Evaluating Modes of Influenza Transmission Observational Study of Community Acquired Influenza

Evaluating Modes of Influenza Transmission Work Package 1: Observational Study of Community Acquired Influenza

The recent swine origin influenza pandemic (2009), new emergence of swine origin H3N2v, and delayed availability of vaccine for these agents highlight the need to test and optimize public health intervention strategies to reduce transmission of influenza. We will use a new technology for biological particle collection (U.S. Provisional Patent Application No. 61/162,395, McDevitt et al., Aerosol Sci Technol 2013) to make fundamental observations on infectious respiratory droplets in a study of up to 200 naturally occurring seasonal influenza cases. We will collect respiratory droplets shed by participants while breathing normally, talking, and spontaneously coughing. We will characterize the size distribution of droplets containing infectious virus. We will use these basic data to examine the roles of large and small respiratory droplets and examine how the interaction of host factors and virus type impact the shedding of infectious respiratory droplets. Subjects will be recruited through a web based respiratory illness surveillance system, health clinics and advertisement in the campus community. Sitting in the collection booth will not create additional discomfort or risk for volunteers already suffering from influenza infection. We will recruit up to 1000 persons with symptoms of acute respiratory illness for screening with collection of nasopharyngeal swabs and questionnaire. From among those screened, we will recruit 250 to give exhaled breath samples, and ask 50 people with influenza to return for follow up exhaled breath samples on up to two subsequent days. We hypothesize that (1) fine aerosols (<5 microns in aerodynamic diameter) will contain more viral copies than coarse aerosol particles (>= 5 microns) (2) fine aerosols will contain culturable virus indicating that the fine aerosols are infectious, (3) aerosol shedding will correlate with virus load measured by swabs, (4) presence of active cough during sampling will be associated with increased aerosol shedding, (5) clinical symptoms and signs, including fever can be used to predict viral aerosol shedding.

This study is a follow-on to earlier projects funded by the US Centers for Disease Control and Prevention (CDC) and the National Institute for Allergy and Infectious Diseases (NIAID) that developed the sampler and studied the impact of surgical masks on reducing viral aerosol release by persons infected with influenza virus. The funding organizations have no direct control over the study design, execution, or reporting and no access to identifiable human data. The CDC IRB has determined that the CDC is not engaged in human subjects research in this cooperative agreement.

Hypotheses:

• Fine particle aerosols will contain greater numbers of viral copies than will coarse aerosol particles.
• Clinical symptoms and signs, including fever can be used to predict viral aerosol shedding
• Fine aerosols will contain culturable virus indicating that the fine aerosols are infectious
• Aerosol shedding will correlate with virus load measured by nasopharyngeal and throat swabs
• Presence of active cough during sampling will be associated with increased aerosol shedding with a stronger correlation to be found with coarse than fine particle virus aerosols

Inclusion Criteria:

• Presence of symptomatic respiratory infection or other evidence of respiratory infection:

  • During the influenza season, subjects will be enrolled if they have

    • influenza-like illness (symptoms of fever and either cough or sore throat) and either
    • a positive point of care rapid test for influenza infection or
    • objectively documented fever in the setting of a documented local influenza outbreak (presence of rapid test or PCR confirmed cases).
    • Onset within the previous 48 hours

  • Prior to onset of influenza season and if we have not achieved enrollment of our target population by the end of flu season, we will enroll subjects with cough, coryza (stuffy runny nose, sore throat, sneezing), and malaise (fatigue) characteristic of the 'common cold' often resulting from Human Rhinovirus, RSV, parainfluenza, and to some extent influenza virus.

Exclusion Criteria:

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