Article #69: Nipah Virus - The 1998-1999 Malaysia Outbreak

Nipah virus (NiV) is a zoonotic virus (it is transmitted from animals to humans) and can also be transmitted through contaminated food or directly between people. In infected people, it causes a range of illnesses from asymptomatic (subclinical) infection to acute respiratory illness and fatal encephalitis. The virus can also cause severe disease in animals such as pigs, resulting in significant economic losses for farmers. Nipah virus was first recognised in 1999 during an outbreak among pig farmers in, Malaysia. This outbreak resulted in nearly 300 human cases and more than 100 deaths, and caused substantial economic impact as more than 1 million pigs were killed to help control the outbreak. No new outbreaks have been reported in Malaysia since 1999. (Nipah Virus , n.d.)

It was also recognized in Bangladesh in 2001, and nearly annual outbreaks have occurred in that country since. The disease has also been identified periodically in eastern India. Other regions may be at risk for infection, as evidence of the virus has been found in the known natural reservoir (Pteropus bat species) and several other bat species in a number of countries, including Cambodia, Ghana, Indonesia, Madagascar, the Philippines, and Thailand. (Nipah Virus , n.d.)

The NiV belongs to the Henipavirus genus under the family Paramyxoviridae. This genus also contains Cedar virus (CedPV) and Hendra virus (HeV), an emerging virus that can cause severe respiratory illness and deadly encephalitis in humans. It is a negative sense, single-stranded, nonsegmented, enveloped RNA virus possessing helical symmetry. The RNA genome, from the 3´-5´, contains consecutive arrangement of six genes, viz., nucleocapsid (N), phosphoprotein (P), matrix (M), fusion glycoprotein (F), attachment glycoprotein (G) and long polymerase (L). The N, P and L attached to the viral RNA forming the virus ribonucleoprotein (vRNP). F and G proteins are responsible for cellular attachment of the virion and subsequent host cell entry. (Ternhag and Penttinen 2005; Ciancanelli and Basler 2006; Bossart et al. 2007).

The newly produced precursor F protein (F0) is cleaved into two subunits, viz., F1 and F2, by host protease. The fusion peptide of the virus contained in the F1 subunit drives the viral and host cellular membrane fusion for the virus entry (Eaton et al. 2006). The virus M protein mediates morphogenesis and budding. Antibody to the G protein is essential for neutralization of the NiV infectivity (Bossart et al. 2005; White et al. 2005). It is quite noteworthy that through the coordinated efforts of the fusion (F) (class I) and attachment (G) glycoproteins the target cell (i.e. host cell) is entered upon after binding by the enveloped Henipaviruses including NiV. Interactions between Class B ephrins (viral receptors) on host cells and the NiV glycoprotein (G) trigger conformational changes in the latter, leading to activation of F glycoprotein and membrane fusion (Steffen et al. 2012). It is believed that the strategies of replication as well as fusion of the ephrin receptors are responsible for greater pathogenicity of these viruses. Multiple accessory proteins encoded by Henipaviruses aid in host immune evasion (Marsh and Wang 2012).

Nipah virus can survive for up to 3 days in some fruit juices or mango fruit, and for at least 7 days in artificial date palm sap (13% sucrose and 0.21% BSA in water, pH 7.0) kept at 22 °C. The virus has a half-life of 18 h in the urine of fruit bats. NiV is relatively stable in the environment, and remains viable at 70 °C for 1 h (only the viral concentration will be reduced). It can be completely inactivated by heating at 100 °C for more than 15 min (de Wit et al. 2014). However, the viability of the virus in its natural environment may vary depending on the different conditions. NiV can be readily inactivated by soaps, detergents and commercially available disinfectants such as sodium hypochlorite (Hassan et al. 2018).

Figure 2 Structure of Nipah Virus

NiV transmission occurs via consumption of virus-contaminated foods and contact with infected animals or human body fluids. Risk factors include close proximity viz., touching, feeding or attending virus infected person, thus facilitating contact to droplet NiV infection. Recently, experimental studies with aerosolized NiV in Syrian hamsters revealed that NiV droplets (aerosol exposure) might play a role in transmitting NiV during close contact (Escaffre et al. 2018).

Figure 3 Transmission pathway of Nipas Virus

1. Fruit bats acts as natural reservoir of Nipah viruses. Fruit bats with NiV feeds on date palm sap. Virus can survive in solutions that are rich in sugar, viz., fruit pulp.

2. Virus transmitted to human through the consumption of date palm sap.

3. Fruit bats of Pteropus spp. which are NiV reservoirs visited such fruit trees and got opportunity to naturally spill the drop containing virus in the farm to contaminate the farm soil and fruits.

4. Contaminated fruits are consumed by pigs and other animals. Pigs act as intermediate as well as amplifying host. Combination of close surroundings of fruiting trees, fruits-like date palm, fruit bats, pigs and human altogether form the basis of emergence and spread of new deadly zoonotic virus infection like Nipah.

5. Pork meat infected with NiV are exported to other parts.

6. Consumption of infected pork can act as a source of infection to human. 7. Close contact with NiV affected human can lead to spread of NiV to other persons.

Currently there are no licensed treatments available for Nipah virus (NiV) infection. Treatment is limited to supportive care, including rest, hydration, and treatment of symptoms as they occur. There are, however, immunotherapeutic treatments (monoclonal antibody therapies) that are currently under development and evaluation for treatment of NiV infections. One such monoclonal antibody, m102.4, has completed phase 1 clinical trials and has been used on a compassionate use basis. In addition, the antiviral treatment remdesivir has been effective in nonhuman primates when given as post-exposure prophylaxis, and may be complementary to immunotherapeutic treatments. The drug ribavirin was used to treat a small number of patients in the initial Malaysian NiV outbreak, but its efficacy in people is unclear. (Treatment , n.d.)

References

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