Viruses from Bushmeat

Ebola and Marburg viruses

Ebola virus (EBOV) and Marburg virus (MARV) belong to the Filoviridae family and have a non-segmented (-)sense RNA genomes. EBOV was first identified near the Ebola River in an outbreak in Zaire (now the Democratic Republic of Congo or DRC) in 1976. There are four strains of EBOV Zaire, Sudan, Ivory Coast and Reston. Ebola-Zaire appears to be the deadliest strain with up to 89% of cases being fatal (Sullivan et al. 2003a).

Humans acquire Ebola from a number of different sources which include coming into contact with infected chimpanzees, gorillas, monkeys, duikers and porcupines (Feldmann et al. 2004 and Lawson 2002). All of these mammals are sources of bushmeat (Wilkie and Carpenter 1999). There is a constant risk in Ebola endemic areas that indigenous people will continue to eat bushmeat despite the risk of Ebola infection. Walsh et al. (2003) found that infection of NHPs is not only causing outbreaks of Ebola in human populations it is also causing a rapid reduction in ape populations and Ebola along with hunting could push ape populations towards extinction.

There have been a number of outbreaks which can be traced back to contact with blood or body fluids of an infected mammal, for example Leroy et al. (2004) state that serological tests of an Ebola survivor from Mekambo, Gabon in 2002 and the L gene of EBOV extracted from a gorilla matched indicating gorillas as the source of the outbreak. By looking at epidemic chains and tracing back to the index patients a number of mammalian species have been indicated as the source of the outbreak. The first recorded transmission of EBOV from chimpanzees to humans without the tracing-back of epidemic chains occurred in 1995. In an article by Morell (1995) the unusual deaths of a number of chimpanzees in the Tai forest in the Ivory Coast lead to an autopsy on a chimpanzee body, which was carried out by three scientists all of which became infected with Ebola. Serological tests on this unknown strain of Ebola lead to its discovery as the fourth strain of Ebola, Ebola-Ivory Coast.

Bats are also thought to be sources for viral infection of humans (Feldmann et al. 2004). Swanepoel et al. (1996) found that fruit and insectivorous bats when experimentally infected with Ebola act as a reservoir for Ebola via an increase in viral titres without being affected at all by the virus. Morvan et al. (1999) also speculated that small rodents and shrews could be the reservoir for EBOV but their investigation was inconclusive and the reservoir source remains elusive.

Secondary infection does occur whereby human-to-human transmission takes place. This is often seen amongst families and even to healthcare workers (HCWs) who are trying to treat the disease (nosocomial transmission, transmission of a disease from patient to a HCW). In some villages there is a problem with burial rituals because removal of certain body parts takes place, this would probably spread infection further (Lawson 2002 and WHO Ebola Factsheet 2004).

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The clinical manifestations of Ebola are characteristic and have even been exploited in Hollywood as a disease of extreme severity, the film Outbreak. Incubation of the disease is between 2-21 days but commonly incubates for 5-12 days. Initial symptoms of the disease include muscle pain, malaise, head aches, a sore throat and then fever. Nausea, vomiting and watery diarrhea occur with some patients developing a maculopapular rash, red eyes and have hiccups. Some patients go on to develop the characteristic haemorrhagic symptoms, coagulation abnormalities result in bloody diarrhea, epistaxis (bleeding from the nose), gum haemorrhage bleeding can occur at any orifice or any area of skin and internal bleeding also takes place in the gastrointestinal tract and the lungs. If the patient does not recover by the second week then they will drop into a coma and die from necrosis of the liver and spleen, cerebral oedema and multiple organ failure (CDC Ebola Factsheet 2002, Sullivan et al. 2003a, WHO Ebola 1997, WHO Ebola Factsheet 2004). EBOV and MARV are clinically indistinguishable therefore MARV can be as devastating as EBOV as witnessed in Angola, April 2005 (WHO Disease Outbreak News Marburg Virus Update 9 2005).

With a mortality rate of 50-90% EBOV is an extremely deadly virus that can be obtained from bushmeat and should be treated with great concern.

Monkeypox virus

Monkeypox virus (MPV) is a member of the Poxviridae family and the Orthopoxvirus genus. The variola virus (smallpox) is also a member of the Orthopoxvirus genus and there is a 96.3% homology between the two species and they only differ in the end regions of the genomes. Although they probably originated from a common ancestor both viruses have evolved separately (Douglass and Dumbell, 1992). As well as being very similar genetically they are also difficult to distinguish clinically.

