Stephen Gire, MPH

Harvard UniversityFrom 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

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

GUINEASIERRA 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