Revision history

1. Summary
2. The disease
3. Routine prevention activities
4. Surveillance objectives
5. Data management
6. Communications
7. Case definition
8. Laboratory testing
9. Case management
10. Control of environment
11. Contact management
12. Special situations
13. References
14. Appendices

1. Summary

Public health priority

Urgent.

Case management

No known effective treatment. Isolate case with standard and contact precautions for the duration of illness. Determine the source of infection.

Contact management

Urgently assess the need for post-exposure prophylaxis in people exposed to mammalian animals or confirmed human cases. Use of human rabies immunoglobulin (HRIG) and rabies vaccine is dependent on the type of exposure and prior vaccination.

2. The disease

Infectious agents

Rabies lyssavirus, Australian bat lyssavirus (ABLV), and other lyssaviruses such as European bat 1 lyssavirus (EBLV 1) and EBLV 2, are members of the Rhabdoviridae family, genus Lyssavirus. Sixteen closely related but distinct lyssavirus species have been formally recognised. ^[1] Rabies virus and other lyssaviruses cause the disease rabies.

Reservoir

All mammals are susceptible to rabies and therefore are possible reservoirs. Dogs are the principal reservoir in developing countries and are responsible for 99% of human infections. ^[2] Other reservoirs and important vectors include wild and domestic Canidae, including dogs, foxes, coyotes, wolves and jackals; and bats, cats, monkeys, skunks, raccoons, and mongooses. Other mammals may rarely be infected.

Australia is currently free of rabies in terrestrial (land dwelling) mammals. However, evidence of ABLV infection has been documented in several species of flying foxes (also known as fruit bats) and insectivorous microbats. It is assumed that all Australian bat species have the potential to carry and transmit ABLV. ABLV has not been isolated from bats outside Australia. However, several lyssavirus species have been found in bats in other countries considered free of terrestrial rabies. It is assumed that bats anywhere in the world have the potential to carry and transmit lyssaviruses.

Mode of transmission

Rabies lyssavirus is transmitted by the virus-laden saliva of an infected animal introduced via a bite or scratch, or by contamination of mucous membranes or broken skin. Person-to-person transmission via saliva is extremely rare and has not been well documented. There have been rare reports of rabies transmission by transplantation of infected tissues/organs ^{[3, 4]} and via inhalation of virus-laden aerosol in laboratory settings. ^{[5, 6]} Aerosol transmission in humans has not been proven in the natural environment but based on animal experiments it remains theoretically possible. ^{[7, 8]}

The only three known human cases of ABLV infection occurred in people who had been bitten or scratched by bats. It is assumed that the mode of transmission for ABLV and other lyssaviruses is similar to that of rabies lyssavirus. Bat or other animal blood, urine, and faeces are not considered to be infectious. ^[9]

Incubation period

The incubation period for rabies virus infection is usually 3-8 weeks, rarely as short as a few days or as long as several years.10 The length of the incubation period depends on many factors including wound severity, wound location in relation to nerve supply, proximity to the brain, size of inoculum of virus and the degree of protection provided by clothing and other host factors. ^[10] The incubation period for ABLV and other lyssavirus infections is less certain but is assumed to be similar to rabies lyssa virus; the first two documented cases of ABLV infection had likely incubation periods of approximately 4 weeks and over 2 years, respectively. ^[11] The likely incubation for the third case has not been confirmed

Infectious period

The infectious period for rabies lyssavirus infection has been described reliably only in dogs, cats and ferrets, in which communicability usually commences 3-7 days before onset of clinical signs and persists throughout the course of the illness. ^[10] The period of communicability of ABLV and other lyssaviruses is not known.

Clinical presentation and outcome.

As the clinical disease caused by classical rabies lyssavirus and other lyssaviruses appears to be indistinguishable, the term ‘rabies’ refers to disease caused by any of the known lyssaviruses. Rabies is an almost invariably fatal, acute viral encephalomyelitis. Initial symptoms include fever and sensory changes (pain or paraesthesia) at the site of a preceding animal bite. Other reported prodromal symptoms include a sense of apprehension, headache and malaise. There are 2 clinical forms of rabies. Encephalitic or furious rabies presents in about two-thirds of cases, and is characterised by hyperactivity and aerophobia and/or hydrophobia followed by delirium with occasional convulsions. The second form, paralytic or dumb rabies, presents in about one-third of cases, with paralysis of limbs and respiratory muscles with sparing of consciousness. ^[12] Phobic spasms may be absent in the paralytic form. Death from cardiac or respiratory failure occurs within a few days for furious rabies and within 1-2 weeks for the paralytic form of the disease. ^[2,^10]

People at increased risk of disease

The risk of infection after the bite of a rabid animal can range from less than 1% to over 80%, presumably related to the size of inoculum, severity of bite, nerve density in the area of the bite, proximity of the bite to the central nervous system, vaccination status and immunocompetence. ^[13] People at increased risk of rabies/ABLV infection are those whose occupational, volunteering, or recreational activities put them at increased risk of exposure, i.e. being bitten or scratched by animals in rabies-enzootic countries or by bats anywhere in the world. In Australia, therefore, risk is greatest in those who holiday or work in countries in which rabies is enzootic, and in those most likely to come into contact with bat species, including wildlife carers, wildlife officers, veterinarians and those who live in areas where bats are common and have direct contact with bats.

