Influenza Virus Infection Transmission in Humans Clinical Trial
— EMITOfficial title:
Evaluating Modes of Influenza Transmission Work Package 1: Observational Study of Community Acquired Influenza
| Verified date | March 2018 |
| Source | University of Maryland |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
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.
| Status | Completed |
| Enrollment | 178 |
| Est. completion date | March 2013 |
| Est. primary completion date | March 2013 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 10 Years and older |
| Eligibility |
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: |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Maryland School of Public Health | College Park | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| University of Maryland | Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
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. — View 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. Epub 2013 Jan 25. — View 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. — View 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):1 — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Correlation of exhaled virus in community acquired and experimental infection | 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. | At enrollment and up to 2 days of follow-up | |
| Other | RSV and other respiratory infections | Hypothesis: RSV and cases with other respiratory infections who are not infected with influenza will have the infecting agent present in exhaled breath aerosols | At enrollment | |
| Primary | Viral copy number in exhaled breath aerosol coarse and fine particle fractions | 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). | At enrollment and over 2 days follow-up | |
| Secondary | Correlation of exhaled particle counts and viral copy numbers | 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 | At enrollment and over 2 days follow-up | |
| Secondary | Impact of multiple infection | Hypothesis: co-infection with other respiratory agents will increase aerosol production | At enrollment and over 2 days of follow-up |