The emergence of Nipah virus, a highly pathogenic paramyxovirus

https://doi.org/10.1016/j.jcv.2008.08.007Get rights and content

Abstract

Nipah virus first emerged in Malaysia and Singapore between 1998 and 1999, causing severe febrile encephalitis in humans with a mortality rate of close to 40%. In addition, a significant portion of those recovering from acute infection had relapse encephalitis and long-term neurological defects. Since its initial outbreak, there have been numerous outbreaks in Bangladesh and India, in which the mortality rate rose to approximately 70%. These subsequent outbreaks were distinct from the initial outbreak, both in their epidemiology and in their clinical presentations. Recent developments in diagnostics may expedite disease diagnosis and outbreak containment, while progress in understanding the molecular biology of Nipah virus could lead to novel therapeutics and vaccines for this deadly pathogen.

Introduction

Nipah virus (NiV) is a highly pathogenic paramyxovirus that first emerged in Malaysia and Singapore in 1999. Due to its high pathogenicity, biosafety level-4 containment is required to work with live NiV in laboratories. Since its initial outbreak, NiV has re-emerged in Bangladesh and in India. This review focuses on the epidemiological and clinical findings from these subsequent outbreaks, and compares these findings to those from the initial outbreak. Recent progress in NiV molecular biology is discussed, along with new diagnostic tests and potential therapeutics.

Section snippets

Epidemiology

The first known human infections with NiV were detected during an outbreak of severe febrile encephalitis in peninsular Malaysia and Singapore from the fall of 1998 to the spring of 1999. A total of 276 patients with viral encephalitis due to NiV were reported in peninsular Malaysia and Singapore, mostly among adult males who were involved in pig farming or pork production activities, with 106 fatalities (case fatality rate (CFR)—38.5%).1, 2, 3, 4 In spite of isolation of NiV from urine,

Clinical presentation

NiV causes rapid acute encephalitis with a high mortality rate. The incubation period during the Malaysian outbreak ranged from 4 days to 2 months, with a majority of patients reporting within 2 weeks or less. The primary clinical features were fever, headache, dizziness, vomiting, and reduced levels of consciousness. Distinctive clinical signs included segmental myoclonus, hypertension, tachycardia, areflexia, and hypotonia.20 The direct cause of death was likely due to effects of encephalitis

Virus reservoir

Despite the ability of NiV to infect across many mammalian species (dogs, cats, ferrets, pigs, horses), the absence of neutralizing antibody in non-infected hosts indicated that these were ‘dead-end hosts’.29 Since HeV had been detected in fruit bats of the Pteropus genus, they were seen as the logical reservoir for NiV.30 Neutralizing antibodies to NiV were found primarily in Pteropus hypomenalus and Pteropus vampyrus during initial surveillance studies, but virus was not isolated.31 It was

Virology and molecular biology

NiV is a single-stranded, negative-sense RNA virus belonging to the family Paramyxoviridae, in the subfamily Paramyxovirinae, in the genus Henipavirus that it shares with HeV (Fig. 1A). The genome of NiV consists of six genes (N-P-M-F-G-L) flanked by a 3′ leader and 5′ trailer region (Fig. 1B).39 The large genome length of NiV (18,246 nucleotides for Malaysian strain (NiV-M)), 18,252 nucleotides for Bangladesh strain (NiV-B) and HeV (18,234 nucleotides) compared to other paramyxoviruses is due

Diagnostics and antivirals

During the initial NiV outbreak, enzyme-linked immunosorbent assays (ELISAs) specific for detecting anti-HeV IgM and IgG were used to diagnose NiV infection. A NiV-specific ELISA was eventually transferred to surveillance labs in Malaysia.57 For cases in which the ELISAs gave equivocal results, negative-stained cerebrospinal fluid (CSF) specimens was subjected to transmission electron microscopy to visually confirm the presence of NiV.58 Immunohistochemistry was crucial in detecting NiV antigen

Conclusions

Since its emergence in Malaysia, NiV has been a recurring threat to human health in Southeast Asia. The comparative worsening of clinical findings and CFRs from the Bangladesh and India outbreaks compared to the Malaysian outbreak reinforce the need to improve preventative measures against NiV infection wherever possible. Expanding the surveillance and laboratory capacity for diagnosing encephalitis in outbreak-prone areas is crucial to early detection and containment of outbreaks.

As an RNA

References (82)

  • A.M. Flenniken et al.

    Distinct and overlapping expression patterns of ligands for Eph-related receptor tyrosine kinases during mouse embryogenesis

    Dev Biol

    (1996)
  • P. Hooper et al.

    Comparative pathology of the diseases caused by Hendra and Nipah viruses

    Microbes Infect

    (2001)
  • K.T. Wong et al.

    Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis

    Am J Pathol

    (2002)
  • P. Daniels et al.

    Laboratory diagnosis of Nipah and Hendra virus infections

    Microbes Infect

    (2001)
  • V.T. Chow et al.

    Diagnosis of Nipah virus encephalitis by electron microscopy of cerebrospinal fluid

    J Clin Virol

    (2000)
  • V. Guillaume et al.