Disease occurrence and public health significance

Australia is free from terrestrial rabies. Only two imported human cases have been reported in Australia, in people from enzootic areas. ^{[14, 15]} Rabies lyssavirus is enzootic in Asia (including Southeast Asia where large numbers of Australians travel), Africa, North and South America and parts of Europe. Worldwide, it is estimated that rabies virus is responsible for more than 55,000 deaths per year, almost all in rural areas of Asia and Africa, with the highest incidence in children under 15 years. ^[16] Rabies is estimated to have at least as much public health impact in tropical countries as dengue fever (when comparing disability-adjusted life years) and results in an estimated annual global financial burden of over US$ 1 billion. ^{[16, 17]} Most human deaths follow dog bites for which adequate post-exposure prophylaxis was not or could not be provided. Post-exposure prophylaxis initiated at an early stage using rabies vaccine in combination with rabies immunoglobulin is effective in preventing death. In Australia, rabies is subject to quarantine controls under Commonwealth biosecurity legislation - currently the Quarantine Act 1908. The primary concern is the prevention of the introduction of rabies virus to local dog and wildlife populations.

ABLV is unique to Australia and was first identified in 1996 in an encephalitic black flying fox. Three human cases have subsequently been reported, in 1996, 1998 and 2013 with all three cases developing fatal encephalitis after being bitten or scratched by bats. ^{[11, 18-20]} To date, virological and/or serological evidence of ABLV infection has been found in all four species of flying foxes (megachiropterans) found in Australia, and at least seven genera of Australian insectivorous bats. ^[21] Any Australian bat should be considered a potential carrier of the virus. The risk of human exposure to ABLV is related to the extent of human contact with Australian bats.

In 2013 two horses from the same Queensland property were confirmed to be infected with ABLV. Both horses displayed neurological signs and were euthanased. ^[22] The risk of secondary transmission to humans is thought to be very low; however, a risk assessment should be conducted following any potential exposure (see Domestic animals exposed to a bat in Australia).

Four human deaths have been documented following bat exposures in Europe (in Ukraine, the Russian Federation, Finland and Scotland). All presented with clinical features of rabies. The causative viruses were identified as EBLV 1a, EBLV 2a, EBLV 2b, and one untyped lyssavirus. ^{[23, 24]} Spillover infections with EBLV have been reported in 5 sheep, 2 cats and a stone marten in Europe. ^[25-27]

3. Routine prevention activities

Pre-exposure vaccination

Pre-exposure vaccination with rabies vaccine is recommended for people whose occupation (including volunteer work) or recreational activities place them at increased risk of being bitten or scratched by bats, and, following a risk assessment, those who work in or travel to rabies-enzootic countries. (WHO maintain maps of rabies-enzootic areas; The UK Health Protection Agency (HPA) maintains a list of terrestrial rabies risk by country).

Current recommendations for pre-exposure vaccination include:

• bat handlers, veterinarians, wildlife officers, and others who come into direct contact with bats; laboratory personnel working with live lyssaviruses
• expatriates and travellers (following a risk assessment) who will be spending time in rabies-enzootic areas
• people working with mammals in rabies-enzootic areas. ^[9]

Pre-exposure vaccination with rabies vaccine consists of 3 doses by intramuscular (IM)* injection; with the second dose 7 days after the first and the third dose 21-28 days after the first dose. Although the third dose can be given as early as Day 21, there are no data to support the use of an even more accelerated schedule for those with limited time before travel to a rabies-enzootic country. ^[9]

Booster doses are not required for anyone who has received 3 or more previous IM doses of rabies vaccine, if their only exposure risk is travelling to or living in a rabies enzootic area. ^[16] Booster doses may be required if there is an ongoing occupational (including volunteer work) exposure risk, on the basis that there may be increased likelihood of an inapparent exposure occurring. An algorithm outlining the approach to booster doses is provided at Appendix 1. Consult the current edition of The Australian Immunisation Handbook if further information on vaccine administration and booster doses are required. ^[9]

* As described in The Australian Immunisation Handbook, there are two rabies vaccine preparations available in Australia, one a human diploid cell vaccine (HDCV) and the other a purified chick embryo cell vaccine (PCECV). PCECV must be given by the IM route, but HDCV may be given by either the IM or subcutaneous (SC) route. For simplicity, all descriptions of administration of rabies vaccine in these Guidelines refer to the IM route.

