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NIPAH VIRUS
DR. SUBRAHAM PANY
POST GRADUATE DEPARTMENT OF COMMUNITY MEDICINE
OVERVIEW
 Introduction
 History & Problem Statement
 Transmission
 Disease in Humans
 Disease in Animals
 Climatic correlation
 Risk of Exposure
 Prevention and Control
 Actions to Take
SYNONYMS
 NiV
 Barking Pig Syndrome
 Porcine Respiratory and Encephalitis Syndrome
 Porcine Respiratory and Neurologic Syndrome
 Nipah virus (NiV) is a member of the
family Paramyxoviridae,
genus Henipavirus.
 NiV was initially isolated and identified in
1999 during an outbreak of encephalitis &
respiratory illness among pig farmers &
people with close contact with pigs in
Malaysia, Indonesia and Singapore.
INTRODUCTION
 Its name originated from Sungai Nipah, a
village in the Malaysian Peninsula where
pig farmers became ill with encephalitis.
 Given the relatedness of NiV to Hendra
virus, bat species were quickly singled
out for investigation & flying foxes of
the genus Pteropus were subsequently
identified as the reservoir for NiV.
[REF: http://www.cdc.gov/vhf/nipah/]
http://www.cdc.gov/vhf/nipah/
Locations Of Henipavirus Outbreaks (Red Stars–hendra Virus; Blue
Stars–nipah Virus) And Distribution Of Henipavirus Flying Fox
Reservoirs (Red Shading–hendra Virus ; Blue Shading–nipah Virus)
http://cid.oxfordjournals.org/content/49/11/1743.full
PROBLEM STATEMENT:
 In the 1999 outbreak, Nipah virus caused
a relatively mild disease in pigs, but
nearly 300 human cases with over 100
deaths were reported.
 In order to stop the outbreak, more than a
million pigs were euthanized, causing
tremendous trade loss for Malaysia.
 Since this outbreak, no subsequent cases
(in neither swine nor human) have been
reported in either Malaysia or Singapore.
[REF: MMWR, Outbreak of Hendra-like virus—Malaysia and Singapore,
1998-1999. Apr 9, 1999;48(3):265-9.]
 In 2001, NiV was again identified as the
causative agent in an outbreak of human
disease occurring in Bangladesh.
 Genetic sequencing confirmed this virus as
Nipah virus, but a strain different from the one
identified in 1999.
 In the same year, another outbreak was
identified retrospectively in Siliguri, India with
reports of person-to-person transmission in
hospital settings.
 Outbreaks occur almost annually in Bangladesh
and have been reported several times in India.
[REF:Chadha MS, Comer JA, Lowe L, et al. Nipah virus-associated encephalitis
outbreak, Siliguri, India.Emerging Infectious Disease 2006;12(2):235-40].
[REF: HT Chong et al. (2009) Nipah virus and bats. Neurology Asia; 14: 73–76]
Ann Indian Acad Neurol 2006;9:137-44
TRANSMISSION
 Direct contact with infected bats, infected pigs, or from other NiV infected
people.
 In Malaysia and Singapore:
 No occurrence of person-to-person transmission was reported in this outbreak.
 Conversely, person – to – person
transmission of Nipah virus in
Bangladesh and India is regularly
reported.
 Direct exposure to infected bats. A
common example is consumption
of raw date palm sap contaminated
with infectious bat excretions.
[REF: Field HE, Mackenzie JS, Daszak P. Henipaviruses: emerging paramyxoviruses associated with fruit
bats. Current Topics Microbiology and Immunology 2007;315:133-59.]
NIPAH WILDLIFE STUDIES
 Numerous wild animals trapped and tested
 8 different species of fruit bats sampled
 4 of the 8 species had antibody against Nipah virus
 Nipah virus isolated:
 In urine from Pteropus hypomelanus in Malaysia
 In Urine from Pteropus lylei in Thailand
These are several of the hog confinement barns that were affected during the
Malaysia Nipah virus outbreak. The reservoir fruit bats live in these caves and
feed on the fruit trees that are in close proximity to the hog confinement barns.
This picture shows additional hog confinement barns in Malaysia.
There are many fruit trees & caves close to this location.
A picture taken by infrared
night observation showing
a small fruit bat (in circle)
licking sap from the
shaved surface of a date
palm tree without any
intervention
CLIMATIC ORIGIN OF NIPAH VIRUS OUTBREAK
 1997 and 1998 were ugly, hazy years for Malaysia.
