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Ebola 101: the virology behind the outbreak Amy L. Hartman, Ph.D. Assistant Professor Dept. Infectious Diseases and Microbiology Pitt Graduate School of Public Health and Center for Vaccine Research Historic Ebola outbreaks 1976 – 2014 50 – 90 % mortality rate Updated 2014, CDC.gov Day of infection Start of incubation period 6-12 days Day 0 – 3: Early febrile phase: fever, fatigue, malaise, body aches Days 3 – 10: Gastrointestinal phase: abdominal pain, nausea, vomiting, watery diarrhea, persistent fever, body aches, hiccups Fatal cases: Severe dehydration, rapid breathing, loss of consciousness Death 7 – 12 days after onset of illness Recovery: Resolution of GI symptoms, rehydration Human Clinical Disease Important interventions: Fluid & electrolyte replacement Anti-nausea, antidiarrheal therapy Later complications: Secondary infections, encephalitis, neurological abnormalities Schieffelin et al. 2014 NEJM; Chertow et al. 2014 NEJM Diagnostic testing for Ebola PCR-based diagnostic testing not reliable until 72 hours after onset of symptoms Field’s Virology FIGURE 32.12. Virus in the blood in fatal vs. surviving cases Outbreak in Uganda 2000 - 2001 Towner et al. 2004. J Virology Human-to-human transmission of Ebola • Virus shed in bodily fluids – Blood, saliva (oral/nasal secretions), urine/feces, vomit, sweat, breast milk • Direct contact with bodily fluids is required for transmission • Mucosal surfaces are main entry point of the virus – Eyes, mouth, nose Activities historically associated with Ebola transmission • Healthcare workers • Traditional healers • Spillover from bat reservoir • Traditional burial practices Direct contact with sick patients Direct handling of dead bodies Interaction with bats and/or bat caves Bushmeat trade • Consumption of wild animal meat Why is Ebola so pathogenic? Virus replicates to high levels in many cell types Causes direct tissue/cell death Causes vascular leakage 50 – 90 % fatality rate Causes coagulation abnormalities Inhibits the immune response Induces of harmful inflammatory responses Post-exposure treatments From Dye et al., PNAS 2012 Prophylactic (preventative) vaccines Ann Intern Med. Published online August 21, 2014. doi:10.7326/M14-1904 Rapid testing of Ebola vaccines • NIAID/GSK – Chimpanzee adenovirus type 3 (ChAd3) vector – Monovalent and bivalent versions – Express Ebola glycoprotein (Zaire & Sudan) • Public Health Agency Canada – Vesicular Stomatitis Virus (VSV) vector – Express Ebola glycoprotein Current West African outbreak Nov 30th: 17,145 cases with 6,070 deaths Cumulative cases in West Africa What makes this outbreak different from previous Similarities • • • • • • Transmission Symptoms Incubation period Serial time R0 Fatality rate Differences • • • • Scale (30x) Urban setting Other socioeconomic issues Increased human mobility Factors influencing Ebola outbreaks Ecological Virological • Climate change • Effect on bat reservoir & spillover dynamics • Characteristics of the virus strain Sociological • • Human behavior Urban environment Questions?