title: Seasonal patterns in human A (H5N1) virus infection: analysis of global cases.
abstract: BACKGROUND
  Human cases of highly pathogenic avian influenza (HPAI) A (H5N1) have high mortality. Despite abundant data on seasonal patterns in influenza epidemics, it is unknown whether similar patterns exist for human HPAI H5N1 cases worldwide. Such knowledge could help decrease avian-to-human transmission through increased prevention and control activities during peak periods.
  
  
  METHODS
  We performed a systematic search of published human HPAI H5N1 cases to date, collecting month, year, country, season, hemisphere, and climate data. We used negative binomial regression to predict changes in case incidence as a function of season. To investigate hemisphere as a potential moderator, we used AIC and the likelihood-ratio test to compare the season-only model to nested models including a main effect or interaction with hemisphere. Finally, we visually assessed replication of seasonal patterns across climate groups based on the Köppen-Geiger climate classification.
  
  
  RESULTS
  We identified 617 human cases (611 with complete seasonal data) occurring in 15 countries in Southeast Asia, Africa, and the Middle East. Case occurrence was much higher in winter (n = 285, p = 0.03) than summer (n = 64), and the winter peak occurred across diverse climate groups. There was no significant interaction between hemisphere and season.
  
  
  CONCLUSIONS
  Across diverse climates, HPAI H5N1 virus infection in humans increases significantly in winter. This is consistent with increased poultry outbreaks and HPAI H5N1 virus transmission during cold and dry conditions. Prioritizing prevention and control activities among poultry and focusing public health messaging to reduce poultry exposures during winter months may help to reduce zoonotic transmission of HPAI H5N1 virus in resource-limited settings.
authors.affiliation: Quantitative Sciences Unit, Stanford University Department of Medicine, Stanford, California, United States of America.
authors.forename: Maya B
authors.initials: MB
authors.lastname: Mathur
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California, United States of America.
authors.forename: Rita B
authors.initials: RB
authors.lastname: Patel
authors.affiliation: Kaiser Permanente Southern California, Pasadena, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Gould
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Uyeki
authors.affiliation: Center for Health Policy and Center for Primary Care and Outcomes Research, Stanford University, Stanford, California, United States of America.
authors.forename: Jay
authors.initials: J
authors.lastname: Bhattacharya
authors.affiliation: Department of Languages, Literatures, and Cultures, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California, United States of America.
authors.forename: Yoshi
authors.initials: Y
authors.lastname: Gillaspie
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California, United States of America.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Chae
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California, United States of America; Center for Health Policy and Center for Primary Care and Outcomes Research, Stanford University, Stanford, California, United States of America.
authors.forename: Nayer
authors.initials: N
authors.lastname: Khazeni
mesh_terms: D002980:Climate; D005843:Geography; D006801:Humans; D015994:Incidence; D053124:Influenza A Virus, H5N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D038622:Internationality; D012044:Regression Analysis; D012621:Seasons