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EBOLA-RESTON virus in pigs

Disease situation in swine in the Philippines

An Unfolding Situation

December 2008 - Over the past several weeks, FAO has engaged with officials at the Philippine Department of Agriculture in Manila and other national and international agencies (i.e. the World Health Organization, the World Organisation for Animal Health, the United States Department of Agriculture, the Centers for Disease Control and Prevention of the United States Department of Health and Human Services and the Australian Animal Health Laboratory) to better understand the laboratory findings of Ebola Reston virus in pigs in the Philippines. This situation represents the first time that the virus, a known primate pathogen, has been identified in a food-producing animal.

The laboratory findings came about after the Bureau of Animal Industry (BAI) of the Philippine Department of Agriculture undertook field investigation and sample collection activities related to suspected outbreaks of porcine reproductive and respiratory syndrome (PRRS). PRRS had been affecting several swine production areas in the Philippines and was characterized by having a greater virulence than what had been described decades earlier in North America and Europe. Such increased virulence in the PRRS virus (an Arterivirus) had also been seen in 2006 and 2007 in China and Viet Nam, respectively.

BAI sent samples to a laboratory with enhanced PRRS experience to facilitate PRRS characterization and to rule out other swine pathogens, such as porcine circovirus, classical swine fever virus (a Pestivirus), or Nipah virus (a Paramyxovirus) using classical and molecular diagnostic laboratory techniques.

During the laboratory investigations, viral particles and genetic sequencing showed that several of the swine samples were infected with: the PRRS virus; circovirus; other agents; and the Ebola Reston virus. Previously, no Ebolavirus had ever been found in swine tissues.

Questions & Answers
What is Ebola hemorrhagic fever, what is Reston, and what is Ebola Reston?

Ebola hemorrhagic fever (EHF) is the common term for a disease caused by a group of viruses belonging to genus Ebolavirus of the family Filoviridae to which humans and other primates are susceptible. The only other known virus in this family is the Marburg virus.  The Ebola virus and EHF are named after the Ebola River in the Democratic Republic of the Congo – formerly Zaire – which reported the first recognized outbreak in 1976.

EHF is often fatal in primates. In humans it is characterized by fever, vomiting, diarrhoea, generalized muscle and joint pain, and sometimes internal and external bleeding. Fatality rates in humans (i.e. individuals that contract the disease and then die from it) can be high, ranging from 50 to 90 percent with the Sudan or the Zaire species of the virus. Multiple organ failure is the usual cause of death. No approved vaccine is available, and treatment relies on supportive care including the infusion of intravenous fluids. Transmission between infected patients or affected animals and care providers or researchers can be avoided by using strict barrier-nursing procedures and employing the proper use of appropriate personal protective equipment.

In the fall of 2007, over 260 people became ill with a suspicion of EHF in the village of Kampungu, Democratic Republic of the Congo. Of that total, nearly 190 people died. The previous recorded outbreak in the Democratic Republic of Congo was in 1995, when 245 people died.

The ecology of Ebolavirus is not fully understood. Non-human primates are believed to be infected directly from the natural reservoir. Subsequently, the virus circulates or spreads by horizontal transmission (e.g. ape-to-ape) within a primate population. Transmission can take place after direct contact with infected blood, secretions or excretions. Transmission is also possible through contact with contaminated inanimate objects or vegetation. Laboratory research and field findings indicate that monkeys probably do not represent the natural reservoir.

Field investigations in the Congo basin in Africa linked the first human cases of Ebola infection to contact with wild mammals hunted or found sick or dead in the rainforest (i.e. gorillas, chimpanzees, monkeys, forest antelopes, duikers and porcupines). Animal-to-human transmission occurred through direct human contact with infected animal blood or fresh organs. Human-to-human transmission occurred either through direct contact with patients or their secretions or later contact with the infected corpse during traditional funeral ceremonies.

The Reston (or Ebola Reston) virus is the only known filovirus of Asian origin with genetic characteristics similar to the virus first identified in Zaire. It was first discovered in crab-eating macaques (Macaca fascicularis) at the Hazleton Laboratories located in Reston, Virginia (USA) in 1989, when quarantined monkeys became ill and some died. These monkeys had been imported weeks earlier from the Philippines.
There is one notable difference between Ebola Reston and other Ebola viruses from Africa: although Ebola Reston can infect humans, it has not been shown to produce clinical disease or symptoms in humans. Ebola Reston also causes a lower fatality rate in monkeys compared to that caused by African Ebola viruses. Co-infection of Ebola Reston with another virus (e.g. simian hemorrhagic fever virus) exacerbates the disease in monkeys and increases the fatality rate.

Several animal caretakers in the 1989–90 Reston incidents seroconverted (i.e. developed an immune response as determined by antibody levels specific for the virus). One of the animal caretakers accidentally cut himself while performing a necropsy (i.e. post-mortem evaluation) on an infected monkey. He did not become ill, even though the virus was isolated from his blood. Seroconversion in humans has also been documented in the Philippines, but illness has not been reported.

The Ebola Reston virus was once again introduced through the importation of cynomolgus macaques from the Philippines to the United States in 1990 and 1996 and into Europe in 1992. The Philippines is one of the world’s major sources of cynomolgus macaques, which are often used for biomedical research.

After the first cases in the Democratic Republic of Congo (formerly Zaire), a second strain of Ebolavirus was found in 1976 among cotton factory workers in Nzara, the Sudan. This strain was responsible for a large epidemic. In May 2004, the Sudan Ebola virus was reported in Yambio County, the Sudan and resulted in five deaths.

