Transcript Ebola - Xiaohua Yu
Ebola
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
factory outbreak.
were not captured and tested for the presence of Ebola after the
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.
Year
1976 1976 1976* 1977 1979 1989 1990 1992 1994 1994 1995 1996 1996 1996 1996 1996 2000-2001 2001 - 2002 (Oct 01 - March 02) 2001 - 2002 (Oct. 01 - March 02) 2002 - 2003 (Dec 02 - April 03) 2003 (Nov - Dec) 2004 2004(Feb)* 2004 (may)*
Ebola outbreak chronology Ebola subtype
Ebola-Zaire Ebola-Sudan Ebola-Sudan Ebola-Zaire
Country
Zaire [Democratic Republic of the Congo (DRC)] Sudan England Zaire * Lab Accidents
No. of human cases
318 284 1 1
Percentage of deaths among cases
88% 53% 0% 100% Ebola-Sudan Ebola-Reston Ebola-Reston Ebola-Reston Ebola-Zaire Ebola-Ivory Coast Ebola-Zaire Ebola-Zaire Ebola-Zaire Ebola-Zaire Ebola-Reston Ebola-Reston Ebola-Sudan Ebola-Zaire Ebola-Zaire Ebola-Zaire Ebola-Zaire Ebola-Sudan Sudan USA USA Italy Gabon Ivory Coast Democratic Republic of the Congo (formerly Zaire) Gabon Gabon South Africa USA Philippines Uganda Gabon Republic of Congo Republic of Congo Republic of Congo Sudan Maryland-USA Russia 34 0 0 0 49 1 315 31 60 2 0 0 425 65 59 143 35 17 1 1 65% 0% 0% 0% 59% 0% 81% 68% 75% 50% 0% 0% 53% 82% 75% 89% 83% 41% 0% 100%
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=1 8