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39 SeSSion 4 Experimental âBench Scienceâ Approaches to Investigating the Spread of Disease in Airports and on Aircraft James J. McDevitt, Harvard School of Public Health Donald K. Milton, University of Maryland School of Public Health Charles P. Gerba, University of Arizona InterventIons for PreventIng the transmIssIon of Influenza vIrus James J. McDevitt and Donald K. Milton in light of the 2009 H1n1 flu pandemic and threats of pandemic from highly virulent H5n1 avian flu, much attention has focused on influenza virus. However, according to a 2007 national Academy of Sciences report, Preparing for an Influenza Pandemic: Personal Protective Equipment for Healthcare Workers, our understanding of the transmission of influenza is woe- fully inadequate (1). it is important to elucidate the mode of transmission for infectious respiratory diseases, such as influenza, to develop and implement effective inter- ventions to prevent transmission. There are three basic modes of transmission of respiratory viruses: direct con- tact with another person (e.g., kissing) or with large drop- lets expelled from the respiratory tract, indirect contact with inanimate objects contaminated with respiratory secretions, and inhalation of fine particles either directly released from the respiratory tract or resulting from the evaporation of large droplets. Recently published review articles addressing transmission of influenza virus reach vastly different conclusions about transmission of influ- enza virus. A review by Tellier largely concluded that influenza is transmitted by fine aerosols (2), while Brank- ston and colleagues generally concluded that influenza is transmitted directly by large droplets (3). Consider- ing this uncertainty, our research efforts have focused on two areas of intervention that are likely to have a large impact on influenza transmission: decontamination of contaminated surfaces and the use of surgical masks as source control, nonpharmaceutical interventions. Decontamination of Surfaces Contaminated with Influenza Virus The goal of our surface decontamination research is to prevent the secondary spread of influenza virus via contaminated fomites. Research has demonstrated the presence and survival of influenza virus in many environ- ments (4). Decontaminating small objects or occupied spaces is easily accomplished by applying disinfectants to surfaces. However, decontaminating large complex structures such as commercial aircraft, trains, and buses requires large amounts of time and effort, resulting in significant downtime for the use of that resource. While preventing secondary spread of influenza is our goal, decontamination needs to meet the following require- ments: no (or minimal) harm to surfaces, electrical sys- tems, and mechanical components; no harmful residues remaining after treatment; and fast turnaround time. Taking these requirements into consideration, we evalu- ated the following candidate decontamination methods: low-concentration vaporous hydrogen peroxide (VHP), triethylene glycol (TeG) vapor, and heat with moisture. Briefly, our experimental protocol consisted of apply- ing liquid suspensions of influenza virus onto stainless steel coupons, allowing the suspension to dry, and expos- ing the coupons to the test environment. Control cou- pons, which were not exposed to the test environment, were used to calculate the magnitude of influenza virus
40 ReSeARCH on THe TRAnSMiSSion of DiSeASe in AiRPoRTS AnD on AiRCRAfT reduction. Test and control coupons were repeatedly rinsed and the rinse solution was assayed for influenza infectivity with a fluorescent focus reduction assay (5, 6). Reductions of influenza were expressed as logarithmic (log) reductions. A log reduction of 1.0 is equivalent to a 10-fold decrease (90%) and a reduction of 2.0 is equiva- lent to a 100-fold decrease (99%), and so on. initial survival experiments were done at ambient conditions to determine the ânatural,â baseline decay rate for influenza virus. The number of log reductions versus time was generally linear, and our results showed 0.08 log reduction per hour. for VHP, generally, reduc- tion marginally increased with increased exposure time or VHP concentration. At a VHP concentration of 10 parts per million (ppm), about 2 log reductions were observed after 2.5 min of exposure and the number increased to about 3.2 log reductions after 15 min (maxi- mum exposure time measured). At a VHP concentration of 90 ppm (the highest concentration evaluated), about 3.2 log reductions were observed after 2.5 min of expo- sure and the number increased to about 4.7 log reduc- tions after 15 min. VHP experiments were performed at about 25Â°C and 58% to 65% relative humidity (RH) (7). for TeG vapor concentrations ranging from 