3. Introduction
• Nipah virus infection is a newly emerging zoonosis that causes severe
disease in both animals and humans. The natural host of the virus are
fruit bats of the Pteropodidae Family, Pteropus genus.
• Nipah was first identified during an outbreak of disease that took place in
Kampung Sungai Nipah, Malaysia in 1998. On this occasion, pigs were
the intermediate hosts. However, in subsequent Nipah virus outbreaks,
there were no intermediate hosts. In Bangladesh in 2004, humans became
infected with Nipah virus as a result of consuming date palm sap that had
been contaminated by infected fruit bats. Human-to-human transmission
has also been documented, including in a hospital setting in India.
6. structure
• Nipah virus is a highly pathogenic emergent paramyxovirus causing deadly
encephalitis in humans. Its replication requires a constant supply of
unassembled nucleoprotein (N(0)) in complex with its viral chaperone, the
phosphoprotein (P). To elucidate the chaperone function of P, we
reconstituted nipah virus the N(0)-P core complex and determined its crystal
structure. The binding of the N-terminal region of P blocks the
polymerization of N by interfering with subdomain exchange between N
protomers and keeps N(0) in an open conformation, ready to grasp an RNA
molecule. We found that a peptide derived from the N-binding region of P
protects cells against viral infection and demonstrated by structure-based
mutagenesis that this peptide acts by inhibiting N(0)-P formation.
7. Genome and proteins
• Single stranded negative sense RNA, 18246 bp (Malaysian isolate) and 18252 bp
(bngladesh isolate)
• Genome has six transcriptional unit that six structural proteins. They are nucleocapsid
(N), phosphoprotein (P), matrix protein (M), fusion protein (F), glycoprotein (G) and
polymerase (L)
• Protein associated with genome: large (L) protein, phospoprotein (P)
• Viral proteins: fusion protein (F) and attachment glycoprotein protein (G)
• Phosphoprotein (P): it role as a polymerase cofactor, enhancing polymerase
processivity and allowing the encapsidation of the newly synthesized viral genomes
and antigenomes.
• Phosphorotein of Nipah virus has an additional role in immunosuppression: blocking
interferon signaling by binding host STAT-1.
9. Predisposing FACTORS
• Nipah virus infection in humans causes a range of clinical presentations, from
asymptomatic infection (subclinical) to acute respiratory infection and fatal
encephalitis.
• The case fatality rate is estimated at 40% to 75%. This rate can vary by outbreak
depending on local capabilities for epidemiological surveillance and clinical
management.
• Nipah virus can be transmitted to humans from animals (such as bats or pigs), or
contaminated foods and can also be transmitted directly from human-to-human.
• Fruit bats of the Pteropodidae family are the natural host of Nipah virus.
• There is no treatment or vaccine available for either people or animals. The primary
treatment for humans is supportive care.
• The 2018 review of the WHO list of Blueprint priority diseases indicates that there is
an urgent need for accelerated research and development for the Nipah virus.
10. • The symptoms start to appear within 3–14 days after exposure. Initial
symptoms are fever, headache, drowsiness followed by disorientation
and mental confusion. These symptoms can progress into coma as fast as
in 24–48 hours. Encephalitis, inflammation of the brain, is a potentially
fatal complication of nipah virus infection. Respiratory illness can also
be present during the early part of the illness. Nipah-case patients who
had breathing difficulty are more likely than those without respiratory
illness to transmit the virus. The disease is suspected in symptomatic
individuals in the context of an epidemic outbreak.
symptoms
11. • The risk of exposure is high for hospital workers and caretakers of
those infected with the virus. In Malaysia and Singapore, Nipah virus
infection occurred in those with close contact to infected pigs. In
Bangladesh and India, the disease has been linked to consumption of
raw date palm sap (toddy) and contact with bats.
risk
12. • Laboratory diagnosis of Nipah virus infection is made using reverse
transcriptase polymerase chain reaction (RT-PCR) from throat swabs,
cerebrospinal fluid, urine and blood analysis during acute and
convalescent stages of the disease. IgG and IgM antibody detection can
be done after recovery to confirm Nipah virus infection.
Immunohistochemistry on tissues collected during autopsy also
confirms the disease. Viral RNA can be isolated from the saliva of
infected persons.
diagnosis
13. • Prevention of Nipah virus infection is important since there is no effective
treatment for the disease. The infection can be prevented by avoiding
exposure to bats in endemic areas and sick pigs. Drinking of raw palm sap
(palm toddy) contaminated by bat excrete, eating of fruits partially
consumed by bats and using water from wells infested by bats should be
avoided. Bats are known to drink toddy that is collected in open containers,
and occasionally urinate in it, which makes it contaminated with the virus.
Surveillance and awareness are important for preventing future outbreaks.
The association of this disease within reproductive cycle of bats is not well
studied. Standard infection control practices should be enforced to prevent
nosocomial infections. A subunit vaccine using the Hendra G protein was
found to produce cross-protective antibodies against henipavirus and
nipavirus has been used in monkeys to protect against Hendra virus,
although its potential for use in humans has not been studied
prevention
14. • Currently there is no effective treatment for Nipah virus infection. The treatment
is limited to supportive care. It is important to practice standard infection control
practices and proper barrier nursing techniques to avoid the transmission of the
infection from person to person. All suspected cases of Nipah virus infection
should be isolated and given intensive supportive care. Ribavirin has been shown
effective in in vitro tests, but has not yet been proven effective in humans.
Passive immunization using a human monoclonal antibody that targets the Nipah
G glycoprotein has been evaluated in the ferret model as post-exposure
prophylaxis. The anti-malarial drug chloroquine was shown to block the critical
functions needed for maturation of Nipah virus, although no clinical benefit has
yet been observed. m102.4, a human monoclonal antibody, has been used in
people on a compassionate use basis in Australia and was in pre-clinical
development in 2013.
treatment
15. • Nipah virus outbreaks have been reported in Malaysia, Singapore,
Bangladesh and India. The highest mortality due to Nipah virus infection
has occurred in Bangladesh. In Bangladesh, the outbreaks are typically
seen in winter season. Nipah virus first appeared in Malaysia in 1998 in
peninsular Malaysia in pigs and pig farmers. By mid-1999, more than 265
human cases of encephalitis, including 105 deaths, had been reported in
Malaysia, and 11 cases of either encephalitis or respiratory illness with
one fatality were reported in Singapore. In 2001, Nipah virus was
reported from Meherpur District, Bangladesh and Siliguri, India. The
outbreak again appeared in 2003, 2004 and 2005 in Naogaon District,
Manikganj District, Rajbari District, Faridpur District and Tangail
District. In Bangladesh, there were also outbreaks in subsequent years.
outbreak
16. • In May 2018, an outbreak was reported in the Kozhikode district of
Kerala, India. Eighteen deaths have been recorded, including one
healthcare worker. Those who have died are mainly from the districts
of Kozhikode and Malappuram, including a 31-year-old nurse, who
was treating patients infected with the virus. As of 31 May 2018, about
16 people are being quarantined because they had contact with the sick.
This incident has caused panic throughout the state. Blood samples
have been sent for testing. India is seeking help from Australia by
importing monoclonal antibodies to a Nipah virus antigen. However,
the treatment is experimental and has not yet been tested on humans.
India is also importing ribavirin tablets from Malaysia.
outbreak