Agent

The Nipah virus is a type of paramyxovirus that belongs to the Henipavirus genus of the Paramyxoviridae family, which is under the Paramyxovirinae subfamily and Mononegavirales order. The Pteropus fruit bat serves as the reservoir host for NiV, and the virus has a half-life of 18 h within the bats’ urine [7].

NIV is an enveloped, negative-sense, single-stranded RNA virus with 6 genes, each being a coding sequence when read consecutively from 3’ to 5’ direction and include:

a.

N – Nucleocapsid.

b.

P – Phosphoprotein.

c.

M – Matrix.

d.

F – Fusion.

e.

G – Glycoprotein.

f.

L – Large Polymerase.

Of these, G and F are essential for cell entry into the susceptible hosts. M protein allows viral budding and morphogenesis. L, N and P encode for proteins that coordinate to form the RNA-dependent RNA polymerase or RdRP. P gene also encodes for 3 other proteins other than the P protein, namely, V, W and C proteins which determine virulence.

Genetic Analysis to identify hosts exhibiting higher potential for viral replication using codon usage revealed humans and bats to be the ones the virus showed maximum adaptability towards. The study also helped to choose suitable experimental animals for vaccine and other studies. Of these the African green monkey was the most optimal [8].

Host

The Nipah virus’s natural reservoir is the fruit bats that belong to the Pteropus genus, also known as flying foxes. Pigs, that get infected with the Nipah virus, act as an intermediate host. Furthermore, humans can also become hosts for the Nipah virus [7, 9,10,11]. Figure 1 depicts the geographical distribution of Nipah virus and Pteropus spp [12].

Fig. 1

: Distribution of nipah virus affected countries and potential countries under threat of future nipah virus outbreak

Environment

The destruction and fragmentation of animal habitats can cause increased interaction between wildlife, domestic animals, and humans, thereby increasing the risk of zoonotic disease spread [11]. A study conducted in Thailand aimed to map potential contact zones for bats, pigs, and humans by identifying areas where flying fox colonies are found. The study found that these colonies are typically located in areas surrounded by water, vegetation, and controlled or protected religious sites. In India and Bangladesh, a more recent study used Geographic Information System (GIS) technology to focus on bats carrying the Nipah virus (NiV). The study examined the potential shift in the distribution of the Pteropus medius species, using data from 2015 onwards, under various future socioeconomic and environmental scenarios. Additionally, the study predicted an increased risk of NiV transmission events as a result of these shifts. The findings suggested a probable rise in the risk of NiV transmission in these regions due to factors such as population growth and ongoing environmental degradation [11]. The findings of this study were later retracted, but they suggested that it might be crucial to put in place strong public health measures in regions where there is a high risk of the NiV virus being transmitted from Pteropus medius bats to humans. Doing so could help to minimize and manage potential NiV outbreaks in the future.

Transmission

In 1998, there was an unprecedented concurrent outbreak of an infectious disease in pigs with respiratory illness and humans with neurological disease in Kampung Sungai Nipah, Malaysia. A common causative agent was strongly suspected, given that the majority of human cases had direct contact with affected pigs. The disease rapidly spread as infected pigs were transported through Malaysia and into Singapore, resulting in 276 human cases, 106 fatalities, and the culling of over 1,000,000 pigs. The causative agent, named Nipah virus, was isolated from the cerebrospinal fluid of a human fatality and proved to be closely related to the Hendra virus. Despite no further cases of Nipah virus infection being identified in Malaysia, significant outbreaks occurred in India in 2001 and 2007, with multiple outbreaks and isolated cases reported in Bangladesh since 2001. Additionally, in 2014, a small outbreak of encephalitis in two villages in the Philippines was directly linked to the slaughtering and consumption of horses with neurological disease. Serologic evidence strongly indicates that horses and humans were infected with Nipah virus or a Nipah-like virus. Much like the Hendra virus, the Nipah virus originates from Pteropus spp. fruit bats. Zoonotic transmission of the Hendra virus in Australia and the Nipah virus in Malaysia and the Philippines occurred through an amplifying host, such as pigs and horses. In Bangladesh, zoonotic transmission is believed to occur directly from bats to humans, mainly through ingesting sap of raw dates from palm trees contaminated with the Nipah virus by fruit bats. The Henipavirus genus includes five species: Hendra virus, Nipah virus, Cedar virus, Ghanaian bat virus, and Mojiang virus. Cedar virus does not cause illness in animals or humans. Ghanaian bat virus and Mojiang virus have no direct evidence of causing disease in humans. However, Mojiang virus RNA was found in rats where workers may have acquired fatal pneumonia earlier. Henipavirus infection has been found in pigs and humans in Africa, indicating potential zoonotic transmission [13].

There has been a debate over the transmission route of the Nipah Virus, although being a bat-borne virus, one can say that the common transmission route is man-to-man transmission. A study done by Nikolay et al. [14] from the study in Bangladesh supports the dominance of finding transmission from person to person. However, studies from Malaysia and Singapore suggest probable transmission of virus is through workers working in pig farms suggestive of pigs being one of the cause of transmission to humans [15, 16].

A study conducted to observe the transmission of a virus through a hamster model indicates the importance of nasal and oropharyngeal shedding in the transmission process. The findings were consistent with previous experiments involving Nipah virus infections in pigs, where virus excretion was observed in both inoculated and contact pigs. It concluded that transmission mode from pig-to-pig, pig-to-human, and human-to-human is the same and is facilitated by direct contact with Nipah virus-containing nasal and oropharyngeal secretions. However, the specific mechanism of transmission is yet for investigation [17].

Transmission happens through contact with excretions or secretions of infected animals, ingestion of fruit contaminated with NiV or close contact with infected human bodily fluids [10].

Malaysia: The spread of the virus from bats to pigs is a result of consuming fruits that have been tainted by bats carrying NiV. The virus is then transmitted to humans from infected pigs through direct contact. Human-to-human transfer can occur through direct contact, air, or contaminated objects [10].

Bangladesh: It has been reported that the primary mode of transmission in Bangladesh are date palm sap consumption and person-to-person contact [9].

India: The NiV outbreaks in Bangladesh and in parts of India like West Bengal and Kerala exhibit comparable patterns in the spread of the virus among humans, characterized by direct human-to-human spread without involvement of intermediary hosts. These outbreaks primarily occurred within healthcare settings and notably impacted caregivers, and individuals in close proximity to the infected individuals [10].

Fig. 2

Routes of transmission of NiV in A- Malaysia, B- Bangladesh and C- India

Figure 2 depicts : A - In Malaysia, transmission predominantly occurs through the consumption of bat-bitten fruits contaminated with NiV-M by pigs, subsequently leading to human infections among workers handling these animals; B - Similarly, in Bangladesh, NiV-B spreads through the consumption of palm sap tainted with bat saliva and excreta, further disseminated via nosocomial transmission; C - In India, while the potential for direct bat-to-human transmission, particularly in Kerala, has been hypothesised, conclusive evidence remains insufficient. However, nosocomial transmission of NiV-B has been documented in Kerala and West Bengal, underlining the multifaceted nature of NiV dissemination across regions.