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Simon Cauchemez & Neil Ferguson
MRC Centre for Outbreak Analysis and Modelling Imperial College London
Dynamics of spread of H1N1
Spread around the world
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New Zealand
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Victoria - Australia
UK
fluTracker, oct 21th
USA
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Brazil
Mexico
Analysis of epidemiological data – WHO informal mathematical modelling network
Southern Hemisphere analysis
• First wave finished. Can analyse ILI or confirmed case epi curves and age distribution.
• R estimates depend on epidemic growth rate
Variable estimates of R – low in Australasia (1.1-1.3), higher in South America (1.3-1.6)
Overall best guess – R=1.3-1.4. • Infection attack rates estimates depend
on age-dependent susceptibility profile (less well estimated):
Infection AR=20-40%. • ILI attack rate likely to be 25%-50% of
infection attack rate. • Very low case fatality ratios (<0.005%)
(see also Presanis et al PLoS Currents Influenza 2009).
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Victoria - Australia
Opatowski et al, In preparation
UK - data
Whole population 5-15 yr old
• 3% of English population have sought care for ILI since May 2009. • But true illness/infection rates in the community may be much higher. • 2.5% of those seeking care are being hospitalised at present.
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UK – analysis and modelling
• A range of epidemic models fitted the June-July increase well, and the decline after schools closed.
• But predicting the autumn required the ratio of infections to those seeking care to be known.
• Best guess assessment is of ratio of 3, giving second wave smaller than or comparable to first – but a lot of uncertainty.
US trends
• Google Flu Trends:
Indicates epidemic has reached level of activity comparable with 2007-8 seasonal flu epidemic.
Growth rate slow – doubling time never got below 17 days, and has now reduced. Consistent with R~1.2.
Google trend
ILI
• ILI surveillance:
Looked like epidemic had peaked 2 weeks ago, but ILI increasing again.
But doubling time of current wave always >8 days (now ~20 days).
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Continental Europe
• France did not have a spring-summer epidemic, but is also seeing slow growth of ILI at the current time.
• Considerable variation across EU in progress of pandemic.
What will be the impact of seasonality on transmission?
France
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Household transmission
• US analysis (collaboration with CDC):
216 households with a probable or confirmed case;
12% mean household secondary attack rate for Acute Respiratory Illness, 8% SAR for ILI - low compared with previous pandemics.
• UK data (collaboration with HPA):
8% household SAR for confirmed H1N1 infection, 11% for ILI (in the presence of AV use).
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Household size
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Age-specific patterns
US
UK
• Analysis of household data indicated
Children are >2 fold more susceptible to infection than adults.
>50 yr are less susceptible than 19-50 yr.
• ILI and confirmed case age distributions indicates marked drop in susceptibility with age.
• Estimated mean incubation period of 1.5-2 days from outbreak in a bus.
• UK analysis: Serial interval (time lag between onset in a case and onset in the people they
infect) estimated from 58 identified transmission pairs– median 3.5 days. Allowing some to be tertiary transmission, estimate median true serial interval of
2.5-3 days.
• US household analysis gives mean serial interval of 2.6 days.
Natural history
US UK
Effectiveness of antivirals
• UK is only country to adopt universal treatment policy.
• From UK FF100 database, estimate that treatment of index within 3 days reduced lab-confirmed H1N1 in household contacts by 3.4 (1.5-8.6) fold (4.5% vs 13%).
• Effect on ILI less (11% vs 15%).
• But most contacts were prophylaxed at the same time as treatment was given – so only combined impact of treatment and prophylaxis can be estimated.
• Dominant effect likely to be from prophylaxis.
Vaccination
• If no constraint on timing / resources / acceptability, targeting key transmitters (children) is expected to have very substantial on spread.
• But timing may affect prioritisation (HCWs, risk groups, key transmitters). • Public perception of severity may affect take-up, acceptability of universal vaccination. • If epidemic is past peak, UK modelling shows targeting risk groups more effective at
reducing deaths than targeting transmitters. • But even if the main wave has passed, vaccination (esp. with adjuvanted vaccine) may offer
protection against drift variants in later years.
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A B C A – may be the situation in a few N hemisphere developed countries.
B – more likely scenario for most.
C – scenario for many developing & S hemisphere countries.
Policy options also depend on scale of ramp-up and timescale over which vaccine order completed.
Summary
• Generation time mean of 2.5-3 days (comparable with seasonal flu).
• Incubation period mean of 1.5-2 days (comparable with seasonal flu).
• Analysis of S. Hemisphere countries suggests R in 1.1-1.5 range.
• UK second wave expected to be smaller or same size as first.
• US epidemic likely to peak in the next few weeks.
• General picture is of low ILI attack rate (~10%), low health impact (<5% of population seeking care), with most transmission in children <18.
• Nothing to suggest epidemic in continental Europe will not be comparable with UK, US, NZ, Australia.
• But the effect of seasonal variation in flu transmissibility uncertain.