Nipah Virus infection

N

Abdulrahman Mohammed

L-2102-V-21-D

School of Public Health and Zoonoses

GADVASU

NIPAH VIRUS

INFECTION

OVERVIEW

Organism

History

Epidemiology

Transmission

Disease in Humans

Disease in Animals

Prevention and Control

Actions to Take

SYNONYMS

Barking Pig Syndrome

Porcine Respiratory and Encephalitis

Syndrome

Porcine Respiratory and Neurologic

Syndrome

AGENT

Genus Henipavirus

◦ Virus discovered, 1999

◦ Related to Hendra virus

Severe, rapidly progressive

encephalitis in humans

◦ High mortality rate

◦ Close contact with infected pigs

Severe, respiratory disease in pigs

NIPAH VIRUS STRUCTURESingle-stranded negative sense RNA, 18,246 nucleotides in length

HISTORY

1998-1999: Peninsular Malaysia

◦ Human febrile encephalitis, high mortality

◦ New virus discovered

1999: Singapore

◦ Outbreak in abattoir workers

◦ Pigs imported from Malaysia

● Since 2001 – Bangladesh, India

Introduction Nipah is the name of the 1st village the virus struck near

Kuala Lumpur in Malaysia.

Nipah virus is similar to Hendra virus that was discovered in Australia in 1994.

Nipah virus was discovered in 1999. It is a paramyxovirus in the genus Henipavirus; Hendra virus is also within this genus.

Different variants of Nipah virus were involved in outbreaks in Malaysia, Bangladesh, and India, and at least two major strains of Nipah virus were isolated from pigs in Malaysia.

Nipah virus causes severe, rapidly progressive encephalitis in humans, and severe respiratory illness in pigs. Some pigs may also demonstrate nervous system signs.

Nipah virus infection has a high mortality rate in humans. Transmission of the disease to humans is associated with close contact with infected pigs. Nipah virus survives in the environment for long periods in favorable conditions; it survives for days in fruit bat urine and contaminated fruit juice

Center for Food Security and Public

Health, Iowa State University, 2011

THE MODE OF TRANSMISSION:

from animal to animal &from animal to human (uncertain)

require close contact with contaminated tissue or body fluids from infected animals.

Nipah antibodies have been detected in pigs, other domestic & wild animals. The role of species other than pigs in transmitting infection to other animals - not yet determined.It is unlikely that Nipah virus is easily transmitted to manNipah is transmitted from animals to humans more readily than Hendra. Despite frequent contact between fruit bats & humans there is no serological evidence of human infection among bat careers. Pigs were the apparent source of infection among most human cases in Malaysian outbreak of Nipah, but other sources, such as infected dogs and cats, cannot be excluded. Human-to-human transmission of Nipah virus - not reported.

TRANSMISSION

Reservoir

Flying foxes (fruit bats)

◦ Carry the virus

◦ Are not affected

Virus found in

◦ Urine

◦ Partially eaten fruit (saliva?)

No known secondary host

The primary reservoir for Nipah virus are flying foxes (also known as fruit bats) of the genus Pteropus.

Transmission of Nipah virus from bats to swine has not been shown conclusively; however, there are various biologically plausible means for infected secretions of primary hosts to enter pigs, including direct contact with infected secretions, contaminated fruit or dead bats.

Scavenging animals may also play a role in the transport of virus into proximity of pigs. Flying foxes are able to carry the virus without being affected by it.

Investigation of potential secondary hosts (peridomestic species) have also been conducted. Rats, house shrews, dogs, and chickens have been tested, but no indication of a secondary host has been found.

TRANSMISSION

Pigs in Malaysia

◦ Direct contact

◦ Contact with body fluids

◦ Aerosolization of respiratory or

urinary secretions

◦ Vertical transmission across the placenta?

◦ Semen and iatrogenic spread?

It is unclear how the virus was transmitted from bats to pigs in Malaysia. However, it is suspected that fruit trees close to pig confinement areas are foraged by the bats and the virus is spread by urine or saliva-contaminated partially-eaten fruit on which the pigs feed.

