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4.16.1 Virology
Lyssaviruses are single-stranded RNA viruses in the family Rhabdoviridae, genus Lyssavirus. There are 12 known
species within the genus Lyssavirus, including the classical rabies virus and other closely related lyssaviruses such as
the Australian bat lyssavirus (ABLV) and European bat lyssaviruses. 1
4.16.2 Clinical features
Rabies is a zoonotic disease caused by human exposure to saliva or nerve tissue of an animal infected with rabies virus
or other lyssaviruses. As the clinical disease caused by classical rabies virus and other lyssaviruses is indistinguishable,
the term ‘rabies’ refers to disease caused by any of the known lyssavirus species. 2-5 Human exposure can occur via a
scratch or bite that has broken the skin, or via direct contact with the mucosal surface of a person, such as nose, eye or
mouth. Most human cases of rabies occur after animal bites – cases after animal scratches, the licking by animals of
open wounds or contact of animal saliva with intact mucous membranes are very rare. Aerosol transmission has never
been well documented in the natural environment.6 There has been transmission of rabies virus reported following
tissue or organ transplantation from donors who died with undiagnosed rabies.7 Transmission of rabies virus to humans
through unpasteurised milk may be possible; however, rare reports of transmission via this route have not been
confirmed.8
Once a person is infected, the incubation period of rabies is usually 3 to 8 weeks, but can range from as short as a week
to, on rare occasions, several years. The risk of rabies is higher, and the incubation period shorter, after severe and
multiple wounds proximate to the central nervous system (such as on the head and neck) and in richly innervated sites
(such as the fingers).
Rabies is almost invariably fatal. Typically, in the prodromal phase of rabies, which lasts up to 10 days, the patient may
experience non-specific symptoms such as anorexia, cough, fever, headache, myalgia, nausea, sore throat, tiredness and
vomiting.9 Paraesthesiae and/or fasciculations at or near the site of the wound may be present at this stage. Anxiety,
agitation and apprehension may also occur. Most rabies patients present with the furious or encephalitic form. 10 In the
encephalitic phase, objective signs of nervous system involvement include aerophobia, hydrophobia, bizarre behaviour,
disorientation and hyperactivity. Signs of autonomic instability such as hypersalivation, hyperthermia and
hyperventilation may occur.10 The neurological status of the patient deteriorates over a period of up to 12 days, and the
patient either dies abruptly from cardiac or respiratory arrest, or lapses into a coma.
4.16.3 Epidemiology
The epidemiology of rabies varies depending on the lyssavirus species and the animal host. Lyssaviruses have been
found in all continents, except Antarctica.11 Rabies that is due to the classical rabies virus and occurs in land dwelling
(terrestrial) mammals is present throughout much of Africa, Asia, the Americas and Europe, where the virus is
maintained in certain species of mammals, particularly dogs. In countries where rabies vaccination of domestic animals
is widespread (North America and Europe), wild animals such as raccoons and foxes are important reservoirs. The
continual maintenance of rabies in animal populations in these countries is referred to as enzootic rabies. Australia, New
Zealand, Japan, Papua New Guinea and Pacific island nations are currently free of rabies in terrestrial mammals.
However, a country’s status can change at any time. For example, in 2008 on the island of Bali, Indonesia, rabies was
reported in dogs, with cases later reported in humans. 12 Prior to this, Bali had been considered free of rabies, although
rabies was known to occur in other areas of Indonesia. 13
In some parts of the world, bats are important reservoirs of classical rabies as well as other lyssaviruses, with bat
lyssaviruses found in areas that are considered free from terrestrial rabies. ABLV was first reported in bats in 1996;
since then, three cases of fatal encephalitis caused by ABLV have been reported in Australians, in 1996, 1998 and
2013.2,14,15 All three patients had been either bitten or scratched by bats. Evidence of ABLV infection has been
identified in all four species of Australian fruit bats (flying foxes) and in several species of Australian insectivorous
bats.4,16-18 It should therefore be assumed that all Australian bats have the potential to be infected with ABLV. Different
regions in Australia have reported higher risk of potential ABLV exposures. 19,20 ABLV has not been isolated from bats
outside Australia. However, closely related lyssaviruses are found in bats in other countries. For example, European bat
lyssavirus 1 and European bat lyssavirus 2 have been isolated in bats in some parts of Europe. Four human deaths from
European bat lyssavirus variants have been reported in Europe, all with no record of prophylactic rabies
immunisation.3,5 As such, bats anywhere in the world should be considered a potential source of lyssaviruses and a
potential risk for acquiring rabies, depending on the exposure. There are rare reports of bat lyssavirus infections in other
animals.21-23 The first confirmed cases of ABLV in terrestrial mammals in Australia occurred in two horses in
Queensland in 2013.24
Information on the global occurrence of rabies can be obtained from reputable international authorities. 11,25,26 In
addition, advice on potential lyssavirus exposures and their management should be obtained by contacting the relevant
Australian state/territory health authorities (refer to 4.16.12 Public health management of lyssavirus infections below).
