Transmission of Ebola

It is still unknown how primates contract filoviruses in nature. The secondary cases of infection have been the result of contact with contaminated blood, organs, or bodily secretions. Ebola can also be transmitted through the handling of an ill chimpanzee, or the corpse of one. Amongst humans, Ebola is transmitted person to person by contact with infected bodily fluids and/or tissues. There is also evidence of a possible respiratory way of transmission of Ebola in nonhuman primates. Even if Ebola is transmitted via the respiratory route to nonhuman primates, humans may be resistant to the airborne transmission of Ebola (may not have the right receptors).

Ebola Classification and Taxonomy

Ebola Zaire, Ebola Sudan, Ebola Cote d'Ivoire, and Ebola Reston are the four known strains (subtypes) of Ebola. Ebola and Marburg in the filovirus family, in which they are the only members. Filoviruses are negative, noninfectious, polymorphic, non-segmented, single-stranded RNA viruses, and have variable lengths. Infectious Ebola virions are usually 920 nm (nanometers - one billionth of a meter) in length and 80 nm in diameter. 

For a picture of a genome of Ebola Zaire, click here.

Ebola Tissue Tropism and Pathogenesis

After being transmitted to a new host, the virus enters a cell through a mechanism that has yet to be determined. Once inside the host cell's cytoplasm, the filovirus uncoats itself and releases transcribes negative RNA into a positive strand. This positive, single stranded RNA will then be used as the template for new viral genomes. Soon after the infection, the cell develops cytoplasmic inclusion bodies that contain the highly structured viral nucleocapsid (the nucleocapsid contains the genome and can sometimes have other proteins in it as well).

Not very much is known about the pathogenesis of filoviruses, but we do know that Ebola attacks cells that are important to the function of lymphatic tissues. These can be found in fibroblastic reticular cells (FRC) among the loose connective tissue under the skin and in the FRC conduit (FRCC) in lymph nodes. This allows the virus to rapidly enter the blood.

The time sequence of infection and spread of Ebola is difficult to speculate on because most studies have been conducted on the host after it had died (they are at the end stage of infection).

While some regions of the body and organ systems may be at earlier stages of infection at the time of death, it is not a good idea to use this information to derive a theory on the sequence of infection and spread. Only through analytical experiments within an organism where consecutive necropsies are performed on animals euthanized according to a time course, could the actual sequence of infection be characterized.
 

Ebola Immune Response and Host Defenses

Due to the nature of the hemorrhagic fever that filoviruses cause, not much is known about the host immune response to infection. Antibodies that are produced primarily attack the surface of the virus. There is very little or no cross-reactivity or cross-immunity amongst the filoviruses. Researchers are not even sure if antibodies to one Ebola stain will convey immunity against different Ebola strain.

 
Ebola Reservoir/Natural Host

Despite the investment of much effort and time, the natural host/reservoir of Ebola has yet to be determined. There are several promising theories, but the natural host/reservoir has yet to be identified, conclusively.

The promising theories:

1. Bats

2. Plants

3. Insects

Bats:

Evidence Supporting Bats as the Vector

· Bats were found in the roof of the Nzara Cotton Factory during the Ebola Sudan outbreak in 1976. The index case and the two other primary cases worked in the Nzara Cotton Factory, and since the three men did not live close to each other, and did not have any social contact outside of the Nzara Cotton Factory, the Nzara Cotton Factory is considered to be the point of infection for these three men.

· The first case of the Ebola Sudan outbreak in 1979 also worked at the Nzara Cotton Factory.

· A study done at the National Institute of Virology, South Africa has shown that Ebola can replicate in fruit bats and other bats in the Tadarida genus (the genus of bats at the Nzara Cotton Factory), and it can then pass through their stool.

· Infectious Ebola virions have been found in the stool of bats (called "guano"), which could have transmitted Ebola to humans or to another intermediate vector.

· Bats in a cave at Mount Elgon have been involved in the transmission of Marburg (a filovirus closely related to Ebola) on two separate occasions. However, bats and guano collected from Mount Elgon have not tested positive for the Ebola virus.

Evidence Against Bats as the Vector

· Bats were not the only organisms found in the Cotton Factory, so the three men could have contracted Ebola Sudan from another source.

· Ebola has never been found in bats captured during the Ebola outbreaks. However, the bats that were captured for testing were captured well after the start of an outbreak, so the bats that could have been infected with Ebola could have died before the investigative team began collecting sample specimens. The specific species that was found living at the Nzara Cotton Factory, Tadarida (mops) trevori were not captured and tested for the presence of Ebola.

· Ebola Zaire is highly pathogenic in other bats of the Tadarida genus, as well as in other species that are common in Africa. If bats are the vector, they would most likely be an intermediate host, because of Ebola's high pathogenicity in them.

