Rabies is an acute, progressive viral disease caused by the rabies lyssavirus, which attacks the nervous system of mammals, including humans. The virus produces fatal encephalitis, which is the inflammation of the brain and spinal cord. Once the characteristic clinical signs of the disease begin to appear, the infection is considered virtually 100% fatal, underscoring the urgent need for timely intervention.
Transmission and Viral Journey
The rabies virus is primarily transmitted to humans through the saliva of an infected animal, usually following a bite that breaks the skin. Non-bite exposures, such as scratches or infected saliva contacting mucous membranes or open wounds, are also possible transmission routes.
Once introduced, the virus replicates in muscle cells near the inoculation site. It then binds to receptors at the neuromuscular junction, entering the peripheral nervous system. The virus uses retrograde axonal transport to travel up the peripheral nerves toward the central nervous system (CNS).
The time for the virus to reach the CNS determines the incubation period, which is highly variable, ranging from less than a week to over a year. Factors influencing this period include the distance from the brain, the wound severity, and the amount of virus introduced. Bites closer to the head or neck generally result in shorter incubation times.
Pathogenesis: How the Virus Damages the Central Nervous System
After reaching the brain and spinal cord, the rabies virus replicates rapidly within neuronal tissue, leading to widespread neurological dysfunction. The virus is highly neurotropic, specifically targeting and thriving within nerve cells. This replication causes encephalitis, which is the direct cause of the severe clinical signs.
The primary mechanism of damage is not immediate neuronal death, but a profound disruption of normal nerve cell function. Specific viral proteins interfere with critical cellular processes, causing mitochondrial dysfunction and oxidative stress within the neurons. This disruption impairs synaptic transmission and communication pathways between nerve cells.
The resulting neurological effects include the disruption of neurotransmitter balance, responsible for the behavioral changes seen in the disease. Viral accumulation in brainstem areas involved in serotonin regulation is implicated in aggressive behavior. Once replication is widespread in the CNS, the virus travels outward to infect sites like the salivary glands, completing the transmission cycle.
Clinical Manifestations and Symptom Phases
The progression of rabies follows a predictable course divided into distinct phases after the initial, often asymptomatic incubation period. The first is the prodromal phase, which is non-specific and typically lasts for two to ten days. Symptoms during this stage include malaise, fever, headache, nausea, and fatigue.
A specific sign is paresthesia, an abnormal sensation like tingling or burning, at or near the original bite site. This local neurological symptom reflects the virus’s initial movement into the peripheral nerves.
The disease then progresses into the acute neurological phase, categorized into two forms: furious rabies and paralytic rabies. Furious rabies accounts for about 80% of cases and is characterized by hyperactivity, agitation, and extreme excitability. Patients often experience hydrophobia—a painful, involuntary spasm when attempting to drink—and aerophobia, a similar reaction triggered by drafts of air.
Paralytic rabies, or “dumb” rabies, is less common and dominated by muscle weakness, often beginning in the bitten limb and spreading as an ascending paralysis. This form is calmer and lacks extreme agitation. Both forms eventually lead to delirium, coma, and ultimately death, usually due to respiratory failure.
Laboratory Diagnosis and Testing Methods
Diagnosing rabies in a living person presents a challenge because early, prodromal symptoms are non-specific, resembling a common flu. Due to the near-universal fatality once symptoms begin, diagnosis relies on a combination of tests, and treatment must be initiated immediately based on exposure risk.
The definitive confirmation of rabies relies on post-mortem testing of brain tissue. The Direct Fluorescent Antibody (DFA) test is the gold standard, detecting viral antigens within the brain cells for a rapid and highly accurate result.
For diagnosis before death, a multi-sample approach is used since no single test is perfectly sensitive. Samples are collected and analyzed for the presence of the virus or the body’s immune response:
- Saliva for Reverse Transcription-Polymerase Chain Reaction (RT-PCR) testing to detect genetic material.
- A skin biopsy from the nape of the neck, analyzed for viral antigen in the cutaneous nerves.
- Cerebrospinal fluid tested for rabies-specific antibodies.
- Serum tested for rabies-specific antibodies.
Prevention and Post-Exposure Protocol
Prevention focuses on two main strategies: pre-exposure vaccination for high-risk individuals and immediate post-exposure prophylaxis (PEP) following potential exposure. Pre-exposure vaccination is recommended for people in high-risk occupations, such as veterinarians, animal control officers, and travelers to endemic areas. This vaccine series provides baseline immunity that simplifies the PEP process if exposure occurs.
Post-Exposure Prophylaxis is the primary step in preventing human rabies after a suspected exposure. The first action is aggressive wound management, involving thoroughly washing the wound with soap and water for at least 15 minutes to remove the virus.
Following wound care, PEP consists of two components: passive and active immunization. The passive component is Rabies Immune Globulin (RIG), which provides immediate, short-term antibodies to neutralize the virus. RIG is administered once on day zero, infiltrated directly into and around the wound site up to the maximum calculated dose of 20 IU/kg.
The active component is the rabies vaccine, which stimulates the immune system to produce long-lasting antibodies. For individuals not previously vaccinated, the standard is a four-dose regimen administered intramuscularly in the deltoid muscle on days 0, 3, 7, and 14 following the exposure. The vaccine and the RIG must be administered at separate anatomical sites to avoid interference with the vaccine’s effectiveness.