The Australian Immunisation Handbook 10th edition (updated August 2017) 1
4.16.4 Rabies vaccines
Mérieux Inactivated Rabies Vaccine – Sanofi Pasteur Pty Ltd (human diploid cell vaccine [HDCV]).
Lyophilised powder in a monodose vial with 1.0 mL distilled water as diluent. Each 1.0 mL reconstituted dose
contains ≥2.5 IU inactivated rabies virus; 100–150 µg neomycin; ≤70 mg human serum albumin; trace of phenol
red (indicator). May contain trace amounts of bovine gelatin and -propiolactone.
Rabipur Inactivated Rabies Virus Vaccine – CSL Limited/Novartis Vaccines and Diagnostics Pty Ltd (purified
chick embryo cell vaccine [PCECV]). Lyophilised powder in a monodose vial with 1.0 mL distilled water as
diluent. Each 1.0 mL reconstituted dose contains ≥2.5 IU inactivated rabies virus; trace amounts of neomycin,
chlortetracycline, trometamol, -propiolactone, monopotassium glutamate and amphotericin B. May contain
trace amounts of bovine gelatin and egg protein.
There are two inactivated rabies cell culture-derived vaccines available in Australia.
The Mérieux vaccine is a lyophilised, stabilised suspension of inactivated Wistar rabies virus that has been cultured on
human diploid cells and then inactivated by β-propiolactone. This human diploid cell vaccine (HDCV) is coloured off-
white, but after reconstitution with the diluent it turns a pinkish colour due to the presence of phenol red. The vaccine
does not contain a preservative.
Rabipur is a lyophilised, stabilised suspension of inactivated Flury LEP rabies virus that has been cultured on purified
chick embryo cells and then inactivated by β-propiolactone. This purified chick embryo cell vaccine (PCECV) does not
contain a preservative.
Rabies vaccine is effective and safe when used for pre-exposure prophylaxis (PreP) and post-exposure prophylaxis
(PEP) for rabies virus.27,28 Although data on the effectiveness of rabies vaccine as prophylaxis against other lyssaviruses
are limited, the available animal data and clinical experience support its use. 20,29-34
4.16.5 Rabies immunoglobulin
Imogam Rabies Pasteurized – Sanofi Pasteur Pty Ltd (human rabies immunoglobulin [HRIG]). Each 1.0 mL
contains IgG class human rabies antibodies with a minimum titre of 150 IU; 22.5 mg glycine; 1 mg sodium
chloride. Supplied in 2 mL vials.
Human rabies immunoglobulin (HRIG) is prepared by cold ethanol fractionation from the plasma of hyperimmunised
human donors.
In exceptional circumstances, such as product shortages, other HRIG products may be made available for use in
Australia. For example, KamRAB Rabies Immune Globulin (Kamada, Israel), although not registered by the TGA, has
been made available under the Special Access Scheme due to a critical shortage of alternative products. Advice on the
use of HRIG products will be provided by state and territory health authorities (refer also to 4.16.12 Public health
management of lyssavirus infections above).
4.16.6 Transport, storage and handling
Rabies vaccine
Transport according to National vaccine storage guidelines: Strive for 5.35 Store at +2°C to +8°C. Do not freeze.
Both rabies vaccines must be reconstituted by adding the entire contents of the diluent container to the vial and shaking
until the powder is completely dissolved. Reconstituted vaccine should be used immediately.
Human rabies immunoglobulin
Transport according to National vaccine storage guidelines: Strive for 5.35 Store at +2°C to +8°C. Do not freeze. Protect
from light.
HRIG should be used immediately once the vial is opened.
4.16.7 Dosage and administration
Rabies vaccine
The dose of rabies vaccine for use in PreP and PEP is 1.0 mL, to be given by IM injection and is the same for infants,
children and adults.
Table 4.16.1: Lyssavirus exposure categories, to be used in conjunction with Figure 4.16.1 or 4.16.2 to
determine appropriate post-exposure prophylaxis
The relevant state/territory health authority should be contacted about any of the following potential exposures, in order
to conduct a detailed risk assessment and advise on management. (Refer also to 4.16.12 Public health management of
lyssavirus infections below.)
