Table of Contents
Case Scenario
Mr. Luke, a 48-year-old retired police officer, came to see the physician complaining of worsening left arm pain and paresthesia for seven days. On examination, the patient looked agitated and confused with decreased left finger movement. Also, it was revealed that he had a fever (39.4C), flaccid paralysis and sensory loss in the left upper arm, sensory loss in the mid-chest area, hypoesthesia, and hyporeflexia in the right upper arm.
He was admitted to the ward, and one day later, he developed respiratory failure and was intubated. All the investigation results came out normal. Later on, his family revealed that he was bitten by a stray dog but did not seek medical care. Unfortunately, he died two days later.
What is Rabies?
Rabies is a zoonotic infectious disease caused by the rabies virus, a single-stranded RNA virus within the family of rhabdoviruses. It attacks the nervous system causing severe neurological problems, and eventually death of the infected patient. Although it is preventable with vaccines, it has a mortality of 100%. This means that if one gets infected with the rabies virus, death is imminent.
In up to 99% of cases, domestic dogs are responsible for rabies virus transmission to humans. The virus will enter the human body through a bite wound caused by a rabid animal, usually via saliva. The bite wound usually is a deep bite or a scratch wound.
Following inoculation, the virus replicates at the site of the wound in the muscles and connective tissue. Then it enters the peripheral nerves through the neuromuscular junction and spreads to the CNS, causing its characteristic features. Later on, it will ascend through the spinal cord and finally end up in the brain, causing severe neurological complications like seizures, coma, and even death. The exact pathophysiology of this disease is still not clearly understood.
How Common is Rabies?
Rabies is a major health problem in some countries, with an estimated 55,000 deaths per year worldwide. Most of the developing countries in Asia are victims of rabies. According to the WHO global vaccine research forum, one Asian dies of rabies every 15 minutes, where 15% are mostly under 15 years. More than three billion people in developing countries in Asia are exposed to rabies transmitted via dogs. In Africa, at least 24,000 deaths happen per year. A high number of deaths are reported in poor rural communities and children while numbers of rabies cases reported are minimal in Europe and the United States. It is mainly due to the enforced policy of animal vaccination. In 2006, no human rabies cases were reported in the US.
According to the WHO, every year, more than 29 million people worldwide receive post-bite vaccination. Globally, the economic burden of dog-mediated rabies is around 8.6 billion USD per year. All these statistics indicate the severe burden the world is facing because of rabies.
What will the Patient Complain About?
The incubation period for rabies is generally two to three months but may change from one week to one year, depending on the location of virus entry and the viral load. There are two distinct clinical varieties of rabies, namely, furious rabies and dumb rabies. Furious rabies is the classic variety. The patient will complain of pain and tingling sensation at the site of the bite wound. Apart from that, the patient might complain of fever, malaise, headache. After about ten days, the patient will develop psychiatric symptoms like marked anxiety, agitation, depression, hallucinations, and change of behavior. Even paralysis may be seen. Hyperexcitability is the characteristic feature, and visual or auditory stimuli precipitate this. The patient might complain of fear of water (hydrophobia) and air (aerophobia). Hydrophobia is present in around 50% of the population and is due to pharyngeal spasms occurring during drinking or eating. Also, the fear of air is said to be characteristic of rabies.
Dumb rabies, also known as paralytic rabies, is seen in 20% of the people infected. This form usually has a long course compared to the furious form. The patient will complain of gradual onset of ascending paralysis starting from the site of the wound, and usually, this is symmetrical. Eventually, the patient will be in a coma state, and death will be imminent. This form of rabies resembles Guillain-Barre syndrome and is often misdiagnosed due to its less common presentation.
What are the Signs We Look for in a Patient?
Even though the patient may complain of pain, abnormal sensation, or an ascending paralysis of the muscles, first, we need to see whether the patient is telling the truth. So, a proper neurological examination with a mental state examination is vital. The neurological examination comprised of cranial nerve examination, upper limb, and lower limb examination.
Apart from that, general examination of all organ systems, including respiratory, cardiovascular, gastrointestinal, and genitourinary systems need to be done on the patient. If there are signs like pain, paresthesia, psychiatric symptoms, and other relevant signs compatible with the symptoms, you can suspect rabies quite confidently. But it is crucial to exclude other neurological conditions compatible with rabies features.
How do we Approach the Patient?
As always, we should approach the patient with a good history, examination, and then investigations.
History is the most critical part of a rabid patient assesment. Proper history taking will review the progression of the symptoms as well as the possible cause for the problem. The most common history is the patient coming after a dog bite with or without neurological symptoms.
Features like numbness, hyper or hyporeflexia, reduce muscle power and tone can be seen in a focused neurological examination. Psychotic symptoms like hallucinations, anxiety, depression, sudden behavioral change can be elicited with a proper mental state examination.
Other similar diseases can be excluded by doing basic investigations like full blood count, C-reactive protein assay, renal function tests, and liver function tests. Rabies can be confirmed on a post mortem body by performing a direct fluorescent antibody (DFA) in post mortem brain tissue.
How do We Arrive at a Diagnosis?
The diagnosis of rabies is commonly made with clinical findings. Skin punch biopsies are being used to detect antigens with an immunofluorescent antibody test. Viral RNA can be detected by genome amplification. Isolation of virus from saliva or the presence of antibodies in blood or CSF may support the diagnosis.
