Ebola
The Deadly African Virus
PAPER-203
Ebola Virus Introduction
• First appeared in Africa 1976
• “African Hemorrhagic Fever”
– acute,mostly fatal disease
– causes blood vessel “bursting”
– systemic (all organs/tissues)
– humans and nonhuman primates
• Excluding ‘2000 outbreak
– 1,500 cases
– over 1,000 deaths
Geography
• The link between human infection by the Ebola virus and
their proximity to primates is clear.
-Outbreaks occurred in countries that house 80 percent of
the world’s remaining wild gorilla and chimpanzee
populations.
- The outbreaks coincided with the outbreaks in wild
animals.
- The same distinct viral strains were isolated in animal
carcasses and in the bodies of those who handled those
carcasses.
- These outbreaks were preceded by an abnormally large
death in wild Gorilla populations.
Ebola Taxonomy
Scientific Classification
Order: Mononegavirales
Family: Filoviridae
Genus: Ebola like viruses
Species: Ebola
Subtypes
– Ebola-Zaire, Ebola-Sudan,Ebola-Ivory Coast
• disease in humans
– Ebola-Reston
• disease in nonhuman primates
Copyrighted
Dr. Fre:derick A. Murphy, D.V.M., Ph.D. 1976.
Filoviridae or “Filoviruses”
• Most mysterious virus group
• Pathogenesis poorly understood
• Ebola
– natural history/reservoirs unknown
– exist throughout the world
– endemic to Africa
– filamentous ssRNA-
(antisense) viruses
Image courtesy of the Centers for Disease Control
MOLECULAR STRUCTURE
• Morphology under electron microscope
– filamentous, enveloped RNA virus
– approx. 19 kb in length (1 kb = 1000 RNA
bases/nucleotides) or 60-80 nm in diameter
– single-stranded, linear, non-segmented
– negative-sense RNA (encoded in a 3’ to 5’ direction)
– appears to have “spikes” due to glycoprotein on
outside membrane
• Structure of Ebola genome and proteins
– Transcribed into 8 sub-genomic mRNA proteins: 7
structural and 1 nonstructural
– 7 structural proteins:
– nucleoprotein (NP)
– 4 viral/virion proteins (VP35, VP40, VP30, VP24)
– glycoprotein (GP)
– RNA-dependent RNA polymerase (L protein)
» NP, VP35, VP30, L protein: required for transcription &
replication
» VP40, GP, VP24: associated with the membrane
Ebola Pathogenesis
• Enters Bloodstream
– skin, membranes,open wounds
• Cell Level
– docks with cell membrane
• Viral RNA
– released into cytoplasm
– production new viral proteins/ genetic
material
• New viral genomes
– rapidly coated in protein
– create cores
Copyright: Russell Kightley Media, Australia
Ebola Pathogenesis, cont
• Viral cores
– stack up in cell
– migrate to the cell surface
– produce trans-membrane proteins
– push through cell surface
– become enveloped by cell membrane
• ssRNA-
Genome Mutations
– capable of rapid mutation
– very adaptable to evade host defenses and environmental change
• Theory
– virus evolved to occupy special niches in the wild
Proteins
Clinical Observations
• Incubation period: 2-21 days
• Stage I (unspecific):
-Extreme asthenia (body weakness)
-diarrhea, nausea and vomiting, anorexia
abdominal pain
- headaches
- arthralgia (neuralgic pain in joints)
- myalgia (muscular pain or tenderness), back pain
- mucosal redness of the oral cavity, dysphagia (difficulty in
swallowing)
- conjunctivitis.
- rash all over body except in face
** If the patients don’t recover gradually at this point, there is a high
probability that the disease will progress to the second phase, resulting in
complications which eventually lead to death (Mupapa et al., 1999).
• Stage II (Specific):
- Hemorrhage
- neuropsychiatric abnormalities
- anuria (the absence of urine formation)
- hiccups
- tachypnea (rapid breathing).
