Introduction to

Nipah virus
disease
Heath Emergencies programme
Viral Haemorrhagic Fever team

Photo credits:
Nazmun Nahar/ ICDDRB
byrdyak / Freepik.com

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 Learning objectives

• Describe the signs, symptoms, and

transmission routes of Nipah virus
disease
• List prevention and control measures for
Nipah virus disease.
• Describe areas where Nipah virus
disease is a public health concern.

Image courtesy Prof. CT Tan

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 Nipah virus disease
• Nipah virus disease is caused by Nipah virus, an RNA virus closely
related to Hendra virus, both viruses belong to Family Paramyxoviridae,
Genus Henipavirus.
• Fruit bats of the Pteropodidae family are the natural host of Nipah
virus.
• Nipah virus disease is a zoonotic disease.
• Nipah virus can cause large outbreaks in domestic animals and trigger
important economic losses.
• Nipah virus can be transmitted to humans by direct contact with
animals (such as bats or pigs) or through contaminated foods or
through human-to-human transmission.
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 Nipah virus disease

• Nipah virus infection in humans causes a range of clinical

presentations, from subclinical infection to acute respiratory infection
and fatal encephalitis. The case fatality rate of Nipah virus infection is
estimated at 40–75% but can vary by outbreak depending on
surveillance and clinical management in affected areas.

• There is no treatment or vaccine available for either people or

animals. The primary treatment for humans is supportive care.

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 Nipah virus: natural reservoir
Bats of Pteropodidae family, Pteropus genus.
• Asymptomatic Henipavirus carriers
• Shedding virus in saliva, urine, birthing fluid and products
• Distribution overlaps with Nipah outbreak sites
• Evidence of infection in Pteropus bats from Australia,
Bangladesh, Cambodia, India, Indonesia, Malaysia,
Philippines, Thailand, Timor Leste, Papua New Guinea, PR
China.
• In Africa serological or molecular assays revealed
Henipaviruses infections in Cameroon, Central African
Republic, Democratic Republic of Congo, Gabon, Ghana,
Kenya, Malawi, Madagascar, Nigeria, Republic of Congo,
Rwanda, Sao Tome Principe, South Africa, Tanzania, Uganda Photo credits:

and Zambia. byrdyak / Freepik.com

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 Geographic distribution of Nipah and Hendra
virus diseases outbreaks, 1997-2021.

Map available at: https://www.who.int/images/default-source/health-topics/nipah-virus/geocraphical-distribution-nipah-2008.png?sfvrsn=b32e0557_2

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 Past Nipah virus disease outbreaks
• 1998-1999: first outbreak of fatal encephalitis among pig farmers in
Kampung Sungai Nipah, Perak State, in Peninsular Malaysia with
40% fatality. Outbreak costs estimated to be 625 million USD.
• 1999: small outbreak in Singapore following importation of sick pigs
from Malaysia
• Since 2001 to 2021, Nipah virus disease have been reported :
• in Bangladesh (in Northern and Central districts, every year except
for 2002, 2006, 2016 and 2021)
• in India (West Bengal in 2001 and 2007; and Kerala in 2018, 2019
and 2021)
• in the Philippines (Mindanao in 2014)
• From 1998 to 2021, around 674 human cases of Nipah virus disease
were reported including 400 deaths.
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 Burden of Nipah virus disease

High case fatality ratio

among confirmed cases
3 billion people at risk (45-70%)
Southeast
Asia
and Africa

Nipah virus disease outbreaks can trigger heavy socio-

economic losses, especially for farmers
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 Nipah virus disease transmission
1. Virus reservoir:
fruit bats
The virus maintains itself in
fruit bats. Bats spread the
virus during migration.
2. Epizootics and Palm sap
• Infected fruit bats enter in direct or
indirect contact with other animals or
date palm sap and pass on the
infection.
• Could cause large-scale epidemics in
pig farms (Malaysia 1999).
• Palm sap consumption (Bangladesh)
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3. Primary human transmission
Humans are infected either through:
• handling infected dead or sick
domestic animals;
• Consumption of date palm sap
• or through direct contact with
infected bats (rare event).
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10% Health
Care
Workers
4. Secondary human transmission
• Secondary human-to-human
transmission occurs through direct
contact with the blood, secretions, or
other body fluids of infected persons.
• High transmission risk when
providing direct patient care.
99
 Nipah virus: Transmission
(a) Fruits or fruit products (e.g., raw date palm juice)
• date palm sap contaminated with urine from infected fruit bats
• fruit contaminated with saliva from infected fruit bats
• source of primary infection in Bangladesh; seasonal (Jan to May)
(b) Pig-to-human or domestic animal to human transmission
• initial outbreaks only (Malaysia &Singapore)
• direct contact with ill, dying or dead pig
• exposure to contaminated tissues and body fluids
• droplets respiratory particles or urinary secretions
• occasional transmission from other domestic animals (goat, sheep or cow)
(c) Human-to-human transmission
• direct contact with ill patients (caregivers)
• exposure to body fluids (secretions, excretions)
• in hospital setting.