The majority of human cases (93%) have been related to close contact with pigs, either from direct contact or contact with body fluids, urine, or feces.

Aerosolization of urinary or respiratory secretions may be a possible route of transmission and is being investigated.

The role of dogs and cats (in close contact with infected pigs) in the transmission of the disease is also being explored.

Anecdotal evidence suggests that vertical transmission may occur across the placenta.

Transmission in semen and iatrogenic spread on re-used needles have also been suggested.

TRANSMISSION

Person-to-person

◦ Not reported in Malaysia

◦ Likely in Bangladesh and India

Nosocomial infections

Bat-to-person

◦ Not reported in Malaysia

◦ Common in Bangladesh and India

Contaminated fruit, unpasteurized date palm

juice

How did people get infected in

Malaysia? The outbreak was concentrated

among pig farmers

-92% of cases reported contact with pigs

Compared to controls, persons with Nipah encephalitis were:

-5.6 times more likely to have close contact with pigs

-3.7 times more likely to have contact with sick pigs

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

-urine from Pteropus hypomelanus in

Malaysia

-Urine from Pteropus lylei

-in Cambodia

-in Thailand

Photo courtesy of James Roth, DVM, PhD, ISU

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.

Photo courtesy of James Roth, DVM, PhD, ISU

This picture shows additional hog confinement barns in Malaysia. There are

many fruit trees and caves close to this location

How does Nipah virus transmit from

wildlife to humans in Bangladesh?

Date palm sap collection

Late November through March/April

-A tap is cut in the tree in the evening a clay pot is placed under the tap

-Each morning the pot is removed

-Some sap is sold fresh early in the morning

Fruit bats are a nuisance

-drink juice

-defaecate into juice

occasionally drown in juice

Date palm sap distribution

One of the fatal cases was the son of

a date palm sap collector

-drank date palm sap daily

Heard bats in his date palm trees at night

-found bat excrement on his pot

Several days prior to the outbreak he sent

date palm sap to his relatives in a nearby

homestead

- 3 cases occurred in the family

EPIDEMIOLOGY

1998-1999: Malaysia◦ 265 persons hospitalized; 105 deaths

◦ Primarily adult males with swine contact

◦ Disease in swine Severe respiratory disease

Transmitted by movement of infected pigs

1.1 million pigs culled

Great economic loss

◦ Surveillance and testing

Epidemiology

Shortly after the 1999 outbreak in Singapore, a serological survey of various risk groups was conducted in Singapore. From the 1,469 persons tested, 22 were found to be infected with Nipahvirus. Ten of these individuals were asymptomatic. Of the 12 persons (54.6%) demonstrating symptoms, 9 had encephalitis, 2 pneumonia, and 1 had both.

1999: Singapore◦ 22 seropositive persons (1.5%)

◦ All were male abattoir workers

◦ 12 symptomatic Encephalitis, pneumonia, or both

◦ 10 asymptomatic

Epidemiology

India reported two outbreaks of Nipah virus encephalitis in the eastern state of West Bengal, bordering Bangladesh, in 2001 and 2007. Seventy one cases with 50 deaths (70% of the cases) were reported in two outbreaks.

An outbreak in Siliguri, West Bengal, India in 2001 was linked to nosocomialtransmission in hospitals and ended after effective barrier nursing precautions were put in place.

A second outbreak was reported in 2007 in Nadia district of West Bengal. Thirty cases of fever with acute respiratory distress and/or neurological symptoms were reported and five cases were fatal. All five fatal cases were found to be positive for NiV by RT-PCR.

A 2004 outbreak of Nipah virus occurred in the Faridpur District of Bangladesh in mid-March 2004. Thirty-four human cases were identified, and 26 people (76%) died of the disease. Transmission of the disease may have occurred through close contact with infected patients or exposure to a common source).

