Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

asymptomatic with recent vector exposure

1st line – reassurance

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INITIAL
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asymptomatic with recent vector exposure
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unimmunised: non-bite exposure with no infection risk
1st line – 

reassurance

There is no risk of infection if the exposure involves touching or feeding of animals, or licks on intact skin. If the history is reliable, no treatment is required.

1st line – wound cleansing

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INITIAL
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asymptomatic with recent vector exposure
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unimmunised: non-bite exposure with low infection risk
1st line – 

wound cleansing

Nibbling of uncovered skin or minor scratches or abrasions without bleeding carry a low risk of infection, and post-exposure prophylaxis is required.

The wound should be thoroughly washed and flushed with soap and water (or water alone) for 15 minutes, and disinfected immediately with detergent, iodine, or ethanol.

Plus – multiple-dose immunisation protocol

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INITIAL
|
asymptomatic with recent vector exposure
|
unimmunised: non-bite exposure with low infection risk
Plus – 

multiple-dose immunisation protocol

Treatment recommended for ALL patients in selected patient group

The World Health Organization (WHO) recommends either an intradermal (3-dose) or intramuscular (4-dose or 2-1-1 dose) regimen. The intradermal regimen is preferred as it is the most cost-, dose-, and time-sparing regimen.[34]

The US protocol (recommended by the Advisory Committee on Immunization Practices [ACIP]) involves intramuscular injection into the deltoid area (in adults) or anterolateral aspect of the thigh (in children). The first dose is given as soon as possible after the exposure (day 0). 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).[46] There are 2 vaccines available in the US: human diploid cell vaccine and purified chick embryo cell vaccine. Purified vero cell vaccine and purified duck embryo vaccine are other vaccines that are available internationally and pre-qualified by the WHO.

Immunisation protocols vary; consult local guidance for regimens. For example, in the UK, the specific post-exposure prophylaxis regimen is based on the composite rabies risk, the immunisation status of the patient, and whether the patient is immunosuppressed.[47]

Primary options

WHO protocols

rabies vaccine: 0.1 mL intradermally (divided between 2 sites) on days 0, 3, and 7; 1 dose intramuscularly (1-site) on days 0, 3, 7, and between days 14-28; 2 doses intramuscularly (2-sites) on day 0, followed by an additional dose (1-site) on days 7 and 21

OR

ACIP protocol

rabies vaccine: 1 mL intramuscularly on days 0, 3, 7, and 14 (and 28 in immunocompromised patients)

Consider – rabies immunoglobulin

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INITIAL
|
asymptomatic with recent vector exposure
|
unimmunised: non-bite exposure with low infection risk
Consider – 

rabies immunoglobulin

Additional treatment recommended for SOME patients in selected patient group

The World Health Organization (WHO) recommends use in these types of exposures if the patient is immunosuppressed. Individuals with immunodeficiency should be evaluated on a case-by-case basis.[34] ACIP recommends use in all patients with non-bite exposure.[46]

Human rabies immune globulin (hRIG) is infiltrated into the wound(s) without primary closure. The full dose should be given into the wound(s) and surrounding area if anatomically feasible (loose suturing should be performed if necessary only after infiltration).

If this is not possible, US guidelines recommend any remaining hRIG should be given intramuscularly, although WHO guidance no longer supports this.[34][46] The site used to give intramuscular hRIG must be remote 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.

Use of rabies immune globulin may be delayed by up to 7 days from the first vaccine dose if necessary (e.g., it is not available).

Equine rabies immune globulin (eRIG) may be used in developing countries if hRIG is not available (note: the dose differs to hRIG). 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.[34]

In areas where RIG is limited, allocation should be prioritised for patients with high-risk exposures (e.g., multiple bites, deep wounds).[34]

Primary options

rabies immunoglobulin (human): 20 units/kg (maximum) as a single dose infiltrated into the wound and surrounding tissue

More

1st line – wound cleansing

Back
INITIAL
|
asymptomatic with recent vector exposure
|
unimmunised: bite exposure, licks on broken skin or mucous membrane, or exposure to bat bites or scratches
1st line – 

wound cleansing

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 carry a high risk of infection, and post-exposure prophylaxis is required.

The wound should be thoroughly washed and flushed with soap and water (or water alone) for 15 minutes, and disinfected immediately with detergent, iodine, or ethanol.

Plus – multiple-dose immunisation protocol

Back
INITIAL
|
asymptomatic with recent vector exposure
|
unimmunised: bite exposure, licks on broken skin or mucous membrane, or exposure to bat bites or scratches
Plus – 

multiple-dose immunisation protocol

Treatment recommended for ALL patients in selected patient group

The World Health Organization (WHO) recommends either an intradermal (3-dose) or intramuscular (4-dose or 2-1-1 dose) regimen. The intradermal regimen is preferred as it is the most cost-, dose-, and time-sparing regimen.[34]  

The US protocol (recommended by the Advisory Committee on Immunization Practices [ACIP]) involves intramuscular injection into the deltoid area (in adults) or anterolateral aspect of the thigh (in children). The first dose is given as soon as possible after the exposure (day 0). 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).[46] There are 2 vaccines available in the US: human diploid cell vaccine and purified chick embryo cell vaccine. Purified vero cell vaccine and purified duck embryo vaccine are other vaccines that are available internationally and pre-qualified by the WHO.

