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1.  Air Cleaning Technologies 
Executive Summary
This health technology policy assessment will answer the following questions:
When should in-room air cleaners be used?
How effective are in-room air cleaners?
Are in-room air cleaners that use combined HEPA and UVGI air cleaning technology more effective than those that use HEPA filtration alone?
What is the Plasmacluster ion air purifier in the pandemic influenza preparation plan?
The experience of severe acute respiratory syndrome (SARS) locally, nationally, and internationally underscored the importance of administrative, environmental, and personal protective infection control measures in health care facilities. In the aftermath of the SARS crisis, there was a need for a clearer understanding of Ontario’s capacity to manage suspected or confirmed cases of airborne infectious diseases. In so doing, the Walker Commission thought that more attention should be paid to the potential use of new technologies such as in-room air cleaning units. It recommended that the Medical Advisory Secretariat of the Ontario Ministry of Health and Long-Term Care evaluate the appropriate use and effectiveness of such new technologies.
Accordingly, the Ontario Health Technology Advisory Committee asked the Medical Advisory Secretariat to review the literature on the effectiveness and utility of in-room air cleaners that use high-efficiency particle air (HEPA) filters and ultraviolet germicidal irradiation (UVGI) air cleaning technology.
Additionally, the Ontario Health Technology Advisory Committee prioritized a request from the ministry’s Emergency Management Unit to investigate the possible role of the Plasmacluster ion air purifier manufactured by Sharp Electronics Corporation, in the pandemic influenza preparation plan.
Clinical Need
Airborne transmission of infectious diseases depends in part on the concentration of breathable infectious pathogens (germs) in room air. Infection control is achieved by a combination of administrative, engineering, and personal protection methods. Engineering methods that are usually carried out by the building’s heating, ventilation, and air conditioning (HVAC) system function to prevent the spread of airborne infectious pathogens by diluting (dilution ventilation) and removing (exhaust ventilation) contaminated air from a room, controlling the direction of airflow and the air flow patterns in a building. However, general wear and tear over time may compromise the HVAC system’s effectiveness to maintain adequate indoor air quality. Likewise, economic issues may curtail the completion of necessary renovations to increase its effectiveness. Therefore, when exposure to airborne infectious pathogens is a risk, the use of an in-room air cleaner to reduce the concentration of airborne pathogens and prevent the spread of airborne infectious diseases has been proposed as an alternative to renovating a HVAC system.
Airborne transmission is the spread of infectious pathogens over large distances through the air. Infectious pathogens, which may include fungi, bacteria, and viruses, vary in size and can be dispersed into the air in drops of moisture after coughing or sneezing. Small drops of moisture carrying infectious pathogens are called droplet nuclei. Droplet nuclei are about 1 to 5μm in diameter. This small size in part allows them to remain suspended in the air for several hours and be carried by air currents over considerable distances. Large drops of moisture carrying infectious pathogens are called droplets. Droplets being larger than droplet nuclei, travel shorter distances (about 1 metre) before rapidly falling out of the air to the ground. Because droplet nuclei remain airborne for longer periods than do droplets, they are more amenable to engineering infection control methods than are droplets.
Droplet nuclei are responsible for the airborne transmission of infectious diseases such as tuberculosis, chicken pox (varicella), measles (rubeola), and dessiminated herpes zoster, whereas close contact is required for the direct transmission of infectious diseases transmitted by droplets, such as influenza (the flu) and SARS.
The Technology
In-room air cleaners are supplied as portable or fixed devices. Fixed devices can be attached to either a wall or ceiling and are preferred over portable units because they have a greater degree of reliability (if installed properly) for achieving adequate room air mixing and airflow patterns, which are important for optimal effectiveness.
Through a method of air recirculation, an in-room air cleaner can be used to increase room ventilation rates and if used to exhaust air out of the room it can create a negative-pressure room for airborne infection isolation (AII) when the building’s HVAC system cannot do so. A negative-pressure room is one where clean air flows into the room but contaminated air does not flow out of it. Contaminated room air is pulled into the in-room air cleaner and cleaned by passing through a series of filters, which remove the airborne infectious pathogens. The cleaned air is either recirculated into the room or exhausted outside the building. By filtering contaminated room air and then recirculating the cleaned air into the room, an in-room air cleaner can improve the room’s ventilation. By exhausting the filtered air to the outside the unit can create a negative-pressure room. There are many types of in-room air cleaners. They vary widely in the airflow rates through the unit, the type of air cleaning technology used, and the technical design.
Crucial to maximizing the efficiency of any in-room air cleaner is its strategic placement and set-up within a room, which should be done in consultation with ventilation engineers, infection control experts, and/or industrial hygienists. A poorly positioned air cleaner may disrupt airflow patterns within the room and through the air cleaner, thereby compromising its air cleaning efficiency.
The effectiveness of an in-room air cleaner to remove airborne pathogens from room air depends on several factors, including the airflow rate through the unit’s filter and the airflow patterns in the room. Tested under a variety of conditions, in-room air cleaners, including portable or ceiling mounted units with either a HEPA or a non-HEPA filter, portable units with UVGI lights only, or ceiling mounted units with combined HEPA filtration and UVGI lights, have been estimated to be between 30% and 90%, 99% and 12% and 80% effective, respectively. However, and although their effectiveness is variable, the United States Centers for Disease Control and Prevention has acknowledged in-room air cleaners as alternative technology for increasing room ventilation when this cannot be achieved by the building’s HVAC system with preference given to fixed recirculating systems over portable ones.
Importantly, the use of an in-room air cleaner does not preclude either the need for health care workers and visitors to use personal protective equipment (N95 mask or equivalent) when entering AII rooms or health care facilities from meeting current regulatory requirements for airflow rates (ventilation rates) in buildings and airflow differentials for effective negative-pressure rooms.
The Plasmacluster ion technology, developed in 2000, is an air purification technology. Its manufacturer, Sharp Electronics Corporation, says that it can disable airborne microorganisms through the generation of both positive and negative ions. (1) The functional unit is the hydroxyl, which is a molecule comprised of one oxygen molecule and one hydrogen atom.
Plasmacluster ion air purifier uses a multilayer filter system composed of a prefilter, a carbon filter, an antibacterial filter, and a HEPA filter, combined with an ion generator to purify the air. The ion generator uses an alternating plasma discharge to split water molecules into positively and negatively charged ions. When these ions are emitted into the air, they are surrounded by water molecules and form cluster ions which are attracted to airborne particles. The cluster ion surrounds the airborne particle, and the positive and negative ions react to form hydroxyls. These hydroxyls steal the airborne particle’s hydrogen atom, which creates a hole in the particle’s outer protein membrane, thereby rendering it inactive.
Because influenza is primarily acquired by large droplets and direct and indirect contact with an infectious person, any in-room air cleaner will have little benefit in controlling and preventing its spread. Therefore, there is no role for the Plasmacluster ion air purifier or any other in-room air cleaner in the control of the spread of influenza. Accordingly, for purposes of this review, the Medical Advisory Secretariat presents no further analysis of the Plasmacluster.
Review Strategy
The objective of the systematic review was to determine the effectiveness of in-room air cleaners with built in UVGI lights and HEPA filtration compared with those using HEPA filtration only.
The Medical Advisory Secretariat searched the databases of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, INAHATA (International Network of Agencies for Health Technology Assessment), Biosis Previews, Bacteriology Abstracts, Web of Science, Dissertation Abstracts, and NIOSHTIC 2.
A meta-analysis was conducted if adequate data was available from 2 or more studies and where statistical and clinical heterogeneity among studies was not an issue. Otherwise, a qualitative review was completed. The GRADE system was used to summarize the quality of the body of evidence comprised of 1 or more studies.
Summary of Findings
There were no existing health technology assessments on air cleaning technology located during the literature review. The literature search yielded 59 citations of which none were retained. One study was retrieved from a reference list of a guidance document from the United States Centers for Disease Control and Prevention, which evaluated an in-room air cleaner with combined UVGI lights and HEPA filtration under 2 conditions: UVGI lights on and UVGI lights off. Experiments were performed using different ventilation rates and using an aerosolized pathogen comprised of Mycobaterium parafortuitum, a surrogate for the bacterium that causes tuberculosis. Effectiveness was measured as equivalent air changes per hour (eACH). This single study formed the body of evidence for our systematic review research question.
