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Hendra virus (HeV), scientific name ''Hendra henipavirus'', is a bat-borne
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
that is associated with a highly fatal infection in horses and humans. Numerous disease outbreaks in Australia among horses have been caused by Hendra virus. The Hendra virus belongs to the genus ''
Henipavirus ''Henipavirus'' is a genus of negative-strand RNA viruses in the family ''Paramyxoviridae'', order ''Mononegavirales'' containing six established species, and numerous others still under study. Henipaviruses are naturally harboured by several sp ...
'', which also contains the
Nipah virus Nipah virus, scientific name ''Nipah henipavirus'', is a bat-borne virus that causes Nipah virus infection in humans and other animals, a disease with a high mortality rate. Numerous disease outbreaks caused by Nipah virus have occurred in Sou ...
, which has also caused disease outbreaks.


Pathology

Flying fox ''Pteropus'' (suborder Yinpterochiroptera) is a genus of megabats which are among the largest bats in the world. They are commonly known as fruit bats or flying foxes, among other colloquial names. They live in South Asia, Southeast Asia, Aust ...
es experimentally infected with the Hendra virus develop a viraemia and shed the virus in their urine, faeces and saliva for approximately one week. There is no other indication of an illness in them. Symptoms of Hendra virus infection of humans may be respiratory, including
hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, v ...
and edema of the lungs, or in some cases
viral meningitis Viral meningitis, also known as aseptic meningitis, is a type of meningitis due to a viral infection. It results in inflammation of the meninges (the membranes covering the brain and spinal cord). Symptoms commonly include headache, fever, sen ...
. In horses, infection usually causes one or more of
pulmonary oedema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due to ...
, congestion and neurological signs.
Ephrin B2 Ephrin-B2 is a protein that in humans is encoded by the ''EFNB2'' gene. Function This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases a ...
has been identified as the main receptor for the henipaviruses.


Transmission

Flying fox ''Pteropus'' (suborder Yinpterochiroptera) is a genus of megabats which are among the largest bats in the world. They are commonly known as fruit bats or flying foxes, among other colloquial names. They live in South Asia, Southeast Asia, Aust ...
es have been identified as the reservoir host of Hendra virus. A seroprevalence of 47% is found in the flying foxes, suggesting an endemic infection of the bat population throughout Australia. Horses become infected with Hendra after exposure to bodily fluid from an infected flying fox. This often happens in the form of urine, feces, or masticated fruit covered in the flying fox's saliva when horses are allowed to graze below roosting sites. The seven human cases have all been infected only after contact with sick horses. As a result, veterinarians are particularly at risk for contracting the disease. In 2021 a new variant of Hendra virus named "Hendra virus genotype 2" (HeV-g2) was identified in two flying fox species in Australia. It shares 84% sequence homology to other published Hendra virus genomes.


Prevention, detection and treatment

Three main approaches are currently followed to reduce the risk to humans. * Vaccine for horses. :In November 2012, a vaccine became available for horses. The vaccine is to be used in horses only, since, according to CSIRO veterinary pathologist Dr Deborah Middleton, breaking the transmission cycle from flying foxes to horses prevents it from passing to humans, as well as, "a vaccine for people would take many more years." :The vaccine is a subunit vaccine that neutralises Hendra virus and is composed of a soluble version of the G surface antigen on Hendra virus and has been successful in ferret models. :By December 2014, about 300 000 doses had been administered to more than 100 000 horses. About 3 in 1000 had reported incidents; the majority being localised swelling at the injection site. There had been no reported deaths. :In August 2015, the Australian Pesticides and Veterinary Medicines Authority (APVMA) registered the vaccine. In its statement the Australian government agency released all its data on reported side effects. In January 2016, APVMA approved its use in pregnant mares. * Stall-side test to assist in diagnosing the disease in horses rapidly. :Although the research on the Hendra virus detection is ongoing, a promising result has found using
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
-conjugated magnetic particles and quantum dots. * Post-exposure treatment for humans. :Nipah virus and Hendra virus are closely related paramyxoviruses that emerged from bats during the 1990s to cause deadly outbreaks in humans and domesticated animals.
National Institute of Allergy and Infectious Diseases The National Institute of Allergy and Infectious Diseases (NIAID, ) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's ...
(NIAID)-supported investigators developed vaccines for Nipah and Hendra virus based on the soluble G-
glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosy ...
of the viruses formulated with adjuvants. Both vaccines have been shown to induce strong neutralizing antibodies in different laboratory animals. :Trials began in 2015 to evaluate a
monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...
to be used as a possible complementary treatment for humans exposed to Hendra virus infected horses. * Deforestation Impact. :When considering any zoonosis, one must understand the social, ecological, and biological contributions that may be facilitating this spillover. Hendra virus is believed to be partially seasonally related, and there is a suggested correlation between breeding time and an increase in the incidence of Hendra virus in flying fox bats. :Additionally, recent research suggests that the upsurge in deforestation within Australia may be leading to an increase in the incidence of Hendra virus. Flying fox bats tend to feed in trees during a large part of the year. However, due to the lack of specific fruit trees within the area, these bats are having to relocate and thereby are coming into contact with horses more often. The two most recent outbreaks of Hendra virus in 2011 and 2013 appear to be related to an increased level of nutritional stress among the bats as well as relocation of bat populations. Work is currently being done to increase vaccination among horses as well as replant these important forests as feeding grounds for the flying fox bats. Through these measures, the goal is to decrease the incidences of the highly fatal Hendra virus.


