P R O F. K I S H O R E K U M A R .

COLLEGE OF NURSING
EMS MEMORIAL CO OPERATIVE HOSPITAL AND RESEACH CENTRE
PERINTHALMANNA

NIPAH - NiV Infections

 Nipah Virus Infection

Nipah Virus Infection (NiV) is a newly

emerging infectious zoonosis, of public
health importance, that causes severe
diseases in both animals and humans.

No standard case definition of Nipah disease.

WHO list of Blueprint priority diseases

 World Health Organization’s
Blueprint list of Priority Diseases
Diseases pose major public health risks and need
further R &D, including surveillance and diagnostics.
1. Crimean-Congo haemorrhagic fever (CCHF)
2. Ebola virus disease and Marburg virus disease
3. Lassa fever
4. Middle East Respiratory Syndrome–Corona Virus (MERS-CoV)
and Severe Acute Respiratory Syndrome (SARS)
1. Nipah and henipa viral diseases
2. Rift Valley fever (RVF)
3. Zika
4. Disease X
(a pathogen currently unknown to cause human disease,
explicitly seeking R&D preparedness)
 Past Outbreaks
• Recognized as an outbreak among pig farmers in
Malaysia. No new outbreaks have been reported in
Malaysia and Singapore since 1999. Pigs were the
intermediate hosts.
• First recognized in Bangladesh in 2001 with nearly
annual outbreaks since then.
• In Bangladesh in 2004, humans became infected
with NiV as a result of consuming date palm sap,
contaminated by infected fruit bats.
• NiV is identified periodically in eastern India, with
Human to Human transmission in hospital settings.
 Nipah virus - NiV
Nipah virus, is an RNA virus first identified as a
Zoonotic pathogen, after an outbreak involving Severe
Respiratory Illness in pigs and Encephalitic diseases in
humans in Malaysia and Singapore, in 1998-99.
Named after the Malaysian village -
Kampung Sungai Nipah where it was discovered.
First isolated by Chua et al. in 1999
genus : Henipavirus
(Nipah virus along with closely related Hendra virus)
(Sub)family : Paramyxovirinae.
 Reservoir of NiV / Natural Host
Fruit bats of genus Pteropus
Family: Pteropodidae
Indian host: Pteropus giganteus

• Serologic evidence for NiV has been found in several

other bat species. Genetic heterogeneity in human
population suggests multiple introductions of NiV from
different colonies of fruit bats.
• Since bats are migratory and other regions may be at
risk for NiV infection.
No apparent disease in fruit bats - Symptomless Carriers.
 Pteropus giganteus
Indian Flying Fox / Greater Indian Fruit Bat
 NiV in Domestic Animals
• Nipah can infect domestic animals such as Horses,
Goats, Sheep, Cats and Dogs. But their role in
transmitting infection to humans is not determined.
• Pigs and Horses are potential Multiplier Host/
Intermediate Host for NiV.
• An infected pig can exhibit no symptoms, or acute
feverish illness, labored breathing, and neurological
symptoms such as trembling, twitching and muscle
spasms.
• Nipah should be suspected, if pigs have an unusual
barking cough (barking pig syndrome),
or if human cases of encephalitis are present.
 Mode of Transmission
NiV is a Zoonotic virus
(a virus transmitted to humans from animals)
• As the natural habitats of bats has been lost /
destroyed by human activity, bats get stressed and
hungry, and their immune system gets weaker, their
virus load went up leading to virus spill out in their
urine, saliva, semen and excreta.
• Virus shedding may be associated with the Stressful
Physiological Conditions, Pregnancy and Seasons.

