Ebola Xiaohua YU

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

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 p 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 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 YearEbola subtypeCountryNo. of human casesPercentage of deaths among cases 1976Ebola-ZaireZaire [Democratic Republic of the Congo (DRC)] 31888% 1976Ebola-SudanSudan28453% 1976*Ebola-SudanEngland10% 1977Ebola-ZaireZaire1100% 1979Ebola-SudanSudan3465% 1989Ebola-RestonUSA00% 1990Ebola-RestonUSA00% 1992Ebola-RestonItaly00% 1994Ebola-ZaireGabon4959% 1994Ebola-Ivory CoastIvory Coast10% 1995Ebola-ZaireDemocratic Republic of the Congo (formerly Zaire) 31581% 1996Ebola-ZaireGabon3168% 1996Ebola-ZaireGabon6075% 1996Ebola-ZaireSouth Africa250% 1996Ebola-RestonUSA00% 1996Ebola-RestonPhilippines00% Ebola-Sudan Uganda 42553% (Oct 01 - March 02)Ebola-ZaireGabon6582% (Oct March 02)Ebola-ZaireRepublic of Congo5975% (Dec 02 - April 03)Ebola-ZaireRepublic of Congo14389% 2003 (Nov - Dec)Ebola-ZaireRepublic of Congo3583% 2004Ebola-SudanSudan1741% 2004(Feb)* Maryland-USA10% 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

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Pictures of Outbreaks of Ebola