, there is an exophthalmos, the look directs to one point. The pulse is sharply accelerated, there is a lot of excruciating salivation (sialorea), sweating. At the height of the attack, violent psychomotor agitation (bouts of rage, rabies) occurs with violent and aggressive actions. Patients can hit, bite others, spit, tear their clothes. Consciousness is dimmed, auditory and visual hallucinations of frightening character develop. Possible cardiac and respiratory arrest. In the interictal gap, consciousness usually clears up, patients can correctly assess the situation and reasonably answer questions. After 2-3 days, excitement, if death did not occur at the height of one of the attacks, is replaced by paralysis of the muscles of the limbs, tongue, face.

The period of paralysis of rabies is associated with loss of activity of the cerebral cortex and subcortical structures, characterized by a pronounced decrease in motor and sensitive functions. Convulsions and bouts of hydrophobia cease. Surrounding people often mistaken this condition for improving the condition of the patient, but in reality it is a sign of imminent death. Body temperature rises to 40-42 ° С, tachycardia and hypotension increase. Death occurs within 12-20 hours from paralysis of the heart or respiratory center. The total duration of the disease is 5-8 days, rarely more.

Sometimes a disease without precursors immediately begins with the stage of initiation or the appearance of paralysis. In children, rabies is characterized by a shorter incubation period. Attacks of hydrophobia and sharp excitement may be absent. The disease is manifested by depression, drowsiness, the development of paralysis and collapse. Death can occur a day after the onset of the disease. Bulbar, paralytic (Landry-type), meningoencephalitic and cerebellar forms of the disease are distinguished as variants of the course.

Diagnosis of Rabies

The recognition of the disease is based on epidemiological (bite or salivation of the skin, mucous membranes of a sick person with rabies suspicious animals) and clinical data (characteristic signs of the initial period, alternating with agitation with symptoms such as hydrophobia, aerophobia, drooling, delusions and hallucinations). In general, a blood test is marked lymphocytic leukocytosis with aneosinophilia. Detection of rabies virus antigen is possible in prints from the surface of the cornea. With the death of patients examine the ammonia horn (histologically and immunofluorescent method), which can be found Babesh-Negri.

It is necessary to differentiate from tetanus, encephalitis, hysteroneurosis, atropine and strychnine poisoning, delirium tremens. Tetanus is characterized by tetanic convulsions, trisism, “sardonic smile”, lack of impairment of consciousness and the normal psyche of patients.

In case of encephalitis (lethargic, poliomyelitis, etc.), prior to the development of the paralytic phase, there is no stage of excitation combined with hydrophobia, aerophobia and pronounced sympathicotonia.

The picture of false rabies in hysteroneurosis is characterized by a confused history (often bitten animals are healthy), an abundance of subjective complaints, a lack of objective signs (no respiratory disorders, tachycardia, or dilated pupils) and a long course.

Poisoning drugs exclude on the basis of carefully collected history and the absence of the characteristic cycle of the disease. Attacks of delirium tremens are not accompanied by either water fear or convulsions.

Rabies Treatment

Urgent Care
If signs of discomfort appear in a person bitten by an animal, it is necessary to immediately seek medical assistance.

Effective treatments do not exist. Symptomatic therapy is carried out to reduce the suffering of the patient. The patient is placed in a darkened, isolated from the noise, warm chamber. Morphine, pantopon, aminazine, diphenhydramine, chloral hydrate in enemas are administered in large doses. The introduction of curare-like drugs, the transfer of the patient to artificial respiration can prolong his life. The use of rabies immunoglobulin in the presence of clinical symptoms of the disease is ineffective.

Milwaukee Protocol Artificial Coma Treatment
In 2005, there were reports that the 15-year-old girl from the United States, Gina Gis, was able to survive after being infected with the rabies virus without vaccination, when treatment was started after the onset of clinical symptoms. In the treatment of GIS was introduced into an artificial coma, and then she was introduced drugs that stimulate the body’s immune activity. The method was based on the assumption that the rabies virus does not cause irreversible damage to the central nervous system, but only causes a temporary breakdown of its functions, and thus, if you temporarily “turn off” most of the brain functions, the body will gradually be able to produce enough antibodies to defeat virus. After a week of being in a coma and subsequent treatment, GIS was discharged from the hospital without any signs of being affected by the rabies virus after several months.

However, all subsequent attempts to use the same method on other patients did not lead to success. Among physicians, discussions about why Gina Gis recovered are still ongoing. Some indicate that it could have been infected by a severely weakened form of the virus, or it had an unusually strong immune response.

The third confirmed case in the world, when a person managed to recover from rabies without using a vaccine, is the cure of a 15-year-old adolescent hospitalized with symptoms of rabies in Brazil. A teenager, whose name has not yet been revealed, became infected with rabies as a result of a bat bite in the Brazilian state of Pernambuco. For unknown reasons, the boy was not vaccinated to avoid the development of the disease. In October, the child developed symptoms of a nervous system lesion characteristic of rabies, and he was hospitalized at the University Hospital Oswaldo Cruz University Hospital in Recife, the state capital of Pernambuco. For the treatment of the boy, the doctors used a combination of antiviral drugs, sedatives and injectable anesthetics. According to the attending physicians, a month after the start of treatment, the virus was absent in the boy’s blood. Currently, the child is recovering.

