Nipah Virus Importance

Nipah virus infection is an emerging disease endemic in Southeast Asia. This

Infection virus is carried subclinically in fruit bats of the genus Pteropus, a host to which it
seems well adapted. Illnesses caused by Nipah virus were first described in 1998-
Nipah Virus Encephalitis, 1999, during widespread outbreaks among pigs and people in Malaysia. The virus had
apparently been transmitted from bats to pigs around 1996, and was thereafter
Porcine Respiratory and
maintained in swine populations. It was not detected immediately, as the mortality
Encephalitis Syndrome, rate was low and the illness resembled other pig diseases. Nipah virus subsequently
Porcine Respiratory and spread to pig farmers and abattoir workers in Malaysia and Singapore, causing severe,
Neurologic Syndrome, often fatal, encephalitis in more than 250 people. Some other species, including cats,
Barking Pig Syndrome dogs and goats, were also affected. The Malaysian outbreaks were controlled in both
domesticated animals and humans by culling more than one million pigs. In addition,
pig farming was permanently banned in some high-risk areas.
Last Updated: January 2016 While Nipah virus encephalitis has not been documented in Malaysia since that
time, human cases have been reported regularly in Bangladesh and a neighboring
region of northern India since 2001. Many of these cases seem to be acquired directly
from bats by drinking raw date palm sap, a widely consumed local delicacy. The sap
is thought to become contaminated when bats visit and drink from unprotected sap
collection sites at night. Person-to-person transmission also occurs after close,
unprotected contact. How widely Nipah virus circulates in bats is still uncertain;
however, viral RNA and seropositive bats have also been identified in areas where no
clinical cases have ever been reported. A recent outbreak of neurological disease in
horses and humans in the Philippines also appears to have been caused by this virus.
Etiology
Nipah virus is a member of the genus Henipavirus in the family
Paramyxoviridae. This genus also includes Hendra virus, Cedar virus (an apparently
nonpathogenic virus found in Australian bats) and additional uncharacterized
henipaviruses in various locations.
There seem to be multiple strains of Nipah virus. At least two major strains were
isolated from pigs in Malaysia, and the strains that cause human cases in Bangladesh
and India differ from outbreak strains isolated in Malaysia. A henipavirus that
recently caused an outbreak in the Philippines is also thought to be Nipah virus, based
on RT-PCR results. It appears to be most similar to the viruses from Malaysia.
Species Affected
Fruit bats of the genus Pteropus (flying foxes) are the main reservoir hosts for
Nipah virus. P. vampyrus, the Malayan flying fox, and P. hypomelanus, the island
flying fox, are known to carry this virus in Malaysia. P. giganteus is thought to be an
important host in Bangladesh and India and possibly other locations. Although live
virus has not yet been isolated from this species, Nipah virus RNA has been detected
and many bats are seropositive. Nipah virus also occurs in P. lylei in Thailand and
Cambodia, and P. poliocephalus has been infected experimentally. Viral RNA and/or
antibodies have been found in a few other species of fruit or insectivorous bats,
although their significance is unclear
Many domesticated mammals seem to be susceptible to Nipah virus. This virus
can be maintained in pig populations, but other domesticated animals appear to be
incidental (spillover) hosts. Sick goats, dogs, cats and horses were observed in the
outbreak area in Malaysia, and infections in dogs, a cat, a horse and goats were
confirmed by immunohistochemistry. Sheep might also have been affected, but there
are no confirmatory data, and no evidence of infections could be found in rats. Nipah
virus seems to have affected horses in the Philippines in 2014, based on clinical signs
in the horses and epidemiological links to human patients; however, no tissues were
available from the horses for confirmation. Several cats and a dog that had eaten
tissues from sick horses in the Philippines also died, and seropositive dogs were
reported in the outbreak area. Another study reported seropositive cattle, pigs and
goats in Bangladesh; however, these antibodies did not neutralize Nipah virus, and
could have been caused by related henipaviruses.
www.cfsph.iastate.edu
Email: [email protected] © 2003-2016 page 1 of 9
 Nipah Virus Infection
Experimental infections with Nipah virus have aerosols and direct contact between pigs; virus spread
established in pigs, cats, ferrets, nonhuman primates, guinea between farms was usually associated with pig movements.
pigs, golden hamsters (Mesocricetus auratus) and mice. Although this virus has not been reported, to date, in the
urine of pigs, it can occur in the kidneys, and exposure to pig
Zoonotic potential urine is a risk factor for human infections. Anecdotal
Nipah virus can cause serious illnesses in people. A evidence suggests that vertical transmission may occur across
number of cases have been linked to drinking raw date palm the placenta. Transmission in semen may be possible, and re-
sap, which had probably been contaminated by bats. used vaccination needles may have contributed to the
Drinking fermented date palm sap (alcohol content spread of the virus between pigs in Malaysia.
approximately 4%) appeared to be a risk factor in a few Cats can be infected experimentally by intranasal and
cases. Zoonotic cases were acquired from pigs in Malaysia oral inoculation, and they can shed Nipah virus in
(bat to human transmission appears to be uncommon or respiratory secretions and urine. Cats and a dog that died in
absent in this area), while people who became infected in the Philippines had recently eaten meat from infected
the Philippines had either eaten undercooked meat from horses. In utero transmission has been demonstrated in cats,
sick horses or participated in their slaughter. A few cases in with the detection of virus in the placenta and embryonic
Bangladesh and Malaysia might have been acquired from fluids. Although experimental studies have not been
sick animals of other species (a dog, various livestock), but published in dogs, serological surveys in Malaysia suggest
the evidence in these cases was speculative and/or that Nipah virus did not spread horizontally in dogs during
circumstantial. this outbreak.
Geographic Distribution Humans can be infected by direct contact with infected
Nipah virus might be endemic across much of Southeast swine, probably through the mucous membranes, but
Asia; however, confirmed cases in humans and/or possibly also through skin abrasions. During a recent
domesticated animals have only been reported in Malaysia, Nipah-like outbreak in the Philippines, most patients had
Bangladesh and nearby areas of northern India. The virus that been involved in slaughtering sick horses or had eaten
caused an outbreak in the Philippines has not been undercooked horsemeat from sick horses. In Bangladesh,
completely characterized yet, but it also appears to be Nipah human cases have been linked to drinking unpasteurized
virus. Abattoir workers in Singapore became ill after contact date palm sap (juice). Oral transmission, using artificial
with infected pigs imported from Malaysia; however, there is palm sap spiked with Nipah virus, and respiratory
no evidence that this virus is endemic among pigs in transmission were both demonstrated in a hamster model.
Singapore. Nipah virus has been isolated from bats in Person-to-person transmission can occur after close direct
Cambodia, and viral RNA has been detected in bats in contact, and has been common during some outbreaks in
Thailand and East Timor. Antibodies to Nipah virus or other Bangladesh and India. Humans can shed Nipah virus in
henipaviruses have been found in bats in additional Asian respiratory secretions, saliva, and urine, and contact with
countries (e.g., China, Vietnam) and on other continents; respiratory secretions is thought to be the main route of
however, viral and serological evidence suggests that at least spread. Some people also became ill after unprotected
some of these viruses might be distinct viral species. contact with deceased patients, such as during preparation
of the corpse for burial. Nosocomial transmission has been
Transmission documented in hospitals where infection control measures
In Pteropus bats, Nipah virus has been found are inadequate; however, the risk to healthcare workers
repeatedly in urine, and viral RNA has been detected rarely appeared to be low in Malaysian hospitals.
in oropharyngeal swabs and rectal swabs from naturally or How long Nipah virus can remain viable in the general
experimentally infected bats. It has also been found in fruit environment is uncertain; however, it can survive for up to
that had been partially eaten by bats. Despite high 3 days in some fruit juices or mango fruit, and for at least 7
seroprevalence rates, only a few bats in a colony may shed days in artificial date palm sap (13% sucrose and 0.21%
the virus at any given time, and excretion from the colony BSA in water, pH 7.0) held at 22°C. This virus is reported
may be sporadic. to have a half-life of 18 hours in the urine of fruit bats.
How bats transmit this virus to domesticated animals is Disinfection
uncertain, but ingestion of contaminated fruit, water, or
aborted bat fetuses or birth products (e.g., by pigs) is Like other paramyxoviruses, Nipah virus is readily
suspected. Nipah virus is highly contagious in swine, which inactivated by soaps, detergents and many disinfectants.
can act as amplifying hosts and shed this virus in respiratory Routine cleaning and disinfection with sodium hypochlorite
secretions and saliva. Experimental infections suggest that or commercially available disinfectants is expected to be
shedding may start as early as 2 days after infection and effective. Sodium hypochlorite was recommended for the
persist for up to 3 weeks. During the Malaysian outbreak, disinfection of pig farms in Malaysia.
Nipah virus appeared to be transmitted within a farm by The effect of heat may depend on the substrate. Nipah
virus concentrations decreased but the virus was not

