Lessons learned from the West African Ebola outbreak, Marion Koopmans, ERS 2015

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

F Keesing et al. Nature 468, (2010) doi: /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

Probability of stage 2 and 3 infection depends on: 1.Host abundance 2.Fraction infected 3.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 Filoviridae genus Marburg viruses Genus 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 × × nucleotide substitutions/site/year (Caroll et al., 2013)

Animal surveillance for Ebola, Gabon Rouquet et al., 2005 Outbreaks in animals detected prior to (4/5) human disease outbreaks Convincing evidence for bushmeat related introductions Fruit bats Duikers Primates

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 niche No symptoms Infection cyclical Potential 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., Fatal cases higher loads than survivors 2.Early cases can test negative (depending on detection limit of assay) 3.Late samples can test negative, but whether these persons could transmit is unknown 4.Fatal cases rarely mount antibody response 5.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<  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 contact Body fluids of severely ill and deceased patients No airborne Tx > Contact precautions Quarantine Safe burials

WHO, NEJM, 2014; Kilmarx et al., 2014 Mackay, based on WHO reports Exponential growth phase Ro estimates: Liberia 1.5 Sierra Leone 1.4 Guinee 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 cases Of 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: 0.46 outside Africa: 0.17 Sierra Leone: 0.05

Chevallier et al., 2014

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= / #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