Miriam Nuo

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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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Model Parameters
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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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Basic Control Measures
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Basic Control Measures
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Summarized Results
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Hospital Control Measures
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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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Hospital Control Measures
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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
Deaths
Infections
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 the most
  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 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
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Resources Available
US UK South Africa
Population 298,444,215
60,609,153 44,187,637 (high risk)
(6 x 107)
(6.1 x 106) (11 x
106) 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 ?
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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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