2001: Siliguri, 2007: Nadia, India

◦ Nosocomial transmission

2004: Bangladesh

◦ 34 cases; 26 deaths

◦ Transmission Close contact

Exposure to common source

Epidemiology

2005: Bangladesh◦ 44 cases; 12 deaths

◦ Contaminated palm fruit juice

2007: Bangladesh◦ 7 cases; 3 deaths

◦ Person-to-person transmission

◦ 2013 Since the deadly pathogen appeared in Bangladesh 12 years ago, 188 cases and 146 deaths have been reported; including 12 infections and 10 deaths so far in 2013.

In 2005, an outbreak began in the Tangail District on Bangladesh when 13 people lost consciousness after drinking palm fruit juice. The fruit may have either been contaminated with fruit bat droppings or saliva as the fruit may have been partially eaten by the bats. Blood samples from the suspected cases were sent to the CDC to confirm Nipah virus infection, and one was a confirmed positive. There were a total of 44 cases and 12 deaths from Nipah virus as of February, 2005).

In February 2007 an outbreak of Nipah virus encephalitis occurred in Thakurgaon District of northwest Bangladesh. Seven people were infected, three of whom died. Although the source of infection for the index case was not identified, 50% of Pteropus bats sampled from near the outbreak area 1 month after the outbreak had antibodies to Nipah virus confirming the presence of the virus in the area. The outbreak was spread by person-to-person transmission.

Morbidity and mortality due to Nipah

or Nipah-like virus encephalitis,

South-East Asia Region, 2001-2012

Year/Month Location No. cases No. deathsCase Fatality

Rate

Jan-Feb 2001 Siliguri (India) 66 45 68%

Apr-May

2001

Meherpur

(Bangladesh)13 9 69%

Jan-03Naogaon

(Bangladesh)12 8 67%

Jan 2004Rajbari(

Bangladesh)31 23 74%

Apr-04Faridpur

(Bangladesh)36 27 75%

Jan-Mar 2005Tangail

(Bangladesh)12 11 92%

Jan-Feb 2007Thakurgaon

(Bangladesh)7 3 43%

Mar-07

Kushtia,Pabna,

Natore

(Bangladesh)

8 5 63%

Apr-07Naogaon

(Bangladesh)3 1 33%

Apr-07 Nadia (India) 5 5 100%

Feb-08Manikgonj

(Bangladesh)4 4 100%

Apr-08

Rajbari and

Faridpur

(Bangladesh)

7 5 71%

Jan-09

Gaibandha,

Rangpur and

Nilphamari

(Bangladesh)

3 0 0%

Rajbari

(Bangladesh)1 1 100%

Feb-Mar 2010

Faridpur,

Rajbari,Gopalg

anj,Madaripur 16 14 87.50%

Feb-Mar 2010

Faridpur,

Rajbari,Gopalg

anj,Madaripur

(Bangladesh)

16 14 87.50%

Jan-Feb 2011

Lalmohirhat,

Dinajpur,

Comilla,

Nilphamari and

Rangpur

(Bangladesh)

44 40 91%

Feb-12

Joypurhat,

Rajshahi,

Natore, Rajbari

and Gopalganj

(Bangladesh)

12 10 83%

Total 280 211 75%

Disease in HumansIncubation period: Between 4 & 18 days

In many cases infection is mild or unapparent (sub-clinical).

In symptomatic cases:

onset is usually with "influenza-like" symptoms, with

high fever & muscle pains

Disease may progress to: Inflammation of brain (encephalitis) with drowsiness, disorientation, convulsions &

coma.

50% of clinically apparent cases die

NIPAH PATHOLGY

Causes a diffuse vasculitis

The brain is the most severely

affected organ

-tropism to the brain stem

Virus commonly identified in

-lung

-Kidney

Nipah case definition

Person with fever plus

- New onset seizures OR

- Altered mental status OR

-Severe shortness of breath

Antibody against Nipah virus

OR

-Part of a cluster of similar cases in the same

region, at least one of whom was Nipah

antibody positive

Disease in Human

Complications (Malaysian outbreak)

◦ Septicemia (24%)

◦ GI bleeding (5%)

◦ Renal impairment (4%)

Asymptomatic

◦ Relapse or late-onset encephalitis

◦ Residual neurological deficits

Treatment: Supportive, ribavirin

Septicemia, bleeding from the gastrointestinal tract, renal impairment, and other complications can occur in severely ill patients.

