filoviruses - enivdsymptoms of ebola virus disease (evd) • beginning with high fever...
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Filoviruses
Dr. Olga Dolnik Philipps-University Marburg
Institute of Virology 24.2.2015
ECDC Training Course – Ebola and Marburg Diagnostic 24th February to 27th February 2015
Robert Koch Institute, Berlin
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Taxonomy
Order
Family
Genus
Species
Mononegavirales (ss –RNA)
Rhabdoviridae Paramyxoviridae Filoviridae Bornaviridae
Ebolavirus Marburgvirus Cuevavirus
Zaire
EBOV
Sudan
SUDV
Tai Forest
TAFV
Reston
RESTV
Bundibugyo
BDBV
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First documented Filovirus Outbreak
• Marburg, Frankfurt, Belgrade. • Primary cases: Lab workers
with contact to tissue of imported monkeys (Uganda).
• Secondary cases: relatives, health care workers.
• 32 cases, CFR: 25%.
Werner Slenczka Rudolf Siegert 100 nm
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Conjunctivitis Enanthema
Thrombocytopenia Diarrhea Exanthema Hepatitis
Hemorrhages
Marburg virus hemorrhagic fever
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Imported Marburg fever (Netherlands 2008)
• July 5: – Dutch tourist (41) returning from holiday in Uganda (June 5 – 28) – Presents to the general practitioner with high fever (39°C, 3d) – Admission to the local hospital – Placed in a room with 3 other patients – Malaria diagnostics negative – Bacteriological tests, treatment with ceftriaxone (2 g/day)
• July 7: – Rapid deterioration, liver failure: Hemorrhagic fever as differential
diagnosis included – Transfer to Leiden University Hospital; patient developed rash,
conjunctivitis, diarrhea, liver and kidney failure, hemorrhages. – Extensive bacteriological and virological analyses
• July 10: – Tested positive for Marburg virus at the Bernhard-Nocht-Institut in
Hamburg.
• July 1: – Patient died of cerebral edema.
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The Python cave, Uganda
© René Gottschalk © René Gottschalk
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Marburg virus RNA in animal species collected in the Goroumbwa gold mine, Durba
Swanepoel et al., EID, 2007
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Durba: Bat and human MARV isolates
Phylogenetic tree
Swanepoel et al., EID, 2007
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Since 1976 emerging EBOV outbreaks in central Africa
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EBOV outbreaks in humans
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Ebola virus Reston circulates in Philippines
- Epizootics since 1989 - non pathogenic in humans - pathogenic for cynomolgus macaques (systemic) - symptomatic disease in pigs (lung), asymptomatic infections - transmission to humans (IgG) - REBOV-specific IgG in Rousetttus amplexicaudatus bats
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Transmission and Reservoir
Detection of specific antibodies Isolation of virus specific RNA
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Distribution of fruit bats in equatorial Africa
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Baize et al., 2014
Emergence of Zaire Ebola virus in Guinea
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Regional distribution of confirmed and suspected cases of EVD in October 2014 (WHO)
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1. Densely populated regions with big cities, Conakry (Guinea), Monrovia (Liberia) und Freetown (Sierra Leone)
2. Poor medical infrastructure in rural regions, traditional burial practices 3. Cross-boarder trade and social activities
Three major factors driving continuous transmission of EBOV in West Africa
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Human to human transmission
17
- direct body contact with symptomatic patients - direct contact with body fluids of patients (blood, urine, stool, sweat, saliva, sputum,
semen, breast milk) - direct contact with contaminated surfaces - no air transmission - low kontagiosity (R0 Ebola 1-4, R0 measles 12-18) - moderate thermostability (4°C weeks, room temperature days, 60°C 30min, 5min boiling) - sensitive to UV, detergents, formaldehyde, acids - anti-viral disinfectant (enveloped viruses!), chloric bleach
SW Mitchell end JB McCormic, 1984 Piercy et al., 2010
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Prevention
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Ebolavirus
19
Glycoprotein, GP
ribonucloproteincomplex
matrix, VP40
lipidenvelope
L. Kolesnikova
1977 W. Slenczka
3´ Leader Trailer 5´ NP 35 40 GP 24 30 L
sGP
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Replication cycle
Dolnik et al., Cell Mol Life Sci. 2008
NPC1 actin
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Pathogenesis
Nature reviews Immunology 2007
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• Incubation time 2-21 days
Symptoms of Ebola virus disease (EVD)
• Beginning with high fever (>38,5°C), muscle pain, nausea
• Multiplication of the virus in vital organs like liver, kidney, spleen and lung which causes organ failure
• abdominal pain, diarrhea
• destruction of the vascular endothelium
• sever cases die due to multi-organ failure and shock
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Case definition EVD
clinical, epidemiological, high-risk exposer and laboratory criteria
clinical criteria: fever ≥ 38,6°C and any of the following: - severe headache - vomiting, diarrhea, abdominal pain - unexpected hemorrhagic signs - multi-organ failure epidemiological criteria: within 21 days before the onset of symptoms:- having been in an area with community transmission of EVD - having contact with probable or confirmed EVD case high-risk exposer criteria: - close contact (within 1m) without appropriate personal protection with a probable or confirmed case who was coughing, vomiting bleeding, had diarrhea, unprotected sexual contact with a case up to three month after recovery - direct contact with body fluids from a probable or confirmed case - percutaneous injury or mucosal exposure to body fluids, tissue or laboratory specimens of a probable or
confirmed case - participation in funeral rites with direct exposure to human remains in or from affected area without
personal protection - direct contact with bats, rodents, primates, living or dead, in or from affected area, or bush meat
laboratory criteria: detection of nucleic acid, Ag-ELISA, EM in clinical specimens
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Management of patients with haemorrhagic fevers
• Isolation units, Personnel under full protection • Meldung an das jeweils zuständige
Gesundheitsamt.
(Meldepflicht bei Auftreten und beim Verdacht auf hämorrhagisches Fieber (IfSG).
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25
BSL 4 Laboratory at the Philipps-University in Marburg
BSL4 Lab
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Diagnostic Direct virus detection: Real-time-PCR (Altona Filovirus screen) > RNA detection! Antigen-ELISA (Matrix protein specific antibodies) (Senova) Electron microscopy > detection of virus particles in patient samples Virus cell culture (BSL-4) > CPE
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Diagnostic Antibody detection (Serology): IgM-IgG ELISA Indirect Immunofluorescence Test (IFT) Virus neutralization test
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Vaccine
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Experimental drugs and vaccines in clinical trials
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Thank you for your attention!
Questions?