Rabies is a viral disease that affects the central nervous system and is almost always fatal once symptoms appear. It is spread through the bite or scratch of an infected animal, most commonly dogs. Rabies has one of the highest case fatality rates of any disease. However, it is preventable if treatment is started before symptoms develop. This leads to the key question: can rabies be treated after symptoms occur?
What is rabies and how is it transmitted?
Rabies is caused by a virus in the genus Lyssavirus. Once someone is exposed to rabies, the virus spreads through the nerves to the brain and causes inflammation of the brain and spinal cord.
Rabies spreads through the bite or scratch of an infected animal. The rabies virus is present in the animal’s saliva and gets introduced into the wound. In rare cases, it can also spread through mucous membranes or broken skin that is exposed to infected saliva.
Over 99% of rabies cases in humans are caused by dog bites. However, any mammal can carry and transmit the rabies virus, including bats, raccoons, skunks, and foxes. Rabies is not spread through touching blood, urine, or feces of an infected animal. It also does not spread through contact with non-infected animals.
What are the symptoms of rabies?
The initial symptoms of rabies are non-specific and flu-like. They include:
– Fever
– Headache
– Nausea
– Vomiting
– Fatigue
– Muscle aches
As the disease progresses, more specific neurologic symptoms develop due to inflammation of the brain and spinal cord:
– Anxiety
– Agitation
– Confusion
– Hyperactivity
– Difficulty swallowing
– Excess salivation
– Hallucinations
The disease then leads to paralysis, followed by coma and death. Without treatment, death usually occurs within 7-10 days after onset of symptoms.
Stages of rabies
Rabies infection occurs in two stages:
Stage 1: Prodromal
The first symptoms of rabies are flu-like, lasting 2-10 days. During this time, the virus is incubating and has not yet reached the brain.
Stage 2: Acute Neurologic Phase
In this stage, the virus spreads to the central nervous system. It causes inflammation of the brain and spinal cord leading to the neurologic symptoms described above. This phase progresses rapidly to paralysis, coma, and death within 2-7 days.
Is rabies treatable after symptoms start?
Unfortunately, once clinical symptoms of rabies appear, there is no effective treatment. Rabies has one of the highest fatality rates of any infectious disease, approaching 100% mortality.
Some key reasons rabies is not treatable after symptom onset include:
– The virus spreads quickly to the brain and causes severe damage.
– By the time symptoms appear, it is too late for treatments to work.
– We don’t have antiviral drugs that can stop replication of the rabies virus.
Supportive treatments may be given to ease the symptoms, but these do not cure the disease. Patients with symptomatic rabies require intensive care support, but almost always die.
Why is rabies so deadly after symptoms appear?
There are several reasons why rabies takes such a devastating course once symptoms start:
Swift spread to the central nervous system
After exposure through an animal bite, the rabies virus binds to nerve endings and quickly travels up peripheral nerves until it reaches the brain and spinal cord. The incubation period after exposure is usually 1-3 months, but can vary from under a week to over a year.
Neurotropism
Rabies specifically targets nerve cells. The virus has evolved to exploit nerve pathways to reach the central nervous system where it can replicate.
Blood-brain barrier
The blood-brain barrier protects the brain from toxins and pathogens in the blood. Unfortunately, this also prevents antiviral treatments from reaching the brain at therapeutic levels.
Neuronal dysfunction
The rabies virus causes severe dysfunction and death of nerve cells in the brain and spinal cord. This manifests as the neurologic and cognitive symptoms. Eventually neuronal dysfunction is so severe that it leads to paralysis, coma, and death.
Immune evasion
The rabies virus has evolved clever mechanisms to evade the immune response. It avoids detection by neutralizing antibodies and suppresses innate immune responses.
Can rabies be cured before symptoms start?
The key to surviving rabies is receiving vaccination before symptoms develop.
If given in a timely manner, rabies vaccines are highly effective at preventing the disease, even after exposure. The vaccines work by producing antibodies that neutralize the rabies virus before it can enter the nerves and spread to the brain.
