The history of a rabies-infected patient may be simple and straightforward with a known bite from a rabid animal. Unfortunately, it may be challenging to obtain a history pointing towards rabies due to the potential for a long incubation period and multiple potential transmission methods.

There are five stages of rabies following inoculation: Incubation; Prodrome; Acute Neurologic Illness; Coma; and death.  

Incubation is the period defined as an inoculation to the first onset of symptoms and can range from days to years.

The prodrome phase includes nonspecific symptoms similar to flu-like illnesses with gastrointestinal symptoms, myalgias, and fevers being some of the possible symptoms.

The third stage of rabies is when neurologic symptoms occur. These are classified into one of three categories: encephalitic (also considered "furious"), paralytic (also considered "dumb"), and a rare non-classic form.

• The encephalitic form is most common and presents in approximately 85% of cases. These patients may exhibit hydrophobia or aerophobia, which is when spasms develop as a result of stimuli such as swallowing liquids (hydrophobia).  Agitation and changes in mentation can occur during the encephalitic form, with the potential for autonomic dysfunction, increased deep tendon reflexes, nuchal rigidity, and finding positive Babinski sign. Other examination findings outside the nervous system can include tachycardia, tachypnea, and fever.   This progresses rapidly to hyperactivity.
• The paralytic form of rabies is less common and noted to occur less than 20% of the time. These patients may be confused with Guillain-Barre syndrome as the classically associated hydrophobia, and irritability is not seen. Weakness is a hallmark, though patients may also have altered mentation, ongoing fevers, and bladder dysfunction.
• The final form of rabies is considered non-classic and is rare, generally associated with seizures and more profound motor and sensory symptoms.

Stage 4 of rabies is the coma stage and usually begins within ten days of stage 3. Patients may have ongoing hydrophobia, develop prolonged apnea periods, and have flaccid paralysis.

Following the onset of stage 4, without supportive care due to cardiopulmonary failure, most patients experience death within two to three days. Even with supportive therapy, virtually zero patients survive rabies.

Without a clear-cut rabid bite history, rabies is often a diagnosis of exclusion. In early stages, it may manifest similar to influenza, Coxsackie, enterovirus, and herpes. In later stages, rabies may present similarly to delirium tremens, tetanus, botulism, diphtheria, tick-borne diseases, and Guillain Barre. It is common for physicians to check CBC, electrolytes, cultures, CT, chest x-ray, and MRI and still, have no idea that rabies is the culprit. Unless isolated in a rabies-specific viral culture, detected by polymerase chain reaction (PCR) in saliva, found to have positive antibody titer, or isolated in cerebrospinal fluid (CSF), the diagnosis may continue to be elusive until too late.

Rabies can be diagnosed through multiple routes using CSF, blood, saliva, tears, and tissue biopsies (neck, immunofluorescent stain). CSF analysis can show a pleocytosis and may allow isolation of the virus.  The Centers for Disease Control and Prevention notes that no single test is enough to rule in or out rabies.  Ultimately, a high level of suspicion is required in developed countries due to the rarity of the disease.[9][10][11]

There is no effective treatment for rabies. Prevention is the mainstay of treatment including programs involving domestic animal vaccination, education, and monitoring.[12][13][14]

Wound care is the first step in the treatment of any individual with a feared rabies exposure. Appropriate wound care alone has been noted to be almost 100% effective if initiated within three hours of inoculation. Recommendations include scrubbing the wound and surrounding area with soap and water (solutions include 20% soap solution, povidone, and alcohol solutions), and swabbing deeply for puncture wounds, with irrigation. After cleaning the wound thoroughly the application of a virucidal agent such as benzalkonium chloride or povidone-iodine is recommended.

In the United States, when a bite is known to be from a bat, skunk, raccoon, or fox, treat immediately with rabies vaccine and rabies immune globulin. For all other bites, consult the public health department. Outside of the United States, a dog bite should be treated immediately with vaccine and rabies immune globulin.

Treatment is then initiated based on if the patient was previously immunized or not. For patients with previous immunization, a typical treatment may be with human diploid cell vaccine or purified chick embryo cell vaccine at a dose of 1 mL injected intramuscularly on the day it occurs (day 0) and on day 3.

If the patient has not been previously immunized, the treatment still involves dosing with one of the two vaccines listed above with 1 mL given intramuscularly on days 0, 3, 7, and 14 (and on day 28 if the individual is immunosuppressed). The dose of the vaccine should be given at a site distant to where the second part of treatment (human rabies immune globulin or HRIG) is given. These unimmunized patients are treated with human rabies immune globulin as well at a dose of 20 IU/kg, with preference to infiltrate as much of that dose around the wound as possible. Any remaining dose of human rabies immune globulin not infiltrated to the wound is then given intramuscularly, and as mentioned above is given at a site distant to the vaccine.

Recently, recommendations have been updated in the United States, and since bats are by far the major source of rabies here, any person who awakens from sleep and finds a bat in the room should be urgently immunized.

• Psychosis
• Seizures
• Poisoning with belladonna alkaloids
• Stroke
• Jacob Creutzfeldt disease
• Brain tumor
• Encephalitis
• Tetanus

• Seizures
• Fasciculations
• Psychosis
• Aphasia
• Autonomic instability
• Paralysis
• Coma
• Death

• Neurologist
• Infectious disease
• Neurosurgeon
• Public health

When a diagnosis of rabies is made, an interprofessional team is necessary as the repercussions of this infection go way beyond the acute infection.

Blood transfusions have not been documented to transmit rabies, though it has been suggested to hold donation for one year following exposure prophylaxis. If no exposure was noted, but vaccination occurred there is a recommendation to wait four weeks.

Since rabies is entrenched within the native animal population in the United States, there will continue to be human exposure to this fatal disease. Public health officials take a very active role in preventing rabies, both before exposures as well as after possible exposures.

Animal control has to be notified to determine if the domestic animals require vaccination. In addition, vaccination of workers who may be exposed to rabies may also be necessary.

Patients need to be educated on avoiding contact with wildlife, and if ever bitten, the area should be thoroughly washed to lower the risk of rabies transmission. All dead and sick animals should be handled with heavy gloves. If bitten by a wild animal, one should seek immediate medical assistance. [15][16][17](Level V)

Outcomes

For those who develop symptoms of rabies, survival is rare. Only a handful of survivors exist in the USA after acquiring rabies. For those without symptoms but with rabies vaccine prophylaxis, survival is assured. Individuals who are bitten by a rabid animal need the rabies vaccine and immunoglobulin ASAP for survival- once the symptoms appear, death is inevitable.[18][19] (Level V)