 Massive tropical rainforest in Indonesia were slashed-and-
burned for industrial plantation and pulpwood, resulting in an
impenetrable haze that cloaked the peninsula and the
surrounding Southeast Asian countries for months.
 12 million acres of rainforest were deforested and the haze so
obscured the sunlight in southern Malaysia that flowering and
fruiting trees could not photosynthesize.
 Crops failed throughout the country
 Cases of an unusual febrile encephalitis falling both human and
swine began in the fall of 1998 among the pig farming
communities.
This image from NASA’s Earth Probe Total Ozone Mapping Spectrometer (TOMS) satellite instrument shows the extent of the air pollution
resulting from the Indonesian forest fires in fall of 1997. Source: NASA/GSFC Scientific Visualization Studio, based on data from TOMS.
 Districts of Negeri Sembilan, Sungai Nipah & Bukit Pelanduk, were
stricken by an illness that was initially mistakenly identified as
Japanese encephalitis.
 Government workers provided vaccinations & mosquito fogging.
 Finally, upon the discovery of a novel virus identified as spreading
from pigs to humans, the Malaysian government destroyed 1.1
million pigs destroyed at a cost of $3.5 million.
 Approximately 265 people fell ill and 105 died.
NIPAH CASE DEFINITION:
Person with fever plus
o New onset seizures
o Altered mental status
o Severe shortness of breath
o Antibody against Nipah virus
SIGNS AND SYMPTOMS:
Infection with Nipah virus is associated with encephalitis.
After exposure & an incubation period of 5 to 14 days,
illness presents with 3-14 days of fever & headache,
followed by drowsiness, disorientation & mental
confusion.
These signs and symptoms can progress to coma within
24-48 hours.
Some patients have a respiratory illness during the early
part of their infections, & half of the patients showing
severe neurological signs showed also pulmonary signs.
 Long-term sequelae following Nipah virus infection
have been noted, including persistent convulsions
and personality changes.
 Latent infections with subsequent reactivation of Nipah virus death
have also been reported months and even years after exposure.
 During the Nipah virus disease outbreak in 1998-99, 265 patients
were infected with the virus. About 40% of those patients who
entered hospitals with serious nervous disease died from the illness.
[REF:Hossain MJ, Gurley ES, Montgomery JM, et al. Clinical presentation of Nipah virus infection in
Bangladesh. Clinical Infectious Diseases 2008;46(7):977-84.]
Highly contagious
May be asymptomatic
Acute fever (>104°F)
Severe respiratory disease
Characteristic cough – harsh,
“barking”
Neurological changes
Low mortality
[REF: www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/nipah.html]
DISEASE IN ANIMALS
 Dog
1. Distemper-like signs
2. Fever, respiratory distress
3. Ocular and nasal discharge
 Cat
1. Fever, depression
2. Severe respiratory signs
 Horses
1. Encephalitis
[REF: Center for Food Security and Public Health Iowa State University – 2005]
DIFFERENTIAL DIAGNOSIS:
Differentials for NIPAH:
I. Classical swine fever,
II. Porcine Reproductive & Respiratory Syndrome (PRRS),
III. Pseudorabies,
IV.Swine enzootic pneumoniae,
V. Porcine pleuropneumonia
[REF: http://www.who.int/csr/don/archive/disease/nipah_virus/en/]
RISK OF EXPOSURE
 In the Malaysia and Singapore outbreak, Nipah virus infection
was associated with close contact with Nipah virus-infected pigs.
 In Bangladesh and India, where Nipah virus infection is more
frequent, exposure has been linked to consumption of raw date
palm sap and contact with bats.
 Importantly, human-to-human transmission has been documented
and exposure to other Nipah virus infected individuals is also a
risk factor.
PREVENTION:
 Keep fruit bats away from pigs
 Do not drink unpasteurized fruit juices
 Wash, peel, &/or cook all fruit thoroughly before eating
 Raising awareness of transmission and symptoms is
important in reinforcing standard infection control
practices to avoid human-to-human infections in
hospital settings.
A subunit vaccine, using the Hendra G protein, produces cross-
protective antibodies against HEN V. and NIP V. has been
recently used in Australia to protect horses against Hendra virus.
VACCINATION:
[REF:National Center for Emerging and Zoonotic Infectious Diseases (NCEZID)]
September 19, 2012, Vol 308, No. 11
DIAGNOSIS
 Laboratory diagnosis is made during the acute and convalescent
phases of the disease by using a combination of tests.