** Patients who progressed to phase two almost always die. (Ndambi et
al., 1999)
• Late Complications:
-Arthralgia (joint pain)
- ocular diseases (ocular pain, photophobia and hyperlacrimation)
- hearing loss
- unilateral orchitis( inflammation of one or both of the testes)
** These conditions are usually relieved with the treatment of 1%
atropine and steroids
Clinical Observations
Symptoms and Diagnostic Tests
• Early symptoms
– muscle aches, fever, vomiting
– red eyes, skin rash, diarrhea, stomach pain
• Acute symptoms
– bleeding/hemorrhaging from skin, orifices, internal organs
• Early Diagnosis
• very difficult
• signs & symptoms very similar to other infections
• Laboratory Test
• PCR detection
• ELISA (enzyme-linked immuno-absorbant) assay
Treatment
• No Standard Treatment available
• Patients receive supportive therapy
• treating complicating infections
• balancing patient’s fluids and electrolytes
• maintaining oxygen status and blood pressure
Prevention
• No vaccines!
• Patients are isolated
• Medical Staff Training
– western sanitation practices
• intake
• care during stay
• after patient dies
• Infection-control Measures
– complete equipment and area sterilization
Prevention
After Death
Virus contagious in fluids for days
• Burial use extreme caution
– handling and transport
– cultural practices/ religious belief
– incinerate all waste !!!!
Controlling the spread of Ebola
• a. Hospitals must follow precautionary methods, such as:
1. wearing gloves
2. isolating infected individuals
3. practicing nurse barrier techniques
4. proper sterilization and disposal of all equipment
• b. Burials must be done correctly
1. no washing or touching carcass
2. put into body bags and bury outside city
• c. Report any questionable illness to officials
Ebola Epidemiology
• Reservoirs in Nature
– largely unknown
– possibly infected animals (primates?)
• Transmission
– direct contact blood/secretions of infected person
– possible airborne (Reston primate facility)
• Onset of illness abrupt
– incubation period: 2 to 21 days
– infections are acute and mostly deadly
Latest Morbidity and Mortality Reports
• Ebola-Reston Virus Infection Among Quarantined
Nonhuman Primates -- Texas, 1996
– report describes death and blood testing of cynomolgus
monkey imported from the Philippines held in a private
quarantine facility in Texas
• Outbreak of Ebola Hemorrhagic Fever ---Uganda,
August 2000--January 2001
– report describes surveillance and control activities
related to the EHF outbreak
– presents preliminary clinical and epidemiologic findings
Current Basic Research
• The assembly of Ebola virus nucleocapsid requires virion-
associated proteins 35 and 24 and posttranslational
modification of nucleoprotein
• Report describes distinct VP35 and VP24 proteins mechanism of
regulation for filovirus assembly
• suggests new approaches for viral therapies and vaccines for Ebola
and related viruses
• Detection of antibodies against the four subtypes of Ebola
virus in sera from any species using a novel antibody-phage
indicator assay
• assesses the presence of specific antibodies in serum
• describes development of a novel assay for the detection of
seroconversion irrespective of Ebola virus subtype or animal
species
Bioterrorism
• Since the September 11 bombings in the
United States, the locality of this virus has
become less isolated as the threat of
bioterrorism looms large.
• The Ebola virus is now on the “A” list for
hopeful vaccination development.
• Experiments have even been formed to show
how Ebola can be used as a bioterror agent.
