Urgent.
Respond to a confirmed human case immediately on notification:
Respond to a confirmed equine case, or where heightened suspicion of infection in a horse exists as advised by the relevant animal health agency, immediately on notification:
Assess human exposure:
Note: In the event of a non-equine animal infection, see section 11. Contact management.
Hendra virus (previously called equine morbillivirus) is a paramyxovirus of the genus Henipavirus [1]. The other known agents in this genus are Nipah virus and Cedar virus.
Flying foxes (bats of the genus Pteropus), also known as fruit bats, are the only known natural reservoir [2]. The distribution of flying fox species in Australia is shown in Figure 1. All flying fox species are susceptible - antibody to Hendra virus has been found in 20-50 per cent of flying foxes in mainland Australian populations [3,4]. Since 1994, widespread testing involving 46 other species of animals and arthropods has not shown the natural presence of the virus in any species other than flying foxes.
A three-year longitudinal study (2008-2011) conducted by Biosecurity Queensland, showed Hendra virus excretion in flying foxes can occur at any time of the year. However, the excretion normally occurs periodically rather than continuously, and in geographically-disparate flying fox populations in Queensland [5]. Further research under the National Hendra Virus Research Program (funded by the Intergovernmental Hendra Virus Taskforce) which included the area from northern QLD to southern NSW (encompassing all known equine cases), identified a consistent, strong winter peaking of excretion in central and northern NSW and southern QLD [6]. This study also provided supporting evidence that black and spectacled flying foxes are more likely to be associated with Hendra virus excretion than other species. These findings are consistent with the observed spatiotemporal pattern of infection in horses, and demonstrate that Hendra virus infection prevalence in flying foxes is a fundamental determinant of infection in horses.
Figure 1: Spatial distribution of pteropus bats in Australia[3]
Spillover from flying foxes to horses is rare, possibly occurring through contamination of horse feed, pasture and vegetation by infectious fluids from bats, e.g. bat urine/reproductive products. At the time of the first identified outbreak at Hendra (Brisbane, Queensland) in 1994, testing of nearly 2,000 horses across Queensland, including 906 horses within 1 km of quarantined properties, found no seropositive horses apart from those on the quarantined premises (i.e. no evidence of other spillover events) [7]. Information on incidents by jurisdiction can be found at the Australian Government national pests and diseases outbreaks website
Seven cases of human infection have been detected (as of July 2016), four of which have been fatal. One of the human deaths occurred 13 months after exposure to the virus, which occurred during the post-mortem examination of an affected horse. Notably, this case was hospitalised with aseptic meningitis shortly after exposure (see Case 3, Appendix 1).
All seven cases had a high level of exposure to respiratory secretions and/or other body fluids of horses subsequently diagnosed with Hendra virus infection, or presumed to have Hendra virus infection through review of clinical/epidemiological evidence in the absence of samples for laboratory testing. Three of the cases were exposed to tissues during post-mortem examinations on those horses. Two were probably exposed while performing nasal cavity lavage during the three days before the horse showed any clinical signs of disease. Further details on these cases are presented in Appendix 1.
No cases have been documented in people with medium or lower-exposure levels, including anyone appropriately using personal protective equipment (PPE) [8] and not all people with high-level exposures have become infected. On the evidence available, the most likely mode of transmission is via substantial direct exposure of mucous membranes (or non-intact skin) to respiratory secretions (including large droplets) or blood from an infected horse. Indirect exposure to respiratory secretions or blood, and direct or indirect exposure to other body fluids, may constitute less likely modes of transmission between horses and people. Current evidence does not support airborne exposure as a recognised mode of transmission.
Transmission between horses has mainly occurred in situations of close contact and has been more efficient in stabled situations, with spread between multiple horses occurring in two events in stables (Hendra 1994 and Redlands 2008) and one event on a property with multiple small paddocks (Cawarral 2009), all in Queensland. It is possible that short-term survival of Hendra virus on environmental surfaces and inadvertent human-assisted fomite transmission (e.g. horse gear or veterinary equipment contaminated with secretions or fluids of an infected horse) may contribute to more efficient transmission in stabled situations. Of the 20 equine cases associated with the 1994 outbreak in Hendra, 18 occurred on the index property and the other two on the immediately adjacent property.
No evidence of bat-to-human transmission of Hendra virus. A study of 128 bat carers, the majority of whom reported daily contact with bats and/or a history of bat bites, found no individuals with antibodies to Hendra virus [9].
