Overview of Nipah Virus Infection

The etiologic agent, Nipah virus (genus Henipavirus, family Paramyxoviridae), is an enveloped, negative-sense, single-stranded RNA virus. The virus is closely related to Hendra virus (see Hendra Virus Infection), the only other member of the genus. The human outbreak in Malaysia and Singapore followed contact with infected swine and resulted in encephalitis with ~40% case mortality. The virus is assumed to have been introduced into the swine population from one of the two species of Pteropus found with antibodies during investigation of the outbreak. Pteropus spp range from the Western Pacific through southeast Asia, and south Asia down through coastal African islands, including Madagascar. Several species of Pteropus have been found with antibodies, suggesting that the virus or closely related viruses occur in other areas within the range of this genus of bats. In Malaysia, genetic analysis of virus from human and swine clinical materials strongly supported a single introduction of the virus with spread through the commercial swine population. There was evidence of infection among several other species of domestic animals, including dogs, cats, and horses. Human encephalitis caused by Nipah viruses in south Asia has been a regular occurrence since 2001 in Bangladesh and more recently in adjacent areas of India. In these areas, epidemiology has not supported the role of intermediary domestic species but rather more direct transmission from the flying fox reservoir of the virus. More recently, fruit bats belonging to the family Pteropidae, but not the genus Pteropus, were found to harbor related viruses in Africa.

Infection in pigs is assumed to have been a transfer from the reservoir bat species to pigs. Once the virus was introduced into an intensive swine husbandry setting, infection of animals within premises was rapid, and serologic tests suggested that nearly all pigs on an affected premise were infected. Transmission between premises was thought to be by poor biosecurity procedures and movement of infected animals. Experimental infection of swine with Nipah virus in a high biosecurity facility in Geelong supported that transmission between swine in close contact occurred readily. In south Asia, infection of people appears to occur by indirect means from the reservoir fruit bats; contamination of sap collected in pots on palm trees is a recurring means of infection in regular cases occurring in Bangladesh. Other similar circumstances, such as contact with trees contaminated by bats or consumption of fruit partially eaten by bats, are other documented means of infection in Bangladesh. Person-to-person transmission, although not evident in Malaysia, has also occurred in south Asia.

Because of the danger of human infection from infected pigs and the emergency setting, clinical observations were not detailed in the field during the original epidemic. Most pigs developed a febrile respiratory disease with a severe cough that led to the local names for the disease―“barking pig syndrome” and “one-mile cough.” Encephalitis was also noted, particularly in the sows and boars in affected facilities. The proportion of animals with each form of the disease is uncertain, although the respiratory form predominated. Overall mortality within affected facilities was also not well documented but probably was not >5% among all age groups.

Laboratory diagnosis can be made by isolation of the virus, identification of the RNA by use of reverse transcriptase-PCR, detection of antigens in tissues by immunohistochemical staining with specific antibodies, or serologic tests such as indirect ELISA and virus neutralization tests. The virus is considered biosafety level 4 in the USA and Australia, and stringent laboratory containment at limited laboratories is a special consideration.

Treatment of affected swine was not attempted during the Malaysian emergency. Human patients required intensive care with ventilation support to manage the encephalitis; no specific treatment is available. Ribavirin was administered to some patients, but subsequent studies in laboratory animals suggest that it is ineffective.

Control of the epidemic/epizootic in Malaysia was dependent on the initiation of strict quarantine procedures and the slaughter of all swine from affected facilities. Adherence to appropriate biosecurity and quarantine procedures within facilities, as with other contagious diseases, is of paramount importance in preventing spread of the infection. An active surveillance and slaughter program successfully eliminated the virus from the national commercial swine population, which has remained free of infection. Presence of the virus in reservoir species of bats in a wide geographic range emphasizes the importance of good disease surveillance and biosecurity practices to promote early detection and confine the disease to initial premises should reintroduction occur.

Transmission of the virus from infected pigs to people was largely in an occupational setting, and a study of risk factors associated with human infection suggests that close contact with live infected swine was the means of infection of nearly all human Nipah virus infections in Malaysia.

Continued sporadic clusters in horses and subsequent human cases with Hendra virus in Australia, with serious disease in some of these clusters, emphasize the importance of use of appropriate personal protective equipment in veterinary clinical examinations or postmortem procedures when Hendra or Nipah virus infection is suspected.