Elephant endotheliotropic herpesvirus
Encyclopedia
Elephant endotheliotropic herpesviruses (EEHV) are a type of herpesvirus
, which can cause a highly fatal hemorrhagic disease when transmitted in captivity to young Asian elephant
s. In African elephants, related forms of these viruses, which have been identified in wild populations, are generally benign, occasionally surfacing to cause small growths or lesions. However, some types of EEHV can cause a highly fatal disease in Asian elephants, which kills up to 80% of severely affected individuals. The disease can be treated with the rapid application of antiviral drugs, but this has only been effective in around a third of cases.
The first case of a fatal form of the disease was documented in 1995, though tissue samples from as early as the 1980s have since tested positive for the virus, and localized skin lesions in wild African elephants were recorded in the 1970s. Since 1995, there have been over fifty documented disease cases in North America and Europe, of which only nine have been successfully cured. Those affected are mostly young animals born in captivity, though a small number of older wild-born adults held in zoos have died, and a number of cases caused by the same pathogenic type of EEHV have recently been identified in both orphan and wild calves in Asian elephant populations.
that have been responsible for as many as 70 deaths of both zoo and wild Asian elephants worldwide, especially in young calves. There are currently six known species/types of the probosciviruses, and the most commonly encountered and most pathogenic form EEHV1 also has two chimeric subtypes, 1A and 1B., as well as numerous distinct strains
EEHV1A (originally just known as EEHV1) was the first species/type identified, which causes an acute hemorrhagic disease with a very high mortality rate in Asian elephants. This form of the virus was originally believed to occur naturally in African elephants (occasionally producing skin nodules), and to be transmitted to Asian elephants within captivity, but this concept is still an open question because several other species/types of EEHV(e.g. EEHV2, EEHV3 and EEHV6) instead have now been identified in African elephants., A second lethal subtype, EEHV1B, was identified in Asian elephants in 2001. EEHV3 and EEHV4 have also each been responsible for the deaths of at least one Asian elephant calf
EEHV2 has caused hemorrhagic disease in several African elephants as reported by. Along with EEHV3 and EEHV6 it has also been found in pulmonary lymphoid nodules pulmonary system of several autopsied wild and zoo African elephants.
There are a further five or six species/types and varieties of elephant gammaherpesvirus (EGHVs) found in eye and genital secretions of many healthy Asian and African zoo elephants - e.g. EGHV1, EGHV2, EGHV3A, EGHV3B, EGHV4 and EGHV5 (also called Elephantid herpesviruses EIHV3, EIHV4, EIHV5, EIHV6, ElHV9 and ElHV10 - which are gamma herpesviruses. But these are neither closely related to the EEHVs, nor the known cause of any disease symptoms.
Recent studies have also detected both EEHV1A and EEHV1B as being shed in trunk wash secretions by healthy asymptomatic Asian zoo elephant herdmates of calves that previously had disease. Thus, similar to saliva for most human and animal herpesviruses, the trunk secretions may be a source of transmission for EEHVs. Because of concerns about the origins of EEHV1 and evidence of cross-species transmission for EEHV3, long-term contact between Asian and African elephants has been discouraged, along with avoiding new contacts between young captive-born Asian elephants and wild-born Asian elephants, as the latter may be carriers of the disease. An analysis of a number of North American cases, which ruled out the direct transmission of the virus between any of the affected animals studied, strongly supported the idea of a significant Asian carrier population. This is supported by the fact that some of the deceased calves had no possible contact with any African elephants. Artificial insemination
is not believed to be a transmission factor, though some stillborn calves have tested positive for the virus, indicating it must be transmissible directly from the mother to the child in utero
. A program of enzyme-linked immunosorbent assay testing began in 2005, aiming to test blood samples from around a thousand elephants for antibodies to the virus in order to help identify carriers and possible transmission patterns.
in the head and trunk, or small lymphoid
patches around the genitals, which appear for a few weeks and then regress, suggesting an intermittently active infection which mostly remains dormant. In the second case, it is found in pulmonary nodules
.
In a fatal attack, however, it manifests very quickly. In a number of cases, death has occurred within 24 hours of the onset of the infection, while other cases do not last longer than around five days. The virus attacks endothelial cells, rupturing capillaries and causing blood loss and haemorrhaging; once this reaches the heart, the haemorrhage kills quickly through shock. Symptoms include lethargy and an unwillingness to eat, a rapid heartbeat, and decreased blood-cell count, as well as cyanosis
of the tongue, mouth ulcer
s, and oedema of the head and trunk.
Rapid treatment with famciclovir
, sustained for around a month, has cured six calves infected with EEHV1; however, this treatment is very expensive, only partially effective, and relies on early identification of the infection.
A polymerase chain reaction
test on a blood sample from affected animals will confirm a suspected case by identifying the viral DNA, though it is now common to start famciclovir treatment at the earliest possible moment rather than waiting for confirmation of the case. Prior to the development of the test, or in circumstances where it is not available, the disease may be diagnosed as any of a number of other conditions which have a quick onset leading to rapid death, including encephalomyocarditis and salmonellosis
.