References
• Reemergence of Ebola Virus in Africa; Anthony Sanchez et al,EID Volume 1 * Number 3 July-September 1995
http://www.cdc.gov/ncidod/EID/vol1no3/sanchez.htm
• Viral Hemorrhagic Fever, Healthlink, Medical College of Wisconsin, 2000
http://healthlink.mcw.edu/article/955159073.html
• Isolation and Phylogenetic Characterization of Ebola Viruses Causing Different Outbreaks in Gabon
Emerging Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention ,February 5, 1997
http://www.cdc.gov/ncidod/EID/vol3no1/courbot2.htm
• Hemorrhagic fevers; Julia Barrett, Gale Encyclopedia of Medicine, Gale Research, 1999
http://www.findarticles.com/cf_dls/g2601/0006/2601000652/p1/article.jhtm
l
Key Issues in the Prevention and Control of Viral Hemorrhagic Fevers Clarence J.Peters, MD, Special Pathogens Branch/Division of Viral and
Rickettsial Diseases, National Center for Infectious Diseases/Centers for Disease Control and Prevention, 1997
http://www.cdc.gov/od/ohs/sympsium/symp43.htm
• Scientific Stock Images Library; Russell Kightley Media,Australia
http://www.rkm.com.au/imagelibrary/index.html
• Outbreak of Ebola Hemorrhagic Fever ---Uganda, August 2000--January 2001,
Morbidity and Mortality Weekly Report, Vol 50, No 05;73, 02/09/2001 / 50(05);73-7
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5005a1.htm
• Ebola-Reston Virus Infection Among Quarantined Nonhuman Primates -- Texas, 1996
Morbidity and Mortality Weekly Report, Vol 45, No 15;314 ,April 19, 1996 / 45(15);314-316
http://www.cdc.gov/mmwr/preview/mmwrhtml/00040920.htm
The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein, Huang
Y et al, Mol Cell. 2002 Aug;10(2):307-16. PMID: 12191476 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12191476&dopt=Abstract
Detection of antibodies against the four subtypes of ebola virus in sera from any species using a novel antibody-phage indicator assay.; Meissner F
et al , PMID: 1235035
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12350354&dopt=Abstract

Ebola final

  • 1.
    Ebola The Deadly AfricanVirus PAPER-203
  • 2.
    Ebola Virus Introduction •First appeared in Africa 1976 • “African Hemorrhagic Fever” – acute,mostly fatal disease – causes blood vessel “bursting” – systemic (all organs/tissues) – humans and nonhuman primates • Excluding ‘2000 outbreak – 1,500 cases – over 1,000 deaths
  • 3.
    Geography • The linkbetween human infection by the Ebola virus and their proximity to primates is clear. -Outbreaks occurred in countries that house 80 percent of the world’s remaining wild gorilla and chimpanzee populations. - The outbreaks coincided with the outbreaks in wild animals. - The same distinct viral strains were isolated in animal carcasses and in the bodies of those who handled those carcasses. - These outbreaks were preceded by an abnormally large death in wild Gorilla populations.
  • 4.
    Ebola Taxonomy Scientific Classification Order:Mononegavirales Family: Filoviridae Genus: Ebola like viruses Species: Ebola Subtypes – Ebola-Zaire, Ebola-Sudan,Ebola-Ivory Coast • disease in humans – Ebola-Reston • disease in nonhuman primates Copyrighted Dr. Fre:derick A. Murphy, D.V.M., Ph.D. 1976.
  • 5.
    Filoviridae or “Filoviruses” •Most mysterious virus group • Pathogenesis poorly understood • Ebola – natural history/reservoirs unknown – exist throughout the world – endemic to Africa – filamentous ssRNA- (antisense) viruses Image courtesy of the Centers for Disease Control
  • 6.
    MOLECULAR STRUCTURE • Morphologyunder electron microscope – filamentous, enveloped RNA virus – approx. 19 kb in length (1 kb = 1000 RNA bases/nucleotides) or 60-80 nm in diameter – single-stranded, linear, non-segmented – negative-sense RNA (encoded in a 3’ to 5’ direction) – appears to have “spikes” due to glycoprotein on outside membrane
  • 7.
    • Structure ofEbola genome and proteins – Transcribed into 8 sub-genomic mRNA proteins: 7 structural and 1 nonstructural – 7 structural proteins: – nucleoprotein (NP) – 4 viral/virion proteins (VP35, VP40, VP30, VP24) – glycoprotein (GP) – RNA-dependent RNA polymerase (L protein) » NP, VP35, VP30, L protein: required for transcription & replication » VP40, GP, VP24: associated with the membrane
  • 8.
