Stephen Gire - MIT Ebola Panel

1. Stephen Gire, MPH
Harvard University
From the origin and transmission to clinical outcomes
Ebola in Sierra Leone

2. Ebola primer
Viral Particle
Genome
Expression
levels
Levels

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

18. Clinical signs vary greatly

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