Nipah Virus Disease: Epidemiological, Clinical, Diagnostic and Legislative Aspects of This Unpredictable Emerging Zoonosis

Abstract

Nipah virus (NiV) infection is a viral disease caused by a Henipavirus, belonging to the Paramyxoviridae family, responsible for a zoonosis. The course of the disease can be very serious and lead to death. NiV natural hosts are fruit bats (also known as megabats) belonging to the Pteropodidae family, especially those of the Pteropus genus. Natural infection in domestic animals has been described in farming pigs, horses, domestic and feral dogs and cats. Natural NiV transmission is possible intra-species (pig-to-pig, human-to-human) and inter-species (flying bat-to-human, pig-to-human, horse-to-human). The infection can be spread by humans or animals in different ways. It is peculiar how the viral transmission modes among different hosts also change depending on the geographical area for different reasons, including different breeding methods, eating habits and the recently identified genetic traits/molecular features of main virus proteins related to virulence. Outbreaks have been described in Malaysia, Singapore, Bangladesh, India and the Philippines with, in some cases, severe respiratory and neurological disease and high mortality in both humans and pigs. Diagnosis can be made using different methods including serological, molecular, virological and immunohistochemical methods. The cornerstones for control of the disease are biosecurity (via the correct management of reservoir and intermediate/amplifying hosts) and potential vaccines which are still under development. However, the evaluation of the potential influence of climate and anthropogenic changes on the NiV reservoir bats and their habitat as well as on disease spread and inter-specific infections is of great importance. Bats, as natural reservoirs of the virus, are responsible for the viral spread and, therefore, for the outbreaks of the disease in humans and animals. Due to the worldwide distribution of bats, potential new reports and spillovers are not to be dismissed in the future.

Keywords: Nipah virus; diagnosis; epidemiology; immune response; legislation; pathology; vaccines.

Figure 1

Schematic representation of the NiV structure and viral genome organization. N, P and L proteins interact with the unsegmented single-stranded negative-sense viral RNA genome forming the ribonucleoprotein (RNP) complex. The matrix M protein, used for viral assembly and budding, is associated with the inner side of the envelope which contains the G and F glycoproteins for adhesion to ephrin-B2 and -B3 receptors and fusion, respectively. The P gene products (V, W and C proteins) derive from mRNA editing and alternative open reading frames (ORF). The six coded genes are flanked by a 3′ leader and a 5′ trailer region.

Figure 2

Geographic distribution of Henipavirus outbreaks and fruit bats of the Pteropodidae family. Countries at risk of outbreaks based on collection of positive serological specimens from fruit bats (orange) and countries with reported outbreaks (red) are shown. Violet spots indicate collection sites of fruit bats that resulted positive for Henipavirus, while blue stars indicate sites where Henipavirus outbreaks occurred between 1997 and 2008. Areas indicating the home range of the Pteropus genus of fruit bats (delimited by the green solid contour) and the home range of the Pteropodidae family of fruit bats (areas delimited by the violet dotted contour) are shown. Data source: Global Alert and Response Department, World Health Organization, WHO; map production: Public Health Information and Geographic Information Systems (GIS). Reproduced and adapted according to WHO permission ID: 390902 [65].

Figure 3

Pteropus giganteus, main reservoir of NiV (Fritz Geller-Grimm, 2002, Zoological Garden Berlin, Germany). This photograph is licensed under the Creative Commons Attribution-Share Alike 2.5 Generic license [105].

Figure 4

Schematic representation of the NiV pathogenesis. The virus enters the host through the oral-nasal route and spreads into the upper and lower respiratory system, including bronchi, bronchioles and alveoli where bronchial epithelial cells and type II pneumocytes are the major susceptible cells to infection. The first phase of infection is characterized by pneumonia and acute respiratory distress triggered by the release of inflammatory cytokines and chemokines in the lung. Pulmonary endothelial cells are secondary target cells which allow the virus to enter the peripheral circulation and spread into the body as free virus or carried by leukocytes (especially lymphocytes and monocytes), also causing a severe vasculitis and inducing viremia. The virus can reach different organs and induce multiple organ dysfunction syndrome (MODS). The spread to the brain and central nervous system (CNS) induces the release of inflammatory mediators responsible for systemic clinical signs and eventually leading to severe forms of neurological diseases, which mostly lead the host to death or severe impairment. NiV infection can lead to long-term neurological sequelae, late-onset encephalitis or relapse encephalitis after recovering from a symptomatic initial infection. IL: interleukin; MCP: monocyte chemoattractant protein; G-CSF: granulocyte colony stimulating factor; GM-CSF: granulocyte-macrophage colony stimulating factor; CXCL: C-X-C motif chemokine ligand; TNF-α: tumor necrosis factor alpha.