Describes By : Dr. Robert Rowen


 


 
 



Nipah Virus Disease

This is a totally new disease that first became evident in September 1998 in Malaysia. In March 1999 a previously unknown virus was isolated from an adult male who having had contact with pigs died. The virus was identified as a previously unknown paramyxovirus and the disease was called Nipah Disease from the village in Malaysia where it was first identified.

The virus causes illness and death in both humans and pigs.

Symptoms

Humans
Symptoms may be mild or severe and include:

  • Fever, headaches, encephalitis.

  • Drowsiness, confusion leading to coma.

  • Respiratory failure.

  • High mortality up to 40% reported.

  • A few people have shown no symptoms.

  • The incubation period is from 7 to 21 days.

In 1999 there were over 300 cases and 100 deaths.

All Pigs

  • Morbidity is usually high but mortality is low.

  • Rapid laboured breathing.

  • Very harsh explosive cough.

  • In sows disease may be more pronounced with severe breathing difficulties.

  • Convulsions, death.

  • Pneumonia.

  • Mucopurulent discharges from the nose.

At post mortem the predominant signs are consolidation of the lungs.

Causes / Contributing factors

  • Movement of pigs.

  • Direct pig to pig contact either by mouth, by the respiratory route or aerosol from urinary excretions.

Diagnosis

This is by serological tests, virus isolation and identification. In infected farms sows show high levels of antibodies and in infected areas antibodies have been widespread in dogs but not in rats.

Management control and prevention

The control programme adopted has been in two phases.

  • In 1999 there was a mass culling of pigs in infected areas and severe restrictions on movement of pigs.

  • This has been successful in preventing disease spreading to Singapore where many pigs from Malaysia were slaughtered.

  • The second phase is the identification of carrier herds and their depopulation.


NIPAH VIRUS

Nipah virus is a newly recognized zoonotic virus. The virus was discovered in 1999. It has caused disease both in animals and in humans, through contact with infectious animals. The virus is named after the location where it was first detected in Malaysia. Nipah is closely related to another newly recognized zoonotic virus (1994), called Hendra virus, named after the town where it first appeared in Australia. Both Nipah and Hendra are members of the virus family Paramyxoviridae. Although members of this group of viruses have only caused a few focal outbreaks, the biologic property of these viruses to infect a wide range of hosts and to produce a disease causing significant mortality in humans has made this emerging viral infection a public heath concern.

Natural host

It is currently believed that certain species of fruit bats are the natural hosts of both Nipah and Hendra viruses. They are distributed across an area encompassing northern, eastern and south-eastern areas of Australia, Indonesia, Malaysia, the Philippines and some of the Pacific Islands. The bats appear to be susceptible to infection with these viruses, but do not themselves become ill. It is not known how the virus is transmitted from bats to animals.

Transmission

The mode of transmission from animal to animal, and from animal to human is uncertain, but appears to require close contact with contaminated tissue or body fluids from infected animals. Nipah antibodies have been detected in pigs, other domestic and wild animals. The role of species other than pigs in transmitting infection to other animals has not yet been determined.

It is unlikely that Nipah virus is easily transmitted to man although previous outbreak reports suggest that Nipah virus is transmitted from animals to humans more readily than Hendra virus. Despite frequent contact between fruit bats and humans there is no serological evidence of human infection among bat carers. Pigs were the apparent source of infection among most human cases in the Malaysian outbreak of Nipah, but other sources, such as infected dogs and cats, cannot be excluded. Human-to-human transmission of Nipah virus has not been reported.

Clinical features

The incubation period is between 4 and 18 days. In many cases, the infection is mild or inapparent (sub-clinical). In symptomatic cases, the onset is usually with influenza like symptoms, with high fever and muscle pains (myalgia). The disease may progress to inflammation of the brain (encephalitis) with drowsiness, disorientation, convulsions and coma. Fifty percent of clinically apparent cases die.

Treatment

No drug therapies have yet been proven to be effective in treating Nipah infection. Treatment relies on providing intensive supportive care. There is some evidence that early treatment with the antiviral drug, ribavirin, can reduce both the duration of feverish illness and the severity of disease. However, the efficacy of this treatment in curing disease or improving survival is still uncertain.

Protection of health care professionals

The risk of transmission of Nipah virus from sick animals to humans is thought to be low, and transmission from person-to- person has not yet been documented, even in the context of a large outbreak. Therefore, the risk of transmission of Nipah virus to health care workers is thought to be low. However, transmission without percutaneous exposure (through a break in the skin barrier) is theoretically possible, as respiratory secretions contain the virus. This is why it has been categorized as a biohazardous agent that should be managed in a high-level biosecurity laboratory. It is recommended that close contact with body fluids and infected tissues be avoided if Nipah infection is suspected.