The first human case of MPV was recorded in DRC, 1970 (Bayer-Garner 2005). MPV is now endemic in central and western Africa and epidemics have occurred in the DRC, Cameroon, Gabon and Sierra Leon. Most recently in Africa there has been re-emergence of MPV in Zaire (1996) and Democratic Republic of Congo (1996-1997). During the outbreak in Zaire there were 71 human cases of MPV and 6 fatalities whilst there were 419 cases of MPV recorded in the Democratic Republic of Congo (Di Giulio et al. 2004 and Mukinda et al. 1997).

The reservoirs for MPV are a number of African squirrels, non-human primates and rodents. Di Giulio et al. (2004) in their review mention a serosurvey of animals that live near human settlements in the Congo where Funisciurus spp squirrels were 24% seropositive for MPV and Heliosciurus spp squirrels were 15% positive and non-human primates were 8% positive. A bite from one of these animals or skin-to-skin contact would constitute as a primary infection. A secondary infection occurs via inhalation of MPV material from an infected individual or animal (Bayer-Garner 2005 and Lewis-Jones 2004).

In the USA in June 2003 there was an outbreak of MPV. There were 37 laboratory confirmed cases of MPV out of a suspected 72 and a number of the cases required hospitalization. Although there were no fatalities one child developed encephalitis (Lewis-Jones 2004). The zoonotic vectors for MPV transmission were the exotic pets, prairie dogs. MPV is also enzoonotic because the prairie dogs acquired MPV from imported African animals. The types of animals that transferred MPV to the prairie dogs included a Gambian pouched giant rat, striped mice, rope squirrels and tree squirrels along with genets and palm civets (Di Giulio et al. 2004 and Reynolds et al. 2004). Human cases of MPV occurred in Illinois, Indiana, Ohio, New Jersey, Kansas and Wisconsin (US Department of Health and Human Services 2003).

Before the onset of the papular rash (which is clinically indistinguishable from the papular rash of smallpox figure 5) patients suffer from headaches, malaise, muscle aches, fever and respiratory problems. The clinical manifestations of MPV last two to four weeks and the mortality rate in past epidemics was 11% but 15% in children in the unvaccinated populations (Lewis-Jones 2004). Bayer-Garner (2005) stated that there are slight clinical differences between smallpox and MPV. MPV patients suffer from swollen lymph nodes (lymphadenopathy), "pre-eruptive fever and slower maturation of skin lesions" (Bayer-Garner 2005). Encephalitis as a result of MPV infection has been recorded. Di Giulio and Eckburg (2004) mentioned that in 1968 experimental monkeys were vaccinated against MPV via vaccination with vaccinia virus and the CDC state that this vaccine is >85% effective.

Rabies

Rabies belongs to the order Mononegvirales, and is part of the Rhabdoviridae family and the Lyssavirus genus. There are seven species of Lyssavirus with serotype 1 being classic rabies (CDC Rabies Homepage 2004 and WHO Rabies 2002). Rabies can be acquired from a number of different carnivorous animals that include dogs, cats, ferret, raccoons, and bats (Morrison 2001, Rupprecht et al. 2002, WHO Rabies 2001, and Weber et al. 2001). For the purpose of this project it is important to note that it can be acquired from ferrets which are a common exotic pet. In the USA five to seven million ferrets are kept as pets but there are no recorded cases of rabies acquisition from ferrets (Morrison 2001 and Weber 2001). The most common vectors for rabies are dogs and they cause roughly 35,000 human fatalities annually (Rupprecht et al. 2002). The WHO (2002) estimate that there are 50,000 deaths attributed to rabies annually with 30,000 of these deaths occurring in India and 99% of all deaths occurring in Africa, Asia and South America. Children aged 5-15 are most at risk from rabies.

Rabies is transmitted from the infected animals saliva to humans via a transdermal bite, scratch or even lick to a mucous membrane (mouth, eye, skin lesion). The virus proliferates inside the body in muscle or connective tissues where it had been inoculated. The virus particles then enter peripheral nerves and travel to the CNS by retrograde axonal transport. The formation of inclusion bodies (Negri bodies) in the cells of the hippocampus and cerebellum are a characteristic of postmortem brain slices of rabies fatalities (CDC Rabies Homepage 2004 and WHO Rabies 2002).