 Virus isolation attempts and real time polymerase
chain reaction (RT-PCR) from throat and nasal
swabs, CSF, urine & blood should be performed
in the early stages of disease.
 Antibody detection by ELISA can be used later on.
 In fatal cases, immunohistochemistry on tissues
collected during autopsy may be the only way to confirm diagnosis.
[REF: Lim CCT, Lee KE, Lee WL, et al. Nipah virus encephalitis: Serial MR study of an emerging
disease.Radiology 2002;222(1):219-26].
TREATMENT:
 Treatment is limited to supportive care.
 Standard infection control practices and proper barrier nursing
techniques are important in preventing nosocomial transmission.
 The drug ribavirin has been shown to be effective against the
viruses in vitro, but human investigations to date have been
inconclusive & the clinical usefulness of ribavirin remains
uncertain.
 Passive immunization using a human monoclonal antibody
targeting the Nipah G glycoprotein has been evaluated in the post-
exposure therapy in the ferret model & found to be of benefit.
[REF: Mounts AW, Kaur H, Parashar UD, et al. A cohort study of health care workers to assess nosocomial transmissibility of Nipah
virus, Malaysia, 1999. Journal of Inf. Disease 2001;183(5):810-3.]
NIPAH AS A BIOLOGICAL WEAPON
 CDC Category C Bioterrorism Agent
 Emerging pathogen
 Potentially high morbidity and mortality
 Major health impact
 Aerosolization potential
 Economic impact
 Social disruption (fear, panic)
[REF:Wong KT, Shieh WJ, Kumar S, et al. Nipah virus infection. Pathology and pathogenesis of an emerging paramyxoviral zoonosis.
American Journal of Pathology 2002;161(6):2153-67.]
1. Why is respiratory disease and person-to-person transmission
more common among human NiV infection in Bangladesh
compared to Malaysia?
2. How stable is the genome of Nipah?
3. Is there a substantial risk of mutation that would improve the
efficiency of person-to-person transmission of the virus?
4. How common is unrecognized, including subclinical, infection
with NiV?
[REF: http://www.ncbi.nlm.nih.gov/books/NBK114486/]
UNANSWERED QUESTIONS
? ? ?
THANK YOU.

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Nipah virus

  • 1. NIPAH VIRUS DR. SUBRAHAM PANY POST GRADUATE DEPARTMENT OF COMMUNITY MEDICINE
  • 2.
  • 3. OVERVIEW  Introduction  History & Problem Statement  Transmission  Disease in Humans  Disease in Animals  Climatic correlation  Risk of Exposure  Prevention and Control  Actions to Take
  • 4. SYNONYMS  NiV  Barking Pig Syndrome  Porcine Respiratory and Encephalitis Syndrome  Porcine Respiratory and Neurologic Syndrome
  • 5.  Nipah virus (NiV) is a member of the family Paramyxoviridae, genus Henipavirus.  NiV was initially isolated and identified in 1999 during an outbreak of encephalitis & respiratory illness among pig farmers & people with close contact with pigs in Malaysia, Indonesia and Singapore. INTRODUCTION
  • 6.  Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with encephalitis.  Given the relatedness of NiV to Hendra virus, bat species were quickly singled out for investigation & flying foxes of the genus Pteropus were subsequently identified as the reservoir for NiV. [REF: http://www.cdc.gov/vhf/nipah/]
  • 8.
  • 9. Locations Of Henipavirus Outbreaks (Red Stars–hendra Virus; Blue Stars–nipah Virus) And Distribution Of Henipavirus Flying Fox Reservoirs (Red Shading–hendra Virus ; Blue Shading–nipah Virus) http://cid.oxfordjournals.org/content/49/11/1743.full
  • 10. PROBLEM STATEMENT:  In the 1999 outbreak, Nipah virus caused a relatively mild disease in pigs, but nearly 300 human cases with over 100 deaths were reported.  In order to stop the outbreak, more than a million pigs were euthanized, causing tremendous trade loss for Malaysia.  Since this outbreak, no subsequent cases (in neither swine nor human) have been reported in either Malaysia or Singapore. [REF: MMWR, Outbreak of Hendra-like virus—Malaysia and Singapore, 1998-1999. Apr 9, 1999;48(3):265-9.]
