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Call for Hendra virus antibody testing

Authors:
Australian Veterinary Journal
To the Editor,
The other evening I was called out to yet another horse with colic whose primary veterinarian
had refused to attend because the horse was not currently vaccinated against Hendra virus
(HeV). To be considered current in the manufacturer’s Hendra vaccination registry, annual
boosters are mandated, even though the one study published to date with relevant data on
duration of immunity indicated that annual boosters may be unnecessary in many, and
perhaps even in most, horses.1
The horse had been routinely vaccinated against HeV in the past, but the owner had chosen
not to continue with annual boosters. This decision by horse owners, or refusal to vaccinate at
all, is a common occurrence in my experience and a phenomenon that is well documented in
the veterinary literature.2-4 Disturbingly, there are more studies published on why horse
owners aren’t vaccinating against HeV than there are on the safety and efficacy of the HeV
vaccine. Concerns about vaccine safety, efficacy, cost, and value persist among horse owners
in my practice area.
Rather than continuing to mandate vaccination per the manufacturer’s direction and refuse
service to clients whose horses are unvaccinated or whose HeV vaccination status is lapsed or
unknown, perhaps it’s time we begin taking a more measured approach. I propose we accept
the documentation of HeV-specific antibodies in the horse’s serum as evidence of a HeV-
specific immune response (whether naturally acquired or vaccine induced), with the
likelihood of a rapid anamnestic response in the event of subsequent exposure.
Two separate studies have shown that horses are capable of generating HeV-specific virus
neutralising (VN) antibody titres well above the threshold currently considered protective (
16)5 within one week, whether in response to natural infection6 or vaccination.1 The speed
with which horses generated a vigorous VN antibody response in these studies suggests that a
similarly rapid and robust response is possible — indeed, is likely — in the event of natural
exposure in horses who already have HeV-specific antibodies in their serum.
Of course, the point of booster vaccination is to maintain protective immunity throughout the
risk period. However, humoural immunity is only one component of the immune response to
pathogens, and the inevitable decline in titre in the absence of repeated challenge tells us
nothing about the cell-mediated immune capacity, including immunological ‘memory’, of
that individual. Furthermore, we don’t know the serum VN threshold that is protective
against HeV in real-world situations, where the incubation period may be as long as two
weeks7 and the amount of virus encountered by the horse is likely to be much lower than that
administered during experimental challenge: “the experimental horses were exposed to
considerably higher levels of HeV than have been recovered from flying foxes…”.5
As the authors of the HeV vaccine field study stated, “It is possible that protection from field
exposure to virus may also occur in immunised horses with lower (or even undetectable)
titres. The reasons for this include the rapid time-frame over which extensive mucosal
exposure to infective fluid occurs under experimental conditions and the fact that protection
will depend upon the development of an anamnestic response, in addition to pre-existing
antibody levels.”1
As for concerns about human safety, the one vaccine challenge study published to date
showed that a titre as low as 16 prevented meaningful shedding in the face of massive viral
challenge.5 Again, we don’t know the serum VN threshold that is protective against viral
transmission in real-world situations, but it is likely to be lower than that documented in this
single experimental study, in which the lowest pre-challenge titre of the ten vaccinated horses
was 16 and the horses were challenged with 2 million units of HeV via the oronasal route.
The CSIRO Australian Animal Health Laboratory (AAHL) offers two HeV-specific serum
antibody tests: an ELISA and a VN titre.8 Currently, the cost of the ELISA is comparable to
the retail price of the HeV vaccine. Unfortunately, the VN titre is considerably more
expensive. Although the ELISA provides only three possible results (positive, negative,
inconclusive), a positive ELISA is surely evidence of a HeV-specific immune response and
the potential for a rapid anamnestic response in the face of natural challenge that could be
expected to protect against severe illness at least, and probably from viral transmission as
well.
Instead of denying veterinary care to horses in need, let’s start testing horses for HeV-specific
antibodies and use our knowledge of clinical immunology and the available veterinary
literature to tailor HeV vaccination and other risk-mitigation programs. We may even be able
to encourage better uptake of the vaccine with this approach. One thing is certain: it can only
help our tattered reputation among horse owners.
