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Update from Chief Veterinary Officer, 8 August 2008

We are continuing to receive reports and I would like to thank those who have reported cases recently. With the two current cases so spread apart, it is important to assess reports from the whole of Queensland to build the bigger picture for Hendra virus at this time.

Epidemiology update

An updated epidemiology report relating to the Redlands incident is supplied below. Please note that this should be viewed as an interim report with more detailed reports expected after the response, when all information can be analysed in a more complete manner.

1. Summary of clinical observations of confirmed case horses from Redlands case histories (not all signs seen in all horses):

• dull, depressed
• inappetant
• temperature mostly elevated
• HR, RR mostly elevated
• mucous membranes dark, capillary refill slow
• reduced gut sounds
• colicky
• periodic recumbency
• trembling
• ataxic
• head-tilt, circling
• loss of vision
• change in temperament (aggressive)
• rapid deterioration - most died or were euthanased after one day, two at most.

In other Hendra virus cases in other locations, epistaxis and/or frothy discharge from the nose has been present in some horses.

The recovered horse presented with similar signs but as a slightly milder case than the others. Ataxia and head tilt continued in this horse for approximately three days.

2. Interim epidemiology summary update (7 August 2008)

History and test results:

There have been five confirmed cases of Hendra virus infection in horses at the Redlands premises since 26 June; four severely ill horses were euthanased, and one horse recovered after a less-severe illness. All cases were confirmed by PCR assay on blood and/or nasal swab and/or oral swab and/or tissue samples. Virus has been cultured from one horse at this time. The recovered horse has a high neutralising antibody titre.

PCR results on all other horses in the clinic have been negative, and to date serial serology for neutralising antibodies has been negative in all horses except the recovered horse.

A number of environmental swabs taken from case-horse stalls have been positive by PCR, indicating contamination of the surfaces with infectious body material.

Examination of clinic records identified three horses, which had died or were euthanased in the weeks preceding the first confirmed case (the index case) and fitted the clinical case definition of sudden onset, fever, rapid deterioration over 24/48hrs, and neurological and/or respiratory system involvement.

The first horse was reported to have had multiple neurological manifestations on admission, the second horse was reported to have had mild respiratory disease, and the third horse was reported as depressed on admission and collapsed the following afternoon. The latter two horses had pre-existing medical conditions.

Efforts were made to ascertain the Hendra virus infection status of these horses. Samples available from an external diagnostic laboratory were limited to blood smears for each horse (other samples had been discarded). All were negative by PCR assay, but this result is not regarded as conclusive by the testing laboratory because of the sub-optimal sample. Investigations on the property of origin of all three horses found no evidence of infection in any in-contact horse. On the basis of these investigations, the three horses are regarded as improbable cases.

The source of infection:

The index case (horse #1) appears to be the primary case. This horse was a long-term resident at the clinic, and in the fortnight prior to its illness, was housed in yards overhung by trees. Flying foxes, the recognised natural host of Hendra virus, are regularly observed in trees in the area. It is hypothesised that horse #1 was exposed to infectious body fluids from a flying fox (plausibly via contamination of feed, water or yard rails) and became infected.

The timeline suggests that horse #1 was likely the source of infection for horses #2-4. Incubation period in infected horses in the 1994 outbreak at the Hendra stables ranged from 8-16 days, and in experimentally infected horses, the incubation period has ranged from 4-10 days. Horse #1 was treated in the clinic examination area four days prior to euthanasia. Horses #2-4 were either housed in the clinic area and/or frequently brought to the examination area for treatment during the time of their putative exposure. Horse #5 occupied the stall adjoining that of horse #4 at the time of onset of horse #4's illness.

The examination area and the adjoining stalls appear to have been the focus of transmission plausibly following contamination of surfaces and/or equipment by infectious body fluids (urine, saliva, nasal discharge) from the index case.

Hume Field and Nina Kung
Biosecurity Queensland.

The cooperation of David Lovell and staff from Redlands Veterinary Clinic is acknowledged and appreciated.

Pathology of Hendra virus

This brief overview is not intended to be the definitive description of the pathology of Hendra virus, but to demonstrate that the pathological process supports the clinical signs seen.

Microscopically, lesions of vascular damage and vasculitis are observed and these lesions are consistent with histopathological changes observed in cases of Hendra virus infection. Technically, these are not clinical signs but through the widespread and serious damage to capillary endothelium they make a large contribution to the development of clinical signs and gross post mortem changes observed.

Over the eleven locations where Hendra virus infection has been encountered in horses since August 1994, consistent clinical features have been observed (see: Guidelines for veterinarians handling potential Hendra virus infection in horses):

• acute onset
• fever (greater than 40°C)
• respiratory signs (progressive and deteriorating)
• neurological signs
• colic, and
• facial oedema.

Importantly, except for acute onset and fever these features may not all be present to the same extent and the recent outbreak at Redlands is a good example of neurological signs predominating. Just why this variance exists remains uncertain. However, from the disease pathogenesis perspective it is reasonable to assume that underlying virus-induced damage to vascular endothelium, and the subsequent vasculitis, is playing a major role.

It is known that the virus uses a cell surface glycoprotein, ephrin B2, as a cell receptor and that this receptor has a widespread cellular distribution, especially in vascular endothelial cells. This accounts for the commonly observed outcome of Hendra virus infection, that of systemic involvement of endothelial cells.

In a simplistic sense, the predominant clinical outcome (colic, respiratory, neurological etc.) may depend on which organ system is sustaining severe and compromising endothelial damage.

Update of Redlands premises

No change on the premises - all horses remain clinically healthy and no temperature spikes have been recorded.