  • 11.  In 2001, NiV was again identified as the causative agent in an outbreak of human disease occurring in Bangladesh.  Genetic sequencing confirmed this virus as Nipah virus, but a strain different from the one identified in 1999.  In the same year, another outbreak was identified retrospectively in Siliguri, India with reports of person-to-person transmission in hospital settings.  Outbreaks occur almost annually in Bangladesh and have been reported several times in India. [REF:Chadha MS, Comer JA, Lowe L, et al. Nipah virus-associated encephalitis outbreak, Siliguri, India.Emerging Infectious Disease 2006;12(2):235-40].
  • 12. [REF: HT Chong et al. (2009) Nipah virus and bats. Neurology Asia; 14: 73–76]
  • 13. Ann Indian Acad Neurol 2006;9:137-44
  • 14. TRANSMISSION  Direct contact with infected bats, infected pigs, or from other NiV infected people.  In Malaysia and Singapore:  No occurrence of person-to-person transmission was reported in this outbreak.
  • 15.  Conversely, person – to – person transmission of Nipah virus in Bangladesh and India is regularly reported.  Direct exposure to infected bats. A common example is consumption of raw date palm sap contaminated with infectious bat excretions. [REF: Field HE, Mackenzie JS, Daszak P. Henipaviruses: emerging paramyxoviruses associated with fruit bats. Current Topics Microbiology and Immunology 2007;315:133-59.]
  • 16. NIPAH WILDLIFE STUDIES  Numerous wild animals trapped and tested  8 different species of fruit bats sampled  4 of the 8 species had antibody against Nipah virus  Nipah virus isolated:  In urine from Pteropus hypomelanus in Malaysia  In Urine from Pteropus lylei in Thailand
  • 17. These are several of the hog confinement barns that were affected during the Malaysia Nipah virus outbreak. The reservoir fruit bats live in these caves and feed on the fruit trees that are in close proximity to the hog confinement barns.
  • 18. This picture shows additional hog confinement barns in Malaysia. There are many fruit trees & caves close to this location.
  • 19. A picture taken by infrared night observation showing a small fruit bat (in circle) licking sap from the shaved surface of a date palm tree without any intervention
  • 20. CLIMATIC ORIGIN OF NIPAH VIRUS OUTBREAK  1997 and 1998 were ugly, hazy years for Malaysia.  Massive tropical rainforest in Indonesia were slashed-and- burned for industrial plantation and pulpwood, resulting in an impenetrable haze that cloaked the peninsula and the surrounding Southeast Asian countries for months.  12 million acres of rainforest were deforested and the haze so obscured the sunlight in southern Malaysia that flowering and fruiting trees could not photosynthesize.  Crops failed throughout the country  Cases of an unusual febrile encephalitis falling both human and swine began in the fall of 1998 among the pig farming communities.
  • 21.
  • 22. This image from NASA’s Earth Probe Total Ozone Mapping Spectrometer (TOMS) satellite instrument shows the extent of the air pollution resulting from the Indonesian forest fires in fall of 1997. Source: NASA/GSFC Scientific Visualization Studio, based on data from TOMS.
  • 23.  Districts of Negeri Sembilan, Sungai Nipah & Bukit Pelanduk, were stricken by an illness that was initially mistakenly identified as Japanese encephalitis.  Government workers provided vaccinations & mosquito fogging.  Finally, upon the discovery of a novel virus identified as spreading from pigs to humans, the Malaysian government destroyed 1.1 million pigs destroyed at a cost of $3.5 million.  Approximately 265 people fell ill and 105 died.
  • 24. NIPAH CASE DEFINITION: Person with fever plus o New onset seizures o Altered mental status o Severe shortness of breath o Antibody against Nipah virus
  • 25. SIGNS AND SYMPTOMS: Infection with Nipah virus is associated with encephalitis. After exposure & an incubation period of 5 to 14 days, illness presents with 3-14 days of fever & headache, followed by drowsiness, disorientation & mental confusion. These signs and symptoms can progress to coma within 24-48 hours. Some patients have a respiratory illness during the early part of their infections, & half of the patients showing severe neurological signs showed also pulmonary signs.
  • 26.  Long-term sequelae following Nipah virus infection have been noted, including persistent convulsions and personality changes.  Latent infections with subsequent reactivation of Nipah virus death have also been reported months and even years after exposure.  During the Nipah virus disease outbreak in 1998-99, 265 patients were infected with the virus. About 40% of those patients who entered hospitals with serious nervous disease died from the illness. [REF:Hossain MJ, Gurley ES, Montgomery JM, et al. Clinical presentation of Nipah virus infection in Bangladesh. Clinical Infectious Diseases 2008;46(7):977-84.]