Intradermal vaccination

It is strongly recommended that the IM route be used for pre-exposure vaccination in Australia. Antibody titres at 14 days are lower and wane more rapidly after intradermal (ID) administration of rabies vaccine, and there may be a slower initial immune response following exposure to rabies virus.28, 29 As rabies vaccines are not licensed for ID use in Australia, any use of this method is the practitioner’s own responsibility. If ID rabies pre-exposure vaccination is considered (using a dose of 0.1 mL on Days 0, 7 and 28) it is essential that:

• it is given by those with expertise and regular practice of the ID technique
• it is not administered to anyone who is immunocompromised
• it is not administered to those taking either chloroquine or other antimalarials structurally related to chloroquine (e.g. mefloquine) at either the time of, or within a month following, vaccination
• any remaining vaccine is discarded at the end of the session during which the vial is opened (i.e. within 8 hours)
• the rabies virus neutralising antibody (VNAb) level is checked 14 to 21 days following completion of the pre-exposure course of ID vaccine.
• it is only used for pre-exposure vaccination for classical rabies exposures (there are no data on the protection provided by ID rabies vaccination for the prevention of infection with other lyssaviruses including ABLV). ^[9]

Handling bats

Only appropriately vaccinated and trained people should handle bats. Members of the public are strongly advised not to attempt to handle bats (live or dead), but rather contact the NSW Wildlife Information, Rescue and Education Service (WIRES, 1300 094 737) who can rescue and transport bats to a private veterinarian who normally deals with wildlife. If bats must be handled, every effort should be made to avoid being bitten or scratched, including:

• using appropriate personal protective equipment (PPE), such as puncture-resistant gloves (e.g. Nitrile (double or thicker), Kevlar or suede/leather welding-type gloves) and gauntlets, long sleeved clothing, safety eyewear or face shield to prevent mucous exposures, and a towel to hold the bat
• using a garden fork, spade or other implements to handle dead bats. ^[30]

Travel advice

Travellers should be advised to avoid close contact with bats anywhere in the world. Travellers to rabies-enzootic regions should also be advised to avoid close contact with wild or domestic terrestrial mammals (especially dogs, cats and monkeys). Travellers should also be advised what to do should they be bitten or scratched by an animal while abroad. This advice should include stressing the importance of obtaining as much written detail as possible on any post-exposure management provided overseas. Parents should ensure that their children are careful around animals as children are at optimal height for high-risk bites to the face and head. Rabies pre-exposure vaccination (or if appropriate, booster doses) should be advised pre-travel where indicated by a risk assessment, which should include ease of access to post-exposure prophylaxis (PEP) and likelihood of interaction with animals based on type of accommodation and planned activities. See the Information Sheet for Travellers (Appendix 6) for detailed advice for travellers.

Management of potential human exposure to rabies or other lyssaviruses, including ABLV (see algorithms in Appendices 2 and 3)

Definition of potential exposure

Any bite or scratch from, or mucous membrane or broken skin contact with the saliva or neural tissues of:

• a bat in Australia or elsewhere in the world
• a wild or domestic terrestrial mammal in a rabies-enzootic country - this includes Bali, Indonesia from August 2008 onwards
• a wild or domestic terrestrial mammal in Australia, where there is laboratory confirmation of infection with any lyssavirus – see also Domestic animal exposed to a bat in Australia in Special Situations.

If there are concerns about other potential exposures, expert advice should be sought.

Principles of post-exposure management

Post-exposure management is recommended for any person with a potential exposure. Post-exposure management comprises wound care and administration of a combination of rabies vaccine and human rabies immunoglobulin (HRIG) at varying urgency, depending on:

• Type of exposure (see Table 1)
• Severity (e.g. size and number of wounds) and location of wounds in relation to nerve centres – head, face or neck wounds are generally considered a higher risk and should be attended with greater urgency
• Age of the individual and reliability of information about the event – exposure of young children, mentally disabled persons or other circumstances where a reliable history cannot be obtained may necessitate treatment as a category II or III exposure
• Prior rabies vaccination and/or antibody status of the individual
• Details about the animal exposed to, including: the species, risk of rabies in that species and geographic location, the circumstances of exposure (provoked, unprovoked) and behaviour of the animal. The PEP management pathway will depend on the animal involved in the exposure:
• Appendix 2 should be used for exposures to rabies virus from a terrestrial animal overseas
• Appendix 3 should be used for exposures to lyssaviruses from bats in Australia or overseas
• Time interval since exposure – PEP should be considered regardless of the time interval but may be delayed or discontinued in certain circumstances (see below)
• Availability of the animal for observation or testing (see below).

Table 1: Lyssavirus exposure categories*

* To be used in conjunction with algorithms in Appendices 2 and 3. PEP management pathways differ following potential bat exposures. Source: Modified from WHO 2010. ^[30]

Post-exposure management should generally commence as soon as possible following potential exposure and in all circumstances wound care should occur immediately. The administration and logistics of providing rabies PEP is, however, resource intensive to the health system and demanding on individuals. In certain low-risk circumstances, ordering and commencing PEP may be delayed, or PEP may be discontinued:

• If a traveller presents more than 10 days after being bitten or scratched by a domestic dog, cat or ferret in a rabies-enzootic country, and it can be reliably ascertained that the animal remains healthy, then post-exposure management is not required. Note that this recommendation does not apply to exposures to other animals, including bats, which may be documented to be alive beyond 10 days after the exposure.
• Bats involved in a potential ABLV exposure in Australia should be tested where possible, without placing others at risk of exposure. In such situations PEP can be delayed for 48 hours post-exposure to enable a result from the bat to be received. If results are not likely to be available within 48 hours of exposure then PEP should be commenced. If the bat tests negative, PEP is not required, and may be discontinued if already commenced.
• Afterhours orders of PEP from the Vaccine Centre (open Monday to Friday, 8.30am to 4.30pm) can generally be delayed to the next business day, unless the exposure is deemed of a particular high-risk nature after considering all factors in the risk assessment. All afterhours orders should be approved by the Director of the Public Health Unit (PHU). A guideline and algorithm to assist PHU staff in conducting risk assessments and making decisions with regards to the timelines and circumstances around delaying or discontinuing PEP is available on Sharepoint.