Experimental Results
The eACH rate for the HEPA-UVGI in-room air cleaner was statistically significantly greater when the UV lights were on compared with when the UV lights were off. (P < .05). However, subsequent experiments could not attribute this to the UVGI. Consequently, the results are inconclusive and an estimate of effect (benefit) is uncertain.
The study was reviewed by a scientific expert and rated moderate for quality. Further analysis determined that there was some uncertainty in the directness of the outcome measure (eACH); thus, the GRADE level for the quality of the evidence was low indicating that an estimate of effect is very uncertain.
There is uncertainty in the benefits of using in-room air cleaners with combined UVGI lights and HEPA filtration over systems that use HEPA filtration alone. However, there are no known risks to using systems with combined UVGI and HEPA technology compared with those with HEPA alone. There is an increase in the burden of cost including capital costs (cost of the device), operating costs (electricity usage), and maintenance costs (cleaning and replacement of UVGI lights) to using an in-room air cleaner with combined UVGI and HEPA technology compared with those with HEPA alone. Given the uncertainty of the estimate of benefits, an in-room air cleaner with HEPA technology only may be an equally reasonable alternative to using one with combined UVGI and HEPA technology
In-room air cleaners may be used to protect health care staff from air borne infectious pathogens such as tuberculosis, chicken pox, measles, and dessiminated herpes zoster. In addition, and although in-room air cleaners are not effective at protecting staff and preventing the spread of droplet-transmitted diseases such as influenza and SARS, they may be deployed in situations with a novel/emerging infectious agent whose epidemiology is not yet defined and where airborne transmission is suspected.
It is preferable that in-room air cleaners be used with a fixed and permanent room placement when ventilation requirements must be improved and the HVAC system cannot be used. However, for acute (temporary) situations where a novel/emerging infectious agent presents whose epidemiology is not yet defined and where airborne transmission is suspected it may be prudent to use the in room air cleaner as a portable device until mode of transmission is confirmed. To maximize effectiveness, consultation with an environmental engineer and infection control expert should be undertaken before using an in-room air cleaner and protocols for maintenance and monitoring of these devices should be in place.
If properly installed and maintained, in room air cleaners with HEPA or combined HEPA and UVGI air cleaning technology are effective in removing airborne pathogens. However, there is only weak evidence available at this time regarding the benefit of using an in-room air cleaner with combined HEPA and UVGI air cleaner technology instead of those with HEPA filter technology only.
PMCID: PMC3382390  PMID: 23074468
2.  Natural Ventilation for the Prevention of Airborne Contagion 
PLoS Medicine  2007;4(2):e68.
Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings.
Methods and Findings
The study was carried out in eight hospitals in Lima, Peru; five were hospitals of “old-fashioned” design built pre-1950, and three of “modern” design, built 1970–1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open.
Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion.
In eight hospitals in Lima, opening windows and doors maximised natural ventilation and lowered the risk of airborne infection. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection.
Editors' Summary
Tuberculosis (TB) is a major cause of ill health and death worldwide, with around one-third of the world's population infected with the bacterium that causes it (Mycobacterium tuberculosis). One person with active tuberculosis can go on to infect many others; the bacterium is passed in tiny liquid droplets that are produced when someone with active disease coughs, sneezes, spits, or speaks. The risk of tuberculosis being transmitted in hospital settings is particularly high, because people with tuberculosis are often in close contact with very many other people. Currently, most guidelines recommend that the risk of transmission be controlled in certain areas where TB is more likely by making sure that the air in rooms is changed with fresh air between six and 12 times an hour. Air changes can be achieved with simple measures such as opening windows and doors, or by installing mechanical equipment that forces air changes and also keeps the air pressure in an isolation room lower than that outside it. Such “negative pressure,” mechanically ventilated systems are often used on tuberculosis wards to prevent air flowing from isolation rooms to other rooms outside, and so to prevent people on the tuberculosis ward from infecting others.
Why Was This Study Done?
In many parts of the world, hospitals do not have equipment even for simple air conditioning, let alone the special equipment needed for forcing high air changes in isolation rooms and wards. Instead they rely on opening windows and doors in order to reduce the transmission of TB, and this is called natural ventilation. However, it is not clear whether these sorts of measures are adequate for controlling TB transmission. It is important to find out what sorts of systems work best at controlling TB in the real world, so that hospitals and wards can be designed appropriately, within available resources.
What Did the Researchers Do and Find?
This study was based in Lima, Peru's capital city. The researchers studied a variety of rooms, including tuberculosis wards and respiratory isolation rooms, in the city's hospitals. Rooms which had only natural measures for encouraging airflow were compared with mechanically ventilated, negative pressure rooms, which were built much more recently. A comparison was also done between rooms in old hospitals that were naturally ventilated with rooms in newer hospitals that were also naturally ventilated. The researchers used a particular method to measure the number of air changes per hour within each room, and based on this they estimated the risk of a person with TB infecting others using a method called the Wells-Riley equation. The results showed that natural ventilation provided surprisingly high rates of air exchange, with an average of 28 air changes per hour. Hospitals over 50 years old, which generally had large windows and high ceilings, had the highest ventilation, with an average of 40 air changes per hour. This rate compared with 17 air changes per hour in naturally ventilated rooms in modern hospitals, which tended to have lower ceilings and smaller windows. The rooms with modern mechanical ventilation were supposed to have 12 air changes per hour but in reality this was not achieved, as the systems were not maintained properly. The Wells-Riley equation predicted that if an untreated person with tuberculosis was exposed to other people, within 24 hours this person would infect 39% of the people in the mechanically ventilated room, 33% of people in the naturally ventilated new hospital rooms, and only 11% of the people in the naturally ventilated old hospital rooms.
What Do These Findings Mean?
These findings suggest that natural methods of encouraging airflow (e.g., opening doors and windows) work well and in theory could reduce the likelihood of TB being carried from one person to another. Some aspects of the design of wards in old hospitals (such as large windows and high ceilings) are also likely to achieve better airflow and reduce the risk of infection. In poor countries, where mechanical ventilation systems might be too expensive to install and maintain properly, rooms that are designed to naturally achieve good airflow might be the best choice. Another advantage of natural ventilation is that it is not restricted by cost to just high-risk areas, and can therefore be used in many different parts of the hospital, including emergency departments, outpatient departments, and waiting rooms, and it is here that many infectious patients are to be found.
Additional Information.
Please access these Web sites via the online version of this summary at
Information from the World Health Organization on tuberculosis, detailing global efforts to prevent the spread of TB
The World Health Organization publishes guidelines for the prevention of TB in health care facilities in resource-limited settings
Tuberculosis infection control in the era of expanding HIV care and treatment is discussed in an addendum to the above booklet
The Centers for Disease Control have published guidelines for preventing the transmission of mycobacterium tuberculosis in health care settings
Wikipedia has an entry on nosocomial infections (diseases that are spread in hospital). Wikipedia is an internet encyclopedia anyone can edit
A PLoS Medicine Perspective by Peter Wilson, “Is Natural Ventilation a Useful Tool to Prevent the Airborne Spread of TB?” discusses the implications of this study
PMCID: PMC1808096  PMID: 17326709
3.  Architectural design influences the diversity and structure of the built environment microbiome 
The ISME Journal  2012;6(8):1469-1479.