Immunisation protocols vary; consult local guidance for regimens. For example, in the UK, the specific post-exposure prophylaxis regimen is based on the composite rabies risk, the immunisation status of the patient, and whether the patient is immunosuppressed.[47]

Primary options

WHO protocols

rabies vaccine: 0.1 mL intradermally (divided between 2 sites) on days 0, 3, and 7; 1 dose intramuscularly (1-site) on days 0, 3, 7, and between days 14-28; 2 doses intramuscularly (2-sites) on day 0, followed by an additional dose (1-site) on days 7 and 21

OR

ACIP protocol

rabies vaccine: 1 mL intramuscularly on days 0, 3, 7, and 14 (and 28 in immunocompromised patients)

Plus – rabies immunoglobulin

Back
INITIAL
|
asymptomatic with recent vector exposure
|
unimmunised: bite exposure, licks on broken skin or mucous membrane, or exposure to bat bites or scratches
Plus – 

rabies immunoglobulin

Treatment recommended for ALL patients in selected patient group

Human rabies immune globulin (hRIG) is infiltrated into the wound(s) without primary closure. The full dose should be given into the wound(s) and surrounding area if anatomically feasible (loose suturing should be performed if necessary only after infiltration).

If this is not possible, US guidelines recommend any remaining hRIG should be given intramuscularly, although WHO guidance no longer supports this.[34][46] The site used to give intramuscular hRIG must be remote 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.

Use of rabies immune globulin may be delayed by up to 7 days from the first vaccine dose if necessary (e.g., it is not available).

Equine rabies immune globulin (eRIG) may be used in developing countries if hRIG is not available (note: the dose differs to hRIG). 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.[34]

In areas where RIG is limited, allocation should be prioritised for patients with high-risk exposures (e.g., multiple bites, deep wounds).[34]

Primary options

rabies immunoglobulin (human): 20 units/kg (maximum) as a single dose infiltrated into the wound and surrounding tissue

More

1st line – wound cleansing

Back
INITIAL
|
asymptomatic with recent vector exposure
|
immunised: any exposure with infection risk
1st line – 

wound cleansing

The wound should be thoroughly washed and flushed with soap and water (or water alone) for 15 minutes, and disinfected immediately with detergent, iodine, or ethanol.

Rabies immunoglobulin is not required in these patients.

Plus – multiple-dose immunisation protocol

Back
INITIAL
|
asymptomatic with recent vector exposure
|
immunised: any exposure with infection risk
Plus – 

multiple-dose immunisation protocol

Treatment recommended for ALL patients in selected patient group

The World Health Organization (WHO) recommends either intradermal or intramuscular administration on days 0 and 3, or a 4-site intradermal regimen (four 0.1 mL injections equally distributed over left and right deltoids, thigh, or suprascapular areas during a single visit). The intradermal regimens are preferred as they are the most cost-, dose-, and time-sparing regimens.[34]

The US protocol, recommended by the Advisory Committee on Immunization Practices (ACIP), involves intramuscular injection into the deltoid area (in adults) or anterolateral aspect of the thigh (in children). The first dose is given as soon as possible after the exposure (day 0), with a second dose on day 3.[46] There are 2 vaccines available in the US: human diploid cell vaccine and purified chick embryo cell vaccine. Purified vero cell vaccine and purified duck embryo vaccine are other vaccines that are available internationally and pre-qualified by the WHO.

Immunisation protocols vary; consult local guidance for regimens. For example, in the UK, the specific post-exposure prophylaxis regimen is based on the composite rabies risk, the immunisation status of the patient, and whether the patient is immunosuppressed.[47]

Primary options

WHO protocols

rabies vaccine: one dose intradermally/intramuscularly on days 0 and 3; 0.1 mL intradermally injected four times (equally distributed over left and right deltoids, thigh, or suprascapular areas)

OR

ACIP protocol

rabies vaccine: 1 mL intramuscularly on days 0 and 3

ACUTE

symptomatic rabies

1st line – palliative care

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ACUTE
|
symptomatic rabies
1st line – 

palliative care

Occasional rabies survivors are noted, but there is no recognised curative medical therapy.

The patient should be isolated to minimise the number of medical staff who might need later prophylaxis. Standard precautions are recommended (e.g., masks, gloves, eye/face protection, gowns).

Rabies immunisation or immunoglobulin is contraindicated during active disease, as it confers no benefit and may be harmful.

Many experts recommend palliation. Given that spasms in rabies (hydrophobia and aerophobia) are stimulus driven, recommendations include 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]

Primary options

haloperidol: 0.5 to 10 mg orally every 1-4 hours initially, titrate according to response, maximum 100 mg/day

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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