Rabies is a deadly viral disease that affects the central nervous system. It is spread through the saliva of infected animals and can be transmitted to humans through bites or scratches. Rabies has one of the highest case fatality rates of any infectious disease – almost 100% if left untreated. However, rabies is also preventable if treatment is administered promptly after exposure. Significant progress has been made over the years in developing vaccines and treatments. But finding an effective cure that can save lives once the symptoms have set in remains elusive.
What is rabies and how does it spread?
Rabies is caused by a virus called Rabies lyssavirus that belongs to the Rhabdoviridae family. It attacks the nervous system and brain once it enters the body. The virus is present in the saliva of infected mammals and can be transmitted through bites, scratches, or licks to broken skin or mucous membranes. Over 99% of rabies transmissions to humans occur through dog bites. However, any mammal can become infected and spread rabies, including bats, raccoons, skunks, foxes, and monkeys among others.
The rabies virus travels through the nerves towards the brain in a process called centrifugal spread once it enters the body. This can take weeks or months. During this time, there are no symptoms. Once it reaches the brain and spinal cord, it causes inflammation of the brain and leads to the symptoms associated with rabies. From there, it spreads centrifugally again through the nerves to the salivary glands and is released in the saliva, ready to infect another host.
What are the symptoms?
Rabies has an incubation period that lasts for 1-3 months on average. During this time, there are no symptoms. Once the symptoms start manifesting, rabies progresses rapidly.
The first symptoms are nonspecific and include:
– Fever
– Headache
– Nausea
– Fatigue
– Discomfort or tingling at the site of exposure
As the disease progresses, more specific neurologic symptoms appear:
– Anxiety and agitation
– Hallucinations and delirium
– Hyperactivity and hypersensitivity to external stimuli
– Excess salivation and trouble swallowing liquids
– Hydrophobia or fear of water
– Insomnia
– Partial paralysis
Ultimately, it leads to seizures, coma, and death usually within 7-10 days from when the first symptoms appear.
How deadly is rabies?
Rabies has one of the highest case fatality rates of any infectious disease. It is almost always fatal once clinical symptoms have appeared, with less than 10 documented cases of human survival from symptomatic rabies without treatment.
According to the WHO, rabies causes approximately 59,000 deaths worldwide each year, over 95% of which occur in Africa and Asia where canine rabies is endemic. India has the highest rate of rabies deaths, accounting for about 35% of global deaths. Children under the age of 15 make up about 40% of those killed by rabies annually.
With proper post-exposure prophylaxis, rabies is 100% preventable. However, not all bite victims globally have access to vaccines and immunoglobulin needed for effective prevention. Lack of awareness and treatment-seeking behavior also contribute to poor outcomes.
How is rabies diagnosed?
Because the initial symptoms of rabies are nonspecific, it can be challenging to diagnose based on clinical features alone. Some tests used to confirm rabies include:
– Detection of rabies viral antigens in a biopsy of the neck skin taken after the onset of symptoms. This test has a sensitivity of >97%.
– Virus isolation through cell culture techniques like the mouse inoculation test – inoculating tissue samples into mice to see if they develop rabies. This is less widely available now.
– Detecting viral RNA in saliva, urine, or spinal fluid samples by RT-PCR techniques.
– Measuring rabies virus-specific binding antibodies in blood serum or cerebral spinal fluid.
MRI and CT scans may show subtle changes in rabies encephalitis but are not used definitively for diagnosis. Due to the lack of readily available, inexpensive diagnostic tests, rabies is very likely underdiagnosed worldwide.
How is rabies treated?
Unfortunately, no effective curative treatment exists for rabies once the symptoms have appeared. Intensive supportive care in hospitals aims to relieve symptoms, but this is ultimately palliative. Sedatives, antivirals, and therapeutic coma are some measures used. But patients almost always succumb within 7-10 days.