There is no evidence of person-to-person transmission of Hendra virus. Serological testing in 169 health-care worker contacts and four household contacts of the first three human cases found no individuals with antibodies to Hendra virus [10]. Testing of contacts of the subsequent four human cases also produced uniformly-negative results [11]. Investigation of two of three surviving human Hendra virus cases found no evidence of prolonged virus shedding following acute infection [12]). However, recommendations are to avoid close contact with respiratory secretions and other body fluids of symptomatic human cases. As a precaution, standard, contact and droplet precautions, and airborne precautions for aerosol-generating procedures [13], should be implemented for management of suspected or confirmed human cases.
There is no evidence of person-to-horse transmission of Hendra virus [14]. However, it is recommended that suspected human cases avoid close contact with horses until the diagnosis has been clarified and a case confirmed, until the possibly-human infectious period has passed.
Disease has been induced under experimental conditions in cats, ferrets, hamsters, guinea pigs, horses and pigs. Experimentally-infected horses can excrete viral RNA in nasal secretions from three-five days before showing clinical signs of disease [15, 16, 17]. This underpins recommendations that any procedures on apparently healthy horses that may cause aerosolisation or splashes, should be performed with appropriate infection control precautions including PPE. See section 9. Case management - Isolation and restriction for definitions of aerosols and droplets.
Two dogs on properties with Hendra virus-infected horses have shown evidence of Hendra virus infection. The first antibody positive dog was identified in July 2011 on a property in Queensland where three horses developed Hendra virus infection. The second dog was identified in July 2013 on a NSW property where one horse had developed Hendra virus infection. Although the source of exposure for the dogs cannot be definitively ascertained, horse-to-dog transmission is the most plausible scenario given that both dogs had potential opportunity for exposure to infected horses. There is no evidence that bat-to-dog. dog-to-person, or dog-to-horse, transmission occurs.
Horses are considered to be the animal most associated with transmission due to their ability to amplify the virus. However, animal health experts believe dogs to be a potential transmission risk (refer to Draft V 4.0 AUSVETPLAN, in press).
Updated statistics on Hendra virus incidents, including locations, dates and confirmed horse cases, may be found on the Queensland Government website.
Hendra virus infection symptoms in humans have developed between five to 21 days after exposure to an infectious horse.
The incubation period in horses appears to be three-6 days, although the incubation period in one horse in the 2009 Bowen event may have been 31 days (personal communication, Steven Donohue [Queensland Health] and Hume Field [Biosecurity Queensland], November 2009).
The potential infectious period in humans is unknown, as no evidence exists of person-to-person transmission to date. While the risk of transmission is probably negligible, for public health purposes, human cases should be considered potentially infectious while symptomatic.
Most transmission of Hendra virus to humans has occurred during contact after the infected horse had developed clinical signs of Hendra virus illness.
For human public health trace-back purposes, horses should be considered potentially infectious from 72 hours prior to the onset of clinical signs of disease. Careful assessment is required of how closely the horse was observed for the onset of illness.
Viral genetic material has been detected by PCR in experimentally-infected horses three-five days before the onset of symptoms [8, 16, 17]. In this experimental study, the virus challenge was administered oronasally to three horses and viral genetic material was then identified in nasal swabs from each of the horses from two days post challenge. In the 2008 Redlands outbreak related to two humans, high-risk exposures (daily nasal cavity lavage) occurred during the last three days of the incubation period for one of the infected horses [11].
Given the theoretical potential for virus transmission beyond 72 hours prior to illness onset in the horse, individuals with specific medium-to-high or high-level exposure events (see Appendix 4: Exposure assessment form) in the 73-120 hours prior to the horse becoming sick, should be identified. Specifically, an invasive oral or respiratory tract procedure on the horse such as dental work and nasal endoscopy, without the use of appropriate use of infection control procedures including PPE. Detailed accounts of the specific exposures should be obtained and the significance of these exposures then considered by an expert panel.
The documented human cases to date have presented with:
Further detail on these seven cases is included in Appendix 1.
No cases of asymptomatic infection have been identified from extensive testing of human contacts associated with Hendra virus events up to July 2016.
In horses, Hendra virus has a clear predisposition for targeting endothelial cells of blood vessels, with clinical signs dependent on the sequence in which organs are affected. Documented equine cases to date have typically presented with acute onset of clinical signs, including increased body temperature and increased heart rate, and rapid progression to death associated with either respiratory or neurological signs (or a mix of these). Some horses have also shown evidence of multi-organ involvement.