The affected animals are mostly young Asian elephants that had been born in captivity,with half the cases in North America being between the ages of one and three years (and three-quarters between one and eight years old). Some cases have affected newborns or adult elephants born in the wild (oldest aged 40 years), and three recorded cases have affected African elephants. The first documented fatal case for African elephants was Kijana, an eleven-month old male in 1996. In recent years, a number of cases have been attributed to EEHV1 among wild Asian elephants.
The first suspected case in Asia was in 2005, though it was not until the fifth suspected case that the presence of the virus could be confirmed. This case was reported in 2006, with the death of a young wild-born female calf at an elephant sanctuary in Cambodia. The virus was identified as part of the EEHV1 group, the same as previously identified in the North American and European captive populations, but there was no plausible transmission path for the virus from those cases to Asia. It is unclear if this infection reflects an endemic infection in the wild population, or if the other captive elephants in the sanctuary were carriers, and further research has been noted as "urgently required" to study the situation in regions with wild Asian elephant populations.
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...
, which can cause a highly fatal hemorrhagic disease when transmitted in captivity to young Asian elephant
Asian Elephant
The Asian or Asiatic elephant is the only living species of the genus Elephas and distributed in Southeast Asia from India in the west to Borneo in the east. Three subspecies are recognized — Elephas maximus maximus from Sri Lanka, the Indian elephant or E. m. indicus from mainland Asia, and E. m....
s. In African elephants, related forms of these viruses, which have been identified in wild populations, are generally benign, occasionally surfacing to cause small growths or lesions. However, some types of EEHV can cause a highly fatal disease in Asian elephants, which kills up to 80% of severely affected individuals. The disease can be treated with the rapid application of antiviral drugs, but this has only been effective in around a third of cases.
The first case of a fatal form of the disease was documented in 1995, though tissue samples from as early as the 1980s have since tested positive for the virus, and localized skin lesions in wild African elephants were recorded in the 1970s. Since 1995, there have been over fifty documented disease cases in North America and Europe, of which only nine have been successfully cured. Those affected are mostly young animals born in captivity, though a small number of older wild-born adults held in zoos have died, and a number of cases caused by the same pathogenic type of EEHV have recently been identified in both orphan and wild calves in Asian elephant populations.
Virus and transmission
The EEHVs are members of the proboscivirus genus, a novel clade within the mammalian betaherpesvirusesBetaherpesvirinae
Betaherpesvirinae is a subfamily of Herpesviridae distinguished by reproducing less quickly than other subfamilies of Herpesviridae.Betaherpesvirinae establish latency in leukocytes...
that have been responsible for as many as 70 deaths of both zoo and wild Asian elephants worldwide, especially in young calves. There are currently six known species/types of the probosciviruses, and the most commonly encountered and most pathogenic form EEHV1 also has two chimeric subtypes, 1A and 1B., as well as numerous distinct strains
EEHV1A (originally just known as EEHV1) was the first species/type identified, which causes an acute hemorrhagic disease with a very high mortality rate in Asian elephants. This form of the virus was originally believed to occur naturally in African elephants (occasionally producing skin nodules), and to be transmitted to Asian elephants within captivity, but this concept is still an open question because several other species/types of EEHV(e.g. EEHV2, EEHV3 and EEHV6) instead have now been identified in African elephants., A second lethal subtype, EEHV1B, was identified in Asian elephants in 2001. EEHV3 and EEHV4 have also each been responsible for the deaths of at least one Asian elephant calf
EEHV2 has caused hemorrhagic disease in several African elephants as reported by. Along with EEHV3 and EEHV6 it has also been found in pulmonary lymphoid nodules pulmonary system of several autopsied wild and zoo African elephants.
There are a further five or six species/types and varieties of elephant gammaherpesvirus (EGHVs) found in eye and genital secretions of many healthy Asian and African zoo elephants - e.g. EGHV1, EGHV2, EGHV3A, EGHV3B, EGHV4 and EGHV5 (also called Elephantid herpesviruses EIHV3, EIHV4, EIHV5, EIHV6, ElHV9 and ElHV10 - which are gamma herpesviruses. But these are neither closely related to the EEHVs, nor the known cause of any disease symptoms.
Recent studies have also detected both EEHV1A and EEHV1B as being shed in trunk wash secretions by healthy asymptomatic Asian zoo elephant herdmates of calves that previously had disease. Thus, similar to saliva for most human and animal herpesviruses, the trunk secretions may be a source of transmission for EEHVs. Because of concerns about the origins of EEHV1 and evidence of cross-species transmission for EEHV3, long-term contact between Asian and African elephants has been discouraged, along with avoiding new contacts between young captive-born Asian elephants and wild-born Asian elephants, as the latter may be carriers of the disease. An analysis of a number of North American cases, which ruled out the direct transmission of the virus between any of the affected animals studied, strongly supported the idea of a significant Asian carrier population. This is supported by the fact that some of the deceased calves had no possible contact with any African elephants. Artificial insemination
Artificial insemination
Artificial insemination, or AI, is the process by which sperm is placed into the reproductive tract of a female for the purpose of impregnating the female by using means other than sexual intercourse or natural insemination...
is not believed to be a transmission factor, though some stillborn calves have tested positive for the virus, indicating it must be transmissible directly from the mother to the child in utero
In utero
In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...