1.7 to 2.5 ppm, the number of log reductions versus time fol- lowed a linear relationship with a decontamination rate of 1.3 log reductions per hour. TeG vapor experiments were performed at 25Â°C to 29Â°C and 45% to 55% RH (7). Heat and RH experiments were carried out at 55Â°C, 60Â°C, and 65Â°C and 25%, 50%, and 75% RH. Surface inactivation of influenza virus increased with increasing temperature, RH, and exposure time. Greater than 5 log reductions of influenza virus on surfaces was achieved at temperatures of 60Â°C and 65Â°C, exposure times of 30 and 60 min, and RH of 50% and 75%. our data also suggest that ambient humidity is a better predictor of surface inactivation than RH and allows for predicting survival by using two parameters instead of three, which greatly simplifies analysis and interpretation of virus sur- vival data. Surgical Masks as a Source Control for Influenza Transmission We hypothesize that patients infected with influenza virus exhale infectious influenza virus aerosols. These aerosol particles are at their largest size and highest velocity as they exit the nose and mouth. Thus, surgi- cal masks, which are normally considered inefficient for particle removal, may be able to capture a significant portion of these aerosols. The following specific aims were used to test these hypotheses: (a) measure num- ber and size distribution of exhaled influenza viruses, and (b) measure the effect of wearing a surgical mask on the release of virus aerosol by patients. The research presented here was completed in two phases. The first phase was preliminary research to measure the output of influenza in infected patients, and the second phase consisted of measuring the utility of surgical masks to prevent the release of influenza virus aerosols from infected patients. During Years 1 and 2 of the study, we used an ex- halair (Pulmatrix inc., Lexington, Massachusetts) to col- lect exhaled breath from subjects infected with influenza virus within 3 days of the onset of symptoms. The ex- halair uses light scattering to measure particle number and size and a Teflon filter to collect particles for later analysis by quantitative reverse transcriptionâpolymerase chain reaction (qRT-PCR) to measure influenza virus ribonucleic acid (RnA). During Year 1 of the study, car- ried out in Hong Kong, subjects wore a continuous posi- tive airway pressureâtype mask, breathed tidally for 3 min for the particle characterization phase, and breathed tidally for 15 min for the filter collection phase. The fil- ter was washed and analyzed by qRT-PCR as described (8). influenza status of each subject was confirmed by qRT-PCR of nasal swabs. Virus was detected in exhaled breath of four (33%) of the 12 studied patients, with generation rates ranging from <3.2 to 20 influenza RnA copies per minute. Particle count data showed that 87% of particles had an aerodynamic equivalent diameter <1 micrometer (ÂµmAeD) and that fewer than 0.1% of par- ticles were >5 ÂµmAeD, which suggests that virus, detected by qRT-PCR, was present in fine particles generated dur- ing tidal breathing (8). During Year 2 of the study, carried out at the Uni- versity of Massachusetts, Lowell, testing similar to that for Year 1 was done, with the following exceptions: the particle counting phase was completed with a mouth- piece and nose clips rather than a continuous positive airway pressure mask, filter collection was performed for 30 min rather than 15 min, and an additional fil- ter sample was collected while the subject was asked to cough 10 times. The filter was washed and analyzed by qRT-PCR as described. influenza virus RnA was detect- able in exhaled aerosols during tidal breathing but was more frequent in coughing than in tidal breathing. The generation rates were <3.2 to 20 RnA copies/min for tidal breathing and 0.1 to 419 RnA copies per cough. During Year 3 of the study, also carried out at the University of Massachusetts, Lowell, surgical masks were evaluated as source control nonpharmaceutical interventions. During this study, we collected exhaled breath from influenza-positive subjects who were wear- ing ear-loop surgical masks for 30 min while tidal breath- ing and performing 10 voluntary coughs every 10 min. A second sample was collected from the same subject without a mask while tidal breathing and coughing as for the initial sample. Samples were collected with the G-ii