Potential exposure sustained from a terrestrial animal in a rabies-enzootic area, or any potential exposure sustained
from a bat anywhere in the world: Dogs and monkeys are the usual exposures in Asia, Africa and Central and
South America, but exposures to other terrestrial mammals and bats must also be assessed for potential classical
rabies virus transmission. If a traveller presents >10 days after being bitten or scratched by either a domestic dog,
cat or ferret in a rabies-enzootic country, and it can be reliably ascertained that the animal has remained healthy
(>10 days after the exposure), PEP is not required. Otherwise, PEP appropriate for the category and source of
exposure (refer to Figure 4.16.1 or 4.16.2) should be administered, even if there has been a considerable delay in
reporting the incident.
Potential exposure to Australian bats: This includes situations where the exposure may be difficult to categorise
because a person is unaware or unable to communicate that an exposure has occurred when in close proximity to a
bat (e.g. a person with an intellectual disability, an intoxicated person, a child, or a person who has been sleeping in
a confined space with a bat present). If possible, and without placing others at risk of exposure, the bat should be
kept and arrangements promptly made for testing the bat for ABLV. Following wound management (refer below),
the administration of HRIG and rabies vaccine can be withheld if the bat’s ABLV status will be available within 48
hours of the exposure. If the result will not be available within 48 hours, the appropriate post-exposure prophylaxis
should begin as soon as is practicable, following the bat exposure algorithm as outlined in Figure 4.16.2. Where a
bat is tested at a reference laboratory and later found to be negative for ABLV, then PEP for the person exposed to
that bat can be discontinued.
Vaccine type/route administered Rabies vaccine schedule in HRIG Category III terrestrial
overseas/ rabies immunoglobulin Australia animal exposures and Category II
(RIG) and III bat exposures only*
Nerve tissue vaccine Recommence schedule starting from Administer HRIG if no RIG already
day 0 given
Do not give HRIG if more than 7
days since 1st dose of vaccine (day 0)
Unsure/unknown/poor Recommence schedule starting from Administer HRIG if no RIG already
documentation day 0 given
Do not give HRIG if more than 7
days since 1st dose of vaccine (day 0)
Well documented, RIG (equine or Align with nearest due dose and No HRIG needed
human) given, plus vaccine given resume schedule administering
either IM or ID vaccine IM (IM or SC if HDCV
used)
2 vaccine doses given IM on day 0 Give a further 2 doses; the 1st dose Administer HRIG if no RIG already
Irrespective of whether RIG (equine on day 7 and the 2nd dose on day 14 given
or human) was administered at same Do not give HRIG if more than 7
time as the 1st doses of vaccine days since 1st doses of vaccine (day
0)
Immunocompromised with vaccines Irrespective of number of previous Administer HRIG if no RIG already
administered ID doses, administer a 5-dose schedule given
IM (IM or SC if HDCV used) and Do not give HRIG if more than 7
check serology (refer to ‘Serological days since 1st dose of vaccine (day 0)
testing following rabies vaccination’
below)
* Refer to Table 4.16.1 Lyssavirus exposure categories and Figures 4.16.1 and 4.16.2 for further information of PEP pathways, including HRIG
administration following either a terrestrial animal or bat exposure.
No prophylaxis is ‡ ‡
Non-immune, Previously Non-immune,
required if contact *†
immunocompetent immunised immunocompetent
history is reliable
§
Vaccinate Vaccinate¶
4 doses administered IM on Both immunocompetent and
days 0, 3, 7 and 14. Human immunocompromised persons – 2 doses
rabies immunoglobulin (HRIG) delivered IM on days 0 and 3. HRIG is
is not indicated. not indicated.
†
Category I Category II or III
• Touching or feeding Nibbling of uncovered skin, any scratches or abrasions with/without
animals, licks on intact bleeding, single or multiple transdermal bites or scratches, contamination
skin of mucous membrane with saliva from licks, or licks on broken skin
• Exposure to blood,
urine or faeces
*‡ §
Previously immunised Non-immune, immunocompetent
# #
Vaccinate¶ Vaccinate and administer HRIG
No prophylaxis is
required if contact history Both immunocompetent and HRIG is administered only once, and
is reliable immunocompromised persons as soon as possible after the
– 2 doses delivered IM on days initiation of PEP (HRIG is not
0 and 3. Human rabies indicated beyond the 7th day after
immunoglobulin (HRIG) is not the 1st vaccine dose on day 0).
indicated. Rabies vaccination is 4 doses
administered IM on days 0, 3, 7 and
14.
Perform serology
i) Every 6 months for laboratory staff at risk
ii) Every 2 years for veterinary workers, bat handlers or
any other workers who are likely to need to handle bats.
* Immunocompromised patients’ serology should be checked 14 to 21 days post booster dose and a further dose offered if the result remains <0.5
IU/mL.