Hendra Virus Infection: Introduction - The Merck Veterinary Manual

Hendra Virus Infection: Introduction
(Equine morbillivirus pneumonia, Acute equine respiratory syndrome)

Etiology and Pathogenesis

Epidemiology and Transmission

Clinical Findings

Lesions

Diagnosis

Treatment, Prevention, and Control

Zoonotic Risk

Equine morbillivirus pneumonia is an acute viral respiratory infection of horses caused by Hendra virus. Characteristic clinical signs include fever, anorexia, depression, increased respiratory and heart rates, respiratory distress, and death in a high percentage of affected animals. Facial edema, frothy nasal discharge, cyanotic/jaundiced mucous membranes and mild neurologic signs have been less frequently observed in field and/or experimental cases of the disease.

Etiology and Pathogenesis:

Hendra virus is a large, pleomorphic enveloped RNA virus, and the prototype virus of the genus Henipavirus. Although initially considered to be more closely related to members of the genus Morbillivirus than to other genera in the family Paramyxoviridae, studies have shown only low-level sequence homology with respiroviruses, morbilliviruses, and rubuloviruses and negligible immunologic cross-reactivity with other paramyxoviruses, reacting very weakly by immunofluorescence and protein immunoblot analysis with antiserum to rinderpest virus. Hendra virus is antigenically related to Nipah virus ( Nipah Virus Infection: Introduction), with which it shares ~90% amino acid homology. Both viruses have been classified in a new genus, Henipavirus, in the subfamily Paramyxovirinae, family Paramyxoviridae. Hendra and Nipah viruses vary with regard to the species they infect and mode(s) and ease with which each can be transmitted.

Interstitial pneumonia of variable severity is the principal finding in natural or experimental cases of infection in horses exposed by the respiratory or parenteral routes. Hendra virus, unlike morbilliviruses such as measles and distemper, has a specific tropism for vascular tissues, regardless of route of challenge. In early infection, the vascular lesions range from edema and hemorrhage of vessel walls, fibrinoid degeneration with pyknotic nuclei in endothelial and tunica media cells, to the presence of numerous giant cells in the endothelium and sometimes the tunica media of affected vessels (both venules and arterioles). As the disease progresses, there is destruction of alveolar walls, with the appearance of alveolar and intravascular macrophages. There is evidence that virus becomes more widely distributed in various tissues throughout the body, presumably as a result of a leukocyte-associated viremia. The virus has been demonstrated in the vascular endothelium of subarachnoid and cerebral vessels and also affects the vasculature of the renal glomerulus and pelvis, lamina propria of the stomach, spleen, various lymph nodes and myocardium. In addition to its vascular tropism, Hendra virus can also be neurotropic, causing neuronal necrosis and focal gliosis.

Epidemiology and Transmission:

Naturally occurring disease caused by Hendra virus has been reported only in horses and humans. Experimentally, disease has been produced in cats and guinea pigs, but not in mice, rats, rabbits, chickens, or dogs. The clinical response and pathologic findings in cats are very similar to those observed in horses. Serologic surveys have revealed a high prevalence of neutralizing antibodies to Hendra virus in wild-caught flying foxes or fruit bats ( Pteropus spp ) in Australia and Papua New Guinea. Fruit bats experience subclinical infection and are considered the natural reservoir of the virus. Natural outbreaks of disease have been infrequent and reported only in Australia. The geographic distribution of the virus appears to be limited to Australia and Papua New Guinea. Hendra virus appears to be minimally contagious. Under field conditions, transmission between infected and noninfected horses occurs infrequently. Experimentally, attempted aerosol transmission from virus-infected horses to in-contact horses or cats was unsuccessful. Nonetheless, the possibility of respiratory transmission cannot be completely ruled out. The frothy nasal discharge commonly observed in naturally affected horses, which represents virus-rich exudate from the lungs, could potentially provide a source of virus for aerosol transmission. Although absent in the nasal cavities, trachea, conjunctival sacs, mouth, and feces, Hendra virus has been found in the urine of experimentally infected horses and cats. This route of infection may have been responsible for transmission of the virus from cat to horse in one experimental study. Based on available field and laboratory data, infection of humans or animals appears to require direct contact with virus-infective secretions (lung exudates), excretions (urine), or tissues.

Available epidemiologic, serologic, and virologic evidence implicates pteropid bats as the natural reservoir of Hendra virus. There is field and experimental proof of vertical transmission, with isolates recovered from the uterine fluid and fetal tissues of a grey-headed flying fox ( Pteropus poliocephalus ) and a black flying fox ( P alecto ). The infrequent occurrence and sporadic nature of outbreaks suggest that exposure of horses to Hendra virus is a chance event. While horses may have been infected through contact with food or water contaminated with material from infected pteropid bats (secretions, excreta, or tissues from mothers or fetuses), the mechanism of spread remains to be determined.