If unsure about delaying or discontinuing PEP, discuss with CDOnCall before ordering.

Wound care

Regardless of previous rabies vaccination, immediate cleansing of the wound is an important measure for minimising transmission risk. ^[31] Animal studies have shown that immediate and thorough cleansing of the wound reduces the risk of infection. ^{[32], [33]} All wounds should be washed thoroughly for at least 5 minutes with soap and copious water, as soon as possible after the exposure. A virucidal antiseptic solution such as povidone-iodine or alcohol should be applied. ^[16] The wound should not be sutured unless unavoidable, and then only after HRIG administration, where indicated.

Consideration should also be given to the possibility of tetanus and other wound infections, and appropriate measures taken. In the event of mucous membrane (eyes, nose, mouth) exposure immediately flush with copious water.

Post-exposure prophylaxis for people not previously vaccinated

Immunocompetent people should receive 4 doses of rabies vaccine by IM injection on days 0, 3, 7 and 14. Where applicable, a single dose of HRIG should also be given as outlined in Appendices 2 and 3.

Immunosuppression

Immunocompromised people (whether through disease or treatment) should receive five doses of vaccine IM on Days 0, 3, 7, 14 and 28, for both rabies and other lyssavirus (including ABLV) potential exposures. Where applicable, a single dose of HRIG should also be given, as outlined in Appendices 2 and 3. A person who is immune-suppressed should have rabies virus neutralising antibody (VNAb) titre checked 2 to 3 weeks after completion of the vaccine regimen. If the titre is <0.5 IU/ml a further dose of vaccine should be given and serology re-checked 2 to 3 weeks later. Where the titre remains suboptimal (<0.5 IU/mL) an infectious diseases expert should be consulted about the need for further doses.

Post-exposure prophylaxis for people previously vaccinated

People who have documented evidence of a completed IM course of pre-exposure prophylaxis or PEP using an appropriate cell culture based rabies vaccine at any time in the past, or who have documented rabies VNAb titres ≥0.5 IU/ml ^[16] (e.g. at any time subsequent to a course of ID pre-exposure vaccination), should receive 2 doses of vaccine IM on Days 0 and 3. HRIG is not required. If vaccination status is uncertain, management should occur as for people not previously vaccinated.

Immunosuppression

Previously vaccinated people who are immunocompromised (whether through disease or treatment) should have rabies virus neutralising antibody (VNAb) titre checked 2 to 3 weeks after the second dose of vaccine. If the titre is <0.5 IU/ml an infectious diseases expert should be consulted about the total number of doses required for PEP.

Rabies vaccine use

For adults and children one year of age or older, the rabies vaccine should be administered into the deltoid area, as administration in other sites may result in reduced neutralising antibody titres. In infants under 12 months of age, administration into the anterolateral aspect of the thigh is recommended. Corticosteroids and immunosuppressive therapy can interfere with the development of active immunity and, therefore, if possible, should not be administered during the period of PEP. ^[34]

HRIG use

HRIG, where indicated, should be infiltrated at a dose of 20 IU/kg in and around all wounds. The HRIG product routinely used in NSW is typically supplied in 2mL vials containing 150 IU/mL. The following formulae can be used to calculate the volume and number of vials of HRIG required:

• Total units required (x) = Patient weight in kg x 20 IU
• Volume of HRIG needed to administer in mL (y) = (x) ÷ 150 IU
• Total number of vials needed to order (round up where required) = (y) ÷ 2

It is imperative that as much HRIG as possible is given in and around the wound/s. It may be diluted if there are multiple wounds but as much as possible should go into and around the wounds. The balance of any HRIG dose that cannot safely be infiltrated in and around the wound, or the whole HRIG dose in situations such as mucous membrane exposures (where there is no wound), should be given IM (not into fat) at a site distant (e.g. alternative deltoid, lateral thigh, or gluteal muscle, depending on volume) to that where rabies vaccine is given.

HRIG is given to provide localised anti-rabies antibody protection while the person mounts an immune response to the rabies vaccine. HRIG should be administered with the first dose of rabies vaccine (Day 0). If this is not possible, HRIG can be given up to Day 7 following the first dose of vaccine, but it is not recommended from Day 8 onwards as it may suppress the immune response to the vaccine.

