What are the symptoms of rabies?

Rabies, also known as rabies, is an acute infectious disease of the central nervous system caused by rabies virus. More common in dogs, wolves, cats and other carnivores. Many people are infected by being bitten by sick animals. Once the disease occurs, the mortality rate is almost 100%. The clinical manifestations are mania, anxiety, fear of wind and water, salivation and pharyngeal muscle spasm, which eventually leads to paralysis and life-threatening. Vaccination is of great significance in this disease.

[etiology]

Rabies virus belongs to RNA rhabdovirus. Rabies virus has two main antigens. One is the glycoprotein antigen on the outer membrane of the virus, which can bind to acetylcholine receptor, making the virus neurotoxic and producing neutralizing antibodies and hemagglutination inhibition antibodies in vivo. Neutralizing antibody has protective effect. The other is the nuclear protein antigen, which can produce complement-binding antibodies and precipitate in the body without protection. Viruses isolated from patients and sick animals are called natural viruses or stree viruses, which are characterized by strong virulence. However, after many times, the rabbit brain becomes a fixed virus, and its toxicity is reduced, so it can be made into a vaccine.

Rabies virus is easily inactivated by ultraviolet rays, formaldehyde, 50 ~ 70% ethanol, mercury chloride and quaternary ammonium compounds (bromogeramine). Its suspension loses its vitality after 30 ~ 60 minutes at 56℃ or 2 minutes at100℃, and it has strong resistance to phenol. It can be stored in freeze-drying for several years.

[epidemiology]

Rabies occurs in many countries in the world. After the liberation of China, due to various preventive measures, the incidence rate dropped significantly. In recent years, due to the increasing number of dogs, the incidence rate has an upward trend.

① The main source of rabies infection in developing countries is sick dogs, and the spread of human rabies accounts for about 80 ~ 90%, followed by cats and wolves. In developed countries, wild animals such as foxes, vampire bats, skunks and raccoons have gradually become important sources of infection due to the control of canine rabies. The saliva of sick animals contains a large number of viruses, which are contagious a few days before the onset. Animals such as dogs and cats with recessive infection (asymptomatic virus) are also contagious.

② Transmission route: 50% ~ 90% of the saliva of sick animals contains rabies virus, which enters the human body from the skin injury mainly through being bitten or scratched by sick animals. Mucosa is also an important entrance for the virus. For example, the conjunctiva of the eyes is touched by the saliva of sick animals, and the anal mucosa is touched and licked by dogs, which can cause disease. It can also be infected by contaminated saliva that pollutes the external environment (stones, branches, etc.). ) and then pollute the common wounds. In addition, there are reports of infection through respiratory tract and digestive tract.

③ Susceptible people are generally susceptible to rabies, especially veterinarians, animal breeders and hunters. If you don't take preventive immunization after being bitten by a sick animal, the incidence will reach 15% ~ 60%. Generally speaking, there are more men than women. The incidence in winter is lower than that in other seasons.

④ Epidemic characteristics: The disease is an infectious disease of warm-blooded animals, widely publicized, and often seen in places with high density of domestic dogs. The disease occurs all year round, but the incidence rate is slightly lower in winter. Most of the patients are rural young adults and children, and they have more opportunities to contact domestic dogs or wild animals.

[Pathogenesis and pathological changes]

Rabies virus has a strong affinity for nerve tissue. The pathogenesis can be divided into three stages: ① A small amount of local tissue reproduction. After the virus invaded from the bite site, it slowly propagated in the striated cells near the wound and invaded the peripheral nerves in about 4 ~ 6 days. At this point, the patient has no conscious symptoms. ② Invasion of the central nervous system by peripheral nerves. The virus quickly ascends along the peripheral afferent nerve, reaches the dorsal root ganglion, multiplies in large numbers, and then invades the spinal cord and the central nervous system, mainly invading the neurons in the brain stem and cerebellum. However, it can also terminate in a certain part of the diffusion process, forming a special clinical manifestation. ③ stage of spreading to various organs. The virus invades various tissues and organs from the central nervous system, and then spreads along efferent nerves, such as eyes, tongue, salivary glands, skin, heart and adrenal medulla. Due to the damage of vagus nerve nucleus, glossopharyngeal nerve nucleus and hypoglossal nerve nucleus, respiratory muscle and swallowing muscle spasm may occur. Clinically, there are symptoms such as water phobia, dyspnea and dysphagia. Sympathetic nerve stimulation increases saliva secretion and sweating. When vagal ganglion, sympathetic ganglion and cardiac ganglion are damaged, cardiovascular system dysfunction or sudden death may occur.