In November 1994 a novel Ebola virus was isolated by a researcher infected during a post-mortem exam of a dead chimpanzee in the Tai Forest in Côte d'Ivoire.

More recently, in November 2007, the Ugandan Ministry of Health reported an outbreak of EHF in the Bundibugyo District of western Uganda.

Marburg virus was actually the first human haemorrhagic fever identified to be caused by a filovirus. In humans, Marburg haemorrhagic fever is a severe and highly fatal disease. Case fatality rates vary greatly; from 25 percent in the initial laboratory-associated outbreak in 1967 in Marburg and Frankfurt am Mein (Germany) to more than 80 percent in the Democratic Republic of Congo from 1998 to 2000 and in the largest known Marburg haemorrhagic fever outbreak in Angola in late 2004. In the Germany outbreak the virus was shown to have been introduced by the importation of infected African green (i.e. vervet) monkeys (Cercopithecus aethiops) from Uganda. More recent human cases have occurred in individuals entering caves or mines inhabited by numerous bats in the Democratic Republic of Congo and Uganda.

Ebola antibodies have been found in free-living chimpanzees, drills and baboons. Chimpanzees and gorillas in the wild and rhesus, vervet, and cynomolgus monkeys in laboratories can develop fatal illnesses after inoculation with Ebola viruses.

No Ebola viruses were found from samples taken from some 30 000 mammals, birds, reptiles, amphibians, and arthropods in outbreak regions between 1976 and 1998. Recent studies have demonstrated the presence antibodies and genetic fragments of Ebola or Marburg viruses in different species of bats. In Uganda in 2008, Marburg viruses were isolated from frugivorous bats.

The situation requires further evaluation by medical, veterinary and biology experts. Testing for the presence of the Ebola Reston virus or antibodies in swine populations, animal handlers and wildlife species will be helpful to understand the chain of events. Understanding how the pigs may have become infected, the mode of transmission between pigs and the potential for spill over to humans is very important toward the design an appropriate public health response. The investigation will take time – with the earliest results expected in weeks to months. Although it is too early to know, there are no reports of sick or ailing people that have had contact with the pigs according to the Philippine Ministry of Health and the Bureau of Animal Industry.

This remains unknown. However, pigs can become infected. While animal illness and mortality were experienced on the farms where the pigs infected with the Ebola Reston virus were bred and raised, other isolated infectious diseases may have caused the outbreaks; the Ebola Reston virus may not have been the sole or main actor. It will be important to identify the different pathogens isolated from the sick or dying pigs from the Philippines and test them individually in carefully planned laboratory experiments under proper biosafety conditions. Necessary and specific laboratory tools (called “reagents”) are being developed to test swine and other animals throughout the Philippines to see how extensive the infection is in Philippine swine populations.

This also remains unknown. It is premature at this time to make sweeping statements regarding the possible risk of infection based on four caretakers infected with the Ebola Reston virus. Producers, veterinarians, health officials, and market intermediaries will need to collaborate closely to develop the answer. Studies need to be carried out in the affected swine commercial sectors, with animal handlers, throughout the market chain and its intermediaries, and with consumers before fuller insights can be gained and advice be provided. Investigators plan to: retrace marketing and butchering operations to likely consumers and through interviews; ask these consumers about recent illnesses in their families or close associations; perform blood tests (using \ specific Ebola Reston reagents); and advise appropriate audiences on improved hygiene in general. The planned laboratory studies should also reveal valuable and critical information.

The experience of the animal caretakers in Reston, Virginia in 1989 gives insight into the human risk posed by this particular filovirus. Although there was high exposure and a normal immune response, no clinical disease was noted.

Sick animals, regardless of the cause should not enter the food chain, nor should carcases or scraps from sick or dead animals be fed to other animals or disposed of in an improper manner. Veterinary and public health inspectors should ensure that animals destined for slaughter do not have a fever and are clinically healthy; consumers should be weary when prices appear too good to be true.

Handling and preparation of meat should be done in a clean environment (with a clean table top, utensils and knife) and the meat should be well-cooked. The above-mentioned elements are all general principles for good hygiene and thorough cooking, which are essential to destroy any bacteria, parasites or viruses that may be present.

Producers, marketers, butchers and market stall owners must be made aware of the situation through awareness efforts by veterinary and public health authorities as to the knowns and unknowns of this evolving situation. People involved in animal production and sale must also be made aware of their responsibility to provide safe food to consumers, which include their own families and friends.

It is not recommended to handle known pork meat infected with Ebola Reston virus since the true risk of infection and consequences are unknown.

When a country has an animal health problem (of known or unknown origin), the authorities should immediately self-impose a ban on exports to neighbours and trading partners. Although this is likely to cause a significant and negative economic impact on the animal industry, an appropriate, self-imposed ban will increase the country’s credibility and maintain the safety of its neighbours and trading partners. Moreover, should a country knowingly allow exportation to continue and the disease spread regionally or transcontinentally, the negative economic impact will increase in the longer term, with the country’s credibility being held in doubt for years or decades to come. Perhaps most importantly, should the animal health problem be of a zoonotic nature (transmissible between animals and humans), the situation could have disastrous implications that far exceed the economic concerns.

Naturally occurring Ebola antibodies have been found in chimpanzees, drills, and baboons. Chimpanzees, gorillas, rhesus, vervet and cynomolgus monkeys have develop clinical illness and frequently die when infected with any of the Ebola viruses. Among wildlife, primates, bats and a few other species in Africa are known to be infected by Ebolavirus under natural conditions. Among livestock and pets, swine are currently the only domestic species found to have been infected.

FAO will update this brief as more information
becomes available


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