the role of cross-immunity and vaccines on the survival of less fit flu-strains
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The role of cross-immunity and vaccines on the survival of less fit flu-strains. Miriam Nu ño Harvard School of Public Health Gerardo Chowell Los Alamos National Laboratory Xiaohong Wang , Carlos Castillo-Chavez Arizona State University. Flu Epidemic and Pandemic Events. - PowerPoint PPT PresentationTRANSCRIPT
The role of cross-immunity and vaccines on the survival of less
fit flu-strainsMiriam Nuño
Harvard School of Public HealthGerardo Chowell
Los Alamos National LaboratoryXiaohong Wang, Carlos Castillo-Chavez
Arizona State University
Flu Epidemic and Pandemic Events
1918 Spanish Flu (H1N1): 500,000 deaths in US and 20 million worldwide.
1957 Asian Flu (H2N2): 70,000 deaths in US.
1968 Hong Kong Flu (H3N2): 34,000 deaths in US.
1976 Swine Flu Scare (H1N1 related??)
1977 Russian Flu Scare (H1N1 related)
1997 Avian Flu Scare (H5N1, human human)
Aquatic birds reservoir of all 15 subtypes of influenza A viruses
Pigs are suspected to be the mixing vessel for influenza viruses
People, pigs and aquatic birds main variables associated with interspecies transfer of flu and emergence of new human pandemic strains
Transmission of flu virus has been shown between pigs and humans
The Reservoirs of Influenza A Viruses
What characterizes a successful invader? The establishment of an existing strain Quarantine The role of cross-immunity
The likelihood of coexistence Phenotypic diversity Invasion under sub-threshold condition
Cross-immunity?Infection with an influenza subtype A strain may provide cross protection against other antigenically similar circulating strains
H1N1H2N2
Influenza type A
H1N1 H3N2
Little evidence support the existence of cross-immunity between influenza A subtypes
Houston and Seattle studies show that cross-immunity exists between strains within the same subtype.
1974 Study < 3% With Prior A/HONG KONG/68 (H3N2) OR
A PRIOR A/ENGLAND/72 (H3N2)GOT A/PORT CHALMERS/73
vs. 23% With NO Prior Experience
1976 Appearance of A/VICTORIA/75 (H3N2)Relative Frequency of First Infected/Previously Infected
(By Another Strain of H3N2 was approximately 59%)
Experimental Evidence of cross-immunity
1977 Co-circulating H1N2 strains
Individuals born before 1952 “GOT” a strain of H1N1 DETECTION OF ANTIBODY-POSITIVE SERA YOUNG: Changed From 0% to 9%.
OLDER: Did not change (remained at 9%)
1982 (Glezen) No Cross-Immunity Between Subtypes
(H1N1 & H3N2)
Experimental Evidence of cross-immunity
Exhibits subtype specificity
Exhibits cross-reactivity to variants within a subtype, but with reduced cross-reactivity for variants that are anti-genically distant from the initial variant
Exhibits a duration of at least five to eight years
Be able to account for the observation that resistance to re-infection with H1N1 may last 20 years
Cross-immunity Summarized
Model
Measure of the average reduced susceptibility to Strain j gained by a host after recovery with Strain i.
ij
0 total immunity (strain j cannot invade)
(0,1) intermediate immunity (strain j likely invade)
1 no immunity (strain j likely invade)
1+ immune deficiency (case not considered here)
Cross-immunity in the model ( )ij
Flu Invasion Conditions (Nuño et al.,)
Pathogen’s invasion determined by
where , the mean transmission rate for Strain i is
denoted by while describes the mean infectious
period of strain i . Invasion of a fully susceptible population is ONLY
possible when
),max( 210
ii
ii
iii
1
10
Flu Invasion and Coexistence
measures the ability of strain 2 to invade a strain-1 endemic population
12
Number of secondary cases that strain-2 infected individuals generate in the susceptible fraction (primary infection)
Number of secondary cases generated by strain-2 infected individuals among the partially immune proportion (secondary infection)
AS ~/~1
AR ~/~1
AR
AS
~~
~~
1
2
212
1
22
212
ASnaive~~
1
22
22
ARimmunecross~~
1
2
2122
Uncertainty and Sensitivity Analysis of the Invasion Reproductive Number 1
2
Uncertainty analysis of quantities its variability generated from the uncertainty of the input parameters in (1).
12
Sensitivity Analysis evaluates the relative impact of to changesin the parameters in (1).
12
(1)
Model Parameters and Distributions
Uncertainty Analysis
.10 size ofeach samples 10for 1 exceeds that
y probabilit and of variancemean, for the Estimates51
2
12
0.3.mean ith immunity w-crossfor quantified are 1)( ecoexistenc to and ofon contributi
The 10. of size sample with and for y probabilit
ingcorrespond and variancemean, for the estimates 10 of sMean value
12
immune-cross2
naive2
immune-cross2
naive2
.ssimulation Carlo Monte10 using )8.0,3.0( regimesimmunity
-cross separate for two of functionson distributi Cumulative5
ij
12
parameter.input each and and ,between
s)(PRCC' tscoefficienn correlatiorank partial Summarizedimmune-cross
2naive2
12
Sensitivity Analysis
Contribution of to Coexistence12
Immune-specific Contributions to Coexistence
Estimation of the Contribution of to Coexistence:12 8.012
Estimation of the Contribution of to Coexistence: 12 3.012
Conclusions & Future Direction Invasion and coexistence are possible when
the level of cross-immunity is moderate, even under sub-threshold condition.
Cross-immunity reduces the likelihood of invasion.
Transmission rate is the most sensitive parameter in (positively correlated)
Study the role of quarantine on invasion and coexistence
12
Acknowledgement
NIH, NSF, MTBI and SAMSI