Buildings are complex ecosystems that house trillions of microorganisms interacting with each other, with humans and with their environment. Understanding the ecological and evolutionary processes that determine the diversity and composition of the built environment microbiome—the community of microorganisms that live indoors—is important for understanding the relationship between building design, biodiversity and human health. In this study, we used high-throughput sequencing of the bacterial 16S rRNA gene to quantify relationships between building attributes and airborne bacterial communities at a health-care facility. We quantified airborne bacterial community structure and environmental conditions in patient rooms exposed to mechanical or window ventilation and in outdoor air. The phylogenetic diversity of airborne bacterial communities was lower indoors than outdoors, and mechanically ventilated rooms contained less diverse microbial communities than did window-ventilated rooms. Bacterial communities in indoor environments contained many taxa that are absent or rare outdoors, including taxa closely related to potential human pathogens. Building attributes, specifically the source of ventilation air, airflow rates, relative humidity and temperature, were correlated with the diversity and composition of indoor bacterial communities. The relative abundance of bacteria closely related to human pathogens was higher indoors than outdoors, and higher in rooms with lower airflow rates and lower relative humidity. The observed relationship between building design and airborne bacterial diversity suggests that we can manage indoor environments, altering through building design and operation the community of microbial species that potentially colonize the human microbiome during our time indoors.
PMCID: PMC3400407  PMID: 22278670
aeromicrobiology; bacteria; built environment microbiome; community ecology; dispersal; environmental filtering
4.  The Infectiousness of Tuberculosis Patients Coinfected with HIV 
PLoS Medicine  2008;5(9):e188.
The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB.
Methods and Findings
All air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour.
A small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.
Using a guinea pig detection system above an HIV-tuberculosis ward, Rod Escombe and colleagues found that most transmitted tuberculosis originated from patients with inadequately treated multidrug-resistant tuberculosis.
Editors' Summary
Every year, more than nine million people develop tuberculosis—a contagious infection usually of the lungs—and nearly two million people die from the disease. Tuberculosis is caused by Mycobacterium tuberculosis. These bacteria are spread in airborne droplets when people with the disease cough or sneeze. Most people infected with M. tuberculosis never become ill—their immune system contains the infection. However, the bacteria remain dormant within the body and can cause tuberculosis years later if host immunity declines. The symptoms of tuberculosis include a persistent cough, weight loss, and night sweats. Diagnostic tests for the disease include chest X-rays, the tuberculin skin test, and sputum cultures (in which bacteriologists try to grow M. tuberculosis from mucus brought up from the lungs by coughing). Tuberculosis can usually be cured by taking several powerful antibiotics daily for several months.
Why Was This Study Done?
Scientists performed definitive experiments on airborne tuberculosis transmission in the 1950s by exposing guinea pigs to the air from a tuberculosis ward. They found that a minority of patients actually transmit tuberculosis, that the infectiousness of transmitters varies greatly, and that effective antibiotic treatment decreases infectiousness. Since the 1950s, however, multidrug-resistant (MDR) and more recently extensively drug-resistant (XDR) strains of M. tuberculosis have become widespread. Treatment of drug-resistant tuberculosis is much more difficult than normal tuberculosis, requiring even more antibiotics, and for long periods, up to 2 years and beyond. In addition, HIV (the virus that causes AIDS) has emerged. HIV weakens the immune system so HIV-positive people are much more likely to develop active tuberculosis (and to die from the disease, which also speeds the development of HIV/AIDS) than people with a healthy immune system. Have these changes altered tuberculosis transmission between people? The answer to this question might help to optimize the control of tuberculosis infection, particularly in hospitals. In this study, the researchers investigate current patterns of tuberculosis infectiousness among HIV-positive patients by recreating the 1950s guinea pig model for tuberculosis transmission in a hospital in Lima, Perú.
What Did the Researchers Do and Find?
The researchers passed all the air from an HIV–tuberculosis ward over guinea pigs housed in an animal facility on the hospital's roof. The guinea pigs were tested monthly with tuberculin skin tests, and tissues from positive animals were examined for infection with M. tuberculosis. Sputum was also collected daily from the patients on the ward. The researchers then used the timing of patient admissions and guinea pig infections, together with the drug susceptibility patterns and DNA fingerprints of the M. tuberculosis strains isolated from the animals and the patients, to identify which patients had infected which guinea pigs. Finally, they used a mathematical equation to calculate the relative infectiousness of each patient in airborne infectious units (“quanta”) per hour. During the 505 study days, although 97 HIV-positive patients with tuberculosis were admitted to the ward, just ten patients were responsible for virtually all the characterized cases of tuberculosis among the guinea pigs. Six of these patients had MDR tuberculosis that had been suboptimally treated. The average patient infectiousness over the entire study period was 8.2 quanta per hour—six times greater than the average infectiousness recorded in the 1950s. Finally, the three most infectious patients (all of whom had suboptimally treated MDR tuberculosis) produced 226, 52, and 40 quanta per hour.
What Do These Findings Mean?
These findings show that a few inadequately treated HIV-positive patients with MDR tuberculosis caused nearly all the tuberculosis transmission to guinea pigs during this study. They also show for the first time that tuberculosis infectiousness among HIV-positive patients is very variable. The increase in the average patient infectiousness in this study compared to that seen in the 1950s hints at the possibility that HIV infection might increase tuberculosis infectiousness. However, studies that directly compare the tuberculosis infectiousness of HIV-positive and HIV-negative patients are needed to test this possibility. More importantly, this study demonstrates the potentially high infectiousness of inadequately treated MDR TB patients and their importance in ongoing TB transmission. These findings suggest that rapid, routine testing of antibiotic susceptibility should improve tuberculosis control by ensuring that patients with MDR TB are identified and treated effectively and quickly. Finally, they re-emphasize the importance of implementing environmental control measures (for example, adequate natural or mechanical ventilation of tuberculosis wards, or crowded waiting rooms or emergency departments where tuberculosis patients may be found) to prevent airborne tuberculosis transmission in health-care facilities, particularly in areas where many patients are HIV positive and/or where MDR tuberculosis is common.
Additional Information.
Please access these Web sites via the online version of this summary at
The US National Institute of Allergy and Infectious Diseases provides information on all aspects of tuberculosis, including multidrug-resistance tuberculosis, and on tuberculosis and HIV
The US Centers for Disease Control and Prevention provide several fact sheets and other information resources about all aspects of tuberculosis (in English and Spanish)
The World Health Organization's 2008 report on global tuberculosis control—surveillance, planning, financing provides a snapshot of the current state of the global tuberculosis epidemic and links to information about all aspects of tuberculosis and its control (in several languages)
HIVInsite provides detailed information about coinfection with HIV and tuberculosis
• Avert, an international AIDS charity, also provides information about the interaction between HIV and tuberculosis
Tuberculosis Infection-Control in the Era of Expanding HIV Care and Treatment is a report from the World Health Organization
PMCID: PMC2535657  PMID: 18798687
5.  Upper-Room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission 
PLoS Medicine  2009;6(3):e1000043.
Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air.
Methods and Findings
For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers.
Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings.
Using a guinea-pig detection model, Rod Escombe and colleagues find that upper-room UV lamps in hospital rooms can substantially reduce airborne transmission ofMycobacterium tuberculosis.
Editors' Summary
Tuberculosis—a contagious infection, usually of the lungs—kills nearly 2 million people annually. It is caused by Mycobacterium tuberculosis, bacteria that are spread in airborne droplets when people with tuberculosis cough or sneeze. Most people infected with M. tuberculosis do not become ill—their immune system contains the infection. However, the bacteria remain dormant within the body and can cause disease years later if immunity declines because of, for example, infection with human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS). The symptoms of tuberculosis include a persistent cough, weight loss, and night sweats. Infection with M. tuberculosis is diagnosed using the tuberculin skin test. Tests for tuberculosis itself include chest X-rays and sputum cultures (in which bacteriologists try to grow M. tuberculosis from mucus brought up from the lungs by coughing). Tuberculosis can usually be cured by taking several powerful antibiotics daily for several months. Drug-resistant tuberculosis is much harder to cure, requiring multiple second-line antibiotics for up to two years or more. Tuberculosis transmission can be reduced by, for example, hospitalizing people with tuberculosis in isolation wards in which negative-pressure mechanical ventilation is used to reduce the concentration of infectious airborne droplets.
Why Was This Study Done?