41exPeRiMenTAL âBenCH SCienCeâ APPRoACHeS exhaled breath air sampler (United States Provisional Patent Application no. 61/162,395). Briefly, subjects sat with their face directed into an obliquely truncated steel cone into which air was drawn by a vacuum pump at 160 L/min. The air then passed through a 5 ÂµmAeD slit impactor with a Teflon collection substrate. The collec- tion substrate was washed and analyzed by qRT-PCR as described (9). forty-one subjects were tested and there was a significant reduction in the proportion of cases with detectable influenza in the samples collected while subjects were wearing surgical masks versus not wearing a mask for particles >5.0 ÂµmAeD. References Goldfrank, L. R., and C. T. Liverman. 1. Preparing for an Influenza Pandemic: Personal Protective Equipment for Healthcare Workers. national Academies Press, Washing- ton, D.C., 2008. Tellier, R. Review of Aerosol Transmission of influenza 2. A Virus. Emerging Infectious Diseases, Vol. 12, no. 11, 2006, pp. 1657â1662. Brankston, G., L. Gitterman, Z. Hirji, C. Lemieux, and M. 3. Gardam. Transmission of influenza A in Human Beings. Lancet Infectious Diseases, Vol. 7, no. 4, 2007, pp. 257â 265. Boone, S. A., and C. P. Gerba. Significance of fomites 4. in the Spread of Respiratory and enteric Viral Disease. Applied and Environmental Microbiology, Vol. 73, no. 6, 2007, pp. 1687â1696. fabian, P., J. J. McDevitt, e. A. Houseman, and D. K. 5. Milton. Airborne influenza Virus Detection with four Aerosol Samplers Using Molecular and infectivity Assays: Considerations for a new infectious Virus Aerosol Sam- pler. Indoor Air, Vol. 19, no. 5, 2009, pp. 433â441. fabian, P., J. J. McDevitt,W.-M. Lee, e. A. Houseman, 6. and D. K. Milton. An optimized Method to Detect influ- enza Virus and Human Rhinovirus from exhaled Breath and the Airborne environment. Journal of Environmental Monitoring, Vol. 11, no. 2, 2009, pp. 314â317. Rudnick, S. n., and J. J. McDevitt. inactivating influenza 7. Viruses on Surfaces Using Hydrogen Peroxide or Triethyl- ene Glycol at Low Vapor Concentrations. American Jour- nal of Infection Control, 2009. fabian, P., J. J. McDevitt,W. H. DeHaan, R. o. P. fung, 8. B. J. Cowling, K. H. Chan, G. M. Leung, and D. K. Mil- ton. influenza Virus in Human exhaled Breath: An obser- vational Study. Public Library of Science One, Vol. 3, no. 7, 2008, p. e2691. van elden, L. J., M. nijhuis, P. Schipper, R. Schuurman, 9. and A. M. van Loon. Simultaneous Detection of influenza Viruses A and B Using Real-Time Quantitative PCR. Jour- nal of Clinical Microbiology, Vol. 39, no. 1, 2001, pp. 196â200. the role of fomItes In transmIssIon of Pathogens In aIrPorts and on aIrPcraft Charles P. Gerba inanimate objects or fomites consist of porous and nonpo- rous surfaces and objects that serve as vehicles for trans- mitting infectious diseases. During and after an illness, pathogenic microorganisms can be shed in large numbers in body excretions and secretions, including blood, feces, urine, saliva, and mucus. fomites become contaminated with pathogens by direct contact with body fluids, con- tact with hands, contact with aerosols (large droplets), sneezing, coughing, vomiting, and contact when airborne organisms settle after resuspension from a contaminated surface. once a fomite is contaminated, transfer of infec- tious microbes may readily occur between fomites and humans, or vice versa, and between two fomites (e.g., contaminated sponges used to wipe a surface). Respiratory and enteric microorganisms can be readily transmitted when the hand becomes contaminated from contact with a fomite and the infectious microorganisms are transferred to a portal of entry (eyes, nose, mouth). Contact with the face is fairly frequent in children. Under 2 years of age, contact occurs about 81 times per hour. This number decreases to about 15.5 times per hour in adults (1). factors controlling the probability of infec- tion by this route include the frequency with which the fomite is contaminated, survival of the organism on the fomite, efficiency of transfer from the fomite to the hand, survival on the skin, and efficiency of transfer to the face. Viruses have a greater probability of being transmitted by fomites because of the greater probability of becoming infected with fewer organisms. for many enteric viruses, the dose to infect 50% of those exposed is only 1 to 100 viruses. enteric bacteria may be excreted in numbers as great as 1010 per gram of feces and enteric viruses as much as 1011 per gram of feces. Most bacteria causing respiratory and enteric infec- tions usually survive only a few hours on dry surfaces, although enteric bacteria are capable of growing in moist environments (sponges, mops, cloths) in large numbers. Respiratory viruses such as influenza may survive from a matter of hours to several days on fomites (2). in con- trast, enteric viruses, such as norovirus and hepatitis A virus, can live days to weeks on fomites. Survival of organisms on surfaces is related to the nature of the sus- pending fluid (longer survival in bodily fluids), tempera- ture (longer survival at lower temperatures), RH (varies with the organism), and the nature of the surface (gener- ally longer survival on porous surfaces). The efficiency of transfer of organisms varies with the type of fomite and can vary from 0.01% to >50%. Generally, transfer is more efficient from hard nonpo- rous surfaces such as stainless steel and porous surfaces
