The Potential Impact of Different Vaccination Policies

The potential impact of different vaccination policies

Rosalind Eggo, John Edmunds, Anton Camacho, Adam Kucharski, Sebastian Funk, Alexis Robert, Conall Watson, Stefan Flasche

London School of Hygiene & Tropical Medicine [email protected] Summary & key questions 1. Vaccination of health care workers – What is impact of prophylactic vaccination? 2. Ring vaccination – Clearly effective (clinical trial) – Are there conditions when it might fail to control an outbreak? 3. Mass vaccination (district level) – What effect if vaccines had been available during the current outbreak? HCW: questions

• Do HCW play an active role in driving the transmission during the increasing phase of the epidemic? • What are the benefits (direct and indirect) of vaccinating HCW before an epidemic?

Population size Confirmed & probable cases Location 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 Outbreak in Kikwit (1995)

76 of 317 cases (24%) were HCW

6 April, 1 st case at Kikwit General Hospital

Undetected outbreak 4 & 10 May, control measures start 15

10 occupation hcw com incidence 5

Jan Feb Mar Apr May Jun Jul Transmission tree (Kikwit)

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

1 COM 21 secondary cases 100% are COM

262/317 (83%) known index cases Model fit

Fit the model to the second part of the outbreak, from 6 April 1995

Community incidence com, incidence_obs hcw,HCW incidence_obs incidence

20 20

15 15 Level 50% 95% 10 value 10

5 5

0 0

Apr 15 May 01 May 15 Jun 01 Jun 15 Apr 15 May 01 May 15 Jun 01 Jun 15 date Vaccination characteristics

• Single dose vaccine • 80% efficacy • Protective 1 week post-vaccination • All-or-nothing immunity • 1 year protection • 100,000 doses deployed per week in community

1. HCW prophylaxis +/- reactive community vaccination 2. Reactive HCW + community vaccination • Base scenario: vaccinate all HCW before the epidemic only • Reactive vaccination : - 20 April: 2 weeks after first case in Kikwit General Hospital - 10 May: arrival of international response team Reactive community vaccination: cases averted Communitycom HCW hcw 100 100

75 75

50 50

25 25

proportionof avertedcases 0 0

20 April 10 May Only HCW 20 April 10 May Only HCW

• Vaccination of HCW can prevent cases in both HCW and community • Rapid community vaccination can avert a large fraction of cases • Late start to the community campaign results in little additional benefit • Number of doses very different (900 in HCW vs 150,000 in community) Reactive HCW & community vaccination: cases averted Communitycom HCW hcw 100 100

75 75

50 50 25 25 proportion ofproportioncases averted 0 0

20 April 10 May Only HCW 20 April 10 May Only HCW • Without early start to HCWCampaign campaign, star protectiont date of HCW is lower • Even ~1 month delay from 1 st case to vaccination of HCW diminishes effect • Both in HCW and community Limitations of HCW model

• Definition of HCW may vary – Both geographically and through time • Depletion of HCW – Due to morbidity/mortality – Leaving posts • Homogeneous mixing of HCW and community members • Duration of protection of vaccine is key Ring vaccination

All individuals, i.e. including unvaccinated

• Randomised clinical Delayed trial gives clearest evidence of effectiveness of ring Early vaccination policy

• Are there conditions EVD % confirmed when it might fail to control an outbreak?

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

• 80% efficacy • 70% of individuals in rings are vaccinated • 2 days from case identification to vaccination of contacts • 7 days to onset of immunity Ring vaccination model

AB C

Vaccine: • 80% efficacy • 70% of individuals in rings are vaccinated • 2 days from case identification to vaccination of contacts • 7 days to onset of immunity Ring vaccination model

A B Index case Traced contact Missed case

C Vaccine: • 80% efficacy • 70% of individuals in rings are vaccinated • 2 days from case identification to vaccination of contacts • 7 days to onset of immunity Input data • Initial (i.e. missed) cases have R=7 • Other cases have R=0.66 • With funeral and hospital transmission omitted, initial cases have R=2.5

Faye et al (2015) The Lancet Infectious Diseases Model can generate realistic epidemics • Each colour is a transmission chain • Distribution comparable to observed data Proportion of cases not in known chain

