Factsheets about a new Paramyxovirus isolated during the viral encephalitis outbreak in Negri Sembilan
During the current outbreak of viral encephalitis in Negri Sembilan, there was evidence that another agent could be involved. Unlike known JE outbreaks which affect mainly children, this outbreak involved mainly adults working in pig farms. Many well-spaced acute and convalescent samples were negative for JE serologically and there were cases even in those who had received full immunization with mouse brain derived inactivated JE vaccine. In addition, there were anecdotal accounts of pigs dying, another piece of useful information to alert us of the possibility of another agent, not JE.
A virus which gives rise to severe syncytial formation in Vero cells was isolated from the cerebrospinal fluid of 12 patients with viral encephalitis. This virus, isolated in the Department of Medical Microbiology, University of Malaya, was taken to the Center for Disease Control and Prevention, Atlanta, USA. Preliminary evidence showed that it is possibly a new paramyxovirus related to Hendra virus.
Hendra virus was first discovered in 1994 after an explosive outbreak of severe, fatal respiratory disease affecting racehorses and humans. Twenty-one racehorses in the Brisbane suburb of Hendra were infected; 14 died of clinical disease. The trainer and a stable hand were also infected, and the trainer died. A second incident occurred in Mackay, a coastal town approximately 1,000 km north of Brisbane. Two horses and a farmer died, the latter of severe meningoencephalitis. The death of the horses and the initial infection of the farmer occurred in 1994 and preceded the Brisbane outbreak and the virus is believed to have then entered a latent phase for 1 year before reacting to cause fatal encephalitis. Experimental studies have shown that in horses and cats, after subcutaneous, intranasal and oral administration, the virus causes fatal pneumonia. Black fruit bats infected by subcutaneous, intranasal or oral routes contract a subclinical infection and generate an antibody response. Endothelial cell tropism and formation of syncytia in blood vessels are common pathologic findings in both overt and subclinical infections. In January 1999, another horse, near Cairns, died of the disease.
Extensive seroepidemiologic studies found no evidence of Hendra virus among horses, other farm animals or more than 40 species of wildlife in Queensland. However, the most likely wildlife source would be either birds or fruit bats. Subsequent studies showed that fruit bats were the natural hosts on serologic grounds and by virus isolation, with widespread evidence of infection in four species of bats. Thus, it is now clearly established that Hendra virus is a fruit bat virus and is widely distributed throughout the range of pteropid bats in Australia. Serologic evidence of infection of fruit bats has also been reported in Papua New Guinea.
Transmission of the virus
It has been shown experimentally that Hendra virus can cause severe clinical disease in cats and guinea pigs. There is infection, but no disease, in fruit bats and rabbits. No infection or disease occurs in dogs, chickens, rat and mice. Infected animals excrete the virus in their urine. Most importantly, the research also shows the virus is not carried on the breath of horses. This helps to explain why it is not highly contagious. Rigorous hygiene practices in horse stables could greatly assist the eradication of the outbreak.
New Malaysian Paramyxovirus
This new Malaysian Paramyxovirus was first tested in CDC, Fort Collins and found not to be related to any known arboviruses. In addition, reverse-transcriptase polymerase chain reaction using consensus primers directed against alphaviruses, flaviviruses and bunyaviruses were negative. At CDC, Fort Collins, electron microscopy on a grid of infected cells prepared in the University of Malaya showed foci of thickening plasma membrane with hairy-like projections suggestive of virus morphogenesis at the cell membrane. The virus appears as pleomorphic, envelope particles (spherical and elongated) of 200 to 300+ nanometer and helical nucleocapsids were noted within the envelope. Multinucleated cells were prominent and the nuclei appear normal. The virus particles are compatible with paramyxoviruses and cross-react with Hendra virus antibody by immunofluorescence. CDC Atlanta has developed a serological test for Hendra IgM and a number of serum samples from the current outbreak has been shown to be positive.
The 8-member CDC team invited by the Ministry of Health, Malaysia, to investigate the outbreak has been augmented by two Australians, one from the Department of Primary Industries, Queensland and the other from the Australian Animal Health Laboratory, Geelong, Australia. Preliminary results showed that this new Hendra-like virus is the major cause of the viral encephalitis outbreak in Negri Sembilan. Being a new virus, we can only infer that it shares certain properties with the Australian Hendra virus. Further characterization of this virus is on going in CDC and in the University of Malaya.
It is hoped that the various preventive measures undertaken by the government will be effective to curb the spread of this outbreak which has, to date, claimed over 60 lives and ruined the pig industry.
- Dr. Chua Kaw Bing and Prof. Lam Sai Kit
- Department of Medical Microbiology
- Faculty of Medicine
- University of Malaya
- Kuala Lumpur.
- 29 March 1999
- Image:Electron Microscopy of a Vero cell infected with the "new virus" showing the viral particles 200 - 300 nm in size (A & B) and its morphogenisis at the cell membrane (C). Arrow shows the viral nucleocappsid in transverse section. Click on picture for bigger image.
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More information on paramyxoviruses and this new virus at Paramyxoviridae
More information on Japanese Encephalitis
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