| disease | Rabies (Surgery) |
| alias | Hydrophobia |
Rabies, also known as hydrophobia, is an acute zoonotic central nervous system infectious disease caused by the rabies virus. It is commonly found in carnivorous animals such as dogs, wolves, and cats. Humans are usually infected through bites from infected animals. Clinical symptoms include characteristic agitation, anxiety, fear of wind and water, drooling, and pharyngeal muscle spasms, eventually leading to paralysis and life-threatening conditions.
bubble_chart Epidemiology
Rabies occurs in many countries around the world. After the liberation of our country, due to the implementation of various preventive measures, the incidence rate has significantly decreased. In recent years, as dog ownership has gradually increased, the incidence rate has shown an upward trend.
(1) Source of infection In developing countries, the main source of rabies infection is rabid dogs, accounting for about 80-90% of human rabies cases transmitted by dogs, followed by cats and wolves. In developed countries, as canine rabies is under control, wild animals such as foxes, vampire bats, skunks, and raccoons have gradually become important sources of infection. The saliva of infected animals contains a large amount of the virus, which becomes infectious several days before the onset of symptoms. Latently infected animals like dogs and cats can also be infectious.
(2) Transmission route The primary mode of transmission is through bites or scratches from infected animals, allowing the virus to enter the human body through skin injuries. Mucous membranes are also important entry points for the virus. For example, contamination of the conjunctiva by the saliva of an infected animal or licking of the anal mucosa by a dog can lead to infection. Additionally, there have been reports of infection through the respiratory and digestive tracts.
(3) Susceptibility Humans are generally susceptible to rabies, with veterinarians, animal handlers, and hunters being particularly at risk. The incidence is generally higher in males than in females. The incidence rate is lower in winter compared to other seasons.The rabies virus is an RNA-type rhabdovirus transmitted through saliva. The rabies virus has two main antigens. One is the glycoprotein antigen on the outer membrane of the virus, which can bind to acetylcholine receptors, giving the virus its neurotoxicity and inducing the production of neutralizing antibodies and hemagglutination-inhibiting antibodies in the body. Neutralizing antibodies have a protective effect. The other is the nucleoprotein antigen in the inner layer, which can induce the production of complement-fixing antibodies and precipitin in the body but offers no protection. The virus isolated from patients and infected animals is called the natural virus or street virus (street virus), characterized by strong virulence. However, after multiple passages through rabbit brains, it becomes the fixed virus (fixed virus), with reduced virulence, making it suitable for vaccine production.
The rabies virus is easily inactivated by ultraviolet light, formaldehyde, 50–70% ethanol, mercuric chloride, and quaternary ammonium compounds (e.g., benzalkonium bromide). Its suspension loses viability after 30–60 minutes at 56°C or 2 minutes at 100°C and is highly resistant to phenol. It can be preserved for several years under freeze-drying.
The rabies virus has a strong affinity for nervous tissue. It travels centripetally along peripheral nerves and the fluid in the perineural spaces to the corresponding dorsal root ganglia and spinal cord segments near the bite site. From there, it ascends the spinal cord to the brain, where it replicates. Subsequently, it spreads along efferent nerves to the salivary glands, rendering the saliva infectious. The pathogenesis can be divided into three stages: ① Localized replication phase. After entering through the bite wound, the virus slowly replicates in nearby striated muscle cells for about 4–6 days before invading peripheral nerves. During this period, the infected person shows no symptoms. ② Invasion of the central nervous system phase. The virus rapidly ascends along afferent peripheral nerves to the dorsal root ganglia, where it replicates extensively before invading the spinal cord and central nervous system, primarily affecting neurons in the brainstem and cerebellum. However, the virus may halt its spread at certain locations, leading to specific clinical manifestations. ③ Systemic dissemination phase. The virus spreads from the central nervous system along efferent nerves to various tissues and organs, such as the eyes, tongue, salivary glands, skin, heart, and adrenal medulla. Damage to the vagus, glossopharyngeal, and hypoglossal nuclei can cause spasms in respiratory and swallowing muscles, clinically presenting as hydrophobia, dyspnea, and dysphagia. Sympathetic nerve stimulation increases saliva production and sweating. Damage to the vagal, sympathetic, and cardiac ganglia may result in cardiovascular dysfunction or sudden death.