Pathological changes were mainly acute diffuse encephalomyelitis with normal meninges. Brain parenchyma and spinal cord congestion, edema and tiny bleeding. Spinal cord lesions are more obvious in the lower segment, because the virus is transferred to the nerve along the injury site and enters the brain through the dorsal root ganglion and spinal cord, so the lesions of the corresponding dorsal root ganglion and spinal cord segment at the bite site are often very serious. The medulla oblongata, hippocampus, pons and cerebellum were also obviously damaged.

In most cases, 1 to several round or ovoid eosinophilic inclusions with a diameter of about 3 ~ 10μ m can be seen in the cytoplasm of swollen or degenerated nerve cells, that is, negri's body. It is common in nerve cells of hippocampus and cerebellum, and occasionally found in pyramidal cell layer, spinal nerve cells, posterior horn ganglion and sympathetic ganglion of cerebral cortex. The endosome is a virus colony, which is a specific and diagnostic lesion of the disease, but about 20% patients are negative.

In addition, salivary gland acinar cells, gastric mucosal wall cells, pancreatic acinar cells and epithelium, epithelial cells of upper renal duct, adrenal medullary cells and so on. Will degenerate rapidly.

[Clinical manifestations]

The incubation period ranges from 10 days to 10 years, mostly 1 ~ 3 months. Children, head and face bites, deep wounds and incomplete wounds have a short incubation period. In addition, it is also related to the number, virulence and host immunity of invasive viruses.

The clinical manifestations of typical cases are divided into three stages:

① Most prodromal patients have symptoms such as low fever, burnout, fatigue, headache, irritability, fear, nausea and general malaise. Sensitive to pain, sound, wind, light and other stimuli, and have a feeling of tight throat. About 50 ~ 80% patients have numbness, itching, tingling or insects crawling and mosquitoes walking in and around the healed wound. This is caused by the stimulation of peripheral neurons by virus reproduction. This period lasts 1 ~ 4 days.

② The excitability increases during the exciting period or the spasmodic period. The patient is conscious and in an excited state, showing extreme fear and irritability, and is very sensitive to water, wind, sound, touch and other stimuli, causing paroxysmal pharyngeal muscle spasms and dyspnea.

Fear of water is a special symptom of this disease, but it does not necessarily occur in every case, nor does it necessarily appear in the early stage. Typical manifestations are drinking water, seeing water, smelling running water or talking about drinking water, which will cause severe laryngeal muscle spasm. Therefore, patients are extremely thirsty, afraid of drinking water, unable to swallow when drinking water, often accompanied by hoarseness and dehydration.

Fear of the wind is also a common symptom of this disease. Breeze, blowing and cross-flow can cause pharyngeal muscle spasm. Others, such as sound, light, touch and so on. , can also cause the same attack.

It is often accompanied by respiratory accessory muscle spasm, which leads to dyspnea and even generalized painful convulsions. Due to the hyperactivity of autonomic nervous system, patients have sweating, increased saliva secretion, body temperature above 40℃, increased heart rate, elevated blood pressure and dilated pupils, but they are more conscious. With the aggravation of excitement, some patients have mental disorders, disorientation, hallucinations, delirium and so on. The course of the disease progresses rapidly, and most of them die of respiratory or circulatory failure during the attack. This period lasts 1 ~ 3 days.

(3) Spasm is relieved or stopped during paralysis, and the patient gradually becomes quiet, resulting in flaccid paralysis, especially limb paralysis. Eye muscles, facial muscles and masticatory muscles can also be involved. Feeling drops, reflex disappears, breathing is slow and incomplete, heartbeat is weak, consciousness is unclear, and people can quickly die of respiratory paralysis and circulatory failure. This period is about 6- 18 hours.

The course of disease is generally within 6 days, and it is rare to exceed 10 days.