Period of HRIG shortage

Recurrent shortages of HRIG have occurred in Australia. From time to time, HRIG prioritisation measures may be implemented, at the recommendation of the Communicable Diseases Network Australia. Similarly, special arrangements may be made for use of unregistered HRIG or equine RIG products. In such circumstances, CDNA and the Communicable Diseases Branch, Health Protection NSW will provide advice on variations to recommendations provided in these guidelines. PHU staff should consult Sharepoint for the current status and endorsed protocol for rationing HRIG stocks.

Management of PEP in people who have begun prophylaxis overseas

The principle of management of PEP in people who have begun prophylaxis overseas is to continue the course of treatment with an appropriate cell culture derived vaccine. International advisory groups state that cell culture based vaccines can be used interchangeably to complete a treatment course. ^[9] HRIG should be given if indicated, as outlined in Appendices 2 and 3, if RIG (whether equine or human) was not given and the person presents up to Day 7 following the first vaccine dose. If the person presents from Day 8 onwards then HRIG should not be administered.

A number of WHO endorsed rabies PEP schedules are used overseas. These include:

• Zagreb schedule (2 doses on day 0, single doses on days 7 and 21)
• Essen schedule (doses given on days 0, 3, 7, 14 and either 28 or 30)
• Modified Essen schedule (doses given on days 0, 3, 7 and 14)

Table 2 provides recommended courses of action for continuation of PEP in Australia after it has been commenced overseas, for the scenarios most commonly encountered. Other situations should be dealt with on a case by case basis, informed by the following considerations:

• HRIG should not be administered on Day 8 or later following the first documented dose of rabies vaccine, even if recommencing an interrupted vaccine course, on the basis that HRIG may suppress the immune response to rabies vaccine
• Where there is good documentation that one or more doses of an appropriate cell culture based vaccine + RIG (equine or human) have been given, the schedule can generally be continued, with appropriate realignment.

In situations which are not straightforward, seek expert advice on an appropriate schedule, including consideration as to whether testing of rabies VNAb titres is indicated.

Table 2: Post-exposure prophylaxis commenced overseas and recommended completion in Australia

IM = intramuscular; ID = intradermal. * See Table 1 ‘Lyssavirus exposure categories’ above and Appendices 2 and 3.

4. Surveillance objectives

• To rapidly identify people potentially exposed to rabies virus or other lyssaviruses (including ABLV) and to provide appropriate advice and prophylaxis
• To monitor the epidemiology of rabies virus and other lyssavirus (including ABLV) infection and potential exposures to better inform prevention strategies, including travel advice.

5. Data management

The following should be entered on NCIMS within one working day of notification:

• confirmed or suspected cases of rabies virus or other lyssavirus (including ABLV) infection
• all potential human exposures notified to PHUs, regardless of whether or not PEP is required, or if PEP has already been completed (e.g. where the full course has been completed overseas or through private purchase).

The event type and condition should be assigned in NCIMS as follows:

Table 3: Classification of potential exposures and cases on the NSW Notifiable Conditions Information Management System (NCIMS)

When entering potential exposures on NCIMS, it is most important to capture:

• details about the place of exposure/acquisition under both the ‘Clinical’ and ‘Risk History’ packages
• details about the animal exposed to, and for bat exposures in Australia, if testing was completed and the test results
• the person’s occupation (under the Demographic package) and if in a high-risk occupation (under the Risk History package, especially for bat exposures in Australia
• if PEP was recommended and details on the course of PEP completed.

These data are used to monitor and manage rabies vaccine and HRIG resources, and inform future actions to mitigate unnecessary use of PEP where possible.

6. Communications

Doctors should contact their local PHU on 1300 066 055 for advice on potential exposures to rabies or ABLV. PHU staff will help arrange rabies vaccine and HRIG where required. Where indicated, authorised PHU staff can order PEP via the NSW Vaccine Centre Online Ordering System. Before placing orders, it is critical for PHU staff to review the patient’s weight and calculate the amount of HRIG required to avoid unnecessary repeat orders.

Any case where rabies or ABLV infection is being considered as part of a differential diagnosis should be immediately reported to the local PHU by telephone. PHU staff will investigate the possible source/s of infection, facilitate laboratory testing, and determine whether others may be at risk of infection who may require PEP.

If local transmission of rabies or other lyssavirus to a terrestrial animal is suspected, the NSW Department of Primary Industries should be contacted urgently by phoning the Emergency Animal Disease Watch Hotline on 1800 675 888.

Members of the public are strongly advised to not attempt to handle bats. PHUs or the public should rather contact WIRES (1300 094 737) who will collect and transport the bat to a veterinarian who normally deals with wildlife.

7. Case definition

Only confirmed cases of rabies virus or other lyssavirus (including ABLV) infection are notifiable. See the Department of Health website for the current national surveillance case definition. See Contact management for the definition of a potential rabies/ABLV exposure.

