Faculty of Medicine >
PhD Theses: Medicine >
Please use this identifier to cite or link to this item:
|Title: ||Pathology and pathogenesis of Nipah virus infection in humans and animal model|
|Authors: ||Wong, Kum Thong|
|Keywords: ||Nipah virus|
NiV transmission to humans
|Issue Date: ||Dec-2008 |
|Publisher: ||University Malaya|
|Abstract: ||In 1998, an outbreak of acute encephalitis in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus (NiV). Subsequently, outbreaks were also reported in Bangladesh and India. So far, the number of people infected is more than 500 with mortality between 40-70%. NiV is closely related to Hendra virus (HeV), both belonging to the new genus, Henipavirus (family Paramyxoviridae). The natural host of henipaviruses is the pteropid or fruit bat whose range includes Africa, Asia- ceania and Australia. In the NiV outbreaks in Malaysia and Singapore, the intermediate host was the pig, while in Bangladesh and India, direct bat-to-human and human-to-human transmission occurred. Acute NiV infection may be asymptomatic; symptomatic cases present with fever and headache or acute encephalitis often associated with coma. Most patients recovered without serious sequelae but a small percentage developed relapsed/late-onset NiV encephalitis. HeV infection is also associated with relapsed encephalitis but acute encephalitis has not been previously reported.
To study the human pathology of NiV infection, 31 cases of acute infections and 3 cases of relapsed/late-onset encephalitis were examined. These findings were compared with human HeV, and infections in a hamster model (Mesocricetus auratus). Tissues were examined by histology, immunohistochemistry, electron microscopy, in situ hybridisation and other molecular techniques.
In acute NiV infection, there were systemic vasculitis and discrete, plaque-like, parenchymal necrosis and inflammation in most organs, particularly in the central nervous system (CNS). Vascular endothelial damage, multinucleated syncytia and vasculitis resulted in thrombosis, vascular occlusion, ischaemia and microinfarction. Viral antigens were immunolocalised to the vascular wall. Viral inclusions, nucleocapsids, antigens and RNA were also detected in extravascular parenchymal cells especially in neurons. The pathogenesis of acute NiV infection appears to be a unique dual mechanism of vasculitis-induced thrombosis, ischaemia/microinfarction, and direct parenchymal cell infection.
In relapsed/late-onset NiV encephalitis, CNS-limited lesions consisted of mildly inflamed, vacuolated necrotic lesions merging with confluent areas of more extensive neuronal necrosis and increasing inflammation. Some lesions had a distinctive concentric or wave-like morphology. There were neuronal viral inclusions, antigen/RNA and nucleocapsids but vasculitis was absent throughout. These findings suggest that relapsed/late-onset encephalitis is a recurrent infection rather than post-infectious encephalitis, and that reinfection is unlikely to have arisen from extraneural foci.
The case of acute HeV infection that had no clinical encephalitis showed evidence of systemic vasculitis and parenchymal cell involvement. Virus inclusions and antigens/RNA were found especially in neurons. Relapsed HeV encephalitis was characterised by severe meningoencephalitis with neuronal infection, inflammatory cells and reactive blood vessels. Vasculitis was absent. Hence, human HeV infection appears to be similar to acute and relapsed NiV encephalitis, respectively.
Hamsters with acute henipavirus infections demonstrated vasculitis, thrombosis and the rare endothelial syncytia in blood vessels of multiple organs. Viral antigens/RNA and nucleocapsids were localized in vascular and extravascular tissues in the CNS and other organs. Infectious virus and/or RNA could be recovered from tissues and urine.
The pathology and pathogenesis of acute henipavirus infection in humans and hamsters appears to be very similar. Human relapsed/late-onset NiV encephalitis and relapsed HeV encephalitis are both recurrent infections. Thus, the henipaviruses share common biological characteristics including the ephrin B2 virus entry receptor, pathology and pathogenesis.|
|Description: ||Thesis (PhD) -- Faculty of Medicine, University of Malaya, 2008.|
|Appears in Collections:||PhD Theses: Medicine|