After the development of antibiotics capable of killing M. tuberculosis in the mid 20th century, it seemed that tuberculosis would become a disease of the past. But in the mid 1980s, drug-resistant M. tuberculosis strains began to emerge, the HIV/AIDS epidemic took hold, and tuberculosis resurged to today's worrying levels. New ways of reducing tuberculosis transmission, particularly in health care settings and in resource-limited settings, are now urgently needed. The need for effective infection control measures is especially urgent in HIV care programs where highly susceptible individuals frequently mix with people with tuberculosis. In this study, the researchers use a guinea pig air-sampling model (which was first used in the 1950s to show that tuberculosis is an airborne infection) to investigate whether upper-room ultraviolet (UV) lights in patient rooms and negative air ionization can prevent airborne tuberculosis transmission. UV light kills M. tuberculosis; negative ionization gives airborne particles a charge that makes them stick to surfaces.
What Did the Researchers Do and Find?
The researchers exposed a group of control guinea pigs kept in a special air-sampling enclosure to untreated air from an HIV–TB ward in Lima (Perú). Another group of animals (the UV group) breathed air from the same ward, but only on the days that UV lights suspended near the ward's ceiling were turned on, together with mixing fans to mix up the room air. The “ionizer group” had a negative ionizer switched on in their enclosure when they were exposed to ward air (each group of animals was exposed to ward air every other day). The animals were tested monthly with the tuberculin skin test and all were examined for tuberculosis disease when they became infected with tuberculosis or at the end of the 535-day experiment. 35% of the control animals, 14% of the ionizer group animals, and 9.5% of the UV group animals developed M. tuberculosis infections. Tuberculosis disease was found in 8.6% of the control animals but in only 4.3% and 3.6% of the animals in the ionizer and UV groups, respectively. A “time-to-event analysis” also showed that UV lights and ionizers reduced tuberculosis infection and disease. Finally, an analysis of the data using an airborne infection model indicated that ionizers and UV lights prevented 60% and 70% of tuberculosis infections, respectively.
What Do These Findings Mean?
These findings indicate that upper-room UV lights, combined with adequate air mixing, or negative air ionization with special large-scale ionizers can prevent most airborne tuberculosis transmission to guinea pigs exposed to hospital room air. The effectiveness of these approaches in reducing tuberculosis transmission between people is likely to be similar, although remains to be tested. Nevertheless, this first study of the effect of upper-air UV light and of negative air ionization on airborne transmission in a clinical setting suggests that both approaches could be potentially important tuberculosis infection control measures. Furthermore, the UV light approach might provide a relatively low-cost intervention for possible use in waiting rooms and other overcrowded settings where patients with undiagnosed, untreated tuberculosis—individuals who tend to be highly infectious—are likely to come into contact with other susceptible patients, health care workers, and visitors.
Additional Information.
Please access these Web sites via the online version of this summary at
The US National Institute of Allergy and Infectious Diseases provides information on all aspects of tuberculosis, including multidrug-resistance tuberculosis, and on tuberculosis and HIV
The US Centers for Disease Control and Prevention provide several fact sheets and other information resources about all aspects of tuberculosis, including Guidelines for preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005 (some information in Spanish is also available)
The World Health Organization's 2008 report “Global Tuberculosis Control—Surveillance, Planning, Financing” provides a snapshot of the current state of the global tuberculosis epidemic and links to information about all aspects of tuberculosis and its control (in several languages)
Tuberculosis Infection-Control in the Era of Expanding HIV Care and Treatment is another report from the World Health Organization
HIVInsite provides detailed information about the combination of HIV infection and tuberculosis
Avert, an international AIDS charity, also provides information about the interaction between HIV and tuberculosis
GHD (Global Health Delivery) Online is an online resource dedicated to TB infection control, and is moderated by world experts
PMCID: PMC2656548  PMID: 19296717
6.  Tuberculosis among Health-Care Workers in Low- and Middle-Income Countries: A Systematic Review 
PLoS Medicine  2006;3(12):e494.
The risk of transmission of Mycobacterium tuberculosis from patients to health-care workers (HCWs) is a neglected problem in many low- and middle-income countries (LMICs). Most health-care facilities in these countries lack resources to prevent nosocomial transmission of tuberculosis (TB).
Methods and Findings
We conducted a systematic review to summarize the evidence on the incidence and prevalence of latent TB infection (LTBI) and disease among HCWs in LMICs, and to evaluate the impact of various preventive strategies that have been attempted. To identify relevant studies, we searched electronic databases and journals, and contacted experts in the field. We identified 42 articles, consisting of 51 studies, and extracted data on incidence, prevalence, and risk factors for LTBI and disease among HCWs. The prevalence of LTBI among HCWs was, on average, 54% (range 33% to 79%). Estimates of the annual risk of LTBI ranged from 0.5% to 14.3%, and the annual incidence of TB disease in HCWs ranged from 69 to 5,780 per 100,000. The attributable risk for TB disease in HCWs, compared to the risk in the general population, ranged from 25 to 5,361 per 100,000 per year. A higher risk of acquiring TB disease was associated with certain work locations (inpatient TB facility, laboratory, internal medicine, and emergency facilities) and occupational categories (radiology technicians, patient attendants, nurses, ward attendants, paramedics, and clinical officers).
In summary, our review demonstrates that TB is a significant occupational problem among HCWs in LMICs. Available evidence reinforces the need to design and implement simple, effective, and affordable TB infection-control programs in health-care facilities in these countries.
A systematic review demonstrates that tuberculosis is an important occupational problem among health care workers in low and middle-income countries.
Editors' Summary
One third of the world's population is infected with Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). In many people, the bug causes no health problems—it remains latent. But about 10% of infected people develop active, potentially fatal TB, often in their lungs. People with active pulmonary TB readily spread the infection to other people, including health-care workers (HCWs), in small airborne droplets produced when they cough or sneeze. In high-income countries such as the US, guidelines are in place to minimize the transmission of TB in health-care facilities. Administrative controls (for example, standard treatment plans for people with suspected or confirmed TB) aim to reduce the exposure of HCWs to people with TB. Environmental controls (for example, the use of special isolation rooms) aim to prevent the spread and to reduce the concentration of infectious droplets in the air. Finally, respiratory-protection controls (for example, personal respirators for nursing staff) aim to reduce the risk of infection when exposure to M. tuberculosis is unavoidably high. Together, these three layers of control have reduced the incidence of TB in HCWs (the number who catch TB annually) in high-income countries.
Why Was This Study Done?
But what about low- and middle-income countries (LMICs) where more than 90% of the world's cases of TB occur? Here, there is little money available to implement even low-cost strategies to reduce TB transmission in health-care facilities—so how important an occupational disease is TB in HCWs in these countries? In this study, the researchers have systematically reviewed published papers to find out the incidence and prevalence (how many people in a population have a specific disease) of active TB and latent TB infections (LTBIs) in HCWs in LMICs. They have also investigated whether any of the preventative strategies used in high-income countries have been shown to reduce the TB burden in HCWs in poorer countries.
What Did the Researchers Do and Find?
To identify studies on TB transmission to HCWs in LMICs, the researchers searched electronic databases and journals, and also contacted experts on TB transmission. They then extracted and analyzed the relevant data on TB incidence, prevalence, risk factors, and control measures. Averaged-out over the 51 identified studies, 54% of HCWs had LTBI. In most of the studies, increasing age and duration of employment in health-care facilities, indicating a longer cumulative exposure to infection, was associated with a higher prevalence of LTBI. The same trend was seen in a subgroup of medical and nursing students. After accounting for the incidence of TB in the relevant general population, the excess incidence of TB in the different studies that was attributable to being a HCW ranged from 25 to 5,361 cases per 100, 000 people per year. In addition, a higher risk of acquiring TB was associated with working in specific locations (for example, inpatient TB facilities or diagnostic laboratories) and with specific occupations, including nurses and radiology attendants; most of the health-care facilities examined in the published studies had no specific TB infection-control programs in place.
What Do These Findings Mean?
As with all systematic reviews, the accuracy of these findings may be limited by some aspects of the original studies, such as how the incidence of LTBI was measured. In addition, the possibility that the researchers missed some relevant published studies, or that only studies where there was a high incidence of TB in HCWs were published, may also affect the findings of this study. Nevertheless, they suggest that TB is an important occupational disease in HCWs in LMICs and that the HCWs most at risk of TB are those exposed to the most patients with TB. Reduction of that risk should be a high priority because occupational TB leads to the loss of essential, skilled HCWs. Unfortunately, there are few data available to indicate how this should be done. Thus, the researchers conclude, well-designed field studies are urgently needed to evaluate whether the TB-control measures that have reduced TB transmission to HCWs in high-income countries will work and be affordable in LMICs.
