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William G Lindsley,
Terri A Pearce,
Judith B Hudnall,
Kristina A Davis,
Stephen M Davis, Melanie A Fisher,
Rashida Khakoo,
Jan E Palmer,
Karen E Clark,
Ismail Celik,
Christopher C Coffey,
Francoise M Blachere,
Donald H Beezhold
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ABSTRACT: The question of whether influenza is transmitted to a significant degree by aerosols remains controversial, in part, because little is known about the quantity and size of potentially infectious airborne particles produced by people with influenza. In this study, the size and amount of aerosol particles produced by nine subjects during coughing were measured while they had influenza and after they had recovered, using a laser aerosol particle spectrometer with a size range of 0.35 to 10 μm. Individuals with influenza produce a significantly greater volume of aerosol when ill compared with afterward (p = 0.0143). When the patients had influenza, their average cough aerosol volume was 38.3 picoliters (pL) of particles per cough (SD 43.7); after patients recovered, the average volume was 26.4 pL per cough (SD 45.6). The number of particles produced per cough was also higher when subjects had influenza (average 75,400 particles/cough, SD 97,300) compared with afterward (average 52,200, SD 98,600), although the difference did not reach statistical significance (p = 0.1042). The average number of particles expelled per cough varied widely from patient to patient, ranging from 900 to 302,200 particles/cough while subjects had influenza and 1100 to 308,600 particles/cough after recovery. When the subjects had influenza, an average of 63% of each subject's cough aerosol particle volume in the detection range was in the respirable size fraction (SD 22%), indicating that these particles could reach the alveolar region of the lungs if inhaled by another person. This enhancement in aerosol generation during illness may play an important role in influenza transmission and suggests that a better understanding of this phenomenon is needed to predict the production and dissemination of influenza-laden aerosols by people infected with this virus. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a PDF file of demographic information, influenza test results, and volume and peak flow rate during each cough and a PDF file containing number and size of aerosol particles produced.].
Journal of Occupational and Environmental Hygiene 07/2012; 9(7):443-9. · 1.19 Impact Factor
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William G Lindsley,
Francoise M Blachere,
Kristina A Davis,
Terri A Pearce, Melanie A Fisher,
Rashida Khakoo,
Stephen M Davis,
Mark E Rogers,
Robert E Thewlis,
Jose A Posada,
John B Redrow,
Ismail B Celik,
Bean T Chen,
Donald H Beezhold
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ABSTRACT: Considerable controversy exists with regard to whether influenza virus and respiratory syncytial virus (RSV) are spread by the inhalation of infectious airborne particles and about the importance of this route, compared with droplet or contact transmission.
Airborne particles were collected in an urgent care clinic with use of stationary and personal aerosol samplers. The amounts of airborne influenza A, influenza B, and RSV RNA were determined using real-time quantitative polymerase chain reaction. Health care workers and patients participating in the study were tested for influenza.
Seventeen percent of the stationary samplers contained influenza A RNA, 1% contained influenza B RNA, and 32% contained RSV RNA. Nineteen percent of the personal samplers contained influenza A RNA, none contained influenza B RNA, and 38% contained RSV RNA. The number of samplers containing influenza RNA correlated well with the number and location of patients with influenza (r= 0.77). Forty-two percent of the influenza A RNA was in particles < or = 4.1 microm in aerodynamic diameter, and 9% of the RSV RNA was in particles < or = 4.1 microm.
Airborne particles containing influenza and RSV RNA were detected throughout a health care facility. The particles were small enough to remain airborne for an extended time and to be inhaled deeply into the respiratory tract. These results support the possibility that influenza and RSV can be transmitted by the airborne route and suggest that further investigation of the potential of these particles to transmit infection is warranted.
