|Year : 2018 | Volume
| Issue : 2 | Page : 65-68
Nipah virus: Biology, disease, treatment, control, and prevention
Department of Microbiology, MGIMS, Sevagram, Wardha, Maharashtra, India
|Date of Web Publication||11-Oct-2018|
Dr. Rahul Narang
Department of Microbiology, MGIMS, Sevagram, Wardha, Maharashtra - 442 102
Source of Support: None, Conflict of Interest: None
Nipah virus (NiV), an RNA virus, belongs to genus Henipahvirus of family Paramyxoviridiae. First isolated and identified in Malaysia in 1999, NiV affects humans as well as animals such as pigs, cattle, cats, dogs, ponies etc. Fruit bats of genus Pteropus serve as reservoir host for NiV. Bangladesh has experienced almost annual outbreaks while there have been few outbreaks in India, the latest was in Kerala state in 2018. NiV has become an important human pathogen causing acute encephalitis syndrome associated with high mortality. Central nervous and respiratory systems are involved mainly along with multi-organ vasculitis and infection of endothelial cells. In early stages of disease, laboratory diagnosis can be made by isolation as well as real time polymerase chain reaction (RT-PCR) from throat swabs, nasal swabs, cerebrospinal fluid, urine and blood. In later stages, serological tests for antibody detection using ELISA are useful. Immuno-histochemistry on tissues collected after autopsy can also be performed. There is no specific treatment available for this infection and supportive therapy along with barrier nursing is mode of treatment. Monoclonal antibodies and vaccines against NiV have been found effective in animals but are yet to be tested in humans. The infection can be prevented in endemic areas by reducing exposure to fruit bats, pigs and date palm sap.
Keywords: Biology, disease, Nipah virus, prevention and control, treatment
|How to cite this article:|
Narang R. Nipah virus: Biology, disease, treatment, control, and prevention. J Mahatma Gandhi Inst Med Sci 2018;23:65-8
| Introduction|| |
Nipah virus (NiV) belongs to genus Henipavirus and is a member of the family Paramyxoviridae. NiV was initially isolated and identified in 1999 during an outbreak in Malaysia and Singapore. In that outbreak, it caused an acute encephalitis syndrome in late 1998 and early 1999., In Malaysia, the outbreak probably started around pig farms in Ipoh, in the state of Perak, and was disseminated by the movement of sick pigs to a second epicenter 260 km South in the state of Negeri Sembilan. Later, the infection spread to workers in an abattoir in Singapore where pigs originating from Negeri Sembilan were kept and slaughtered., There were 105 deaths among 265 reported cases of encephalitis, a mortality rate of nearly 40%. Majority of patients presented with a severe acute encephalitis syndrome, but some also had significant pulmonary manifestations.,, A syncytium-forming virus was isolated from the cerebrospinal fluid (CSF) of several patients. Electron microscopy (EM) showed an enveloped virus with filamentous nucleocapsids. On negative staining, the virus showed a herringbone structure, characteristic of the family Paramyxoviridae. Reactivity of infected culture cells and tissues from fatal cases with anti-Hendra antibodies by immunofluorescence and immunohistochemistry (IHC) as well as detection of anti-Hendra IgM antibodies in the serum and CSF at that time had suggested the possibility of Hendra or Hendra-like virus infection. Preliminary autopsy findings showed that the central nervous system (CNS) was a major target.,, Viral genomic sequencing provided evidence that this previously unknown virus was related to, but distinct from, Hendra virus., The virus was subsequently named Nipah virus after Kampung Sungai Nipah (Nipah River Village), where the first viral isolates were obtained., Since NiV was related to Hendra virus, immediate attention was shifted to bat species for investigation and bats of the genus Pteropus (flying foxes) were found to be the reservoir for NiV. Serologic studies also suggested that NiV infection occurred in dogs, cats, and two polo ponies and bats in the outbreak area in Malaysia. In that outbreak, NiV caused a relatively mild disease in pigs, but humans suffered more. To stop the outbreak, more than a million pigs were culled and buried leading to major trade loss for Malaysia. Since that outbreak, no subsequent cases (in neither swine nor human) were reported in either Malaysia or Singapore.
