Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: McMillen CM[original query] |
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Assessment of influenza virus exposure and recovery from contaminated surgical masks and N95 respirators
Blachere FM , Lindsley WG , McMillen CM , Beezhold DH , Fisher EM , Shaffer RE , Noti JD . J Virol Methods 2018 260 98-106 Healthcare workers (HCWs) are at significantly higher risk of exposure to influenza virus during seasonal epidemics and global pandemics. During the 2009 influenza pandemic, some healthcare organizations recommended that HCWs wear respiratory protection such as filtering facepiece respirators, while others indicated that facemasks such as surgical masks (SMs) were sufficient. To assess the level of exposure a HCW may possibly encounter, the aim of this study was to (1.) evaluate if SMs and N95 respirators can serve as "personal bioaerosol samplers" for influenza virus and (2.) determine if SMs and N95 respirators contaminated by influenza laden aerosols can serve as a source of infectious virus for indirect contact transmission. This effort is part of a National Institute for Occupational Safety and Health 5-year multidisciplinary study to determine the routes of influenza transmission in healthcare settings. A coughing simulator was programmed to cough aerosol particles containing influenza virus over a wide concentration range into an aerosol exposure simulation chamber virus/L of exam room air), and a breathing simulator was used to collect virus on either a SM or N95 respirator. Extraction buffers containing nonionic and anionic detergents as well as various protein additives were used to recover influenza virus from the masks and respirators. The inclusion of 0.1% SDS resulted in maximal influenza RNA recovery (41.3%) but with a complete loss of infectivity whereas inclusion of 0.1% bovine serum albumin resulted in reduced RNA recovery (6.8%) but maximal retention of virus infectivity (17.9%). Our results show that a HCW's potential exposure to airborne influenza virus can be assessed in part through analysis of their SMs and N95 respirators, which can effectively serve as personal bioaerosol samplers. |
Inhibition of influenza A virus matrix and nonstructural gene expression using RNA interference.
McMillen CM , Beezhold DH , Blachere FM , Othumpangat S , Kashon ML , Noti JD . Virology 2016 497 171-184 Influenza antiviral drugs that use protein inhibitors can lose their efficacy as resistant strains emerge. As an alternative strategy, we investigated the use of small interfering RNA molecules (siRNAs) by characterizing three siRNAs (M747, M776 and M832) targeting the influenza matrix 2 gene and three (NS570, NS595 and NS615) targeting the nonstructural protein 1 and 2 genes. We also re-examined two previously reported siRNAs, M331 and M950, which target the matrix 1 and 2 genes. Treatment with M331-, M776-, M832-, and M950-siRNAs attenuated influenza titer. M776-siRNA treated cells had 29.8% less infectious virus than cells treated with the previously characterized siRNA, M950. NS570-, NS595- and NS615-siRNAs reduced nonstructural protein 1 and 2 expression and enhanced type I interferon expression by 50%. Combination siRNA treatment attenuated 20.9% more infectious virus than single siRNA treatment. Our results suggest a potential use for these siRNAs as an effective anti-influenza virus therapy. |
Viable influenza A virus in airborne particles expelled during coughs vs. exhalations
Lindsley WG , Blachere FM , Beezhold DH , Thewlis RE , Noorbakhsh B , Othumpangat S , Goldsmith WT , McMillen CM , Andrew ME , Burrell CN , Noti JD . Influenza Other Respir Viruses 2016 10 (5) 404-13 BACKGROUND: In order to prepare for a possible influenza pandemic, a better understanding of the potential for airborne transmission of influenza from person to person is needed. OBJECTIVES: The objective of this study was to directly compare the generation of aerosol particles containing viable influenza virus during coughs and exhalations. METHODS: Sixty-one adult volunteer outpatients with influenza-like symptoms were asked to cough and exhale three times into a spirometer. Aerosol particles produced during coughing and exhalation were collected into liquid media using aerosol samplers. The samples were tested for the presence of viable influenza virus using a viral replication assay (VRA). RESULTS: Fifty-three test subjects tested positive for influenza A virus. Of these, 28 (53%) produced aerosol particles containing viable influenza A virus during coughing, and 22 (42%) produced aerosols with viable virus during exhalation. Thirteen subjects had both cough aerosol and exhalation aerosol samples that contained viable virus, 15 had positive cough aerosol samples but negative exhalation samples, and 9 had positive exhalation samples but negative cough samples. CONCLUSIONS: Viable influenza A virus was detected more often in cough aerosol particles than in exhalation aerosol particles, but the difference was not large. Since individuals breathe much more often than they cough, these results suggest that breathing may generate more airborne infectious material than coughing over time. However, both respiratory activities could be important in airborne influenza transmission. Our results are also consistent with the theory that much of the aerosol containing viable influenza originates deep in the lungs. |