Key area of uncertainty

Guinea, 2015. Weekly proportion not in known chain. Data from Situation Reports If missed cases associated with superspreading, ring • No vaccination 1 index case vaccination might fail to stop large outbreak (i.e. >500 • Ring vaccination 5 index cases clusters) even if small proportion of cases missed Missed case R = 7 If missed cases associated with superspreading, ring • No vaccination 1 index case vaccination might fail to stop large outbreak (i.e. >500 • Ring vaccination 5 index cases clusters) even if small proportion of cases missed Missed case R = 7 Missed case R = 2.5

If no funeral or hospital superspreading events, ring vaccination can prevent large outbreaks even if ~40-50% cases missed Limitations of ring vaccination model

• Reliance on data from early part of the epidemic • Clustering of cases and contacts is not included • No depletion of susceptibles Model for mass vaccination

• Mass vaccination at the regional level - Liberia: county - Sierra Leone: district • Meta-population model - Importations from neighbouring regions - Rate dependent on size & proportional to cases Base case results

1500 Liberia no vaccination Vaccination (base case) 1000 vaccination 80% efficacy 500 Protection for 10 years Incidence

Trigger: 10 cases per region 0 0 10 20 30 40 50 2 week delay to start 800 Weeks Sierra Leone 100,000 doses per region 600 no vaccination vaccination per week 400

70% coverage Incidence 200

0 0 10 20 30 40 50 Weeks Sierra Liberia Leone Delay in vaccine 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 Cases Averted Weeks Sierra Doses Deployed Sierra Leone Liberia Leone Liberia Limitations of mass vaccination model • Doses – Reactive vaccination ends only when coverage is reached, or the end of the simulation (1 year) • Importation of cases – number of importations proportional to the local simulated epidemic – do not account for the region that imported cases are from • Homogeneous mixing – widely used in epidemiology due to their tractability and accuracy in large populations • Guinea – More spatial heterogeneity Summary General approach – Impossible to tell what next epidemic will be like – What if vaccine had been available in past outbreaks Ring vaccination – Trial demonstrates the effectiveness of this strategy – Least effective if cases who “escape detection” have high reproduction number – May need to widen ring &/or supplement with more widespread vaccination • Stockpile implications Mass vaccination (district, country, etc) – Effectiveness of vaccination depends on timing • Late vaccination has little impact HCW vaccination (prophylactic) – HCW at very high risk, particularly at the outset of Ebola epidemics – May also play a role in amplifying initial spread • Vaccination of HCW has potential population-level effects, i.e. limiting spread to the community Acknowledgements & further details More detailed weekly assessments and district-level forecasts at: http://cmmid.lshtm.ac.uk/research/ebola/

For further details on models, email: [email protected]

Data: • MoHs • WHO • MSF Extra slides Ring vaccination All individuals

• Randomised clinical trial Delayed gives clearest evidence of effectiveness of ring vaccination policy Early

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

Transmission model

Vaccination delays 80% efficacy and 70% vaccinated means: Rv = (1-0.7*0.8) Rw = 0.44 Rw Transmission trajectories

4 • 3 examples showing 3 Bo distribution of Reproduction 2 1 number in fitted model 0 0 10 20 30 40 50 • Use 100 trajectories to 5 4 Kono simulate epidemics 3 2 • Captures public health 1 0 0 10 20 30 40 50 responses & behavioural 0 10 20 30 40 50 changes 5 Reproduction number Reproduction 4 Tonkolili 3 2 1 0 0 10 20 30 40 50 weeks Model for mass vaccination

Model fitted to • Liberia region-specific data • Reproduction number (in each region) allowed to vary over time Sierra – Captures public Leone health responses & behavioural changes • Simulations: allow model to run with and without vaccination • No vaccination If missed cases associated with superspreading, ring • Ring vaccination vaccination might fail to stop large outbreak (i.e. >500 • Mass vaccination clusters) even if small proportion of cases missed 1 index case 5 index cases • No vaccination If missed cases associated with superspreading, ring • Ring vaccination vaccination might fail to stop large outbreak (i.e. >500 • Mass vaccination clusters) even if small proportion of cases missed 1 index case 5 index cases

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