The potential impact of different policies

John Edmunds, Anton Camacho, Roz Eggo, Adam Kucharski, Sebasan Funk, Alexis Robert, Conall Watson, Stefan Flasche

London School of Hygiene and Tropical [email protected] Ring vaccination

All individuals, i.e. Including unvaccinated

• Randomised clinical trial Delayed gives clearest evidence of effecveness of ring vaccinaon policy Early • Are there condions when it might fail to control an outbreak?

Henao-Restrepo et al. Lancet (2015) Ring vaccination

Transmission model

Vaccination delays 80% efficacy and 70% vaccinated means:

Rv = (1-0.7*0.8)Rw = 0.44Rw • Initial (i.e. missed) cases have R=7 • Or R=2.5 if individuals with funeral and hospital transmission omitted • Other cases have R=0.66

Faye et al (2015) The Lancet Infectious Diseases If missed cases associated with superspreading, ring 0= No vaccination vaccination might fail to stop large outbreak (i.e. >500 1= Ring vaccination clusters) even if small proportion of cases missed 2= Mass vaccination

If no funeral or hospital superspreading events, ring vaccination can prevent large outbreaks even if ~40-50% cases missed Model for mass vaccination

- Mass vaccinaon at the regional level - Liberia: county - Sierra Leone: district - Meta-populaon model - Importaons from neighbouring regions - Rate dependent on size & proporonal to cases Base case results 1500 Liberia no vaccination Vaccinaon (base case) 1000 vaccination 80% efficacy 500 Trigger: 10 cases per region Incidence 2 week delay to start 0 0 10 20 30 40 50 100,000 doses per region Weeks 800 per week Sierra Leone 600 no vaccination 70% coverage vaccination 400

Incidence 200

0 0 10 20 30 40 50 Weeks 15000 Liberia Sierra Leone 10000

total cases 5000

0

no vacc reactive no vacc reactive vaccination vaccination Delay in availability 1500 Liberia no vaccination 1000 immediate from 1 Aug 2014 500 from 1 Oct 2014 Incidence

0 0 10 20 30 40 50 Weeks 800 Sierra Leone 600 no vaccination immediate 400 from 1 Aug 2014 from 1 Oct 2014 Incidence 200

0 0 10 20 30 40 50 Weeks Cases Averted Doses Deployed Sierra Leone 10000 Sierra Leone Liberia 3.5 mil

8000 3 mil

2.5 mil Liberia 6000 2 mil

4000 1.5 mil doses deployed cases averted 1 mil 2000 0.5 mil

0 0 mil

1 Aug 1 Oct 1 Aug 1 Oct 1 Aug 1 Oct 1 Aug 1 Oct no vacc no vacc no vacc no vacc immediate immediate immediate immediate HCW: questions

• Do HCW play an acve role in driving the transmission during the increasing phase of the epidemic? • What would have been the benefit (direct and indirect) of vaccinang HCW before this epidemic?

Locaon Populaon size Confirmed & probable cases Community HCW Community HCW Kikwit (1995) 200,000 900 241 76 Liberia (2014) 4.3 m 11.7 k 5 k 378 Sierra Leone (2014) 6.3 m 6.2 k 9 k 307 Guinea (2014) 10.5 m 1.7 k 3.7 k 195 Transmission tree (Kikwit)

health-care worker 1 HCW community 39 secondary cases 25 (69%) are HCW

1 COM 21 secondary cases 100% are COM

262/316 (83%) known index cases Vaccination

• Vaccine type: single dose. • Vaccine efficacy: 70, 80 or 90%. • Protecve 1 week post vaccinaon. • All-or-nothing immunity. • Immunity lasts for 1 year. • Scenario 1: vaccinate all health-care workers before the epidemic. • Scenario 2: vaccine campaign in the community: – 100,000 doses per week (2 weeks to vaccinate all Kikwit area) – Starts on 20 April (2 weeks aer the inial case in Kikwit General Hospital) or on 10 May (arrival of internaonal response team) • Scenario 3: scenario 1 + 2 Proportion of cases averted

Comparing Scenario 1 and Scenario 3, Timing of campaign com hcw 100 100

● ● ● ● ● ● ● ● ● ● ● ● 75 75 ● ● ● ● ● ● ● ● ●

50 50

●

25 25

● ● ● ● ● proportion of cases averted 0 0

20 April 10 May Only HCW 20 April 10 May Only HCW Vaccine efficacy community cases can be averted • Later starts to the campaign (>34 days) result in lile addional benefit to vaccinang only HCW before the epidemic Summary General approach – Impossible to tell what next epidemic will be like – What if vaccine had been available in past outbreaks Ring vaccinaon – Trial demonstrates the effecveness of this strategy – Least effecve if cases who “escape detecon” have high reproducon number – May need to widen ring &/or supplement with more widespread vaccinaon • Stockpile implicaons Mass vaccinaon (district, country, etc) – Effecveness of vaccinaon depends on ming • Late vaccinaon has lile impact HCW vaccinaon (prophylacc) – HCW at very high risk, parcularly at the outset of Ebola epidemics – May also play a role in amplifying inial spread • Vaccinaon of HCW has potenal populaon-level effects General approach – i.e. liming spread to the community Acknowledgements & further details More detailed weekly assessments and district-level forecasts at: hp://cmmid.lshtm.ac.uk/research/ebola/

Data: • MoHs • WHO • MSF

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