Zoonotic InfectionsPublication Exclusive

Ebola: The zoonotic aspects

When WHO announced the first appearance of a new, fatal emerging disease in Central Africa, the report included the following information: “electron microscopy studies on specimens from Sudan and Zaire have revealed a virus morphologically similar to Marburg virus.” Marburg virus disease (MVD) was already known as a highly pathogenic zoonotic disease. It was initially discovered in 1967 in the German city of Marburg, where cases of hemorrhagic fever with a fatality rate of more than 25% occurred among laboratory workers who had contact with the blood, organs or cell-cultures from a batch of African green monkeys (grivets, Chlorocebus aethiops) imported from northwestern Uganda. Cases also were seen in medical personnel who treated the patients and in one family member indicating human-to-human transmission. A similar event involved laboratory personnel in Frankfurt and Belgrade, where tissues of Ugandan grivets were handled.

The closeness of the new virus to Marburg virus was established in three laboratories. In deference to the countries involved and to the lack of specific knowledge of the original natural source of the virus, it was decided that no names of countries or specific towns be used, and the new virus was coined Ebola virus, after the small river in Zaire (now the Democratic Republic of the Congo, or DRC), north of Yambuku, the village of origin of the patient from whom the first isolate was obtained. The two viruses, characterized by filamentous infectious viral particles, have been grouped in the family Filoviridae. This family currently includes the genus Ebolavirus and the genus Marburgvirus. The genus Ebolavirus (EBOV) currently consists of five species: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SUDV), Tai forest ebolavirus (TAFV), Bundibugyo ebolavirus (BDBV) and Reston ebolavirus (RESTV). RESTV is considered to be nonpathogenic to humans but has been found to infect pigs (in the Philippines). Most of the outbreaks so far, including the current major one, have been caused by ZEBOV.

Experimental infection trials in rhesus and vervet monkeys with ZEBOV, carried out in 1977 in the Microbiological Research Establishment in Porton, United Kingdom, led to the death of all of them 6 to 12 days after infection. Their disease course and hematological, gross pathology and histopathological changes were very similar to those observed in man, with disseminated intravascular coagulation shown to be a prominent feature of the disease.

Since 1976, 23 outbreaks of Ebola virus were identified in humans across Africa. It has become agreed, though not always demonstrable, that each outbreak started with a single infection of the index human case sourced from the virus reservoir, subsequently spreading further by human-to-human transmission.

Arnon Shimshony

Arnon Shimshony

Which reservoir species are responsible for maintaining Ebola transmission between outbreaks is not well understood, but over the last decade significant progress has been made in narrowing down the list of likely hosts. Primates have been known to harbor filoviral infections since 1967, when Marburg virus was identified in African green monkeys. Significant mortality also has been reported in wild primate populations across Africa, most notably in gorilla (Gorilla gorilla) and chimpanzee (Pan troglodytes) populations. Contact with the tissues of dead nonhuman primates was a source of infection for humans on at least two occasions in Africa. Nevertheless, the lethality of the viruses for nonhuman primates, combined with their declining populations and limited geographical range, suggest that, like humans, they are incidental victims of infection and are not true reservoir hosts.

A large survey of small mammals in and around Gabon identified three species of fruit bats infected with Ebola viruses — Hypsignathus monstrosus (hammer-headed bat/big-lipped bat), Epomops franqueti (Franquet’s epauletted fruit bat) and Myonycteris torquata (little collared fruit bat). Subsequent serological surveys and evidence linking the potential source of human outbreaks to bats lend support to the hypothesis of a bat reservoir. This, coupled with repeated detection of Marburgvirus in the Egyptian fruit bat Rousettus aegypticus in Kenya, support the suspicion that Chiroptera (bats) play an important role in the natural life-cycle of the filoviruses. The postulated role of bats as an EBOV reservoir also was supported by the results of an experiment in the National Institute for Virology, Sandringham, South Africa, in 1996, where 33 varieties of 24 species of plants, 13 species of vertebrates (seven reptiles, three bats, two rodents and one pigeon) and six species of invertebrates were experimentally inoculated with EBOV. The only species that could be infected were bats; this was followed by replication and circulation of high titers of the virus without necessarily becoming ill.

