Evaluating Modes of Influenza Transmission Observational Study of Community Acquired Influenza (EMIT)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Donald K. Milton, University of Maryland
ClinicalTrials.gov Identifier:
NCT01769430
First received: January 14, 2013
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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.


Condition
Influenza Virus Infection Transmission in Humans

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Evaluating Modes of Influenza Transmission Work Package 1: Observational Study of Community Acquired Influenza

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Viral copy number in exhaled breath aerosol coarse and fine particle fractions [ Time Frame: At enrollment and over 2 days follow-up ] [ Designated as safety issue: No ]
    Participants will sit for 30 minutes with their face inside the cone/funnel of the Gesundheit-II (G-II)human bioaerosol collector (McDevitt JJ et al. Aerosol Sci Technol 2013, in press). Subjects are free to tidal breathe, cough, and talking. A conventional slit impactor collects particles > 5.0 μm. Condensation of water vapor is used to grow remaining particles for efficient collection by a 1.0 μm slit impactor and be deposited into a buffer-containing collector. Samples are assayed by RT-PCR and viral culture. The method was previously used to assess effectiveness of surgical masks for containing influenza virus aerosols (Milton DK, et al. PLoS Pathogens 2013, in press).


Secondary Outcome Measures:
  • Correlation of exhaled particle counts and viral copy numbers [ Time Frame: At enrollment and over 2 days follow-up ] [ Designated as safety issue: No ]
    Hypothesis: exhaled particle numbers counted with an optical particle counter (Exhalair, Pulmatrix, Inc, Lexington, MA) during tidal breathing will correlate with exhaled viral copy numbers, especially in the fine particle fraction

  • Impact of multiple infection [ Time Frame: At enrollment and over 2 days of follow-up ] [ Designated as safety issue: No ]
    Hypothesis: co-infection with other respiratory agents will increase aerosol production


Other Outcome Measures:
  • Correlation of exhaled virus in community acquired and experimental infection [ Time Frame: At enrollment and up to 2 days of follow-up ] [ Designated as safety issue: No ]
    These data will be used to compare subjects with community acquired influenza with donor subjects artificially infected with influenza in EMIT-Work Package 3 and with recipient subjects exposed the the donors. We will test the hypothesis that the donor subjects in EMIT-WP3 produce similar amounts of viral aerosol as do community acquired infection cases. We will also examine whether recipients exposed only to aerosols differ from those exposed by contact and large droplet as well as aerosol routes with respect to exhaled aerosol virus.

  • RSV and other respiratory infections [ Time Frame: At enrollment ] [ Designated as safety issue: No ]
    Hypothesis: RSV and cases with other respiratory infections who are not infected with influenza will have the infecting agent present in exhaled breath aerosols


Biospecimen Retention:   Samples With DNA

viral cultures, viral RNA, viral cDNA, NP swabs, exhaled breath particles


Enrollment: 178
Study Start Date: December 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Community acquired respiratory infection
Measurement of exhaled breath aerosol

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

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Students, faculty, and staff at the University of Maryland College Park and residents of the surrounding communities

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:

-

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01769430

Locations
United States, Maryland
University of Maryland School of Public Health
College Park, Maryland, United States, 20742
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Donald K Milton, MD, DrPH University of Maryland
  More Information

Additional Information:
Publications:
Responsible Party: Donald K. Milton, Professor and Director MIAEH School of Public Health, University of Maryland
ClinicalTrials.gov Identifier: NCT01769430     History of Changes
Other Study ID Numbers: 017086-001, 1U01IP000497, 3U01CI000446, RC1AI086900
Study First Received: January 14, 2013
Last Updated: January 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
influenza virus
aerosol transmission
contact transmission
large droplet transmission
airborne infection

Additional relevant MeSH terms:
Influenza, Human
Virus Diseases
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 29, 2014