Queensland authorities came under attack yesterday for being unprepared for a Hendra virus outbreak after it was found that they’d only stocked 15 doses of virus antibodies.
But the case for stocking up is weak because treatment with these antibodies isn’t necessarily effective and its hard to predict the probability and severity of outbreaks.
Although Hendra virus has a high case-fatality ratio, only seven humans have been infected in 20 separate outbreaks since 1994. Four of those infected have died.
There is no proven treatment for the virus although the novel monoclonal antibody offers some hope. The only current treatment is supportive, which means patients must get a high level of attention in intensive care units.
Antiviral medications aren’t effective although experience is limited because of the recent discovery of the virus.
Antibodies are important for protection against and recovery from a range of viral infections. Human monoclonal antibodies specifically targeting different viruses have been developed for respiratory syncytial virus (RSV), Severe Acute Respiratory Syndrome-Associated coronavirus (SARS-CoV), Nipah and Hendra viruses.
But experimental evidence of the antibodies’ efficacy in fighting Hendra virus in animal studies is limited.
Part of the problem is that traditional animal models of mice, guinea pigs and rabbits are unsuitable for studying the virus as it doesn’t infect these animals.
Cats and golden hamsters are used instead, but data from these less well-studied animal models cannot always be extrapolated to humans.
Data from human clinical trials assessing the efficacy (and adverse effects) of Hendra virus monoclonal antibodies are unsurprisingly lacking given the extremely low incidence of infection.
So, what is the role of these monoclonal antibodies? Should they be given to everyone exposed to horses infected with Hendra virus or should they be reserved for patients confirmed as infected with the virus?
Essentially, monoclonal antibodies should be used judiciously – on a case-by-case basis – after a thorough risk assessment of the degree of exposure to sick horses, or the clinical features of the illness.
This tentative approach is particularly important because questions about dosage and optimal timing of administration remain unanswered.
Prevention of infection must remain the main focus of attention. Horses should be prevented from eating contaminated food, and sick horses should be isolated while awaiting confirmatory laboratory tests.
More importantly, standard hygiene practices should be strictly followed to prevent horse-to-human transmission. This applies particularly to veterinarians and horse owners.
The culling of flying foxes, which infect horses with the virus, is unlikely to contain a Hendra outbreak as:
there’s a very large population of flying foxes;
all four species (grey-headed, black, spectacled and little-red) are potential reservoirs;
distressed flying foxes can excrete more virus; and
their ability to migrate could potentially transfer the problem to other parts of the country.
A prototype vaccine developed by CSIRO has recently been shown to prevent infection in horses exposed to the virus.
This has the potential to break the animal-to-human transmission chain, preventing disease in animals and humans at the same time.
Anatomy of Hendra infection
Hendra virus is a paramyxovirus native to Australia. It threatened to stop the Melbourne Cup in 1994, when thirteen horses and a horse-trainer died of a then unknown illness in the suburb of Hendra, approximately nine kilometres north-east of Brisbane.
It’s related to Nipah virus, which emerged in Malaysia in 1999 causing encephalitis in humans following widespread infection in pigs.
Flying foxes, common along the east coast of Australia, are the natural reservoir of Hendra virus, and human infection occurs with horses acting as intermediate hosts.
Horses are infected by exposure to food contaminated by the urine, saliva and birth by-products of flying foxes. There is no documented human-to-human transmission.
The incubation period of Hendra virus infection is 5 to 21 days, and it affects the respiratory and nervous systems.
The symptoms depend on the organs affected: similar to influenza (fever, cough, sore-throat, headache) when the lungs are involved and sometimes progressing to severe pneumonia; or meningitis/encephalitis (fever, headache, confusion) when there’s nervous system involvement.
Infection in horses produces a wide range of signs, including fever, restlessness, difficulty walking from poor balance and muscle twitching; and resulting in death within a few days.
Many research agendas about Hendra virus remain, including the investigation of the complex ecosystem of flying foxes; the lack of disease in other Australian states where flying foxes are prevalent; the virulence of the virus in different animal species; and the further development of animal and human vaccines and specific antiviral treatments.