Influenza Model General conclusions and Discussion Antigenic Drift of Influenza A related to vaccination and pandemic planning Sido Mylius 1 , Sander van Noort 2 , Jacco Wallinga 1 , Odo Diekmann 2 1 Centre for Infectious Disease Epidemiology National Institute for Public Health and the Environment (RIVM) 2 Department of Mathematics, Utrecht University The Netherlands DIMACS June 29, 2005 Sido Mylius Antigenic Drift of Influenza A
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InfluenzaModel
General conclusions and Discussion
Antigenic Drift of Influenza Arelated to vaccination and pandemic planning
Sido Mylius 1, Sander van Noort 2,Jacco Wallinga 1, Odo Diekmann 2
1 Centre for Infectious Disease EpidemiologyNational Institute for Public Health and the Environment (RIVM)
2 Department of Mathematics, Utrecht University
The Netherlands
DIMACS June 29, 2005
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
Contents
InfluenzaThe virusEpidemics and pandemicsInterventions
ModelGoal and ingredientsResultsConclusions and remarks
General conclusions and . . . Discussion
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
Virus characteristics
I RNA virus, family OrthomyxoviridaeI 3 types: A, B, CI Waterfowl (ducks, geese) are a natural
reservoir for type AI Influenza A: antigenic subtypes,
corresponding to surface proteinshaemagglutinin (H), neuraminidase (N)
I 15 H- and 9 N- subtypesI Variation within subtypes: strainsI Rapidly evolving . . .
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
Antigenic drift and phylogeneticsExample: phylogeny of HA1 domain of A/H3N2
Fitch et al. (1997)
I Less viral diversity than expectedI Antigenic driftI Serial replacement of
predominant strains
I ‘Slender trunk’ with shortbranches
I ‘Competitive exclusion’
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
Antigenic drift and phylogeneticsExample: phylogeny of HA1 domain of A/H3N2
Fitch et al. (1997)
I Less viral diversity than expectedI Antigenic driftI Serial replacement of
predominant strains
I ‘Slender trunk’ with shortbranches
I ‘Competitive exclusion’
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
Antigenic drift and phylogeneticsExample: phylogeny of HA1 domain of A/H3N2
Fitch et al. (1997)
I Less viral diversity than expectedI Antigenic driftI Serial replacement of
predominant strains
I ‘Slender trunk’ with shortbranches
I ‘Competitive exclusion’
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
Immune response
I Low cross-immunity between strains
I Strain-specific long-lived immunityI Host memory of viral epitopesI ≈ (life)long
I Strain-aspecific short-lived immunityI Large amounts of antibodies/CTLs still presentI ≈ weeks (months)
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
EpidemicsAnnual ‘winter epidemics’ in temperate regions
AntiviralsExample scenario: pandemic with 50 % infected
50 100 150 200 250days
500
1000
1500
2000
2500
3000
3500
4000# beds
Number of Dutch hospital beds occupied,without (red) and with (green) early therapeutic use of oseltamivir
for 80 % of all people with ILI
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
Vaccinationand its problems
I Long production delay (≈ 0.5 yr) ⇒
I Epidemics (antigenic drift):I Every year predict which strains to incorporateI Mismatch
I Pandemics (antigenic shift):I Probably too lateI Not successful yet for every subtype
I Additional selection pressure on virus ⇒ ?
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
Vaccinationand its problems
I Long production delay (≈ 0.5 yr) ⇒
I Epidemics (antigenic drift):I Every year predict which strains to incorporateI Mismatch
I Pandemics (antigenic shift):I Probably too lateI Not successful yet for every subtype
I Additional selection pressure on virus ⇒ ?
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
The virusEpidemics and pandemicsInterventions
Vaccinationand its problems
I Long production delay (≈ 0.5 yr) ⇒
I Epidemics (antigenic drift):I Every year predict which strains to incorporateI Mismatch
I Pandemics (antigenic shift):I Probably too lateI Not successful yet for every subtype
I Additional selection pressure on virus ⇒ ?
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
Goal and ingredientsResultsConclusions and remarks
ModelGoal
Question:
How are the influenza A ‘slender trunk’ phylogeny,immune response, and seasonal dynamics related?
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
Goal and ingredientsResultsConclusions and remarks
Starting point
Ferguson et al. (2003) 1
I Multiple-strain model with mutationI Individual-based, stochasticI Spatially structured (patch dynamics, N/S hemispheres)I Long-lived and short-lived immune response
I Short-lived strain-transcending immunity essentialto restrict viral diversity
1N.M. Ferguson, A.P. Galvani and R.M. Bush, 2003.Ecological and immunological determinants of influenza evolution,Nature 422(6930) : 428–433
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
Goal and ingredientsResultsConclusions and remarks
Another modelIngredients 1
I Multiple-strain ‘hybrid’ simulation model:
I Deterministic ‘high-R0’ SIR-model in winterI Stochastic ‘low-R0’ in summer
I Renewal (births and deaths) once a yearI Constant population sizeI Homogeneous mixingI Small, constant import of infectious hosts in summer
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
Goal and ingredientsResultsConclusions and remarks
Another modelIngredients 2
I Cross-immunity between mutant and parent strainexponentially distributed
I Cross-immunity between arbitrary strainsmultiplicative by descent
I Polarized immunity & reduced transmission(Gog & Grenfell, 2002)
I Number of mutants descending from each strainPoisson-distributed(cumulative infection days × per-host mutation prob.)
Sido Mylius Antigenic Drift of Influenza A
InfluenzaModel
General conclusions and Discussion
Goal and ingredientsResultsConclusions and remarks