42 ReSeARCH on THe TRAnSMiSSion of DiSeASe in AiRPoRTS AnD on AiRCRAfT (cloth). Transfer from the hand to the face varies from 10% or more (3). By knowing the degree of fomite contamination in an environment, survival, and transfer efficiencies, it is pos- sible to model the probability of infection and the poten- tial impact of interventions (4). Surprisingly few studies have been done on the occur- rence of respiratory and enteric pathogens on fomites in indoor environments. Such information is useful for the targeted use of cleaning and disinfecting efforts to reduce the risk of exposure. We have found that common high- touch areas and shared fomites become the most con- taminated (5). Many other factors are important such as frequency with which an object or surface is cleaned or disinfected. for example, television remote controls and other types of electronic equipment tend to be more contaminated as they are seldom cleaned or disinfected (6). Also, cleaning tools (mops, cloths) can spread patho- genic organisms in an environment if disinfectants are not used. When traveling, a common area we all share are pub- lic restrooms. Public restrooms have been implicated in outbreaks of Salmonella, Shigella, hepatitis A virus, and norovirus. We have found a greater frequency of enteric bacteria on fomites in airport and airplane restrooms than in hospital, fast-food restaurant, and office building restrooms. This finding probably reflects the high traffic in these restrooms. The most contaminated restrooms are in aircraft, probably because of the limited number of restrooms per passenger and the ease of using hand washing facilities (i.e., small sinks, water automatically shuts off). The common occurrence of enteric viruses in laboratory wastes collected from aircraft indicates that passengers are infected (7). in homes with persons infected with influenza, the virus can be isolated on more than half the fomites tested (phones, television remote controls) (6). norovirus is also commonly isolated on fomites in schools and other public environments (8). Thus, individuals infected with these viruses can be expected to contaminate any environment they occupy. We have also detected fecal bacteria as well as norovirus on passenger trays, suggesting that these areas are not regularly cleaned or disinfected. Risks are reduced from fomite transmission if proper hand washing, use of hand sanitizers, and disinfection of key areas are practiced. All these interventions have been shown to reduce risks of infection by 30% to 50% (8). other potential interventions in aircraft and airports could include use of more persistent disinfectants, self- sanitizing surfaces, and surfaces that reduce transfer of microbes to the hands. To develop effective interven- tions, a better understanding of the occurrence of micro- bial contamination on fomites in aircraft and airports is needed. in this way, effective interventions can be devel- oped and monitored for success. References 1. nicas, M., and D. Best. A Study Quantifying the Hand- to-face Contact Rate and its Potential Application to Predicting Respiratory Tract infection. Journal of Occu- pational and Environmental Hygiene, Vol. 5, 2008, pp. 347â352. 2. Boone, S. A., and C. P. Gerba. Significance of fomites in the Spread of Respiratory and enteric Viral Disease. Applied and Environmental Microbiology, Vol. 73, no. 6, 2007, pp. 1687â1696. 3. Rusin, P., S. Maxwell, and C. P. Gerba. Comparative Surface-to-Hand and finger-to-Mouth Transfer efficiency of Gram Positive, Gram negative Bacteria, and Phage. Journal of Applied Microbiology, Vol. 93, 2002, pp. 585â 592. 4. nicas, M., and R. M. Jones. Relative Contributions of four exposure Pathways to influenza infection Risk. Risk Analysis, Vol. 29, 2009, pp. 1292â1303. 5. Reynolds, K. A., P. M. Watt, S. A. Boone, and C. P. Gerba. occurrence of Bacteria and Biochemical Markers on Public Surfaces. International Journal of Environmental Health Research, Vol. 15, 2005, pp. 225â234. 6. Boone, S. A., and C. P. Gerba. The occurrence of influ- enza A Virus on Household and Day Care Center fomites. Journal of Infection, Vol. 51, 2005, pp. 102â109 7. Shieh, Y. S., R. S. Baric, and M. D. Sobsey. Detection of Low Levels of enteric Viruses in Metropolitan and Air- plane Sewage. Applied and Environmental Microbiology, Vol. 63, 1997, pp. 4401â4407. 8. Bright, K., S. A. Boone, and C. P. Gerba. occurrence of Bacteria and Viruses on elementary Classroom Surfaces and the Potential Role of Classroom Hygiene in the Spread of infectious Diseases. Journal of School Nursing, Vol. 26, no. 1, 2010, pp. 33â41.