Epidemiology of influenza: is there a role for climate ? Cécile Viboud, Fogarty International Center, National Institutes of Health, Bethesda, MD, USA SEARCH Workshop French Embassy, Dec 14-15, 2009

Outline Introduction Global circulation and evolution of human seasonal influenza viruses Influenza and climatic factors Conclusion

Seasonal influenza epidemics Wintertime epidemics in temperate areas, seasonality highly diverse in the Tropics Disease burden 5-15% of the population sick every winter; ~48,000 deaths in the US each year (1990-present), mostly in the elderly. Cycling of strains 3 influenza (sub-)type co-circulate today : A/H3N2, A/H1N1, B Antigenic drift produces new A/H3N2 strains every 2-5 years Mortality impact and transmissibility varies with circulating subtype: A/H3N2 > B > A/H1N1 Emergence of swine-origin A/H1N1 in Spring 2009. Simonsen et al, Arch Intern Med, 2005; Cox et at, Lancet, 2000

Inter-annual variability in influenza-related mortality impact

Inter-annual variability in influenza transmissibility: England & Wales, 1918-1970 R for seasonal influenza average ~ 1.1-1.3 R for pandemic influenza: 1.9-5.5 Viboud et al, Vaccine, 2006; also Mills et al, Nature, 2004; Andreasen et al, JID, 2008

Transmission and Evolution of Influenza in the Tropics Spatial transmission of influenza across Brazil Key role of the Tropics in the persistence and evolution of influenza viruses

Influenza virus seasonal patterns and latitude Data from WHO FluNet, 1997-2005 Adapted from Viboud et al, PLos Med, 2006

Spread of seasonal influenza across Brazil, based on influenza-related mortality data Major winter peak Small summer peak P&I deaths, Brazil Alonso et al, Am J Epidemiol, 2006

Southward traveling wave of influenza across Brazil Phase Latitude J F M A S O N D -35 -30 -25 -20 -15 -10 -5 +5 +5oN P<0.001 early late -30oS Alonso et al, Am J Epidemiol, 2006

Proposed source-sink model of influenza A/H3N2 evolution A. Global migration model B. Local evolution model Comparison of NY and NZ sequence data suggests global migration No in-situ evolution or persistence of influenza in temperate locations Genetic diversity seeded from the Tropics to Temperate locations: Tropics = reservoir and source of new influenza A/H3N2 variants Nelson et al, Plos Path, 2007; Rambaut et al, Nature, 2008

Global Network of Influenza A/H3N2 Spread - E-SE Asia 6-9 months ahead South America late Between-year variations Role of large population centers, diversity of seasonal patterns, transportation fluxes Russell et al, Science, 2008

Influenza and climatic factors

Role of Absolute Humidity: 1) Re-interpretation of laboratory experiments Increased virus survival and transmission at low AH. Lowen et al, PNAS, 2006; Shaman et al PNAS, 2008; Shaman et al, submitted

Role of Absolute Humidity 2) Fit to epidemiological data in the US Drop in AH 10-20 days before epidemic onset, across US states P<0.0005 SIRS model driven by AH can reproduce seasonal patterns of influenza

Absolute Humidity vs other environmental factors Relative humidity: discordant results Solar radiation: discordant results Temperature: statistically linked but no experimental support; controlled in indoor settings School closing: weaker statistical support

Global seasonal patterns of influenza: peak epidemic month Bloom-Feshbach et al, unpubl.

Distribution of seasonal peaks Tamerius et al, unpubl.

Relationship with vapor pressure (~ AH) All locations Temperate Tropics No association with relative humidity or sunshine hours, but similar association with temperature or precipitations. Tamerius et al, unpubl.

Seasonal variations in influenza transmissibility Boston, ILI ED visits Outbreak possible Pandemic season Epidemic season No outbreak

Conclusions and perspectives Influenza seasonal patterns very pronounced Large inter-annual variability in epidemic impact, timing, transmissibility. Tropics key to explain to evolution and circulation of A/H3N2 viruses Absolute humidity interesting candidate to explain influenza seasonal forcing. Can it fully explain seasonal patterns in the Tropics or are there other triggers? Data on influenza virus surveillance in the Tropics crucial. Given enough susceptibles, epidemic will occur (pandemic)

Acknowledgements James Tamerius, Arizona State University Jeff Shaman, Oregon State University Wladimir Alonso (NIH, FIC) Mark Miller (NIH, FIC) Lone Simonsen (George Washington U; NIH, FIC) Multinational Influenza Seasonal Mortality Study collaborators Bryan Grenfell, Ginny Pitzer (Princeton University; NIH, FIC) Gerardo Chowell (Arizona State University) Marc Lipsitch (Harvard School of Public Health)