Hendra virus: Rare in humans, but problematic in animal populations

On May 17, a horse fell ill in the township of Tewantin on the Sunshine Coast, Queensland, Australia.

A vet, wearing protective equipment, examined the horse and sent material for laboratory testing. The laboratory confirmed a Hendra virus (HeV) infection. Eleven people, including the owner, her 12-year-old daughter and the vet, were regarded as potential contacts and put under observation, although there was no indication that any of them contracted the virus. None of them exhibited signs of infection in the first round of testing. Of these 11, only the mother-daughter pair were considered to be at greater risk and were offered treatment with an experimental monoclonal neutralizing antibody.

The two volunteered for the experimental drug antiserum, which awaits its acceptance in humans. No sickness in them had been observed during the following month; it is not known whether the antiserum worked or the two were actually not infected.

HeV infection, also known as equine morbillivirus pneumonia and acute equine respiratory syndrome, is an emerging viral disease of horses and humans in Australia, with very high fatality rates in both species.

Although this disease is uncommon, cases have been reported since it was first recognized in 1994, when two people, a stable hand and the trainer, were infected while attending a sick horse at a stable in the suburb of Hendra, Brisbane. The stable hand recovered, but the trainer died. Between 1994 and 2009, HeV was confirmed 13 times, involving about 45 horses and seven humans, on or east of the Great Dividing Range from Cairns to northern New South Wales. However, HeV could potentially occur wherever there are bats of the genus Pteropus, such as fruit bats or flying foxes.

So far, the disease was restricted to Australia, but antibodies to HeV have also been detected in flying foxes in Papua New Guinea.

Human infections have occurred from handling infected horses, so great care should be taken regarding personal protective measures. In particular, contact with blood and other body fluids (especially respiratory and nasal secretions, saliva and urine) and tissues should not occur.

HeV is a member of the genus Henipavirus in the family Paramyxoviridae.

This genus includes the closely related Nipah virus, initially isolated in 1999 upon examining samples from an outbreak of encephalitis and respiratory illness among pig farmers in the village of Sungai Nipah in Peninsula Malaysia and also in Singapore. Current understanding of HeV epidemiology is limited; however, horses appear to be incidental hosts infected by contact with flying foxes.

The virus is probably transmitted between bats, mainly by horizontal rather than vertical transmission; they appear to be the reservoir host, whereas horses and humans seem to be spillover hosts for HeV. The virus is thought to be spread by environmental contamination and ingested or inhaled by the horse. The upper respiratory tract and/or the oropharynx are the most likely sites of entry. The index case is usually a horse kept outside, near flying fox activity. Humans have been infected during close contact with sick horses and during necropsies, probably via body fluids or aerosols. Four of the seven clinical cases in humans were fatal, including two veterinarians.

Disease control currently relies on management strategies that prevent contact between flying foxes and horses and barrier precautions to prevent transmission from suspect horse cases to humans or other horses. Horse-to-horse transmission seems to be rare, related to housed animals and close contact. There is no evidence of human-to-human, human-to-horse or bat-to-human spread of HeV.

Infection in humans

In published cases, the initial symptoms developed in 5 to 12 days. One person became ill shortly after contact with infected horses but recovered before developing recurrent, fatal encephalitis a year later.

As of December, HeV infections have been reported in seven people, all after contact with sick horses. The syndromes have included influenza-like illness and progressive encephalitis. The two initial cases were characterized by a serious influenza-like disease with fever, myalgia and respiratory signs. One of the two people died; the other recovered in 6 weeks. In the third case, a mild meningoencephalitic illness was followed by a long asymptomatic period before fatal encephalitis developed a year later. The fourth person reported a self-limited influenza-like illness with a dry cough, sore throat, cervical lymphadenopathy, fatigue, body aches and a fever that lasted for about 1 week. The three last cases, in 2008 and 2009, include two fatalities; the last one, a veterinarian, died in August 2009.

HeV infections can be diagnosed by virus isolation, the detection of nucleic acids or serology.

Because HeV is a very rare disease, proven drug therapies have not been developed. Treatment with antiviral drugs, combined with supportive care, has been tried in recent cases. A monoclonal antibody preparation, found effective in experimental animals (ferrets and monkeys), was tried in August 2009 to save the life of the Rockhampton, Australia vet before he died from HeV in hospital.

Infection in animals

Naturally occurring infections have not been reported in any species other than horses or flying foxes. In a survey conducted in the Brisbane area, where the initial cases were reported in horses, all 500 cats tested were seronegative.

Clinically presenting natural infections have been documented only in horses. Experimental infections have been established in cats, horses and guinea pigs. Dogs, mice, rats, rabbits and chickens do not develop clinical signs after inoculation. Of the latter four species, significant seroconversion occurred only in rabbits.

Infected horses usually experience a brief, severe respiratory or neurological disease with a high case fatality rate. The incubation period is estimated to be 5 to 16 days. Two syndromes, one characterized primarily by respiratory disease and the other mainly by neurological signs, have been reported. Most known cases progressed rapidly to death within days. Other reported clinical signs include colic and straining to defecate. Some horses have had difficulty urinating or dribbled urine in the terminal stages. Milder cases have also been seen, and a few horses have recovered.

In experimentally infected cats, the incubation period was 4 to 8 days. Fever and increased respiratory rates were followed by severe illness and death within 24 hours.

Experimental infections in guinea pigs resulted in generalized, fatal vascular disease. Flying foxes appear to remain asymptomatic, and all infected animals may not seroconvert.

In horses with the respiratory syndrome, post-mortem lesions have been found mainly in the lower respiratory tract, including marked pulmonary edema, dilation of the pulmonary lymphatics, and congestion and ventral consolidation of the lungs.

In experimentally infected cats, severe pulmonary edema, hydrothorax and edematous bronchial lymph nodes were seen. Experimentally infected cats can transmit the infections to horses or cats that are in close contact. No naturally infected cats have been identified.

Humans have been infected, to date, only during close contact with sick horses. Necropsies are a particularly high-risk procedure, but any contact with blood, tissues or secretions (including on fomites) also carries a risk.

For more information on the Hendra virus infection, please go to www.cfsph.iastate.edu/Factsheets/pdfs/ hendra.pdf.

Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.