Two types of vaccines are used:
Pre-exposure vaccination
Pre-exposure vaccines are given to people at high risk of rabies exposure such as veterinarians, animal handlers, certain laboratory workers, and travelers going to areas with endemic rabies. The vaccines prime the immune system to mount a rapid antibody response if exposed to rabies.
Post-exposure prophylaxis
If someone is bitten by a potentially rabid animal, post-exposure prophylaxis (PEP) is highly successful at preventing disease, as long as it is administered before symptoms occur.
PEP includes:
– Wound cleaning
– Injection of rabies immune globulin into and around the bite wound
– A series of rabies vaccine shots over 2-4 weeks
The immune globulin provides immediate antibodies to neutralize any virus, while the vaccines stimulate the immune system to mount a protective antiviral response.
PEP is nearly 100% effective when administered promptly and correctly. Of the 55,000 people who receive PEP each year in the U.S. after rabid animal bites, only 1-3 cases of rabies are reported.
Why does rabies treatment only work before symptoms?
Rabies vaccines and immunoglobulin are effective when given before symptoms because they work by priming the immune system to neutralize the virus. This prevents the rabies virus from entering the nerves and spreading to the brain where it causes severe damage.
However, once in the brain, the virus is sheltered from antibodies and immune cells that remain in the circulatory system and interstitial fluid. The blood-brain barrier that protects the brain also limits delivery of therapies.
So rabies treatments only work during the early prodromal phase while the virus is still spreading through the body and has not yet reached the central nervous system. Once in the brain, the virus rapidly causes severe inflammation and dysfunction that quickly becomes fatal.
Are there any experimental treatments for symptomatic rabies?
Currently there are no treatments that can cure rabies once symptoms appear. However, researchers are investigating experimental therapies that may offer a glimmer of hope in the future. These include:
New antiviral drugs
Researchers are working to develop antivirals capable of crossing the blood-brain barrier and stopping replication of the rabies virus. Potential targets include blocking viral entry, inhibiting replication, and suppressing aspects of the viral life cycle.
Immune modulators
Some experimental therapies aim to boost the immune response against the rabies virus by administration of cytokines or other immunomodulatory molecules. The hope is enhancing the antiviral immune response may prolong survival.
RNA interference
Small interfering RNAs (siRNAs) or microRNAs could theoretically be designed to inhibit viral gene expression and replication. Delivery across the blood-brain barrier remains a challenge.
Neural stem cells
Introducing neural stem cells aims to replace nerve cells damaged by rabies virus infection. However, clinical effectiveness remains unproven.
Unfortunately all experimental treatments have failed to provide a survival benefit to date. But future research offers hope that medicines may extend life even briefly after rabies symptom onset.
How long can someone survive with rabies after symptoms start?
The typical survival time after onset of rabies symptoms is only 7-10 days. Rarely, with intensive hospital care, some patients survive for up to 1-2 weeks. The longest documented survival with symptomatic rabies is just over 3 weeks.
Survival longer than a month is extremely rare. Only a handful of cases exist in the medical literature.
Factors allowing slightly prolonged survival include:
– Young age
– Good intensive care support
– Partial immunity from prior vaccination
– Aggressive experimental treatment protocols
However, no cases of true long term survival of rabies once symptoms develop have been medically confirmed. If untreated, the disease remains nearly 100% fatal.
Conclusion
Rabies is essentially 100% fatal once clinical signs and symptoms appear. No current treatments can cure or meaningfully prolong survival once the virus has spread to the brain and early neurologic symptoms start.
Prevention is therefore the key. Timely administration of rabies vaccines and immunoglobulin after exposure, but before symptoms start, is highly effective at preventing development of the disease.
Ongoing research provides hope that new therapies may someday be able to treat rabies even after onset of symptoms. But for now, rabies remains incurable and prevention throughprompt vaccination remains the sole way to escape this devastating disease.