1. 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

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

3. 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

4. Inter-annual variability in influenza-related mortality impact

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

6. 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

7. Influenza virus seasonal patterns and latitude
Data from WHO FluNet,
Adapted from Viboud et al, PLos Med, 2006

8. 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

9. 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

10. 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

11. 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

12. Influenza and climatic factors

13. 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

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

15. 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

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

17. Distribution of seasonal peaks
Tamerius et al, unpubl.

18. 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.

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

20. 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)

21. 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)