Christine King BVSc, MANZCVS (equine), MVetClinStud
Anima Vet
Park Ridge, Queensland
Submitted 28 August 2020
References
1. Tan RHH, Hodge A, Klein R, et al. Virus-neutralising antibody responses in horses
following vaccination with Equivac® HeV: a field study. Aust Vet J 2018;96:161–166.
https://doi.org/10.1111/avj.12694
2. Manyweathers J, Field H, Longnecker N, et al. "Why won't they just vaccinate?" Horse
owner risk perception and uptake of the Hendra virus vaccine. BMC Vet Res 2017;13(1):103.
https://doi.org/10.1186/s12917-017-1006-7
3. Goyen KA, Wright JD, Cunneen A, et al. Playing with fire — What is influencing horse
owners' decisions to not vaccinate their horses against deadly Hendra virus infection?. PLoS
One 2017;12(6):e0180062. http://doi.org/10.1371/journal.pone.0180062
4. Wiethoelter AK, Sawford K, Schembri N, et al. "We've learned to live with it" — A
qualitative study of Australian horse owners' attitudes, perceptions and practices in response
to Hendra virus. Prev Vet Med 2017;140:67-77. https://doi.org/
10.1016/j.prevetmed.2017.03.003
5. Middleton D, Pallister J, Klein R, et al. Hendra virus vaccine, a One Health approach to
protecting horse, human, and environmental health. Emerg Infect Dis 2014;20(3):372–379.
https://doi.org/10.3201/eid2003.131159
6. Colling A, Lunt R, Bergfeld J, et al. A network approach for provisional assay recognition
of a Hendra virus antibody ELISA: test validation with low sample numbers from infected
horses. J Vet Diagn Invest 2018;30(3):362–369. https://doi.org/10.1177/1040638718760102
7. Broder CC, Weir DL, Reid PA. Hendra virus and Nipah virus animal vaccines. Vaccine
2016;34(30):3525–3534. https://doi.org/10.1016/j.vaccine.2016.03.075
8. https://aahl.csiro.au/info/companion_and_equine_testing.aspx
Article
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Obtaining statistically sound numbers of sera from Hendra virus (HeV)-infected horses is problematic because affected individuals usually die or are euthanized before developing a serum antibody response. As a consequence, test validation becomes a challenge. Our approach is an extension of OIE principles for provisional recognition and included 7 validation panels tested across multiple laboratories that provided estimates for test performance characteristics. At a 0.4 S/P cutoff, 16 of 19 sera from HeV-infected horses gave positive results in the HeV soluble G, indirect ELISA (HeVsG iELISA; DSe 84.2% [95% CI: 60.4–96.6%]); 463 of 477 non-infected horse sera tested negative (DSp 97.1% [95% CI: 95.1–98.4%]). The HeVsG iELISA eliminated almost all false-positive results from the previously used HeV iELISA, with marginally decreased relative sensitivity. Assay robustness was evaluated in inter-laboratory and proficiency testing panels. The HeVsG iELISA is considered to be fit for purpose for serosurveillance and international movement of horses when virus neutralization is used for follow-up testing of positive or inconclusive serum samples.
