Rabies remains a significant global health concern, affecting over 150 countries and territories, predominantly in Asia and Africa. This viral, zoonotic, and neglected tropical disease tragically claims tens of thousands of lives each year, with a staggering 40% of victims being children under the age of 15. Alarmingly, dog bites and scratches are responsible for 99% of human rabies cases, highlighting the critical role of dog vaccination and bite prevention strategies.
Once the rabies virus infiltrates the central nervous system and clinical symptoms manifest, the disease is invariably fatal in 100% of cases. However, this grim outcome is entirely preventable. Prompt post-exposure prophylaxis (PEP) is highly effective in halting the virus before it reaches the central nervous system. This crucial intervention includes thorough wound cleansing, a course of the human rabies vaccine, and, in certain cases, the administration of rabies immunoglobulins (RIG). Therefore, anyone bitten or scratched by a potentially rabid animal must immediately seek PEP without delay.
The World Health Organization (WHO) and its global partners are committed to eradicating human deaths caused by dog-mediated rabies through a comprehensive One Health approach. This strategy emphasizes mass dog vaccination campaigns, ensuring widespread access to PEP, training healthcare professionals, enhancing disease surveillance, and implementing community awareness programs focused on bite prevention.
Rabies: A Closer Look
Dog-Mediated Rabies: The Primary Threat
Rabies is a preventable viral disease that impacts the central nervous system. It is zoonotic, meaning it is transmitted from animals to humans. In a staggering 99% of human rabies cases, domestic dogs are the source of the virus transmission. Children, particularly those between 5 and 14 years old, are disproportionately affected by this disease.
Rabies affects all mammals, including not only dogs but also cats, livestock, and various wildlife species. The virus spreads through saliva, typically via bites, scratches, or direct contact with mucous membranes (such as the eyes, mouth, or open wounds). Once clinical signs of rabies appear, the disease is almost invariably fatal.
The global economic burden of rabies is estimated at approximately US$ 8.6 billion annually. This substantial figure encompasses lost lives and livelihoods, the costs of medical care and related expenses, and the immeasurable psychological trauma inflicted by the disease.
Rabies is present on every continent except Antarctica. Global estimates indicate around 59,000 rabies deaths each year. However, underreporting is a significant issue, meaning the actual number of cases may be much higher than officially documented figures.
Classified as a neglected tropical disease (NTD), rabies disproportionately impacts marginalized populations. While effective human vaccines and immunoglobulins exist, they are often inaccessible or unaffordable for those who need them most. In 2018, the average estimated cost of rabies post-exposure prophylaxis (PEP) was around US$ 108, excluding travel expenses and lost income. This cost can be a prohibitive financial burden for individuals living on just US$ 1–2 per day. Despite these challenges, over 29 million people globally receive human rabies vaccine each year.
Rabies Transmission Beyond Dogs
In the Americas, where dog-mediated rabies is largely under control, the primary source of human rabies has shifted to hematophagous (blood-feeding) bats. Bat-related rabies is also becoming an increasing public health concern in Australia and parts of Western Europe.
Human rabies infections from other wild animals like foxes, raccoons, and skunks are very rare. Bites from small rodents are not known to transmit rabies. Contracting rabies through unusual routes such as inhaling virus-containing aerosols, consuming raw meat or milk from infected animals, or via organ transplantation is exceptionally rare. Although theoretically possible, human-to-human transmission through bites or saliva has never been confirmed.
Recognizing Rabies Symptoms
The incubation period for rabies, the time between exposure and the onset of symptoms, typically ranges from 2 to 3 months. However, this period can vary from as short as one week to as long as one year. Factors influencing the incubation period include the location of the bite and the amount of virus introduced into the body. Initial rabies symptoms are often non-specific, including fever, pain, and unusual sensations like tingling, prickling, or burning at the bite site. As the virus progresses to the central nervous system, it causes progressive and fatal inflammation of the brain and spinal cord. While medical management can be provided for clinical rabies, a cure is exceptionally rare, and survivors often suffer from severe neurological deficits.
Rabies manifests in two primary forms:
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Furious Rabies: This form is characterized by hyperactivity, erratic behavior, hallucinations, lack of coordination, hydrophobia (fear of water), and aerophobia (fear of drafts or fresh air). Death typically occurs within a few days due to cardio-respiratory arrest.
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Paralytic Rabies: Accounting for approximately 20% of human rabies cases, paralytic rabies follows a less dramatic and usually longer course than furious rabies. Muscle paralysis gradually develops, starting at the site of the bite or scratch. The patient slowly progresses into a coma, eventually leading to death. Paralytic rabies is frequently misdiagnosed, contributing to the underreporting of rabies cases.
Diagnosing Rabies
Currently, there are no WHO-approved diagnostic tests to detect rabies infection before the onset of clinical symptoms. Clinical diagnosis of rabies is challenging without a clear history of exposure to a potentially rabid animal or the presence of characteristic symptoms like hydrophobia or aerophobia. Accurate assessment of the risk of rabies exposure is crucial for determining whether PEP is necessary. Once rabies symptoms appear, the disease is invariably fatal, and medical care focuses on providing comprehensive and compassionate palliative care to alleviate suffering.