© 2003-2016 www.cfsph.iastate.edu  Email: [email protected] page 2 of 9

 Nipah Virus Infection
completely eliminated in artificial palm sap held at 70°C for virus resulted in severe respiratory signs with fever,
1 hour. However, it was completely inactivated by heating depression, an increased respiratory rate and dyspnea.
at 100°C for more than 15 minutes. Three cats thought to have been infected during an outbreak
in the Philippines were found dead, while a fourth was
Infections in Animals moribund with terminal bleeding from the nose and mouth.
Experimentally infected ferrets developed severe
Incubation Period depression, serous nasal discharge, coughing, dyspnea,
The incubation period in pigs is estimated to be 7 to 14 tremors and hindlimb paresis. Neurological and/or
days, but it may be as short as four days. Experimentally respiratory signs, which can be severe, have also been
infected cats developed clinical signs after 6-8 days and reported in some experimentally infected hamsters.
experimentally infected ferrets after 6-10 days. An unproductive cough, poor growth, severe
respiratory signs and deaths were documented in naturally
Clinical Signs infected goats in Malaysia. Two goats associated with a
Nipah case in Bangladesh had a febrile neurological
Pigs
syndrome, but whether their illness was caused by Nipah
Subclinical infections appear to be common in pigs. virus or another disease is unknown.
Symptomatic infections are usually acute febrile illnesses,
but fulminating infections and sudden death have also been Infections in fruit bats appear to be asymptomatic.
seen. In general, mortality is low except in young piglets. Post Mortem Lesions
A respiratory syndrome appears to be the most common In pigs, lesions may be found in the lungs, brain or
presentation in 1-6 month old pigs, with clinical signs that both organs. Lung lesions range from mild to severe, and
may include fever, nasal discharge, open-mouthed breathing, can include varying degrees of consolidation, petechial or
rapid and labored respiration and a loud barking cough. ecchymotic hemorrhages, and emphysema. On cut surface,
Hemoptysis can occur in severe cases. Pigs in this age group the interlobular septa may be distended. The bronchi and
occasionally develop neurological signs such as trembling, trachea may contain frothy, sometimes bloodstained, fluid.
twitching, muscle spasms, myoclonus, weakness in the hind In the brain, there may be congestion of the cerebral blood
legs, spastic paresis, lameness, an uncoordinated gait when vessels and meningeal edema. Mottled, enlarged and
they are driven or hurried, and generalized pain that is congested lymph nodes were also reported in some
particularly evident in the hindquarters. One experiment experimentally infected pigs. The kidneys may be
suggested that bacterial meningitis might be a contributing congested with petechiae in the renal capsule and cortex,
factor in some animals, especially when the neurological but are often normal.
signs develop later in the course of the disease.
In dogs, necropsy lesions have been reported only for
Similar clinical signs can occur in sows and boars, two animals. In one dog, diffuse red-pink mottling and
although neurological signs appear to be more common in consolidation were seen in the lungs, with exudates in the
sows than younger animals. Reported signs in these pigs bronchi and trachea. The visceral pleura were yellowish-
include agitation, head pressing, nystagmus, chomping of cream and opaque. Irregular reddening was noted in the
the mouth, tetanus-like spasms, seizures and apparent renal capsules and cortices. In addition, nonsuppurative
pharyngeal muscle paralysis. Some sows aborted during meningitis, signs of cerebral and hepatic vascular
Nipah virus outbreaks, generally during the first trimester. degeneration, and necrosis and inflammation of the adrenal
Sudden death may also be seen. gland were seen. Similar lesions were reported in the other
In piglets, common signs include open-mouthed dog, although there was severe autolysis.
breathing, leg weakness with muscle tremors, and twitching. Lesions in experimentally infected cats included
Deaths may also occur due to starvation if the dam is ill. hydrothorax, consolidation and edema in the lungs, edema
Other species of the pulmonary lymph nodes and froth in the bronchi.
Horses thought to be infected with Nipah virus in the Meningitis was reported in some cats after
Philippines either developed acute, fatal neurological signs histopathological examination. More subtle lesions were
or died suddenly with no apparent preceding illness. seen in earlier stages of the disease; they included
Although significant numbers of dogs and cats may have numerous small hemorrhagic nodules in the lungs, scattered
been infected on farms in Malaysia, clinical cases have hemorrhagic nodules on the visceral pleura, and, in one cat,
been published for only two dogs. One of these animals had edema of the bladder serosa with dilation of the serosal
died of the illness, and the clinical signs were not described. lymphatic vessels. Generalized vasculitis was seen in one
In the other dog, the disease resembled canine distemper; naturally infected cat in Malaysia, particularly in the brain,
the clinical signs included fever, respiratory distress, kidney, liver and, to a lesser extent, the lung.
conjunctivitis, and mucopurulent nasal and conjunctival Nonsuppurative meningitis was reported in an infected
discharges. Experimental inoculation of cats with Nipah horse in Malaysia.