8. Laboratory testing

Testing guidelines - humans

Testing for rabies or ABLV is indicated for persons where rabies or ABLV infection is being considered in the differential diagnosis of a clinically compatible illness. Routine serological tests and antigen detection tests cannot distinguish between the different lyssaviruses, but they can be identified by PCR and culture. No laboratory tests are currently available to diagnose rabies in humans before the onset of clinical disease. In the early stages of disease, saliva and CSF can be tested by virus culture and PCR. Antibody testing can also be performed on CSF. A positive serum antibody test is diagnostic of infection with a lyssavirus provided the person has never been immunised against rabies and may assist in the diagnosis of rabies in advanced clinical disease. Any negative test on a symptomatic person is not definitive, as viral shedding in body secretions is intermittent and early tests may be negative for antibody. Therefore repeat testing is often indicated. Post mortem, the standard diagnostic techniques include positive fluorescent antibody test (FAT) and nucleic acid test (NAT) on fresh brain smears, and NAT and culture from tissues. Further information is available from the Public Health Laboratory Network (PHLN) case definition website.

Refer to The Australian Immunisation Handbook for information on routine serological testing for immunity in people who may be occupationally exposed to rabies virus or other lyssaviruses (including ABLV) or who have impaired immunity.

Testing and specimen submission guidelines - animals

Testing of animals for rabies virus or other lyssaviruses (including ABLV) is indicated in any situation where a person has been exposed to a potentially infected animal. Where possible, PHU staff should arrange for safe handling, euthanasia where relevant, and ABLV testing of bats that have been involved in potential human exposures – refer to the Guidelines for testing bats involved in human exposures available on Sharepoint.

Only appropriately trained and vaccinated individuals should handle potentially infected animals. Members of the public are strongly advised to not attempt to handle bats. PHUs or the public should rather contact WIRES (1300 094 737) who will collect and transport the bat to a veterinarian who normally deals with wildlife. The veterinarian (or other appropriately trained official) will euthanase the bat, and prepare and package it for transport in accordance with DPI’s Australian Bat Lyssavirus Guidelines for Veterinarians and Vet Lab Manual. Before shipping specimens, submitters should contact the Emergency Animal Disease Hotline (1800 675 888) to confirm arrangements e.g. for sampling, transport and specimen reception.

A positive result from NAT, FAT or virus culture on fresh brain smear of the animal is diagnostic of rabies. PEP is not required and may be discontinued following a negative NAT or FAT result.

Occasionally, implicated animals may be tested in overseas countries where Australians have been exposed – PHUs should endeavour to liaise with the overseas laboratory or public health authorities in such circumstances to ascertain the result.

Reference laboratories

The diagnosis of rabies due to rabies virus or ABLV can be confirmed in humans by Queensland Health Forensic and Scientific Services (QHFSS), and in animals in NSW by the Elizabeth Macarthur Agricultural Institute (EMAI) or Australian Animal Health Laboratory (AAHL). PHUs should refer to the Guidelines for testing bats involved in human exposures available on Sharepoint.

Queensland Health Forensic and Scientific Services (QHFSS)

Kessels Road
Coopers Plains
QLD 4108
Ph 07 3274 9111
Fax 07 3274 911

State Veterinary Diagnostic Laboratory (SVDL), Elizabeth Macarthur Agricultural Institute (EMAI)

Woodbridge Road
Menangle NSW 2568
Ph 1800 675 623 (office hours only)

Australian Animal Health Laboratory (AAHL)

5 Portarlington Rd
East Geelong
VIC 3219
Ph 03 5227 5000
Fax 03 5227 5555

9. Case management

Response times

On the same day of notification of a confirmed case of human disease begin follow up investigation and notify the Communicable Diseases Branch, Health Protection NSW.

Response procedure

Case investigation

PHU staff conducting the investigation should ensure that action has been taken to:

• confirm the onset date and symptoms of rabies or ABLV illness
• confirm results of laboratory tests
• seek the doctor's permission to contact the case (where possible) or relevant care-giver
• interview case (if possible) or carer and determine source of infection - see Exposure Investigation.

Exposure Investigation

Determine the history of contact with bats (in Australia or overseas) or any other mammal in a rabies-enzootic country. Determine the type of animal (and for bats the species if possible), the circumstances and type of exposure, and whether other people or animals may also have been exposed.

Case treatment

There is no known effective treatment for rabies or ABLV infection. A small number of patients have survived rabies following intensive experimental and/or supportive treatment. ^[35-37]

Education

The rabies factsheet should be available to carers, and provides information about the nature of infection and mode of transmission. See Appendix 5.

Isolation and restriction

Isolate patient with standard and contact precautions for the duration of the illness.

Active case finding

Active case finding should occur to determine if any other people or animals were exposed to the source animal of the case. Exposed people should be urgently assessed for post-exposure prophylaxis; exposed animals should be managed by veterinary authorities.

10. Control of environment

Any suspected infected animals should be isolated from other animals and humans, and veterinary investigation/management sought. Bats involved in a potential ABLV exposure in Australia should be tested where possible, without placing others at risk of exposure.