The forecast is always unfavorable. There are descriptions of isolated cases of recovery of patients who received a full course of immunization with rabies vaccine and sick after its termination.

Rabies Prevention

Measures to prevent rabies among animals are regulation of the density of wild animals; catching homeless dogs and cats; compliance with the rules of keeping domestic dogs (registration, use of muzzles, keeping on a leash, etc.); mandatory annual preventive immunization of dog rabies.

The course of preventive immunization is carried out by persons professionally associated with the risk of infection with rabies (dog dogs, hunters – fishermen, veterinary workers, etc.).

Dogs, cats and other animals that have bitten people or animals are subject to immediate delivery by the owner to the nearest veterinary medical institution for examination and quarantine under the supervision of specialists within 10 days. The results of such observations of animals in writing are reported to the medical institution in which the affected person is vaccinated. If the animal did not fall during the observation period, then it is probably healthy.

Non-specific prophylaxis
The best preventative measure is local wound care. The bite area should immediately be thoroughly cleaned with a 20% solution of mild medical soap. Deep bite wounds are washed with a stream of soapy water using a catheter. Burning a wound or stitching is not recommended.

Specific prophylaxis (immunoglobulin + vaccine)
The best specific prevention is passive immunization with a rabies immunoglobulin or rabies serum followed by active immunization (vaccination). Passive and active immunization is carried out simultaneously, but different drugs can not be administered in the same place.

Indications for Rabies Vaccination
General secondary prophylaxis (vaccination) begin immediately with:

• all bites, scratches, salivation of the skin and mucous membranes caused by obviously rabid, suspicious of rabies or unknown animals;
• when injured by objects contaminated with saliva or the brain of rabid or rabies suspicious animals;
• when biting through clothes, if it is damaged by the teeth;
• when biting through thin or knitted clothes;
• when biting, salting and scratching healthy animals at the time of contact, if it is sick, died or disappears during a 10-day observation;
• with wild rodent bites;
• in the event of obvious salivation or damage to the skin of a person suffering from rabies.

When it is not necessary to vaccinate against rabies
Vaccinations do not:

• with bites through intact thick or multi-layered clothing;
• when injured by birds of prey;
• for bites by domestic mice or rats in areas where rabies has not been registered for the last 2 years;
• in case of accidental use of thermally processed meat and milk of rabid animals;
• if the animal remains healthy for 10 days after being bitten;
• if the animal bites for 10 days or more before their illness;
• with mousy and moderate bites, inflicted by healthy animals at the time of the bite, with favorable data (there is no rabies in the area, isolated animal content, the bite is provoked by the victim himself, the dog is vaccinated against rabies). However, in this case, a 10-day veterinary observation is established for the animals in order to begin vaccinations in case of manifestation of rabies, as well as death or disappearance;
• in the case of provoked salivation of intact skin by unidentified pets in areas that are safe for rabies;
• in cases of contact with a person suffering from rabies, if there was no obvious exacerbation of the mucous membranes or damage to the skin.

The procedure for vaccination against rabies
Active immunization is started immediately. The vaccine is administered intramuscularly 1 ml 5 times: on the day of infection, then on the 3rd, 7th, 14th and 28th day). With such a scheme, a satisfactory immunity is always created, so routine serological testing is not recommended. The WHO also recommends the 6th injection 90 days after the first.

Adverse reactions to vaccine against rabies
At the injection site there may be mild reactions in the form of pain, swelling and thickening. In some cases, these reactions may be stronger. In addition, it is possible to increase the temperature to 38 degrees Celsius and above, the increase in lymph nodes, arthritis and dyspeptic disorders. Sometimes there is a headache, general malaise, chills, myalgias and allergic reactions.

Special instructions
Vaccination against rabies is carried out as an outpatient and inpatient. Persons with severe bites living in rural areas are to be hospitalized; re-vaccinated; persons who have diseases of the nervous system or allergies; pregnant women, as well as persons vaccinated with other drugs in the previous two months.

Corticosteroids and immunosuppressants can lead to a suppression of the immune response to the vaccine. Therefore, if it is necessary to carry out vaccination while taking these drugs, the determination of the level of antibodies is mandatory for deciding on the additional course of treatment

During vaccinations, it is necessary to monitor the patient’s state of health. With complaints of deterioration, hospitalization is necessary, and vaccinations are temporarily suspended. The victim must be examined by a neurologist and therapist. The question of the continuation or termination of vaccinations is resolved advisory neuropathologist, rabiologist and therapist.

In order to ensure proper immunity and prevent post-vaccination complications, use of any alcoholic beverages is contraindicated during the course of vaccination and for 6 months after its termination. It is necessary that during the vaccination period the patient does not overwork, avoid overcooling and overheating. In some cases, it is recommended to transfer to a lighter job or issue a sick-list.

The use of other vaccines simultaneously with the rabies is not allowed. However, if necessary, emergency tetanus prophylaxis can be performed. Sore rabies vaccinations are not carried out.