Written by Maya Cherian, Public Health Medical Officer
Reviewed by Dr Nick Walsh MD PhD(epi) BScMed(hons) MPH FAFPHM FAChAM, Abigail Trewin AM. BHSc (Para) MPH&TM, Dr Timothy Gray MBBS(Hons) BMedSci(hons), MPH&TM FRACP FRCPA
“relatively rare in the experience of the individual practitioner, [which,] when once encountered leaves on his mind a more indelible stamp of horror than any other he will meet” 2
Rabies has induced fear in humans for centuries, with images of werewolves and vampires. The first recorded description of canine rabies occurred around 500 B.C.E. and writings by Aristotle (322BC – 384 BC) described dogs suffering from madness and causing other animals to be diseased after being bitten.3
Despite centuries of documented disease and the discovery of the rabies vaccine by Louis Pasteur in 1885, the World Health Organization (WHO) estimates rabies causes 59, 000 deaths annually (Figure 1). Of those, 40% of deaths occur in children less than 15 years old and 95% occur in Asia and Africa.4 Additionally, rabies causes extreme financial burden on health systems, with an estimated cost of US$8.6 billion per year.4
Rabies is a 100% vaccine-preventable zoonotic virus, classified as a neglected tropical disease (NTD).5 NTDs are a group of 20 diseases prioritised by the WHO, predominantly found in tropical and subtropical areas that impact the most vulnerable and marginalised populations.6 Significant global progress has been made against NTDs since 2010, with 42 countries, territories and areas eliminating at least one NTD.6
The virus and disease
Rabies virus (RABV) belongs to the Rhabdoviridae family and Lyssavirus genus. Other lyssaviruses include Australian Bat Lyssavirus (ABVL), with RABV and ABLV having similar natural histories. Three cases of ABLV have been reported in Australia following a bite or scratch from a bat, all which were fatal.7
Human exposure to RABV can be caused by an animal scratch or bite that has broken the skin, direct contact of the virus with the mucosal surface of a person, or tissue or organ transplantation from donors who have died with undiagnosed rabies. Numerous host reservoirs exist for RABV (Figure 1); however, currently, dogs contribute up to 99% of all rabies transmission to humans.4
The incubation period for RABV varies, from 5 days to several years (usually 2-3 months). Rabies presents in two clinical forms, furious and paralytic rabies. Presenting in two-thirds of cases, furious rabies is characterised by hyperactivity, aerophobia and/or hydrophobia followed by delirium, while paralytic rabies is characterised by limb and respiratory paralysis with sparing of consciousness.9 There is no known effective treatment for rabies. Once clinical symptoms appear, rabies is nearly 100% fatal with death usually occurring within 7-10days.9
In 19902, a 10 year-old girl presented to Westmead Hospital Sydney, with left arm, shoulder and chest pain which upon admission progressed to high fevers, autonomic instability, agitation, disorientation, hallucination and violent behaviour. Following a twenty-one day admission, the girl died with rabies diagnosed on autopsy. On review the patient had symptoms of furious rabies followed by paralytic rabies, with hydrophobia thought to have not occurred due to early sedation, intubation and fluids. There was no history of bites or overseas travel in the previous five years and prior to that, her family had spent the previous two years in a compound in Hong Kong where animals were excluded. This history suggested an incubation period of more than six years.
Australia has been able to remain free of rabies, with the Department of Agriculture, Fisheries and Forestry working with international partners, at the Australian border and with Australian communities to ensure Australia is free from rabies.10 Outside of Australia, rabies is present in 150 countries. Within the Western Pacific region, Cambodia, China, Lao People’s Democratic Republic, Mongolia, Philippines and Vietnam have endemic human rabies and within the South-East Asia region, Bangladesh, India, Indonesia, Myanmar, Nepal, Sri Lanka and Thailand have endemic human rabies (Figure 2).
Pre and post-exposure prophylaxis
Rabies is endemic in a number of countries surrounding Australia and pre-exposure prophylaxis (PrEP) is required for all AUSMATeers deploying to certain location (based on travel advice). Hence it is imperative for AUSMATeers to get vaccinated if they want to be considered for deployment. The rabies PrEP course includes a primary course of three vaccinations on day 0, 7 and 21-28 and a booster dose 1 year after the primary course has commenced. Serology is undertaken every 3 years and a booster dose administered if levels are <0.5IU/mL.
The administration of PrEP decreases or eliminates (determined by the timeframe between exposure and PrEP) the need for post-exposure prophylaxis (PEP) (details below) and removes the indication for immunoglobulin (excluding severely immunocompromised people).7
Potential transmission of the RABV to humans requires an ‘emergency response’ or PEP (Figure 3) which consists of:
- washing with soap and water for at least 15 minutes and local treatment as soon as possible
- a course of rabies vaccine
- administration of rabies immunoglobulin or monoclonal antibodies.
The PEP measures required are determined once a risk assessment is complete (Figure 3).9 Animal licks on the skin is a common presentation that can be faced. The risk assessment takes into consideration contamination of mucous membranes and skin integrity which then determines which exposure category is appropriate and subsequent PEP requirements. The fear that rabies induces within the population cannot be underestimated and although not clinically indicated, can lead to PEP being provided.
