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E. Bottieau
Avondseminarie ITG
18/12/2014
Introductie
On March 10, 2014, hospitals and public health services in Guéckédou and Macenta
alerted the Ministry of Health of Guinea about clusters of a mysterious disease
characterized by fever, severe diarrhea, vomiting, and an apparent high fatality
rate.
Yambuku, mission hospital, Zaire
Ebola epidemics in the past
602 cases 72% death
315 cases 81% death
425 cases 53% death
413 cases 51% death
Baize S et al. N Engl J Med 2014.
Ebola virus disease (EVD) epidemic in West Africa
March 2014: WHO alert
EVD epidemic in West Africa: initial transmission
Alert due to cluster of cases
March 2014
Baize S et al. N Engl J Med 2014.
Initial single case ! Dec 2013
Cumulative reported cases of EVD in Guinea, Liberia and Sierra Leone Mar 25-Dec 10, 2014 (n=17908)
EVD epidemic in West Africa: current situation
7
Ebolavirus: phylogenetic analysis “Fruit bat”
Carroll SA et al. J Virol 2013
Family Filoviridae
Zaire ebolavirus
Sudan ebolavirus
Bundibugyo ebol.
(Reston ebol.)
(Taï Forest ebol.)
8
Ebolavirus: viral structure “Fruit bat”
• Negative strand RNA virus
• Small genome (7 viral genes)
• Surface glycoprotein (GP)
• RNA Polymerase (L)
• 4 structural proteins
9
Ebolavirus: transmission “Fruit bat”
10
Ebolavirus: transmission “Fruit bat”
Human Human
11
EVD: pathogenesis
Ansart AA. J Autoimm 2014
12
EVD: event timeline “Fruit bat”
Inoculation (“challenge”)
Onset clinical symptoms
(Death)
Prepatent Symptomatic Recovery
5d (sd 4) 9d (sd 7)
7d (sd 5)
Early symptoms
% Fever 87 Fatigue 77 Vomiting 68 Diarrhea 66
% Cough 30 Dyspnea 23 Dysphagia 33 Sore throat 22 Bleeding 18 Confusion 13 Jaundice 10
Hosp. (Discharge)
16d (sd 6)
Late symptoms
WHO response team N Engl J Med 2014
13
EVD: clinical features and predictors of death
WHO response team N Engl J Med 2014
14
EVD: risk factors for death - age
Age: 0-5 years Age: 5-40 years Age: > 40 years
15
EVD: risk factors for death - EBOV load
Schieffelin JS et al. N Engl J Med 2014
16
EVD: viral detection over time in body fluids
17
EVD in the field: pictures MSF
18
EVD treatment: supportive care (Europe/USA)
19
EVD experimental treatments
Immunotherapy
Antivirals
Vaccines
Convalescent plasma Study Guinea: Jan 2015/ITG
Monoclonal antib. (Zmapp)
Equine polyclonal immunoglobulins
100% protective NHP/used in humans
Phase 1 planned in Apr 2015
Favipiravir (Toyama/Fuji)
Brincidofovir (Chimerix)
TKM-100802 (Tekmira)
AVI-7537 (Sarepta)
BCX 4430 (BioCryst)
NA; Study Guinea: Dec 2014 /INSERM
RNA anti-sense; phase 1 ongoing
RNA anti-sense; study NHP ongoing
NA; study NHP ongoing
NA; Study Guinea: Jan 2015/Oxford
• Cocktail of 3 monoclonal antibodies
• 100% protective in NPH up to 5 days post-challenge
• Used in a few human cases
• Few doses available
• 3 IV administrations with 3 days interval
20
EVD in USA: ZMapp
Lyon GM et al. N Engl J Med 2014
21
EVD vaccines
cAd3 EBOV GP (GSK) Phase 1 ongoing
rVSV EBOV GP (NewLink Genetics) Phase 1 ongoing
22
EVD epidemic: new and total cases, Dec 10, 2014
WHO roadmap Dec 10, 2014.
+/- 18000 cases
23
EVD epidemic: cases weekly reported: recent trends
WHO roadmap Dec 10, 2014
Liberia Sierra Leone
Guinea
Case fatality rate • Total: 75 % • Hospital: 60 %
• Post conflict environment in affected countries
• Porous borders between countries
• First epidemic in urban setting
• Extensive mobility and air travel in West Africa
• Inefficient healthcare system
• Traditional burial practices
• Negative cultural practices and traditional beliefs
• First occurrence of Ebola in West Africa (no institutional memory)
• Health workers not trained to respond and protect themselves
• Inadequate and late international response
• High level of resistance to the Ebola outbreak response
Current EVD in West Africa: why so different ?
• Largest and most persistent EVD outbreak ever
• Widespread under-reporting of new cases
• No persuasive evidence that the epidemic is under control
• Low but existing risk of importation to Belgium
Current EVD in West Africa: conclusions
Bedankt voor uw aandacht
26
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