Additional Information.
Please access these Web sites via the online version of this summary at
• US National Institute of Allergy and Infectious Diseases patient fact sheet on tuberculosis
• US Centers for Disease Control and Prevention information for patients and professionals on tuberculosis
• MedlinePlus encyclopedia entry on tuberculosis
• NHS Direct Online, from the UK National Health Service, patient information on tuberculosis
• US National Institute for Occupational Health and Safety, information about tuberculosis for health-care workers
• American Lung Association information on tuberculosis and health-care workers
PMCID: PMC1716189  PMID: 17194191
7.  Inactivation of Poxviruses by Upper-Room UVC Light in a Simulated Hospital Room Environment 
PLoS ONE  2008;3(9):e3186.
In the event of a smallpox outbreak due to bioterrorism, delays in vaccination programs may lead to significant secondary transmission. In the early phases of such an outbreak, transmission of smallpox will take place especially in locations where infected persons may congregate, such as hospital emergency rooms. Air disinfection using upper-room 254 nm (UVC) light can lower the airborne concentrations of infective viruses in the lower part of the room, and thereby control the spread of airborne infections among room occupants without exposing occupants to a significant amount of UVC. Using vaccinia virus aerosols as a surrogate for smallpox we report on the effectiveness of air disinfection, via upper-room UVC light, under simulated real world conditions including the effects of convection, mechanical mixing, temperature and relative humidity. In decay experiments, upper-room UVC fixtures used with mixing by a conventional ceiling fan produced decreases in airborne virus concentrations that would require additional ventilation of more than 87 air changes per hour. Under steady state conditions the effective air changes per hour associated with upper-room UVC ranged from 18 to 1000. The surprisingly high end of the observed range resulted from the extreme susceptibility of vaccinia virus to UVC at low relative humidity and use of 4 UVC fixtures in a small room with efficient air mixing. Increasing the number of UVC fixtures or mechanical ventilation rates resulted in greater fractional reduction in virus aerosol and UVC effectiveness was higher in winter compared to summer for each scenario tested. These data demonstrate that upper-room UVC has the potential to greatly reduce exposure to susceptible viral aerosols. The greater survival at baseline and greater UVC susceptibility of vaccinia under winter conditions suggest that while risk from an aerosol attack with smallpox would be greatest in winter, protective measures using UVC may also be most efficient at this time. These data may also be relevant to influenza, which also has improved aerosol survival at low RH and somewhat similar sensitivity to UVC.
PMCID: PMC2527528  PMID: 18781204
8.  Characterization of UVC Light Sensitivity of Vaccinia Virus▿  
Applied and Environmental Microbiology  2007;73(18):5760-5766.
Interest in airborne smallpox transmission has been renewed because of concerns regarding the potential use of smallpox virus as a biothreat agent. Air disinfection via upper-room 254-nm germicidal UV (UVC) light in public buildings may reduce the impact of primary agent releases, prevent secondary airborne transmission, and be effective prior to the time when public health authorities are aware of a smallpox outbreak. We characterized the susceptibility of vaccinia virus aerosols, as a surrogate for smallpox, to UVC light by using a benchtop, one-pass aerosol chamber. We evaluated virus susceptibility to UVC doses ranging from 0.1 to 3.2 J/m2, three relative humidity (RH) levels (20%, 60%, and 80%), and suspensions of virus in either water or synthetic respiratory fluid. Dose-response plots show that vaccinia virus susceptibility increased with decreasing RH. These plots also show a significant nonlinear component and a poor fit when using a first-order decay model but show a reasonable fit when we assume that virus susceptibility follows a log-normal distribution. The overall effects of RH (P < 0.0001) and the suspending medium (P = 0.014) were statistically significant. When controlling for the suspending medium, the RH remained a significant factor (P < 0.0001) and the effect of the suspending medium was significant overall (P < 0.0001) after controlling for RH. Virus susceptibility did not appear to be a function of virus particle size. This work provides an essential scientific basis for the design of effective upper-room UVC installations for the prevention of airborne infection transmission of smallpox virus by characterizing the susceptibility of an important orthopoxvirus to UVC exposure.
PMCID: PMC2074914  PMID: 17644645
9.  Dynamics of Airborne Influenza A Viruses Indoors and Dependence on Humidity 
PLoS ONE  2011;6(6):e21481.
There is mounting evidence that the aerosol transmission route plays a significant role in the spread of influenza in temperate regions and that the efficiency of this route depends on humidity. Nevertheless, the precise mechanisms by which humidity might influence transmissibility via the aerosol route have not been elucidated. We hypothesize that airborne concentrations of infectious influenza A viruses (IAVs) vary with humidity through its influence on virus inactivation rate and respiratory droplet size. To gain insight into the mechanisms by which humidity might influence aerosol transmission, we modeled the size distribution and dynamics of IAVs emitted from a cough in typical residential and public settings over a relative humidity (RH) range of 10–90%. The model incorporates the size transformation of virus-containing droplets due to evaporation and then removal by gravitational settling, ventilation, and virus inactivation. The predicted concentration of infectious IAVs in air is 2.4 times higher at 10% RH than at 90% RH after 10 min in a residential setting, and this ratio grows over time. Settling is important for removal of large droplets containing large amounts of IAVs, while ventilation and inactivation are relatively more important for removal of IAVs associated with droplets <5 µm. The inactivation rate increases linearly with RH; at the highest RH, inactivation can remove up to 28% of IAVs in 10 min. Humidity is an important variable in aerosol transmission of IAVs because it both induces droplet size transformation and affects IAV inactivation rates. Our model advances a mechanistic understanding of the aerosol transmission route, and results complement recent studies on the relationship between humidity and influenza's seasonality. Maintaining a high indoor RH and ventilation rate may help reduce chances of IAV infection.
PMCID: PMC3123350  PMID: 21731764
10.  The application of ultraviolet germicidal irradiation to control transmission of airborne disease: bioterrorism countermeasure. 
Public Health Reports  2003;118(2):99-114.
Bioterrorism is an area of increasing public health concern. The intent of this article is to review the air cleansing technologies available to protect building occupants from the intentional release of bioterror agents into congregate spaces (such as offices, schools, auditoriums, and transportation centers), as well as through outside air intakes and by way of recirculation air ducts. Current available technologies include increased ventilation, filtration, and ultraviolet germicidal irradiation (UVGI) UVGI is a common tool in laboratories and health care facilities, but is not familiar to the public, or to some heating, ventilation, and air conditioning engineers. Interest in UVGI is increasing as concern about a possible malicious release of bioterror agents mounts. Recent applications of UVGI have focused on control of tuberculosis transmission, but a wide range of airborne respiratory pathogens are susceptible to deactivation by UVGI. In this article, the authors provide an overview of air disinfection technologies, and an in-depth analysis of UVGI-its history, applications, and effectiveness.
PMCID: PMC1497517  PMID: 12690064
11.  Concentrations and size distributions of airborne influenza A viruses measured indoors at a health centre, a day-care centre and on aeroplanes 
The relative importance of the aerosol transmission route for influenza remains contentious. To determine the potential for influenza to spread via the aerosol route, we measured the size distribution of airborne influenza A viruses. We collected size-segregated aerosol samples during the 2009–2010 flu season in a health centre, a day-care facility and onboard aeroplanes. Filter extracts were analysed using quantitative reverse transcriptase polymerase chain reaction. Half of the 16 samples were positive, and their total virus concentrations ranged from 5800 to 37 000 genome copies m−3. On average, 64 per cent of the viral genome copies were associated with fine particles smaller than 2.5 µm, which can remain suspended for hours. Modelling of virus concentrations indoors suggested a source strength of 1.6 ± 1.2 × 105 genome copies m−3 air h−1 and a deposition flux onto surfaces of 13 ± 7 genome copies m−2 h−1 by Brownian motion. Over 1 hour, the inhalation dose was estimated to be 30 ± 18 median tissue culture infectious dose (TCID50), adequate to induce infection. These results provide quantitative support for the idea that the aerosol route could be an important mode of influenza transmission.
