The introduction of a Hendra virus (HeV) vaccine, confirmation of infection in a second dog and recent developments in the understanding of recrudescent HeV infection have necessitated review of the management of vaccinated animals on infected premises (IPs), the risk posed by close contact companion animals and the policy of mandatory euthanasia of infected animals irrespective of their clinical state.
In late 2012 a HeV vaccine was released under a minor use permit. The vaccine had to be administered by an approved veterinarian at prescribed intervals and details of the batch number and horse details recorded on a dedicated database. Any adverse events associated with the use of the vaccine had to be reported as well. These requirements by the Australian Pesticides and Veterinary Medicines Authority (APVMA) were in order to gather more information to support full registration of the product. The company was also required to undertake additional animal studies including duration of immunity and impact of colostral immunity to support full registration of the vaccine and these APVMA requirements have not as yet been completed.
There is strong experimental evidence to support the efficacy of the vaccine in protecting against challenge and this has been substantiated in field trials. A key message used to promote widespread adoption of the vaccine uptake has been that when the label protocol is followed the vaccine provides for good immunity to HeV challenge.
The management of vaccinated horses on premises where HeV infection had been confirmed required consideration. Before HeV vaccine was available close contact horses on IPs had to undergo testing to prove they had not been exposed to HeV infection and remained in quarantine for 21 days. With the availability of an effective vaccine it was inconsistent to promote vaccination as the single most important risk mitigation strategy for horse owners and on Infected Premises treat close contact vaccinated horses as high risk.
This issue was of most concern to organizers of horse events who wanted to know how vaccinated horses would be treated at events like shows or gymkhanas if HeV infection was suspected or confirmed.
The new policy position of both NSW and Qld is that horses that have a current HeV vaccination certificate will be assessed as low risk and generally not be subjected to any restrictions. It is possible that horses grossly contaminated by oral or nasal discharges from close contact with a clinical case and who may pose a risk for mechanical transmission of infection may require a topical disinfectant treatment but those circumstances are not likely to be very common.
In July 2013 a dog on an IP on the mid north coast was confirmed as infected with HeV. The only abnormality the owner observed was that on two occasions the dog yelped without apparent provocation. Other than that the dog was behaving completely normally. It had been seen near where a clinically infected horse had been euthanased which is the probable mode of infection.
The dog was euthanased and PCR positive results were recorded for kidney, liver, spleen, lymph nodes, heart, brain, pharynx, spinal cord and blood although live virus was not isolated from any site.
Australian Animal Health Laboratory (AAHL) undertook a National HeV research project to examine the transmission risk posed by infected dogs. They infected naïve dogs with HeV at a dose rate lethal for horses and sampled the dogs at regular intervals. Virus was isolated from the experimentally infected dogs’ oral secretions at day 4 and 6 post infection and this virus was able to induce infection in naïve ferrets.
The dogs displayed only minor clinical signs (mild inappetance, conjunctivitis and scleral injection) and one of the study authors noted that the clinical signs were so mild and transient that they would be unlikely to be noticed by even the most observant owner.
These research and field developments have necessitated the need to develop more stringent guidelines for the management of companion animals on IPs than has been the case in the past including the use of PPE (personal protective equipment) when handling these animals by owners.
The policy of mandatory euthanasia for seropositive animals was based around concerns that convalescent or recrudescent infection which has been recognised for other paramyxoviruses may pose a future transmission risk. The key assumption here is that convalescent and recrudescent infection would have similar pathogenesis and transmission pathways as acute infection.
Recrudescent infection was seen in the first human HeV case in Qld and recognised in several human Nipah cases and has also been seen with human measles infection. The likelihood of recrudescence infection in HeV infected animals in Australia could not be determined as all confirmed cases were euthanased. These human cases all presented as chronic encephalitis and in all cases examined virus was not able to be isolated from any sites sampled despite evidence of viral replication. In two recent fatal human HeV cases patients were sampled in the convalescent stage of the illness and again no live virus could be isolated despite evidence of viral multiplication in the central nervous system (CNS).
The National HeV Taskforce commissioned a research project to look at transmission risk from convalescent animals. This work was carried out at AAHL and used both ferrets and mice. This study found that the encephalitis in the laboratory animals observed was consistent with extension of infection within the brain through neurones that were related to each other by means of synaptic connections. Immunochemistry further confirmed that only the neurones and not the other cells in the CNS were involved in the spread of virus within the CNS in these chronic encephalitis cases due to HeV. Using mouse neuron cultures that allowed the growth medium surrounding axons to be separated from that around the cell bodies, it was shown that virus replication in neurons was not associated with the production of an infectious viral particle from the neuronal cell membrane.
The conclusion from these experimental and field studies and published papers on recrudescent infection in humans is that convalescent and recrudescent infection in animals is very unlikely to pose any future transmission risk. It is proposed to request Animal Health Committee (AHC) to support a move away from mandatory euthanasia and allow management of these animals who are infected but recover on a case by case basis.
The use of an expert panel has been suggested as a mechanism to assist decision making for these cases.
There currently is no validated DIVA (Differentiation between Infected and Vaccinated Animals) to distinguish vaccinated from infected animals. One benefit from adoption of this proposal would be that countries which currently base their reluctance to allow entry of HeV seropositive animals on the basis that they are a transmission risk would not have the support of our present policy position to support their claims.
Most of the research findings reported here and some of the slides used in the presentation were provided by Dr Deborah Middleton from AAHL. Sarah Britton assisted with preparation of this report.