After exposure to the RABV, appropriate wound washing, vaccination and administration of immunoglobulin if indicated is nearly 100% effective in preventing rabies.13 A recent rabies death in the USA,14 was the first reported failure of PEP in the Western hemisphere. The breakthrough infection, despite appropriate PEP administration (for an immunocompetent person), was deemed to be due to immunosuppression from an undiagnosed metastatic prostatic adenocarcinoma and highlights the need for adequate immune response to rabies PEP vaccination.
Public Health response
To decrease global rabies, a One Health response is required. This is an acknowledgment of the collaborative, multi-sectoral and transdisciplinary approach required to optimise the health of humans, animals and the environmental. In the case of rabies, a collaboration between human and veterinary health sectors in needed.
Zero by 203015 is a global goal, to reduce dog-mediated rabies deaths to zero by 2030. The World Health Organization (WHO), World Organization for Animal health (WOAH), Food and Agriculture Organization of the United Nations (FAO) and the Global Alliance for Rabies Control (GARC) have formed the United Against Rabies collaboration to achieve the goal.
A three-pronged approach has been outlined for the prevention of rabies.15
- Increased awareness and improved education
- Increased and effective dog vaccination – herd immunity reached at 70% vaccination coverage13
- Equitable, affordable and timeless access to health care, medicine and vaccines.
From a financial point of view, there is a considerable cost differential between PEP and dog vaccination, US$108.07 for PEP, a cost out of reach for affected population who maybe living on US$1-$2 per day, and US$4.03 for dog vaccination.
GAVI, The Vaccine Alliance (GAVI) was set up as a global partnership in 2000, with the goal of creating equal access to new and underused vaccines for children living in the poorest countries. The inclusion of the rabies vaccine in the 2018 Vaccine Investment Strategy of GAVI, will ensure subsidised access to human rabies vaccine in low and middle-income GAVI-eligible countries. The rollout out of the rabies vaccine was paused due to the COVID pandemic, however the GAVI board has announced the restarting of the rabies vaccination program (and other programs) as of June 2023.16
Mass parenteral vaccination of dogs, has been challenging especially in resource-poor settings, challenges including the vaccination of free-roaming dogs and maintaining adequate hear immunity. Calls have been made for alternative approaches with oral rabies vaccination promoted by WHO, FAO and WAOH.17
28 September is recognised as World Rabies Day and with a One Health approach, it is hoped that Zero by 2030 will be achieved.
References:
1 Royal Veterinary College | Rabies publicity posters | Wellcome Collection
2 Grattan-Smith PJ, O’Regan WJ, Ellis PS, O’Flaherty SJ, McIntyre PB, Barnes CJ. Rabies A second Australian case, with a long incubation period. Med J Aust. 1992 May 4;156(9): 651-4.
3 Blanton JD, Wallace RM. The Ancient Curse: Rabies. Microbiol Spec. 2015 Dec 18; 3(6).
4 Rabies | World Health Organization
5 Neglected Tropical Diseases | World Health Organization
6 Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021–2030 | World Health Organization
7 Rabies and other lyssaviruses | Australian Immunisation Handbook
8 Epidemiology of Rabies | World Health Organization
9 Rabies and other lyssavirus – CDNA National Guidelines for Public Health Units | Australian Government Department of Health and Aged Care
10 Protecting Australia from Rabies | Australian Government Department of Agriculture, Fisheries and Forestry
11 Rabies | Global Health Observatory | World Health Organization
12 Control of Neglected Tropical Diseases | World Health Organization
13 WHO Expert Consultation on Rabies Third Report | World Health Organization
14 Holzbauer SM, Aschrodt CA, Prabhu RM, Asch-Kendrick RJ, Ireland M, Klumb C et al. Fatal Human Rabies Infection With Suspected Host-Mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure – Minnesota, 2021. Clinical Infectious Diseases, 2023 Oct 15; 77(8): 1201-1208.
15 Food and Agriculture Organization of the United Nations, World Organization for Animal Health, World Health Organization, Global Alliance for Rabies Control. Zero to 2030 | World Health Organization
16 From rabies to hepatitis: Gavi to start rolling out new vaccines to lower-income countries | GAVI
17 Food and Agriculture Organization of the United Nations, World Organization for Animal Health, World Health Organization. Oral vaccination of dogs against rabies
Dr Maya Cherian
Public Health Medical Officer
Maya joined the NCCTRC Public Health Directorate in 2023 as a Public Health Registrar, a final year advanced trainee with the Australasian Faculty of Public Health Medicine. Maya comes to NCCTRC after working for the Office of the Chief Health Officer and the Health Statistics and Informatics branch within NT Health. Maya has been able to gain experience in the areas of Aboriginal health, public policy, communicable diseases and statistics whilst in the NT. Maya is excited to contribute to the fabric of the organisation and assist in enhancing the public health components of NCCTRC, through education, research and enhancing capabilities alongside the public health workforce on the AUSMAT roster.