During the period from 1998 to 1999, large-scale outbreak of NiV infection in pigs occurred in Malaysia, which resulted in 257 cases of human infection including 105 cases of death. Another two events of NiV infection occurred in Malaysia in June 2000. Meanwhile, due to the import of pigs from Malaysia, 11 cases of NiV infection in humans was reported, including 1 case of death. During the period from 2001 to 2005, five events of NiV infection in humans were reported consecutively, with a total of 69 death cases.

During the prevalence of NiV infection in Malaysia, NiV carried by fox bats may infect pigs with a tiny probability, which then proliferated in pigs in a large quantity and rapidly spread to other pigs via contacts. Humans were then infected via close contacts to these pigs. However, in the events occurring in Bangladesh, most of the NiV infected people had no history of close contacts to pigs, and pigs in these areas also had no sign of NiV infection. Therefore, pigs did not play an important role in the events occurring in Bangladesh. But the initial route of transmission for human infection remains unknown. In the events occurring in Malaysia, no evidence has been found to prove spreading of the virus between humans; while in the events occurring in Bangladesh, conclusive evidence has been found to prove spreading of the virus from person to person.

Although NiV can infect a variety of livestock by fruit bats, pig is still the main source of infection. Recent reports have demonstrated that NiV can spread via contaminated food or spread from person to person.

NiV possibly spreads via body fluid or blood, such as contacts to body fluid from patients. The routes of transmission may include direct contact to urine, body fluid, or tracheal secretions from infected pigs, sharing needle, artificial fertilizing, and vertical transmission from mother to infant. The transmitting route of NiV from person to person is not the major route of its transmission. Mosquitoes and other insects are not the media for its spreading. Although other natural hosts such as hounds, cats, Percheron, wild pigs, and rats could be infected, the virus fails to spread widely due to rapid death of these infected animals. In the outbreaks of NiV infection by humans, pig plays an important role, which spreads the virus via contacts or airborne transmission. After NiV infection by pigs, the virus can multiply in their bodies in large quantities. Viremia may persist for a long period of time, during which the virus may be spread externally via respiratory tract, urine, feces, and saliva. In addition, starlings such as mynas and grackles seek food in the piggery, which often peck ticks on the back of pigs and fly within one piggery or among piggeries. Therefore, starlings may be another route of transmission for NiV.

Workers working in piggeries or slaughterhouses have much more chances to contact to diseased pigs due to their job. Therefore, this population is the high-risk population for NiV infection.

NiV interacts with the host cell surface receptor ephrin B2 via G protein to recognize and adhere to the surface of host cells. Ephrin B2 is ligand of the subgroup Eph B in receptor tyrosine kinases (RTKs). Eph and its ephrin ligands play an important role in the processes of CNS development, angiogenesis, and tumor formation. Ephrin B2 is mainly expressed in neuronal cells, smooth muscle cells, arterial endothelial cells, and capillaries, which is consistent to the tropism of NiV to endothelial cells and the nervous system. Ephrin B2 is conservative in mammals, which may be related to the fact that many mammals are susceptible to NiV. In addition, ephrin B3, one of the homogeneous proteins of ephrin B2, is also capable of independently facilitating NiV gaining its access into cells, which is possibly one of the NiV receptors. After the invasion of NiV into the endothelial cells, it replicates itself rapidly and affects the synthesis of interferon and its functions under effects of multiple proteins such as P, V, W, and C protein to evade the defense system of the host. Meanwhile, it fuses with endothelial cells under the effects of proteins F and G to form endothelial syncytium, with following rupture of the cell to release the virus. The emergence of endothelial syncytium is characteristically an NiV infection, with a detection rate of 25 % by pathological examination in clinically diagnosed cases. In addition, NiV can also infect neurons directly, where it grows and proliferates to cause neurological symptoms.

NiV infection can involve any system of human body. By autopsy, the brain is found to be the most seriously affected organ, with possible involvements of the gray matter, white matter, basal ganglia, cerebellum, brain stem, and spinal cord. Other organs may also be involved, including the lungs, heart, and kidneys. The basic pathological changes are multiple organs vasculitis and endothelial cell inflammation. Vasculitis commonly occurs in minor arteries, arterioles, capillaries, and venules, which is characterized by vascular wall necrosis, thrombosis, and infiltration of inflammatory cells like leukocytes and monocytes. The infection of CNS shows extensive and scattering small necrotic foci. By immunohistochemical assays, NiV antigen can be detected in CNS tissues, especially in vascular endothelial cells with vasculitis, endothelial syncytium, and parenchymal cells. A small amount of viral antigens can also be detected in other tissues. The occurrence of death in patients with NiV infection is commonly from extensive focal infarction of brain tissues caused by atrophy of large quantities of infected neurons.