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Monath, Thomas P.. "Ecology of Marburg and Ebola Viruses: Speculations and Directions for Future Research." The Journal of Infectious Diseases 179.s1 (1999): S127-S138. Print.
Ecology of Marburg and Ebola Viruses: Speculations and Directions for Future Research
Abstract
Marburg and virulent Ebola viruses are maintained in hosts that are rare and have little contact with humans or do not readily transmit virus. Bats (particularly solitary microchiropteran species) are leading contenders as reservoir hosts. Virus transfer to humans occurs by contact with the primary reservoir or via an intermediate animal that acquired infection from the reservoir and is, in turn, hunted by humans. An interesting possibility is that filoviruses may be arthropod or plant viruses, with non?blood-feeding arthropods transmitting the virus to intermediate hosts or humans during oral ingestion or envenomation. Paradoxically, in Africa, Ebola virus disease has high lethality and high seroprevalence as determined by the IFA test. If the seroreactivity is confirmed by more specific tests, then the Ebola virus serogroup in Africa probably contains an antigenically cross-reactive, enzootic, nonpathogenic agent(s). Such viruses may have separate life cycles or may give rise to virulent strains by mutation.
The enigma surrounding the natural transmission cycles of Ebola (EBO) and Marburg (MBG) viruses remains a challenge for scientific research. Since my charge in preparing this paper was to present hypotheses, to stimulate nonlinear thinking, and to suggest new avenues for investigation, what follows is speculation, extrapolation, and conjecture. The reader should keep in mind that certain hypotheses may not be consistent with the prevailing views of some filovirologists.
During outbreaks of EBO virus disease in the Democratic Republic of the Congo (DRC) and Sudan, most cases resulted from interhuman spread [1?4] and provide no information about the natural transmission cycle. Ecologic studies aimed at uncovering the source of infection of the index cases in these outbreaks were initiated months after the acquisition of infection, so it is uncertain whether materials collected are representative of those existing at the time and place of human exposure. Some of these investigations have been of heroic scale, with the relatively nonselective collection of thousands of vertebrate and arthropod species for virologic testing. Unfortunately, only a small fraction of the specimens collected have actually been tested. Recent EBO disease outbreaks in C?te d'Ivoire and Gabon have more clearly defined the ecologic setting in which virus transmission occurs [5?7]. These localities have been selected for longitudinal studies aimed at uncovering the reservoir of EBO virus, and the results are awaited with great interest.
We should remain humble about our ability to unravel the mysteries of EBO and MBG virus transmission. The reservoir may be a rare species or one that rarely contacts clinical hosts, or if contact is made, the virus may not be easily transmitted. Infection in the host species may itself be an unusual event. Biodiversity in the areas in which transmission occurs is high; the implicated species may represent a tiny fraction of the total biota, and it may be very difficult to capture. Vertebrate hosts involved in transmission may not mount a detectable or durable immune response, and positive serologic results may not reveal whether the immunized host is primary or incidental to the transmission cycle. Reagents are lacking for detection of antibodies in some species. As will be pointed out later, it is possible that the filoviruses represent a diverse complex of agents with different transmission cycles, as is the case for the lyssavirus and vesiculovirus genera, raising the difficulty of interpreting heterologous cross-reacting antibodies. Virulent strains of EBO and MBG virus may not persist in a local reservoir but rather cause wandering epizootics that return at long intervals to any one location. It is also possible that the virulent filovirus strains do not have sustained transmission cycles at all but arise from time to time by mutation from enzootic variants.
...(For the full article http://jid.oxfordjournals.org/conten...nt_1/S127.full )
Continued...
Conclusions and Avenues for Future Research
For the first time in the 30 years since the discovery of filoviruses, it is possible to identify with some precision the geographic location and habitat in which virus circulates or is repeatedly reintroduced. In Gabon and C?te d'Ivoire, chimpanzees have acquired infection, suggesting that further studies of the feeding habits and interspecific contacts between these animals and potential reservoir species would provide important clues to the source of infection and might narrow the range of potential reservoirs within the forest biota. Speculations about possible reservoir hosts have been derived from events surrounding index cases of human MBG and EBO diseases, from geographic distribution of EBO subtypes, and from paradigms presented by transmission cycles of rhabdoviruses and paramyxoviruses. The suspicion that bats may be involved in the ecology of filoviruses warrants intensive study in the context of the presumed transmission foci in C?te d'Ivoire and Gabon. However, other possible reservoirs also need to be considered, and field studies consequently should include arboreal mammals and birds.