SEASONALITY:
Winter to Spring (December - May)
Outbreaks of Nipah in South Asia
have a Strong Seasonal Pattern and
a Limited Geographical Range.
 Mode of Transmission - Zoonotic
• Consumption of fruits or fruit products contaminated
with urine or saliva from infected fruit bats is the most
likely source of infection in India.
• Drinking fresh date palm sap, contaminated by fruit bats
esp during the winter season, lead to indirect
transmission of NiV. eg: Bangladesh Outbreak
• Nipah virus is highly contagious in pigs, spread by
coughing, even during incubation period (4 - 14 days).
Predominant Mode of Transmission is via respiratory
droplets, Direct contact with throat or nasal secretions
from the pigs, or contact with the tissue of a sick animal.
eg: 90% of Malaysian outbreak
 Mode of Transmission - Human to Human
• Human to Human Transmission of NiV through close
contact with people's secretions and excretions has
been reported among family and care givers of NiV
patients or their visitors. (about 50%) .
• Most cases of Secondary Transmission have involved
family and friends of infected NiV.
• Nosocomial transmission of the virus was also
reported among hospital staff through contact with
infected secretions, excretions, blood or tissues.
eg: Siliguri outbreak
NIPAH is not an airborne disease
 NiV - Epidemiology
Incubation period: 4 to 21 days.
interval from infection to the onset of symptoms
a maximum delay of 2 months between exposure and
onset of illness has also been observed.
Incidence Rate:
Status of NiV infection in many countries is not known.
NiV has infected 477+ people and killed 252+ since 1998.
No evidence of increased incidence / severity among
pregnant women, infants or immuno-compromised.
Duration of Illness:
Median duration from onset to death was 6 days
(ranging from 1 to 47 days)
 NiV – Morbidity / Mortality
Case Fatality Rate: 40%-75% (upto 100% in certain outbreaks)
YEAR LOCALITY MORBIDITY MORTALITY CASE FATALITY
RATE
1998- MALAYSIA 265 105 40 %
1999 SINGAPORE 11 1 09 %
SILIGURI – INDIA 66 45 68 %
2001
BANGLADESH 13 09 69 %
2003 -05 BANGLADESH 89 68 76 %
BANGLADESH 15 08 53 %
2007
NADIA - INDIA 05 05 100 %
2008 BANGLADESH 13 07 54 %
2009 - 12 BANGLADESH 76 65 86 %
2018 KERALA 18 16 89 %
As on 24th May 2018
 Nipah - Viral Pathology
NiV is an enveloped, negative-sense, single-stranded
RNA virus. The viral G protein attaches to the host cell
Ephrin B2 and/or B3 receptors, to initiate host viral entry.
Pathological features:
• Disseminated, multi-organ Vasculopathy
Endothelial infection / ulceration
Vasculitis, Vasculitis-induced thrombosis / occlusion
Parenchymal ischemia/microinfarction
• Parenchymal cell infections
in the CNS, lung, kidney and other major organs.
Unique dual pathogenic mechanism of
Vasculitis-induced Microinfarction & Neuronal Infections
causes severe tissue damage in the CNS.
 Range of Clinical presentations - NiV
Subclinical - Asymptomatic Infections
In general, severe clinical features manifest as an acute
Encephalitic Syndrome or less frequently as a
Pulmonary Syndrome.
Symptoms in humans are similar to influenza such as
Fever, Headaches, Myalgia, Vomiting, Sore Throat and
Acute Respiratory Infections.
Pulmonary Syndrome:
Cough, Atypical Pneumonia, Severe Respiratory
Problems, Acute Respiratory Distress Syndrome and
Abnormal Chest X-ray findings.
 Neurological Symptoms - NiV
Altered Mental Status, Unconsciousness, Severe
Weakness, Areflexia / Hyporeflexia with Hypotonia,
consistent with a high prevalence of Acute Encephalitis.
Dizziness, drowsiness, altered consciousness, Pinpoint
Pupils with variable reactivity, Abnormal Doll’s Eye
Reflex etc indicate Acute Encephalitis.
Fatal Encephalitis and Seizures in severe cases may
progress to Disorientation or Coma within 24 - 48 hrs.
Encephalitis may present as Acute or Late Onset.
Meningism, Neuropsychiatric sequelae,
Cerebellar signs, gait / movement disorders, Nystagmus,
Tachycardia, Hypertension etc. also may be present.
 Prognosis - NiV
Those recovered from an acute episode may have relapses
Those who survive acute encephalitis make a full recovery.
Long term residual neurological consequences such as
Seizure Disorder and Personality Changes have been
reported in 20% of survivors.
Most intriguing complication of Nipah is Relapsing
Encephalitis, or Delayed Onset Encephalitis which may
occur weeks to years after a symptomatic or even
asymptomatic NiV infection.
Older Patients, especially those having Diabetes Mellitus
and those with Severe Brain-stem Involvement, carried a
poorer prognosis than other Nipah patients.
 Suspect Nipah Case
A Person from an area / locality affected by
Nipah virus disease outbreak , who has:
Acute Fever onset of altered mental status or seizure
and/or
Acute Fever with severe headache
and/or
Acute Fever with Cough or shortness of breath
Additionally A suspect case can be any person with Acute fever
& one or more of the following.
Neurological signs such as confusion, unconsciousness,
neck stiffness, focal weakness/paralysis, vomiting.
or respiratory symptoms or
physical contact, sharing of ADL
 PROBABLE NIPAH CASE:
Case definitions:
A Suspect case who resided in same locality of
suspect/confirmed case of Nipah during an outbreak
and
who Died before complete diagnostic specimens could
be collected.
OR
A Suspect case who came in direct contact with a
confirmed case during an outbreak
and
who Died before complete diagnostic specimens could
be collected.
 NIPAH - CONTACT
A person who came in contact with a confirmed or
probable Nipah case in at least one of the following
ways:
• Was admitted simultaneously in a hospital ward
• Shared room with a suspect/confirmed case of Nipah
• Direct close contact with the suspect/confirmed Nipah
case during the illness including during transportation.
• Direct close contact with the deceased/ suspect /
confirmed Nipah case at a funeral or burial rituals.
• Touched the blood or body fluids (saliva, urine, vomitus
etc.) or clothes/linens of suspect/confirmed Nipah case.
contacts need to be followed up for appearance of
symptoms for the longest incubation period (21 days)
 CONFIRMED NIPAH CASE:
Case definitions:
A Suspected case who has laboratory confirmation of
Nipah virus infection either by
Isolation of Nipah virus or
identification of Nipah Virus
by PCR from
Respiratory secretions,
Urine, or
CSF-Cerebro-Spinal Fluid.