The clinical signs, particularly of early Hendra virus infection, may be non-specific, although progression from onset to death is typically rapid, occurring over a couple of days. Less severe infections have been identified in horses being monitored during an outbreak; these horses are typically second or third-generation cases. From figures to date, approximately 75% of infected horses can be expected to die. Those that survive often have mild signs and seroconvert during the recovery period. In past incidents, all horses that have tested positive for Hendra virus have been euthanised [8]. Please refer to the most recent AUSVETPLAN Response Policy Brief for Hendra virus infection for detail on current management of horses infected with Hendra virus.
People who are more likely to be exposed to infected horses may be at increased risk, e.g. veterinarians, horse trainers and stable workers.
All events since Hendra virus infection was first identified in 1994 have occurred in Queensland or New South Wales. However, given the distribution of flying foxes (Figure 1) and frequency of horse movements among states and territories, cases could occur anywhere in Australia.
Veterinary practitioners and staff handling confirmed or suspected equine cases should follow appropriate infection control procedures, including wearing appropriate PPE (refer to ‘Guidelines for veterinarians handling potential Hendra virus infection in horses’ [8]).
Horse owners or carers should minimise unnecessary human contact with sick horses and take appropriate preventive hygiene measures (refer to the Workplace Health and Safety Queensland document ‘Hendra virus - information for horse properties and other horse related businesses’ [18]).
Horse owners and carers can take steps to protect horses from becoming infected with Hendra virus by reducing exposure to flying foxes, e.g. by placing feed bins and water troughs under cover and away from areas where flying foxes feed or roost (refer to the Workplace Health and Safety Queensland document ‘Hendra virus - information for horse properties and other horse related businesses’ [18] and Biosecurity Queensland.
An equine vaccine for Hendra virus infection in horses has been available in Australia since November 2012 (Equivac® HeV).
Surveillance for equine cases is the responsibility of [NSW DPI]. Appropriate processes should be in place to ensure relevant surveillance information is shared promptly at state and territory level among animal and human health agencies.
Confirmed human cases should be entered onto the [Notifiable Conditions Information Management System (NCIMS)], ideally within one working day following notification.
Hendra virus infection in humans is not currently nationally notifiable and there is no national case definition. The following is based on the Queensland case definition as at October 2011, reviewed in February 2015.
A confirmed case requires:
Exposure, within 21 days prior to onset of symptoms, to a horse with confirmed Hendra virus infection, or where heightened suspicion of Hendra virus infection exists as advised by [NSW DPI].
Clinically-compatible acute illness, (see section 2. The disease - Clinical presentation and outcome).
NB: For case definitions in horses see the current AUSVETPLAN Hendra Virus Response Policy Brief [8].
Human testing may be indicated when there:
As at July 2016, Queensland Health Forensic and Scientific Services (QHFSS) is the only human health laboratory in Australia that tests for Hendra virus. Tests available include nucleic acid testing (NAT) and serology. Virus isolation is usually attempted on acute phase specimens, particularly when NAT is positive.
Testing of human samples is also available, on request, from the Australian Animal Health Laboratory (AAHL), (Geelong, Victoria) and may be available on request from some state animal health laboratories. Tests available from AAHL include NAT, virus isolation and virus neutralisation test (VNT).
NAT can be performed on respiratory samples (deep nasal swab or nasopharyngeal aspirate), serum (preferable to blood), cerebrospinal fluid (CSF), urine and tissue samples.
Minimum CSF, serum, liquid respiratory or urine sample volume is 0.5 ml. Tissue samples (minimum rice grain size) should be in viral transport medium, not fixed. Respiratory swab samples should be dry, or in viral transport medium. Chill all samples immediately upon collection (4oC) and transport cool (4oC) not frozen, within 24 hours.
QHFSS currently performs a screening microsphere immunoassay (MIA) for IgM and IgG and can differentiate between individuals with natural antibodies and those administered therapeutic monoclonal antibodies. If positive, the MIA is followed by a confirmatory immunofluorescence assay (IFA) that can be quantified. As with all serological tests, false positive results can occur. If MIA and IFA are positive in the absence of positive NAT, and if there is any question that this represents true infection, specimens may be referred to AAHL for VNT. Where serological testing is indicated, a baseline sample should ideally be collected as early as possible after exposure and stored for testing in parallel with subsequent samples. Minimum sample volume of CSF or serum is 0.5 ml. Transport cool (4oC) within 24 hours.
The earliest laboratory evidence of infection in human Hendra virus cases has been positive nucleic acid testing in blood, respiratory specimens, then urine, with serology becoming positive two to five days after onset of symptoms.