Outbreaks of Nipah and Hendra viruses

From September 1998 to April 1999, there was a large outbreak of encephalitis in Malaysia. During the investigation of this outbreak, Nipah virus, a previously unrecognized virus, was identified as the causal agent. A total of 265 people were infected, of whom 105 died. Ninety-three percent of cases had occupational exposure to pigs. An associated outbreak among abattoir workers in Singapore during March 1999 led to 11 cases, with one death. These workers had been handling pigs that had been imported from the outbreak areas in Malaysia.

There have been three recognized outbreaks of Hendra virus in Australia in 1994 and 1999. Three human cases, leading to two deaths, were recorded in the 1994 and 1995 outbreaks. In 1995 a horse was infected, with associated human cases. The precise mode of virus transmission to the three Australian patients is not fully understood. All three individuals appear to have acquired their infection as a result of close contact with horses which were ill and later died.

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

Nipah Virus probe team honoured with Merdeka Award

PETALING JAYA: The courage shown by the investigation team dealing with the highly infectious Nipah Virus, an unknown disease in 1999 with no known cure and rapidly fatal, was exemplary, said Universiti Malaya Medicine Faculty’s Prof C.T. Tan. Prof Tan, who headed the Nipah Virus Investigating Team in 1999, after the outbreak started in 1998, said it was “the entire team’s effort” which led to their success in identifying the virus and bringing it under control. “Initially, the virus was thought to be the Japanese encephalitis (JE) carried by mosquitoes. “But we found that it was not JE, and that this virus spread directly from pigs to humans, the solution was to cull the infected pigs to stop the spread of the virus. And then the infection came under control,” he said. Prof Tan and his team, consisting of specialists and researchers from the fields of virology, neurology, pathology, radiology, infectious diseases and intensive care, were joint recipients of the Merdeka Award under the Health, Science and Technology Category. The Star is the official media of the Merdeka Awards. “I’m very, very pleased. This award is very meaningful for our team and an affirmation of the good work that we have done,” Prof Tan said in an interview last Wednesday. They were honoured for their “contribution in the understanding of the causes, effects and control of the Nipah encephalitis viral infection”, which had infected 350 people, and killed 105 persons.

The other recipient of the award in the same category was Prof Datuk Dr Khalid Kadir. Both teams received a certificate, a trophy and one half of the RM500,000 cash prize. Prof Tan, a neurologist whose main work is on epilepsy, said the team had also worked out the management strategy and treatments of the infection. In the scientific world, the team has received international recognition with their journals published in the New England Journal of Medicine, Lancet, Annals of Neurology, American Journal of Pathology and Journal of Virology. They have also been made World Health Organisation (WHO) consultants, and were in Bangladesh in 2004 during a Nipah encephalitis outbreak there. Asked what his team planned to do with the RM250,000 award money, Prof Tan said the money could be used for projects that they have problems getting funding for. “This is our recognition outside the scientific world. It’s a great morale boost for good science,” he said.


Nipah Virus, Malaysia, May 1999

Emerging Disease Notice

Summary

  • Nipah virus is a previously unknown virus of the family Paramyxoviridae that has been identified in the northern peninsula of Malaysia.  The virus has caused illness and death in humans and pigs.

  • The apparent source of infection for humans is direct contact with pigs.  Transmission of virus is thought to be from body fluids of infected pigs.  Human-to-human transmission has not been documented.

  • In pigs, the disease is not well documented.  Clinical signs in pigs appear to include rapid and labored breathing; an explosive and nonproductive cough; and neurologic changes, including lethargy or aggressive behavior.

  • The natural reservoir of the virus is not yet unknown.  Virus has been isolated from humans, pigs, and one dog. Bats, two horses, dogs, and at least one cat have reportedly shown serologic evidence of Nipah virus infection.

  • Malaysia exported over one million live pigs in 1997, mostly if not entirely to Singapore.

  • The U.S. imported no live pigs from Malaysia or Singapore in 1998 or 1999, but did import some swine leather and other products that may have come from pigs.  In 1997, the U.S. imported some mammalian wildlife from both Malaysia and Singapore.

  • About 330 thousand airline passengers arrived in the U.S. on direct flights from Malaysia and Singapore in 1997.

  • It seems prudent for U.S. pork producers to stay aware of the situation and to maintain adequate biosecurity.