PMCID: PMC3119883  PMID: 21300628
influenza; bioaerosol; size distribution; aerosol transmission; emissions; deposition
12.  Aerosol Susceptibility of Influenza Virus to UV-C Light 
The person-to-person transmission of influenza virus, especially in the event of a pandemic caused by a highly virulent strain of influenza, such as H5N1 avian influenza, is of great concern due to widespread mortality and morbidity. The consequences of seasonal influenza are also substantial. Because airborne transmission appears to play a role in the spread of influenza, public health interventions should focus on preventing or interrupting this process. Air disinfection via upper-room 254-nm germicidal UV (UV-C) light in public buildings may be able to reduce influenza transmission via the airborne route. We characterized the susceptibility of influenza A virus (H1N1, PR-8) aerosols to UV-C light using a benchtop chamber equipped with a UVC exposure window. We evaluated virus susceptibility to UV-C doses ranging from 4 to 12 J/m2 at three relative humidity levels (25, 50, and 75%). Our data show that the Z values (susceptibility factors) were higher (more susceptible) to UV-C than what has been reported previously. Furthermore, dose-response plots showed that influenza virus susceptibility increases with decreasing relative humidity. This work provides an essential scientific basis for designing and utilizing effective upper-room UV-C light installations for the prevention of the airborne transmission of influenza by characterizing its susceptibility to UV-C.
PMCID: PMC3298127  PMID: 22226954
13.  Human Occupancy as a Source of Indoor Airborne Bacteria 
PLoS ONE  2012;7(4):e34867.
Exposure to specific airborne bacteria indoors is linked to infectious and noninfectious adverse health outcomes. However, the sources and origins of bacteria suspended in indoor air are not well understood. This study presents evidence for elevated concentrations of indoor airborne bacteria due to human occupancy, and investigates the sources of these bacteria. Samples were collected in a university classroom while occupied and when vacant. The total particle mass concentration, bacterial genome concentration, and bacterial phylogenetic populations were characterized in indoor, outdoor, and ventilation duct supply air, as well as in the dust of ventilation system filters and in floor dust. Occupancy increased the total aerosol mass and bacterial genome concentration in indoor air PM10 and PM2.5 size fractions, with an increase of nearly two orders of magnitude in airborne bacterial genome concentration in PM10. On a per mass basis, floor dust was enriched in bacterial genomes compared to airborne particles. Quantitative comparisons between bacterial populations in indoor air and potential sources suggest that resuspended floor dust is an important contributor to bacterial aerosol populations during occupancy. Experiments that controlled for resuspension from the floor implies that direct human shedding may also significantly impact the concentration of indoor airborne particles. The high content of bacteria specific to the skin, nostrils, and hair of humans found in indoor air and in floor dust indicates that floors are an important reservoir of human-associated bacteria, and that the direct particle shedding of desquamated skin cells and their subsequent resuspension strongly influenced the airborne bacteria population structure in this human-occupied environment. Inhalation exposure to microbes shed by other current or previous human occupants may occur in communal indoor environments.
PMCID: PMC3329548  PMID: 22529946
14.  Control of airborne infectious diseases in ventilated spaces 
Journal of the Royal Society Interface  2009;6(Suppl 6):S747-S755.
We protect ourselves from airborne cross-infection in the indoor environment by supplying fresh air to a room by natural or mechanical ventilation. The air is distributed in the room according to different principles: mixing ventilation, displacement ventilation, etc. A large amount of air is supplied to the room to ensure a dilution of airborne infection. Analyses of the flow in the room show that there are a number of parameters that play an important role in minimizing airborne cross-infection. The air flow rate to the room must be high, and the air distribution pattern can be designed to have high ventilation effectiveness. Furthermore, personalized ventilation may reduce the risk of cross-infection, and in some cases, it can also reduce the source of infection. Personalized ventilation can especially be used in hospital wards, aircraft cabins and, in general, where people are in fixed positions.
PMCID: PMC2843946  PMID: 19740921
airborne disease; cross-infection; ventilated spaces; room air distribution; indoor environment
15.  Source, significance, and control of indoor microbial aerosols: human health aspects. 
Public Health Reports  1983;98(3):229-244.
The usual profile of indoor microbial aerosols probably has little meaning to healthy people. However, hazardous microbial aerosols can penetrate buildings or be generated within them; in either case, they can have significant adverse effects on human health. These aerosols can be controlled to some extent by eliminating or reducing their sources. In this regard, careful consideration should be given in building construction to the design of ventilation and air-conditioning systems and to the flooring material, so that these systems and the flooring material will not act as microbial reservoirs. It is evident that in spite of the considerable body of data available on indoor microbial aerosols, little is known of their true significance to human health except in terms of overt epidemic disease. Continued research is needed in this area, particularly in respect to situations of high risk in such locations as hospitals and schools for young children.
PMCID: PMC1424447  PMID: 6867255
16.  Severe acute respiratory syndrome (SARS): lessons learnt in Hong Kong 
Journal of Thoracic Disease  2013;5(Suppl 2):S122-S126.
Many healthcare workers were infected while looking after the SARS patients on the medical wards in 2003. The high infectivity of the SARS coronavirus with peak viral load on day 10 of illness when patients were ill, overcrowding of the old medical wards with low air changes/hr (ACH), and aerosol-generating procedures while resuscitating the patients were the major factors. Procedures reported to present an increased risk of SARS transmission include tracheal intubation, non-invasive ventilation, tracheotomy and manual ventilation before intubation whereas oxygen therapy and bed distance <1 m were also implicated. Studies based on laser visualization technique with smoke particles as smokers in the human patient simulator has shown that oxygen therapy via Hudson mask and nasal cannula could disperse exhaled air of patients to 0.4 and 1 m respectively whereas jet nebulizer could disperse exhaled air >0.8 m from the patient. Bigger isolation rooms with 16 ACH are more effective than smaller isolation rooms with 12 ACH in removing exhaled air and preventing room contamination but at the expense of more noise and electricity consumption. Non-invasive ventilation via face masks and single circuit can disperse exhaled air from 0.4 to 1 m. Both higher inspiratory pressures and use of whisper swivel device (to facilitate carbon dioxide removal) could increase the exhaled air leakage and isolation room contamination during on-invasive ventilation. Addition of a viral-bacterial filter during manual ventilation by bagging may reduce the exhaled air leakage forward and yet increase the sideway leakage. N95 mask was more effective than surgical mask in preventing expelled air leakage during patient’s coughing but there was still significant sideway leakage to 15 cm. Clinicians should be aware of air leakage from the various face masks and adopt strict infection control measures during resuscitation of patients with severe respiratory infections. Carefully designed clinical trials are required to determine the optimal timing and dosage of any antiviral agents, convalescent plasma, and immuno-modulating agents in the treatment of the possibly immune-mediated lung injury in SARS and newly emerged infection such as the Middle East Respiratory Syndrome.
PMCID: PMC3747521  PMID: 23977432
Severe acute respiratory syndrome (SARS); management; lessons; Middle East Respiratory Syndrome (MERS)
17.  A ventilation intervention study in classrooms to improve indoor air quality: the FRESH study 
Environmental Health  2013;12:110.
Classroom ventilation rates often do not meet building standards, although it is considered to be important to improve indoor air quality. Poor indoor air quality is thought to influence both children’s health and performance. Poor ventilation in The Netherlands most often occurs in the heating season. To improve classroom ventilation a tailor made mechanical ventilation device was developed to improve outdoor air supply. This paper studies the effect of this intervention.
The FRESH study (Forced-ventilation Related Environmental School Health) was designed to investigate the effect of a CO2 controlled mechanical ventilation intervention on classroom CO2 levels using a longitudinal cross-over design. Target CO2 concentrations were 800 and 1200 parts per million (ppm), respectively. The study included 18 classrooms from 17 schools from the north-eastern part of The Netherlands, 12 experimental classrooms and 6 control classrooms. Data on indoor levels of CO2, temperature and relative humidity were collected during three consecutive weeks per school during the heating seasons of 2010–2012. Associations between the intervention and weekly average indoor CO2 levels, classroom temperature and relative humidity were assessed by means of mixed models with random school-effects.