For suspected human cases:
For human contacts of an equine case:
Commence investigation immediately on notification of a confirmed human or equine case, or where notified by an animal health agency of heightened suspicion of infection in a horse on clinical and epidemiological grounds.
On notification of a confirmed equine case, or where an animal health agency has heightened suspicion on clinical and epidemiological grounds:
On notification of a confirmed human case, or where a public health unit considers there is heightened suspicion on clinical and epidemiological grounds:
For all confirmed human or equine cases, an incident management team should be established to manage the public health response.
Close liaison with [NSW DPI] is necessary and regular interagency meetings should be held to ensure a coordinated response. [SafeWork NSW] should be involved early if the event occurs in a workplace.
Responsibility of the treating medical practitioner. Advice should be sought from an infectious diseases physician.
Cases should be informed about the nature of infection, mode of transmission and other relevant information.
Aerosols: Microscopic particles < 5 μm in size that are the residue of evaporated droplets and are produced when a person coughs, sneezes, shouts, or sings. These particles can remain suspended in the air for prolonged time periods and can be carried on normal air currents in a room or beyond, to adjacent spaces or areas receiving exhaust air.
Droplets: Small particles of moisture generated when a person coughs or sneezes, or when water is converted to a fine mist by an aerator or shower head. These particles, intermediate in size between drops and droplet nuclei, can contain infectious microorganisms and tend to quickly settle from the air such that risk of disease transmission is usually limited to persons in close proximity (e.g. at least one metre) to the droplet source.
Source: National Health and Medical Research Council
State and territory animal health agencies are responsible for managing confirmed or suspected equine cases to prevent exposure to other horses, domestic animals or people. For confirmed equine cases, this may include quarantining the property, euthanising the infected horse or horses, tracing of animals that have recently moved from the property, isolating and testing other animals that may have been exposed, and vaccinating other horses on the property. Quarantining the property allows animal health agencies to prevent or control movements of potentially-infectious animals, products and fomites on the property, and is common in managing many notifiable diseases of livestock.
Hendra virus is killed by heat, drying and cleaning with detergents, so disinfecting contaminated fomites and surfaces on the property is usually allowed to occur naturally over time. In past incidents, confirmed equine cases have been euthanised in accordance with nationally-agreed policy, to prevent further risk of transmission, provided it is done humanely and the carcass is safely disposed of. Please refer to the most recent AUSVETPLAN policy for Hendra virus infection for detail on current management of horses infected with Hendra virus.
Animals (including horses and other domestic animals such as dogs) that may have been exposed, are isolated from other animals on the property and a series of tests are performed over a number of weeks to determine whether they have become infected. Vaccination of other horses on the property may be recommended. Once the remaining animals on the property are shown to be free of infection, the property is released from quarantine [8].
Suspected equine cases (those with consistent clinical signs) are isolated from other animals on the property and human contact with the horse is minimised until test results are available. If contact with the horse cannot be avoided given that it may require high levels of care due to illness, advice will be provided by [NSW DPI] to the owner or carer on appropriate infection control procedures, including using PPE. Private veterinarians attending suspected equine cases will use PPE during examinations and any associated procedures due to the exposure risk associated with such contact with the horse. Owners will also need to practise infection control procedures as advised by the attending private veterinarians, in compliance with workplace health and safety requirements.
In the past, researchers have visited properties where infection has been confirmed, to look for evidence of recent flying fox activity, in an to attempt to identify possible risk factors for transmission of virus from bats to horses, by profiling case properties. This is separate from the response mounted by animal health authorities, but helps to provide information on how to prevent future spillover of Hendra virus to horses. Such visits are likely to continue while research funding is available.
In human health-care facilities, environmental cleaning procedures should be conducted in accordance with Australian infection control guidelines [13].
The aim of identifying contacts is to:
People who have had direct or indirect exposure of skin or mucous membranes to body fluids (including sharps injuries) of a horse, determined by [NSW DPI] to be a confirmed case of Hendra virus infection, or of a horse where heightened suspicion of infection exists on clinical and epidemiological grounds as advised by [NSW DPI].
People who have had close contact with a symptomatic confirmed human case or person where heightened suspicion of infection exists on clinical and epidemiological grounds as determined by the relevant public health unit (including household or household-like contacts, sexual partners, and anyone with direct or indirect exposure of skin or mucous membranes to body fluids).
A detailed understanding of human contact with the animal should be obtained and expert advisory group input should be sought.