© 2003-2016 www.cfsph.iastate.edu  Email: [email protected] page 3 of 9

 Nipah Virus Infection
Diagnostic Tests Prevention
Nipah virus infections can be diagnosed by virus Good biosecurity is important in preventing infections
isolation, the detection of antigens or nucleic acids, and on pig farms; strategies should target routes of contact with
serology. Histopathology also aids diagnosis. In swine, Nipah other pigs as well as fruit bats. Fruit tree plantations should
virus has been detected in respiratory secretions, blood and be removed from areas where pigs are kept. Wire screens
various tissues including the bronchial and submandibular can help prevent contact with bats when pigs are raised in
lymph nodes, lung, spleen, kidney and brain. In open-sided pig sheds. Run-off from the roof should be
experimentally infected cats, this virus has been found in the prevented from entering pig pens. Fruits that may have been
lung and spleen, and less often, in the kidney, lymph nodes contaminated by bats should not be fed to pigs or other
and other organs. It can also be detected in feline blood, urine livestock. Feeding spoiled or contaminated date palm sap to
and respiratory secretions. In dogs, viral antigens or RNA livestock, as is sometimes done in endemic areas, also
have been found in the brain, lung, spleen, kidney, adrenal appears to be a dangerous practice.
gland and liver. Stringent precautions should be used to Early recognition of infected pigs can help protect
protect people when collecting samples from animals. other animals and humans. Due to the highly contagious
Standardized sampling procedures, including limited nature of the virus in swine populations, mass culling of
sampling techniques to help safeguard personnel (e.g., seropositive animals may be necessary. Quarantines are
‘keyhole’ sampling of target tissues such as lung and lymph also important in containing an outbreak; in Malaysia,
nodes), have been published for the closely related Hendra Nipah virus mainly seemed to spread between farms in
virus, but do not appear to be available for Nipah virus. infected pigs. Fomites and equipment should be cleaned
Reverse transcription-polymerase chain reaction (RT- and disinfected. Other animals, including dogs and cats,
PCR) assays on blood, secretions, excretions or tissue should be prevented from contacting infected pigs or
samples can be used for a rapid diagnosis. Virus isolation is roaming between farms. No vaccines are currently available
available in a limited number of laboratories, as Nipah virus for any species.
is a BSL4 pathogen and must be cultured under high-
security conditions. This virus is often isolated in Vero
Morbidity and Mortality
cells, but many other cell lines (e.g., RK-13, BHK and There are few studies on the epidemiology of Nipah
porcine spleen cells) can also be used. Nipah virus can be virus infections in flying foxes. Studies from Malaysia
cultured in embryonated chicken eggs; however, this reported that 9-17% of Pteropus vampyrus and 21-27% of
system is not generally employed due to the ease of culture P. hypomelanus had antibodies to this virus; however, the
in cells. Isolated viruses can be identified by methods such frequency and timing of virus shedding in bats is unknown.
as RT-PCR, immunostaining or virus neutralization. Some studies have suggested that it may be uncommon
Electron or immunoelectron microscopy may also be and/or intermittent.
helpful. Molecular methods (e.g., RT-PCR), comparative Nipah virus was widespread in pigs during the 1998-
immunostaining or differential neutralization assays can 1999 outbreak in Malaysia. Before this virus was
distinguish Hendra and Nipah viruses. Viral antigens can be eradicated from domesticated swine, seropositive animals
detected directly in tissues with immunoperoxidase or were found on approximately 5.6% of all pig farms. On
immunofluorescence assays. one farm, more than 95% of all sows and 90% of the
Serology can be helpful, especially in pigs, which are piglets had antibodies to this virus. The morbidity rate is
often infected subclinically. Both virus neutralization and estimated to approach 70-100%, but the mortality rate is
ELISAs have been used in animals. Nipah virus can cross- low (e.g., 1-5% in 1-6 month old pigs) except in piglets.
react with Hendra virus and other henipaviruses in these Mortality in the latter age group was approximately 40%
assays. These reactions can be distinguished with in Malaysia, although neglect of the piglets by sick sows
comparative neutralization tests. may have also played a role.
The frequency of Nipah virus infections in other
Treatment species is unknown, although other domesticated animals
No specific antiviral treatment is available for Nipah were infected from pigs during outbreaks in Malaysia.
virus. Infected animals have generally been killed to prevent While clinical cases were only confirmed in two dogs, a
the virus from being transmitted to human caretakers. number of dogs are said to have died on infected farms.
Farmers also reported illnesses in cats and goats.
Control Serological surveys found seroprevalence rates of 15%-
Disease reporting 55% in dogs, 4%-6% in cats, and 1.5% in goats in the
outbreak area. Infections in horses seemed to be rare during
Veterinarians who encounter or suspect a Nipah virus
this outbreak: only five horses out of more than 3200 were
infection should follow their national and/or local
positive by serology, and viral antigens were found in a
guidelines for disease reporting. In the U.S., state or federal
single horse that died with signs of meningitis. Direct bat to
veterinary authorities should be informed immediately.
animal transmission might be uncommon. In 2004, no feral