According to the published epidemiological investigation, the index case of the current major Ebola epidemic took place in Meliandou, Guéckédou Prefecture, Guinea, in December 2013, probably from bat source. In March 2014, when the dimensions of the epidemic became alarming, the sale and consumption of bats was officially banned in Guinea. It was said that people who eat the animals often boil them into a sort of spicy pepper soup. Other ways of preparing the bats to eat included drying them over a fire.

Fifty-one surveyed locations reporting infections in animals were identified in the literature since the discovery of the disease in 1976. These included 17 infections in gorillas, nine in chimpanzees, 18 in fruit bats and two in duikers (a forest deer, Cephalophus spp.). A large proportion of the great ape cases originated from the DRC/Gabon border, coinciding with the main known distributions of both chimpanzees and gorillas and representing a period of well-documented great ape Ebola outbreaks in and around the Lossi Animal Sanctuary, DRC. All animal isolations of Ebola viruses have come from countries that also have reported index cases of human outbreaks, with the exception of several seropositive bats from a survey in southern Ghana.

While fruit bats are considered a natural reservoir, the involvement of other species in the EBOV transmission cycle is unclear, especially for domesticated animals. Dogs and pigs are so far the only domestic animals identified as species that can be infected with EBOV. In 2009, REBOV was the first EBOV reported to infect swine with indicated transmission to humans (asymptomatic); and a survey in Gabon found more than 30% seroprevalence for EBOV in dogs during the Ebola outbreak in 2001 and 2002. While infections in dogs appear to be asymptomatic, pigs experimentally infected with EBOV can develop clinical disease, depending on the virus species and possibly the age of the infected animals. In the experimental settings, pigs can transmit ZEBOV to naive pigs and macaques; however, their role during Ebola outbreaks in Africa needs to be clarified. In case pigs or dogs become — following further required studies — implicated in the transmission of an African species of EBOV to humans, development of veterinary vaccines might need to be considered.

The possible role of dogs in Ebola epidemiology became a matter of publicized debate in October 2014 when a pet dog in Spain suspected to have been exposed to EBOV infection during the illness of its owner was precautionarily euthanized. Another dog owned by an Ebola patient in Texas was quarantined and released after 21 days in the absence of disease or proven infection. The issue has been later addressed by an expert panel of the European Food Safety Agency. Their conclusions, published Dec. 4, 2014, included the following: “The probability of human exposure to the virus through contact with exposed pets is difficult to assess and may range from very low to high depending on the specific circumstances. It is recommended that risk be assessed jointly by veterinary and public health authorities using a case-by-case approach. In the absence of information about possible EBOV infection in pets and the potential for onward transmission, full precautionary measures should be taken when handling pets of persons infected with EBOV.”

The World Organisation for Animal Health (OIE) recently published its experts’ views and guidelines on Ebola, summarizing:

“Ebola is most likely initially transmitted from animals such as bats and nonhuman primates to humans through hunting and collection of sick or dead wild animals and handling or consumption of uncooked bush meat. In rural areas fruit bats are a popular source of forest meat for humans and are prepared by hand to be dried, smoked and/or cooked. Infection could also be transmitted to humans by handling or consumption of forest fruits contaminated with bat saliva or feces in affected areas.

“The OIE is in full accordance with [WHO] recommendations, to avoid contact with wild animals, including bats, monkeys and rodents, in affected areas.”

References:

EFSA. EFSA Journal. 2014;12:3930.
OIE. OIE experts review current knowledge on Ebola virus disease. http://www.oie.int/for-the-media/press-releases/detail/article/oie-experts-review-current-knowledge-on-ebola-virus-disease. (2014).
Pigott DM. Elife. 2014;doi:10.7554/eLife.04395.
WHO. Epidem Rec. 1976;51:325-332.

For more information:

Arnon Shimshony, DVM, is an associate professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail animal diseases zoonoses moderator. Shimshony was chief veterinary officer, State of Israel, from 1974 to 1999. He also is a member of the Infectious Disease News Editorial Board. 

