Hendra Virus

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Etiology/Bacteriology

Taxonomy

| Order = Monoegavirales |Family = [[Paramyxoviridae]] |Genus = [[Henipavirus]] |Species = Hendra Virus
|NCBI: Taxonomy Genome: Genome|}

Description

Hendra Virus is a member of the Paramyxoviridae virus family, which also includes the Measles virus, Canine Distemper virus, and Mumps virus. [3] It shares the genus Henipavirus with Nipah virus. [3] Hendra virus first broke out in 1994 at a stable in Hendra, a town in Queensland, Australia. In this initial outbreak, the virus killed 13 horses and infected two humans, killing one. [4] There have been several outbreaks of Hendra since then, all concentrated in Queensland and New South Wales in Australia.[5] Flying foxes are believed to be the reservoir of Hendra virus, based on the detection of Hendra virus antibodies in the blood of several flying fox species and the discovery of a Hendra-like virus in a healthy flying fox. [6] Hendra Virus has been documented to affect horses and humans. In horses, an infection is generally characterized by depression, fever, and a frothy discharge from the nose. [4] In humans, flu-like symptoms occur, but the disease has been reported to progress to encephalitis in some fatal cases. [7]

Pathogenesis

Transmission

Flying foxes, bats from the genus Pteropus are considered to be the reservoir hosts of Hendra virus. This is due to to the detection of Hendra virus antibodies in Black flying foxes (Pteropus alecto), grey-headed flying foxes (Pteropus poliocephalus), little red flying foxes (Pteropus scapulatus), and spectacled flying foxes (Pteropus conspicillatus) in 1995.[6] This was further confirmed by the isolation of a Hendra-like virus from a healthy grey-headed flying fox. [6] Typically, transmission between infected flying foxes and horses happens first. The mechanism of transmission is still not completely clear, but several hypotheses have been proposed. In the most plausible, horses become infected by eating pasture contaminated with flying fox foetal tissues or birthing fluids.[6] This hypothesis was proposed because many Hendra infections fall within the birthing period of flying foxes (August to October), and the virus has been isolated from uterine fluid, foetal liver, and foetal lung of flying foxes in 2000.[8,9] In another proposed theory, horses become infected with the virus when they eat pellets of masticated fibrous fruit discarded by flying foxes.[6] Once a horse become infected, transmission from horse to horse, and from horses to humans, occurs through close contact with infected body fluids and secretions. [9]

Infectious Dose and Viral Spread

Currently, the infectious dose of Hendra virus is not known.[10] However, it is clear that after acquisition of an infectious dose of virus, the Hendra virus appears to spread systematically through the body, focusing on the lymph nodes and respiratory system. In experimentally infected horses, Hendra virus was recovered from lymph nodes, lung, kidney, brain and cerebrospinal fluid, as well as being detected in nasal swabs, blood, urine, and feces. [10]. In the original 1994 epidemic, the virus was detected in the lung, liver, kidney and spleen of the human fatality. [11] Keep editing

Epidemiology

As of 2008, all of the Hendra virus outbreaks have occurred in Queensland and New South Wales in Australia.[5] By that point, 29 horses and 7 human cases have been documented. Spillovers of Hendra virus to humans occurs after prolonged contact with dead or dying infected horses and their body fluids. This is evident by the fact that 5 of the 7 confirmed cases were veterinarians or their assistants, who performed necropsies or invasive procedures on Hendra virus infected horses.[12] The remaining cases involved trainers or stable workers who interacted closely with the infected horses.[4] It is interesting to note that one of the most recent Hendra virus outbreaks, in 2008, was characterized by encephalitis, instead of the respiratory symptoms seen in earlier outbreaks.[5] Whether this is due to genetic changes in the virus or some other factor still remains to be seen.

Clinical Presentation

Incubation Period and Disease Progression

Inoculation with Hendra virus is believed to occur via inhalation of aerosolized infectious fluid.[13] It is also possible that the virus can enter the body through abrasions in the skin, because two fatal cases from the 1994 outbreak had abrasions on their arms and hands while working with infected or dead horses.[11] Research has shown that Hendra virus invades the epithelial cells of the lower respiratory tract early in the course of disease. In the later stages of the disease, the virus progresses to invade the endothelial cells of the lungs, allowing it to reach the bloodstream and spread by circulating independently or binding to leukocytes.[13] Circulating through the bloodstream allows Hendra virus to reach other target organs including the spleen, kidneys, and the brain. To infect the brain, the virus must pass through the blood brain barrier.[13] The disease progression of Hendra virus has varied widely among cases. In the initial 1994 outbreak, one human case had mild symptoms and was ill for 6 weeks, while the fatal case deteriorated quickly and died after 6 days.[4] In a 1994 case diagnosed postmortem, the initial symptoms lasted for 12 days. However, approximately a year later, the patient developed encephalitis and died after 25 days in the hospital.[11] In another case, a veterinarian developed mild, flu-like symptoms that lasted for 8 days.[9] It has not been determined what causes the differences between Hendra virus cases, but it is likely that many factors, such as the amount of virus exposure, the immune strength of the host, and pre-existing health conditions likely play a role. For instance, the fatal case in the 1994 outbreak smoked heavily and showed signs of a Legionella infection at the time of his death.[4] Both of these factors could have weakened his immune system, making it easier for Hendra virus to reach a fatal concentration.