© 2003-2016 www.cfsph.iastate.edu  Email: [email protected] page 4 of 9

 Nipah Virus Infection
cats living near an infected bat colony on Tioman Island, Diagnostic Tests
Malaysia had antibodies to Nipah virus. Nipah virus infections in people can be diagnosed by
There have apparently been no significant outbreaks virus isolation, serology and RT-PCR, as in animals. In
among domesticated animals during human outbreaks in humans, this virus has been isolated from blood, throat or
Bangladesh and India, and there are no published reports of nasal swabs, cerebrospinal fluid (CSF) and urine samples, as
proven cases in animals from this region. Whether this is well as from a variety of postmortem tissues. It is most likely
due to little or no virus transmission to these animals, or to be recovered from clinical samples early in the illness, and
limited surveillance and diagnostics is unclear. A recent virus isolation from the CSF is a poor prognostic sign. In
human outbreak in the Philippines was linked to contact patients who have died, immunohistochemistry can also be
with sick horses, although it could not be confirmed that the used to detect viral antigens in tissues. Nipah virus antigens
horses were infected (no tissues were available). Four cats are most likely to be found in the central nervous system
and one dog died soon after eating tissues from sick horses (CNS), followed by the lung or kidney.
during this outbreak. Antibodies to Nipah virus were Serological tests used in humans include ELISAs to
detected in dogs but not cats in the area. detect henipavirus-specific IgM or IgG, and serum
neutralization. Antibodies to Nipah virus occur in serum
Infections in Humans and/or CSF. IgM can be found in a significant number of
patients during the illness. A rising titer, using acute and
Incubation Period convalescent sera, is also diagnostic.
Clinical cases in humans usually become apparent
several days to 14 days after exposure; however, incubation Treatment
periods as short as 2 days or as long as a month or more Treatment is supportive, with some patients requiring
have been reported. Some people with mild or subclinical measures such as mechanical ventilation. Ribavirin
infections can develop late-onset encephalitis months or appeared to be promising in some outbreaks, but had little
years later. One such case occurred after 11 years. or no effect on the outcome in animal models, and its
efficacy is currently considered to be uncertain. Other
Clinical Signs potential treatments, such as the administration of
Although some Nipah virus infections can be antibodies to Nipah virus, are being investigated in
asymptomatic or mild, most recognized clinical cases have preclinical studies.
been characterized by respiratory disease and/or acute
neurological signs. The initial symptoms are flu-like, with Control
fever, headache, sore throat and myalgia. Nausea, vomiting Pigs seem to be important amplifying hosts for Nipah
and a nonproductive cough may also be seen. This virus, and preventing infections in this species can
prodromal syndrome may be followed by encephalitis, with decrease the risk of infection for humans. Sick animals
symptoms such as drowsiness, disorientation, signs of should not be used for food, even if the meat is to be
brainstem dysfunction, convulsions, coma and other signs. cooked, as the slaughter process can increase human
Segmental myoclonus was common in patients with exposure to viruses in the tissues. Close contact with fruit
encephalitis in Malaysia, and cases of meningitis, as well as bats and their secretions and excretions should also be
encephalitis, were documented in the Philippines. Nipah avoided. Bats have been observed visiting date palm sap
virus infections in some patients appear as respiratory collection sites at night, and can contaminate collection
disease, including atypical pneumonia or acute respiratory pots with urine and saliva. While the general
distress syndrome. These patients may or may not develop recommendation is to avoid drinking any unpasteurized
neurological signs. Septicemia, bleeding from the juices in endemic regions, keeping bats away from sap
gastrointestinal tract, renal impairment and other collection sites with protective coverings (e.g., bamboo
complications are possible in severely ill patients. Survivors sap skirts) may be helpful in areas where people are
of encephalitis may have mild to severe residual unlikely to stop drinking raw date palm sap. Smearing
neurological deficits, or remain in a vegetative state. lime on the collection area to discourage bats appeared to
Some people infected with Nipah virus develop have little inhibitory effect in one study. Fruit should be
relapsed encephalitis or late-onset encephalitis, months or washed thoroughly, peeled or cooked before eating. Good
years later. The latter syndrome occurs in a person who was personal hygiene, including hand washing, is likely to
initially asymptomatic or had a non-neurological illness. reduce the risk of infection from the environment.
The clinical signs usually develop acutely, with symptoms Nipah virus has been classified as a Hazard Group 4/
that may include fever, headache, seizures and focal BSL4 pathogen; infected animals, body fluids and tissue
neurological signs. Some cases are fatal. samples must be handled with appropriate biosecurity
precautions. People who come in close contact with
potentially infected animals should wear protective
clothing, impermeable gloves, masks, goggles and boots.