Or any case positive for Nipah IgM antibody

 Laboratory Diagnosis / Investigations
Confirmatory Tests:
 Real Time Polymerase Chain Reaction (RT-PCR) from
bodily fluids
 Enzyme-linked Immunosorbent Assay (ELISA) for
detection of Viral Antigen and Antibody responses.
---------------------
Luminex assays (binding or blocking/inhibition assays)
formats for detection of NiV-specific antibodies
Serology: Serum Neutralization Test
Monoclonal antibody-based Immunohisto-Chemistry
Histopathology
Virus Isolation by cell culture
Rapid test: (point-of-care) test: As of today, no such test available
 Sample collection
Recommended Sample: Within 4 days of Onset
oThroat swab in viral transport medium
oUrine 5 ml in universal sterile container
oBlood in red vacutainer (5ml)
oCSF (1-2 ml) in sterile container
Clinical Sample Quality, Quantity, Type, Timing of Collection and
Time necessary to Transfer Samples to lab affect accuracy of result.
NiV is classified as a Bio-security level (BSL) 4 agent and needs
BSL-2 facilities to safely study NiV without a risk of it
‘escaping and infecting’ more people.
Universal /Standard Droplet/ Bio-Continment precautions
 NiV - Diagnosis
Diagnosed together with clinical history and laboratory
confirmation during acute and convalescent phase.
Designated NiV testing centre for Kerala: MCVR – Manipal
Sample Transport:
Tripple Pack Container under Cold Chain (20C- 80C),
Along with complete casesheet info
under prior intimation.
Initial signs and symptoms are non-specific, and diagnosis
is often not suspected. This can hinder accurate
diagnosis and outbreak detection as well as institution of
effective and timely infection control/ outbreak response
activities.
 Treatment of NiV
Mostly focused on managing fever.
Severely ill individuals need to be hospitalized.
Ventilators and Oxygen supplementation may be required
Transfer to ICU and Intensive supportive care to treat
severe respiratory and neurologic complications is usual.
There is no effective treatment for Nipah virus disease
Many drugs are not effective or with no proven efficacy
 Drugs ?????
• Chloroquine not effective
• Convalescent plasma ?
• immunomodulation ?
• Falvipiravir from Japan
• monoclonal antibodies m102.4, ? From
australia
• ribavarin may alleviate the symptoms of
nausea, vomiting, and convulsions.
• Ribavirin is a guanosine analogue and broad
 Prevention
• Healthcare workers caring for patients with
suspected or confirmed NiV should implement
Standard Precautions when caring for patients
and handling specimens from them.
• The main strategy is to prevent NiV in humans.
Establishing appropriate surveillance
• systems will be necessary so that NiV
outbreaks can be detected quickly and
• appropriate control measures initiated.
 Prevention
• There is no treatment or vaccine available for
either people or animals.
• There is currently a licensed horse vaccine for
HeV.
• A vaccine is being developed. A recombinant
sub-unit vaccine formulation protects against
lethal Nipah virus challenge in cats.21 ALVAC
Canarypox vectored Nipah F and G vaccine
appears to be a promising vaccine for swine
and has potential as a vaccine for humans.
 Standard precautions
• Standard precautions are meant to reduce the risk of
transmission of bloodborne and other pathogens from
both recognized and unrecognized sources. They are the
basic level of infection control precautions which are to
be used, as a minimum, in the care of all patients.
• Promotion of a safety climate is a cornerstone of
prevention of transmission of pathogens in health care.
Standard precautions should be the minimum level of
precautions used when providing care for all patients.
Risk assessment is critical. Assess all health-care activities
to determine the personal protection that is indicated.
Implement source control measures for all persons with
respiratory symptoms through promotion of respiratory
hygiene and cough etiquette.
 Standard precautions
• 1 Hand hygiene
• 2. Gloves
• 3. Facial protection (eyes, nose, and mouth)
• 4. Gown
• 5. Prevention of needle stick and injuries from other
sharp instruments
• 6. Respiratory hygiene and cough etiquette Persons with
respiratory symptoms should apply source control
measures:
• 7. Environmental cleaning
• 8. Linens
• 9. Waste disposal
 Hand hygiene
• major component of standard precautions and one of the most effective methods to
prevent transmission of pathogens associated with health care.