Serologic evidence, while open to criticism with respect to specificity, suggests the existence of nonpathogenic strains of EBO virus (but not MBG virus) and that frequent contact occurs between humans and nonpathogenic EBO strains. Serologic testing of wild vertebrates would provide important clues to the hosts involved in transmission. The development of validated serologic assays and reagents for surveying the diverse array of potential vertebrates in the areas under study is a priority for research. Experimental infection studies of selected vertebrate groups would provide important information about the host range of virulent EBO strains and MBG virus and should include determinations of antibody responses to virus infection. Experimental infection should be extended to various arthropod groups, including nonhematophagous and plant-feeding species, thereby sharpening the focus of field investigations.
Assuming a vertebrate species is ultimately implicated in filovirus ecology, it is important to consider in advance how such information will be used. Aside from satisfying the curiosity of the scientific community and the public, there are both potentially useful and destructive consequences. If the virus reservoir is a species that is occasionally hunted or gathered by humans, useful interventions through public health education could be developed. The fact that chimpanzees are already known to be intermediate hosts and the source of human EBO virus infections suggests that hunting these animals should be strongly discouraged as a public health principle. This would be consistent with the precarious position of the great apes, who are under pressure by habitat destruction and hunting, and thus the relationship to virus infection might be usefully exploited by conservation groups. If bats are implicated, avoidance of bats could be promulgated as a public health measure. Care should be taken to assure that bats are not destroyed, since these animals play extremely beneficial roles in the control of insects and in plant pollination. Similar principles apply to other vertebrate hosts that would be implicated in transmission of these rare filovirus diseases. The discoverers of the natural history of filoviruses will bear the responsibility of ensuring that the knowledge is applied in a practical way, consistent with the goals of public health and the principles of conservation.
Monath, Thomas P.. "Ecology of Marburg and Ebola Viruses: Speculations and Directions for Future Research." The Journal of Infectious Diseases 179.s1 (1999): S127-S138. Print.
Ecology of Marburg and Ebola Viruses: Speculations and Directions for Future Research
Abstract
Marburg and virulent Ebola viruses are maintained in hosts that are rare and have little contact with humans or do not readily transmit virus. Bats (particularly solitary microchiropteran species) are leading contenders as reservoir hosts. Virus transfer to humans occurs by contact with the primary reservoir or via an intermediate animal that acquired infection from the reservoir and is, in turn, hunted by humans. An interesting possibility is that filoviruses may be arthropod or plant viruses, with non?blood-feeding arthropods transmitting the virus to intermediate hosts or humans during oral ingestion or envenomation. Paradoxically, in Africa, Ebola virus disease has high lethality and high seroprevalence as determined by the IFA test. If the seroreactivity is confirmed by more specific tests, then the Ebola virus serogroup in Africa probably contains an antigenically cross-reactive, enzootic, nonpathogenic agent(s). Such viruses may have separate life cycles or may give rise to virulent strains by mutation.
The enigma surrounding the natural transmission cycles of Ebola (EBO) and Marburg (MBG) viruses remains a challenge for scientific research. Since my charge in preparing this paper was to present hypotheses, to stimulate nonlinear thinking, and to suggest new avenues for investigation, what follows is speculation, extrapolation, and conjecture. The reader should keep in mind that certain hypotheses may not be consistent with the prevailing views of some filovirologists.
During outbreaks of EBO virus disease in the Democratic Republic of the Congo (DRC) and Sudan, most cases resulted from interhuman spread [1?4] and provide no information about the natural transmission cycle. Ecologic studies aimed at uncovering the source of infection of the index cases in these outbreaks were initiated months after the acquisition of infection, so it is uncertain whether materials collected are representative of those existing at the time and place of human exposure. Some of these investigations have been of heroic scale, with the relatively nonselective collection of thousands of vertebrate and arthropod species for virologic testing. Unfortunately, only a small fraction of the specimens collected have actually been tested. Recent EBO disease outbreaks in C?te d'Ivoire and Gabon have more clearly defined the ecologic setting in which virus transmission occurs [5?7]. These localities have been selected for longitudinal studies aimed at uncovering the reservoir of EBO virus, and the results are awaited with great interest.