At baseline, mean CO2 concentration for all schools was 1335 ppm (range: 763–2000 ppm). The intervention was able to significantly decrease CO2 levels in the intervention classrooms (F (2,10) = 17.59, p < 0.001), with a mean decrease of 491 ppm. With the target set at 800 ppm, mean CO2 was 841 ppm (range: 743–925 ppm); with the target set at 1200 ppm, mean CO2 was 975 ppm (range: 887–1077 ppm).
Although the device was not capable of precisely achieving the two predefined levels of CO2, our study showed that classroom CO2 levels can be reduced by intervening on classroom ventilation using a CO2 controlled mechanical ventilation system.
PMCID: PMC3893609  PMID: 24345039
Ventilation; Schools; Carbon dioxide; Indoor air quality; Intervention
18.  Building sickness syndrome in healthy and unhealthy buildings: an epidemiological and environmental assessment with cluster analysis 
OBJECTIVES—Building sickness syndrome remains poorly understood. Aetiological factors range from temperature, humidity, and air movement to internal pollutants, dust, lighting, and noise factors. The reported study was designed to investigate whether relations between symptoms of sick building syndrome and measured environmental factors existed within state of the art air conditioned buildings with satisfactory maintenance programmes expected to provide a healthy indoor environment.
METHODS—Five buildings were studied, three of which were state of the art air conditioned buildings. One was a naturally ventilated control building and one a previously studied and known sick building. A questionnaire was administered to the study population to measure the presence of building related symptoms. This was followed by a detailed environmental survey in identified high and low symptom areas within each building. These areas were compared for their environmental performance.
RESULTS—Two of the air conditioned buildings performed well with a low prevalence of building related symptoms. Both of these buildings out performed the naturally ventilated building for the low number of symptoms and in many of the environmental measures. One building (C), expected to perform well from a design viewpoint had a high prevalence of symptoms and behaved in a similar manner to the known sick building. Environmental indices associated with symptoms varied from building to building. Consistent associations between environmental variables were found for particulates (itchy eyes, dry throat, headache, and lethargy) across all buildings. There were persisting relations between particulates and symptoms (headache, lethargy, and dry skin) even in the building with the lowest level of symptoms and of measured airborne particulates (building B). There were also consistent findings for noise variables with low frequency noise being directly associated with symptoms (stuffy nose, itchy eyes, and dry skin) and higher frequency noise being relatively protective across all buildings.
CONCLUSIONS—This is the first epidemiological study of expected state of the art, air conditioned buildings. These buildings can produce an internal environment better than that of naturally ventilated buildings for both reported symptoms and environmental variables. The factors associated with symptoms varied widely across the different buildings studied although consistent associations for symptoms were found with increased exposure to particulates and low frequency noise.

Keywords: building sickness syndrome; particulates; low frequency noise
PMCID: PMC1740017  PMID: 10935944
19.  Indirect health effects of relative humidity in indoor environments. 
A review of the health effects of relative humidity in indoor environments suggests that relative humidity can affect the incidence of respiratory infections and allergies. Experimental studies on airborne-transmitted infectious bacteria and viruses have shown that the survival or infectivity of these organisms is minimized by exposure to relative humidities between 40 and 70%. Nine epidemiological studies examined the relationship between the number of respiratory infections or absenteeism and the relative humidity of the office, residence, or school. The incidence of absenteeism or respiratory infections was found to be lower among people working or living in environments with mid-range versus low or high relative humidities. The indoor size of allergenic mite and fungal populations is directly dependent upon the relative humidity. Mite populations are minimized when the relative humidity is below 50% and reach a maximum size at 80% relative humidity. Most species of fungi cannot grow unless the relative humidity exceeds 60%. Relative humidity also affects the rate of offgassing of formaldehyde from indoor building materials, the rate of formation of acids and salts from sulfur and nitrogen dioxide, and the rate of formation of ozone. The influence of relative humidity on the abundance of allergens, pathogens, and noxious chemicals suggests that indoor relative humidity levels should be considered as a factor of indoor air quality. The majority of adverse health effects caused by relative humidity would be minimized by maintaining indoor levels between 40 and 60%. This would require humidification during winter in areas with cold winter climates. Humidification should preferably use evaporative or steam humidifiers, as cool mist humidifiers can disseminate aerosols contaminated with allergens.
PMCID: PMC1474709  PMID: 3709462
20.  Potential for airborne transmission of infection in the waiting areas of healthcare premises: stochastic analysis using a Monte Carlo model 
BMC Infectious Diseases  2010;10:247.
Although many infections that are transmissible from person to person are acquired through direct contact between individuals, a minority, notably pulmonary tuberculosis (TB), measles and influenza are known to be spread by the airborne route. Airborne infections pose a particular threat to susceptible individuals whenever they are placed together with the index case in confined spaces. With this in mind, waiting areas of healthcare facilities present a particular challenge, since large numbers of people, some of whom may have underlying conditions which predispose them to infection, congregate in such spaces and can be exposed to an individual who may be shedding potentially pathogenic microorganisms. It is therefore important to understand the risks posed by infectious individuals in waiting areas, so that interventions can be developed to minimise the spread of airborne infections.
A stochastic Monte Carlo model was constructed to analyse the transmission of airborne infection in a hypothetical 132 m3 hospital waiting area in which occupancy levels, waiting times and ventilation rate can all be varied. In the model the Gammaitoni-Nucci equation was utilized to predict probability of susceptible individuals becoming infected. The model was used to assess the risk of transmission of three infectious diseases, TB, influenza and measles. In order to allow for stochasticity a random number generator was applied to the variables in the model and a total of 10000 individual simulations were undertaken. The mean quanta production rates used in the study were 12.7, 100 and 570 per hour for TB, influenza and measles, respectively.
The results of the study revealed the mean probability of acquiring a TB infection during a 30-minute stay in the waiting area to be negligible (i.e. 0.0034), while that for influenza was an order of magnitude higher at 0.0262. By comparison the mean probability of acquiring a measles infection during the same period was 0.1349. If the duration of the stay was increased to 60 minutes then these values increased to 0.0087, 0.0662 and 0.3094, respectively.
Under normal circumstances the risk of acquiring a TB infection during a visit to a hospital waiting area is minimal. Likewise the risks associated with the transmission of influenza, although an order of magnitude greater than those for TB, are relatively small. By comparison, the risks associated with measles are high. While the installation of air disinfection may be beneficial, when seeking to prevent the transmission of airborne viral infection it is important to first minimize waiting times and the number of susceptible individuals present before turning to expensive technological solutions.
PMCID: PMC2939637  PMID: 20727178
21.  Exposure to halogenated hydrocarbons in the indoor environment. 
The indoor environment has frequently been ignored as a significant source of exposure to air pollutants. To date there are a number of documented examples of levels of indoor air pollutants greatly exceeding those levels which commonly occur in the outdoor environment. Among these instances are airborne buildup of polynuclear aromatics and cadmium from cigarette smoke, lead from burning candles, and vinyl chloride from use of aerosols containing this substance as a propellant. These examples suggest that there may be additional sources of indoor air pollutants, particularly halogenated hydrocarbons from aerosol products, which have heretofore not been generally recognized as important. The present paper endeavors to review those instances where halogenated hydrocarbons in the indoor air environment may build up to concentrations of potential public health concern. These considerations may be especially relevant in future years as increasing efforts are being made to insulate buildings more efficiently as a means to conserve energy. The available data strongly suggest that halogenated hydrocarbons are an important class of air pollutants in the indoor environment and that their presence in the outdoor environment should also be carefully examined. In this regard, halogenated hydrocarbons in the outdoor environment may also contaminate indoor air spaces.
PMCID: PMC1475171  PMID: 1175557
22.  Modeling the airborne survival of influenza virus in a residential setting: the impacts of home humidification 
Environmental Health  2010;9:55.
