Rabies

Introduction

Rabies is one of the oldest and most feared zoonotic diseases, known for its devastating effects on both humans and animals. The term “rabies” is derived from the Latin word rabere, which means “to rage,” reflecting the frenzied behavior seen in some animals and humans affected by the disease. Rabies is caused by the rabies virus, a member of the Lyssavirus genus in the family Rhabdoviridae. This disease is nearly always fatal once clinical symptoms appear, making prevention through vaccination and education critically important.

Epidemiology

Rabies is present in nearly every continent, with the exception of Antarctica. The World Health Organization (WHO) estimates that rabies causes around 59,000 human deaths annually, primarily in Asia and Africa. More than 95% of human rabies cases result from bites by rabid dogs, emphasizing the role of domestic animals in its transmission.

Global Burden

• Africa and Asia: These continents account for the majority of human rabies cases due to limited access to vaccines and healthcare facilities.
• Americas and Europe: Rabies control programs have significantly reduced the incidence of rabies in these regions, but wildlife reservoirs like raccoons, skunks, and bats remain a concern.
• Australia and Oceania: Rabies is not endemic, but there is surveillance for bat lyssaviruses, which are closely related.

Virology

The rabies virus is a single-stranded, negative-sense RNA virus. Its bullet-shaped morphology is characteristic. The genome of the rabies virus encodes five structural proteins:

1. Nucleoprotein (N): Protects the viral RNA.
2. Phosphoprotein (P): Facilitates replication.
3. Matrix protein (M): Involved in virus assembly and release.
4. Glycoprotein (G): Critical for host cell attachment and immune response.
5. Large protein (L): Functions as the RNA polymerase.

The virus enters the nervous system by binding to nicotinic acetylcholine receptors at neuromuscular junctions and propagates to the central nervous system (CNS), where it causes encephalitis.

Transmission

Rabies is primarily transmitted through the saliva of infected animals. Transmission occurs via:

• Bites: The most common mode.
• Scratches: If the skin is broken.
• Mucosal exposure: Contact of infected saliva with mucous membranes.
• Rare cases: Inhalation of aerosolized virus or organ transplantation from an infected donor.

Reservoirs

• Domestic Animals: Dogs are the primary source of human rabies in most developing countries.
• Wildlife: Bats, raccoons, foxes, and skunks are significant reservoirs in developed countries.

Pathophysiology

After exposure, the rabies virus enters peripheral nerves or directly infects muscle cells. From there, it travels retrograde along peripheral nerves to the CNS. Once in the CNS, the virus spreads rapidly, causing inflammation of the brain and spinal cord. The virus then travels centrifugally to other tissues, including the salivary glands, cornea, and skin, facilitating further transmission.

Incubation Period

The incubation period for rabies is typically 1-3 months but can range from days to years. Factors influencing the incubation period include:

• Location of the bite (closer to the head or CNS results in a shorter period).
• Severity of the bite.
• Immune status of the individual.

Clinical Manifestations

Rabies progresses through several stages:

1. Prodromal Phase (1-7 days)

• Nonspecific symptoms such as fever, fatigue, headache, and anxiety.
• Pain or paresthesia at the site of the bite, known as “pathognomonic tingling.”

2. Excitation Phase (Furious Rabies)

• Hyperactivity and agitation.
• Hydrophobia (fear of water) due to painful spasms of the throat.
• Aerophobia (fear of drafts of air).
• Periods of confusion and hallucination.

3. Paralytic Phase (Dumb Rabies)

• Progressive muscle weakness leading to paralysis.
• Absence of hydrophobia or hyperactivity, making it harder to diagnose.

4. Coma and Death

• Without intensive care, rabies invariably progresses to coma and death within 2-10 days after the onset of symptoms.

Diagnosis

Diagnosing rabies can be challenging, especially during the early stages. Laboratory tests include:

In Humans

• Direct Fluorescent Antibody Test (DFA): Detects viral antigens in skin biopsies.
• RT-PCR: Identifies viral RNA in saliva or cerebrospinal fluid.
• Serological Tests: Detect antibodies in serum or cerebrospinal fluid.

In Animals

• Post-mortem DFA: Gold standard for detecting rabies in brain tissue.

Prevention

Rabies is a vaccine-preventable disease. Prevention strategies include:

1. Pre-Exposure Prophylaxis (PrEP)

Recommended for:

• Veterinarians and animal handlers.
• Laboratory workers handling the rabies virus.
• Travelers to high-risk areas.

2. Post-Exposure Prophylaxis (PEP)

PEP should be administered immediately after exposure and includes:

• Wound Care: Washing the wound thoroughly with soap and water.
• Rabies Immunoglobulin (RIG): Administered to provide passive immunity.
• Rabies Vaccine: A series of doses over 14 days.

Treatment

Once clinical symptoms appear, rabies is nearly always fatal. Experimental treatments, such as the Milwaukee Protocol, have had limited success and remain controversial. This protocol involves:

• Inducing a coma to protect the brain.
• Administering antiviral drugs.

Despite these measures, the success rate is minimal, emphasizing the importance of prevention.

Public Health and Control Measures

1. Dog Vaccination Programs

Mass vaccination of dogs is the most effective way to reduce human rabies cases. Studies show that vaccinating at least 70% of the dog population can break the transmission cycle.

2. Stray Dog Control

Implementing humane methods to manage stray dog populations can reduce the risk of rabies transmission.

3. Public Education

Raising awareness about rabies prevention, recognizing symptoms, and seeking timely PEP can save lives.

4. Surveillance

Monitoring and reporting cases in both humans and animals help track progress in controlling the disease.

Challenges in Rabies Control

• Access to Vaccines: Limited availability and high cost in low-income countries.
• Cultural Barriers: Misconceptions and traditional beliefs may delay seeking medical attention.
• Wildlife Reservoirs: Controlling rabies in wildlife is more complex and requires targeted strategies.
• Infrastructure: Inadequate healthcare and veterinary services hinder effective rabies control.

Advances in Rabies Research

1. Improved Vaccines

• Developing longer-lasting and single-dose vaccines.
• Exploring oral vaccines for wildlife reservoirs.

2. Diagnostic Tools

• Faster and more accurate diagnostic methods like portable PCR devices.

3. Novel Therapies

• Investigating antiviral drugs and monoclonal antibodies.

Conclusion

Rabies remains a significant public health concern despite being preventable. Global efforts to eliminate rabies, such as the WHO’s goal to achieve “Zero by 30” (zero human deaths from dog-mediated rabies by 2030), require coordinated strategies involving vaccination, education, and access to medical care. Continued research, funding, and collaboration are essential to eradicate this ancient and deadly disease.