ICAM-1 regulates the survival of influenza virus in lung epithelial cells during the early stages of infection
Othumpangat S , Noti JD , McMillen CM , Beezhold DH . Virology 2015 487 85-94 Intercellular cell adhesion molecule-1 (ICAM-1) is an inducible cell surface glycoprotein that is expressed on many cell types. Influenza virus infection enhanced ICAM-1 expression and messenger RNA levels. Human bronchial epithelial cells (HBEpC) and nasal epithelial cells, on exposure to different strains of influenza virus (H1N1, H3N2, and H9N1) showed significant increase in ICAM-1 gene expression (p<0.001) along with the ICAM-1 protein levels (surface and secreted). Depleting ICAM-1 in HBEpC with ICAM-1 siRNA and subsequently infecting with H1N1 showed increased viral copy numbers. Influenza virus infection in HBEpC resulted in up-regulation of NF-kB protein and the lack of ICAM-1 decreased NF-kB activity in NF-kB luciferase reporter assay. Addition of exogenous IL-1beta to HBEpC induced the ICAM-1 expression and decreased matrix gene copy number. Taken together, HBEpC induced ICAM-1 plays a key role in modulating the influenza virus survival possibly through the NF-kB pathway. |
High humidity leads to loss of infectious influenza virus from simulated coughs
Noti JD , Blachere FM , McMillen CM , Lindsley WG , Kashon ML , Slaughter DR , Beezhold DH . PLoS One 2013 8 (2) e57485 BACKGROUND: The role of relative humidity in the aerosol transmission of influenza was examined in a simulated examination room containing coughing and breathing manikins. METHODS: Nebulized influenza was coughed into the examination room and Bioaerosol samplers collected size-fractionated aerosols (<1 microM, 1-4 microM, and >4 microM aerodynamic diameters) adjacent to the breathing manikin’s mouth and also at other locations within the room. At constant temperature, the RH was varied from 7-73% and infectivity was assessed by the viral plaque assay. RESULTS: Total virus collected for 60 minutes retained 70.6-77.3% infectivity at relative humidity ≤23% but only 14.6-22.2% at relative humidity ≥43%. Analysis of the individual aerosol fractions showed a similar loss in infectivity among the fractions. Time interval analysis showed that most of the loss in infectivity within each aerosol fraction occurred 0-15 minutes after coughing. Thereafter, losses in infectivity continued up to 5 hours after coughing, however, the rate of decline at 45% relative humidity was not statistically different than that at 20% regardless of the aerosol fraction analyzed. CONCLUSION: At low relative humidity, influenza retains maximal infectivity and inactivation of the virus at higher relative humidity occurs rapidly after coughing. Although virus carried on aerosol particles <4 microM have the potential for remaining suspended in air currents longer and traveling further distances than those on larger particles, their rapid inactivation at high humidity tempers this concern. Maintaining indoor relative humidity >40% will significantly reduce the infectivity of aerosolized virus. |
Detection of infectious influenza virus in cough aerosols generated in a simulated patient examination room
Noti JD , Lindsley WG , Blachere FM , Cao G , Kashon ML , Thewlis RE , McMillen CM , King WP , Szalajda JV , Beezhold DH . Clin Infect Dis 2012 54 (11) 1569-77 BACKGROUND: The potential for aerosol transmission of infectious influenza virus (ie, in healthcare facilities) is controversial. We constructed a simulated patient examination room that contained coughing and breathing manikins to determine whether coughed influenza was infectious and assessed the effectiveness of an N95 respirator and surgical mask in blocking transmission. METHODS: National Institute for Occupational Safety and Health aerosol samplers collected size-fractionated aerosols for 60 minutes at the mouth of the breathing manikin, beside the mouth, and at 3 other locations in the room. Total recovered virus was quantitated by quantitative polymerase chain reaction and infectivity was determined by the viral plaque assay and an enhanced infectivity assay. RESULTS: Infectious influenza was recovered in all aerosol fractions (5.0% in >4 mum aerodynamic diameter, 75.5% in 1-4 mum, and 19.5% in <1 mum; n = 5). Tightly sealing a mask to the face blocked entry of 94.5% of total virus and 94.8% of infectious virus (n = 3). A tightly sealed respirator blocked 99.8% of total virus and 99.6% of infectious virus (n = 3). A poorly fitted respirator blocked 64.5% of total virus and 66.5% of infectious virus (n = 3). A mask documented to be loosely fitting by a PortaCount fit tester, to simulate how masks are worn by healthcare workers, blocked entry of 68.5% of total virus and 56.6% of infectious virus (n = 2). CONCLUSIONS: These results support a role for aerosol transmission and represent the first reported laboratory study of the efficacy of masks and respirators in blocking inhalation of influenza in aerosols. The results indicate that a poorly fitted respirator performs no better than a loosely fitting mask. |
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