© 2003-2016 www.cfsph.iastate.edu  Email: [email protected] page 5 of 9

 Nipah Virus Infection
Because Nipah virus can be transmitted from person to Internet Resources
person, barrier nursing should be used when caring for
infected patients. Patients should be isolated, and personal Centers for Disease Control and Prevention. Nipah Virus
protective equipment such as protective clothing, gloves http://www.cdc.gov/vhf/nipah/
and masks should be used. Good hygiene and sanitation
Food and Agriculture Organization of the United Nations.
are important; in one study, hand washing helped prevent
Manual on the Diagnosis of Nipah Virus Infection
disease transmission. Vaccines are currently not available
in Animals.
for humans.
http://www.fao.org/DOCREP/005/AC449E/AC449E00.htm
Morbidity and Mortality The Merck Veterinary Manual
Nipah virus has emerged repeatedly into humans in http://www.merckvetmanual.com
Southeast Asia, with more than 500 cases identified as of
2016. The first known cases occurred in Malaysia (and WHO Emergencies preparedness, response :
abattoir workers in Singapore) in 1998-1999, although Nipah Virus
retrospective diagnosis shows that human infections also http://www.who.int/csr/don/archive/disease/nipah_virus/en/
occurred in 1997. Approximately 283 cases of encephalitis World Organization for Animal Health (OIE)
(including late onset cases) were reported in Malaysia http://www.oie.int
during these outbreaks, with 109 deaths. Most people
were infected by contact with pigs, and human cases were OIE Manual of Diagnostic Tests and Vaccines for
not seen after seropositive animals had been culled. Terrestrial Animals
However, sporadic cases and clusters have been reported http://www.oie.int/international-standard-setting/terrestrial-
most years from Bangladesh, and occasionally from India, manual/access-online/
since 2001. These infections tend to be clustered in certain OIE Terrestrial Animal Health Code
regions, although isolated cases have been reported from http://www.oie.int/international-standard-setting/terrestrial-
other areas. Outbreaks in Bangladesh are seasonal and code/access-online/
occur mainly between December and May, which is also
the period when date palm sap is harvested. Drinking raw Acknowledgements
date palm sap is thought to be responsible for a number of
cases, but person-to-person transmission is also This factsheet was written by Anna Rovid Spickler, DVM,
significant, and nosocomial outbreaks have occurred in PhD, Veterinary Specialist from the Center for Food
hospitals where barrier nursing precautions were Security and Public Health. The U.S. Department of
inadequate. Additional routes of exposure, such as contact Agriculture Animal and Plant Health Inspection Service
with bat excretions when climbing trees, have been (USDA APHIS) provided funding for this factsheet through
suspected in some cases. a series of cooperative agreements related to the
Serological studies suggest that some human development of resources for initial accreditation training.
infections may be asymptomatic or mild, although the
The following format can be used to cite this factsheet.
prevalence of such cases is currently unclear. In the
Spickler, Anna Rovid. 2016. Nipah Virus Infection.
Malaysian outbreak, the subclinical infection rate was
Retrieved from http://www.cfsph.iastate.edu/DiseaseInfo/
estimated to be 8-15%. In clinical cases, the fatality rate
factsheets.php.
has ranged from 38% to approximately 70-75% in various
outbreaks, with higher rates reported from some small
case series. The case fatality rate is reported to be much References
higher in Bangladesh and India than Malaysia, but AbuBakar S, Chang LY, Ali AR, Sharifah SH, Yusoff K, Zamrod
whether this is due to strain variability or to differences in Z. Isolation and molecular identification of Nipah virus from
healthcare is uncertain. One study reported a higher pigs. Emerg Infect Dis. 2004;10:2228-30.
mortality rate in people with diabetes. Among surviving Arankalle VA, Bandyopadhyay BT, Ramdasi AY, Jadi R, Patil
patients, an estimated 19-32% have residual neurological DR, Rahman M, Majumdar M, Banerjee PS, Hati AK,
deficits, and higher rates have been reported in patients Goswami RP, Neogi DK, Mishra AC. Genomic
with more severe neurological signs. In Malaysia, late characterization of Nipah virus, West Bengal, India. Emerg
onset or relapsed encephalitis occurred in <5% and < 10% Infect Dis. 2011;17(5):907-9.
of patients, respectively, with an overall case fatality rate Berhane Y, Weingartl HM, Lopez J, Neufeld J, Czub S, Embury-
of 18%. Hyatt C, Goolia M, Copps J, Czub M. Bacterial infections in
pigs experimentally infected with Nipah virus. Transbound
Emerg Dis. 2008;55(3-4):165-74.
Breed AC, Field HE, Epstein JH, Daszak P. Emerging
henipaviruses and flying foxes – Conservation and
management perspectives. Biol Conserv. 2006;131:211-20.

