Approach
Rabies should be suspected in any patient with a history of animal exposure who has an unexplained encephalitis or myelitis. It is a rare cause of encephalitis in industrialised nations; therefore, more common causes should be simultaneously considered and excluded. Symptoms of rabies progress rapidly over a period of days. If this rapid progression does not occur, rabies infection is less likely.[13][38][39]
Rabies is a notifiable disease in many countries. Cases should be reported immediately to local health authorities.
History
It is important to establish whether the patient has had a documented or likely exposure from a known vector. Known vectors include dogs, bats, raccoons, skunks, foxes, jackals, and mongooses. Most patients in the US contract rabies from bats.[17] A history of a bat bite or contact with a bite may be present. Some patients may report finding a bat in the home. However, in many cases, there is no history of contact with bats or any other vector, so the absence of an animal exposure history should not be used to exclude rabies.
Dogs are the main vectors in most rabies-endemic developing countries. The red fox is the main vector in Western Europe. Vectors in other countries include coyotes; red, arctic, and grey foxes; jackals; mongooses; raccoons; skunks; and wolves.[18] In the UK, the UK Health Security Agency has also issued information. NaTHNaC/Travel Health Pro: rabies factsheet Opens in new window
People at elevated risk for exposure to rabies include:[33]
People working with live rabies virus in research or vaccine production facilities
People performing diagnostic testing for rabies in laboratories
People with frequent bat contact
People who interact with animals who could be rabid
People who perform animal necropsies
People whose occupational or recreational activities typically involve animal contact
Selected travellers (depending on occurrence of animal rabies in destination country, availability of treatments, intended activities, and duration of stay).
Occupations at higher risk include animal handlers, field biologists, cavers, missionaries, veterinarians, and some laboratory workers. Children are at highest risk of infection because of their height, developmental skills, and proximity to dogs in the street.[33]
Clinically, rabies has 2 forms: encephalitic (furious) and paralytic. Both have non-specific prodromes of fever, chills, malaise, sore throat, vomiting, headaches, and paraesthesias. Pain or paraesthesias at the site of the animal bite are often present in both forms. Pruritus is another common presenting feature.
In the encephalitic form, the prodrome is followed by symptoms of altered mental status, agitation, hyperactivity, tremors, hypersalivation, mydriasis, dysphagia, hydrophobia with hydrophobic spasms, and aerophobia. The patient often maintains alertness and cognition at intervals. Hydrophobic spasms may progress to cause seizures. The encephalitic symptoms are followed by paralysis. As paralysis sets in, patients may have involvement of the bladder or bowel sphincters, leading to faecal or urinary incontinence. Coma and death follow rapidly.
In the paralytic form, there are no early changes in mental status. Ascending weakness rapidly progresses to flaccid paralysis, coma, and death.
There is the suggestion that milder forms of rabies may exist.[2][3][4]
Physical examination
Fever is a key sign of rabies, and the diagnosis of rabies is unlikely unless the patient is at least intermittently febrile. Hydrophobia and aerophobia are the most specific signs. Severe laryngeal or diaphragmatic spasms and a sensation of choking occur.
In rabies-endemic countries, offering a cup of water to elicit hydrophobia and fanning air at the face (or placing nasal cannulae) to elicit aerophobia are common manoeuvres. The patient can have signs of autonomic instability, including hypertension, profuse hypersalivation, marked tachycardia, priapism, and hyperthermia. Signs of paralysis appear late in the disease course. Numbness and weakness typically affect the same side of the body as the bite. Careful neurological examination excludes paresis associated with conversion disorders.[39][40]
Investigations to diagnose rabies
Diagnosis relies on viral antigen detection, viral antibody detection, viral RNA detection, or virus isolation.[41] Establishing the diagnosis usually requires the simultaneous testing of saliva, a skin biopsy, CSF, and serum. The virus is more likely to be detected at the beginning of the clinical course.
Saliva is tested using PCR for rabies RNA. Most patients with rabies have a positive result with repeated testing, as PCR testing is very sensitive. Viral culture can be used to isolate the virus if the results of other tests are equivocal. A negative result in saliva alone does not exclude rabies. A positive result is also an indication of the infectivity of patient and of the need for patient isolation and prevention measures in healthcare personnel.
A 5- to 6-mm skin biopsy is taken from the posterior region of the neck at the hairline. Rabies can be detected by direct fluorescent antibodies against rabies antigens or PCR for rabies RNA. PCR testing is very sensitive.
CSF is examined microscopically and tested for biochemical markers and the presence of rabies antibodies. A lymphocytic pleocytosis is detectable in 60% of patients in the first week and 85% of patients in the second week. CSF protein levels may be mildly elevated (>0.5 g/dL [>50 mg/dL]), with a low to normal glucose concentration. CSF quinolinic acid is high early on, and lactate progressively increases over days. Rabies can be detected in CSF by detection of neutralising antibodies.
Serum and CSF are tested for the presence of neutralising antibodies but are rarely diagnostic at presentation. Antibodies may not be detected at early stages of the disease, but serial tests will demonstrate increase in antibody levels by day 14 of hospitalisation. A positive result in serum indicates infection only in patients who have not been immunised; a positive result in CSF is always diagnostic.
A negative result in any 1 sample alone does not exclude rabies. Results in saliva, skin biopsy, CSF, and serum (in non-immunised patients) must all be negative. If the results are negative and the clinical suspicion is high, the tests should be repeated.[38][39][42]
Investigations to exclude other causes
CSF should also be tested to exclude other treatable causes of encephalitis. CSF is usually sent to test for HSV (using PCR), enterovirus (using PCR), and West Nile virus (detection of antibodies). Serological tests for arboviruses, Bartonella, and rickettsial infection should also be considered. Testing for CSF N-methyl-D-aspartate (NMDA) glutamate receptor antibodies is necessary to exclude this common mimic of rabies.[43]
An MRI of the head may be performed to exclude other causes of neurological symptoms, and is generally normal in the first week of rabies.[42]
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