History


Emergence

Hendra virus (originally called "Equine morbillivirus") was discovered in September 1994 when it caused the deaths of thirteen
horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million yea ...
s, and a trainer at a training complex at 10 Williams Avenue, Hendra, a suburb of
Brisbane Brisbane ( ) is the capital and most populous city of the Australian state of Queensland, and the third-most populous city in Australia and Oceania, with a population of approximately 2.6 million. Brisbane lies at the centre of the South ...
in
Queensland ) , nickname = Sunshine State , image_map = Queensland in Australia.svg , map_caption = Location of Queensland in Australia , subdivision_type = Country , subdivision_name = Australia , established_title = Before federation , establishe ...
, Australia. The
index case The index case or patient zero is the first documented patient in a disease epidemic within a population, or the first documented patient included in an epidemiological study. It can also refer to the first case of a condition or syndrome (not n ...
, a mare called Drama Series, brought in from a paddock in Cannon Hill, was housed with 19 other horses after falling ill, and died two days later. Subsequently, all of the horses became ill, with 13 dying. The remaining six animals were subsequently euthanised as a way of preventing relapsing infection and possible further transmission. The trainer, Victory ('Vic') Rail, and the stable foreman, Ray Unwin, were involved in nursing the index case, and both fell ill with an influenza-like illness within one week of the first horse's death. The stable hand recovered but Rail died of respiratory and
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
. The source of the virus was most likely frothy nasal discharge from the index case. A second
outbreak In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
occurred in August 1994 (chronologically preceding the first outbreak) in
Mackay Mackay may refer to: *Clan Mackay, the Scottish clan from which the surname "MacKay" derives Mackay may also refer to: Places Australia * Mackay Region, a local government area ** Mackay, Queensland, a city in the above region *** Mackay Airpor ...
1,000 km north of Brisbane resulting in the deaths of two horses and their owner. The owner assisted in
necropsies An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any di ...
of the horses, and within three weeks was admitted to hospital suffering from meningitis. He recovered, but 14 months later developed neurologic signs and died. This outbreak was diagnosed retrospectively by the presence of Hendra virus in the brain of the patient.