Negri bodies in brain tissue are detected at the postmortem at 90% of the population. Negri bodies are eosinophilic, cytoplasmic ovoid bodies, two to ten millimeters in diameter, and seen commonly in neurons of the hippocampus and cerebellum. Usually, the diagnosis should be made pathologically on the biting animal using genome amplification, immunofluorescent test on brain tissue, or tissue culture of the brain.
How do we Manage a Patient with Rabies?
You cannot do much about it once the patient is diagnosed with rabies CNS infection, as death is virtually inevitable. As mentioned earlier, the infection will start on the site of the wound, which will ascend to peripheral nerves, spinal cord, and eventually the brain, leading to coma and ultimately death.
So, the management of the patient is based on symptomatic therapy. The patient should be nursed in a quiet, darkened room, and proper nutritional, respiratory support should be provided according to the patient’s condition. Drugs such as morphine, diazepam, chlorpromazine can be used for pain relief and sedation, especially in excitable patients.
How can We Prevent Rabies?
Prevention of rabies can be divided into three main categories. They are pre-exposure prophylaxis, post-exposure prophylaxis, and control of rabies. Pre-exposure prophylaxis can be given to people who are at high risk of contracting rabies, such as veterinarians, animal handlers, and laboratory workers. Three doses of human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCEV) can be given by subcutaneous or intramuscular route on days zero, seven, and 28 to increase the immunity against the virus.
Post-exposure prophylaxis is given if an individual gets infected with the virus due to a suspected bite from a rabid animal. This consists of thoroughly washing the wound site with soap and water and immediate vaccination. Extensive wound washing includes immediate and thorough flushing and washing the wound for a minimum of 15 minutes with soap, water, detergent, povidone-iodine, or other substances that remove and kill the rabies virus. Human rabies immunoglobulin and a post-exposure prophylaxis vaccine are considered. Protection mediated by this method gives good coverage almost up to 100%.
According to the WHO, after an individual gets bitten by a rabid animal, the severity of contact needs to be considered. WHO gives three categories regarding contacting suspected rabid animals. Category one is considered when there’s no apparent wound over the skin. It includes touching or feeding animals, animals licking on intact skin. It is considered as the lowest risk group. No post-exposure prophylaxis is given, and only thorough washing of the area is encouraged WHO gives three categories regarding contacting suspected rabid animals. Wound washing and immediate vaccination are important. As for immediate vaccination, HDCV or PCEV is encouraged. In category three, there will be deep intradermal wounds with bleeding, contamination of mucus membrane or broken skin with saliva from animal licks, and also exposures due to direct contact with bats. This is considered the highest risk group. Apart from thorough washing, vaccination with human rabies immunoglobulin and pre-exposure vaccine needs to be given immediately. Also, the risk of contact is increased if the bitten mammal is a known reservoir for rabies if the exposure occurs in a geographical area where rabies is still present, if the animal is sick or ill-looking and displays abnormal behavior, if the bite is unprovoked, if the animal’s saliva is in contact with a mucous membrane of the individual, and if the animal has not been vaccinated.
Control of rabies is done by mainly vaccinating domestic animals. Vaccination and sterilization of stray dogs is a good control measure that can be taken. Implementation of rules and legislation for the transportation of animals should also be considered. Also, when it comes to handling wild animals, it must be done with great care.
And if possible, relevant authorities should be informed immediately, the suspected animal should be identified, removed from the community, and should be put under surveillance to identify any symptoms suggestive of rabies.
Let’s Get Back to Our Patient
Our patient, Mr. Luke died unfortunately due to a health problem that could have been prevented easily. If he has admitted as soon as he gets bitten by the stray dog, the proper post-exposure prophylaxis treatment could have been given, and his death would have been prevented easily. He was presented to the hospital only after he started getting the symptoms of rabies. By that time, the doctors could not do anything other than taking care of the patient with symptomatic treatment. So, it is crucial to understand that seeking immediate medical care is vital if you get bitten by a stray dog or a wild animal.
In conclusion
Rabies is a zoonotic viral infection transmitted commonly by domestic or wild animals. It is transmitted mainly by the saliva of the animal through mucus membranes or an opened wound. It will replicate on the muscle tissue around the wound, enter into the peripheral nerves and ascend to the brain through the spinal cord which will be seen as ascending paralysis. The virus will mainly affect the nervous system causing serious neurological complications. Some of the neurological symptoms are severe pain, paresthesia, hydrophobia, aerophobia, and other psychotic symptoms like depression and anxiety.
Rabies has 100% mortality, meaning that once the infection sets in, death cannot be prevented. Therefore, prevention is of utmost importance. Prevention is mainly done by pre-exposure prophylaxis, post-exposure prophylaxis, and finally, controlling the carriers of rabies. Awareness of the general population regarding rabies viral infection is also essential.
References
- Kumar and Clarke’s clinical medicine, 10E
- Yousaf, M. Z., Qasim, M., Zia, S., Khan, M. u., Ashfaq, U. A., & Khan, S. (2012). Rabies molecular virology, diagnosis, prevention and treatment. Virology journal, 9, 50. https://doi.org/10.1186/1743-422X-9-50
- https://www.who.int/news-room/fact-sheets/detail/rabies