The Next Plague Ramsha Kudia MCB5505 Taxonomy Family Paramyxoviridae Subfamily Paramyxovirinae Genus Avulavirus Newcastle disease virus Genus Henipavirus Hendravirus Nipahvirus Genus Morbillivirus ID: 566223
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Nipah Virus
The Next Plague?
Ramsha Kudia
MCB5505Slide2
Taxonomy
Family: Paramyxoviridae
Subfamily Paramyxovirinae
Genus Avulavirus
Newcastle disease virus
Genus Henipavirus
Hendravirus
Nipahvirus
Genus Morbillivirus
Measles virus
Rinderpest virus
Genus Respirovirus
Sendai virus
Human parainfluenza viruses 1 and 3, as well some of the viruses of the common cold
Genus Rubulavirus
Mumps virus
Human parainfluenza viruses 2 and 4
Subfamily Pneumovirinae
Bovine respiratory syncytial virus
Human respiratory syncytial virus
Murine pneumonia virusSlide3
Henipavirus
Only zoonotic paramyxoviruses and are highly pathogenic
Genome size 18.2 kb, about 15% larger than other family members Biosafety level 4 because of pathogenicity, high mortality, and lack of treatment
The genus is able to infect a broad range of animal species, which is uncommon among the family
High mutation ratesSlide4
Virion Structure
Non-segmented, negative sense, single stranded RNA
EncapsulatedPolymorphic, but usually spherical or filamentousHelical nucleocapsid Slide5
Viral Genome
The genome contains 6 genes, which code for 9 proteins
Leader sequence at 3’ end and trailer at 5’ endN = nucleocapsid gene
protects from nuclease digestion
P = phosphoprotein
binds to the N and L proteins and forms part of the RNA polymerase complex
the P gene utilizes multiple reading frames to make different accessory proteins, which are not essential for replication, but may aid in survival
C protein regulates viral RNA synthesis and may be a virulence factor
M = matrix protein
organizes and maintains virion structure
F = fusion protein
Fusion requires a neutral pH
G = glycoprotein, attachment bind to sialic acid on the cell surface and facilitate cell entryL = Large polymerasecatalytic subunit of RNA dependent RNA polymeraseSlide6
Replication and Transcription
Replication occurs in cytoplasm
The virus attaches to host surface receptors by G glycoproteinEnvelope fuses with plasma membrane and the ribonucleocapsid is released into the cytoplasm
viral RNA dependent RNA polymerase binds to the encapsidated genome at the leader region
The polymerase sequentially transcribes each genes by recognizing start and stop signals flanking viral genes
mRNAs are capped and polyadenylated by the L protein during synthesis
Replication starts when there is enough nucleoprotein to encapsidate the new virion
Matrix proteins line the cytoplasmic side of the plasma membrane
The ribonucleocapsid interacts with the matrix protein and buds off, obtaining its envelope from the plasma membraneSlide7
History
The virus was first discovered in 1999 in Malaysia
There have been 12 outbreaks since thenNamed after cityWhen the disease first appeared, people thought it was Japanese Encephalitis (JE)
Authorities spent 5 months vaccinating people against JE and killing mosquitoes, which was a waste of time
There were features that made it different from JE; for example, it infected adults more often then children
There was also a disease in pigs going around
Some believed it was related to Hendravirus
When the disease spread out of Ipoh, it was discovered the pigs were transmitting disease
After determining cause, 1,000,000 pigs were shot and buried, destroying half the country's pig market
Found that one of the original locations of the outbreak in pigs was near the forest where there were fruit bats
The farm was also surrounded by fruit trees, which offered food for bats
Pigs had been infected by bats, which caused a problem because pigs could be stopped from crossing borders, but bats could notSlide8
geographic distribution of Nipah virus overlaps with that of Pteropus genus of batsSlide9
Animal Pathology
Most pigs suffered from respiratory illness, while neurological symptoms were less common
Nipah outbreaks in pigs and other domestic animals (horses, goats, sheep, cats and dogs) were first reported during the initial Malaysian outbreak in 1999
Many pigs had no symptoms, but others developed acute feverish illness, labored breathing, and neurological symptoms such as trembling, twitching and muscle spasms
Generally, mortality was low except in young piglet
The incubation time for pigs 4-14 days
Pigs are infectious during incubation
Pigs spread disease by coughingSlide10
Natural Host
Predominately family Pteropodidae – fruit bats
10 genera and 23 species of bats in a large part of Asia and Africaaggregate with a density of more than 3,000 bats/m2, in population of up to several million individual animals
long distance flyers, with some species travelling up to 640 km during seasonal migration
Migratory bats have been shown to exchange novel viruses with non-migratory onesSlide11
Geographic distribution of seropositive bats is growingSlide12
Pathogenesis in Humans
Targets microvascular endothelial cells
At autopsy, microscopic evaluation revealed widespread vasculitis, endothelial cell destruction and focal perivascular necrosis in small vessels in the lung, heart, an kidney with the most severe damage observed in the vessels of the CNS