The pathological changes mainly consist of acute disseminated encephalomyelitis, with the cerebral membranes mostly normal. The brain parenchyma and spinal cord exhibit congestion, edema, and minor hemorrhages. The spinal cord lesions are more pronounced in the lower segments, as the virus enters the nerves through the injured site, travels via the dorsal root ganglia and spinal cord to the brain, making the corresponding dorsal root ganglia and spinal cord segments of the bite site often severely affected. Damage to the medulla oblongata, hippocampus, pons, and cerebellum is also notably significant.
In most cases, one to several round or oval eosinophilic inclusion bodies, known as Negri bodies, with a diameter of about 3–10 μm, can be observed in the cytoplasm of swollen or degenerated nerve cells. These are commonly found in the nerve cells of the hippocampus and cerebellar Purkinje tissue, and occasionally in the pyramidal cell layer of the cerebral cortex, spinal cord neurons, posterior horn ganglia, and sympathetic ganglia. Negri bodies are viral colonies and represent a specific and diagnostically valuable lesion for this disease, though approximately 20% of patients test negative.
Additionally, acute degeneration may occur in the acinar cells of the salivary glands, parietal cells of the gastric mucosa, pancreatic acini and epithelium, renal tubular epithelium, and adrenal medullary cells.
bubble_chart Clinical Manifestations
The incubation period varies greatly, ranging from as short as 10 days to as long as 1 year, with most cases falling between 1 to 3 months. Children, those with head or facial bites, or those with deep wounds that were not thoroughly debrided tend to have shorter incubation periods. Additionally, it is also related to the quantity and virulence of the invading virus as well as the host's immunity.
(1) **Prodromal Stage**: Most patients experience symptoms such as fever, headache, lack of strength, poor appetite, nausea, and general discomfort. They become sensitive to stimuli such as pain, sound, wind, and light, and may feel a tightening sensation in the throat. About 50–80% of patients report numbness, itching, stabbing pain, or sensations like crawling insects or ants near the wound site. This is caused by the virus multiplying and stimulating surrounding neurons. This stage lasts 1–4 days.
(2) **Excitement Stage or Spasmodic Stage**: Patients are usually conscious but in a state of excitement, exhibiting extreme fear, irritability, and heightened sensitivity to stimuli like the sound of water or wind, which can trigger episodic pharyngeal muscle spasms and difficulty breathing.
Hydrophobia is a distinctive symptom of this disease, though it may not appear in every case or may not manifest early. The classic presentation involves severe pharyngeal muscle spasms triggered by drinking, seeing water, hearing the sound of water from a river, or even talking about drinking. As a result, patients experience extreme thirst but fear drinking, and even if they attempt to drink, they cannot swallow. This is often accompanied by hoarseness and dehydration.
Fear of wind is another common symptom, where even a slight breeze, draft, or crosswind can induce pharyngeal muscle spasms. Other stimuli such as noise, bright light, or touch may also provoke similar episodes.
Due to autonomic nervous system hyperactivity, patients may exhibit profuse sweating, excessive salivation, a body temperature exceeding 40°C, rapid heart rate, elevated blood pressure, and dilated pupils, though most remain conscious. As the excitement intensifies, some patients may develop mental disturbances, disorientation, hallucinations, or delirium. The disease progresses rapidly, with most patients succumbing to respiratory or circulatory failure during an episode. This stage lasts 1–3 days.
(3) **Paralytic Stage**: Spasms decrease or cease, and the patient gradually becomes calm, developing flaccid paralysis, particularly in the limbs. The eye muscles, facial muscles, and masticatory muscles may also be affected. Breathing becomes slow and irregular, the heartbeat weakens, and consciousness fades, ultimately leading to death due to respiratory paralysis and circulatory failure. This stage lasts approximately 6–18 hours.
bubble_chart Auxiliary Examination
1. Blood Picture The total white blood cell count ranges from 12 to 30×109/L, with neutrophils accounting for over 80% in most cases.
