Respiratory Protection for Healthcare Workers in the Workplace Against Novel H1N1 Influenza A: A Letter Report (2009)

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September 1, 2009 Thomas R. Frieden, M.D., M.P.H. Jordan Barab, M.A. Director Acting Assistant Secretary for Centers for Disease Control and Occupational Safety and Prevention Health, Department of Labor 1600 Clifton Road, NE Occupational Safety and Health Atlanta, GA 30333 Administration 200 Constitution Avenue, NW Room S2315 Washington, DC 20210 Dear Dr. Frieden and Mr. Barab: On behalf of the Institute of Medicine (IOM) Committee on Respira- tory Protection for Healthcare Workers in the Workplace Against Novel H1N1 Influenza A, we are pleased to report our conclusions and recom- mendations. At the request of the Centers for Disease Control and Pre- vention (CDC) and the Occupational Safety and Health Administration (OSHA) the Institute of Medicine convened this committee to provide recommendations regarding the necessary respiratory protection for healthcare workers in their workplace against novel H1N1 influenza A (nH1N1). The committee was also charged with considering, to the ex- tent feasible, the available evidence regarding the potential for exposure among healthcare workers; the groups of workers at highest risk; the de- grees of risk for various patient care activities; and the extent of knowl- edge of the virus’ transmissibility, severity, virulence, and potential to change. The committee was also asked to pay attention to current guid- ance documents on personal protective equipment (PPE), particularly those offered by the CDC and the World Health Organization (WHO) for both nH1N1 as well as seasonal influenza. The committee was not charged with considering the economic and logistical considerations re- garding PPE. The committee had significant concerns about the level of healthcare workers’ compliance with the use of PPE, recognizing the noteworthy controversy that exists regarding how compliance affects the clinical effectiveness of PPE, and therefore its relevance to clinical 1 

2 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS guideline decision making. More research is needed to better understand and address this issue. To accomplish its charge within the 8-week timeframe, the commit- tee held a 4-day meeting that included a day-and-a-half public workshop (Appendix A). Panel discussions focused on the current clinical experi- ence with nH1N1, influenza transmission, clinical and community stud- ies on preventing seasonal influenza or other respiratory virus transmission, risks to healthcare workers in various settings, the efficacy and effectiveness 1 of respirators and of medical masks, 2 and decision making in infection control. Additionally, 12 individuals provided com- ments during the public comment session. This report also benefits from the work of prior IOM committees and workshops that have examined issues related to PPE and to pandemic influenza (IOM, 2005a,b, 2006, 2007, 2008a,b). This report focuses on the scientific and empirical evidence regard- ing the efficacy of various types of personal respiratory protection tech- nologies as one measure to protect healthcare workers against nH1N1. The committee concludes that an emphasis is needed on implementing a range of strategies across all levels of the hierarchy of controls to mini- mize risk and decrease the number of healthcare workers and other pa- tients exposed to patients with suspected or confirmed nH1N1. The committee provides the following findings and recommendations and provides additional detail in the report that follows. Studies on influenza transmission show that airborne (inhalation) transmission is one of the potential routes of transmission. The commit- tee based its decisions on comparisons of the experimental evidence on the efficacy of respirators and medical masks and not on their effective- ness in the clinical setting due to the fact that the availability of data is quite limited on clinical effectiveness. Further, clinical effectiveness re- quires consideration of numerous implementation factors such as com- pliance and availability of supply. N95 respirators are documented to filter out 95 to 99 percent of relevant particles and have maximum effec- tiveness when properly fitted to the face of users through fit testing (Qian 1 Efficacy is defined as the extent to which a specific intervention produces a beneficial result under ideal circumstances. Effectiveness is defined as a measure of the accuracy or success of an intervention when carried out in an average clinical environment (PDR, 1995). 2 The committee uses the term medical masks to refer to procedure masks and surgical masks. Because of the wide variety in the types of masks referred to in the articles and presentations reviewed by the committee, the committee uses this term to encompass all types of masks used in healthcare facilities. 

LETTER REPORT 3 et al., 1998). Research results on the filtration and fit of medical masks show wide variation in penetration of aerosol particles (4 percent to 90 percent) and inadequate fit suggesting that the use of medical masks is unlikely to be effective against airborne transmission (Oberg and Brosseau, 2008). Medical masks are not designed to provide a tight seal to the face, and there was considerable evidence in laboratory studies of leakage of materials under and around the medical mask from the un- fitted margins. The committee found a paucity of studies comparing the clinical effectiveness of respirators versus medical masks in preventing the transmission of influenza viruses. Several studies are underway or in publication. Recommendation 1: Use Fit-Tested N95 Respirators Healthcare workers (including those in non-hospital settings) who are in close contact with individuals with nH1N1 influ- enza or influenza-like illnesses should use fit-tested N95 respi- rators or respirators that are demonstrably more effective as one measure in the continuum of safety and infection control efforts to reduce the risk of infection. • The committee endorses the current CDC guidelines and recommends that these guidelines should be con- tinued until or unless further evidence can be provided to the effect that other forms of protection or other guidelines are equally or more effective. • Employers should ensure that the use and fit testing of N95 respirators be conducted in accordance with OSHA regulations, and healthcare workers should use the equipment as required by regulations and em- ployer policies. Healthcare organizations and workers need consistent and clear nH1N1 guidelines that can be implemented across all healthcare facili- ties. The committee again acknowledges that many implementation is- sues factor into the policy decision-making process for PPE guidance, but the committee was not charged with considering these factors, which include cost, availability of equipment, and other considerations in the implementation of such guidance. For example, policies may be influ- enced by the degree to which healthcare workers are effectively immu- nized with nH1N1 influenza vaccines. 

