Approach
The most commonly encountered clinical situation is an asymptomatic patient with potential rabies exposure. The type of post-exposure prophylaxis (PEP) required depends on the type of exposure and the immunisation status of the patient. PEP should be started immediately if rabies is suspected; laboratory diagnosis is not required. Symptomatic rabies is rare, and almost always fatal. The treatment is either palliative or supportive. Aggressive management protocols may be considered in exceptional circumstances; however, they do not reliably result in survival without severe sequelae.[41] Effective antiviral agents do not exist.
Management of rabies exposure
PEP consists of an effective rabies vaccine and administration of rabies immunoglobulin (if necessary) after cleaning and disinfection of the wound. PEP is highly effective and should be given to any asymptomatic patient with a documented or likely exposure, regardless of the time that has elapsed since the exposure. However, PEP should not be given to symptomatic patients.[46]
In the US, the Advisory Committee on Immunization Practices (ACIP) defines exposures as bite or non-bite.[46]
The World Health Organization (WHO) defines 3 categories of exposure:[34]
Category I: touching or feeding of animals, or licks on intact skin (no risk of infection if the history is reliable).
Category II: nibbling of uncovered skin, or minor scratches or abrasions without bleeding (low risk of infection).
Category III: single or multiple transdermal bites or scratches, licks on broken skin, contamination of mucous membrane with saliva from licks, or exposure to bat bites or scratches (high risk of infection).
The PEP protocol depends on whether the patient has previously been immunised against rabies. Pre-exposure rabies immunisation is reserved for people at increased risk of contracting rabies. See Prevention.
If a non-immunised patient has had a bite or non-bite exposure as defined by ACIP criteria, or a category II or III exposure as defined by WHO criteria, PEP is required, and consists of the following steps:[34][46]
The unclosed wound is immediately and thoroughly washed and flushed with soap and water (or water alone) for 15 minutes, and disinfected with detergent, iodine, or ethanol.
For bite or non-bite exposure (ACIP criteria) or category III (WHO criteria) exposure, human rabies immune globulin (hRIG) is infiltrated into the wounds without primary closure (loose suturing should be performed if necessary only after infiltration). It should be administered once as soon as possible after the initiation of PEP, and not beyond day 7 after the first dose of vaccine. The full dose should be given into the wound and surrounding area if anatomically feasible. If this is not possible, ACIP recommend that any remaining hRIG should be given intramuscularly, although WHO guidance no longer supports this. The site used to give intramuscular hRIG must be remote from the wound and from the site used to give the vaccine. The total dose should not be exceeded; if the calculated dose is insufficient to infiltrate all wounds, sterile saline may be used to dilute the hRIG to allow thorough infiltration. hRIG may not be available in developing countries, and equine rabies immune globulin (eRIG) may be used in these locations; both have shown similar clinical outcomes in the prevention of rabies. eRIG is less costly than hRIG and can now be administered without initial skin testing. In areas where RIG is limited, allocation should be prioritised for patients with high-risk exposures (e.g., multiple bites, deep wounds).
For bite or non-bite exposure (ACIP criteria) or category II and III exposures (WHO criteria), rabies vaccination should be given:
The ACIP recommends that the vaccine be given intramuscularly and must be given at the correct site. In adults, this is the deltoid area. In children, the anterolateral aspect of the thigh is acceptable. The gluteal area must never be used. The first dose is given as soon as possible after the exposure. Further doses are given 3, 7, and 14 days after the initial dose (an additional dose at 28 days is recommended if the patient is immunocompromised).
The WHO recommends either an intradermal (3-dose) or intramuscular (4-dose or 2-1-1 dose) regimen. The intradermal regimen is preferred as it the most cost-, dose-, and time-sparing regimen.
If a patient vaccinated against rabies has bite or non-bite exposure (ACIP criteria) or has a category II or III exposure (WHO criteria), PEP is required, but the protocol is modified. Rabies immunoglobulin is not recommended. The wound is cleansed and a 2-dose intradermal or intramuscular regimen is given consisting of an immediate dose and a second dose 3 days later. The WHO also recommends a 1-dose (4-site) intradermal regimen. If repeat exposure occurs within 3 months of PEP, further PEP is not required.[34][46]
In the UK, the UK Health Security Agency recommends using the combined country/animal risk and the category of exposure to determine a composite rabies risk (designated as green, amber, or red). The specific PEP regimen is based on the composite rabies risk, the immunisation status of the patient, and whether the patient is immunosuppressed.[47]
UKHSA: summary of rabies risk assessment and post-exposure treatment Opens in new window
PEP does not have any contraindications if purified rabies immunoglobulin and vaccine are used. It is recommended in children and pregnant women.
Other treatments may include antibiotics and tetanus prophylaxis depending on the presentation.
Management of symptomatic rabies
The patient should be isolated and standard precautions for infectious patients observed. Rabies immunisation or immunoglobulin is contraindicated during active disease, as it confers no benefit and may be harmful. Occasional rabies survivors are noted, but there is no recognised curative medical therapy. Many experts recommend palliation. Given that spasms in rabies (hydrophobia and aerophobia) are stimulus driven, standard therapies follow those for tetanus, which involve seclusion, room darkening, and restraint. The only study of palliation in rabies recommends haloperidol.[48][49] Other agents that may be used to relieve symptoms include opioid analgesics, anticonvulsants (for seizures), and neuromuscular blockers.[50]
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