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Hendra virus is a zoonotic paramyxovirus, which causes severe respiratory and neurological disease in horses and humans. Since 2012, the Hendra virus sub-unit G vaccine has been available for horse vaccination in Australia. Uptake of the vaccine has been limited and spillover events of Hendra virus infection in horses continue to occur. We conducted an online, questionnaire-based cross-sectional study of 376 horse owners belonging to a variety of different equestrian clubs in Queensland, Australia, to identify risk factors for non-vaccination against Hendra virus. A total of 43.1% (N = 162) of horse owners indicated that they currently did not vaccinate against Hendra virus infection, while 56.9% (N = 214) currently vaccinated against Hendra virus infection. A total of 52 risk factors were evaluated relating to equestrian activities, horse management, perceived risk and severity of horse and human infection with Hendra virus, side effects of Hendra vaccination, other vaccinations conducted by horse owners and horse owners’ attitudes towards veterinarians. The final multivariable logistics regression model identified the following risk factors associated with increased odds of non-vaccination against Hendra virus: 1) perceived low risk (compared to high) of Hendra virus infection to horses (considering the horse owners’ location and management practices) or horse owners were unsure about the risk of infection, 2) perceived moderate severity (compared to very severe or severe) of Hendra virus infection in humans, 3) horse owners non-vaccination of their pets, 4) horse owners non-vaccination against strangles disease in horses, 5) handling of more than three horses per week (compared to one horse only) and 6) perceived attitude that veterinarians had a high motivation of making money from Hendra virus vaccination (compared to veterinarians having a low motivation of making money from Hendra virus vaccination). Horse owners were more likely to vaccinate against Hendra virus if horses were used for dressage, show jumping or eventing. The study also identified horse owners’ concerns about side-effects and about the lack of evidence on vaccine efficacy. © 2017 Goyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Article
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Background Hendra virus is a paramyxovirus that causes periodic serious disease and fatalities in horses and humans in Australia first identified in 1994. Pteropid bats (commonly known as flying-foxes) are the natural host of the virus, and the putative route of infection in horses is by ingestion or inhalation of material contaminated by flying-fox urine or other bodily fluids. Humans become infected after close contact with infected horses. Horse owners in Australia are encouraged to vaccinate their horses against Hendra virus to reduce the risk of Hendra virus infection, and to prevent potential transmission to humans. After the vaccine was released in 2012, uptake by horse owners was slow, with some estimated 11-17% of horses in Australia vaccinated. This study was commissioned to examine barriers to vaccine uptake and potential drivers to future adoption of vaccination by horse owners. Methods This study examined qualitative comments from respondents to an on-line survey, reporting reasons for not vaccinating their horses. The study also investigated scenarios in which respondents felt they might consider vaccinating their horses. ResultsSelf-reported barriers to uptake of the Hendra virus vaccine by horse owners (N = 150) included concerns about vaccine safety, cost, and effectiveness. Reduction in vaccination costs and perception of immediacy of Hendra virus risk were reported as being likely to change future behaviour. However, the data also indicated that horse owners generally would not reconsider vaccinating their horses if advised by their veterinarian. Conclusion While changes to vaccine costs and the availability data supporting vaccine safety and efficacy may encourage more horse owners to vaccinate, this study highlights the importance of protecting the relationship between veterinarians and horse owners within the risk management strategies around Hendra virus. Interactions and trust between veterinarians and animal owners has important implications for management of and communication around Hendra virus and other zoonotic disease outbreaks.
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In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease. Download MP3 Length: 1:13
Article
Objective To determine the antibody responses to a commercial Hendra virus vaccine (Equivac® HeV) in a field environment. Methods A group of 61 horses received a primary vaccination course comprising two doses administered 3–6 weeks apart (V1, V2) and a 3rd dose (V3) given 6 months after the second. This was followed by booster vaccinations at 12 monthly intervals (V4, V5). Antibody titres were assessed using a virus‐neutralisation test. Results Neutralising antibodies against HeV were not detected prior to vaccination. Antibodies were detected in 54/57 horses at 3 weeks after V1 and 51/51 had titres ≥ 32 at 8 weeks after V2. At 6 months after V2, antibody titres decreased in most (31/34) horses and were not detected in three horses. A rapid increase in antibody titres was recorded in 35/36 horses at 1 week following V3. By the first annual booster vaccination (V4), antibodies were still detectable in 29/29 horses, although titres had decreased; in 26/29 horses, titres remained ≥ 32. All horses showed an increase in antibody titres after V4. There was no statistically significant increase in mean antibody titre after V5, compared with after V4. Conclusion Horses administered Equivac® HeV, using a primary vaccination course followed by annual booster vaccinations, mounted an effective secondary immune response and acquired antibody responses that were consistent with protective immunity against HeV in the form of virus‐neutralising antibodies. No adverse events were observed after vaccine administration.