title: Characterization of regional influenza seasonality patterns in China and implications for vaccination strategies: spatio-temporal modeling of surveillance data.
abstract: BACKGROUND
  The complexity of influenza seasonal patterns in the inter-tropical zone impedes the establishment of effective routine immunization programs. China is a climatologically and economically diverse country, which has yet to establish a national influenza vaccination program. Here we characterize the diversity of influenza seasonality in China and make recommendations to guide future vaccination programs.
  
  
  RESULTS
  We compiled weekly reports of laboratory-confirmed influenza A and B infections from sentinel hospitals in cities representing 30 Chinese provinces, 2005-2011, and data on population demographics, mobility patterns, socio-economic, and climate factors. We applied linear regression models with harmonic terms to estimate influenza seasonal characteristics, including the amplitude of annual and semi-annual periodicities, their ratio, and peak timing. Hierarchical Bayesian modeling and hierarchical clustering were used to identify predictors of influenza seasonal characteristics and define epidemiologically-relevant regions. The annual periodicity of influenza A epidemics increased with latitude (mean amplitude of annual cycle standardized by mean incidence, 140% [95% CI 128%-151%] in the north versus 37% [95% CI 27%-47%] in the south, p<0.0001). Epidemics peaked in January-February in Northern China (latitude ≥33°N) and April-June in southernmost regions (latitude <27°N). Provinces at intermediate latitudes experienced dominant semi-annual influenza A periodicity with peaks in January-February and June-August (periodicity ratio >0.6 in provinces located within 27.4°N-31.3°N, slope of latitudinal gradient with latitude -0.016 [95% CI -0.025 to -0.008], p<0.001). In contrast, influenza B activity predominated in colder months throughout most of China. Climate factors were the strongest predictors of influenza seasonality, including minimum temperature, hours of sunshine, and maximum rainfall. Our main study limitations include a short surveillance period and sparse influenza sampling in some of the southern provinces.
  
  
  CONCLUSIONS
  Regional-specific influenza vaccination strategies would be optimal in China; in particular, annual campaigns should be initiated 4-6 months apart in Northern and Southern China. Influenza surveillance should be strengthened in mid-latitude provinces, given the complexity of seasonal patterns in this region. More broadly, our findings are consistent with the role of climatic factors on influenza transmission dynamics. Please see later in the article for the Editors' Summary.
authors.affiliation: Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yu
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Wladimir J
authors.initials: WJ
authors.lastname: Alonso
authors.affiliation: Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Luzhao
authors.initials: L
authors.lastname: Feng
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Cécile
authors.initials: C
authors.lastname: Viboud
mesh_terms: D001499:Bayes Theorem; D002681:China / Q000453:epidemiology; D002980:Climate; D058872:Epidemics; D062305:Geographic Mapping; D006761:Hospitals; D006801:Humans; D015994:Incidence; D009980:Influenza A virus; D009981:Influenza B virus; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D016014:Linear Models; D008954:Models, Biological; D011159:Population Surveillance; D012621:Seasons; D012959:Socioeconomic Factors; D013696:Temperature; D014611:Vaccination