Clinical Infectious Diseases 03/2010; 50(5):693-8. · 9.15 Impact Factor
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William G Lindsley,
Francoise M Blachere,
Robert E Thewlis,
Abhishek Vishnu,
Kristina A Davis,
Gang Cao,
Jan E Palmer,
Karen E Clark, Melanie A Fisher,
Rashida Khakoo,
Donald H Beezhold
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ABSTRACT: Influenza is thought to be communicated from person to person by multiple pathways. However, the relative importance of different routes of influenza transmission is unclear. To better understand the potential for the airborne spread of influenza, we measured the amount and size of aerosol particles containing influenza virus that were produced by coughing. Subjects were recruited from patients presenting at a student health clinic with influenza-like symptoms. Nasopharyngeal swabs were collected from the volunteers and they were asked to cough three times into a spirometer. After each cough, the cough-generated aerosol was collected using a NIOSH two-stage bioaerosol cyclone sampler or an SKC BioSampler. The amount of influenza viral RNA contained in the samplers was analyzed using quantitative real-time reverse-transcription PCR (qPCR) targeting the matrix gene M1. For half of the subjects, viral plaque assays were performed on the nasopharyngeal swabs and cough aerosol samples to determine if viable virus was present. Fifty-eight subjects were tested, of whom 47 were positive for influenza virus by qPCR. Influenza viral RNA was detected in coughs from 38 of these subjects (81%). Thirty-five percent of the influenza RNA was contained in particles>4 µm in aerodynamic diameter, while 23% was in particles 1 to 4 µm and 42% in particles<1 µm. Viable influenza virus was detected in the cough aerosols from 2 of 21 subjects with influenza. These results show that coughing by influenza patients emits aerosol particles containing influenza virus and that much of the viral RNA is contained within particles in the respirable size range. The results support the idea that the airborne route may be a pathway for influenza transmission, especially in the immediate vicinity of an influenza patient. Further research is needed on the viability of airborne influenza viruses and the risk of transmission.
PLoS ONE 01/2010; 5(11):e15100. · 4.09 Impact Factor
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ABSTRACT: Withholding iron from potential pathogens is a host defense strategy. There is evidence that iron overload per se compromises the ability of phagocytes to kill microorganisms. Several hypotheses exist to explain the association of hemochromatosis with infection. A combination of mechanisms likely contributes to the increase in susceptibility to infection in these patients. A review of the current literature delineating various pathogens to which patients with hemochromatosis are potentially susceptible, and recent advances in the understanding of the association of hemochromatosis with infection, are discussed.
International Journal of Infectious Diseases 12/2007; 11(6):482-7. · 1.94 Impact Factor
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ABSTRACT: To determine whether daily high-dose vitamin C alters the steady-state pharmacokinetics of indinavir, a protease inhibitor indicated for treatment of the human immunodeficiency virus type 1.
Prospective, open-label, longitudinal, two-period time series.
University medical center.
Seven healthy volunteers.
Indinavir 800 mg every 8 hours was given to subjects for four doses on days 1 and 2. Plasma samples were then collected for indinavir pharmacokinetic determination. After a 7-day washout period, subjects were given vitamin C 1000 mg/day for 7 days. Beginning on day 6 of vitamin C administration, indinavir 800 mg every 8 hours was restarted for four doses. Plasma was then collected from subjects to determine indinavir pharmacokinetics. All subjects were given a vitamin C content-controlled diet for 1 week before the study began and throughout the study period.
Steady-state plasma samples were collected before dosing (0 hr) and 0.5, 1, 2, 3, 4, and 5 hours after dosing to determine indinavir pharmacokinetics. Parameters of interest were maximum plasma concentration (C max ), time to C max , area under the plasma concentration-time curve from 0-5 hours after the dose (AUC 0-5 ), an extrapolated 8-hour AUC (AUC 0-8 ), trough (minimum) plasma concentration (C min ), and oral clearance. Mean steady-state indinavir C max was significantly reduced (20%) after 7 days of vitamin C administration (10.3 +/- 1.5 vs 8.2 +/- 2.9 microg/ml, p=0.04). The corresponding mean AUC 0-8 was also significantly decreased (14%; 26.4 +/- 7.2 vs 22.7 +/- 8.1 microg*hr/ml, p=0.05). Although not statistically significant, the mean indinavir C min was 32% lower in the presence of vitamin C (0.27 +/- 0.17 C vs 0.18 +/- 0.08 microg/ml, p=0.09). Indinavir oral clearance and half-life were not significantly different.
Concomitant administration of high doses of vitamin C can reduce steady-state indinavir plasma concentrations. Subtherapeutic concentrations of antiretroviral agents have been associated with viral resistance and regimen failure, but the clinical significance of our findings remains to be established.
Pharmacotherapy 03/2005; 25(2):165-70. · 2.90 Impact Factor