    Ebola Pathogenesis • EntersBloodstream – skin, membranes,open wounds • Cell Level – docks with cell membrane • Viral RNA – released into cytoplasm – production new viral proteins/ genetic material • New viral genomes – rapidly coated in protein – create cores Copyright: Russell Kightley Media, Australia
  • 9.
    Ebola Pathogenesis, cont •Viral cores – stack up in cell – migrate to the cell surface – produce trans-membrane proteins – push through cell surface – become enveloped by cell membrane • ssRNA- Genome Mutations – capable of rapid mutation – very adaptable to evade host defenses and environmental change • Theory – virus evolved to occupy special niches in the wild
  • 10.
  • 11.
    Clinical Observations • Incubationperiod: 2-21 days • Stage I (unspecific): -Extreme asthenia (body weakness) -diarrhea, nausea and vomiting, anorexia abdominal pain - headaches - arthralgia (neuralgic pain in joints) - myalgia (muscular pain or tenderness), back pain - mucosal redness of the oral cavity, dysphagia (difficulty in swallowing) - conjunctivitis. - rash all over body except in face ** If the patients don’t recover gradually at this point, there is a high probability that the disease will progress to the second phase, resulting in complications which eventually lead to death (Mupapa et al., 1999).
  • 12.
    • Stage II(Specific): - Hemorrhage - neuropsychiatric abnormalities - anuria (the absence of urine formation) - hiccups - tachypnea (rapid breathing). ** Patients who progressed to phase two almost always die. (Ndambi et al., 1999) • Late Complications: -Arthralgia (joint pain) - ocular diseases (ocular pain, photophobia and hyperlacrimation) - hearing loss - unilateral orchitis( inflammation of one or both of the testes) ** These conditions are usually relieved with the treatment of 1% atropine and steroids Clinical Observations
  • 13.
    Symptoms and DiagnosticTests • Early symptoms – muscle aches, fever, vomiting – red eyes, skin rash, diarrhea, stomach pain • Acute symptoms – bleeding/hemorrhaging from skin, orifices, internal organs • Early Diagnosis • very difficult • signs & symptoms very similar to other infections • Laboratory Test • PCR detection • ELISA (enzyme-linked immuno-absorbant) assay
  • 14.
    Treatment • No StandardTreatment available • Patients receive supportive therapy • treating complicating infections • balancing patient’s fluids and electrolytes • maintaining oxygen status and blood pressure
  • 15.
    Prevention • No vaccines! •Patients are isolated • Medical Staff Training – western sanitation practices • intake • care during stay • after patient dies • Infection-control Measures – complete equipment and area sterilization
  • 16.
    Prevention After Death Virus contagiousin fluids for days • Burial use extreme caution – handling and transport – cultural practices/ religious belief – incinerate all waste !!!!
  • 17.
    Controlling the spreadof Ebola • a. Hospitals must follow precautionary methods, such as: 1. wearing gloves 2. isolating infected individuals 3. practicing nurse barrier techniques 4. proper sterilization and disposal of all equipment • b. Burials must be done correctly 1. no washing or touching carcass 2. put into body bags and bury outside city • c. Report any questionable illness to officials
  • 18.
    Ebola Epidemiology • Reservoirsin Nature – largely unknown – possibly infected animals (primates?) • Transmission – direct contact blood/secretions of infected person – possible airborne (Reston primate facility) • Onset of illness abrupt – incubation period: 2 to 21 days – infections are acute and mostly deadly
  • 19.
    Latest Morbidity andMortality Reports • Ebola-Reston Virus Infection Among Quarantined Nonhuman Primates -- Texas, 1996 – report describes death and blood testing of cynomolgus monkey imported from the Philippines held in a private quarantine facility in Texas • Outbreak of Ebola Hemorrhagic Fever ---Uganda, August 2000--January 2001 – report describes surveillance and control activities related to the EHF outbreak – presents preliminary clinical and epidemiologic findings
  • 20.
