MISMS: International influenza research activities at the Fogarty International Center, NIH

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1 MISMS: International influenza research activities at the Fogarty International Center, NIH Stacey Knobler and Gerardo Chowell For the Multinational Influenza Seasonal Mortality Study Group (MISMS) Division of International Epidemiology and Population Studies Workshop on Health and Economic Impact of Influenza, Bali, Indonesia, 5 June 2012

2 - Introduction to MISMS activities - Disease burden studies Outline - Influenza seasonality & implications for vaccination strategies - MISMS Case Study: Epidemiology of the 2009 pandemic in Mexico

3 Global collaborative effort established in 2001 at the Fogarty International Center, NIH Describe epidemiology of influenza viruses at regional and national, sub-national levels Transmission patterns Time trends and geographical variations by age Evaluation of control strategies Evolutionary dynamics Antigenic and genetic characteristics of influenza viruses Human, avian, and swine populations. 3

4 Multinational Influenza Seasonal Mortality Study (MISMS) Network Aims Supports research, data collection and sharing, workshops and training activities. v v Core Capacities Network of 350+ collaborators in >50 countries >120 publications describing the global epidemiology and evolutionary dynamics of influenza viruses 9 regional workshops; 120+ investigators trained MISMS regional workshops Genomic or epidemiologic data acquired/analyzed and ongoing data collection In development

5 1. Influenza disease burden studies: the importance of national data

6 Statistical models to infer influenza mortality burden Few laboratory tests conducted in routine surveillance Death often follows secondary bacterial infection, after primary virus infection has been cleared Need to rely on statistical methods applied to broad death categories: excess mortality approach Mortality burden depends on: Age Dominant virus subtype Prior exposure to related viruses Co-infections? Simonsen et al, Arch Intern Med, 2005; Cox et at, Lancet, 2000

7 Excess mortality rates among seniors 65+ are higher in South Africa than in US, Crude seasonal excess mortality rates per 100,000 South Africa USA RR (South Africa/USA) Agestandardized rates RR (South Africa/USA) Rates standardized for socioeconomic differences RR (South Africa/USA) P&I deaths * 1.1 Respiratory deaths * 3.5* 1.5 All cause deaths * 4.1* 2.6* * P for between-country difference < Differences between South Africa and the US most pronounced with allcause mortality and age-adjustment Cohen et al, Clin Infect Dis 2010

8 2. Influenza virus seasonality and optimal timing for vaccination

9 Diversity of influenza seasonality patterns globally Bismarck, ND, USA Singapore Fortaleza, Brazil Sydney, Australia

10 Regional latitudinal gradient in seasonality of influenza January July December Data from WHO FluNet, Adapted from Viboud et al, PLos Med, 2006

11 Latitude Southward traveling wave of influenza mortality across Brazil +5 0 early +5 o N P<0.001 late J F M A M J J A S O N D Phase Alonso et al, 11 Am J Epidemiol, o S

12 Variation in influenza seasonal patterns across China: Influenza B is more winter-seasonal than influenza A (collaboration with Dr Yu, Chinese CDC) Flu A Flu B Viboud et al, unpubl.

13 Evaluation of vaccine match at the hemisphere level Influenza A/H3N2-70% of vaccine updates based on data from Temperate regions -2% of global population lives in the S. H. temperate regions, 41% in the Tropics, 57% in the N. H. temperate regions -S.H. recommendations increased vaccine match for influenza A/H3N2 from 31% to 51% (P<0.05) Richard et al, Vaccine, 2009

14 3. Epidemiology of the 2009 A/H1N1 pandemic in Mexico

15 Mortality age-shift to younger populations Chowell et al, NEJM, 2009

16 Chowell, Echevarria-Zuno, Viboud, Simonsen, et al. Plos Medicine A/H1N1 influenza in Mexico Prospective surveillance put in place for 2009 A/H1N1 pandemic (Echevarria et al. Lancet 2009) Network of 1099 health care units and 259 hospitals across Mexico Comprises Mexican formal workers and their families (~40% of Mexican pop)

17 Spatial and temporal patterns Fall wave Summer wave Spring wave

18 Impact of mandatory school closures 18-day period of mandatory school closures Social distancing implemented in the greater Mexico City area was associated with a 29-37% reduction in influenza transmission (using ILI and H1N1pdm curves) School closures, other social distancing Chowell et al. Plos Medicine 2011

19 Changes in the age distribution of cases ~3 weeks earlier than fall wave peak timing

20 Case fatality ratio, Mexico, 2009 Admission delays <2 days decreased risk of death by 55-77% ~50% ~9% CFR ~1.1% CFR ~2.4% Antiviral treatment decreased risk of death by 48% After adjusting for age, gender, pandemic wave, and geographic region Underlying medical conditions not considered Chowell et al. BMC Infectious Diseases 2012

21 Conclusion/Perspectives Seasonal disease burden studies Recognize the importance of examining national and sub-national data to best inform public health decision making Methods reflect integration of viral surveillance data, mortality data and modeling Differences between epidemics and pandemics (age patterns, seasonality) Role of co-infections (HIV, bacterial pathogens, others) Heterogeneity and seasonality of transmission dynamics are key to optimizing vaccination strategies (lack of existing data/analysis) Opportunities for collaboration with MISMS (epidemiologic and genetic data analysis and training)are available: 21

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