Postmortem confirmation of rabies infection is achieved using various laboratory techniques. These methods detect the rabies virus itself, viral antigens (proteins), or viral nucleic acids in infected tissues, typically brain tissue, skin, or saliva. (Refer to Laboratory techniques in rabies Vol. 1 and Vol. 2 for detailed information). When feasible, testing the biting animal is also recommended to confirm rabies infection.
Rabies Prevention Strategies
Vaccinating Dogs: Stopping Rabies at the Source
Vaccinating dogs, including puppies, through mass dog vaccination programs is the most cost-effective and impactful approach to preventing rabies in humans. This strategy effectively stops rabies transmission at its animal source. Culling or eliminating free-roaming dog populations is not an effective rabies control measure.
Public Awareness and Education
Public education campaigns targeting both children and adults are essential components of rabies prevention programs. These initiatives should focus on educating the public about dog behavior, bite prevention strategies, appropriate actions to take if bitten or scratched by a potentially rabid animal, and responsible pet ownership.
Human Rabies Vaccination: Pre- and Post-Exposure
Effective rabies vaccines are available for humans, providing protection both before and after potential exposure to the virus. As of 2024, the WHO has pre-qualified only three human rabies vaccines globally: RABIVAX-S (Serum Institute of India Pvt. Ltd.), VaxiRab N (Zydus Lifesciences Limited), and VERORAB (Sanofi Pasteur).
Pre-exposure prophylaxis (PrEP) is recommended for individuals at high risk of rabies exposure. This includes laboratory workers handling live rabies viruses, animal disease control personnel, and wildlife rangers, or anyone whose occupation or activities may involve direct contact with potentially infected animals. PrEP may also be advisable for individuals traveling to or residing in remote, rabies-endemic areas with limited access to post-exposure treatment. It is crucial to remember that PrEP does not eliminate the need for PEP if an exposure occurs. Anyone bitten or scratched by a suspected rabid animal must still seek post-exposure care immediately.
Post-exposure prophylaxis (PEP) is the emergency medical response following a potential rabies exposure. PEP aims to prevent the rabies virus from reaching the central nervous system and causing infection. Effective PEP, as outlined in WHO guidelines, involves:
- Thorough wound washing: Immediately and extensively wash the wound with soap and water for at least 15 minutes.
- Rabies vaccine administration: A course of rabies vaccine is essential.
- Rabies immunoglobulin (RIG) administration: In category III exposures, rabies immunoglobulin or monoclonal antibodies should be administered into and around the wound, if indicated.
Understanding Exposure Risk and PEP Recommendations
The need for PEP depends on the nature of contact with a potentially rabid animal. The WHO categorizes rabies exposures and recommends PEP measures accordingly:
| Categories of Contact with Suspect Rabid Animal | Post-Exposure Prophylaxis Measures |
|---|---|
| Category I – Touching or feeding animals, animal licks on intact skin (no exposure) | Washing of exposed skin surfaces, no PEP |
| Category II – Nibbling of uncovered skin, minor scratches or abrasions without bleeding (exposure) | Wound washing and immediate vaccination |
| Category III – Single or multiple transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from animal licks, exposures due to direct contact with bats (severe exposure) | Wound washing, immediate vaccination and administration of rabies immunoglobulin/monoclonal antibodies |
Note: Category II and III exposures necessitate human rabies vaccination.
Ensuring Rabies Vaccine Quality
The WHO emphasizes that all human rabies vaccines should adhere to WHO standards to guarantee their quality, safety, and efficacy. The use of substandard rabies vaccines has unfortunately led to public health failures in several countries, highlighting the importance of vaccine quality control.
Intradermal (ID) vs. Intramuscular (IM) Vaccine Administration
WHO recommends transitioning from intramuscular (IM) to intradermal (ID) administration of human rabies vaccines for PEP. Intradermal administration offers significant advantages. It requires a smaller vaccine volume and fewer doses, resulting in cost reductions of 60–80% without compromising safety or effectiveness. The reduced number of doses also improves patient adherence to the complete PEP regimen.
WHO’s Global Rabies Response
Rabies is a prioritized disease in WHO’s 2021–2030 Roadmap for the global control of NTDs. This roadmap sets progressive, region-specific targets aligned with the global strategic plan to eliminate human deaths from dog-mediated rabies by 2030, also known as the “Zero by 30” initiative. Key components of WHO’s response include:
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Improving access to human rabies vaccines: WHO collaborates with partners like Gavi, the Vaccine Alliance, to enhance vaccine access. Gavi included human rabies vaccines in its 2021–2025 Vaccine Investment Strategy, and WHO is working with Gavi to implement this program in 2024 despite pandemic-related delays.
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Providing technical guidance: WHO offers technical support to countries in developing and implementing national rabies elimination plans, with a focus on strengthening surveillance and reporting systems.
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Building One Health workforce capacity: WHO encourages countries to leverage rabies elimination programs as a platform for fostering multisectoral collaboration and strengthening their One Health workforce.
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Promoting the United Against Rabies (UAR) forum: WHO, along with the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (WOAH, formerly OIE), launched the UAR multi-stakeholder forum. This forum advocates for action and investment in rabies control at all levels.
