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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


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Outline

  • Motivation

  • Control Interventions

  • Model and Assumptions

  • Reproduction Numbers

  • Results: US, UK, South Africa Scenarios

  • Current Pandemic Preparedness Plans


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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


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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


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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)


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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


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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


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Other Public Health Interventions

  • Isolation and Quarantine

  • Face masks

  • Behavioral changes



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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)


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Intervention Reproduction Numbers

Control Reproduction Number:

Vaccination Reproduction Number:

Antiviral Reproduction Number:

Combined Reproduction Number:



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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%


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Baseline Scenarios

(no interventions)






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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


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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%


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Baseline Scenarios

(no interventions)


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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%


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Baseline Scenarios

(no interventions)



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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


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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


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Assessing Flu Pandemic Preparedness Plans:

US, UK and South Africa

Preparedness and Communication

Surveillance and Detection

Response and Containment


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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


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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


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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 ?


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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


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