Disclosure: Shimshony reports no relevant financial disclsoures.

When WHO announced the first appearance of a new, fatal emerging disease in Central Africa, the report included the following information: “electron microscopy studies on specimens from Sudan and Zaire have revealed a virus morphologically similar to Marburg virus.” Marburg virus disease (MVD) was already known as a highly pathogenic zoonotic disease. It was initially discovered in 1967 in the German city of Marburg, where cases of hemorrhagic fever with a fatality rate of more than 25% occurred among laboratory workers who had contact with the blood, organs or cell-cultures from a batch of African green monkeys (grivets, Chlorocebus aethiops) imported from northwestern Uganda. Cases also were seen in medical personnel who treated the patients and in one family member indicating human-to-human transmission. A similar event involved laboratory personnel in Frankfurt and Belgrade, where tissues of Ugandan grivets were handled.

The closeness of the new virus to Marburg virus was established in three laboratories. In deference to the countries involved and to the lack of specific knowledge of the original natural source of the virus, it was decided that no names of countries or specific towns be used, and the new virus was coined Ebola virus, after the small river in Zaire (now the Democratic Republic of the Congo, or DRC), north of Yambuku, the village of origin of the patient from whom the first isolate was obtained. The two viruses, characterized by filamentous infectious viral particles, have been grouped in the family Filoviridae. This family currently includes the genus Ebolavirus and the genus Marburgvirus. The genus Ebolavirus (EBOV) currently consists of five species: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SUDV), Tai forest ebolavirus (TAFV), Bundibugyo ebolavirus (BDBV) and Reston ebolavirus (RESTV). RESTV is considered to be nonpathogenic to humans but has been found to infect pigs (in the Philippines). Most of the outbreaks so far, including the current major one, have been caused by ZEBOV.

Experimental infection trials in rhesus and vervet monkeys with ZEBOV, carried out in 1977 in the Microbiological Research Establishment in Porton, United Kingdom, led to the death of all of them 6 to 12 days after infection. Their disease course and hematological, gross pathology and histopathological changes were very similar to those observed in man, with disseminated intravascular coagulation shown to be a prominent feature of the disease.

Since 1976, 23 outbreaks of Ebola virus were identified in humans across Africa. It has become agreed, though not always demonstrable, that each outbreak started with a single infection of the index human case sourced from the virus reservoir, subsequently spreading further by human-to-human transmission.

Arnon Shimshony

Arnon Shimshony

Which reservoir species are responsible for maintaining Ebola transmission between outbreaks is not well understood, but over the last decade significant progress has been made in narrowing down the list of likely hosts. Primates have been known to harbor filoviral infections since 1967, when Marburg virus was identified in African green monkeys. Significant mortality also has been reported in wild primate populations across Africa, most notably in gorilla (Gorilla gorilla) and chimpanzee (Pan troglodytes) populations. Contact with the tissues of dead nonhuman primates was a source of infection for humans on at least two occasions in Africa. Nevertheless, the lethality of the viruses for nonhuman primates, combined with their declining populations and limited geographical range, suggest that, like humans, they are incidental victims of infection and are not true reservoir hosts.

A large survey of small mammals in and around Gabon identified three species of fruit bats infected with Ebola viruses — Hypsignathus monstrosus (hammer-headed bat/big-lipped bat), Epomops franqueti (Franquet’s epauletted fruit bat) and Myonycteris torquata (little collared fruit bat). Subsequent serological surveys and evidence linking the potential source of human outbreaks to bats lend support to the hypothesis of a bat reservoir. This, coupled with repeated detection of Marburgvirus in the Egyptian fruit bat Rousettus aegypticus in Kenya, support the suspicion that Chiroptera (bats) play an important role in the natural life-cycle of the filoviruses. The postulated role of bats as an EBOV reservoir also was supported by the results of an experiment in the National Institute for Virology, Sandringham, South Africa, in 1996, where 33 varieties of 24 species of plants, 13 species of vertebrates (seven reptiles, three bats, two rodents and one pigeon) and six species of invertebrates were experimentally inoculated with EBOV. The only species that could be infected were bats; this was followed by replication and circulation of high titers of the virus without necessarily becoming ill.