© 2003-2016 www.cfsph.iastate.edu  Email: [email protected] page 6 of 9

 Nipah Virus Infection
Breed AC, Meers J, Sendow I, Bossart KN, Barr JA, Smith I, Cobey S. The Henipavirus Ecology Collaborative Research Group
Wacharapluesadee S, Wang L, Field HE. The distribution of [HERG]. Virus and bat information: Nipah virus [online].
henipaviruses in Southeast Asia and Australasia: is Wallace's HERG; 2005. Available at:
line a barrier to Nipah virus? PLoS One. 2013;8(4):e61316. http://www.henipavirus.org/virus_and_host_info/virus_and_h
Broder CC. Henipavirus outbreaks to antivirals: the current status ost_info.htm.* Accessed 9 Nov 2007.
of potential therapeutics. Curr Opin Virol. 2012;2(2):176-87. Daniels P, Ksiazek T, Eaton BT. Laboratory diagnosis of Nipah
California Department of Food and Agriculture. Malaysian and Hendra virus infections. Microbes Infect. 2001:3:289-95.
outbreak of Nipah virus in people and swine [online]. de Wit E, Munster VJ. Animal models of disease shed light on
Available at: http://www.cdfa.ca.gov/ahfss/ah/pdfs/nipah.pdf.* Nipah virus pathogenesis and transmission. J Pathol.
Accessed 12 Nov 2001. 2015;235(2):196-205.
Centers for Disease Control and Prevention (CDC). Update: de Wit E, Prescott J, Falzarano D, Bushmaker T, Scott D,
outbreak of Nipah virus -- Malaysia and Singapore, 1999. Feldmann H, Munster VJ. Foodborne transmission of Nipah
MMWR Morb Mortal Wkly Rep. 1999;48:335-7. virus in Syrian hamsters.PLoS Pathog. 2014;10(3):e1004001
Chadha MS, Comer JA, Lowe L, Rota PA, Rollin PE, Bellini WJ, Dups J, Middleton D, Long F, Arkinstall R, Marsh GA, Wang LF.
Ksiazek TG, Mishra A. Nipah virus-associated encephalitis Subclinical infection without encephalitis in mice following
outbreaks, Siliguri, India. Emerg Infect Dis. 2006;12:235-40. intranasal exposure to Nipah virus-Malaysia and Nipah virus-
Chakraborty A, Sazzad HM, Hossain MJ, Islam MS, Parveen S, Bangladesh. Virol J. 2014;11:102.
Husain M, Banu SS, Podder G, Afroj S, Rollin PE, Daszak P, Eaton BT, Broder CC, Middleton D, Wang LF. Hendra and Nipah
Luby SP, Rahman M, Gurley ES. Evolving epidemiology of viruses: different and dangerous. Nat Rev Microbiol.
Nipah virus infection in Bangladesh: evidence from outbreaks 2006;4:23-35.
during 2010-2011. Epidemiol Infect. 2016;144(2):371-80. Epstein JH, Abdul Rahman S, Zambriski JA, Halpin K, Meehan
Chan KP, Rollin PE, Ksiazek TG, Leo YS, Goh KT, Paton NI, G, Jamaluddin AA, Hassan SS, Field HE, Hyatt AD, Daszak
Sng EH, Ling AE. A survey of Nipah virus infection among P; Henipavirus Ecology Research Group. Feral cats and risk
various risk groups in Singapore. Epidemiol Infect. for Nipah virus transmission. Emerg Infect Dis. 2006;12:
2002;128:93-8. 1178-9.
Chew MH, Arguin PM, Shay DK, Goh KT, Rollin PE, ShiehWJ, Field H, Young P, Yob JM, Mills J, Hall L, Mackenzie J. The
Zaki SR, Rota Pa, Ling AE, Ksiazek TG, Chew SK, Anderson natural history of Hendra and Nipah viruses. Microbes Infect.
LJ. Risk factors for Nipah virus infection among abattoir 2001;3:307-14.
workers in Singapore. J Infect Dis. 2000;181:1760-3. Geisbert TW, Mire CE, Geisbert JB, Chan YP, Agans KN,
Ching PK, de los Reyes VC, Sucaldito MN, Tayag E, Columna- Feldmann F, Fenton KA, Zhu Z, Dimitrov DS, Scott DP,
Vingno AB, et al. Outbreak of henipavirus infection, Bossart KN, Feldmann H, Broder CC. Therapeutic treatment
Philippines, 2014.Emerg Infect Dis. 2015;21(2):328-31 of Nipah virus infection in nonhuman primates with a
Chowdhury S, Khan SU, Crameri G, Epstein JH, Broder CC, neutralizing human monoclonal antibody. Sci Transl Med.
Islam A, Peel AJ, Barr J, Daszak P, Wang LF, Luby SP. 2014;6(242):242ra82.
Serological evidence of henipavirus exposure in cattle, goats Goh KJ, Tan CT, Chew NK, Tan PSK, Kamarulzaman A, Sarji
and pigs in Bangladesh. PLoS Negl Trop Dis. SA, Wong KT, Abdulla BJ, Chua KB, Lam SK. Clinical
2014;8(11):e3302. features of Nipah virus encephalitis among pig farmers in
Chua KB. Epidemiology, surveillance and control of Nipah virus Malaysia. N Engl J Med. 2000;342:1229-35.
infections in Malaysia. Malays J Pathol. 2010;32(2):69-73. Gurley ES, Montgomery JM, Hossain MJ, Bell M, Azad AK,
Chua KB. Nipah virus outbreak in Malaysia. J Clin Virol. Islam MR, Molla MAR, Carroll DS, Ksiazek TG, Rota PA,
2003;26:265-75. Lowe L, Comer JA, Rollin P, Czub M, Grolla A, Feldmann H,
Chua KB, Bellini WJ, Rota PA, Harcourt BH, Tamin A, et al.. Luby SP, Woodward JL, Breiman RF. Person-to-person
Nipah virus: a recently emergent deadly paramyxovirus. transmission of Nipah virus in a Bangladeshi community.
Science. 2000;288:1432-1435. Emerg Infect Dis. 2007;13:1031-7.
Chua KB, Koh CL, Hooi PS, Wee KF, Khong JH, Chua BH, Chan Halpin K, Hyatt AD, Fogarty R, Middleton D, Bingham J, Epstein
YP, Lim ME, Lam SK. Isolation of Nipah virus from JH, Rahman SA, Hughes T, Smith C, Field HE, Daszak P;
Malaysian Island flying foxes. Microbes Infect. 2002;4: Henipavirus Ecology Research Group. Pteropid bats are
145-51. confirmed as the reservoir hosts of henipaviruses: a
comprehensive experimental study of virus transmission. Am
Chua KB, Lam SK, Goh KJ, Hooi PS, Ksiazek TG, J Trop Med Hyg. 2011;85(5):946-51
Kamarulzaman A, Olson J, Tan CT. The presence of Nipah
virus in respiratory secretions and urine of patients during an Halpin K, Mungall BA. Recent progress in henipavirus research.
outbreak of Nipah virus encephalitis in Malaysia. J Infect. Comp Immunol Microbiol Infect Dis. 2007;30:287-307.
2001;42:40-3. Harit AK, Ichhpujani RL, Gupta S, Gill KS, Lal S, Ganguly NK,
Clayton BA, Middleton D, Bergfeld J, Haining J, Arkinstall R, Agarwal SP. Nipah/Hendra virus outbreak in Siliguri, West
Wang L, Marsh GA. Transmission routes for Nipah virus from Bengal, India in 2001. Indian J Med Res. 2006;123:553-60.
Malaysia and Bangladesh. Emerg Infect Dis. Hasebe F, Thuy NT, Inoue S, Yu F, Kaku Y, Watanabe S, Akashi
2012;18(12):1983-93. H, Dat DT, Mai le TQ, Morita K. Serologic evidence of nipah
virus infection in bats, Vietnam.Emerg Infect Dis.
2012;18(3):536-7.