Microvasucular blood vessels of several organs exhibit syncytia or multinucleated giant endothelial cells, accompanied by vascular inflammation
Not a feature of other viral encephalides
Greatest viral load seen in the CNSSlide13
Symptoms
Incubation 4-18 days
The onset of symptoms ranged from 24 hours to 1 monthSymptomatic to nonsymptomatic ratio 3:1
Some symptoms similar to influenza
Fever
Muscle pain
Headache
Pneumonia and systemic infection in rare cases
Seizures, abnormal pupillary reflexes, absent doll's eye reflex, profound tachycardia, hypertension, tremor, dysarthria
Reduced level of consciousness
Inflammation of brain
Disorientation
Coma Encephalitis can be acute or late onsetAcute can result in relapseSlide14
Transmission
Bat-to-pig
Half-eaten fruit from batsPig-to-many animalsDirect contact or by aerosols
Pig-to-human
From direct contact with pigs
Bat-to-human
Humans eating fruit with bat saliva
Bat urine, feces, saliva
Human-to-human
Possibly through aerosol
Contamination with human excretions
Spread in healthcare settingsSlide15
Diagnosis
serum neutralizationenzyme-linked immunosorbent assay (ELISA)
polymerase chain reaction (PCR) assayimmunofluorescence assayvirus isolation by cell cultureSlide16
Epidemiology
There have been outbreaks almost every year since it was discovered
Is a problem in Bangladesh Slide17
Outbreaks in of the Nipah Virus have seasonal pattern in South Asia
Limited geographical distribution
Transmission in Bangladesh also showed human-to-human transmissionSlide18
Current Nipah Virus Outbreak
Bangladesh Bans Sale of Palm Sap After an Unusually Lethal Outbreak
By DONALD G. McNEIL Jr.
Published: March 21, 2011
Bangladesh is suffering an outbreak of deadly Nipah virus, causing the government to adopt an unusual prevention tactic: a ban on the sale of fresh palm sap.
The virus, carried by bats, was identified only in 1999. It causes dangerous brain inflammation in humans and is infectious. The Bangladeshi outbreak is unusually lethal
, killing 35 of the 40 people known to have been infected
.
The first known outbreak of Nipah virus was in Malaysia, where most victims raised or butchered pigs that were the source of infection. The pigs are believed to have rooted beneath bat colonies in trees, eating food contaminated by droppings. But
the Bangladesh outbreak happened without a swine vector
.
Bangladeshis
like drinking date palm sap, which is gathered “in a way similar to maple syrup collection,” said Dr. Jonathan H. Epstein, a veterinarian with the EcoHealth Alliance, which is helping Bangladesh track the virus.
Gatherers called gachis climb high into the trees, shave the bark with machetes and hang clay pots on the trunks to collect the sap at night. Large fruit bats called Indian flying foxes are attracted and lap up the running sap, sometimes fouling the pots with
their saliva, urine or feces.
Many people in the tropics leave palm sap to ferment into wine — and fermentation might kill the virus. But most Bangladeshis are Muslim, and do not drink alcohol, Dr. Epstein said.
The government health agency is also trying to persuade the gachis to put what he called “bamboo skirts” over the mouths of their collecting jars.
“The gachis like them,” he said. “They keep the stuff pure, so they can sell it for more.”Slide19
Prevention and Treatment
Pig farmers should quarantine suspected animals and avoid direct contact
The virus can easily be killed with bleach or detergents like sodium hypochoriteFruit should be washed and peeled before consumption
Boil date palm oil
Avoid contact with infected humans as it is possible to be infected by aerosols
There is no vaccine or treatment for Nipah Virus
Treatment is mostly focused on managing fever and the neurological symptoms
Ribavarin is used to treat symptoms such as nausea, vomiting, and convulsions
Vaccine is being developed
Recombinant sub-unit vaccine formulation protects against lethal Nipah virus in catsSlide20
Potential For Bioterrorism
Cause fear and panicNo effective treatment
Economic lossCan spread through aerosols or foodSlide21
References
Fong, I. W., and Ken Alibek.
New and Evolving Infections of the 21st Century. New York, NY: Springer, 2007. 279-93. Hsu, V. "Nipah and Hendra Viruses." Perspectives in Medical Virology 16 (2006): 179-99.
Knipe, David M. "Fields Virology by David M Knipe and Peter M Howley | Free EBooks Download - EBOOKEE!" Web. Apr. 2011.
Strauss, James H., and Ellen G. Strauss. Viruses and Human Disease. San Diego: Academic, 2002. 147-55.
Tabor, Edward. Emerging Viruses in Human Populations. Amsterdam: Elsevier, 2007. 179-94.
"ViralZone: Henipavirus." ExPASy Proteomics Server. Web. Apr. 2011. <http://expasy.org/viralzone/all_by_species/85.html>.
"WHO | Nipah Virus (NiV) Infection." Web. Apr. 2011. <http://www.who.int/csr/disease/nipah/en/index.html>.
"WHO | Nipah Virus." Web. Apr. 2011. <http://www.who.int/mediacentre/factsheets/fs262/en/>.
Wolf, Mike C., Oscar A. Negrete, and Benhur Lee. "Pathobiology of Henipavirus Entry: Insights into Therapeutic Strategies." Future Virology 2.3 (2007): 267-82. Slide22
Any Questions?