Outbreak in Australia

As of June 2014, a total of fifty outbreaks of Hendra virus have occurred in Australia, all involving infection of horses. As a result of these events, eighty-three horses have died or been euthanized. A further four died or were euthanized as a result of possible Hendra infection. Case fatality rate in humans is 60% and in horses 75%. Four of these outbreaks have spread to humans as a result of direct contact with infected horses. On 26 July 2011 a dog living on the Mt Alford property was reported to have HeV antibodies, the first time an animal other than a flying fox, horse, or human has tested positive outside an experimental situation. These events have all been on the east coast of Australia, with the most northern event at
Cairns, Queensland Cairns (, ) is a city in Queensland, Australia, on the tropical north east coast of Far North Queensland. The population in June 2019 was 153,952, having grown on average 1.02% annually over the preceding five years. The city is the 5th-most-p ...
and the event furthest south at Kempsey, New South Wales. Until the event at
Chinchilla, Queensland Chinchilla is a rural town and locality in the Western Downs Region, Queensland, Australia. In the , the locality of Chinchilla had a population of 6,612 people. Chinchilla is known as the 'Melon Capital of Australia', and plays host to a Mel ...
in July 2011, all outbreak sites had been within the distribution of at least two of the four mainland flying foxes (fruit bats);
Little red flying fox The little red flying-fox (''Pteropus scapulatus'') is a megachiropteran bat native to northern and eastern Australia. The species weighs about half a kilogram, one US pound, and is the smallest species of ''Pteropus'' in mainland Australia. '' ...
, ''(
Pteropus scapulatus The little red flying-fox (''Pteropus scapulatus'') is a megachiropteran bat native to northern and eastern Australia. The species weighs about half a kilogram, one US pound, and is the smallest species of ''Pteropus'' in mainland Australia. ' ...
)'', black flying fox, ''(
Pteropus alecto The black flying fox or black fruit bat (''Pteropus alecto'') is a bat in the family Pteropodidae. It is among the largest bats in the world, but is considerably smaller than the largest species in its genus, ''Pteropus''. The black flying fox ...
)'',
grey-headed flying fox The grey-headed flying fox (''Pteropus poliocephalus'') is a megabat native to Australia. The species shares mainland Australia with three other members of the genus ''Pteropus'': the little red '' P. scapulatus'', spectacled '' P. conspicill ...
, ''(
Pteropus poliocephalus The grey-headed flying fox (''Pteropus poliocephalus'') is a megabat native to Australia. The species shares mainland Australia with three other members of the genus ''Pteropus'': the little red '' P. scapulatus'', spectacled '' P. conspicilla ...
)'' and
spectacled flying fox The spectacled flying fox (''Pteropus conspicillatus''), also known as the spectacled fruit bat, is a megabat that lives in Australia's north-eastern regions of Queensland. It is also found in New Guinea and on the offshore islands including Wood ...
, ''( Pteropus conspicillatus)''. Chinchilla is considered to be only within the range of little red flying fox and is west of the Great Dividing Range. This is the furthest west the infection has ever been identified in horses. The timing of incidents indicates a seasonal pattern of outbreaks. Initially this was thought to possibly be related to the breeding cycle of the little red flying foxes. These species typically give birth between April and May. Subsequently, however, the Spectacled flying fox and the Black flying fox have been identified as the species more likely to be involved in infection spillovers. Timing of outbreaks also appears more likely during the cooler months when it is possible the temperature and humidity are more favourable to the longer term survival of the virus in the environment. There is no evidence of transmission to humans directly from bats, and, as such it appears that human infection only occurs via an intermediate host, a horse. Despite this in 2014 the
NSW Government The Government of New South Wales, also known as the NSW Government, is the Australian state democratic administrative authority of New South Wales. It is currently held by a coalition of the Liberal Party and the National Party. The Governmen ...
approved the destruction of flying fox colonies.


Events of June–August 2011

In the years 1994–2010, fourteen events were recorded. Between 20 June 2011 and 28 August 2011, a further seventeen events were identified, during which twenty-one horses died. It is not clear why there was a sudden increase in the number of spillover events between June and August 2011. Typically HeV spillover events are more common between May and October. This time is sometimes called "Hendra Season", which is a time when there are large numbers of fruit bats of all species congregated in SE Queensland's valuable winter foraging habitat. The weather (warm and humid) is favourable to the survival of henipavirus in the environment. It is possible flooding in SE Queensland and Northern NSW in December 2010 and January 2011 may have affected the health of the fruit bats. Urine sampling in flying fox camps indicate that a larger proportion of flying foxes than usual are shedding live virus. Biosecurity Queensland's ongoing surveillance usually shows 7% of the animals are shedding live virus. In June and July nearly 30% animals have been reported to be shedding live virus. Present advice is that these events are not being driven by any mutation in HeV itself. Other suggestions include that an increase in testing has led to an increase in detection. As the actual mode of transmission between bats and horses has not been determined, it is not clear what, if any, factors can increase the chance of infection in horses. Following the confirmation of a dog with HeV antibodies, on 27 July 2011, the Queensland and NSW governments will boost research funding into the Hendra virus by $6 million to be spent by 2014–2015. This money will be used for research into ecological drivers of infection in the bats and the mechanism of virus transmission between bats and other species. A further 6 million dollars was allocated by the federal government with the funds being split, half for human health investigations and half for animal health and biodiversity research.


References


External links


'hendrafacts'



The Australian Pesticides and Veterinary Medicines Authority - Hendra vaccine registration and data release
- August 2015
Hendra virus factsheet
CSIRO
The science and mystery of hendra virus
– by Renee du Preez (ABC Rural) – ''Australian Broadcasting Corporation''. {{Taxonbar, from=Q1604979 Henipavirus Horse diseases Viral diseases Zoonoses