Lessons learned from the West African Ebola outbreak, Marion Koopmans, ERS 2015m.koopmans@erasmusmc.nl ; @MarionKoopmans

Wilson, M.L., Ecology and infectious disease, in Ecosystem Change and Public Health: A Global Perspective, J.L. Aron and J.A. Patz, Editors. 2001, Johns Hopkins University Press: Baltimore. p. 283-324.

http://www.gao.gov/products/GAO-12-55

F Keesing et al. Nature 468, 647-652 (2010) doi:10.1038/nature09575

Drivers and locations of emergence events for zoonotic infectious diseases in humans from 1940–2005.

Probability of further spread greatly increased

Population growth Global travel and trade

1950

2000

2015

Probability of stage 2 and 3 infection depends on:

1.Host abundance2.Fraction infected3.Frequency of 'encounters’ 4.Probability of transmission

per encounter

• phylo distance host • microbe's characteristics• Host characteristics

Wolfe et al., 2007

Start outbreak EBOV

March 10, 2014 notification unknown disease characterized by fever, severe diarrhea, vomiting and high fatality rate in Guéckédou and Macenta in Guinea.

March 22, EVD reported by Guinea to WHO. March 27, EVD suspected cases in Liberia and Sierra Leone related to

outbreak in Guinea. April 3d: ZEBOV Dx

*Time to diagnosis: > 3 weeks

Gastro-enteritis syndrome at clinical presentation

High case fatality rate

First outbreak in West Africa

Baize et al. 2014

< 2 yr old

< seeding through HCW

Diagnose

Feldmann and Geisbert, 2011

Family Filoviridaegenus Marburg virusesGenus Ebolaviruses.Genus Cueva viruses

(Spain, New)

5 species: Sudan (SUDV) Zaire (EBOV) Tai Forest (TAFV) Bundibugyo (BDBV) Reston (RESTV)

Case fatality rate 0-70%Zaire EBOV highest

Soluble GP, frequency depends on sequence specific RNA editing (Mohan et al., 2012)

2.2 × 10-4 - 7.06 × 10-4 nucleotide substitutions/site/year (Caroll et al., 2013)

Animal surveillance for Ebola, Gabon 2001-3

Rouquet et al., 2005

Outbreaks in animals detected prior to (4/5) human disease outbreaks

Convincing evidence for bushmeat related introductions

Fruit batsDuikersPrimates

Saez et al., EMBO Mol Med, 2014

Single zoonotic event in Meliandou, bat-borne, followed by human2human transmisison

Fruit Bats as reservoir for EBOV

Leroy et al., 2005

Overlapping ecological nicheNo symptomsInfection cyclicalPotential source of introduction into West Africa

Potential under-reporting of Ebola (Schoepp et al., 2014)

Initial factors contributing to Ebola outbreak

Bush meat consumption Outbreak in new region Non-specific syndrome Poor healthcare sector, delayed diagnostics Lack of PPE and training Cultural beliefs

> seemingly uncontrollable spread

Shedding kinetics Ebola

Towner et al., 2004; Ksiazeck et al., 1999; Reusken et al., 2014

1. Fatal cases higher loads than survivors2. Early cases can test negative (depending on detection limit of

assay)3. Late samples can test negative, but whether these persons could

transmit is unknown4. Fatal cases rarely mount antibody response5. Are the data the same for the current strain?

Courtesy of Pierre Rolin, US CDC

Nosocomial Tx Ebola

Ftika et al., Ebola Sudan, 2013 AR Unprotected contact HCW 81% Limited physical contact HCW 21% Visiting same room 0%

Baron et al., Ebola Sudan 1983 Unprotected HCW, nursing 67% Unprotected HCW, contact, no nursing 13%

Francesconi et al., Uganda, 2013 Contact body fluids p<0.0001 Funeral ritual p< 0.02 Sharing meal, room , no increased risk

Borchert et al., Marburg outbreak, 2007 Non-invasive procedures: 19% consistent use of PPE Invasive procedures: 29% consistent use of PPE

Direct contactBody fluids of severely ill and deceased patientsNo airborne Tx

>

Contact precautionsQuarantineSafe burials

WHO, NEJM, 2014; Kilmarx et al., 2014Mackay, based on WHO reports http://virologydownunder.blogspot.com.au/

Exponential growth phaseRo estimates:

Liberia 1.5Sierra Leone 1.4Guinee 1.8

Shifting factors contributing to HCAI:

Awareness>availability of PPE>contact in social environment>fatigue

9% of total health workforce!

Incidence of Ebola, HCW

Sierra Leone, May-October

3,854 casesOf these, 199 HCW

Population: 80.4 per 100,000 (1 in 1250)

HCW: 8,285 per 100,000 (1 in 12)

Kilmarx et al., 2014

Nosocomial transmission outside region

Toth et al., 2015

transmissions/case: 0.46outside Africa: 0.17Sierra Leone: 0.05

Chevallier et al., 2014

http://www.npr.org/sections/health-shots/2014/10/02/352983774/no-seriously-how-contagious-is-ebola

How infectious is ebola?

Control strategy

Rapid case finding and ascertainment Local outbreak teams, laboratory capacity

Isolation Holding centres, triage units, lab capacity

Contact tracing Outbreak teams

Decontamination Treatment

Massive fluid replacement, electrolytes, malaria

Social mobilization Certificates, education, patient care, post ebola care

Surveillance Swab teams

Nrs 175, 179, and 183 on the UN human development index (ranked from 1-185)

UN Human development index 2013http://issuu.com/undp/docs/hdr14-report-en?e=3183072/9245907#search

Location of treatment centres

Big challenge: treatment and vaccine trials

Conclusions

The Ebola outbreak is a clear example of the changing epidemiology of emerging infections

Ebola greatly overwhelmed local health infrastructures Long term stable and prepared infrastructures needed to address EID

threats Forward thinking in terms of vaccine and drug development needed for

low probability high impact diseases