• Hand washing (40–60 sec): wet hands and apply soap; rub all surfaces; rinse hands and
dry thoroughly with a single use towel; use towel to turn off faucet.
• Hand rubbing (20–30 sec): apply enough product to cover all areas of the hands; rub
hands until dry.
• Summary indications:
Before and after any direct patient contact and between patients, whether or not gloves are
worn. Immediately after gloves are removed. Before handling an invasive device.
After touching blood, body fluids, secretions, excretions, non-intact skin, and
contaminated items, even if gloves are worn. During patient care, when moving from a
contaminated to a clean body site of the patient. After contact with inanimate objects in
the immediate vicinity of the patient.
Perform hand hygiene by means of hand rubbing or hand washing (see detailed indications in
table). Perform hand washing with soap and water if hands are visibly soiled, or
exposure to spore-forming organisms is proven or strongly suspected, or after using the
restroom. Otherwise, if resources permit, perform hand rubbing with an alcohol-based
preparation. Ensure availability of hand-washing facilities with clean running water.
Ensure availability of hand hygiene products (clean water, soap, single use clean towels,
alcohol-based hand rub). Alcohol-based hand rubs should ideally be available at the point
of care.
 Gloves
• Wear when touching blood, body fluids, secretions,
excretions, mucous membranes, nonintact skin. Change
between tasks and procedures on the same patient after
contact with potentially infectious material. Remove
after use, before touching non-contaminated items and
surfaces, and before going to another patient. Perform
hand hygiene immediately after removal.
Facial protection (eyes, nose, and mouth)
• Wear (1) a surgical or procedure mask and eye
protection (eye visor, goggles) or (2) a face shield to
protect mucous membranes of the eyes, nose, and mouth
during activities that are likely to generate splashes or
sprays of blood, body fluids, secretions, and excretions.
 Gown
• Wear to protect skin and prevent soiling of clothing
during activities that are likely to generate splashes or
sprays of blood, body fluids, secretions, or excretions.
Remove soiled gown as soon as possible, and perform
hand hygiene.
 Prevention of needle stick and injuries
from other sharp instruments
• Use care when: Handling needles, scalpels, and other
sharp instruments or devices. Cleaning used
instruments. Disposing of used needles and other sharp
instruments.
 Respiratory hygiene and cough etiquette
• Persons with respiratory symptoms should apply source
control measures: Cover their nose and mouth when
coughing/sneezing with tissue or mask, dispose of used
tissues and masks, and perform hand hygiene after
contact with respiratory secretions. Health-care facilities
should: Place acute febrile respiratory symptomatic
patients at least 1 metre (3 feet) away from others in
common waiting areas, if possible. Post visual alerts at
the entrance to health-care facilities instructing persons
with respiratory symptoms to practise respiratory
hygiene/cough etiquette. Consider making hand
hygiene resources, tissues and masks available in
common areas and areas used for the evaluation of
patients with respiratory illnesses.
 Environmental cleaning
• Use adequate procedures for the routine cleaning and
disinfection of environmental and other frequently
touched surfaces.
 8. Linens
• Handle, transport, and process used linen in a manner
which: Prevents skin and mucous membrane exposures
and contamination of clothing. Avoids transfer of
pathogens to other patients and or the environment.
 9. Waste disposal
• Ensure safe waste management. Treat waste
contaminated with blood, body fluids, secretions and
excretions as clinical waste, in accordance with local
regulations. Human tissues and laboratory waste that is
directly associated with specimen processing should also
be treated as clinical waste. Discard single use items
properly.
• environmental decontamination
 10. Patient care equipment
Handle equipment soiled with blood, body fluids,
secretions, and excretions in a manner that prevents skin
and mucous membrane exposures, contamination of
clothing, and transfer of pathogens to other patients or
the environment. Clean, disinfect, and reprocess
reusable equipment appropriately before use with
another patient.
 control
Controlling Nipah virus in domestic animals
