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Stephen Gire, MPH
Harvard University
From the origin and transmission to clinical outcomes
Ebola in Sierra Leone
Ebola primer
Viral Particle
Genome
Expression
levels
Levels
Suzuki, Y. & Gojobori, T. The origin and evolution of Ebola and Marburg viruses. Mol Biol Evol 14, 800-806 (1997)
Marburg and Ebola diverged
nearly 10,000 years ago
Filoviruses have ancient origins
Exposure to Ebola is very high in some populations
Over 10,000 cases to date (25,000 adjusted for underreporting)
2.5x under r
eporting
index
Cases doubling every 15-20 days
Stephen gire slides
Stephen gire slides
Stephen gire slides
Rapid sequencing of initial cases in Sierra Leone
Deep sequencing to reveal new insights on EVD
Over 99% coverage of genome at
2000x
Origin and transmission of 2014 EVD outbreak
West African Ebola virus diverged from Central African lineages c. 2004
Diversity data consistent with single importation events from the reservoir
Ebola crosses from Guinea to Sierra Leone - 2 distinct clades enter via 12 travelers
Sierra Leone falls into three main genetic clusters
NS
S
NC
GUINEA
SIERRA LEONE CLUSTER 1
SIERRA LEONE CLUSTER 2
SIERRA LEONE CLUSTER 3
NP VP35 VP40 GP VP30 VP24 L POLYMERASE
Ebola population changes during the 2014 outbreak
Ebola evolution over 3 weeks in Sierra Leone
Monitoring the fixation of mutations during infection
Using genomic surveillance to refine current diagnostics
Clinical signs vary greatly
An early and robust IgG response is indicative of survival
Baize, S. et al. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nature medicine 5, 423-426(1999)
Older patients almost always end in fatal cases
Supportive care and clinical monitoring of EVD patients
Intravenous fluid therapy (100%)
Anti-malarial treatment (55%)
Antibiotic treatment (93%) - mainly ceftriaxone
Pain relief (27%) - paracetamol
Conventional PCR
qPCR retrospectively
Clinical symptoms
Vitals
Supportive Care
Diagnosis
Clinical monitoring
Metabolic panel
n=44
Viral load is a good indicator of outcome
Elevation of CRE and BUN is significant both to EVD and
outcome
Significance to EVD Significance to outcome
Dehydration and worsening renal function play significant role in
disease progression
Extensive liver damage from Ebola is often fatal
Significance to EVD Significance to outcome
ALT and AST significant to EVD; AST significant to outcome
Physical parameters that may indicate outcome
Ebola prognostic scoring test for outcomes
0
1.5
3
4.5
6
7.5
EPS7 EPS 10
Fatal
Non-fatal
p<o.oo1

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Stephen gire slides

  • 1. Stephen Gire, MPH Harvard University From the origin and transmission to clinical outcomes Ebola in Sierra Leone
  • 3. Suzuki, Y. & Gojobori, T. The origin and evolution of Ebola and Marburg viruses. Mol Biol Evol 14, 800-806 (1997) Marburg and Ebola diverged nearly 10,000 years ago Filoviruses have ancient origins
  • 4. Exposure to Ebola is very high in some populations
  • 5. Over 10,000 cases to date (25,000 adjusted for underreporting) 2.5x under r eporting index
  • 6. Cases doubling every 15-20 days
  • 10. Rapid sequencing of initial cases in Sierra Leone
  • 11. Deep sequencing to reveal new insights on EVD Over 99% coverage of genome at 2000x
  • 12. Origin and transmission of 2014 EVD outbreak West African Ebola virus diverged from Central African lineages c. 2004 Diversity data consistent with single importation events from the reservoir Ebola crosses from Guinea to Sierra Leone - 2 distinct clades enter via 12 travelers
  • 13. Sierra Leone falls into three main genetic clusters NS S NC GUINEA SIERRA LEONE CLUSTER 1 SIERRA LEONE CLUSTER 2 SIERRA LEONE CLUSTER 3 NP VP35 VP40 GP VP30 VP24 L POLYMERASE
  • 14. Ebola population changes during the 2014 outbreak
  • 15. Ebola evolution over 3 weeks in Sierra Leone
  • 16. Monitoring the fixation of mutations during infection
  • 17. Using genomic surveillance to refine current diagnostics
  • 19. An early and robust IgG response is indicative of survival Baize, S. et al. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nature medicine 5, 423-426(1999)
  • 20. Older patients almost always end in fatal cases
  • 21. Supportive care and clinical monitoring of EVD patients Intravenous fluid therapy (100%) Anti-malarial treatment (55%) Antibiotic treatment (93%) - mainly ceftriaxone Pain relief (27%) - paracetamol Conventional PCR qPCR retrospectively Clinical symptoms Vitals Supportive Care Diagnosis Clinical monitoring Metabolic panel n=44
  • 22. Viral load is a good indicator of outcome
  • 23. Elevation of CRE and BUN is significant both to EVD and outcome Significance to EVD Significance to outcome Dehydration and worsening renal function play significant role in disease progression
  • 24. Extensive liver damage from Ebola is often fatal Significance to EVD Significance to outcome ALT and AST significant to EVD; AST significant to outcome
  • 25. Physical parameters that may indicate outcome
  • 26. Ebola prognostic scoring test for outcomes 0 1.5 3 4.5 6 7.5 EPS7 EPS 10 Fatal Non-fatal p<o.oo1