EbolaEbola

　 Xiaohua 　 YU

2008

http://www.srpublications.com/tools/health_and_wellness/ebola.jpg

Ebola

Family: Filoviridae– Ebola and Marburg are only 2 (known) members

Genus: Ebolavirus– Named after the Ebola River where it was first found

Species: Multiple different species. Commonly named after region of outbreak

– Examples: Zaire ebolavirus Sudan ebolavirus Reston ebolavirus Ivory Coast ebolavirus

Ebola Phylogenetic Tree

Structure

Filovirus: like other members of this family, Ebola is thread-like in structure– Variable shapes

“U” shaped Coiled Circular Branched

http://bepast.org/docs/photos/Ebola/em_ebola.jpg

Size

Ebola virion is typically 80nm in diameter with the average length ~1000nm.The known morphological differences amongst the Ebola viruses are:

– Ebola Sudan (SEBOV) Average length: 974 to 1063 nm (1)

– Ebola Zaire (ZEBOV) Average length: 990 to 1086 nm (1)

– Ebola Reston (REBOV) Average length: 1026 to 1083 nm (1)

Genomic Content

Members of the genus Ebolavirus are helical, non-segmented, negative, single-stranded RNA viruses, polymorphic, noninfectious, and have variable lengths.– RNA viruses are highly mutable

Other well known (-)ssRNA viruses:– Influenza– Measles– Rabies

Genomic Content cont.

19 kilobases of Genomic material Genome encodes 7 structural proteins

Gene Function

Ebola virus: unravelling pathogenesis to combat a deadly disease. Hoenen et al. Trends in Molecular Medicine. May 2006, 12(5).

Diagram of Ebola Replication in a Host Cell

Transmission

There is no conclusive evidence for how wild animals contract an EBOV infection.

Modes of Human Infection – Contact with contaminated blood, tissue/organs, semen or other

bodily secretions.– Handling of ill or dead animals. – Evidence suggesting respiratory transmission in non-human

primates. No evidence that this is possible in humans. Common Modes of Contact

– Family burial ceremonies– Re-using EBOV contaminated needles and/or syringes in hospitals– Health care workers aiding in an outbreak– Eating contaminated meat from wild

Diagnosis

Laboratory tests (PCR and ELISA) can be performed to detect the presence of many genes and antigens in an infected individual.

EBOV can be cultured in vitro. New diagnostic tests are attempting to use

saliva and urine to determine if an individual has Ebola– Much more reasonable for use in the field

Symptoms continued

Incubation Period: 2-21 days Early symptoms followed by:

– Vomiting– Diarrhea– Rash– Loss of full kidney and liver function– Low white blood cell counts– Increased liver enzyme activity– Internal and external bleeding

Does not occur in all cases, but gives rise to the name hemorrhagic fever

EBOV Effect on Tissue

Ebola virus: unravelling pathogenesis to combat a deadly disease. Hoenen et al. Trends in Molecular Medicine. May 2006, 12(5).

EBOV Effects on Immune System

High mortality rate believed to be the result of EBOV proteins capability of defeating the immune system– Elimination of Innate IS with VP24 and VP35

proteins– Prevention of enhancement of Adaptive response– Infected macrophages induces apoptosis in

lymphocytes

Therapy and Treatment

To date, there is not very much that medicine can do to cure them. The best therapy (probably, the only way) available is to keep an individual as comfortable as possible through hydration plus electrolytes.

There is no effective vaccine or post-exposure treatment currently available for Ebola

Current Vaccine Research

Development of a cAdVax-Based Bivalent Ebola Virus Vaccine That Induces Immune Responses against both the Sudan and Zaire

Species of Ebola Virus

Wang et al. Journal of Virology, Mar 2006. p. 2738-2746

-Vaccine using EBOV glycoproteins from both Sudan and Zaire species.

-Protected mice against challenge with lethal dose with EBOV due to large immune response. Vaccinated mice had 100% survival rate (control=0).

-Shows hope for a preventative vaccine, but effectiveness in mice is not even close to meaning it will be effective in humans.

Current Vaccine Research

Effective Post-Exposure Treatment of Ebola Infection

Feldmann et al. PLoS Pathogens Jan 2007 Vol. 3 Iss. 1

-Single injection of live-attenuated recombinant virus expressing the ZEBOV provided post-exposure treatment of rodents and nonhuman primates.

