Nipah Virus

Agent
Hosts
Epidemiology
Nipah=20 As a Biological Weapon
Clinical=20 Features
Laboratory=20 Diagnosis
Treatment
Prevention=20 and Control
Public=20 Health Issues
References=20

Agent

Nipah, an emerging medical and veterinary = concern, is=20 a virus that mainly affects pigs and humans. It first = appeared in=20 1998 in Malaysia, where it caused significant damage to the = local=20 swine industry as well as the loss of over 100 human lives = (see References:=20 CDC 1999). The virus subsequently was imported to Singapore = via live=20 pigs, and 11 more industry workers died (see References:=20 Ahmad 2000). An outbreak in Bangladesh in April 2004 = is=20 ongoing and is being watched carefully; according to news = sources,=20 infection has been confirmed or is suspected in at least 29 = people,=20 and 25 have died. Because the natural history of the virus = is not=20 entirely known, more research is needed to fully = characterize this=20 newly emerging zoonotic agent.

Viral Classification

Family: Paramyxovirus=20
Formerly in the genus = Morbillivirus, now=20 classified in a new genus along with the similar Hendra = virus (70%=20 to 88% nucleotide homology, 67% to 92% amino acid = homology):=20 Henipavirus (see References:=20 Bossart 2002, Mackenzie 2001)

Virion Morphology

Helical=20
Enveloped with distinct surface = projections=20
150 to 200 nm in diameter; 10,000 to = 10,040 nm long=20
Spherical or filamentous, but pleomorphic = forms=20 occur

Genetic Composition

RNA virus=20
Single stranded=20
Mostly negative-sense, but positive-sense = template=20 strands exist=20
15,200 to 15,900 nucleotides long =

Environmental Survival

Unknown: This is a point of concern for = control and=20 eradication programs.

Source: Pig Disease Information = Centre (see References).=20

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Hosts

Nipah virus has been shown to cause clinical = disease=20 in swine and humans as well as serologic changes in several = common=20 farm animals and in various bat species.

Natural reservoir: The virus's = natural=20 reservoir includes three species of Pteropid fruit = bat=20 (also referred to as flying foxes). Many Malaysian = piggeries have=20 nectar-bearing fruit trees on their property, which would = offer=20 the opportunity for introduction of the virus into their = swine=20 herds (see References:=20 Enserink 2000).=20
Affected hosts: Pigs, humans, and = possibly=20 one dog have been reported with clinical illness caused by = Nipah=20 virus (see References:=20 Nor 1999).=20
Potential seropositive animals: = Rats, cats,=20 dogs, goats, horses. It is unknown at this time whether=20 seropositive animals could be a source of disease = transmission.=20

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Epidemiology

Given the relatively recent emergence of the = virus,=20 many aspects of Nipah virus remain vague. Transmission among = swine=20 herds is not well documented and much of what is reported is = retrospective study. Researchers are continuing to increase = the=20 current body of knowledge on the mysteries behind Nipah = virus.

Transmission

Nipah is presumably derived from a fruit = bat virus=20 that spread to swine and adapted over a few years in = closely=20 confined swine herds. Once established within the swine=20 population, the virus had ample opportunity to adapt to = human=20 hosts.=20
Close contact with infected animal = secretions=20 and/or tissues may transmit the virus between pigs.=20
The mode of disease spread between farms = has not=20 been established.

Laboratory trials suggest the following = variations in=20 presentation of illness in pigs by different routes of = transmission.=20

Clinical Presentation of Nipah = Virus by=20 Route of Exposure
Route of exposure =	Characteristics =
Oral inoculation	=97Incubation period 14-16 = days =97Mild=20 clinical signs and gross pathology
Parenteral inoculation	=97Narrow study of two pigs = revealed a more=20 severe disease, closer resembling natural=20 exposure =97Incubation period about 7-10 days =
In-contact pigs	=97Rapid = infection =97Neutralizing=20 antibodies detected at day 14
Adapted from Nor 1999 (see = References).=20

Viral Replication

Replication takes place in the tonsils and = the=20 respiratory epithelium. This suggests that the virus may be=20 transmitted in part by pharyngeal and bronchial secretions. =

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Nipah As a Biological Weapon =

Nipah virus is important as a potential = biological=20 weapon (targeted to animals, humans, or both) for the = following=20 reasons:

Even a small outbreak in pigs could = result in mass=20 culling of affected herds, thereby causing substantial = economic=20 loss to the industry or to the national economy of the = affected=20 country.=20
Nipah virus can infect humans and the = case-fatality=20 rate may be as high as 50%.=20
There is no effective treatment or = vaccine for the=20 disease in either pigs or humans (although ribavirin may = reduce=20 mortality in humans with encephalitis).=20
Little is known about Nipah virus, so an = outbreak=20 in animals or humans could cause substantial fear and = social=20 disruption.

