1. Measles Vaccination in Epidemic Contexts RF Grais, ACK Conlan, MJ Ferrari, C Dubray, A Djibo, F Fermon, M-E Burny, KP Alberti, I Jeanne, BS Hersh, PJ Guerin, ON Bjornstad, BT Grenfell June 1, 2006

2. Background 2005 2004 2003 2005 2002 8015 2505 10880 40857 17624 Ndjamena, Chad Adamawa, Nigeria Niamey, Niger Kinshasa, DRC Cases Length (months)YearPlace 1 6 12+

3. Rationale Operational guidance for MSF WHO guidelines (1999) –Spread so fast its always too late –Scarce resources best invested elsewhere –Based on literature review and mathematical models of epidemics in non-African settings

4. Objectives 1.Measure the impact of vaccination interventions 2.Examine: Timing of interventions in course of epidemic Age range to vaccinate Intervention vaccination coverage 3.Generalize to other settings

5. Overview of methodology 1.Estimate effective reproductive ratio Chain-Binomial/MLE Ferrari, et al, 2005, Math Biosc, 98(1), 14-26 2.Recreate epidemic & simulate interventions Individual-based model Niamey, Niger 2003-2004 as a case study 3.Generalize results Standard epidemic model with vaccination

6. Niamey, Niger (2003-2004): 2.8 Kinshasa, DRC (2005-6): 1.9 Ndjamena, Chad (2005): 2.5 I NI I I I R= avg number secondary cases generated by one case in a partially immune population 1) Estimating the Effective Reproductive Ratio (R)

7. 2) Recreating an epidemic, Niamey, Niger 2003-2004: Key Assumptions Constant –15 day delay between decision and delivery –10 day intervention –Vaccine efficiency = 85% Variable –2 age ranges for vaccination (standard): 6m to 59m 6m to <15y –Interventions: 2, 3 or 4 months after epidemic starts vaccination coverage: 30% – 100%

8. 2) Model Overview: Niamey, Niger Probability of infection: age immune status vaccination status location in the city status of other children contact decreases with distance time

9. 2) Model Overview: Niamey, Niger Probability of infection: age immune status vaccination status location in the city status of other children contact decreases with distance time

10. 2) Model Overview: Niamey, Niger Probability of infection: age immune status vaccination status location in the city status of other children contact decreases with distance time

11. 2) Model Overview: Niamey, Niger Probability of infection: age immune status vaccination status location in the city status of other children contact decreases with distance time

12. 2) Model Overview: Niamey, Niger Probability of infection: age immune status vaccination status location in the city status of other children contact decreases with distance time

13. 2) Proportion cases prevented by intervention coverage and time: 6 to 59m, Niamey, Niger 0 10 20 30 40 50 60 70 80 90 100 30405060708090100 Intervention Coverage (%) Proportion of Cases Prevented (%) 2 months 3 months 4 months + 6 months

14. 2) Proportion cases prevented by intervention coverage and time: 6 to 15y, Niamey, Niger 0 10 20 30 40 50 60 70 80 90 100 30405060708090100 Intervention Coverage (%) Proportion of cases prevented (%) 2 months 3 months 4 months

15. 3) Generalizing to different scenarios (ex.: 50% coverage, 10 days, 100 000 persons) Proportion reduction in number of cases R Day of intervention

16. Conclusions More time than we thought to intervene 3 Key Factors –Timing –Age range for vaccination –Vaccination coverage objective Benefit even when late –Up to 8% = 800 cases Revision of WHO guidelines

17. Acknowledgements Ministries of Health, Niger, Nigeria, Chad, DRC MSF-F and MSF-B in field and Paris WHO Survey teams Study participants Center for Infectious Disease Dynamics CERMES EPIET

18. Simulated Measles Cases in Niamey, Niger (2003-2004) 8.1% [4.9, 8.9] averted with intervention on day 161 (p = 0.25)

19. S V EIR V 1- VE S 1- VE E Model Overview: Niamey

20. Estimating R We model the time course of an epidemic as a chain of binomial infection events from the pool of susceptible (S) individuals such that the probability of I infected individuals at time t is given by: S 0 is the initial number of susceptible individuals, we can write a likelihood for the time series of case counts, I t, in terms of the transmission rate, , and the initial number of susceptibles, S 0.

21. Reported measles cases in Niamey, Niger (2003-2004) (10880 cases)

22. Reported Measles Cases, N’Djamena, Chad (2004-2005) (8015 cases) Mass vaccination

23. Reported measles cases, Kinshasa, DRC, 2002-2003

24. Measles Cases, Adamawa State, Nigeria (2004-2005) (2505 cases) No more data available

25. Reported measles cases, Kinshasa, DRC 2005