    Current Basic Research •The assembly of Ebola virus nucleocapsid requires virion- associated proteins 35 and 24 and posttranslational modification of nucleoprotein • Report describes distinct VP35 and VP24 proteins mechanism of regulation for filovirus assembly • suggests new approaches for viral therapies and vaccines for Ebola and related viruses • Detection of antibodies against the four subtypes of Ebola virus in sera from any species using a novel antibody-phage indicator assay • assesses the presence of specific antibodies in serum • describes development of a novel assay for the detection of seroconversion irrespective of Ebola virus subtype or animal species
  • 21.
    Bioterrorism • Since theSeptember 11 bombings in the United States, the locality of this virus has become less isolated as the threat of bioterrorism looms large. • The Ebola virus is now on the “A” list for hopeful vaccination development. • Experiments have even been formed to show how Ebola can be used as a bioterror agent.
  • 22.
    References • Reemergence ofEbola Virus in Africa; Anthony Sanchez et al,EID Volume 1 * Number 3 July-September 1995 http://www.cdc.gov/ncidod/EID/vol1no3/sanchez.htm • Viral Hemorrhagic Fever, Healthlink, Medical College of Wisconsin, 2000 http://healthlink.mcw.edu/article/955159073.html • Isolation and Phylogenetic Characterization of Ebola Viruses Causing Different Outbreaks in Gabon Emerging Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention ,February 5, 1997 http://www.cdc.gov/ncidod/EID/vol3no1/courbot2.htm • Hemorrhagic fevers; Julia Barrett, Gale Encyclopedia of Medicine, Gale Research, 1999 http://www.findarticles.com/cf_dls/g2601/0006/2601000652/p1/article.jhtm l Key Issues in the Prevention and Control of Viral Hemorrhagic Fevers Clarence J.Peters, MD, Special Pathogens Branch/Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases/Centers for Disease Control and Prevention, 1997 http://www.cdc.gov/od/ohs/sympsium/symp43.htm • Scientific Stock Images Library; Russell Kightley Media,Australia http://www.rkm.com.au/imagelibrary/index.html • Outbreak of Ebola Hemorrhagic Fever ---Uganda, August 2000--January 2001, Morbidity and Mortality Weekly Report, Vol 50, No 05;73, 02/09/2001 / 50(05);73-7 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5005a1.htm • Ebola-Reston Virus Infection Among Quarantined Nonhuman Primates -- Texas, 1996 Morbidity and Mortality Weekly Report, Vol 45, No 15;314 ,April 19, 1996 / 45(15);314-316 http://www.cdc.gov/mmwr/preview/mmwrhtml/00040920.htm The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein, Huang Y et al, Mol Cell. 2002 Aug;10(2):307-16. PMID: 12191476 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12191476&dopt=Abstract Detection of antibodies against the four subtypes of ebola virus in sera from any species using a novel antibody-phage indicator assay.; Meissner F et al , PMID: 1235035 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12350354&dopt=Abstract

Editor's Notes

  • #3 (monkeys, gorillas,chimpanzees)
  • #6 biosafety level 4 agents because of the extreme pathogenicity of certain strains and the lack of a protective vaccine or effective antiviral drug
  • #9 Examples of coiled virions are shown in the background.
  • #10 The core of the Ebola protein thought to mediate membrane fusion
  • #14 Nosocomial transmission(spread of a disease within a health-care setting, Non disposabel needles or syringes:they, or may not have been sterilized, but only rinsed before reinsertion into multi-use vials of medicine. lack of protective clothing contact with contaminated objects improper sterilization of medical equipment
  • #16 Medical Resources scarce Africa
  • #17 Handling and transport protective clothing body sealed in body bag and coffin sanitation of all equipment before and after risk for exposure special steps need to be taken to protect the family and community from illness. family only why open casket not possible some practices cannot be done
  • #20 Reference:last modified January 08, 2002 Internet: http://www.cdc.gov/ncidod/EID/vol1no3/sanchez.htm; © 1994-1998 Stephan Spencer & Jean-Yves Sgro. Web Design By Internet Concepts LLC