© 2003-2016 www.cfsph.iastate.edu  Email: [email protected] page 7 of 9

 Nipah Virus Infection
Hooper P, Zaki S, Daniels P, Middleton D. Comparative Mungall BA, Middleton D, Crameri G, Bingham J, Halpin K,
pathology of the diseases caused by Hendra and Nipah Russell G, Green D, McEachern J, Pritchard LI, Eaton BT,
viruses. Microbes Infect. 2001;3:315-22. Wang LF, Bossart KN, Broder CC. Feline model of acute
Hooper PT, Williamson MM. Hendra and Nipah virus infections. nipah virus infection and protection with a soluble
Emerg Infect Dis. 2000;16:597-603. glycoprotein-based subunit vaccine. J Virol. 2006;80:
Hooper PT, Williamson MM. Hendra and Nipah virus infections.. 12293-302.
Vet Clin North Am Equine Pract. 2000;16:597-603. Mungall BA, Middleton D, Crameri G, Halpin K, Bingham J,
Hsu VP, Hossain MJ, Parashar UD, Ali MM, Ksiazek TG, Eaton BT, Broder CC. Vertical transmission and fetal
Kuzmin I, Niezgoda M, Rupprecht C, Bresse J, Breiman RF. replication of Nipah virus in an experimentally infected cat.
Nipah virus encephalitis reemergence, Bangladesh. Emerg J Infect Dis. 2007;196:812-6.
Infect Dis. 2004;10:2082-7. Nahar N, Paul RC, Sultana R, Gurley ES, Garcia F, Abedin J,
Hyatt AD, Daszak P, Cunningham AA, Field H,. Gould AR. Sumon SA, Banik KC, Asaduzzaman M, Rimi NA, Rahman
Henipaviruses: Gaps in the knowledge of emergence. M, Luby SP. Raw sap consumption habits and its association
Ecohealth. 2004;1:25-38. with knowledge of Nipah virus in two endemic districts in
Bangladesh. PLoS One. 2015 9;10(11):e0142292.
Khan SU, Gurley ES, Hossain MJ, Nahar N, Sharker MA, Luby
SP.A randomized controlled trial of interventions to impede Ong KC, Wong KT. Henipavirus encephalitis: Recent
date palm sap contamination by bats to prevent Nipah virus developments and advances. Brain Pathol. 2015;25(5):605-13.
transmission in Bangladesh. PLoS One. 2012;7(8):e42689. Parashar UD, Sunn LM, Ong F, Mounts AW, Arif MT, et al.
Khan MS, Hossain J, Gurley ES, Nahar N, Sultana R, Luby SP. Case-control study of risk factors for human infection with a
Use of infrared camera to understand bats' access to date palm new zoonotic paramyxovirus, Nipah virus during a 1998-1999
sap: implications for peventing Nipah virus outbreaks of severe encephalitis in Malaysia. J Infect Dis.
transmission.Ecohealth. 2010;7(4):517-25. 2000;181:1755-9.
Lam SK, Chua KB. Nipah virus encephalitis outbreak in Malaysia. Peterson AT. Mapping risk of Nipah virus transmission across
Clin Infect Dis. 2002;34; S48-S51. Asia and across Bangladesh. Asia Pac J Public Health.
2015;27(2):NP824-32.
Li Y, Wang J, Hickey AC, Zhang Y, Li Y, Wu Y, Zhang H, Yuan
J, Han Z, McEachern J, Broder CC, Wang LF, Shi Z. Rahman SA, Hassan SS, Olival KJ, Mohamed M, Chang LY,
Antibodies to Nipah or Nipah-like viruses in bats, China. Hassan L, Saad NM, Shohaimi SA, Mamat ZC, Naim MS,
Emerg Infect Dis. 2008;14(12):1974-6. Epstein JH, Suri AS, Field HE, Daszak P; Henipavirus
Ecology Research Group.Characterization of Nipah virus from
Luby SP, Gurley ES, Hossain MJ. Transmission of human infection naturally infected Pteropus vampyrus bats, Malaysia.Emerg
with Nipah virus. Clin Infect Dis. 2009;49(11):1743-8. Infect Dis. 2010;16(12):1990-3.
Luby SP, Rahman M, Hossain MJ, Blum LS, Husain MM, Gurley Rahman MA, Hossain MJ, Sultana S, Homaira N, Khan SU, et al.
E, Khan R, Ahmed BN, Rahman S, Nahar N, Kenah E, Comer Date palm sap linked to Nipah virus outbreak in Bangladesh,
JA, Ksiazek TG. Foodborne transmission of Nipah virus, 2008. Vector Borne Zoonotic Dis. 2012;12(1):65-72.
Bangladesh. Emerg Infect Dis. 2006;12:1888-94.
Reynes JM, Counor D, Ong S, Faure C, Seng V, Molia S, Walston
Mackenzie JS, Chua KB, Daniels PW, Eaton BT, Field HE, et al. J, Georges-Courbot MC, Deubel V, Sarthou JL. Nipah virus in
Emerging viral diseases of Southeast Asia and the Western Lyle’s flying foxes, Cambodia. Emerg Infect Dis.
Pacific. Emerg Infect Dis. 2001;7(3 Suppl): 497-504. 2005;11:1042-7.
Marsh GA, de Jong C, Barr JA, Tachedjian M, Smith C, et al. Sahani M, Parashar UD, Ali R, Das P, Lye MS, Isa MM, Arif MT,
Cedar virus: a novel henipavirus isolated from Australian bats. Ksiazek TG, Sivamoorthy M; Nipah Encephalitis Outbreak
PLoS Pathog. 2012;8(8):e1002836. Investigation Group. Nipah virus infection among abattoir
Mathieu C, Horvat B. Henipavirus pathogenesis and antiviral workers in Malaysia, 1998-1999. Int J Epidemiol.
approaches. Expert Rev Anti Infect Ther. 2015;13(3):343-54. 2001;30:1017-20.
Middleton DJ, Morrissy CJ, van der Heide BM, Russell GM, Sendow I, Ratnawati A, Taylor T, Adjid RM, Saepulloh M, Barr J,
Braun MA, Westbury HA, Halpin K, Daniels PW. Wong F, Daniels P, Field H. Nipah virus in the fruit bat
Experimental Nipah virus infection in pteropid bats (Pteropus Pteropus vampyrus in Sumatera, Indonesia. PLoS One.
poliocephalus). J Comp Pathol. 2007;136(4):266-72. 2013;8(7):e69544.
Middleton DJ, Weingartl HM. Henipaviruses in their natural Sherrini BA, Chong TT. Nipah encephalitis - an update. Med J
animal hosts. Curr Top Microbiol Immunol. 2012;359:105-21. Malaysia. 2014;69 Suppl A:103-11.
Middleton DJ, Westbury HA, Morrissy CJ, van der Heide BM, Tan CT, Tan KS. Nosocomial transmissibility of Nipah virus. J
Russell GM, Braun MA, Hyatt AD. Experimental Nipah virus Infect Dis. 2001;184:1367.
infection in pigs and cats. J Comp Path. 2002;126:124-36. United Kingdom, Department of Health Social Services and
Mills JN, Alim AN, Bunning ML, Lee OB, Wagoner KD, Amman Public Safety [DHSSPS]. Hendra virus and Nipah virus.
BR, Stockton PC, Ksiazek TG.Nipah virus infection in dogs, Management and control [online]. DHSSPS; 2000 Sept.
Malaysia, 1999. Emerg Infect Dis. 2009;15(6):950-2. Available at: http://webarchive.nationalarchives.gov.uk/
Mohd Nor MN, Gan CH, Ong BL. Nipah virus infection of pigs in 20130107105354/http://www.dh.gov.uk/en/Publicationsandsta
peninsular Malaysia. Rev Sci Tech. 2000;19:160-5. tistics/Publications/PublicationsPolicyAndGuidance/DH_4010
423. Accessed 7 Nov 2007.
Uppal PK. Emergence of Nipah virus in Malaysia. Ann N Y Acad
Sci. 2000;916: 354-7.

