Reston virus also known as Ebola-Reston virus (RESTV) is one of the six virus species of the Ebola virus in the family Filoviridae 1). Although three filoviruses have been identified in animals in Asia 2), Ebola-Reston virus is the only filovirus isolated from Asia that is known to infect humans 3). Reston virus is known to cause disease in nonhuman primates and pigs, but not in people 4). There have been five documented Reston virus outbreaks in animals epidemiologically linked to the Philippines 5). Reston virus was detected in non-human primates in the periods 1989–1990, 1992–1993 and 1996 6); in pigs in 2008–2009 7); and again in non-human primates in 2015 8). These non-human primates were cynomolgus macaques used for preclinical research, drug development, disease modelling, experimental infections, and biological production, with breeders being collected from wildlife trapping areas mostly in southern Philippines 9). Four of of the five outbreaks were investigated by the Philippines Field Epidemiology Training Program 10).
In this risk assessment study conducted in the Philippines 11), the risk of Reston ebola virus occurring in humans in the Philippines and its potential pathogenicity in humans were both assessed as moderate. Animals involved in Reston ebola virus outbreaks in the Philippines were non-human primates and domestic pigs. The presence of Reston ebola virus in pigs poses a possibility of genetic evolution of the Reston ebola virus. Although Reston ebola virus has been identified in humans, there was no death or illness attributed to the infection 12). The Philippines Inter-agency Committee on Zoonoses oversees collaboration between the animal and human health sectors for the prevention and control of zoonoses.
Reston ebola virus in humans was deemed likely to occur since Reston ebola virus infection has been detected in humans, pigs, bats and non-human primates from different locations within the Philippines 13). With pigs as a host of Reston ebola virus, the likelihood of further human contact with infected animals is high, and the likelihood of the virus entering the food-chain is possible. If Reston ebola virus remains non-pathogenic to humans, the consequence will remain minor.
To date, there has been no evidence of Reston ebola virus pathogenicity in humans and no deaths or illness among the 105 Reston ebola virus-positive humans 14). However, some changes in the genetic sequence of Reston ebola virus could result in a virus more virulent in humans, especially if there is interspecies transmission 15). Should Reston ebola virus spread and become pathogenic in humans in the Philippines, the health consequences would escalate. Further evaluation would be needed if it occurred to establish the evolving risks. Response to the event would depend on the Reston ebola virus pathogenicity.
Enhanced surveillance is needed, and exposure of humans to animals and environmental sources should be controlled. Strict implementation of quarantine and filovirus testing of all non-human primates for export should be continued. Sentinel testing of other non-human primates within the Philippines should be considered to detect potentially latent diseases and prevent their introduction into a larger laboratory animal colony. Serological testing of domestic pigs in areas with a history of Reston ebola virus should be considered, especially if there are unusual pig deaths. Testing would allow detection of the virus before it enters the food-chain, thus limiting the possible emergence of a more pathogenic strain due to replication in livestock.
Future studies will shed light on Reston ebola virus pathogenicity and its consequences on animal and human health. Follow-up and serological studies on Reston ebola virus-positive humans should be done. Research studies on Reston ebola virus epidemiology, viral genetics, reservoir, potential hosts, clinical disease in humans and animals including incubation period, risk factors for infection, pathogenesis in coinfection and immunocompromised hosts, mechanism and prevention of transmission and public health impact should also be undertaken.
Reston ebola outbreak
There were five documented Reston ebola virus outbreaks in animals epidemiologically linked to the Philippines 16). The first outbreak was in November 1989 in Reston, Virginia, United States of America (USA) when quarantined non-human primates from the Philippines became ill and died 17). Epidemiological investigation in the monkey-breeding facilities in the Philippines at that time revealed Reston ebola virus-infected animals in the facilities 18). This was the first-ever Ebola virus detected outside of Africa and was the first known natural infection of Ebola virus in non-human primates 19).
From 1992 to 1993, Reston ebola virus was detected in an non-human primate quarantine facility in Sienna, Italy, and infected non-human primates were again traced back to the Philippines 20). In March 1996, imported macaques from the Philippines tested positive for Reston ebola virus in another facility in Texas, USA 21). In October 2008, Reston ebola virus RNA was unexpectedly identified in pig tissue samples sent from the Philippines for porcine reproductive and respiratory syndrome (PRRS) strain analysis in the Plum Island Animal Disease Center in Greenport, New York, USA 22). Joint investigation by the Philippines Field Epidemiology Training Program, the Bureau of Animal Industry and international experts revealed that the positive samples came from two commercial pig farms 23). Reston ebola virus was detected in the Philippines in September 2015 in monkeys bound for export 24). Risk communication was done to allay public fears. It was emphasized that Reston ebola virus is the mildest type of Ebola and does not pose the same threat as the Democratic Republic of the Congo Ebola virus in West Africa 25).
Across these five Reston ebola virus outbreaks in animals, a total of 1445 humans were tested for Reston ebola virus; all had been occupationally exposed to non-human primates or pigs or were close contacts of seropositive persons 26). A total of 105 people (7%) were positive; most (100/105, 95%) were pig handlers and abattoir workers from the 2008–2009 investigations after the detection of Reston ebola virus in pigs in Pangasinan and Bulacan 27).
