Hendra Virus

Brett Tennent-Brown • Andrew W. Van Eps • GabrieUe Landolt

Hendra virus (HeV) was first identified in September 1994 following the deaths of 14 Thoroughbred horses and 1 human during an outbreak of respiratory disease at racing stables located in Hendra, Queensland, Australia.¹ Severe, acute respiratory disease due to HeV occurred sporadically over the subsequent 14 years; however, neurologic signs have predominated in cases since 2008.

■ Etiology and Epidemiology HeV and the closely related Nipah virus together form the genus Henipavirus in the family Paramyxoviridae. Henipavirus infection is dependent on the G and F viral glycoproteins. The G glycoprotein is a receptor binding protein that binds ephrin-B2 and ephrin-B3, whereas the F protein mediates fusion of the viral and host cell membranes.² Ephrin-B2 and ephrin-B3 are widespread on host's vascular endothelial cells, and as a consequence, HeV infection results in a vasculitis that particularly affects the respiratory and central nervous systems.^3,4

HeV causes natural disease in horses and humans,¹ and disease has been experimentally induced in cats, guinea pigs, and mice.⁵ The natural reservoirs for HeV are four species of pteropid bats (fruit bats or flying foxes) that are widely dis­tributed throughout northern and eastern Australian.⁶ HeV infection of bats is asymptomatic and apparently widespread; serologic surveys indicate a high prevalence of HeV antibodies in bats, including those in areas where equine or human disease has not been documented.⁷ Following experimental infection of bats, virus can be detected in blood, saliva, urine, feces, placental tissues, and aborted pups.⁸ Transmission between bats is thought to occur by exposure of naive animals to virus- contaminated urine or feces within the roost.⁹

Most equine cases have occurred between June and Decem­ber, although the reason for this apparent seasonality is unclear.

HeV poses a serious zoonotic risk to animal caretakers and attending veterinarians. All reported human HeV infections have been linked to close contact with infected horses, and direct bat-to-human or human-to-human transmission has not been reported.^1,11,12 Although the risk of viral transmission appears to increase as the disease progresses, virus is shed at low levels prior to the appearance of clinical signs in experi­mental infections. Horse-to-human transmission is thought to require direct physical contact with nasopharyngeal secre- tions¹³; however, the virus can survive for several hours in the environment, and transmission by fomites might be possible. The risk of human infection is particularly high in the terminal stages of disease, and postmortem examinations should be postponed in suspect cases until HeV infection has been ruled out by appropriate testing.

■ Clinical Signs The incubation period in experimentally infected horses ranges between 5 and 16 days and in humans appears to be between 5 and 21 days.^13-15 Prior to 2008, signs of acute severe respiratory disease predominated in equine HeV infections. However, since 2008, neurologic signs have been described more commonly and might be the result of a minor genetic change to the virus. Approximately 75% of cases are fatal, and these typically progress rapidly. although recently several HeV-positive horses have been described with a more gradual disease progression. Sudden death of one or more horses without obvious signs of illness should raise suspicion of HeV infection.

■ Pathology Gross changes at postmortem include edematous (submandibular and bronchial) lymph nodes, dilated pulmonary lymphatics, subpleural hemorrhages, and pulmonary consolida­tion and edema. Edema of other tissues may also be apparent. Histologically, HeV infection is characterized by a systemic vasculitis, particularly of the respiratory tract, brain, and meninges. Perivascular lymphocyte cuffing, neuronal necrosis, and focal gliosis have been observed in the brain. Perhaps the most notable histologic finding in HeV infection is the presence of syncytial giant cells containing cytoplasmic inclusion bodies in the pulmonary vascular endothelium.¹⁶ Using electron microscopy, pleomorphic enveloped particles containing the helical nucleocap- sid characteristic of the paramyxoviruses can be observed within cytoplasmic inclusions.^17,18 Hendra virus has unique morphologic characteristics that can be useful for diagnosis; the envelope is covered with spikes of 10 and 18 nm length, which gives the particle a unique “double fringed” appearance.^17,19

■ Diagnosis In regions where the virus is known to occur, HeV infection should be considered in any horse exhibiting a high fever and signs of acute lower respiratory tract or neurologic disease. It should be noted that not all infected horses have a fever when evaluated. HeV infection should also be considered in cases of sudden death.

