Hendra virus is a significant pathogen in the context of both human and horse health. The condition is relatively uncommon, but the consequences of infection are severe.
The Virus
Hendra virus is a Henipavirus that belongs to family Paramyxoviridae. It is an enveloped, single-stranded, non-segmented RNA genome virus. Along with Hendra virus, Nipah virus, Moijang virus, Ghana virus, and the non-pathogenic Cedar virus make up the Henipavirus genus. All of these viruses are harboured by bats as natural reservoirs, with the exception of Moijang virus, which is resident in rodents.
Hendra virus was named after the suburb in Brisbane where the first outbreak was described in a Thoroughbred racing stable in 1994. There are two variants of Hendra virus, with a second variant (HeV-g2) recently detected in 2 fatal horse and flying fox infections. Of interest and concern was that the new variant has been identified in Grey-headed flying foxes in Melbourne and Adelaide, and a single Little Red flying fox in Broome, as well as causing the death in a horse near Newcastle in NSW in October 2021. This horse death was the southern-most Hendra detection reported to date, although one horse case was reported in 2019 140 km further north, near Scone in the upper Hunter region. Infections with the original strain were restricted to Port Douglas in Queensland and Kempsey in northern NSW.
The Disease
Hendra virus infection was first identified in horses and humans in 1994. Since that time there have more than 80 disease episodes in Queensland and New South Wales. There have been seven spillover cases from horses to humans, including four fatalities. Direct transmission of Hendra virus from bats to humans has not been described. Hendra virus can be shed by flying foxes via saliva, urine, faeces or birthing fluids.
The virus has a preference to infect arteries, resulting in widespread vasculitis. It can also cause breakdown of alveolar walls and neuronal necrosis and focal gliosis.
The reported incubation period in horses varies between 3 and 16 days. Disease onset is sudden with rapid deterioration over 24-48 hours common. Because of the widespread nature of the pathology a variety of clinical signs can occur. The most common early reported sign was fulminant pulmonary disease, manifest by pulmonary oedema. This sign led to the early misdiagnosis of left-sided cardiac failure with pulmonary oedema.
Other commonly reported signs centre on neurologic dysfunction. These include obtundation, aimless wandering, head tilt, vision loss, muscle fasciculations, urinary incontinence, ataxia, weakness and collapse. Fever appears to be inconsistent, whereas tachycardia, and tachypnoea are common.
Reservoir Hosts – Bats
Bats are important in controlling nocturnal insects and pests, important in reseeding deforested land, pollinating plants, and providing a natural fertilizer (guano). However, they also harbour important and dangerous viruses that can infect humans and several animal species. These include filoviruses (Ebola and Marburg), paramyxoviruses (Hendra and Nipah), lyssaviruses (Rabies, ABLV), and a range of coronaviruses (SARS-CoV-1, MERS-CoV, PEDV, SADS-CoV). It has been speculated that SARS-CoV-2 may have also evolved in bats.
Interestingly, bats harbour many of these viruses and rarely show signs of disease, the exception being the lyssaviruses. Bats have developed a fine balance between disease defence and disease tolerance, which permits this species to be an ideal reservoir for viruses. Bats can transfer these viruses directly to humans, or via other hosts, such as palm civets and racoon dogs for SARS-CoV-1, dromedary camels for Middle Eastern Respiratory Syndrome (MERS), pigs for Menangle and Nipah viruses, and via horses for Hendra virus.
There are four Australian flying fox species, and all species have had Hendra virus antibodies detected, with a prevalence of up to 25%. Along with Hendra virus, Australian flying foxes can also carry Nipah and Cedar virus. Henipavirus infections are typically asymptomatic in bats. The infected bats usually have low levels of viral shedding, with the shedding heavily influenced by climate and the bat’s reproductive and socioecological factors. This includes shortages of food, extreme temperatures, dry conditions, and use of wintering roosts.
A recent investigation between climate and Hendra virus outbreaks reported that seasonal climatic factors (monthly temperature), along with multi-annual climatic variability and long-term climate-based anomalies (land temperature) all impact Hendra events. The prevalence of Hendra virus disease has often shown multi-year periods between outbreaks, suggesting that the viral dynamics are not annual. They concluded that there was a 7 month time lag between an ENSO-driven event, either a peak El Niño (warm phase in the Pacific) or a peak La Niña (cool phase) climate event and HeV outbreaks. The current phase outlook and history is available at the BOM website. The last peak was a La Niña event in late January/early February 2022.
Diagnosis
The clinical signs associated with infection are diverse. Consequently, it is very important to act as if Hendra virus infection is present. This includes wearing of PPE and collecting appropriate samples. The central sample is a nasal swab to be submitted for RT-PCR.
Problems have emerged with routine testing of cases infected with the new HeV-g2 strain, with both the traditional quantitative RT-PCR and ELISA failing to detect viral RNA and antibody, respectively. This has led to new, updated PCR methodology now in use in Australian diagnostic laboratories.
Recently, a new antibody ELISA was developed that Differentiate the Infected horse from the Vaccinated Animal (DIVA). The subunit vaccine is based on the Hendra virus Glycoprotein (HeV-G). This new ELISA detects antibodies directed against the vaccine and natural infection, and also detects antibodies against the Hendra virus Nucleoprotein (HeV-N) only present in natural infections.
Prevention
There are a number of advisable strategies for horses in endemic regions. These include:
- Horses should not be housed in pastures with fruiting trees that attract flying foxes. If this can’t be avoided then fence off trees.
- Remove feed and water sources away from trees, and ideally under protective shelter.
- Sick horses should be isolated immediately and not travelled.
- Personal protective equipment (PPE) should be worn by those interacting with sick horses.
A recombinant subunit vaccine was developed and subsequently approved by the APVMA in 2012. The vaccine is called Equivac HeV and is marketed by Zoetis Australia. The vaccine schedule includes two initial doses (3-6 weeks apart), a third dose 6 months after the second dose, followed by an annual boosters. This is a markedly effective vaccine that prevents disease in horses, and perhaps more importantly, prevents spill-over of virus to humans. The APVMA reported a very low rate of adverse reactions to the vaccine at 0.001%, most of which were injection site reactions and lethargy. The vaccine, when administered according to schedule, will achieve adequate levels of neutralizing antibody. Recent data indicate that the vaccine is effective against both known variants, due to conserved glycoprotein antigens.
Despite potential serious outcomes, death in horses and humans, it is estimated that less than 20% of Australian horses are vaccinated. Factors reported for not vaccinating included concerns over cost, vaccine safety, and vaccine effectiveness. Of further concern was the finding in one study that owners would not reconsider their decision to not vaccinate based on recommendations by their veterinarian. Many vets in endemic areas will not see horses that are unvaccinated. This created resentment by horse owners who viewed that vaccination was now mandatory.
Tags: Haemopoietic; Zoonoses