Clinical trial NCT01769430: Evaluating Modes of Influenza Transmission Observational Study of Community Acquired Influenza
Official title: Evaluating Modes of Influenza Transmission Work Package 1: Observational Study of Community Acquired Influenza
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Influenza Virus Infection Transmission in Humans
Keywords: influenza virus
aerosol transmission
contact transmission
large droplet transmission
airborne infection
Lead sponsor: University of Maryland, College Park
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2013-01-16
Enrollment: 178
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Students, faculty, and staff at the University of Maryland College Park and residents of the surrounding communities

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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:

-

Primary outcomes:
measure: Viral Copy Number in 30-minute Exhaled Breath Sample
timeFrame: Daily measurements on days 1 through 3 post onset of symptoms (each person contributed 1 to a max of 3 samples). Reported values are the geometric mean over all samples and persons.
measure: Total Fine Aerosol Infectious Influenza Virus in 30-minute Exhaled Breath Sample
timeFrame: Daily measurements on days 1 through 3 post onset of symptoms (each person contributed 1 to a max of 3 samples). Reported values are the geometric mean over all samples and persons.
Secondary outcomes:
Other outcomes:
measure: Comparison of Exhaled Virus in Community Acquired and Experimental Infection
timeFrame: Maximal shedding during days 1-3 post onset of symptoms (natural infections) or days 1-4 post inoculation (nasally inoculated volunteers)
Locations:
city: College Park
country: United States
facility: University of Maryland School of Public Health
state: Maryland
Study officials:
affiliation: University of Maryland
name: Donald K Milton, MD, DrPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fabian P, McDevitt JJ, DeHaan WH, Fung RO, Cowling BJ, Chan KH, Leung GM, Milton DK. Influenza virus in human exhaled breath: an observational study. PLoS One. 2008 Jul 16;3(7):e2691. doi: 10.1371/journal.pone.0002691.
citation: Milton DK, Fabian MP, Cowling BJ, Grantham ML, McDevitt JJ. Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks. PLoS Pathog. 2013 Mar;9(3):e1003205. doi: 10.1371/journal.ppat.1003205. Epub 2013 Mar 7.
citation: McDevitt JJ, Koutrakis P, Ferguson ST, Wolfson JM, Fabian MP, Martins M, Pantelic J, Milton DK. Development and Performance Evaluation of an Exhaled-Breath Bioaerosol Collector for Influenza Virus. Aerosol Sci Technol. 2013 Jan 1;47(4):444-451. doi: 10.1080/02786826.2012.762973. Epub 2013 Jan 25.
citation: Yan J, Grantham M, Pantelic J, Bueno de Mesquita PJ, Albert B, Liu F, Ehrman S, Milton DK; EMIT Consortium. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):1081-1086. doi: 10.1073/pnas.1716561115. Epub 2018 Jan 18.