We should remain humble about our ability to unravel the mysteries of EBO and MBG virus transmission. The reservoir may be a rare species or one that rarely contacts clinical hosts, or if contact is made, the virus may not be easily transmitted. Infection in the host species may itself be an unusual event. Biodiversity in the areas in which transmission occurs is high; the implicated species may represent a tiny fraction of the total biota, and it may be very difficult to capture. Vertebrate hosts involved in transmission may not mount a detectable or durable immune response, and positive serologic results may not reveal whether the immunized host is primary or incidental to the transmission cycle. Reagents are lacking for detection of antibodies in some species. As will be pointed out later, it is possible that the filoviruses represent a diverse complex of agents with different transmission cycles, as is the case for the lyssavirus and vesiculovirus genera, raising the difficulty of interpreting heterologous cross-reacting antibodies. Virulent strains of EBO and MBG virus may not persist in a local reservoir but rather cause wandering epizootics that return at long intervals to any one location. It is also possible that the virulent filovirus strains do not have sustained transmission cycles at all but arise from time to time by mutation from enzootic variants.
...(For the full article http://jid.oxfordjournals.org/conten...nt_1/S127.full )
Continued...
Conclusions and Avenues for Future Research
For the first time in the 30 years since the discovery of filoviruses, it is possible to identify with some precision the geographic location and habitat in which virus circulates or is repeatedly reintroduced. In Gabon and C?te d'Ivoire, chimpanzees have acquired infection, suggesting that further studies of the feeding habits and interspecific contacts between these animals and potential reservoir species would provide important clues to the source of infection and might narrow the range of potential reservoirs within the forest biota. Speculations about possible reservoir hosts have been derived from events surrounding index cases of human MBG and EBO diseases, from geographic distribution of EBO subtypes, and from paradigms presented by transmission cycles of rhabdoviruses and paramyxoviruses. The suspicion that bats may be involved in the ecology of filoviruses warrants intensive study in the context of the presumed transmission foci in C?te d'Ivoire and Gabon. However, other possible reservoirs also need to be considered, and field studies consequently should include arboreal mammals and birds.
Serologic evidence, while open to criticism with respect to specificity, suggests the existence of nonpathogenic strains of EBO virus (but not MBG virus) and that frequent contact occurs between humans and nonpathogenic EBO strains. Serologic testing of wild vertebrates would provide important clues to the hosts involved in transmission. The development of validated serologic assays and reagents for surveying the diverse array of potential vertebrates in the areas under study is a priority for research. Experimental infection studies of selected vertebrate groups would provide important information about the host range of virulent EBO strains and MBG virus and should include determinations of antibody responses to virus infection. Experimental infection should be extended to various arthropod groups, including nonhematophagous and plant-feeding species, thereby sharpening the focus of field investigations.
Assuming a vertebrate species is ultimately implicated in filovirus ecology, it is important to consider in advance how such information will be used. Aside from satisfying the curiosity of the scientific community and the public, there are both potentially useful and destructive consequences. If the virus reservoir is a species that is occasionally hunted or gathered by humans, useful interventions through public health education could be developed. The fact that chimpanzees are already known to be intermediate hosts and the source of human EBO virus infections suggests that hunting these animals should be strongly discouraged as a public health principle. This would be consistent with the precarious position of the great apes, who are under pressure by habitat destruction and hunting, and thus the relationship to virus infection might be usefully exploited by conservation groups. If bats are implicated, avoidance of bats could be promulgated as a public health measure. Care should be taken to assure that bats are not destroyed, since these animals play extremely beneficial roles in the control of insects and in plant pollination. Similar principles apply to other vertebrate hosts that would be implicated in transmission of these rare filovirus diseases. The discoverers of the natural history of filoviruses will bear the responsibility of ensuring that the knowledge is applied in a practical way, consistent with the goals of public health and the principles of conservation.
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