According to the published epidemiological investigation, the index case of the current major Ebola epidemic took place in Meliandou, Guéckédou Prefecture, Guinea, in December 2013, probably from bat source. In March 2014, when the dimensions of the epidemic became alarming, the sale and consumption of bats was officially banned in Guinea. It was said that people who eat the animals often boil them into a sort of spicy pepper soup. Other ways of preparing the bats to eat included drying them over a fire.

Fifty-one surveyed locations reporting infections in animals were identified in the literature since the discovery of the disease in 1976. These included 17 infections in gorillas, nine in chimpanzees, 18 in fruit bats and two in duikers (a forest deer, Cephalophus spp.). A large proportion of the great ape cases originated from the DRC/Gabon border, coinciding with the main known distributions of both chimpanzees and gorillas and representing a period of well-documented great ape Ebola outbreaks in and around the Lossi Animal Sanctuary, DRC. All animal isolations of Ebola viruses have come from countries that also have reported index cases of human outbreaks, with the exception of several seropositive bats from a survey in southern Ghana.

While fruit bats are considered a natural reservoir, the involvement of other species in the EBOV transmission cycle is unclear, especially for domesticated animals. Dogs and pigs are so far the only domestic animals identified as species that can be infected with EBOV. In 2009, REBOV was the first EBOV reported to infect swine with indicated transmission to humans (asymptomatic); and a survey in Gabon found more than 30% seroprevalence for EBOV in dogs during the Ebola outbreak in 2001 and 2002. While infections in dogs appear to be asymptomatic, pigs experimentally infected with EBOV can develop clinical disease, depending on the virus species and possibly the age of the infected animals. In the experimental settings, pigs can transmit ZEBOV to naive pigs and macaques; however, their role during Ebola outbreaks in Africa needs to be clarified. In case pigs or dogs become — following further required studies — implicated in the transmission of an African species of EBOV to humans, development of veterinary vaccines might need to be considered.

The possible role of dogs in Ebola epidemiology became a matter of publicized debate in October 2014 when a pet dog in Spain suspected to have been exposed to EBOV infection during the illness of its owner was precautionarily euthanized. Another dog owned by an Ebola patient in Texas was quarantined and released after 21 days in the absence of disease or proven infection. The issue has been later addressed by an expert panel of the European Food Safety Agency. Their conclusions, published Dec. 4, 2014, included the following: “The probability of human exposure to the virus through contact with exposed pets is difficult to assess and may range from very low to high depending on the specific circumstances. It is recommended that risk be assessed jointly by veterinary and public health authorities using a case-by-case approach. In the absence of information about possible EBOV infection in pets and the potential for onward transmission, full precautionary measures should be taken when handling pets of persons infected with EBOV.”

The World Organisation for Animal Health (OIE) recently published its experts’ views and guidelines on Ebola, summarizing:

“Ebola is most likely initially transmitted from animals such as bats and nonhuman primates to humans through hunting and collection of sick or dead wild animals and handling or consumption of uncooked bush meat. In rural areas fruit bats are a popular source of forest meat for humans and are prepared by hand to be dried, smoked and/or cooked. Infection could also be transmitted to humans by handling or consumption of forest fruits contaminated with bat saliva or feces in affected areas.

“The OIE is in full accordance with [WHO] recommendations, to avoid contact with wild animals, including bats, monkeys and rodents, in affected areas.”

References:

EFSA. EFSA Journal. 2014;12:3930.
OIE. OIE experts review current knowledge on Ebola virus disease. http://www.oie.int/for-the-media/press-releases/detail/article/oie-experts-review-current-knowledge-on-ebola-virus-disease. (2014).
Pigott DM. Elife. 2014;doi:10.7554/eLife.04395.
WHO. Epidem Rec. 1976;51:325-332.

For more information:

Arnon Shimshony, DVM, is an associate professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail animal diseases zoonoses moderator. Shimshony was chief veterinary officer, State of Israel, from 1974 to 1999. He also is a member of the Infectious Disease News Editorial Board. 

Disclosure: Shimshony reports no relevant financial disclsoures.