Exposure assessments of human contacts are required for all confirmed equine cases of Hendra virus infection, and where heightened suspicion of infection in a horse exists on clinical and epidemiological grounds as advised by [NSW DPI]. Exposure assessment of human contacts of confirmed human cases is also recommended. Although risk is generally likely to be negligible, the assessment and provision of information will often provide valuable reassurance.
Obtain information from [NSW DPI] on all horses with confirmed Hendra virus infection, and any epidemiologically-linked equine cases where heightened suspicion of Hendra virus infection exists on clinical and epidemiological grounds (this may include previously sick horses associated with affected properties). Trace-back investigations by [NSW DPI] of horse movements from affected properties may generate considerable workload for public health units by identifying other humans requiring follow-up as contacts of additional equine cases.
Develop a line listing of all people who may have been in contact with confirmed equine cases, or where heightened suspicion of infection in a horse exists on clinical and epidemiological grounds as advised by the relevant animal health agency (contacts of human cases are a lower priority as they are likely to be at negligible risk).
For all human contacts of confirmed equine cases:
The urgency of response to illness in contacts depends on the assessed level of exposure. Clinically-compatible illness (respiratory or neurological symptoms) in a person classified as having high exposure or as having classification uncertainty (medium or high) using the exposure assessment form, should be urgently assessed by or in liaison with an infectious diseases physician.
Further advice for exposure assessment:
As psychological stress and the exacerbation of existing health issues may result from a Hendra virus incident, everyone involved should be strongly encouraged to access their usual health-care practitioner to assess need for ongoing physical and psychological support, medical or workers’ compensation certification and referral to other services as necessary. GPs should be provided with appropriate information and resources, including local public health unit contact details. Initial contact with GPs should preferably be by telephone.
No drug or product is of proven benefit in humans, although monoclonal antibodies show the most promise. Monoclonal antibodies have been shown to protect ferrets from serious disease when given 10 hours after exposure to Nipah virus [20] and when given 10-12 hours after exposure to Hendra virus (personal communication, Deborah Middleton, CSIRO, 20 September 2011). They have also been shown to protect African green monkeys from fatal infection when given 72 hours after exposure to a lethal dose of Hendra virus [21].
As at July 2016, monoclonal antibody had been used on compassionate grounds in 11 people. A Queensland Department of Health and University of Queensland clinical trial to further evaluate the safety of monoclonal antibodies in humans, has been completed at the time of writing, with results awaited.
Wherever possible, an expert panel of public health and infectious diseases practitioners with appropriate experience should be convened as part of the incident management process to review all contacts identified as having classification uncertainty (medium or high) or high-level exposures. The panel will advise whether monoclonal antibody should be offered and on any logistical issues.
The only stock of monoclonal antibodies (as at July 2016), is held in Queensland, access to which for contacts with high-level exposures, can be sought via the Executive Director, Communicable Diseases Branch, Queensland Health.
Provide information about the disease to all contacts of confirmed human and equine cases, and contacts of horses or humans where heightened suspicion of infection exists on clinical and epidemiological grounds, as respectively advised by [NSW DPI] or determined by the relevant public health unit.
If an equine case is confirmed, it may be appropriate for [Public Health Unit officials] to visit the property to provide information and support to key people (e.g. owners and managers) and to assist animal health agency staff in providing information to the local community. Any site visit should complement and not delay the full public health response, which focuses on the timely assessment of exposure and current health status of all people who may have been exposed to infected horses, including animal health practitioners, many of whom may not be available on site.
Hendra virus incidents may be very stressful for people exposed or otherwise involved. Relevant points for stress responses include:
Horse owners are likely to see [NSW DPI] staff arrive with extensive PPE such as full-length fluid resistant overalls, face shields and respirators. Despite explanations (ideally prior to staff arriving), that the use of PPE is a standard, precautionary measure, some people may interpret incorrectly, that Hendra virus is highly infectious and that they are at significantly increased risk of infection and death. All closely-involved persons including family members, owners, and others, and those with minimal exposure, may require repeated reassurance and information. The local community may also need relevant information early in the management of the incident, to minimise misunderstanding and misinformation.
Nil
Appendix 1 - Summary of Human Cases of Hendra Virus Infection and Hendra Virus Infection Events, 1994-2011.Appendix 2 - Hendra Virus fact sheetAppendix 3 - Information for people exposed to a horse infected with Hendra virusAppendix 4 - Exposure Assessment FormAppendix 5 - Public health checklist