For overseas exposures to domestic dogs, cats or ferrets (but not other animals)where observation of the suspected animal is possible, information on whether the dog, cat or ferret remained healthy at least 10 days after the exposure incident may be useful for assessing risk of infection and the need for completion of PEP. ^[38]

Environmental contamination by infected animals is considered negligible; this is based on knowledge of persistence of the classical rabies virus, which is fragile and does not survive for long outside the host. ^[39] It is readily inactivated by heat and direct sunlight. Bats or other animals that have been dead for longer than 4 hours are no longer considered infectious for lyssaviruses. ^[9] Bat or other animal blood, urine, and faeces are not considered to be infectious. ^[9]

Effective long-term control of lyssaviruses requires vaccination of host-species populations. Control of ABLV through vaccination of bats is not possible, and culling flying foxes would not control or eradicate ABLV. The risk of ABLV transmission within captive bat populations may be substantially reduced through quarantining new bat intakes to facilities for a short period of time. Specific guidance for bat carers is provided on the Queensland Government website. ^[22]

11. Contact management

Notification of contacts

Contact tracing is required to provide advice and post-exposure prophylaxis so as to prevent disease in contacts.

Contact definition

Contacts are defined as:

1. Persons who have been exposed to the saliva or neural tissue of an infectious person through mucous membrane or broken skin contact, or
2. Persons who have had mucous membrane or broken skin contact with potentially infected animals. This includes any bat in Australia or overseas, and any wild or domestic mammal in a rabies-enzootic country.

Prophylaxis

Post-exposure prophylaxis is recommended for persons who fit the contact definition above. See Management of potential human exposure to rabies or other lyssaviruses, including ABLV, and follow up using Rabies virus and other lyssavirus post-exposure prophylaxis form (Appendix 4).

Education

The rabies/ABLV factsheet should be available to inform exposed contacts about the nature of infection and mode of transmission. See Appendix 5.

Isolation and restriction

None required.

12. Special situations

Domestic animal exposed to a bat in Australia

Other than bats, two horses and three humans, no other mammals have been documented to naturally contract ABLV infection. There is no evidence that ABLV has ever been passed from a wild (non-bat) or domestic animal to a human, and no definitive evidence that any lyssavirus has ever been passed from a domestic livestock animal to a human. There is, however, a possibility that ABLV spillover to domestic animals could occur occasionally, and a theoretical (although remote) possibility that an infected domestic animal could transmit infection to a human.

Follow-up by PHUs of incidents involving domestic animals which have suffered bites or scratches from bats is not required routinely. PHUs should, however, provide advice in accordance with this guideline if contacted by concerned owners. If the owners are concerned about the health of the domestic animal they should be referred to the NSW Department of Primary Industries. The AUSVETPLAN 2009 disease strategy for ABLV recommends testing of the bat involved in an exposure to a domestic animal. Unless the bat is proven to be negative, veterinarians are advised to take one of three options in regards to the animal: vaccinate and minimise contact with other animals or humans until the vaccination protocol is complete; observe under formal or informal quarantine; or euthanase.

If a domestic animal which has been bitten or scratched by a bat subsequently bites or scratches a human, an expert panel may be convened to advise on management, at the discretion of the managing public health officer. If post-exposure prophylaxis is to be offered to human contacts in any situation involving domestic animals which have suffered bites or scratches from bats, in the absence of a defined human exposure (i.e. bite, scratch or mucous membrane exposure) to the bat, or laboratory confirmed lyssavirus infection in the animal, an expert panel should always be convened. Consultation with animal health colleagues may be indicated.