. A program of enzyme-linked immunosorbent assay testing began in 2005, aiming to test blood samples from around a thousand elephants for antibodies to the virus in order to help identify carriers and possible transmission patterns.
Effects and treatment
In a benign infection, such as that found in some African elephants, the virus can affect either the skin or the pulmonary system. In the former case, it produces small pinkish nodulesNodule (medicine)
For use of the term nodule in dermatology, see Nodule In medicine, a nodule refers to a relatively hard, roughly spherical abnormal structure....
in the head and trunk, or small lymphoid
Lymphoid
Lymphoid is a term used to describe lymph or the lymphatic system.In the context of lymphoid leukemia, it refers specifically to lymphocytes Lymphoid leukemias and lymphomas are now considered to be tumors of the same type of cell lineage. They are called "leukemia" when in the blood or marrow and...
patches around the genitals, which appear for a few weeks and then regress, suggesting an intermittently active infection which mostly remains dormant. In the second case, it is found in pulmonary nodules
Nodule (medicine)
For use of the term nodule in dermatology, see Nodule In medicine, a nodule refers to a relatively hard, roughly spherical abnormal structure....
.
In a fatal attack, however, it manifests very quickly. In a number of cases, death has occurred within 24 hours of the onset of the infection, while other cases do not last longer than around five days. The virus attacks endothelial cells, rupturing capillaries and causing blood loss and haemorrhaging; once this reaches the heart, the haemorrhage kills quickly through shock. Symptoms include lethargy and an unwillingness to eat, a rapid heartbeat, and decreased blood-cell count, as well as cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
of the tongue, mouth ulcer
Mouth ulcer
A mouth or oral ulcer is an open sore in the mouth, or rarely a break in the mucous membrane or the epithelium on the lips or surrounding the mouth. The types of mouth ulcers are diverse, with a multitude of associated causes including: physical abrasion, acidic fruit, infection, other medical...
s, and oedema of the head and trunk.
Rapid treatment with famciclovir
Famciclovir
Famciclovir is a guanine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster . It is a prodrug form of penciclovir with improved oral bioavailability...
, sustained for around a month, has cured six calves infected with EEHV1; however, this treatment is very expensive, only partially effective, and relies on early identification of the infection.
A polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
test on a blood sample from affected animals will confirm a suspected case by identifying the viral DNA, though it is now common to start famciclovir treatment at the earliest possible moment rather than waiting for confirmation of the case. Prior to the development of the test, or in circumstances where it is not available, the disease may be diagnosed as any of a number of other conditions which have a quick onset leading to rapid death, including encephalomyocarditis and salmonellosis
Salmonellosis
Salmonellosis is an infection with Salmonella bacteria. Most people infected with Salmonella develop diarrhea, fever, vomiting, and abdominal cramps 12 to 72 hours after infection. In most cases, the illness lasts four to seven days, and most people recover without treatment...
.
History
The virus has been identified in the pulmonary nodules of African elephants as far back as the 1970s. The first recognised fatal case of EEHV in an Asian elephant was identified at the National Zoo, Washington D.C., in 1995; testing on stored tissue samples was able to identify a number of earlier deaths as being due to the same virus. These cases have so far been identified as early as 1983. Since this date, there have been a total of 54 more cases in North America and Europe, nine of which were successfully treated., quotes 49 cases, but does not include the May 2009 deaths of two calves at Whipsnade Zoo in this calculation. This gives a fatality rate of over 80% among known symptomatic disease cases. In cases where antiviral medication was applied, treatment was effective in about one in three cases. As of 2005, there were twelve cases where famciclovir had been used, eight of which were fatal. As a fraction of the overall population, it has been calculated that of the 78 Asian elephants born in captivity in North America between 1978 and 2007, 19 are known to have died of EEHV, and five more were successfully treated with antiviral medication.The affected animals are mostly young Asian elephants that had been born in captivity,with half the cases in North America being between the ages of one and three years (and three-quarters between one and eight years old). Some cases have affected newborns or adult elephants born in the wild (oldest aged 40 years), and three recorded cases have affected African elephants. The first documented fatal case for African elephants was Kijana, an eleven-month old male in 1996. In recent years, a number of cases have been attributed to EEHV1 among wild Asian elephants.
The first suspected case in Asia was in 2005, though it was not until the fifth suspected case that the presence of the virus could be confirmed. This case was reported in 2006, with the death of a young wild-born female calf at an elephant sanctuary in Cambodia. The virus was identified as part of the EEHV1 group, the same as previously identified in the North American and European captive populations, but there was no plausible transmission path for the virus from those cases to Asia. It is unclear if this infection reflects an endemic infection in the wild population, or if the other captive elephants in the sanctuary were carriers, and further research has been noted as "urgently required" to study the situation in regions with wild Asian elephant populations.