-Treatment needed to be administered within 20-30 minutes post-ZEBOV infection for effectiveness

-Therapy (if can be shown to work in humans) would provide a method to treat healthcare workers who were accidentally infected when treating an individual.

Bioterrorism

Classified as a Catergory A Biological Terrorism agent by the CDC– Targeted for use due to high mortality rate– Low transmissibility, so proper handling may

contain an outbreak in the USA– Possibility of chimeric (genetically engineered)

viruses. Example: part small-pox part Ebola

Containment of Outbreak

The best method to contain an Ebola outbreak is to isolate infected individuals as early as possible.

Backtracking to monitor all people who have come in contact with the infected individual.

ENSURE THAT NO NEEDLES ARE RE-USED!!! This is not a problem in the US, but has been a large problem in Africa.

Ebola Reservoir/Natural Host

– To date, there is no conclusive evidence for a natural reservoir for EBOV

– The promising theories: Monkeys/Chimps/Gorillas Bats Plants Insects

Bats

Evidence:– Tadarida trevori were found in the roof of the Nzara Cotton Factory during the

1976 outbreak of Ebola-Sudan. The outbreak was traced back employees of the factory. The bats are believed to be the source of infection.

Controversies: – Ebola has never been found in captured wild bats during outbreaks. – Lab bats are asymptomatic when infected with lethal doses of EBOV. – Infected factory bats that were captured for testing were captured well after the

start of the outbreak, while the infected bats may have died earlier. – Tadarida trevori were not captured and tested for the presence of Ebola after the

factory outbreak.

Plants

Evidence:– EBOV is highly pathogenic and lethal in vertabrates– This suggests that a non-vertebrate could be the natural host/reservoir. – EBOV antibodies were found in guinea pigs (vegetarians) in the

Democratic Republic of the Congo Controversies:

– Dr. Swanepoel's study of 24 different species of plants failed to identify a species of plant that Ebola replicated in. However, 13 species of plants died from mechanical injury from being inoculated with the virus.

Insects

Evidence– Arthropods 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 replicate in Aedes (Stegomyia) aegypti mosquitoes.

Controversies– Studies of insects found at the outbreak sites have failed to isolate

Ebola 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 by Kunz group attempted to determine if Ebola repilicates in A. aegypti, failed to produce evidence for this theory(4, 6). However, the recent study did not include all strains of Ebola.

Ebola outbreak chronology Year Ebola subtype Country No. of human cases Percentage of deaths among

cases

1976 Ebola-Zaire Zaire [Democratic Republic of the Congo (DRC)]

318 88%

1976 Ebola-Sudan Sudan 284 53%

1976* Ebola-Sudan England 1 0%

1977 Ebola-Zaire Zaire 1 100%

1979 Ebola-Sudan Sudan 34 65%

1989 Ebola-Reston USA 0 0%

1990 Ebola-Reston USA 0 0%

1992 Ebola-Reston Italy 0 0%

1994 Ebola-Zaire Gabon 49 59%

1994 Ebola-Ivory Coast Ivory Coast 1 0%

1995 Ebola-Zaire Democratic Republic of the Congo (formerly Zaire)

315 81%

1996 Ebola-Zaire Gabon 31 68%

1996 Ebola-Zaire Gabon 60 75%

1996 Ebola-Zaire South Africa 2 50%

1996 Ebola-Reston USA 0 0%

1996 Ebola-Reston Philippines 0 0%

2000-2001 Ebola-Sudan Uganda 425 53%

2001　-　2002　(Oct　01　-　March　02) Ebola-Zaire Gabon 65 82%

2001　-　2002　(Oct.　01　-　March　02) Ebola-Zaire Republic　of　Congo 59 75%

2002　-　2003　(Dec　02　-　April　03) Ebola-Zaire Republic　of　Congo 143 89%

2003　(Nov　-　Dec) Ebola-Zaire Republic　of　Congo 35 83%

2004 Ebola-Sudan Sudan 17 41%

2004(Feb)* 　 Maryland-USA 1 0%

2004 (may)* 　 Russia 1 100%

* Lab Accidents

Map of Ebola Outbreaks in Africa

Map of Ebola Reston Infected Monkeys in Philippines

An outbreak in Kikwit, Zaire, 1995

A Movie

http://www.lifeonterra.com/episode.php?id=18

Pictures of Outbreaks of Ebola