Comprehensive Study of H1N1pdm Determinants

The main objective of this study was to identify individual and collective determinants of H1N1pdm infection; therefore we tried to collect comprehensive data about subjects and their environment, in addition to biological samples. Several household visits are carried on by nurses for this purpose (see Figure 3 for details).
· Inclusion visits During the inclusion visit, nurses collected from all subjects detailed data regarding medical history, vaccination and preventive measures against influenza, smoking habits, socioeconomic status, risk perception and beliefs, frequency and characteristics of meetings with other people and housing (personal room, house or apartment). As the households’ addresses were geocoded, we were able to get additional information from public databases regarding the immediate surrounding environment of households. An overview of data collected from questionnaires at entry in the cohort is shown in Figure 4. Blood samples were collected and centralized for serological analyses. For subjects over 10 years, a heparinated tube was also collected to study cellular immunity, as well as a blood sample dedicated to transcript analyses.
· Systematic yearly visits After the inclusion visit, systematic follow-up visits are carried on between influenza seasons. During a systematic visit, a nurse collects or updates individual and environmental data on questionnaires, completes previously missing data, and obtains blood samples from all members of the household. Two waves of systematic follow-up visits have already occurred (summer-fall 2010 and 2011). A third wave is expected by the end of the second year of follow-up (summer 2012).
· Influenza-like illness (ILI) visits During the influenza season (as defined by the French surveillance network [21 ]), we use an active surveillance system order to detect ILIs: all households are called by an interactive voice response system (IVRS) weekly and are asked if any subject has symptoms of ILI (fever ≥ 37.8°C associated with cough or sore throat, as defined by the CDC [22 ]). A free phone number is given to subjects to report symptoms spontaneously between two weekly calls. In case of reported ILI, symptoms are validated by the study team and then three “ILI visits” are organized: nurses visit the household within 48 h after the onset of symptoms, then 3–6 days and 8–12 days after the onset.
· During these visits, a detailed questionnaire collects data about the circumstances of possible exposure to influenza viruses and the chronology of symptoms (if any) in all subjects. Nasal swabs are collected from all subjects. A stool sample and a throat swab are also collected from subjects with ILI, as well as a blood sample from those over 10 years of age. Moreover, a self-swab procedure is previously sent to the households in order to collect virological samples when a visit by a nurse within the first 48 h is not possible. Nasal swabs are used to identify various respiratory viruses by PCR and biochips allowing for multiple diagnosis tests.
· This series of three visits can occur several times in the same household during an influenza season. There were 23 ILI alerts during the 2009–2010 season (as households were still being included) and 143 during the 2010-2011 season, all of which triggered up to three ILI visits.
· Vaccination visits In order to update serological information, a blood sample was collected from subjects who had an influenza vaccination, between 2 and 4 weeks following this vaccination. There was one vaccination visit following the inclusion visits; 29 vaccination visits were conducted following the first wave of follow-up visits and 69 following the second wave.