Nipah virus outbreak

Nipah virus (NiV) is a newly emerging zoonosis that causes severe disease in both animals and humans.

Henipavirus

Nipah virus (NiV) is an RNA virus and along with Hendra virus (HeV) belongs to the family Paramyxoviridae. HeV and NiV have been classified into a new genus within the family Paramyxoviridae as Henipa virus. NiV is closely related to Hendra virus, which is an acute, viral respiratory infection of horses and humans reported from Australia.  Since 2 decades, both have emerged as zoonotic diseases causing disease in humans and livestock in Australia and South East Asia. They cause virulent contagious disease and death.

Nipah infection

During September 1998 and April 1999, 265 persons become ill and 105 of them died of a viral illness in Malaysia. The first case detected in a village, Kampung Baru Sungai Nipah near Kulalumpur. The virus was named after that village. Majority of the patients were working in piggeries, and had contact with pigs. The virus is believed to have jumped from fruit bats which had lost their habitats due to deforestation, to domestic pigs paddocked under the trees, where such bats roost. Pigs were tested positive for the virus. It was highly contagious and spread by coughing. Pigs had acted as intermediate hosts. To contain the disease over a million pigs were killed in Malaysia.  Singapore reported occurrence of a similar disease in eleven abattoir workers exposed to pigs imported from Malaysian farms. There was one death. Since this outbreak, no subsequent cases have been reported in either Malaysia or Singapore.

Fruit bat (flying fox) belonging to the genus Pteropus, is the natural reservoir host of the Nipah and Hendra viruses. It was found that the pig feed of swine herds was contaminated by bat’s urine, faeces, saliva, and fruits partially eaten by the bats.

Nipah virus has been linked to an increase in contact between bats and humans, sometimes involving an intermediate domestic animal host. The increased contact is driven both by human encroachment into the bat’s territory (pigpens, human dwellings, agriculture) and by movement of bats towards human populations due to changes in food distribution and loss of habitat.

Outbreaks in Bangladesh and India

Subsequent outbreaks occurred in Bangladesh and India where there were no intermediate hosts. The initial outbreak occurred in 2001. In Bangladesh humans were infected with NiV due to consumption of raw palm sap that had been contaminated by urine and saliva from infected fruit bats. Even there was chance of getting infection by the individuals who had climbed palm trees coated with the secretions of bats. Following spread to humans, it was transmitted from one person to another through respiratory droplets. The outbreaks of Nipah infection in Bangladesh occurred in the first seven years of the current century as follows (Table 1).

For the first time the Faridpur outbreak showed that six cases demonstrated features of acute respiratory distress syndrome (ARDS) in humans. It implied that the infection must have acquired through droplets. Nipah killed nearly 70% of those it infected in Bangladesh, compared to 40% in Malaysia. Genetic sequencing confirmed that Nipah virus that caused infection in Bangladesh to be a different strain from that seen in Malaysia. Unlike the Malaysian NiV outbreak, outbreaks occurred almost annually in Bangladesh.

During the same period two outbreaks of Nipah illness were reported from the bordering districts in West Bengal, India. There was occurrence of Nipah virus infection in Siliguri, West Bengal, bordering Bangla Desh in 2001 and majority of infected patients (75%) were either hospital staff or visitors of a sick patient suggesting human-to-human transmission.

In 2007 in Nadia District of West Bengal bordering Bangladesh District, Kushtia where eight cases of Nipah virus encephalitis with five fatalities had been reported in 2007, had an outbreak of Nipah illness in 50 persons with 3-5 fatalities.

Transmission

Transmission of the virus to humans takes place via direct contact with infected bats, infected pigs, or from other NiV infected people. Initially humans were apparently infected with NiV only through close contact with infected pigs during the outbreak in Malaysia and Singapore. In Bangladesh infection occurred after consuming date palm sap that had been contaminated by infected fruit bats. Now human-tohuman transmission of NiV is seen in Bangaldesh and India.

Symptoms in Malaysian outbreak of infection were predominantly encephalitic in humans and respiratory in pigs. In subsequent outbreaks in Bangladesh and India, the manifestations have been predominantly respiratory in human suggesting the likelihood of human-to-human transmission.

