What Is Paralytic Rabies

Introduction 

Rabies is a zoonotic disease that is classified in the Family Rhabdoviridae and Genus lyssaviruses. It is one of the deadliest zoonotic diseases, documented in various historical records as far as 4000 years.^1,2 However, it was not identified as a communicable viral disease until the 19th century by Louis Pasteur.³    The word Rabies is derived from the Latin word rare, which in simple terms means ‘to rage’, due to the clinical manifestation that an individual with rabies exhibits.¹ There are two clinical forms of rabies: furious (encephalitic) rabies and paralytic rabies. Paralytic rabies is said to be more common in those who have received a post-exposure vaccination and is characterised by coma and paralysis. The encephalitic form is more known, and its clinical manifestations present as a fever, neurological symptoms, agitation, hallucinations, hydrophobia, and seizures. There have been cases in which the encephalitic and paralytic forms can alternate.5  The pathological foundation of paralytic rabies is not well understood, and it is therefore classified by the World Health Organisation (WHO) as one of the Neglected Tropical Diseases (NTD).⁶ This is due to the lack of attention in developing populations. Countries that are considered to have a risk of rabies include Vietnam, China, Philippines, Malaysia, Cambodia, Lao People’s Democratic Republic, and Malaysia.⁶

Mode of transmission

Rabies is transmitted from the bite of an infected animal. This is the most typical mode of transmission. However, rabies can be contracted through organ transplantation from donors who are unaware of their own infection with rabies.⁷ 

The virus is excreted in the saliva, entering the peripheral nerves before being transported to the neurons in the central nervous system (CNS), whilst evading the host’s immune system response. Once it enters the CNS, it replicates to cause cerebral damage.   

Since it enters the CNS, it is hard to diagnose and treat due to the lack of host antibodies to signify and fight infection. Successful treatment must target the rabies virus before it enters the CNS.¹ 

Most individuals express the encephalitic form (affecting reasoning and cognition), making up 85% of cases. Approximately 80% of individuals exhibit hydrophobia (extreme fear of water). The paralytic form makes up less than 20% of cases. Symptoms exhibited in the paralytic form can be blurred with the Guillain-Barre Syndrome, as the paralytic form does not express hydrophobia or irritability like the encephalitic form. This form was recorded by Gamaleia in 1887, but it was not yet recognised as a form of rabies until many decades later. The other form of rabies can be the non-classified form, which is rare. This is associated with sensory-related symptoms.⁸

Clinical manifestations

Five stages of rabies occur in humans: incubation period, prodrome, acute neurologic period, coma, and death. The typical incubation in humans can be from 2 to 12 weeks, although it can be as short as 4 days and up to 6 years. The incubation period is variable; it can also depend on the site of the bite. For example, if an individual is bitten close to the CNS, this could lead to a shorter incubation period. Symptoms of rabies are identified in the prodromal stage. The symptoms at this stage are non-specific: fever, fatigue, cough, dyspnea, general malaise, nausea, diarrhoea, irritability, and anorexia.⁹ Table 1 provides abnormal symptoms that can occur at this stage. As previously mentioned, other factors can alter the incubation period including; the type of virus, the amount of virus injected, the immune status of the wound, and even the proximity to the nervous system. Children are more likely to be bitten around the head, as it is easier for animals infected with rabies to target in contrast to adults. The next stage is the acute neurologic period, which is when neurologic symptoms transpire. This is where the symptoms can be differentiated between the encephalitic, paralytic, and non-classic forms. As the third stage starts to progress to stage four, the individual will experience paralysis and struggle to functionally breathe, leading to a coma and eventually death. Unfortunately, rabies infection has a case fatality rate of 99.9%.⁴

Table 1: Some of the abnormal symptoms recorded in individuals who contracted rabies.⁹ 

Epidemiology

Currently, the most common reservoir of rabies are dogs, although other mammals can also carry the rabies virus such as raccoons, bats, skunks, wolves, and foxes. Many countries are at risk of rabies. However, some countries are rabies-free. Some of these countries include: Malaysia, Hong Kong, Uruguay, Maldives, Japan, United Kingdom, Spain, Finland, Barbados, Cape Verde, Cogo, French Polynesia, and many more have gained their status as rabies-free. Countries that are considered developing nations, such as Bangladesh, Thailand, Nepal, and India, retain cases of rabies. Currently, most of the cases reported are in India, with 18,500 cases of mortality reported every year.³ There are also reported cases of rabies in African countries like Namibia, Zimbabwe, and Mozambique in poor communities, mostly affecting children. 