The highest number of animals testing positive for Reston ebola virus was in the 1989–1990 investigation when 142/179 (79%) non-human primates tested in the Philippines were antibody positive and 141/279 (51%) were antigen positive 28). Two per cent (3/186) of occupationally exposed animal handlers tested positive 29). This serosurvey was initiated following the report of Reston ebola virus-infected macaques in the USA from two major export facilities in the Philippines 30).
Reston virus modes of transmission
Humans who tested positive in serological studies had daily exposure to pigs or non-human primates 31). The mode of transmission of Reston ebola virus to humans is most likely through close or direct contact with infected animals’ secretions, blood, organs or bodily fluids 32). It is uncertain whether Reston ebola virus can be transmitted to humans through inhalation of infected respiratory secretions, but it has been described in non-human primates. Some studies also found that experimentally infected pigs with Reston ebola virus can shed virus from the nasopharynx, suggesting a route of transmission by aerosol or droplet contact. Further investigations are needed for clarification 33).
There is no indication of human-to-human transmission of Reston ebola virus. In the 1989–1990, 1996 and 2008–2009 investigations, several contacts of Reston ebola virus-positive individuals all tested negative 34). However, human-to-human transmission is potentially possible if an individual were to become viraemic and symptomatic. This has occurred in other filoviruses, and there was a documented three-day viraemia in a human with Reston ebola virus infection 35).
Reston virus geographic distribution
Animal and human infections of Reston ebola virus have occurred in five provinces and two cities in the Philippines 36). Laguna province has had cases in humans and non-human primates 37). The provinces of Pangasinan and Bulacan have had cases in humans and pigs 38). Nueva Ecija province and Valenzuela City have had cases only in humans 39) and Batangas province and Parañaque City have had cases only in non-human primates 40). Some of the infected non-human primates in Laguna were caught in the wild on the island of Mindanao 41). While the geographic origin of Reston ebola virus is hypothesized to be South-East Asia and the Philippines 42), distribution has been shown to be widespread as it also occurs outside Asia 43).
Filoviruses have been identified in Africa, Europe and Asia 44). Serological studies in other countries from 1990 to 2011 found Reston ebola virus in humans in Germany 45), pigs and bats in China 46), orangutans in Indonesia 47) and bats in Bangladesh 48) and South Africa 49).
Reston ebola virus natural reservoirs
Bats have been identified as natural reservoirs of filoviruses, including Ebola and Marburg viruses 50). In the Philippines, there is evidence of Reston ebola virus infections in bats in Quezon City and in the provinces of Bataan, Bulacan and Quezon 51). It is possible that Reston ebola virus was transmitted to non-human primates and pigs from bats since bats inhabit many areas of the country, including the regions around the affected facilities in Bulacan, Pangasinan and Batangas 52). In a 2010 risk assessment of bat exposure among people in Orani, Bataan, bat meat consumption (93%), presence of bats near house (90%) and handling of bats (77%) were common 53).
Reston virus symptoms
Reston ebola virus signs and symptoms manifested by non-human primates were diarrhea, respiratory symptoms, wounds, bleeding, weakness, gastrointestinal infection, anorexia and paralysis 54). Some of the Reston ebola virus-positive pigs had clinical signs that resembled porcine reproductive and respiratory syndrome (PRRS) virus infections 55). However, it was also observed that Reston ebola virus can be asymptomatic in non-human primates and pigs 56). Some animals infected with Reston ebola virus were shown to be immunocompromised or having a coinfection 57). These coinfections included simian hemorrhagic fever (non-human primates, 1989–1990) 58), porcine reproductive and respiratory syndrome (PRRS) (pigs, 2008–2009) 59) and measles (non-human primates, 2015) 60).
In humans, there have been no deaths or illness attributed to Reston ebola virus infection; rather, infection results in a very mild illness 61). Therefore, Reston ebola virus does not pose the same public health threat as the African Ebola virus subtypes 62). As the evidence available relates only to healthy adults, further studies are needed to clarify whether these health effects would be the same for all population groups, such as those with underlying medical conditions, immunocompromised individuals, pregnant women and children 63). However, these population groups may be less likely to be in contact with infected non-human primates, pigs and bats compared to the other groups (healthy, no special condition) as they probably spend more time indoors and are less likely to engage in activities exposing them to the said animals. Reston ebola virus in domestic pigs also increases the opportunity of pig-to-human interspecies transmission because of their frequent and close level of contact 64).
According to the World Health Organization (WHO) experts consultation on Reston ebola virus pathogenicity in humans, the virus is genetically diverse 65) and slight changes in its genetic sequence could result in a more virulent virus in humans. (21) When there was interspecies transmission (e.g. monkeys to pigs), Reston ebola virus was thought to evolve more rapidly 66). In the affected farm in the 2008–2009 Reston ebola virus outbreak in pigs, there was a 0.079% genetic diversity of the virus over a one-year period, and simultaneous samplings in another farm in 2008 found the divergence to be about 4.5% 67). The presence of Reston ebola virus in pigs poses a high potential for genetic evolution since domestic pigs, as compared to non-human primates and bats, have frequent contact with humans 68). With no surveillance for Reston ebola virus in pigs, bats and non-human primates in the wild, it is possible that there is undetected ongoing circulation of the virus in animals, providing opportunity for continued genetic evolution with passage, adaptation and its possible natural selection 69). However, there is no research on Reston ebola virus virulence factors, and it is difficult to tell based on genetic sequence data which Reston ebola virus strain might be pathogenic in humans 70).
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