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Assessing Basic Control Measures, Antivirals, and Vaccine in Curtailing Pandemic Influenza: Scenarios for the US, UK and South Africa. Miriam Nu ño Harvard School of Public Health, USA Gerardo Chowell Los Alamos National Laboratory, USA Abba Gumel
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Assessing Basic Control Measures, Antivirals, and Vaccine in Curtailing Pandemic Influenza: Scenarios for the US, UK and South Africa 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
Outline • Motivation • Control Interventions • Model and Assumptions • Reproduction Numbers • Results: US, UK, South Africa Scenarios • Current Pandemic Preparedness Plans
Motivation • 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
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
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)
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
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
Other Public Health Interventions • Isolation and Quarantine • Face masks • Behavioral changes
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)
Intervention Reproduction Numbers Control Reproduction Number: Vaccination Reproduction Number: Antiviral Reproduction Number: Combined Reproduction Number:
United States Scenario Population Demographics Population Size: 298,444,215 High risk: 6 x 107(~ 20%) Low risk: 2.4 x 108 (~ 80%) Baseline Predictions R0: ~ 1.4-2.4 Case Fatality Rate: 0.37%-2.5% Clinical Attack Rate: 25%-50%
Baseline Scenarios (no interventions)
R R 0 0 Summarized Results: US Scenario No Interventions 20% Basic Control Measures 10% Attack Rate 1.6 1.9 2.1 2.4 1.6 1.9 2.1 2.4 Infections Deaths Hospitalizations
United Kingdom Scenario Population Demographics Population Size: 60,609,153 High risk: 6.1 x 106 (~ 10%) Low risk: 54.9 x 106 (~ 90%) Baseline Predictions R0: ~ 1.28-2.0 Case Fatality Rate: 0.3%-3.0% Clinical Attack Rate: 30%-50%
Baseline Scenarios (no interventions)
South Africa Scenario Population Demographics Population Size: 44,187,637 High risk: (~ 25%-50%) Low risk: (~ 50%-75%) Baseline Predictions* R0: ~ 1.6-2.4 Case Fatality Rate: 4%-4.5% Clinical Attack Rate: 11%-44%
Baseline Scenarios (no interventions)
R R 0 0 Summarized Results: South Africa Scenario No Interventions 20% Basic Control Measures 10% Attack Rate 1.6 1.9 2.1 2.4 1.6 1.9 2.1 2.4 Infections Deaths Hospitalizations
Results • 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 R0 =1.6 • Combined intervention is by far themost effective strategy
Assessing Flu Pandemic Preparedness Plans: US, UK and South Africa Preparedness and Communication Surveillance and Detection Response and Containment
Preparedness Plans Goal: • Minimize the burden of a flu pandemic (morbidity and mortality) • Minimize social disruption Approach: • Antivirals (prophylaxis and therapeutic) • Flu vaccination • Pneumococcal immunization of high-risk groups • Isolation, quarantine and travel restrictions
Current Preparedness Plans United StatesUnited KingdomSouth Africa Basic Control yesyesyes Measures Antivirals Prophylaxis yesrestricted yes Treatmentyesyes yes Flu Vaccine yesyes yes Pneumococcal noyes no Immunization
Resources Available US UKSouth Africa Population298,444,21560,609,15344,187,637 (high risk) (6 x 107)(6.1 x 106)(11 x 106) Life Expectancy (birth)77.85 years78.54 years42.72 years HIV adult prevalence rate0.6% 0.2%21.5% Interventions Antivirals40M-75M 15M? (25% population?)(25%) Flu Vaccine83.1M-100M 14M ?
Closing Remarks • 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