13. References

1. International Committee on Taxonomy of Viruses. Virus Taxonomy: 2018b Release. [updated]
2. World Health Organization. Rabies Fact sheet. [updated 27 Sept 2019]
3. Centers for Disease Control and Prevention. Investigation of rabies infections in organ donor and transplant recipients--Alabama, Arkansas, Oklahoma, and Texas, 2004. MMWR 2004, 53(26):586-9.
4. Centers for Disease Control and Prevention. Human-to-human transmission of rabies via a corneal transplant-France MMWR 1980, 29(3):25-26
5. Winkler WG, Fashinell TR, Leffingwell L, Howard P, Conomy P. Airborne rabies transmission in a laboratory worker. JAMA; 1973, 226(10):1219-21
6. Centers for Disease Control and Prevention. Rabies in a laboratory worker - New York. MMWR; 1977, 26:183-84.
7. Winkler WG, Baker EF, Jr., Hopkins CC. An outbreak of non-bite transmitted rabies in a laboratory animal colony. Am J Epidemiol; 1972, 95(3):267-77
8. Davis AD, Rudd RJ, Bowen RA. Effects of aerosolized rabies virus exposure on bats and mice. J Infect Dis; 2007, 195(8):1144-50
9. Australian Technical Advisory Group on Immunisation. The Australian Immunisation Handbook: 10th ed. Canberra: Australian Government, 2013
10. Heymann DL, editor. Control of Communicable Diseases Manual: 19th ed. Baltimore: United Book Press, 2008
11. Hanna JN, Carney IK, Smith GA et al. Australian bat lyssavirus infection: a second human case, with a long incubation period. Med J Aust; 2000, 172(12):597-9.
12. Jackson AC. Rabies. Neurol Clin; 2008, 26(3):717-26
13. Hattwick MA. Human Rabies. Public Health Rev; 1974, III(3):229-74
14. Bisseru B. Rabies. London: William Heinemann Medical Books, 1972
15. Centers for Disease Control and Prevention. Imported human rabies--Australia, 1987. MMWR. Morbidity and mortality weekly report. 1988; 37(22): 351
16. World Health Organization. Rabies vaccines: WHO position paper. Wkly Epidemiol Rec. 2010; 32(85): 309-320
17. Coleman PG, Fèvre EM, Cleaveland S. Estimating the public health impact of rabies. Emerg Infect Dis; 2004, 10(1):140-2
18. Allworth A, Murray K, Morgan J. A human case of encephalitis due to a lyssavirus recently identified in fruit bats. Communicable Diseases Intelligence. 1996; 20(504-504
19. Grattan-Smith PJ, O'Regan WJ, Ellis PS et al. Rabies. A second Australian case, with a long incubation period. Med J Aust. 1992; 156(9): 651-4
20. Francis J, Nourse C, Vaska V et al. Australian Bat Lyssavirus in a child the first reported case. Paediatrics 2013; 133(4): e1063-e1067
21. Animal Health Australia. Disease strategy: Australian bat lyssavirus (Version 3.0). In: Primary Industries Ministerial Council, ed. Australian Veterinary Emergency Plan (AUSVETPLAN) Edition 3. Canberra, ACT, 2009
22. Queensland Government. Australian bat lyssavirus [cited: 2 May 2019]
23. Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet. 2004; 363(9413): 959-69
24. Fooks AR, McElhinney LM, Pounder DJ et al. Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. J Med Viro. 2003; 71(2): 281-9
25. Dacheux L, Larrous F, Mailles A et al. European bat lyssavirus transmission among cats, Europe. Emerg Infect Dis. 2009; 15(2): 280
26. Tjørnehøj K, Fooks A, Agerholm J, Rønsholt L. Natural and experimental infection of sheep with European bat lyssavirus type-1 of Danish bat origin. J Comp Pathol. 2006; 134(2): 190-201
27. Müller T, Cox J, Peter W et al. Spill‐over of European Bat Lyssavirus Type 1 into a Stone Marten (Martes foina) in Germany. J Vet Med B Infect Dis Vet Public Health. 2004; 51(2): 49-54
28. Warrell MJ, Nicholson KG, Warrell DA et al. Economical multiple-site intradermal immunisation with human diploid-cell-strain vaccine is effective for post-exposure rabies prophylaxis. Lancet. 1985; 1(8437): 1059-62
29. Suntharasamai P, Warrell MJ, Viravan C et al. Purified chick embryo cell rabies vaccine: economical multisite intradermal regimen for post-exposure prophylaxis. Epidemiol Infect. 1987; 99(3): 755-65
30. NSW Department of Primary Industries. Australian bat lyssavirus guidelines for veterinarians: NSW Department of Primary Industries, 2014
31. Rupprecht CE, Hanlon CA, Hemachudha T. Rabies re-examined. Lancet Infect Dis. 2002; 2(6): 327-43
32. Kaplan MM, Cohen D, Koprowski H, Dean D, Ferrigan L. Studies on the local treatment of wounds for the prevention of rabies. Bull World Health Organ. 1962; 26(765-75)
33. Dean DJ, Baer GM, Thompson WR. Studies on the local treatment of rabies-infected wounds. Bull World Health Organ. 1963; 28(4): 477-86
34. Turner GS. Recovery of immune responsiveness to rabies vaccine after treatment of mice with cyclophosphamide. Arch Virol. 1979; 61(4): 321-5
35. Willoughby RE, Jr., Tieves KS, Hoffman GM et al. Survival after treatment of rabies with induction of coma. N Engl J Med. 2005; 352(24): 2508-14
36. Centers for Disease Control and Prevention. Presumptive Abortive Human Rabies - Texas, 2009. MMWR. 2010; 59(7): 185-190
37. Centers for Disease Control and Prevention. Recovery of a patient from clinical rabies - California, 2011 MMWR. 2012; 61(4): 61-65
38. Manning SE, Rupprecht CE, Fishbein D et al. Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008; 57(RR-3): 1-28
39. Animal Health Australia. Disease strategy: Rabies (Version 3.0). In: Primary Industries Ministerial Council, ed. Australian Veterinary Emergency Plan (AUSVETPLAN): 3rd ed. Canberra, ACT, 2011.

14. Appendices

Appendix 1 - Vaccine booster dose algorithm for protection against rabies or other lyssaviruses
Appendix 2 - Post-exposure management algorithm for potential exposure to rabies virus from terrestrial animals overseas
Appendix 3 - Post-exposure management algorithm for potential exposure to lyssaviruses from bats in Australia or overseas
Appendix 4 - Rabies virus and other lyssaviruses (including ABLV) post-exposure prophylaxis form
Appendix 5 - Rabies virus and other lyssaviruses (including and Australian Bat Lyssavirus) fact sheet
Appendix 6 - Rabies information sheet for travellers
Appendix 7 - PHU rabies virus and other lyssaviruses (including ABLV) follow-up checklist