However, modern cell culture vaccines and immunoglobulin therapy have proven very effective at preventing the disease if administered promptly after exposure and before symptoms start. Here are the two main approaches:
– Post-exposure prophylaxis (PEP): This involves wound cleansing, a dose of rabies immunoglobulin injected near the site, and a course of 4 doses of rabies vaccine given over 14 days.
– Pre-exposure prophylaxis (PrEP): For people at high risk of infection like veterinarians, travelers, and lab workers. It involves being vaccinated beforehand. Fewer vaccine doses are then needed after an exposure.
With proper adherence to this regimen, the risk of developing rabies is almost zero. But once symptoms appear, treatment options remain very limited.
What is being done to find an effective cure for symptomatic rabies?
While PEP and PrEP enable prevention, researchers continue efforts to find a treatment cure that can save lives even after symptoms manifest. Some approaches being explored are:
– Antiviral drugs – New antivirals like favipiravir are being tested for inhibiting viral replication in symptomatic patients. But so far, no single antiviral has shown high efficacy. Combination therapy may be more promising.
– Monoclonal antibodies – Antibodies that can neutralize the rabies virus are being investigated as potential therapeutic agents.
– Immune modulators – Drugs that dysregulate the immune response to rabies infection may have a role in combatting the CNS inflammation rabies causes.
– Stem cell therapy – Some early studies are examining if stem cell transplantation can enable regeneration and recovery of rabies-infected nerve cells and reverse symptoms.
– Supportive care – Better ICU care and optimizing the delivery of sedatives, antivirals, etc. may improve outcomes slightly. But alone it has not led to survival once symptoms have appeared.
What progress has been made so far?
No definitive cure for symptomatic rabies exists yet. However, incremental progress provides hope. Some examples:
– The Milwaukee Protocol has enabled the survival of 6 patients out of over 35 treated since 2004 by inducing therapeutic coma and antiviral drugs. But it still has low efficacy.
– Mouse studies in 2018 showed antivirals like favipiravir delayed mortality but did not improve overall survival on their own.
– Studies in mice and dogs using combinations of antivirals, monoclonal antibodies, and anti-inflammatory molecules have shown improved survival compared to single drugs alone.
– Advances in understanding rabies neuropathogenesis and how the virus evades the immune response are paving the way for more targeted treatments.
– Scientists created a safe, controlled rabies infection model in mice using a modified virus that can help rapidly screen new potential anti-rabies drugs.
While no fully reliable cure exists yet, incremental progress continues. Developing combination therapies tailored to different stages of infection may eventually help save lives in the future.
How can rabies be eradicated globally?
Rabies eradication worldwide is a goal researchers and global health organizations are working towards. But it poses several challenges:
– Reservoirs in wildlife like bats and stray dogs act as continuous sources of infection. Stray dog population control and oral immunization of wildlife in high-risk areas are important.
– Effective vaccines need to be made affordable and accessible to all bite victims globally, particularly in lower-income regions.
– Increased public education and awareness can promote prompt treatment-seeking behavior after exposures and save lives.
– Surveillance systems must be strengthened to better estimate rabies burden and analyze trends especially in developing countries.
– More investments and global coordination are needed in rabies control. Leveraging existing interventions for polio, malaria etc. can enhance rabies programs.
– Research into novel, low-cost vaccines, monoclonal antibodies, and other tools should continue.
While eradication faces challenges, the tools exist to eliminate human deaths from rabies. Increased global will and closing these gaps can make rabies the next success story after smallpox and rinderpest.
Conclusion
In summary, while no reliable cure exists yet for symptomatic rabies, the progress made has provided hope that a cure may be possible in the future through enhanced medical care and anti-viral drug therapies. However, the key to eliminating rabies lies in expanding access to effective prevention worldwide and responsible pet ownership. Research continues to find an affordable treatment cure that could save 100% of rabies victims. But preventing exposure and promptly administering existing vaccines and immunoglobulin remain central to saving human lives. Global initiatives focused on frontline control, education, and better access to prophylaxis in all parts of the world will be key to one day making rabies a disease of the past.