    Specific detection of Nipah virus using real-time RT-PCR (TaqMan)

    J Virol Methods

    (2004)
  • S. Wacharapluesadee et al.

    Duplex nested RT-PCR for detection of Nipah virus RNA from urine specimens of bats

    J Virol Methods

    (2007)
  • J.M. Chen et al.

    A comparative indirect ELISA for the detection of henipavirus antibodies based on a recombinant nucleocapsid protein expressed in Escherichia coli

    J Virol Methods

    (2006)
  • M. Eshaghi et al.

    Purification of the extra-cellular domain of Nipah virus glycoprotein produced in Escherichia coli and possible application in diagnosis

    J Biotechnol

    (2005)
  • M. Eshaghi et al.

    Nipah virus glycoprotein: production in baculovirus and application in diagnosis

    Virus Res

    (2004)
  • M. Juozapaitis et al.

    Generation of henipavirus nucleocapsid proteins in yeast Saccharomyces cerevisiae

    Virus Res

    (2007)
  • Y. Kashiwazaki et al.

    A solid-phase blocking ELISA for detection of antibodies to Nipah virus

    J Virol Methods

    (2004)
  • N. Tanimura et al.

    Monoclonal antibody-based immunohistochemical diagnosis of Malaysian Nipah virus infection in pigs

    J Comp Pathol

    (2004)
  • K.N. Bossart et al.

    Neutralization assays for differential henipavirus serology using Bio-Plex protein array systems

    J Virol Methods

    (2007)
  • CDC

    Outbreak of Hendra-like virus—Malaysia and Singapore, 1998–1999

    Morbid Mortal Wkly Rep

    (1999)
  • CDC

    Update: outbreak of Nipah virus—Malaysia and Singapore, 1999

    Morbid Mortal Wkly Rep

    (1999)
  • U.D. Parashar et al.

    Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998–1999 outbreak of severe encephalitis in Malaysia

    J Infect Dis

    (2000)
  • V.P. Hsu et al.

    Nipah virus encephalitis re-emergence, Bangladesh

    Emerg Infect Dis

    (2004)
  • ICDDRB

    Nipah encephalitis outbreak over a wide area of Bangladesh

    Hlth Sci Bull

    (2004)
  • ICDDRB

    Person-to-person transmission of Nipah virus during outbreak in Faridpur District

    Hllth Sci Bull

    (2004)
  • S.P. Luby et al.

    Foodborne transmission of Nipah virus, Bangladesh

    Emerg Infect Dis

    (2006)
  • PROMED-MAIL. Nipah virus, fatal. Bangladesh;...
  • WHO

    Nipah virus outbreak(s) in Bangladesh, January–April 2004

    Wkly Epidemiol Rec

    (2004)
  • M.S. Chadha et al.

    Nipah virus-associated encephalitis outbreak, Siliguri, India

    Emerg Infect Dis

    (2006)
  • A.K. Harit et al.

    Nipah/Hendra virus outbreak in Siliguri, West Bengal, India in 2001

    Indian J Med Res

    (2006)
  • PROMED-MAIL. Nipah virus, fatal. India (West Bengal);...
  • M.J. Hossain et al.

    Clinical presentation of Nipah virus infection in Bangladesh

    Clin Infect Dis

    (2008)
  • E.S. Gurley et al.

    Person-to-person transmission of Nipah virus in a Bangladeshi community

    Emerg Infect Dis

    (2007)
  • E.S. Gurley et al.

    Risk of nosocomial transmission of Nipah virus in a Bangladesh hospital

    Infect Control Hosp Epidemiol

    (2007)
  • B.H. Harcourt et al.

    Genetic characterization of Nipah virus, Bangladesh, 2004

    Emerg Infect Dis

    (2005)
  • K.J. Goh et al.

    Clinical features of Nipah virus encephalitis among pig farmers in Malaysia

    N Engl J Med

    (2000)

    • Cited by (117)

    • Health Emergency Risk Management in World Health Organization – South-East Asia Region during 2014–2023: synthesis of experiences

      2023, The Lancet Regional Health - Southeast Asia

    • Development of a neutralization assay using a vesicular stomatitis virus expressing Nipah virus glycoprotein and a fluorescent protein

      2023, Virology

    • A short communication of Nipah virus outbreak in India: An urgent rising concern

      2022, Annals of Medicine and Surgery
      Citation Excerpt :

      The virus is categorized under the Category C priority pathogen and a biological safety level 4 (BSL-4) pathogen by the Centers for Disease Control and Prevention (CDC). The first cases were reported in Malaysia and Singapore between 1998 and 1999 after its discovery in Sungai Nipah where it took its origin [2]. Following the initial outbreaks in Malaysia and Singapore, India recorded outbreaks in 2001 and 2007.

    • The pathogenesis of Nipah virus: A review

      2022, Microbial Pathogenesis

    • Emerging viruses: Cross-species transmission of coronaviruses, filoviruses, henipaviruses, and rotaviruses from bats

      2022, Cell Reports

    • Phylogenetic and genetic analyses of the emerging Nipah virus from bats to humans

      2020, Infection, Genetics and Evolution
    View all citing articles on Scopus
    View full text
    Published by Elsevier B.V.