In the year 2001, another outbreak of human disease due to NiV was reported in Bangladesh. On genetic sequencing the strain of NiV was different of the one identified in 1999 in Malaysia. Another outbreak was identified in Siliguri, India, in the same year with reports of person-to-person transmission in hospital settings. Unlike the Malaysian NiV outbreak, outbreaks have occurred almost annually in Bangladesh and have been reported several times in India, the latest one was reported from Kozhikode in Kerala state in first half of 2018.
| Biology of Nipah Virus|| |
EM studies of the virus demonstrate features characteristic of a virus belonging to the family Paramyxoviridae. This family of viruses typically possesses a single-stranded nonsegmented RNA genome of negative polarity that is fully encapsidated by protein. The helical nucleocapsid structure is surrounded by envelope derived from the plasma membrane from which the viruses bud. Virus particles vary in size from 120 to 500 nm. The NiV envelope contains two transmembrane glycoproteins, a cell receptor binding glycoprotein (G) and a fusion protein (F). Thin-section EM studies of infected cells reveal filamentous nucleocapsids within cytoplasmic inclusions and incorporated into virions budding from the plasma membrane. Typical “herringbone” nucleocapsid structures, approximately 1.67 + 0.07 μm in length and with an average diameter of 21 nm, are demonstrated in infected cells by means of negative stain preparations. Extracellular virus particles are pleomorphic, with an average diameter of 500 nm. Surface projections along the virion envelope are only sporadically seen by thin-section EM and measure 10 nm in length.
| Pathology Produced by Nipah Virus|| |
During Malaysian outbreak, primary pathology in humans was found to be a multiorgan vasculitis associated with infection of endothelial cells. Occasional endothelial cells of affected vessels developed into multinucleated giant cells characteristic of paramyxovirus infections, whereas other endothelial cells were lysed and sloughed into the vessel lumen. Infection was most prominent in the CNS, where a diffuse vasculitis was noted in the cerebral cortex and brain stem with extension to parenchymal tissue, where extensive areas of rarefaction (lytic) necrosis were seen. Eosinophilic, mainly intracytoplasmic, viral inclusions with a melted-tallow appearance were seen in the affected neurons and other parenchymal cells. Intense immunostaining of endothelial cells and of dead and dying parenchymal cells using an anti-NiV hyperimmune serum was seen in the CNS. Less intense immunostaining was also seen in other tissues, including the lung, heart, spleen, and kidney. These studies demonstrated that NiV infection in humans can cause widespread CNS pathology consistent with severe encephalitis.
| Action at Molecular Level|| |
Endothelial cells are the major cellular targets for NiV, and hence syncytial endothelial cells in blood vessels are considered a characteristic feature of NiV disease. The fusion (F) and attachment (G) proteins of NiV mediate syncytia formation. Cell lines from many animal species are permissive for NiV-envelope-mediated fusion,, suggesting that the receptor for NiV is highly conserved. It has been reported that a membrane-bound ligand for the EphB class of receptor tyrosine kinases (RTKs) named ephrinB2, specifically binds to the attachment (G) glycoprotein of NiV. Transfection of ephrinB2 into nonpermissive cells, other than endothelial cells and neurons that express EphrinB2 on their surface and thus are prone for viral tropism, renders them permissive for NiV fusion and entry.
| Transmission|| |
In different outbreaks, substantial data have implicated flying foxes (Pteropus spp.) as the natural reservoir of NiV. Investigations of Pteropus spp. in Malaysia, Cambodia, and Thailand have consistently identified antibodies against NiV.,,, It has been isolated from Pteropus spp. in Malaysia, Cambodia, and Thailand.,,P. giganteus is the only Pteropus species present in Bangladesh. In the Naogaon, Bangladesh investigation, 2 of 19 P. giganteus specimens had antibody against NiV. Four consecutive annual outbreaks of NiV in the Central and West Bangladesh from 2001 to 2004,, occurred between January and May each year. It was reported that different outbreaks were associated with different exposures – contact with the secretions of an ill person, a sick cow, a herd of pigs, and climbing trees. Isolates of NiV isolated from affected humans in Bangladesh showed considerable genetic diversity. This genetic diversity of NiV isolated from affected persons in Bangladesh suggest substantial diversity of the virus in the wildlife reservoir and repeated spillover of the virus from its reservoir to the human population.