Unresolved Issues

· Numerous bats that were collected during the Ebola Zaire outbreak in Zaire in 1995 still remain in freezers at USAMRIID, and haven't been tested yet.

· The vector/host may be strain specific (a specific organism may only be the vector/host for a specific strain of Ebola).

· When organisms are to be collected for analysis, only a few are collected, therefore there is a low probability that the specific representative organism is going to have the agent even if the particular species is the vector/host.

To see a chart of possible transmission through bats, click here.

Plants:

Evidence Supporting Plants as the Natural Reservoir

· Ebola is extremely pathogenic in vertebrates, killing them quickly rather than allowing persistence of the virus, which suggests that a non-vertebrate could be the natural host/reservoir.

· The reason researchers are having a great difficulty at identifying the natural host/reservoir.

· Primates do not appear to have an immune response to the Ebola virus, which would indicate that vertebrates did not evolve with Ebola (if you believe in the evolution theory).

· Ebola outbreaks in the chimpanzee population in the Tai Forest seem to coincide with the flowering cycle of a particular species of a plant in the forest.

· An agent morphologically similar to a filovirus was found in a leafhopper (Psammotettix species) found in France.

· Ebola virus antibodies were found in guinea pigs (which are vegetarians) in the Democratic Republic of the Congo (formerly known as Zaire).

Evidence Against Plants as the Natural Host/Reservoir

· Dr. Swanepoel's study of 24 different species of plants failed to identify a species of plant that in which Ebola replicated in. However, thirteen species of plants died from mechanical injury from being infected with the virus.

Unresolved Issues

· Were the Ebola antibodies that the guinea pigs in the Democratic Republic of the Congo protective against Ebola? If so, guinea pigs and, perhaps, the flora they eat could be directly involved in the transmission cycle of the Ebola virus.

To see a chart on the possible transmission through plants and arthropods, click here.

Insects:

Evidence Supporting Insects as the Vector

· Insects were around all of the outbreak sites.

· A single replication study conducted during the late 1970s suggested that Marburg virus (a relative of Ebola) could replicated in Aedes (Stegomyia) aegypti mosquitoes.

· A case of Marburg Hemorrhagic Fever in Zimbabwe coincided with a lesion that was compatible with a horsefly or spider bite.

Evidence Against Insects as the Vector

· Studies of insects found at the Ebola outbreak sites have failed to isolate the virus in an insect. However, specimens were not collected at the beginning of the outbreaks. During the first Ebola Sudan outbreak, DDT was sprayed around the hospital and the surrounding area.

· Recent studies to whether Ebola replicates in A. aegypti failed to reproduce the result of the Kunz study. However, the recent study didn't use the strains of Ebola (Ebola Cote d'Ivoire, Ebola Sudan and Ebola Zaire) that are the causative agents of the outbreaks.

Unresolved Issues

· Only a small fraction of the specimens collected have actually been tested for the Ebola virus.

· Insects that were present at the beginning of the outbreaks have not been collected and analyzed.

· The reservoir insect could be a seasonal insect, therefore not present when insect species are collected for analysis.

· A particular type insect could be an intermediate host and not the natural reservoir, or another organism could be the intermediate host obtaining Ebola from a particular insect species.

Ebola Prevention

BioSafety Level 4 Laboratory Suits

All research done on infectious Ebola are done in a maximum biological containment setup known as BioSafety Level 4 (highest BioSafety level). BioSafety Level 4 laboratories require extremely specialized equipment to prevent the spread of the pathogens. If unauthorized construction of a BioSafety Level 4 lab were to begin, the authorities would be alerted by people purchasing the lab equipment.

Ebola is stable and remains infective at room temperature, but it is mostly destroyed at 140°F (60°C). Its infective ability can also be terminated using ultraviolet and gamma radiation, lipid solvents (dissolves the outer lipid membrane), commercial hypochlorite (bleach), and phenolic disinfectants.

Nonhuman Primate Quarantine Regulations:

After the Ebola Reston outbreaks in Reston, Virginia and Alice, Texas, the authorities have implemented a better quarantine program for monkeys imported to the United States.

Ebola Management and Therapy

For people who are unfortunate enough to become infected with Ebola (so far there is no vaccine to use), there is not very much that medications can do to cure them. The only thing that can be done for them is to give them intensive care, as they usually become dehydrated and need fluids constantly replenished.

Promising New Experimental Ebola Hemorrhagic Fever Treatments:

· Hyper immune anti-Ebola serum has been protective in baboons experimentally challenged with Ebola.

· Antibodies from the marrow of Ebola survivors.

· A potential, promising vaccine that offered protection against Ebola to guinea pigs (it still needs to be further tested).