© 2003-2016 www.cfsph.iastate.edu  Email: [email protected] page 8 of 9

 Nipah Virus Infection
Wacharapluesadee S, Hemachudha T. Duplex nested RT-PCR for
detection of Nipah virus RNA from urine specimens of bats. J
Virol Methods. 2007;141:97-101.
Wacharapluesadee S. Lumlertdacha B, Boongird K, Wanghongasa
S, Chanhome L, Rollin P, Stockton P, Rupprecht CE, Ksiazek
TG, Hemachudha T. Bat Nipah virus, Thailand. Emerg Infect
Dis. 2005;11:1949-1951.
Wang LF, Daniels P. Diagnosis of henipavirus infection: current
capabilities and future directions. Curr Top Microbiol
Immunol. 2012;359:179-96. doi: 10.1007/82_2012_215.
Weingartl H, Czub S, Copps J, Berhane Y, Middleton D, Marszal
P, Gren J, Smith G, Ganske S, Manning L, Czub M. Invasion
of the central nervous system in a porcine host by Nipah virus.
J Virol. 2005;79:7528-34.
Williamson MM, Torres-Velez FJ. Henipavirus: a review of
laboratory animal pathology. Vet Pathol. 2010;47(5):871-80.
Wong KT, Grosjean I, Brisson C, Blanquier B, Fevre-Montange
M, Bernard A, Loth P, Georges-Courbot MC, Chevallier M,
Akaoka H, Marianneau P, Lam SK, Wild TF, Deubel V. A
golden hamster model for human acute Nipah virus infection.
Am J Pathol. 2003;163:2127-37.
Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner
J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong
HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR; Nipah Virus
Pathology Working Group. Nipah virus infection: pathology
and pathogenesis of an emerging paramyxoviral zoonosis. Am
J Pathol. 2002;161:2153-67.
World Health Organization [WHO]. Nipah virus [online]. WHO;
2001 Sept. Available at: http://www.who.int/mediacentre/
factsheets/fs262/en/.* Accessed 5 Nov 2007.
World Organization for Animal Health [OIE]. Manual of diagnostic
tests and vaccines for terrestrial animals [online]. Paris: OIE;
2015. Hendra and Nipah virus diseases. Available at:
http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/
2.09.06_NIPAH_HENDRA.pdf. Accessed 20 Dec 2015.
Yadav PD, Raut CG, Shete AM, Mishra AC, Towner JS, Nichol
ST, Mourya DT. Detection of Nipah virus RNA in fruit bat
(Pteropus giganteus) from India. Am J Trop Med Hyg.
2012;87(3):576-8.
Yob JM, Field H, Rashdi AM, Morrissy C, van der Heide B, Rota
P, bin Adzhar A, White J, Daniels P, Jamaluddin A, Ksiazek
T. Nipah virus infection in bats (order Chiroptera) in
peninsular Malaysia. Emerg Infect Dis. 2001;7:439-441.

*Link defunct

© 2003-2016 www.cfsph.iastate.edu  Email: [email protected] page 9 of 9