![]() Since secondary cases shed detectable virus for 3–5 days after illness onset it is important to consider the number and timing of visits in order to maximize the number of secondary cases that can be virologically confirmed. While some case-ascertained studies rely entirely on self-reports of symptoms and signs associated with acute respiratory illnesses ( 12– 17), repeated home-visits can be arranged to collect specimens and allow virologic confirmation of influenza virus infections ( 10, 11, 19– 22). In case-ascertained studies, influenza transmission is typically measured via the secondary attack proportion (SAP), defined as the proportion of household contacts that are infected with influenza virus from the index case ( 15). Case ascertained studies are believed to be the most efficient method of assessing secondary transmission of influenza because smaller sample sizes are required to observe an equivalent number of secondary infections as compared to a cohort study. The latter design is termed a case-ascertained design ( 24), and is the focus of this paper. ![]() Alternatively, households can be enrolled in a study once influenza infection is identified in one member (an ‘index’ case), and followed up to observe secondary infections. While this is regarded as a gold standard for influenza household studies, this design can be extremely resource intensive because the expected number of households in which an infection occurs is relatively small. A cohort of initially uninfected households can be recruited and then followed up through periods of influenza activity ( 3, 23). There are two main types of design for household studies. Historically, household studies have provided invaluable insights into influenza epidemiology ( 3), while recent household studies have investigated the effectiveness of antiviral treatment and prophylaxis ( 4– 8), hand hygiene ( 9– 11), face masks ( 10– 13), and transmissibility of seasonal influenza ( 14) and 2009 pandemic influenza A (H1N1) ( 15– 22). Households are important in influenza epidemiology ( 1), and it has been estimated that around a third of all influenza transmission occurs in households ( 2). Influenza virus is associated with a substantial global burden of morbidity and mortality, yet many characteristics of the disease are poorly understood including transmissibility and its relations with viral shedding during infection, factors affecting infectiousness and immunity, and the effectiveness of interventions to reduce transmission. However, for studies comparing secondary attack proportions between two or more groups, such as controlled intervention studies, designs with reactive home visits following illness reports in contacts were most powerful, while a design with one home visit optimally timed also performed well. For studies estimating the secondary attack proportion, 2–3 follow-up visits with specimens collected from all members regardless of illness were optimal. We compared studies that relied on self-reported illness among household contacts versus studies that used home visits to collect swab specimens for virologic confirmation of secondary infections, allowing for the trade-off between sample size versus intensity of follow-up given a fixed budget. We used a simulation approach parameterized with data from household transmission studies to evaluate alternative study designs. Case-ascertained household transmission studies, in which households including an ‘index case’ are recruited and followed up, are invaluable to understanding the epidemiology of influenza.
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