Diagnosis

Rabies is very difficult to diagnose and treat. During the early stages of rabies, individuals can be misdiagnosed due to the ability of the virus to mimic other infectious and noninfectious diseases. For encephalitic rabies, it can be misdiagnosed as arbovirus, cerebral malaria, and typhoid. On the other hand, paralytic rabies could be misdiagnosed as herpes type B and poliomyelitis. Currently, serial serum and immunofluorescence testing are used to detect rabies. However, the serological tests can only detect 20% of the antibodies of unvaccinated patients who have contracted rabies within 1 to 26 days.⁷

The Fluorescent Antibody Technique also known as FAT is used for postmortem rabies diagnosis. The mechanism of the diagnostic test involves fresh brain spears of the nucleoprotein antigen (N) of the rabies virus. This diagnostic test has an extremely high sensitivity and specificity and provides results within a few hours. Although this is a great diagnostic tool, a post-mortem biopsy can be controversial, and ethical, cultural, and religious factors can influence the number of samples obtained.⁷ Other techniques are shown in Table 2.¹⁰

Table 2: Laboratory diagnostic techniques used for rabies

Treatment

Rabies is treated through wound cleaning and post-exposure prophylaxis (PEP). Experimental studies have demonstrated that cleaning the wound in the initial three hours of exposure to the virus can prevent transmission.¹  PEP is used to also prevent rabies however the administration must be timely in response to infection. When an individual is getting a PEP vaccine, the WHO recommends the person get several doses of varying amounts. Depending on the vaccine, it can vary. For example, the 5-dose Essen regimen is given on days 0, 3, 7, 14, and 28.  If the individual has previously been vaccinated, then they receive two injections: one on day 0 and one on day 3-7. A possible pre-exposure vaccination is usually recommended to anyone who is at high risk of contracting with a wild mammal, which is only required once. Another post-exposure treatment is the administration of rabies immunoglobulin (RIG), which should be given to the patient immediately. RIG works by neutralising the rabies virus as a passive immune treatment. This means that it functions to assist the patient's immune system until they can produce their own neutralising antibody after being vaccinated.  Three sources are used to make RIG; equine rabies immune globulin (ERIG) from vaccinated horses,  human rabies immune globulin (HRIG) from plasma donors (humans), and monoclonal production of antibodies (Mabs) from cell culture.¹¹ It is important to note that if an individual is unvaccinated and shows signs of encephalitic rabies, it is more likely that they will die within a few days. However, if they show symptoms of paralytic rabies, they may be able to survive a few weeks longer.⁴

Prevention and control

Currently, there are certain measures in place to prevent and control the spread of rabies. Raising awareness of avoiding contact with wild animals and the way viruses can transmit into the body is essential to prevent rabies. Additionally, there should be vaccination programmes against mammals that are high-risk reservoirs for rabies, such as cats, dogs, and ferrets.

Summary

Overall, rabies is a deadly zoonotic (animal-borne) disease that can cause varying symptoms, including paralysis, hallucinations, and other serious neurological effects. Rabies is spread through the bite of infected animals and can bypass the human immune system by remaining in the central nervous system. The disease is fatal without rapid access to treatment, which comes in the forms of prophylactic (anticipatory) and post-exposure vaccines- these vaccines introduce some rabies virus antigens to the body so that the host can rapidly fight the infection. Awareness of rabies virus prevalence, transmission, and treatment is essential for combatting this deadly infection.