Laboratory testing is essential for confirmation or exclusion of HeV infection and includes virus isolation, detection of viral nucleic acid in body fluids or tissues, and demonstration of specific serum antibodies. Blood, nasal swabs, oral swabs, or vaginal or rectal mucosal swabs are suitable for quantitative real-time reverse transcriptase PCR (qRT-PCR) testing of both living and dead horses. However, samples collected very early in the disease incubation period can be negative by qRT-PCR testing. Furthermore, not all samples are positive simultaneously, and so collection of multiple samples for PCR is recommended. Detailed guidelines for sample collection, handling, and sub­mission are available from local government sources such as the Queensland Government Department of Agriculture and Fisheries (http://www.daf.qld.gov.au). Appropriate personal protective equipment (protective eyewear, particulate mask, impervious gloves and gown) must be worn when collecting samples from suspect horses. Postmortem examinations pose the highest transmission risk for humans, and necropsies of suspect cases should be postponed until HeV infection has been ruled out.

■ Treatment and Prevention In regions where HeV occurs, owners are advised to reduce contact between fruit bats and horses. Recommendations include to avoid placing feed or water beneath trees in which fruit bats might roost, limit horse access to flowering or fruiting trees that might attract fruit bats, and stable horses at dusk and overnight when fruit bats are most active. Since HeV contains a host cell-derived lipid envelope, inactivation of the virus is possible using compounds that disrupt the lipid envelope (e.g., lysol, sodium dodecyl sulphate [SDS], acetone, methanol).¹⁸

In November 2012, a subunit adjuvanted vaccine containing soluble HeV G proteins was released under a “minor permit” requiring strict conditions for its use.² The vaccine, Equivac® HeV (Zoetis, Parsippany, NJ.), is now fully registered, and the dosing schedule has been adjusted based on studies evaluat­ing the duration of immunity.²⁰ The vaccine can be administered to healthy horses older than 4 months of age; the initial vaccination and booster are administered 21 to 42 days apart, followed by an additional booster at 6 months with annual boosters thereafter.

Crofton Weed Poisoning (Numinbah Horse Sickness, Tallebudgera Horse Disease)

Andrew W. Van Eps • Brett Tennent-Brown

The plant Eupatorium (Ageratina) adenophora is native to Central America but now appears as an intractable weed in many countries, including Australia and New Zealand.¹ Ingestion of large quantities of E. adenophora causes a pneumotoxicosis characterized by increased respiratory effort and rate. Outbreaks of respiratory disease caused by E. adenophora were reported in Southern Queensland and New South Wales in the 1940s and have occurred periodically since then.¹ Respiratory disease caused by E. adenophora has also been reported in New Zealand. The related species Eupatorium riparium is a perennial weed in Queensland and New South Wales and causes a similar syndrome in feeding trials. However, field cases of disease caused by E. riparium have not been reported.²

■ Epidemiology Respiratory disease caused by E. adenophora has been described in horses between ages 18 months and 12 years with no gender predilection. Horses appear to be the only large animal species affected. Flowering stages are more toxic than nonflowering stages, and most cases occur during the summer after ingestion of the plant in spring.^1,3 There is typically a minimum of 2 months between plant ingestion and the appearance of clinical signs.²

■ ClinicalSigns The earliest clinical sign noted in affected animals is coughing that is exacerbated by exercise.^1,3 Respiratory rate and effort are markedly increased, and in some cases a double expiratory effort is apparent.

■ Pathology The toxic principle of E. adenophora is unknown.² Pyrrolizidine alkaloids are suspected because of the condition’s similarity to Crotalaria-associated lung disease (“jaagsiekte”) seen in South African horses. The toxin (or toxins) appears to be absorbed from the GI tract, and inhalation of plant material (e.g., pollen) is not required for disease.

At necropsy, the lungs are firm and do not collapse on opening the thorax. Pulmonary fibrosis is widespread, and there may be cavities containing necrotic material within the parenchyma. The visceral pleura are often thickened and white in appearance, with focal adhesions to the parietal pleura. Hydrothorax, pulmonary edema and emphysema, hydroperi­cardium, and cardiac dilation may be found in horses that die suddenly.^1,3

Sheets of epithelial-like cells lining the alveoli are apparent on histologic examination. Accumulations of inspissated protein are present within the alveoli of most chronic cases, and eosinophils and neutrophils commonly fill the bronchioles and surrounding alveoli.

■ Treatment No effective treatment is known; once diagnosed, the condition is irreversible, although antimicrobials and corticosteroids have improved clinical signs in some cases.

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