2. Immunological Tests
(1) Fluorescent Antibody Test: Collect the patient's saliva, pharyngeal or tracheal secretions, urinary sediment, corneal impression smears, or skin biopsy samples containing neuronal fibers, and detect rabies virus antigen using fluorescent antibody staining.
(2) Enzyme-Linked Immunosorbent Assay (ELISA) for Rabies Virus Antigen: This method can be used for rapid diagnosis and epidemiological purposes. If the patient survives for more than one week, a rise in neutralizing antibody titer may be observed. For patients previously vaccinated against rabies, a neutralizing antibody titer exceeding 1:5000 is required for diagnosis.
(3) Virus Isolation: Inoculate animals with the patient's saliva, cerebrospinal fluid, or postmortem brain tissue suspension to isolate the virus. Identification through neutralization tests can confirm the diagnosis, although the positive rate is relatively low.
(4) Negri Body Examination: Prepare impression smears or pathological sections from the deceased's brain tissue, and examine for Negri bodies using staining microscopy and direct immunofluorescence. The positive rate is approximately 70–80%.
Based on the patient's history of being bitten or scratched by a rabid or suspected rabid animal and typical clinical symptoms, a clinical diagnosis can be made. However, in the early stages of the disease, misdiagnosis is common in children and cases with unclear bite history. Confirmation relies on etiological testing or the detection of Negri bodies in brain tissue during autopsy.
bubble_chart Treatment Measures
(1) General Management Isolate the patient in a single room and avoid unnecessary stimulation. Healthcare workers should preferably be immunized and must wear masks and gloves to prevent infection. The patient's secretions and excretions must be strictly disinfected.
(2) Intensive Monitoring Patients often die within 3–10 days after symptoms appear. The main causes of death include impaired lung qi exchange, secondary pulmonary infections, myocardial damage, and circulatory failure. Therefore, intensive monitoring of respiratory and circulatory complications is essential.
(3) Symptomatic Treatment Provide caloric supplementation and maintain water, electrolyte, and acid-base balance. Administer sedatives to agitated or convulsing patients and dehydration agents for cerebral edema. Perform a tracheotomy if necessary and provide intermittent positive-pressure oxygen therapy. For tachycardia, arrhythmia, or elevated blood pressure, β-blockers or cardiotonic agents may be used.
(4) Combined Use of Hyperimmune Serum and Rabies Vaccine Administer 10–20 ml of hyperimmune serum intramuscularly, or half intramuscularly and the other half as an infiltration injection around the wound, along with seasonal epidemic vaccination.
(5) Interferon May be tried.
(1) Strengthen animal management and control the source of pestilence:
1. Vigorously publicize the dangers of keeping dogs and other wild animals.
2. Stray dogs should be captured and killed as much as possible.
3. Domestic dogs should be strictly confined, registered, and vaccinated.
4. Rabid dogs or wild animals infected with rabies should be immediately shot, burned, or buried deeply. Skinning or consuming their meat is strictly prohibited.
(2) Wound treatment: The primary focus is debridement. Immediately wash the wound and scratched area thoroughly with 20% soapy water and clean water repeatedly for at least 20 minutes. Then apply 75% ethanol or 2% iodine tincture, or rinse with 1% benzalkonium bromide solution to eliminate and kill the virus. If high-titer immune serum is available, it can be infiltrated into the wound after a skin test. The wound should not be sutured. Antibiotics and tetanus antitoxin may also be administered as appropriate.
(3) Vaccination: Veterinarians, animal handlers, hunters, field workers, and medical personnel who may be exposed to rabies virus should receive preventive vaccination. In principle, 1.0ml of rabies vaccine should be administered intramuscularly on days 1, 7, and 28, followed by a booster shot every 1–3 years. Individuals bitten by wolves, foxes, dogs, cats, or other animals should receive preventive vaccination. The method depends on the severity of the injury, the type of vaccine, and the instructions for use. Concurrent use of immune serum yields better results.
This disease should be differentiated from viral encephalitis, tetanus, Guillain-Barré syndrome, poliomyelitis, pseudohydrophobia, post-vaccination encephalomyelitis, and neuro Guanneng syndrome.