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 Clinical features of Nipah virus disease in
humans
• Incubation period: 4 – 45 days
• Infected people initially develops symptoms
including fever, headaches, myalgia (muscle
pain), vomiting and sore throat,
• Neurological manifestations: Dizziness,
drowsiness, altered consciousness, focal
neurological signs of acute encephalitis,
seizure and coma
• Respiratory manifestations
• Atypical pneumonia + fever, cough, headache
• Acute respiratory distress
• Asymptomatic infection has been reported
Image courtesy of International Centre for Diarrhoeal
Disease Research, Bangladesh (ICDDRB)

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 Nipah virus disease in human: sequelae

• 80% who survived acute encephalitis made full

recovery
• 20% with residual neurological sequelae after NiV
encephalitis : persistent convulsions, behavioural
changes
• Small proportion of cases develops relapse or
delayed encephalitis with a 18% mortality rate

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 Nipah virus disease: Diagnosis
• Symptoms are non-specific; clinical diagnosis may be
difficult.
• Differential diagnosis: Japanese Encephalitis, dengue,
influenza, Herpes Simplex Encephalitis, Neisseria
meningitidis, Streptococcus pneumoniae, and
Haemophilus influenzae, etc.
• Patient history / case investigation is essential and
should include:
• Consumption of raw date palm sap / raw fruits
• Exposure to sick domestic animals (pigs, horses, goat,
sheep or cow)
• or stay in area/village where Nipah virus outbreak is
reported

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 Laboratory diagnosis of Nipah virus

Definitive diagnosis requires testing:

• reverse transcriptase polymerase chain reaction
(RT-PCR) assay
• IgG and IgM antibodies enzyme-linked
immunosorbent assay (ELISA)
• Seroneutralization (plaque reduction neutralization
test (PRNT))
• virus isolation by cell culture.

Handling and processing specimen requires suitably equipped laboratories under

maximum biological containment conditions and staff collecting samples should
be trained.
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 Nipah virus disease: clinical management

• Early, aggressive, intensive care support:

monitor fluid and electrolyte balance,
oxygenation, careful rehydration.
• Supportive care for acute respiratory
disease syndrome and encephalitis.
• Supportive drug therapy including
painkillers, anti-convulsant, treatment for
cerebral edema, +/- antibiotics and/or
Nipah virus disease antimalarial drugs if clinically indicated.

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 Key components of Nipah outbreak control

Identify early source of

transmission (fruit
consumption, animals) Care for sick people
National
leadership

Reduce the risk of transmission from source of transmission

and through care associated activities

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 General strategy to control Nipah
outbreaks
• Conduct social and cultural assessments
• Triage in/out
• Engage with key influencers: women and/or
youth associations, traditional healers, local • Barrier nursing
authorities, religious & opinion leaders • Infection control
• Patient management
• Formal and informal Behavioural and
Clinical case • Clinical trials
communication social Psycho-social
support management • Ethics committee
• Address community concerns interventions
Ethical
Media Coordination aspects

• Security, police Epidemiological • Case investigation

• Lodging, food Logistics investigation, • Active case-finding
Control of
surveillance
• Social and epidemiological vectors and
and laboratory • Follow-up of contacts
mobile teams reservoirs in
• Specimens
nature
• Finances, salaries • Laboratory testing
• Transport vehicles • Database analysis
• Investigate for the
Formenty P, Roth C Gonzalez-Martin F et al: Emergent pathogens, international surveillance and international health regulations. Med Mal Infect. 2006 ;36(1):9-15.
source
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 Community engagement and awareness
• Raising awareness through adapted and targeted messages, other way of
communications should focus on specific audiences and context such as :
- Depending on the source of transmission, focus on preventing exposure to
bats and/or contaminated fruits or fruit products or exposure to sick
animals
- Reduce risk of human-to-human transmission in care-associated activities
(in health facilities and at home).
• Targeted training or guidelines must reach specific audience including :
✔ Health care workers,
✔ Care providers,
✔ Farmers,
✔ Veterinarians and wildlife experts.

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 Reducing risk of bat-to-human transmission

Reduce risk of bats-to-human

transmission:
• Protect collection process of date palm
juice (bamboo)
• Wash & peel fruits thoroughly
• Boil freshly collected palm juice
• Discard fruits with signs of bat bites

Photo credit: Nazmun Nahar/ ICDDRB

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 Control of Nipah virus in domestic animals

• Routine cleaning & disinfection of domestic animal farm is expected to be

effective in preventing infection
• Reducing the risk of bat-to-domestic animal transmission: bat proof buildings,
bat exclusion strategy, avoid fruits trees in the animal farm, etc.
• Reducing risk of domestic animal-to-human transmission:
• Avoid or minimize contact with ill or dead domestic animals
• Hand hygiene + use of personal protective equipment(PPE) in particular
during veterinary practices (care, necropsies)
• When an outbreak in domestic animals is suspected:
• Quarantine animal premises
• ± euthanasia or culling of infected animal(s)
• Restrict/ ban animals' movements
• Establish active animal health surveillance system for early warning for
veterinary and human public health authorities.

