Design and analysis of household studies of influenza

Abstract

Background: Influenza viruses cause substantial mortality and morbidity both worldwide and in Hong Kong. Furthermore, the possible emergence of future influenza pandemics remains a major threat to public health. Some studies have estimated that one third of all influenza transmission occurs in households. Household studies have been an important means of studying influenza transmissions and evaluating the efficacy of influenza control measures including vaccination, antiviral therapy and prophylaxis and non-pharmaceutical interventions. Household studies of influenza can be categorized as pertaining to one of two designs: household cohort and case-ascertained. In household cohort studies households are recruited before the start of an influenza season and then monitored during the influenza season for influenza infection. In case-ascertained studies a household is enrolled once influenza infection is identified in a household member.

Objectives: This thesis comprises of two parts. The objective of the first part is to evaluate the resource efficiency of different designs for conducting household studies. The objective of the second part is to estimate community and household transmission parameters during the 2009 A(H1N1) pandemic in Hong Kong.

Methods: Monte Carlo simulation parameterized with data from influenza studies in Hong Kong was used to compare the resource efficiency of competing study designs evaluating the efficacy of an influenza control intervention. Approaches to ascertaining infections in different types of studies, and their implications for resource efficiency were compared. With regard to the second part, extended Longini-Koopman models within a Bayesian framework were used on data from a Hong Kong household cohort study conducted from December 2008 to October 2009. Household and community transmission parameters were estimated by age-groups for two seasonal influenza strains circulating in the winter of 2008-09 and two seasonal and one pandemic strain circulating in the summer of 2009.

Results: Simulations showed that RT-PCR outperformed both serology and self-report of symptoms as a resource efficient means of identifying influenza in household studies. Identification of influenza using self-report of symptomatology performed particularly poorly in terms of resource efficiency due to its low sensitivity and specificity when compared to laboratory methods. Case-ascertained studies appeared more resource efficient than cohort studies but the results were sensitive to the choice of parameter values particularly the serial interval of influenza. In statistical analyses of household data during the winter of 2008-09, it was found that transmissibility of seasonal influenza strains were similar to those previously reported in the literature. Analysis also showed for the summer 2009 the estimates of household transmissibility were similar for seasonal A(H3N2) and pandemic A(H1N1) especially after taking into account that some individuals were likely immune to infection.

Conclusions: Careful consideration of study design can ensure that studies are resource efficient and have sufficient statistical power. Data from a household study suggested that during 2009 seasonal and pandemic influenza had similar transmission patterns.