Background

Nipah virus is a previously unknown virus of the family Paramyxoviridae that has been identified primarily in humans and pigs in Malaysia.  In humans, the virus causes fever, severe headache, myalgia, and signs of encephalitis or meningitis.  The case fatality rate has been about 40%. The first human cases of disease attributed to Nipah virus occurred in late September 1998 in the northern city of Ipoh.  The cases were first attributed to the Japanese encephalitis (JE) virus; however, the epidemiology of the disease was not consistent with JE.  Most of the cases were in adult males who had direct contact with pigs.  In March 1999, Malaysian researchers identified the virus as a previously unknown paramyxovirus.  This was confirmed by the CDC.  The virus was first called Hendra-like virus because it is similar to the Hendra virus, first identified in horses in Australia in 1994.  The virus is now named after the village near Kuala Lumpur from where it was first isolated. As of late April 1999, 257 cases of  febrile encephalitis had been reported in Malaysia, including 100 deaths.  Malaysian states in which these cases have occurred are Perak, Negri Sembilan, and Selangor (map not to scale).  Nipah virus was also confirmed in abattoir workers in Singapore, where many hogs from Malaysia are slaughtered.

The degree of involvement of the Nipah virus and the JE virus in causing human disease was initially in question.  However, scientists now conclude that the role of JE in the outbreak was insignificant, and that most of the cases were due to Nipah virus.  According to Malaysian authorities, of the 146 cases where tests were available, 116 tested positive for Nipah virus, 18 tested positive for both Nipah and JE virus, and 12 tested positive for JE.

In pigs, the Nipah virus is associated with clinical signs and death, although the morbidity and mortality rates are not yet known.  Clinical signs in pigs appear to include rapid and labored breathing; an explosive and nonproductive cough; and neurologic changes, including lethargy or aggressive behavior.
Source:  Promed; NY Times, May 4, 1999; Science Apr 16, 1999;  MMWR, Apr 30, 1999; MMWR, Apr 9, 1999


Transmission and reservoir of the Nipah virus

The apparent source of infection for humans is close contact with pigs.  The specific routes of infection have yet to be determined, however the prevailing thought is that transmission of the virus is through direct contact with body fluids.  Another theory is that humans may become infected via aerosol transmission from respiratory or urinary secretions.

There appear to have been no cases of human-to-human transmission of the virus.  Family members of case patients have remained uninfected.  Further, a survey of physicians, nurses, and pathologists who had direct contact with infected persons found none with encephalitic illness or with serologic evidence of Nipah virus infection.

The natural reservoir of the virus is unknown at this time.  Virus has been isolated from humans, pigs, and one dog. Nucleotide sequence studies of the virus isolates from the dog, pigs, and humans suggest all three isolates are identical.  Reportedly, serologic evidence of Nipah virus infection has been found in bats, two horses, dogs, and at least one cat.  Studies of wildlife are currently ongoing in an attempt to identify the natural reservoir.

With Hendra virus, it is thought that the 3 humans were infected through exposure to blood or other body fluids or excretions from infected horses.  Evidence suggests that fruit bats are the natural host of the Hendra virus.  It has been shown that both bat urine and part of the bat placenta can contain the virus.  In the case of  Hendra virus, one of the human victims died 14 months after he was infected.  (A factsheet on Hendra virus, previously called equine morbillivirus, is available on the APHIS web site.  For a brief review of other paramyxoviruses and details of the Menangle virus, identified in pigs in Australia in 1997, see  Emerging disease notice - New virus of animals and humans emerges in Australia , CEI, November 1998.)
Source: Promed; NY Times, May 4, 1999; Science, Apr 16, 1999; MMWR, Apr 30, 1999; MMWR, Apr 9, 1999.

Control measures in Malaysia
 
The primary control measure has been culling of pigs.  In the 3 affected states, almost 900,000 pigs have been killed.  Transport of pigs within the country has been banned.  Other control measures include educational efforts and national surveillance to detect any additional infected herds.
Source:  MMWR, Apr 30, 1999


What is the country's production and trade in affected animals and animal products?
Malaysia

Pigs are the primary livestock industry in Malaysia.  In 1998, estimated inventories of pigs were 3.3 million head, representing 0.34% of world stocks.  Also in 1998, Malaysia produced an estimated 241,124 metric tons of pig meat.

The two Malaysian states in which most of the human deaths have occurred (Negri Sembilan and Perak) together account for half the swine population in Malaysia.  Inventories in Negri Sembilan, the largest swine-producing state, are normally about 620,000 pigs.