  • 27. Highly contagious May be asymptomatic Acute fever (>104°F) Severe respiratory disease Characteristic cough – harsh, “barking” Neurological changes Low mortality [REF: www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/nipah.html]
  • 28. DISEASE IN ANIMALS  Dog 1. Distemper-like signs 2. Fever, respiratory distress 3. Ocular and nasal discharge  Cat 1. Fever, depression 2. Severe respiratory signs  Horses 1. Encephalitis [REF: Center for Food Security and Public Health Iowa State University – 2005]
  • 29. DIFFERENTIAL DIAGNOSIS: Differentials for NIPAH: I. Classical swine fever, II. Porcine Reproductive & Respiratory Syndrome (PRRS), III. Pseudorabies, IV.Swine enzootic pneumoniae, V. Porcine pleuropneumonia [REF: http://www.who.int/csr/don/archive/disease/nipah_virus/en/]
  • 30. RISK OF EXPOSURE  In the Malaysia and Singapore outbreak, Nipah virus infection was associated with close contact with Nipah virus-infected pigs.  In Bangladesh and India, where Nipah virus infection is more frequent, exposure has been linked to consumption of raw date palm sap and contact with bats.  Importantly, human-to-human transmission has been documented and exposure to other Nipah virus infected individuals is also a risk factor.
  • 31. PREVENTION:  Keep fruit bats away from pigs  Do not drink unpasteurized fruit juices  Wash, peel, &/or cook all fruit thoroughly before eating  Raising awareness of transmission and symptoms is important in reinforcing standard infection control practices to avoid human-to-human infections in hospital settings.
  • 32. A subunit vaccine, using the Hendra G protein, produces cross- protective antibodies against HEN V. and NIP V. has been recently used in Australia to protect horses against Hendra virus. VACCINATION: [REF:National Center for Emerging and Zoonotic Infectious Diseases (NCEZID)]
  • 33. September 19, 2012, Vol 308, No. 11
  • 34. DIAGNOSIS  Laboratory diagnosis is made during the acute and convalescent phases of the disease by using a combination of tests.  Virus isolation attempts and real time polymerase chain reaction (RT-PCR) from throat and nasal swabs, CSF, urine & blood should be performed in the early stages of disease.  Antibody detection by ELISA can be used later on.  In fatal cases, immunohistochemistry on tissues collected during autopsy may be the only way to confirm diagnosis. [REF: Lim CCT, Lee KE, Lee WL, et al. Nipah virus encephalitis: Serial MR study of an emerging disease.Radiology 2002;222(1):219-26].
  • 35. TREATMENT:  Treatment is limited to supportive care.  Standard infection control practices and proper barrier nursing techniques are important in preventing nosocomial transmission.  The drug ribavirin has been shown to be effective against the viruses in vitro, but human investigations to date have been inconclusive & the clinical usefulness of ribavirin remains uncertain.  Passive immunization using a human monoclonal antibody targeting the Nipah G glycoprotein has been evaluated in the post- exposure therapy in the ferret model & found to be of benefit. [REF: Mounts AW, Kaur H, Parashar UD, et al. A cohort study of health care workers to assess nosocomial transmissibility of Nipah virus, Malaysia, 1999. Journal of Inf. Disease 2001;183(5):810-3.]
  • 36. NIPAH AS A BIOLOGICAL WEAPON  CDC Category C Bioterrorism Agent  Emerging pathogen  Potentially high morbidity and mortality  Major health impact  Aerosolization potential  Economic impact  Social disruption (fear, panic) [REF:Wong KT, Shieh WJ, Kumar S, et al. Nipah virus infection. Pathology and pathogenesis of an emerging paramyxoviral zoonosis. American Journal of Pathology 2002;161(6):2153-67.]
  • 37. 1. Why is respiratory disease and person-to-person transmission more common among human NiV infection in Bangladesh compared to Malaysia? 2. How stable is the genome of Nipah? 3. Is there a substantial risk of mutation that would improve the efficiency of person-to-person transmission of the virus? 4. How common is unrecognized, including subclinical, infection with NiV? [REF: http://www.ncbi.nlm.nih.gov/books/NBK114486/] UNANSWERED QUESTIONS ? ? ?