Nipah Virus

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

Agent

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

Viral Classification

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

Virion Morphology

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

Genetic Composition

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

Environmental Survival

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

Source: Pig Disease Information Centre (see References).

Hosts

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

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

Epidemiology

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

Transmission

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

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

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

Viral Replication

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

Nipah As a Biological Weapon

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

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

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

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

Clinical Features

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

Clinical Features of Nipah Virus in Humans

Characteristics:
—Fever
—Migraine
—Vomiting
—Emphysema
—Myalgia
—Encephalitis (may relapse after recovery)
—Meningitis
—Disorientation
—Neurologic deficits (may persist after recovery)
—Coma
—Death

Case-fatality rate: 40%*

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

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

Laboratory Diagnosis

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

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

Treatment

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

Prevention and Control

Control Strategies Following Nipah Outbreak

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

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

Other preventive actions included the following:

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

US Policies Since the Malaysian Outbreak

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

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

Other Considerations for Prevention and Control

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

Public Health Issues

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

Overwhelming epidemiologic evidence suggests that human exposure is caused by direct contact with pigs, probably with infected secretions and discharges.

Reports suggest that between 86% and 93% of human Nipah virus cases have involved occupational exposure to pigs (see References: CDC 1999, University of Wisconsin).
Exposure via contact with other animals has not been ruled out.
The virus is not easily transmitted to humans.
No serologic evidence exists for transmission directly from fruit bats.

No human-to-human transmission has been documented. However, because the virus has been found in respiratory secretions and urine of infected patients, standard and droplet infection control precautions should be maintained for infected hospitalized patients (see References: Mounts 2001). In the current outbreak in Bangladesh, news sources report that epidemiologists suspect that person-to-person transmission may be occurring, but nothing definite has been determined as yet.

References

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

APHIS Center for Emerging Issues. Nipah virus, Malaysia. Emerging Disease Notice, May 1999 [Full text]

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

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

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

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

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

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

Nor MNM. Emergency report on Nipah to the OIE. Disease Information 1999 May 28;12(20)

University of Wisconsin—Madison. Nipah virus. School of Veterinary Medicine tutorial [Web page]

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

Other References of Interest

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

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

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

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

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


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