The Centers for Disease Control and = Prevention (CDC)=20 has listed Nipah virus as a critical biological agent, = Category C.=20 Category C agents are emerging pathogens that could be = engineered=20 for mass dissemination in the future because of:

Availability=20
Ease of production and dissemination=20
Potential for high morbidity and = mortality rates=20 and major health impact

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Clinical Features

The clinical symptoms of Nipah virus vary = among=20 species, as outlined in the tables below.

Clinical Features of Nipah = Virus in=20 Humans

Characteristics:
=97Fever
=97Migraine
=97Vomit= ing
=97Emphysema
=97Myalgia
=97Encephalitis=20 (may relapse after=20 = recovery)
=97Meningitis
=97Disorientation
=97Neurologic=20 deficits (may persist after=20 recovery)
=97Coma
=97Death

Case-fatality rate: 40%* =

*From APHIS Center for = Emerging Issues=20 1999 (see References).=20

Clinical Features of Nipah = Virus in=20 Swine*=86
Developmental stage	Characteristics
All age-groups	Clinical signs that vary with = stage of=20 development: =97Nervous=20 signs =97Twitching/trembling =97Muscle=20 fasciculation =97Tetanic spasm =97Hind limb=20 weakness =97Death 1-2 days after onset of = respiratory=20 distress =97Coagulopathy leading to petechial and = ecchymotic=20 hemorrhage =97Some affected pigs may be=20 asymptomatic =97Virus tends to be vasotropic and = neurotropic=20
Suckling pigs	Disease has not been reported in = this group=20
Young pigs	=97Coughing =97Open-mouth=20 breathing =97Abnormal posturing =97Convulsions =
Weaners and growers	General flu-like ailments=20 = common =97Fever =97Anorexia =97Dyspnea =97Coughing=20
Adults	=97Neuropathy = ~Head=20 bobbing/banging = ~Spasms =20 ~Agitation/biting =97Flatulence =97Early=20 abortion =97Stillbirths =97Sudden=20 = death =97Fever =97Anorexia =97Dyspnea =97Pneumonia =97Coug= hing =97Mucoid=20 nasal secretions, may be yellow-green in color and/or=20 blood-tinged =97Sudden death
Necropsy	=97Lung consolidation, especially = diaphragmatic lobes =97Thickened interlobular=20 septae =97Bronchi saturated with frothy exudates, = may be=20 bloody =97Renal congestion and = hemorrhage =97Visceral organs=20 appear normal
Concurrent death of cats, = dogs, and rats=20 may occur on an affected farm. =86Case-fatality = rate is=20 unknown, since euthanasia is often mandated. Adapted from Nor 1999 (see =* References).=20

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Laboratory Diagnosis =

No standard protocol exists for detecting = Nipah virus=20 at this time. However, several methods have been used to = confirm=20 viral infection:

History/clinical signs=20
Virus isolation (kidney, liver, = cerebrospinal=20 fluid)=20
IgG-, IgM-capture enzyme linked = immunosorbent assay=20 (ELISA)=20
Virus neutralization=20
Immunohistochemistry (lung, kidney, = spleen, heart)=20
Reverse transcriptase polymerase chain = reaction=20 (RT-PCR)

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Treatment

Effective treatment has not been = developed for=20 Nipah infection.=20
Ribavirin, an antiviral drug, may reduce = mortality=20 among patients with encephalitis caused by Nipah virus, = although=20 further study is needed (see References:=20 Chong 2001, WHO 2001).=20
Intensive supportive care is required for = infected=20 humans.

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Prevention and = Control

Control Strategies Following Nipah Outbreak

Upon the discovery of Nipah, Malaysia and = Singapore=20 developed national plans to help eradicate the disease (see = References:=20 Nor 1999):

Phase I: Immediate eradication by = mass=20 culling of pigs (this resulted in the loss of over 1 = million swine=20 and had a significant impact on the pig industry in = Malaysia)=20
Phase II: Antibody surveillance of = high-risk=20 farms to prevent future epidemics=20
Future actions: Further research = into=20 natural hosts, pathogenesis, and epidemiology

Other preventive actions included the = following:

A ban on transporting pigs within the = country=20
A total ban on porcine production (which = has since=20 been lifted)=20
Education about contact with pigs=20
Use of personal protective equipment = among persons=20 exposed to pigs

US Policies Since the Malaysian Outbreak

The United States did not import live = pigs from=20 Malaysia or Singapore during the 1999 Nipah epidemic, and = imports=20 of live pigs from that region have remained minimal.=20
Although pork by-products (such as soups, = broths,=20 leathers, and animal feed products) were shipped to the = United=20 States, there has been no evidence of spread of the virus = within=20 the United States.=20
Travel logs from the affected region to = the Unites=20 States were cross-referenced and investigated (several = travelers=20 were carrying pork products intended for human = consumption). Also,=20 animal imports known to be destined for US zoos and = wildlife parks=20 were inspected. Again, no evidence of infection was found. =
The US Department of Agriculture has = continued to=20 encourage pork producers, associated veterinary personnel, = and the=20 medical community to remain aware of dangerous foreign = animal=20 diseases (including Nipah virus infection) that have the = potential=20 to contaminate United States livestock populations. =