Clinical Findings:

Natural or experimental exposure to Hendra virus results in a high rate of clinical infection. The incubation period in field cases of the disease is usually 8-14 days, but ranges from 5-10 days in experimentally infected horses. Clinical signs include fever (up to 106°F [41°C]), anorexia, lethargy, elevation in respiratory and heart rates, respiratory distress, pneumonia, and frothy clear to blood-tinged nasal discharge, which has been observed only in natural cases of the disease. Additional clinical signs seen in some affected horses include cyanotic or jaundiced mucous membranes, dependent edema (intermandibular space, cheeks, infraorbital fossae, limbs, prepuce), and neurologic signs (ataxia, muscle fasciculation, head pressing). Case fatality may be >60-70% in cases of natural or experimentally acquired infection, with terminal cases dying in extremis. The course of the disease is short; death may occur within 1-3 days. Clinical recovery occurs occasionally.

Lesions:

The principal gross lesions are severe edema and congestion of the lungs and marked dilatation of the subpleural lymphatics. The airways are filled with thick froth, which is often blood-tinged. Additional lesions seen in some affected horses include increased pleural and pericardial fluids, congestion of lymph nodes, hemorrhages in various organs, and slight jaundice.

Microscopically, the primary lesions are those of an acute interstitial pneumonia. Severe vascular damage, with serofibrinous alveolar edema, hemorrhage, thrombosis of capillaries, necrosis of alveolar walls, and alveolar macrophages are evident in the lungs. Widespread fibrinoid degeneration of small blood vessels is seen in many organs, including the lungs, heart, kidneys, spleen, lymph nodes, meninges, alimentary tract, skeletal muscle, and bladder.

The presence of large endothelial syncytial cells is characteristic of infection. Although most prominent in pulmonary capillaries and arterioles, these cells are also observed in other organs (lymph nodes, spleen, heart, stomach, kidneys, and brain). Antigen specific for Hendra virus can be demonstrated in the vascular lesions and along alveolar walls by immunohistochemical staining. Intracytoplasmic viral inclusion bodies can be seen in infected endothelial cells by electron but not light microscopy. Lesions of nonsuppurative meningitis or meningoencephalitis, including perivascular cuffing, neuronal degeneration, and focal gliosis, have been observed in some infected horses.

Diagnosis:

Hendra virus infection should be considered in horses that die after a short febrile illness with prominent necropsy findings of severe interstitial pneumonia with marked distention of the subpleural lymphatics. Confirmation of the diagnosis is based on laboratory examination of appropriate specimens for the detection of Hendra virus, viral antigen, viral nucleic acid, or specific antibodies. Specimens of lung, kidney, spleen, liver, lymph nodes, and brain should be submitted for viral isolation or detection by PCR. The virus can be isolated in a range of cell lines; Vero cells are the cell line of choice. Viral cytopathic effect, which develops after ~3 days, is characterized by syncytia formation in infected cells. Serologic confirmation of infection is based on testing acute and convalescent sera collected 3-4 wk apart, either in a neutralization or a validated ELISA. A comprehensive range of tissues should be collected from suspect fatal cases of the disease for histopathologic examination. Presence of the characteristic vascular lesions is highly suggestive of the infection; specificity of the lesions can be confirmed by immunochemical labeling with Hendra virus reference antiserum.

African horse sickness can clinically mimic Hendra virus infection, and should be considered in the differential diagnosis. Other causes of sudden death that must be ruled out include anthrax, botulism, certain bacterial infections (eg, pasteurellosis, equine influenza, peracute equine herpesvirus 1 infection), and plant or chemical poisoning.

Treatment, Prevention, and Control:

There is no specific antiviral treatment and no vaccine for the disease caused by Hendra virus.

In view of the limited transmissibility under conditions of natural exposure to the virus and the sporadic and infrequent nature of outbreaks of the disease, there is little justification for implementation of a specific control program. The few outbreaks that have occurred in Australia have been dealt with by slaughtering all known infected horses and by imposing movement restrictions within a defined area around affected premises. Contact between horses and bat urine or uterine fluids should be avoided, when feasible.

Zoonotic Risk:

Hendra virus is transmissible to humans. The infection has been fatal in a high percentage of the cases recorded so far, either from a fulminant interstitial pneumonia or from a nonsuppurative encephalitis. Direct contact with infectious respiratory secretions, urine, or tissues appears to be necessary for viral transmission. Special precautions should be taken when conducting a clinical examination or necropsy on a horse suspected of having the disease.