Nipah outbreak in Kerala

Since May 17th 2018  for a fortnight 19 cases of  Nipah have been reported from Kozikode (predominantly) and neighbouring Mallapuram districts of Kerala. Of them 17 have died giving a mortality rate of 89%.The first case was noted in Perambra town near Kozikode. The patient presented with vomiting, high fever and mental agitation suggesting encephalitis. He demonstrated some unusual features like tachycardia, hypertension, hypotonia and areflexia. The condition worsened quickly with loss of consciousness and death. Such features are not commonly encountered in routinely encountered encephalitis. There was death of his younger brother 12 days ago with similar manifestations.  His father and aunt had also contacted the infection and later died. It is noteworthy the cause of the condition was discovered in the second patient hit by an outbreak within 3 days.

Close contact with patient zero has lead to occurrence of seven new cases in Perambra Taluk hospital and 10 in Kozikode Medical College hospital. Nipah virus spreads mainly through respiratory droplets of sick patients.

Spread

Though Nipah virus belongs to Paramyxoviridae family to which measles virus belongs, the infection does not spread widely and it moves only to people within a metre of very sick patients. In Siliguri District hospital the spread of infection was mainly to the hospital attendants. In Bangladesh the infection occurred from patients to other family members. In Kerala it spread among family members and nurse taking care of such patients.

Though it was thought the fruit bat had carried the virus, there was no conclusive evidence. Nipah infection does not last for very long time in bats. The symptoms may develop 5-14 days following exposure to Nipah virus.

Pathology

There is presence of vasculitis with thrombosis, and microinfarctions. Brain tissue shows presence of syncytial giant endothelial cells and viral inclusions. Immunostaining shows presence of viral antigen within neurons and endothelial cells of most affected tissues.

Clinical features

The clinical manifestation of NiV infection varies from asymptomatic infection to acute respiratory syndrome and fatal encephalitis. The symptoms in initial Malaysian outbreak were primarily encephalitic. Later outbreaks have caused respiratory illness in humans, due to increasing  likelihood of human-to-human transmission. This alteration in clinical presentation has highlighted the existence of more dangerous strains of the virus.

The infection presents as an encephalitic syndrome marked by fever, headache, disorientation, mental confusion, and drowsiness. These symptoms can progress to coma within 24 to 48 hours and potentially death. Other manifestations include cough, breathlessness, abdominal pain, nausea, vomiting, weakness, difficulty in swallowing and blurred vision. Thus the patients may develop a respiratory illness during early part of the infection. There can be seizures, myoclonus, cerebellar dysfunction, areflexia, and loss of consciousness. Clinical examination may reveal tachycardia, hyperpyrexia and severe hypertension.

Breathlessness may become unresponsive to oxygen and may necessitate mechanical ventilation.

Investigations

There are no specific laboratory abnormalities. There can be moderate thrombocytopaenia and raised levels of liver enzymes. Cerebrospinal fluid (CSF) examination in patients having neurological manifestations exhibits lymphocytic pleocytosis and elevated protein with normal glucose levels. There can be scattered infiltrates in chest radiographs. There can be severe hypoxia. Magnetic resonance imaging (MRI) of brain may show presence of multiple, small asymmetric focal lesions in subcortical areas and deep white matter reflecting presence of micro-infarction. Electroencephalogram (EEG) shows presence of diffuse slow waves. ELISA and PCR assays can detect viral sequences in tissue or CSF.

Sequlae

Long-term sequelae following Nipah virus infection has been noted which may manifest in the form of persistent fatigue. convulsions and personality changes. Latent infections may exhibit subsequent reactivation of Nipah virus and death, after a variable period of time.

Treatment

There is no specific treatment for Nipah Virus infection. The treatment is essentially intensive supportive care. Features of ARDS necessitate mechanical ventilation. Secondary infection has to be prevented. Ribavirin, an antiviral drug has shown to be effective against the virus in vitro. However, its clinical efficacy remains inconclusive in human clinical trials.

Prevention

No vaccine is available to control spread of Nipah infection. As human-to-human transmission of Nipah virus has been documented, standard infection control practices are to effectively followed to prevent the spread of the disease. Proper hand wash, and use of face masks are necessary for all individuals who are coming in contact with infected persons.

There is need to take precautions by the hospital workers, family members who are taking care of the infected patients. Even the persons who handle and submit laboratory samples and slaughter house workers have to take similar precautions. Avoiding exposure to sick pigs and bats in endemic areas, not drinking raw date palm sap, and not consuming fruits that have fallen on to the ground can help prevent Nipah virus infection.