Laboratory research studies indicate that aerosolized influenza viruses survive for longer periods at low relative humidity (RH) conditions. Further analysis has shown that absolute humidity (AH) may be an improved predictor of virus survival in the environment. Maintaining airborne moisture levels that reduce survival of the virus in the air and on surfaces could be another tool for managing public health risks of influenza.
A multi-zone indoor air quality model was used to evaluate the ability of portable humidifiers to control moisture content of the air and the potential related benefit of decreasing survival of influenza viruses in single-family residences. We modeled indoor AH and influenza virus concentrations during winter months (Northeast US) using the CONTAM multi-zone indoor air quality model. A two-story residential template was used under two different ventilation conditions - forced hot air and radiant heating. Humidity was evaluated on a room-specific and whole house basis. Estimates of emission rates for influenza virus were particle-size specific and derived from published studies and included emissions during both tidal breathing and coughing events. The survival of the influenza virus was determined based on the established relationship between AH and virus survival.
The presence of a portable humidifier with an output of 0.16 kg water per hour in the bedroom resulted in an increase in median sleeping hours AH/RH levels of 11 to 19% compared to periods without a humidifier present. The associated percent decrease in influenza virus survival was 17.5 - 31.6%. Distribution of water vapor through a residence was estimated to yield 3 to 12% increases in AH/RH and 7.8-13.9% reductions in influenza virus survival.
This modeling analysis demonstrates the potential benefit of portable residential humidifiers in reducing the survival of aerosolized influenza virus by controlling humidity indoors.
PMCID: PMC2940868  PMID: 20815876
23.  Inactivation of a Foodborne Norovirus Outbreak Strain with Nonthermal Atmospheric Pressure Plasma 
mBio  2015;6(1):e02300-14.
Human norovirus (NoV) is the most frequent cause of epidemic nonbacterial acute gastroenteritis worldwide. We investigated the impact of nonthermal or cold atmospheric pressure plasma (CAPP) on the inactivation of a clinical human outbreak NoV, GII.4. Three different dilutions of a NoV-positive stool sample were prepared and subsequently treated with CAPP for various lengths of time, up to 15 min. NoV viral loads were quantified by quantitative real-time reverse transcription PCR (RT-qPCR). Increased CAPP treatment time led to increased NoV reduction; samples treated for the longest time had the lowest viral load. From the initial starting quantity of 2.36 × 104 genomic equivalents/ml, sample exposure to CAPP reduced this value by 1.23 log10 and 1.69 log10 genomic equivalents/ml after 10 and 15 min, respectively (P < 0.01). CAPP treatment of surfaces carrying a lower viral load reduced NoV by at least 1 log10 after CAPP exposure for 2 min (P < 0.05) and 1 min (P < 0.05), respectively. Our results suggest that NoV can be inactivated by CAPP treatment. The lack of cell culture assays prevents our ability to estimate infectivity. It is possible that some detectable, intact virus particles were rendered noninfectious. We conclude that CAPP treatment of surfaces may be a useful strategy to reduce the risk of NoV transmission in crowded environments.
Importance  Human gastroenteritis is most frequently caused by noroviruses, which are spread person to person and via surfaces, often in facilities with crowds of people. Disinfection of surfaces that come into contact with infected humans is critical for the prevention of cross-contamination and further transmission of the virus. However, effective disinfection cannot be done easily in mass catering environments or health care facilities. We evaluated the efficacy of cold atmospheric pressure plasma, an innovative airborne disinfection method, on surfaces inoculated with norovirus. We used a clinically relevant strain of norovirus from an outbreak in Germany. Cold plasma was able to inactivate the virus on the tested surfaces, suggesting that this method could be used for continuous disinfection of contaminated surfaces. The use of a clinical strain of norovirus strengthens the reliability of our results as it is a strain relevant to outbreaks in humans.
Human gastroenteritis is most frequently caused by noroviruses, which are spread person to person and via surfaces, often in facilities with crowds of people. Disinfection of surfaces that come into contact with infected humans is critical for the prevention of cross-contamination and further transmission of the virus. However, effective disinfection cannot be done easily in mass catering environments or health care facilities. We evaluated the efficacy of cold atmospheric pressure plasma, an innovative airborne disinfection method, on surfaces inoculated with norovirus. We used a clinically relevant strain of norovirus from an outbreak in Germany. Cold plasma was able to inactivate the virus on the tested surfaces, suggesting that this method could be used for continuous disinfection of contaminated surfaces. The use of a clinical strain of norovirus strengthens the reliability of our results as it is a strain relevant to outbreaks in humans.
PMCID: PMC4311907  PMID: 25587014
24.  Bioaerosols of subterraneotherapy chambers at salt mine health resort 
Aerobiologia  2013;29(4):481-493.
Nowadays, an inhalation of naturally generated aerosols has again become a widely practiced method of balneological treatment of various respiratory diseases. The aim of this study was to characterize the microbial aerosol of subterraneotherapy chambers at the Bochnia Salt Mine Health Resort in southern Poland. The measurements were carried out using a 6-stage Andersen impactor over a period of 1 year in both indoor (i.e., two subterranean chambers, where curative treatments took place) and outdoor air. The maximum bacterial aerosol concentrations in the chambers reached 11,688 cfu/m3. In such interiors, a high-performance method of microbial contaminant reduction need be introduced, especially when large groups of young patients are medically cured. Respecting fungal aerosol, its average indoor concentration (88 cfu/m3) was significantly lower than outdoor level (538 cfu/m3). It confirms that ventilation system provides efficient barrier against this type of biologically active propagules. Among identified micro-organisms, the most prevalent indoors were Gram-positive cocci, which constituted up to 80 % of airborne microflora. As highly adapted to the diverse environments of its human host (skin, respiratory tract), they can be easily released in high quantities into the air. The number of people introduced into such subterranean chambers should be in some way limited. The analysis of microclimate parameters revealed that temperature and relative humidity influenced significantly the level of bacterial aerosol only. Hence, a constant control of these parameters should be scrupulously superintended at this type of subterranean premises.
PMCID: PMC3787802  PMID: 24098066
Air quality; Bioaerosol; Salt mine; Health resort; Subterraneotherapy
25.  Effect of negative air ions on the potential for bacterial contamination of plastic medical equipment 
In recent years there has been renewed interest in the use of air ionizers to control the spread of infection in hospitals and a number of researchers have investigated the biocidal action of ions in both air and nitrogen. By comparison, the physical action of air ions on bacterial dissemination and deposition has largely been ignored. However, there is clinical evidence that air ions might play an important role in preventing the transmission of Acinetobacter infection. Although the reasons for this are unclear, it is hypothesized that a physical effect may be responsible: the production of air ions may negatively charge items of plastic medical equipment so that they repel, rather than attract, airborne bacteria. By negatively charging both particles in the air and items of plastic equipment, the ionizers minimize electrostatic deposition on these items. In so doing they may help to interrupt the transmission of Acinetobacter infection in certain healthcare settings such as intensive care units.
A study was undertaken in a mechanically ventilated room under ambient conditions to accurately measure changes in surface potential exhibited by items of plastic medical equipment in the presence of negative air ions. Plastic items were suspended on nylon threads, either in free space or in contact with a table surface, and exposed to negative ions produced by an air ionizer. The charge build-up on the specimens was measured using an electric field mill while the ion concentration in the room air was recorded using a portable ion counter.
The results of the study demonstrated that common items of equipment such as ventilator tubes rapidly developed a large negative charge (i.e. generally >-100V) in the presence of a negative air ionizer. While most items of equipment tested behaved in a similar manner to this, one item, a box from a urological collection and monitoring system (the only item made from styrene acrylonitrile), did however develop a positive charge in the presence of the ionizer.
The findings of the study suggest that the action of negative air ionizers significantly alters the electrostatic landscape of the clinical environment, and that this has the potential to cause any Acinetobacter-bearing particles in the air to be strongly repelled from some plastic surfaces and attracted to others. In so doing, this may prevent critical items of equipment from becoming contaminated with the bacterium.
PMCID: PMC2873555  PMID: 20384999

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