• Currently, there are no vaccines available against Nipah virus.
Routine and thorough cleaning and disinfection of pig farms (with
appropriate detergents) may be effective in preventing infection.
• If an outbreak is suspected, the animal premises should be
quarantined immediately. Culling of infected animals – with close
supervision of burial or incineration of carcasses – may be
necessary to reduce the risk of transmission to people. Restricting
or banning the movement of animals from infected farms to
other areas can reduce the spread of the disease.
• As Nipah virus outbreaks in domestic animals have preceded
human cases, establishing an animal health surveillance system,
using a One Health approach, to detect new cases is essential in
providing early warning for veterinary and human public health
authorities.
 control
Reducing the risk of infection in people
In the absence of a licensed vaccine, the only way to reduce infection
in people is by raising awareness of the risk factors and educating
people about the measures they can take to reduce exposure to
and decrease infection from NiV.
• Reducing the risk of bat-to-human transmission:
decreasing bat access to date palm sap and to other fresh food
products.
Keeping bats away from sap collection sites- protective coverings (e.g.,
bamboo sap skirts)
Freshly collected date palm juice should be boiled and fruits should be
thoroughly washed and peeled before consumption.
• Reducing the risk of animal-to-human transmission:
• Reducing the risk of human-to-human transmission:
 control
Reducing the risk of infection in people
• Reducing the risk of animal-to-human transmission:
Gloves and other protective clothing should be worn while handling
sick animals or their tissues, and during slaughtering and culling
procedures. As much as possible, people should avoid being in
contact with infected pigs.
Veterinary surveillance of NiV encephalitis in pigs
improving biosecurity on farms,
• Reducing the risk of human-to-human transmission:
Close unprotected physical contact with Nipah virus-infected people
should be avoided. Regular hand washing should be carried out
after caring for or visiting sick people.
Specific measures are also taken in the hospital setting to avoid
further spread of the disease, including isolation of patients
 control
Controlling infection in health-care settings
• Health-care workers caring for patients with suspected or
confirmed NiV infection, or handling specimens from them, should
implement standard infection control precautions for all patients at
all times
• As human-to-human transmission in particular nosocomial
transmission have been reported, contact and droplet precautions
should be used in addition to standard precautions.
• Samples taken from people and animals with suspected NiV
infection should be handled by trained staff working in suitably
equipped laboratories.
• Public have been asked to follow safe hygiene practices, not to
consume fruits/vegetables partly eaten by birds/animals and steps
to be taken while going near the infected persons/areas.
• Hospital-based surveillance
 Burial / death
• handling deceased bodies
• embracing the body of a loved one soon after
their death, or through ritual preparation of a
corpse for religious burial
 Outbreak of Nipah virus encephalitis in Kerala
• On 19 May 2018, a Nipah virus disease (NiV) outbreak was
reported from Kozhikode district of Kerala, India. This is the first
NiV outbreak in South India. As of 28 May, there are 14 deaths, 16
confirmed cases and 12 suspected cases. The two affected
districts are Kozhikode and Mallapuram. A multi-disciplinary team
led by the Indian Government’s National Centre for Disease
Control (NCDC) is in Kerala in response to the outbreak. WHO is
providing technical support to the Government of India as
needed. WHO does not recommend the application of any travel
or trade restrictions or entry screening related to NiV outbreak.
• the Central High-level Team is of the view that the Nipah virus
disease is not a major outbreak and is only a local occurrence.
• The efforts taken so far for containment of the disease have
been fruitful as the disease has not spread to new areas. The
contact tracing strategy adopted has also been successful. It
has been found that all the reported cases including the
suspected cases had direct or indirect contact with the first
casualty/his family prior to contracting the disease
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