Date palm sap collection has been associated with NiV transmission in Bangladesh. There, at the beginning of the season in December, the bark is shaved off on one side of the tree (Phoenix sylvestris) near the top in a V shape, and a small hollow bamboo tap is placed at the base of the V. Sap collectors scrape the area where the bark is denuded so the sap can flow freely and tie a 2-to 4-L clay pot under the tap in the late afternoon. During the night, as the palm sap rises to the top of the tree, some leaks out where the bark is denuded, flows through the tap, and drips into the clay pot. Palm sap collectors climb the trees between 5:00 am and 6:00 am to gather the clay pots.
In a qualitative study, owners of date palm trees reported that they often heard bats at night. Owners viewed the fruit bats as a nuisance because they frequently drank the palm sap directly from the tap or the clay pot. Bat excrement was commonly found on the outside of the clay pot or floating in the sap. Occasionally, dead bats were found floating in the pots. They also reported deaths in persons who drank that date palm sap.
| Clinical Features|| |
After exposure, the incubation period for the disease is 5–14 days after which encephalitis presents with 3–14 days of fever and headache, followed by drowsiness, disorientation, and mental confusion. The patient may progress to coma within 24–48 h. Clinical features of a respiratory involvement may be seen during the initial part of infections, and 50% of the patients who have severe neurological signs may also show pulmonary signs. Long-term sequelae following NiV infection have been noted, including persistent convulsions and personality changes. Latent infections have also been reported with subsequent reactivation of NiV, months and even years after exposure.
In a study published from Malaysia, among the 94 studied patients with NiV, the main presenting features were fever, headache, dizziness, and vomiting. Fifty-two patients (55%) had a reduced level of consciousness and prominent brain stem dysfunction. In that study, the involvement of the brain stem and the upper cervical spinal cord was indicated by signs that included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia. The initial CSF findings were abnormal in 75% of patients. Antibodies against Hendra virus were detected in serum or CSF in 76% of 83 patients tested. Thirty patients (32%) died after rapid deterioration in their condition. An abnormal Doll's eye reflex and tachycardia were factors associated with a poor prognosis. Death was probably due to severe brain stem involvement. Neurologic relapse occurred after initially mild disease in three patients. Fifty patients (53%) recovered fully and 14 (15%) had persistent neurologic deficits.
| Laboratory Diagnosis|| |
In early stages of disease direct demonstration of the virus by isolation can be attempted and real-time polymerase chain reaction (RT-PCR) from throat swabs, nasal swabs, cerebrospinal fluid, urine, and blood should be performed. In later stages, serological tests for antibody (IgM and IgG) detection using ELISA can be used. If patient dies, IHC on tissues collected after autopsy may be the only way to confirm a diagnosis of NiV.
| Treatment|| |
Treatment is limited to supportive care. Standard infection control practices and barrier nursing techniques are important in preventing hospital-acquired infections as NiV encephalitis can be transmitted from person-to-person. Ribavirin, an antiviral medication used to treat hepatitis C, has also been shown to be effective in vitro, but human investigations to date have been inconclusive and the clinical usefulness of ribavirin remains uncertain. Use of a human monoclonal antibody targeting the Nipah G glycoprotein as passive immunization has been evaluated in the postexposure therapy in the ferret model and was found to be of benefit.
| Prevention|| |
In endemic areas, NiV infection can be prevented by limiting exposure to sick pigs and bats and refraining from drinking raw date palm sap. Additional efforts should focus on surveillance and awareness to prevent future outbreaks. For better understanding of the ecology of bats and NiV, research is needed with investigating questions such as the seasonality of disease with reproductive cycles of bats. For surveillance, reliable laboratory assays for early detection of disease in communities and livestock should be used. Awareness should be created regarding transmission and symptoms in the community and standard infection control practices to avoid human-to-human infections in hospital settings should be reinforced. No vaccine is currently approved for human use; however, a number of soluble glycoprotein vaccines have been found protective in experimental animals.
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Conflicts of interest
There are no conflicts of interest.
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