[diagnosis]

(1) Clinical diagnosis According to the past history and typical clinical symptoms of patients bitten or scratched by sick animals or suspected sick animals, a clinical diagnosis can be made. However, in the early stage of the disease, children and people with unclear bite force are easily misdiagnosed. Diagnosis depends on pathogen detection or autopsy to find the matrix in brain tissue.

(2) Laboratory inspection

1. The total number of white blood cells is 12 ~ 30× 109/L, and neutrophils account for more than 80%.

2. Immunological test

(1) Fluorescent antibody detection: Take saliva, pharyngeal or tracheal secretions, urine sediment, corneal prints and skin sections with nerve fibers of patients, and check rabies virus antigen with fluorescent antibody staining.

(2) Detection of rabies virus antigen by enzyme-linked immunosorbent assay: it can be used for rapid diagnosis and epidemiology. If the patient can survive for more than 1 week, the neutralization test shows that the titer will increase. For patients vaccinated with rabies vaccine, the neutralizing antibody must exceed 1: 5000 to diagnose the disease.

(3) Virus isolation: Animals can be inoculated with saliva, cerebrospinal fluid or brain tissue suspension after the death of patients, and the virus can be isolated and confirmed by neutralization test, but the positive rate is low.

(4) Endoplasmic reticulum examination: The positive rate of the dead brain tissue was about 70 ~ 80% by printing smear or making pathological section, staining microscopy and direct immunofluorescence examination.

[Differential diagnosis]

This disease should be differentiated from viral encephalitis, tetanus, Guillain-Barre syndrome, poliomyelitis, pseudophobia, encephalomyelitis after inoculation, neurosis and other diseases.

[therapy]

(a) generally deal with isolated patients in single rooms to avoid unnecessary stimulation. It is best for medical staff to be immunized and wear masks and gloves to prevent infection. The patient's secretions and excreta must be strictly disinfected.

(2) Intensive care patients often die within 3 ~ 10 days after symptoms appear. The main causes of death are lung gas exchange disorder and secondary infection of lung; Myocardial injury and circulatory failure. Therefore, it is necessary to strengthen the monitoring of respiratory and circulatory complications.

(3) Symptomatic treatment, supplementing calories, and paying attention to water, electrolyte and acid-base balance; Sedatives are given to patients with irritability and spasm, and dehydrating agents are given when there is brain edema. When necessary, tracheotomy and intermittent positive pressure oxygen supply were performed. Beta blockers or cardiotonic agents can be used when tachycardia, arrhythmia and high blood pressure occur.

(4) High-priced immune serum combined with rabies vaccine 10 ~ 20 ml of high-priced immune serum is injected intramuscularly, or half of it is injected intramuscularly, and the other half infiltrates around the wound, and vaccination is carried out at the same time.

(5) Try interferon.

Because of the particularity of rabies infection route and clinical manifestations, wound treatment and immune prevention after being bitten by sick animals are actually very important early treatment.

① Immediately after the bite, wash the wound thoroughly with 20% soapy water or 0. 19% bromogeramine for half an hour, and then wipe it with 75% alcohol or 2.5 ~ 5% iodine for 2 ~ 3 times. Deep wounds can be cauterized with concentrated nitric acid, and wounds should not be stitched or bandaged.

② Application of rabies vaccine and anti-rabies serum.

At present, tissue culture vaccine is used in China, and the amount of antigen injected each time is not less than 2.5 international units. The application method is: generally, a bite patient is injected with an ampoule of vaccine intramuscularly at 0, 3, 7, 14 and 30 days. For severe bites (head, face, neck, fingers and multi-site bites) or deep bites (massive bleeding, dysfunction or musculoskeletal bites), in addition to vaccination according to procedures, anti-rabies serum should be injected on the day of vaccination or the day before (within 8 hours after the bite), and the dose should be calculated at 40 international units per kilogram of body weight (in severe cases, it will be increased to 100 international units), and 50% of the injuries will be caused. Allergy test should be done before serum use, and desensitization treatment should be carried out for those who are positive. In order to avoid the interference of serum on the vaccine effect, the second vaccination should be strengthened after the fifth vaccination.

③ Symptomatic treatment should be done after onset to reduce irritation and pain. Patients should stay in bed absolutely, avoid bad stimulation, give oxygen, replenish blood volume, give drugs by nasal feeding, calm down and relieve spasm, and give dehydrating agents when there is brain edema to maintain cardiovascular and respiratory functions.

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