Self-sufficient in the swine industry, Malaysia also exports to other countries in the region.  In 1997, Malaysia was the principal source of swine imports to Singapore.  Malaysia exported 1,046,000 live pigs in 1997, as well as 2,760 metric tons of pig meat.

Malaysia imported 440 live swine and 3,863 metric tons of pig meat in 1997.

Singapore

The swine herd in Singapore totals only 190,000 animals.  This herd is supplemented with the importation of live pigs, principally from Malaysia.  In 1997, a total of 1,046,648 pigs were imported into Singapore, making Singapore the 4th largest importer of live pigs in the world.


Singapore produced a total of 83,900 metric tons of pig meat in 1998.  Singapore's production accounted for less than 1 percent of worldwide production.  Domestic pig meat production is supplemented with imports.  In 1997, pig meat imports totaled 23,006 metric tons (less than 1 percent of worldwide imports).
In 1997, Singapore exported only 348 live pigs and 2,328 metric tons of pig meat.  Exports go principally to other southeastern Asian countries.
Source: United Nations FAO; USDA Foreign Agricultural Service



What are the U.S. imports of affected animals or animal products from the country?


The U.S. imported no live pigs from Malaysia or Singapore in 1998 or in January-February 1999.  The only potentially relevant products that the U.S. imported from Malaysia in 1998 were 56,441 kg of soups, broths, and preparations thereof.  From Singapore, the U.S. imported 7,323 square meters of swine leather, 28,605 kg of soups, broths, and preparations thereof, and an unknown amount of preparations used in animal feed (valued at $739 thousand).  In January-February 1999, the U.S. imported 9,746 kg and 1,050 kg of soups, broths, and preparations thereof from Malaysia and Singapore, respectively.


Because of the potential connection between Nipah virus and wildlife, wildlife import statistics were checked.  According to data form the US Fish and Wildlife Service, 8 unspecified mammals were imported into the US from Malaysia in 1997.  From Singapore, 2 leopards, 50 mongooses, and 2 tigers were imported.  These numbers do not represent all mammals imported from Malaysia or Singapore, as CEI does not have access to the complete wildlife import database.
Source: World Trade Atlas; LEMIS database, US FWS


What is the level of passenger traffic arriving in the United States from the affected country?
 

There are 5 daily direct flights from Singapore to the U.S. west coast, and 1 daily direct flight from Kuala Lumpur to the west coast.  U.S. Department of Transportation data show that, in 1997, 52,375 passengers arrived in the US on direct flights from Malaysia, and 282,375 arrived on direct flights from Singapore.  In addition, there are numerous other routes from Malaysia to the U.S., including via cities in the far east or in Europe.  The World Tourism Organization reports that 80,066 tourists from Malaysia and 114,713 tourists from Singapore arrived in the U.S. in 1996. Of the 240 passengers from Malaysia that were sampled as part of PPQ's agricultural quarantine inspections in fiscal 1998, 73 reported California as the final destination in the U.S.  Other frequent destinations included PA (16), TX (15), WA (15), MA (12), and VA (12).  In all, 33 states were reported as destinations.  Only 1 passenger, whose destination was MN, reported going to visit or work on a farm or ranch while in the U.S.  Eight of the passengers were carrying relevant products, including pork, salami, and unspecified meat.  These numbers are an indication of the amount of animal product illegally entering the U.S. via airline passengers. From the same data, 692 passengers from Singapore reported a total of 41 states as final destinations in the U.S.  California again was the top destination, with 242 passengers.  Other main destinations were NY (98), WA (28), NJ (28), MA (26), TX (23), and FL (23).  One passenger with destination TX reported going to visit or work on a farm or ranch in the U.S.  Six passengers were carrying meat products, including pork, sausage, and soup mixes with meat.
Source:  www.flifo.com; World Tourism Organization; PPQ - Agricultural Quarantine Inspections database

CEI's interpretation:


Direct contact with infected pigs is thought to be the most likely route of virus transmission to humans.  However, routes of transmission between pigs or from humans to pigs are not known.   Given that human-to-human transmission does not appear to occur, it is unlikely, though possible, that humans can transmit the virus to pigs.  The survival of the virus outside of the host is unknown; therefore, the role that mechanical transmission might play in spread of the disease is also unknown. It seems prudent for U.S. pork producers to stay aware of the situation and to maintain adequate biosecurity. The amount of live pigs and pig products imported into the U.S. from Malaysia and Singapore since 1998 has been minimal.  However, until more information is available regarding what animal products may play a role in disease transmission,
the risk these products present is unknown.

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