Today, 8 August 2008, is 15 days since the last case was euthanased. The maximum known incubation period for Hendra virus is 16 days. An uneventful weekend will provide a significant boost to our confidence that the disease situation at Redlands may have at last run its course. Though we will not rest easy until more time and another round of testing is completed.

If Redlands has a 'clear' weekend, the horses will then have completed one full incubation period and all horses will be sampled on Monday 11 August 2008. Results from this testing (PCR and SNT) should be available by the end of the week - samples will need to get to AAHL and the SNT takes three days, provided that tests do not need to be repeated for any reason.

If all goes well and the tests are completed next week and are negative (other than for the known sero-positive horse), we will then undertake a final clinical examination of the horses before lifting quarantine during the week of 18 August 2008. Any suspicion or positive horse in the interim will naturally change all this.

The sero-positive horse remains visually healthy. Seropositive horses have been assessed by an expert Hendra virus working group to be an ongoing but unquantifiable risk of recrudescence with or without virus shedding in the future. Definite information is not available from known Hendra virus scientific research but research with nipah virus shows that recrudescence occurs and has been recorded in around 10% of cases.

Update of Proserpine premises

No changes have occurred on this premises since the last Chief Veterinarian Officer's update. All horses, including the sero-positive horse, remain visually healthy. This horse will be handled under the same process being developed for the sero-positive horse at Redlands.

Sample testing

The main tests being used currently are:

• PCR test on whole blood and other body fluids, aim is to detect a viraemia. This is being performed at both Queensland Health Forensic and Scientific Services Laboratory (QHFSS) and at the Australian Animal Health Laboratory (AAHL). QHFSS is able to conduct this test within 24 hours of receiving samples with AAHL confirming results.
• Serum Neutralisation Test, which aims to detect antibody. It is performed at AAHL. The test takes about three days to run and is used as the definitive test for past exposure.
• PCR, immuno-histochemistry, virus isolation and a range of other tests are being used on post mortem samples.
• The testing done to exclude or confirm Hendra virus in samples submitted for Hendra virus testing will be done free of charge. However, the cost of transport of the samples will be a cost to the veterinary practice dispatching them.

Sample despatch

Guidelines are being developed for the despatch of samples from possible Hendra virus cases and will be available for distribution very soon. In the meantime, contact the laboratory client liaison officer on 07 3362 9471 during business hours if you currently need advice about dispatching Hendra virus samples.

Research on henipa viruses

We have had a number of queries regarding research on Hendra virus, as well as the closely related, nipah virus (collectively referred to as the henipa virus group). Note that Hendra has been identified in bats in all areas of Australia plus Papua New Guinea where bats reside. Nipah seems to be present in south east Asia and extending into Indonesia. There are probably transitional strains between Papua New Guinea and Indonesia.

The organisations working on Hendra and nipah include: DPI&F, AAHL, the Biosecurity Cooperative Research Centre, and the Consortium on Conservation Medicine (based in US and includes CDC, Atlanta). There are also research groups in Bangladesh and Thailand.

There has been enormous progress to date. The fact that we identified fruit bats as the reservoir in two years following first identification in 1994, whereas it took 30 years for ebola virus, was a tremendous achievement in itself. Some specifics:

• The virus has been characterised genetically, and its behaviour in various animals studied in the lab.
• We know which animals are susceptible to the virus - horses, guinea pigs, cats primarily.
• We know in fair detail its pathogenesis.
• There has been much work done on the ecology of fruit bats and the behaviour of Hendra virus in fruit bats. We know that it is closely associated with pregnancy and lactation and that prevalence varies by time, location and the reproductive cycle. We also know which body organs are most likely to be affected and modes of excretion of virus from the body.
• We know that spillover events in horses are rare and are only known to happen in paddock situations where fruit bats are present.
• We know that the virus has a low infectivity (but high mortality) and how to disinfect contaminated environments.

Current work:

• Ongoing studies on the ecology of the virus in bats.
• Studies into bats themselves to give us a better understanding of why a number of emerging diseases seem to be originating in bats.
• Preliminary work has been done that could lead to a vaccine. However this is unlikely to be commercially viable.
• Further study of the factors that lead to spillover from bats to horses, in particular linkages to the reproductive cycle, as well as whether there are periodic epidemics of Hendra virus in bat populations.
• Work to characterise the diversity of strains of Hendra and nipah viruses

Other news

New South Wales Department of Primary Industries has announced that the case at Ballina has been classified as negative. AAHL advised them this morning that they have confirmed that the weak PCR test result was a false positive caused by a reaction to equine genome material in the samples from the suspect horse. The suspicion that the horse was infected with Hendra virus has therefore been removed and the stable complex where the suspect horse is located has been released from quarantine.

Horse events, including the EKKA are continuing as normal.

No other positive cases have been detected to this point in Queensland.

Updated Hendra virus guidelines for veterinarians have been placed on the DPI&F website. Please send your comments on this to simon.bewg@dpi.qld.gov.au to further update of these guidelines.

Draft guidelines for horse owners and carers have been developed and are currently with the Hendra virus working group for comment. Version 1 should be finalised and put on the web early next week. A similar process will then occur to collect comments to contribute to an update of these guidelines.

Note that disease preventative steps for horses revolve around separating or stopping potential contact between horses and flying foxes, including separation from anything potentially contaminated by body fluids from flying foxes. Destruction of flying foxes to prevent contact is not an option; flying foxes are a protected species.

Also, handling of flying foxes by any of your clients is not advised unless they are a registered bat carer. Handling of flying foxes and other bats by humans exposes them to possible Australian bat lyssavirus. People should contact the Environmental Protection Agency or their local bat carer group to get assistance with bats on their premises.

Ron Glanville
Chief Veterinary Officer.

Further information

• Hendra virus timeline June-July 2008 (PDF, 45 kB)
• Hendra virus guidelines for veterinarians (PDF, 216 kB)