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
Model Diagram
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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)
Intervention Reproduction Numbers
Control Reproduction Number:
Vaccination Reproduction Number:
Antiviral Reproduction Number:
Combined Reproduction Number:
Model Parameters
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)
Basic Control Measures
Basic Control Measures
Summarized Results
Hospital Control Measures
Summarized Results: US Scenario
No Interventions
20% Basic Control Measures
10%
Attack Rate
1.6
1.9
2.1
2.4
1.6
R0
Deaths
Hospitalizations
1.9
R0
2.1
2.4
Infections
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)
Hospital Control Measures
Summarized Results: South Africa Scenario
No Interventions
20% Basic Control Measures
10%
Attack Rate
1.6
1.9
2.1
R0
Deaths
2.4
1.6
Hospitalizations
1.9
R0
2.1
2.4
Infections
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 the most 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 States
Basic Control
Measures
yes
United Kingdom
yes
South Africa
yes
Antivirals
Prophylaxis
yes
restricted
yes
Treatment
yes
yes
yes
Flu Vaccine
yes
yes
yes
Pneumococcal
Immunization
no
yes
no
Resources Available
US
UK
South Africa
Population
(high risk)
298,444,215
(6 x 107)
60,609,153
(6.1 x 106)
44,187,637
(11 x 106)
Life Expectancy (birth)
HIV adult prevalence rate
77.85 years
0.6%
78.54 years
0.2%
42.72 years
21.5%
Interventions
Antivirals
Flu Vaccine
40M-75M
(25% population?)
15M
(25%)
?
83.1M-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