1. Miriam Nuño Harvard School of Public Health, USA Gerardo Chowell Los Alamos National Laboratory, USA Abba Gumel University of Manitoba, Canada AIMS/DIMACS/SACEMA Workshop Assessing Basic Control Measures, Antivirals, and Vaccine in Curtailing Pandemic Influenza: Scenarios for the US, UK and South Africa

2. Motivation Control Interventions Model and Assumptions Reproduction Numbers Results: US, UK, South Africa Scenarios Current Pandemic Preparedness Plans Outline

3. Assess the role of several interventions in reducing the burden of a potential flu pandemic Determine the “optimal” flu pandemic preparedness plan? Evaluate current preparedness plans for the US, UK and South Africa Motivation

4. Antivirals Adjunct to flu vaccine for control and prevention Adamantanes: amantadine (A) and rimantadine (R); flu A NA inhibitors: zanamivir (Z) and oseltamivir (O); flu A and B Antivirals differ in side effects, route of administration, approved ages, dosages and costs Used for treatment or prophylaxis

5. Antiviral Treatment Adamantanes can reduce duration of uncomplicated flu A by ~1 day (if administered within 2 days of illness onset ) NA inhibitors provide similar reduction against both flu A and B Recommended duration of treatment with NA inhibitors is 5 days Therapy with adamantanes should be discontinued when clinically possible to reduce resistance (3-5 days of treatment or within 24-48 hours of symptoms disappearance)

6. Antiviral Chemoprophylaxis Adamantanes preventive effectiveness to flu A approximately 70%-90% Only Oseltamivir has been approved for prophylaxis (80% effective) Implementation involves: cost, compliance and potential side effects Maximum-effectiveness approach: taken each day for the duration of flu activity Cost-effective approach : Adamantanes taken during period of peak flu activity Doses vary according to age, risk groups, and other factors

7. Seasonal Flu Vaccine Inactivated (killed-virus) vaccine approved for people older than 6 months; including healthy and chronically ill Nasal-spray (live-weakened) vaccine approved for healthy people 5-49 years (excluding pregnant women) Trivalent dose with 2 type A (H3N2, H1N1) and one type B virus Vaccine updated each year Protecting antibodies develop ~ 2 weeks following vaccination Who should get vaccinated: (1) people at high-risk of complications (2) people caring for high-risk groups High-risk groups include: (1) children 6-59 months, (2) pregnant women, (3) elderly ages 50 + (4) chronically ill of any age, (5) immune compromised

8. Other Public Health Interventions Isolation and Quarantine Face masks Behavioral changes

9. Model Diagram

10. Basic Reproduction Number Average number of new cases generated by an infectious individual during its period of infectiousness in a completely susceptible population (no interventions)

11. Intervention Reproduction Numbers Control Reproduction Number : Vaccination Reproduction Number : Antiviral Reproduction Number: Combined Reproduction Number :

12. Model Parameters

13. United States Scenario Population Demographics Population Size: 298,444,215 High risk: 6 x 10 7 (~ 20%) Low risk: 2.4 x 10 8 (~ 80%) Baseline Predictions R 0 : ~ 1.4-2.4 Case Fatality Rate: 0.37%-2.5% Clinical Attack Rate: 25%-50%

14. Baseline Scenarios (no interventions)

15. Basic Control Measures

17. Summarized Results

18. Hospital Control Measures

22. 0 R 0 R Deaths Hospitalizations Infections 1.6 1.9 2.1 2.4 Summarized Results: US Scenario 10% Attack Rate No Interventions 20% Basic Control Measures

23. Population Demographics Population Size: 60,609,153 High risk: 6.1 x 10 6 (~ 10%) Low risk: 54.9 x 10 6 (~ 90%) United Kingdom Scenario Baseline Predictions R 0 : ~ 1.28-2.0 Case Fatality Rate: 0.3%-3.0% Clinical Attack Rate: 30%-50%

24. Baseline Scenarios (no interventions)

25. Population Demographics Population Size: 44,187,637 High risk: (~ 25%-50%) Low risk: (~ 50%-75%) South Africa Scenario Baseline Predictions * R 0 : ~ 1.6-2.4 Case Fatality Rate: 4%-4.5% Clinical Attack Rate: 11%-44%

26. Baseline Scenarios (no interventions)

27. Hospital Control Measures

28. 10% Attack Rate 1.6 1.9 2.1 2.4 0 R 0 R Deaths Hospitalizations Infections Summarized Results: South Africa Scenario No Interventions 20% Basic Control Measures

29. Optimal intervention strategy is country-specific Antivirals are the best single intervention strategy Therapeutic antivirals preferred over prophylaxis for countries with limited resources Vaccine is the next best single strategy intervention strategy Basic control interventions reduce the burden of a pandemic, however, a pandemic may be prevented if R 0 =1.6 Combined intervention is by far the most effective strategy Results

30. Assessing Flu Pandemic Preparedness Plans: US, UK and South Africa Preparedness and Communication Surveillance and Detection Response and Containment

31. Minimize the burden of a flu pandemic (morbidity and mortality) Minimize social disruption Goal: Antivirals (prophylaxis and therapeutic) Flu vaccination Pneumococcal immunization of high-risk groups Isolation, quarantine and travel restrictions Preparedness Plans Approach:

32. United States United Kingdom South Africa Basic Control yes yes yes Measures Antivirals Prophylaxis yes restricted yes Treatment yes yes yes Flu Vaccine yes yes yes Pneumococcal no yes no Immunization Current Preparedness Plans

33. Resources Available US UK South Africa Population 298,444,215 60,609,153 44,187,637 (high risk) (6 x 10 7 ) (6.1 x 10 6 ) (11 x 10 6 ) Life Expectancy (birth) 77.85 years 78.54 years 42.72 years HIV adult prevalence rate 0.6% 0.2% 21.5% Interventions Antivirals 40M-75M 15M ? (25% population?) (25%) Flu Vaccine 83.1M-100M 14M ?

34. What can be learned from the discussed preparedness plans? Is there a single optimal strategy to prepare for pandemic flu? Hospital and community control measures can go a long way, particularly in developing countries with poor resources Prophylaxis versus therapeutic us of antivirals!! Complications in countries with high HIV and TB prevalence Closing Remarks