The length of incubation of rabies depends on the site of the bite and the size of the inoculation, therefore incubation can last up to 3 weeks to a year. Clinical signs of the disease take two forms furious rabies and paralytic rabies. Initial symptoms after infection include fever and pain at inoculation site. Symptoms associated with furious rabies are linked with spasms for example hydrophobia is classically linked to rabies, people with hydrophobia are scarred to drink fluids because of the spasms that occur when swallowing and aerophobia is another classic symptom. Behavioral changes also transpire for example anxiety, agitation, confusion and fluctuating consciousness. Paralytic rabies is characterized by myoedema and roughly 50% of paralytic rabies patients endure phobic spasm. But both furious and paralytic rabies patients die via respiratory paralysis leading to a coma and then death (Rupprecht et al. 2002, WHO Rabies 1992 and WHO Rabies 2001). If rabies is not treated before the clinical onset of the disease then the patient will die but there is an exception.

Severe Acute Respiratory Syndrome (SARS)

SARS is a member of the Coronaviridae (SARS-CoV). The Coronaviridae consists of three groups but SARS does not belong to any of these, phylogenetic analysis shows that an isolated coronavirus (CoV) from civets has a 99% sequence homology with SARS (Lai 2003). Therefore inter-species transmission of SARS across the species barrier had taken place.

The reservoir for SARS-CoV has been identified in a number of small carnivores which include Chinese ferret badgers (Melogale moschata), raccoon dogs (Nyctereuters procyonoids) and masked palm civets (Paguma larvata) from wet markets in the Guangdong Province (Bell et al. 2004, Guan et al. 2003 and WHO SARS 2004). A SARS-like virus has also been isolated from birds, ferrets, snakes and cats (Bell et al. 2004 and WHO SARS 2004). The majority of these animals are used in traditional medicine or are bushmeat, in fact a number of species of viverrids are eaten as bushmeat in Africa (Bell et al. 2004). As with the bushmeat trade in Africa, there are a number of people that can be part of the chain that handles the exotic meat before it reaches the consumer. For example Xu et al. (2004) recognized that hunters (commercial and subsistent), traders and even chefs were at risk of infection. Therefore the handling of infect meat and animals is mostly associated with SARS contraction rather than the consumption of the meat.

The first case of SARS arose in the Guangdong Province, China in November 2002. It was first described as atypical pneumonia but later discovered to be caused by CoV. At first cases were sporadic but then by February 2003 the epidemic had spread all over the province (Xu et al. 2004). The majority of cases occurred during February and after this large outbreak the number of cases remains relatively high until the end of April. This graph also shows a correlation, as the number of SARS cases in members of the community rises there is a rise in cases of SARS in healthcare workers (HCWs) indicating the probability of nosocomial transmission (Xu et al. 2004). SARS became a pandemic, 28 countries had reported cases of SARS by May 2003 by which time WHO had already announced that SARS was the "first severe infectious disease of the 21^st century" (Bell et al. 2004 and Donnelly et al. 2003).

WHO (2004) have stated that SARS is acquired from infected animals and infected humans via their respiratory secretions, body fluids or excretions. A lack of cleanliness was probably a major factor in the rapid spread of SARS. HCWs contracted the disease whilst treating infected patients and inhaling infected respiratory secretions.

Donnelly et al. (2003) stated that the fatality rate of people under the age of 60 is 13.2% and for people over 60 it is 43.3%. There are a number of clinical symptoms that are related to SARS that occur after a 2-7 day incubation period with the most common symptom being a fever (+38°C). Fever is usually associated with headaches, chills, myalgia, malaise, loss of appetite, vomiting and diarrhea. 3-7 days later lower respiratory tract problems transpire, a non-productive cough may develop and shortness of breath (dyspnea) usually leads to hypoxemia (low oxygen concentration in blood). Respiratory failure results in death. Due to many of the SARS symptoms being similar to influenza symptoms clinicians may use chest radiographies and leukocyte counts to differentiate and establish the extent of the disease (WHO SARS 2004 and Xu et al. 2004).

Simian Foamy Virus

Simian Foamy Virus (SFV) belongs to the Retroviridae. Foamy viruses (FV) have been speculated as being a cause of a plethora of disease, which include multiple sclerosis, Graves disease and Myasthenia Gravis. The human form of SFV, SFVcpz(hu) is not a different strain of FV but a variant strain, genetic sequencing and comparison of SFV and SFVcpz(hu) pol gene shows a 89-92% homology. Phylogenetic analysis has shown that SFVcpz(hu) has originated from SFV strains from chimpanzees and baboons (Hussain et al. 2003, Meiering et al. 2001, Schweizer et al. 1997, Switzer et al. 2004, Wolfe et al. 2004).