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 Prevent human-to-human transmission
What do I do if I think I
have
Nipah virus disease?
Avoid contact with other people
1.
2. Seek health advice immediately
Use gloves and mask and practice
3.
hand-hygiene when caring for
suspected Nipah patient at home.
Photo credit: WHO Bangladesh
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Reduce risk of human-to-human
transmission:
• Avoid or minimize physical contact with ill
patient
• Encourage early treatment in Nipah virus
disease Treatment Center.
• Wash hands regularly with soap and water.
• Use gloves and mask and practice hand-
hygiene when caring for suspected Nipah
patient at home.
• Health care workers should practice Hand
hygiene + use of personal protective
equipment (PPE)
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 Controlling infection in health-care settings

• Nipah human-to-human transmission documented (incl. nosocomial

transmission)
• Always implement Standard Precautions with all patients – regardless of
their diagnosis – in all work practices at all times including safe injection
practices. https://www.who.int/publications/i/item/standard-precautions-in-health-care
• As human-to-human transmission has been reported, in particular in
health-care settings, contact and droplet precautions should be used in
addition to standard precautions. Airborne precautions may be required in
certain circumstances.
• Laboratory workers are also at risk. Samples taken from suspected human
Nipah virus disease cases for diagnosis should be handled by trained staff
and processed in suitably equipped laboratories.
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 Key Public Health challenges

• Difficult to diagnose
• Management of severe cases is
challenging

• Possible large economic impact for

districts reporting Nipah virus disease
outbreaks

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 Nipah virus disease vaccines review
There is no approved vaccine, NiV vaccines for humans are
in pre-clinical stage
1. Live-attenuated vaccines (vector-based MVA, rVSV, MV, Ad, VEE).
• Modified Vaccinia Ankara (MVA) expressing NiV F and G glycoprotein were tested
in animals showing protection against NiV challenge.
• Recombinant vesicular stomatitis virus (rVSV) expressing either N, F or G of the
Malaysian strain of NiV, the vaccine fully protected hamsters from lethal NiV
challenge.
• Live-attenuated Measles Vector (MV) induces strong cellular immunity and durable
responses. A concern related to the use of a measles vector is due to possible
negative effect of pre-existing immunity in human populations.
• Adenoviruses (Ad) vaccine candidates have been shown to induce promising data
in animal models and protects the hamsters against lethal challenge with NiV.
• Venezuelan Equine Encephalitis (VEE) virus-vectored NiV vaccine candidate has
been evaluated in mice and found to induce NiV neutralizing antibodies.

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 Nipah virus disease vaccines review
There is no approved vaccine, NiV vaccines for humans are in
pre-clinical stage
2. A subunit vaccine incorporating recombinant glycoprotein G has been
approved as a veterinary vaccine against Hendra Virus in Australia in 2015.
This vaccine is formulated with an adjuvant. Currently, the vaccine is
administered to horses intra muscularly in 2 doses 6 weeks apart followed by
boosting 6 months later. Then annual boosters are recommended. The
effectiveness of this vaccine in horses suggests this approach may also be of
interest in humans.
3. NiV virus-like particles (VLPs) have also been obtained by co-expression of the
G, F and M proteins under optimized conditions. They appeared as an
alternative vaccine candidate, especially in view of their ability to induce a
neutralizing antibody response in mice.

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 Nipah virus disease therapeutics

There is no approved specific therapeutics against Nipah virus

disease.
1. Ribavirin. During the NiV outbreak in Malaysia in 1998/99,
ribavirin was given empirically to treat 140 patients. The trial was
not randomized. Mortality was lower in treated group (32%)
compared to the controls (54%), corresponding to 36% reduction.
2. Convalescent plasma has not been investigated clinically during
outbreaks of NiV infections

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 Nipah virus disease therapeutics
There is no approved specific therapeutics against Nipah virus disease.
3. Monoclonal antibodies targeting the surface glycoproteins shown efficacy against both
Hendra and Nipah viruses as pre- and post-exposure prophylaxis in animal models.
• Monoclonal Antibodies m102.4 is potent neutralizing and cross-neutralizing activity against
both Hendra and Nipah viruses.
• Effective post-exposure efficacy with m102.4 has been demonstrated in both ferrets and
NHPs infected with either Hendra and Nipah viruses.
• In humans, m102.4 have been used in Australia (10 people exposed to Hendra virus) at
high-dose therapy under compassionate use protocol and all survived with no associated
adverse events.
• A double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4
was implemented in Australia in 2015-16. Dosing were well tolerated and safe, displayed
linear pharmacokinetics, and showed no evidence of an immunogenic response.

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 Research & Development for Nipah disease

• Close to patient diagnostic tests

are in late stage of assessment

• Candidate drugs are in early

stages of testing

• Affected countries are at the

heart of R&D products
development

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 WHO information on Nipah virus
disease
中文 English Français Русский Español ‫عربي‬
https://www.who.int/health-topics/nipah-virus-infection#tab=tab_1

• Technical information
• Fact Sheet
• Disease outbreak news
• Nipah virus map
• Related links

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 Key contact

• Dr Pierre Formenty
-----------------------------------------
Viral Haemorrhagic Fevers team

Health Emergencies Programme

WHO Geneva
formentyp@who.int

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