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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UK

fluTracker, oct 21th

USA

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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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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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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.