Source: APHIS Center for Emerging = Issues (see=20 References).=20

Other Considerations for Prevention and Control

Since the original source of transmission = is=20 various species of fruit bats, it may be possible to = reduce the=20 transmission of Nipah to pigs by removing the fruit source = on a=20 farm (see References:=20 Enserink 2000).=20
Import/export caution and biosecurity = planning=20 should increase.=20
Increased hygiene and updated protocols = on pig=20 operations are necessary.=20
Nipah virus, like the related Hendra = virus, is=20 classified as a biosecurity level 4 (BSL-4) agent.=20
Caution should be taken among heathcare=20 professionals, research investigators, veterinary = personnel, and=20 individuals in close contact with pig production. Although = the=20 risk of transmission is considered low, precautionary = measures are=20 appropriate considering the limited epidemiologic = knowledge to=20 date.

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Public = Health Issues=20

During the Malaysian outbreak, over 250 = cases and 100=20 deaths occurred, indicating that the virus poses a = substantial=20 threat to exposed humans. Observations to date include the=20 following:

Overwhelming epidemiologic evidence = suggests that=20 human exposure is caused by direct contact with pigs, = probably=20 with infected secretions and discharges.=20
- Reports suggest that between 86% and = 93% of human=20 Nipah virus cases have involved occupational exposure to = pigs=20 (see References:=20 CDC 1999, University of Wisconsin).=20
- Exposure via contact with other animals = has not=20 been ruled out.=20
- The virus is not easily transmitted to = humans.=20
- No serologic evidence exists for = transmission=20 directly from fruit bats.
No human-to-human transmission has been = documented.=20 However, because the virus has been found in respiratory=20 secretions and urine of infected patients, standard and = droplet=20 infection control precautions should be maintained for = infected=20 hospitalized patients (see References:=20 Mounts 2001). In the current outbreak in Bangladesh, news = sources=20 report that epidemiologists suspect that person-to-person=20 transmission may be occurring, but nothing definite has = been=20 determined as yet.

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References

Ahmad K. Malaysia culls pigs as Nipah = virus=20 strikes again. (News) Lancet 2000 Jul 15;356(9225):230-1 =

APHIS Center for Emerging Issues. = Nipah virus,=20 Malaysia. Emerging Disease Notice, May 1999

Bossart KN, et al. Membrane fusion = tropism and=20 heterotypic functional activities of the Nipah virus and = Hendra=20 virus envelope glycoproteins. J Virol 2002 = Nov;76(22):11186-9 [Fu= ll=20 text]

CDC. Outbreak of Nipah = virus=97Malaysia and=20 Singapore, 1999. MMWR 1999 Apr 30;48(16) [Full=20 text]

Chong HT, Kamarulzaman A, Tan CT, et = al.=20 Treatment of acute Nipah encephalitis with ribavirin. Ann = Neurol=20 2001 Jun;49(6):810-3 [Abstract]=20

Enserink M. Malaysian researchers = trace Nipah=20 virus outbreak to bats. Science 2000 Jul 28; 289(5479): = 518-9 [Abstr= act]=20

Mackenzie JS, Chua KB, Ua PW, et al. = Emerging=20 viral diseases of Southeast Asia and the Western Pacific. = Emerg=20 Infect Dis 2001 Jun;7(3 Suppl):497-505 [Ful= l=20 text]

Mounts AW, Kaur H, Parashar UD, et al. = A cohort=20 study of healthcare workers to assess nosocomial = transmissibility of=20 Nipah virus, Malaysia, 1999. J Infect Dis 2001 Mar = 1;183(5):810-3=20 [Full=20 text]

Nor MNM. Emergency report on Nipah to = the OIE.=20 Disease Information 1999 May 28;12(20) [Agrolink=20 Malaysia Web page]

University of Wisconsin=97Madison. = Nipah virus.=20 School of Veterinary Medicine tutorial [We= b=20 page]

WHO. Nipah virus fact sheet. Sep 2001 = [Full=20 text]

Other References of Interest

Chua KB, Bellini WJ, Rota PA. Nipah = virus: a=20 recently emergent deadly Paramyxovirus. Science=20 2000;288:1432-5 [Abstract]=20

Pig Disease Information Centre Ltd. = Nipah virus=20 [Web = page]=20

Siegel RD. Nipah virus. Stanford = University=20 course on humans and viruses, Winter 2002

United Kingdom Department of Health. = Hendra=20 virus and Nipah virus: management and Control. Sep 2000 [Full=20 text]

University of Rochester Medical Center.=20 Negative strand DNA virus lecture II (measles, Nipah).=20 Department of Microbiology and Immunology [Web=20 page]

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