Table 1.

Nine objectives of SHIVERS

Objectives	Specific aims	Methods
Obj 1 (Primary): Understand severe respiratory diseases	Measure incidence, prevalence, risk factors, clinical outcomes and severity for hospitalized severe acute respiratory illness (SARI) and associated influenza and other respiratory infections as well as understand influenza contribution to patients not meeting SARI case definition	Active, prospective, continuous, population-based surveillance for influenza and other respiratory pathogens among hospitalized patients with respiratory illness.
Obj 2 (Primary): Assess influenza vaccine effectiveness	Assess the annual effectiveness of seasonal trivalent inactivated influenza vaccine (TIV) in preventing general practice visits and hospitalizations for laboratory-confirmed influenza	Using case test-negative control design
Obj 3: Investigate interaction between influenza and other pathogens	Investigate the potential role of pathogen co-infections (viral–viral, viral–bacteria) in patient outcome, severity, aetiology, demography and underlying risk conditions.	Simultaneous testing by real-time RT-PCR assays for 8 respiratory viruses for all SARI and ILI patients. Simultaneous testing for respiratory virus and bacteria by blood culture, urinary antigen test and PCR for some SARI cases and non-SARI patients.
Obj 4: Understand aetiologies and causes of respiratory mortality	Real-time monitoring all SARI in-hospital deaths and the associated aetiologies	The same methods as objectives 1 and 3
Obj 5: Understand non-severe respiratory diseases	Measure incidence, prevalence, risk factors, clinical spectrums for consultation-seeking influenza-like illness (ILI) and associated influenza and other respiratory infections	Active, prospective, population-based surveillance for influenza and other respiratory pathogens among persons enrolled in sentinel general practices who seek medical consultations.
Obj 6: Estimate influenza infection via serosurvey	Estimate annual incidence of infection and identify potential risk factors for infection with seasonal influenza among different age and ethnic groups	Conducting a serologic cohort study using sentinel general practices recruited for Objective 5
Obj 7: Identify and quantify risk factors for getting influenza	Risk factors include host, socio-economic, underlying medical conditions, health intervention, health service utilization, and environmental and behavioural factors	Using well-characterized socio-demographic distribution data and use case-control design with several comparison/control groups
Obj 8: Assess immune response in severe, moderate influenza cases, related risk groups and individuals with serologically defined influenza infection	Study humoral and cellular immunologic responses in a subset of SARI and ILI patients and risk groups with confirmed influenza and individuals with serologically defined influenza infection.	Measure antihemagglutinin (HA) antibodies, antineuraminidase (NA) antibodies, isotypes of responding antibodies, influenza-specific CD4+, CD8+ T cells, surface markers and key cytokines expression levels
Obj 9: Estimate healthcare, societal economic burden caused by influenza and vaccine cost-effectiveness	Estimate influenza-associated healthcare and societal economic burden and vaccine cost-effectiveness among a range of different subpopulations	Estimate direct medical costs and indirect societal cost (e.g. loss of productivity, loss of earning and loss of life) for the study population and subpopulations