Equine Symptoms

An equine infection of Hendra virus is primarily characterized by respiratory symptoms. Infected horses become depressed, develop a fever and an elevated respiratory rate.[4] As the disease progresses, horses can show more neurologic symptoms such as restlessness, irregular stance, and irritability, as well as the excretion of a frothy, occasionally blood-tinged nasal discharge.[10] Histologically, the lungs become edematous, with dilated lymphatic vessels at their margins. Additionally, lung capillaries become degrade, and the foamy fluid discharged from the nostrils is also found in the airways.[10] The spreading of the virus to other areas of the body causes additional histological abnormalities. A horse that died in the 2004 outbreak was found upon necropsy to have cardiomegaly, an enlarged heart, as well as thickened ventricular walls and an enlarged liver.[9]

Human Symptoms

Flu-like respiratory symptoms are typically the first to appear in a Hendra virus infection. Much like infected horses, human infections begin with fever, muscle pain, headache, and lethargy.[4,13] Depending on unknown factors, the disease course can take several different paths. Some people only have flu-like symptoms, which can last for days or weeks.[4,9] However, in some fatal cases, the respiratory symptoms become more severe, resulting in pneumonia that requires mechanical ventilation. It appears that this progression in the respiratory symptoms occurs when the virus migrates from its initial location in the respiratory epithelial cells to the respiratory endothelial cells. Invasion of the endothelial cells allows Hendra virus to access the bloodstream and disseminate through the body, which leads to multiorgan failure.[13]
Disseminating through the bloodstream allows Hendra virus to invade the central nervous system by crossing the blood brain barrier.[13] There it causes potentially fatal encephalitis, characterized by confusion, ataxia, seizures, ptosis, and other neurological symptoms. In more recent outbreaks, encephalitis after a decrease in respiratory symptoms has been commonly seen in human cases. This represents a marked difference between the recent outbreaks and past outbreaks that were primarily characterized by respiratory symptoms.[5]
Histologically, Hendra virus causes dramatic changes in the tissues and organs. Lungs are typically congested and hemorrhagic with lesions. Microscopically, the tissues are filled with necrotic patches and the presence of giant, multinuclear cells.[11,13] In infections where the virus has spread to the endothelial cells of the lungs, the cells were necrotic, allowing the virus to enter the blood stream.[13] The neural tissue of encephalitic patients is characterized by widespread lesions in the brain, plaque formation in the grey and white matter, thrombosis, necrosis of the brain tissue, edema, inflammation, and deterioration of the blood vessels.[5,13]

References

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2.
3. Wang LF, Yu M, Hansson E, Pritchard LI, Shiell B, Michalski WP, Eaton BT. 2000. The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae. J Virol 74:9972–9979.
4. Murray K, Rogers R, Selvey L, Selleck P, Hyatt a., Gould a., Gleeson L, Hooper P, Westbury H. 1995. A novel morbillivirus pneumonia of horses and its transmission to humans. Emerg Infect Dis 1:31–33.
5. Playford EG, McCall B, Smith G, Slinko V, Allen G, Smith I, Moore F, Taylor C, Kung YH, Field H. 2010. Human Hendra virus encephalitis associated with equine outbreak, Australia, 2008. Emerg Infect Dis 16:219–223.
6. Field H, Young P, Yob JM, Mills J, Hall L, Mackenzie J. 2001. The natural history of Hendra and Nipah viruses. Microbes Infect 3:307–314.
7. Marsh G a., Wang LF. 2012. Hendra and Nipah viruses: Why are they so deadly? Curr Opin Virol 2:242–247.
8. Haplin K, Young PL, Field HE, Mackenzie JS. Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus. J Gen Virol. 2000 Aug;81(Pt 8):1927-32.
9. Hanna JN, McBride WJ, Brookes DL, Shield J, Taylor CT, Smith IL, Craig SB, Smith G. 2006. Hendra virus infection in a veterinarian. Med J Aust 185:562–564.
10. Marsh G a., Haining J, Hancock TJ, Robinson R, Foord AJ, Barr J a., Riddell S, Heine HG, White JR, Crameri G, Field HE, Wang LF, Middleton D. 2011. Experimental infection of horses with Hendra virus/Australia/horse/2008/Redlands. Emerg Infect Dis 17:2232–2238.
11. Paterson DL, Murray PK, McCormack JG. 1998. Zoonotic disease in Australia caused by a novel member of the paramyxoviridae. Clin Infect Dis 27:112–118.
12. Mendez DH, Judd J, Speare R. 2012. Unexpected result of Hendra virus outbreaks for veterinarians, Queensland, Australia. Emerg Infect Dis 18:83–85.
13. Escaffre O, Borisevich V, Rockx B. 2013. Pathogenesis of Hendra and Nipah virus infection in humans. J Infect Dev Ctries 7:308–311.