In the Malaysia outbreak, the mean time from onset of illness to death was 10.3 days. Duration of illness for those that recovered was 14.1 days.

Cases that progress to encephalitis are often fatal. Surviving patients may have mild to severe residual neurological deficits, or remain in a vegetative state.

Patients who recover from neurologic disease may relapse with encephalitis several months to several years later. Encephalitis can also occur as long as four years or more after an asymptomatic or non-encephalitic infection.

In the Malaysian outbreak, the subclinical infection rate was estimated to be 8 to 15%. The case fatality rate in the various outbreaks has varied from 33% to approximately 75%; the overall case fatality rate for all outbreaks in Bangladesh between 2001 and February 2005 was 64%. Current treatment involves intensive supportive care. Early treatment with ribavirin may reduce the severity of the disease.

Disease in Animals

◦ Highly contagious

◦ May be asymptomatic

◦ Acute fever (>104°F)

◦ Severe respiratory disease

Characteristic cough – harsh, “barking”

◦ Neurological changes

◦ Low mortality

Disease in Animals

Dog◦ Distemper-like signs

◦ Fever, respiratory distress

◦ Ocular and nasal discharge

Cat◦ Fever, depression

◦ Severe respiratory signs

Horses◦ Encephalitis

Diagnosis

Differentials for swine

◦ Classical swine fever, PRRS,

pseudorabies, swine enzootic pneumonia,

porcine pleuropneumonia

Diagnostic tests

◦ ELISA

◦ Immunohistochemistry

◦ PCR

◦ Virus isolation

Treatment

No effective drug therapies available yet.

Ribavirin-reduces mortality Recent development for NiV antivirals

focus on inhibitors of fusion and receptor binding

Soluble versions of the G glycoprotein and Ephrin B2 shown to inhibit NiVenvelope-mediated infection

No passive immunoprophylaxis, antiviral chemoprophylaxis, or vaccine is currently available

Recommended Actions Nipah virus is a very dangerous pathogen. It has been classified as

a Biosafety level 4 agent. If you suspect a potential Nipah virus outbreak, contact your state veterinarian, or your state public health veterinarian IMMEDIATELY!

Avoid all contact with potentially infected species (pigs, dogs, cats), until the proper authorities are consulted.

Because Nipah virus can be transmitted from person-to-person, barrier nursing should be used when caring for infected patients. Patients should be isolated, and personal protective equipment, such as protective clothing, gloves, and masks should be used.

IMMEDIATELY notify authorities

Federal

◦ Area Veterinarian in Charge (AVIC)

State

◦ State veterinarian

Quarantine

Prevention and Control

Keep fruit bats away from

pigs

Do not drink unpasteurized

fruit juices

Wash, peel, and/or cook all

fruit thoroughly before

eating

Malaysia outbreak control

Outbreak ceased following the culling

of over 2 million pigs

-Fruit trees no longer permitted above

pig pens

-Pork industry decimated

No cases of Nipah recognized in

Malaysia from people or animals since

Nipah virus (NiV) causes seasonal outbreaks

in humans in Bangladesh that coincide with the

date palm sap harvesting season, November to

March

After intervention (Khan et al., 2012) from 83% to 2%

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

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)

References

Oxford Textbook of Zoonoses World Health Organization

-www.who.int

World Organization for Animal Health (OIE)◦ www.oie.int

U.S. Department of Agriculture (USDA)◦ www.aphis.usda.gov

Centers for Disease Control and Prevention-www.cdc.gov

Center for Food Security and Public Health◦ www.cfsph.iastate.edu

USAHA Foreign Animal Diseases(“The Gray Book”)◦ www.usaha.org/pubs/fad.pdf

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