African green monkeys, chimpanzees, cats, cattle and rhesus macaques have all been found to harbor SFV and the prevalence of SFV is higher in animals in captivity than in wild animals. SFV is a zoonotic disease because it is acquired from NHPs from their saliva via a bite or lick. Meiering et al. (2001) and Wolfe et al. (2004) mention how hunting bushmeat can place humans into direct contact with infected blood and body fluids. Switzer et al. (2004) stated that hunters were not the only group of people at risk, caretakers of NHPs at zoos were also under an occupational risk. In a serosurvey of 186 people who could come into contact with NHPs (zoo workers), nine people were seropostive for SFV, ~5%. SFV viral titres of infected people have risen over 20-30 decades in some cases but yet SFV causes no visible clinical manifestations (Switzer et al. 2004).

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Simian Immunodeficiency Virus (SIV) and Human Immunodeficiency Virus (HIV)

SIV and HIV are group VI viruses and belong to the Retroviridae. Strains of HIV are thought to have originated from serotypes of SIV. HIV is the most important virus of the 21^st century because globally (1980-2000) it has infected over 50 million people and killed 16 million. Therefore HIV is pandemic (Hahn et al. 2000a, Hahn et al. 2000b and Marx et al. 2004). Sub-Saharan Africa has the highest prevalence of HIV cases 25.4 million and 2.3 million deaths in 2004 (UNAIDS). The estimated number of people infected with HIV globally was 39.4 million and there were also 3.1 million deaths in 2004 from AIDS (UNAIDS and WHO 2004).

There are two primary types of HIV; HIV-I and HIV-2. HIV-I is further sub-divided into group M (main group), O (outer linear group) and N (non-M and non-O). HIV-I group M is the main serotype and the major cause of AIDS cases (Sharp et al. 2001). HIV-2 is also subdivided, into groups A-F (Hahn et al. 2000a).

When someone is infected with HIV and their CD4⁺ cell count drops below 200mL^-1 they are diagnosed with AIDS (acquired immune deficiency syndrome). Due to their suppressed immune system AIDS patients usually become infected with opportunistic pathogens such as Mycobacterium tuberculosis, or they develop tumours and become emaciated.

HIV is thought to have evolved from cross-species transmission of SIV, numerous serotypes of SIV can be found in roughly 26 species of monkeys and NHPs including chimpanzees (SIVcpz), sooty mangabeys (SIVsm) and members of the African Green Monkey genus; vervets (SIVagmVer) and grivets (SIVagmGri). SIV can be extremely prevalent among some species of NHPs for example SIVsm can have a prevalence of 22% among sooty mangabey troops (Hahn et al. 2000a and Peeters et al. 2002). Cross-species transmission of SIV serotypes between NHPs and monkeys has been documented by Peeters et al. (2002), in the wild SIVsm had been isolated from yellow baboons, and patas monkeys. Cross-species transmission may occur between NHPs when they come into contact with the infected blood, tissues (hunting) or mucous secretions (bite) of an infected animal. SIV is thought to be predominantly asymptomatic in NHPs (Sharp et al. 2001).

Peeters et al. (2002) mentioned eight zoonotic transfers of SIV to humans. Marx et al. (2004) documented an incidence where laboratory workers acquired SIVsmB670 zoonotically but after infection these workers were asymptomatic. Interestingly inoculation of macaques with SIVhu (the SIVsm extracted from humans) had no effect on the macaques. Sequence analysis showed that SIVsm had undergone a number of deletions after cross-species transfer, which shows that if SIV was to evolve into a strain of HIV and cross the species barrier it needs to adapt to the new host genome so replication and expression can occur.

General consensus of the scientific community states that for SIV to change into HIV, multiple cross-species transmissions must have taken place between NHPs and humans, a minimum of seven times (Hahn et al. 2000a and Sharp 2001). By comparing the env (Corbet et al. 2000 and Yang et al. 2000), gag (Hahn et al. 2000a) and pol (Masciotra et al 2002) gene sequences of SIV and HIV serotypes phylogenetic trees have been constructed which show the evolutionary lineage of SIV/HIV:

A phylogenetic tree of SIV and HIV serotypes and their evolutionary lineages, the x indicates probable points of cross-species transmission (Sharp et al. 2000). From the above figure we can see that HIV-I and HIV-2 are interspersed between different types of SIV therefore indicating that HIV evolved via different cross-species transmissions. HIV-I has evolved from SIVcpz which had been isolated from the chimpanzee subspecies Pan troglodytes troglodytes. Further anaylsis has shown that both SIVcpz and HIV-I have almost identical genomes and both encode the gene vpu, which no other lentivirus encodes. HIV-2 is almost identical to SIVsm isolated from sooty mangabays and we can see in figure 6 that HIV-2 has divulged from SIVsm. SIVsm and HIV-2 both encode Vpx which no other lentivirus encodes (Gao et al. 1999, Hahn et al. 2000a and Sharp et al. 2000). Therefore HIV-I originates from chimpanzees whilst HIV-2 originates from sooty mangabays.

The cross-species transmission of SIV to humans from NHPs occurred via hunting and butchering of these primates for bushmeat and a number of orphan primates are kept as pets after their parents have been killed, bites from these pets could transmit the virus (Wolfe et al. 2004).

Simian T cell Lymphoma Virus (STLV) and Human T cell Lymphoma Virus (HTLV)

STLV and HTLV belong to the Retroviridae. Primate T lymphotrophic virus type 1 (PTLV-I) has been isolated in humans, NHPs and monkeys. The two main serotypes of PTLV-I are STLV-I and HTLV-I. HTLVs are thought to originate from STLVs due to the numerous sequence homologies observed between different subtypes of both HTLV and STLV therefore these viruses co-evolved (Leedertz et al. 2004, Slattery et al. 1999 and Vandamme et al. 1998).

Nerrienet et al. (2004) carried out a serosurvey on 56 chimpanzees and 5 gorillas, Cameroon. Results show that a newly discovered strain of STLV-1, PTR-CAM43 shares a 94.8% homology with another strain of STLV-I, PTR-CAR875. PTR-CAM43 has a 98.2% homology with a strain of HTLV-I (12503) which was isolated from pygmies in the Central African Republic. Nerrienet et al. also discovered a form of STLV subtype B in gorillas, GGO-CAM12 (Nerrienet et al. 2004).

Interspecies transmission of strains of STLV between NHPs is common and has been documented with chimpanzees and red colobus monkeys in Tao National Park, Ivory Coast. Chimpanzees and colobus monkeys are examples of bushmeat and if chimpanzees have contracted STLV-I from colobus monkeys then it is probable that humans will come into contact with the disease as they obviously have done in the past (Leedertz et al. 2004). HTLV and HTLV is a major cause of disease globally. 15-20 million people are thought to be infected with HTLV worldwide and it is endemic in central Africa, the Caribbean, parts of South America, Middle East, Japan, parts of Europe, Indonesia and Australia (HPA HTLV 2003, Slattery et al. 1999 and Vandamme 1998).

HTLV only manifests in 5% of those infected, the rest are asymptomatic carriers. HTLV-I is the cause of Adult T cell leukemia/lymphoma (ATLL), which is a lymphoma of CD4⁺ cells and HTLV-I also causes HTLV-I-associated myelopathy (HAM) which is also known as Tropical Spastic Paraparesis (TSP), which is a neurological disorder. Some people may also suffer from rheumatoid arthritis, dermatitis, asthma and uveitis (inflammation of the eye) (HPA HTLV 2003, Murphy et al. 2004 and Slattery et al. 1999).

HTLV is transmitted in the same fashion as STLV among NHPs and monkeys. HTLV is acquired through sexual contact, it can be passed to children through breast feeding and by coming into contact with infected blood either via consumption (bushmeat) or via blood transfusions and intravenous drug abuse among humans (Vandamme et al. 1998).

Like microbial zoonoses, there are a number of viral zoonoses that can be acquired from bushmeat and exotic pets. There are a number of other viral zoonoses that can be acquired from exotic pets and via contact with bushmeat. For example Herpesvirus simiae or B virus is passed from exotic pet macaques to humans via bites and scratches (Ostrowski et al. 1998). Vartanian et al. (2002) documented the presence of Hepatitis B Virus (HBV) in chimpanzees (Pan troglodytes schweinfurthi) from east Africa and Noppornpanth et al. (2003) mention the presence of HBV in gorillas. With chimpanzees and gorillas being a type of bushmeat in this region there may be a risk of contraction. The consumption of wild Sika deer in Japan lead to the contraction of Hepatitis E Virus (HEV) proving it to be a zoonosis (Tei et al. 2003).

© MicrobiologyBytes 2007.