4 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS It is not the intention of the committee to recommend that all health- care workers use N95 respirators, rather the use of respirators should be for those in initial contact with individuals presenting with unidentified febrile respiratory illnesses and those healthcare workers in close contact with individuals with confirmed or suspected nH1N1. The committee acknowledges that this recommendation, if implemented, could have broader implications for clinical practice, including seasonal influenza and other potential airborne infections; however, the committee was charged only with addressing respiratory protection issues related to nH1N1. As noted throughout the report, the committee emphasizes that respiratory protection is a critical component in the hierarchy of infection prevention and control strategies. The need for research in a number of areas was striking. Due to the lack of a strong and conclusive evidence base, the committee concluded that determination of the relative contribution of each route of influenza transmission is essential for long-term preparedness planning. Further, the committee concluded that a stronger evidence base is needed regard- ing the effectiveness of personal respiratory protection technologies in clinical settings as is the development of improved respiratory protection technologies for healthcare workers. Recommendation 2: Increase Research on Influenza Trans- mission and Personal Respiratory Protection CDC centers (e.g., National Institute for Occupational Safety and Health; National Center for Immunization and Respira- tory Diseases; National Center for Preparedness, Detection, and Control of Infectious Diseases), the National Institutes of Health, and other relevant federal agencies and private insti- tutions should fund and undertake additional research to • resolve the unanswered questions regarding the rela- tive contribution of various routes of influenza trans- mission, • fully explore the effectiveness of personal respiratory protection technologies in a variety of clinical settings through randomized clinical trials, and • design and develop the next generation of personal respiratory protection technologies for healthcare workers to enhance safety, comfort, and ability to per- form work-related tasks. 

LETTER REPORT 5 The committee appreciates the opportunity to provide input into the considerable efforts to prepare for nH1N1 that are ongoing at CDC and OSHA. We would be pleased to brief you and your staffs regarding the findings and recommendations provided in this letter report. Kenneth I. Shine, M.D., Chair M. E. Bonnie Rogers, Dr. P.H., Vice Chair Committee on Respiratory Protection for Healthcare Workers in the Workplace Against Novel H1N1 Influenza A 

6 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS BACKGROUND The risk of influenza to healthcare workers is not a new concern, but the ongoing experience with novel influenza A (nH1N1) makes this issue even more urgent. Among the many considerations for the health and well-being of healthcare workers is the question about what types of per- sonal protective equipment (PPE) (e.g., respirators, gloves, gowns, eye protection, and other equipment) are needed to fully protect these front- line workers. This report focuses on the scientific and empirical evidence regard- ing the efficacy of various types of personal respiratory protective equipment as one measure to protect healthcare workers against nH1N1. The committee was not charged to consider the many factors that may affect policy decisions for PPE guidance including economics, equip- ment supplies, vaccine availability, immunization status, 3 extent of PPE compliance, and logistical considerations in the implementation of such guidance (see Box 1). In this regard, the committee recognizes that while the appropriate choice of PPE may include consideration of worker com- pliance and that PPE comfort and design contribute to clinical effective- ness, the committee focused its examination solely on currently available data on the efficacy of protective respiratory equipment. Further, as dis- cussed below, the committee views PPE as one part of a set of infection control strategies to reduce the potential for nH1N1 infection in health- care workers. In 2008, the Institute of Medicine (IOM) released the report Prepar- ing for an Influenza Pandemic: Personal Protective Equipment for Healthcare Workers; it examined the research needs in PPE and recog- nized the many issues that need to be addressed to improve PPE use in an influenza pandemic (IOM, 2008b). That committee identified three areas in crucial need of research and policy action: (1) routes of influenza transmission, (2) emphasis on worker safety and the appropriate use of PPE, and (3) development and utilization of innovative PPE technologies and certification processes. That 2008 report, as well as other recent IOM 3 The committee acknowledges that vaccines will provide protection but noted the po- tential variability in immunization response as seen in a small study in the 1957 pandemic in which 35 percent of vaccinated healthcare workers developed influenza compared to 55 to 65 percent of unvaccinated healthcare workers (Blumenfeld et al., 1959). 

LETTER REPORT 7 BOX 1 Statement of Task In response to a request from the Centers for Disease Control (CDC) and Prevention and the Occupational Safety and Health Administration, an ad hoc committee of the Institute of Medicine (IOM) will conduct a study and issue a letter report to the CDC director and Assistant Secretary for Occupa- tional Safety and Health by September 1, 2009. The committee will provide recommendations regarding the necessary respiratory protection, as part of personal protective equipment (PPE), for healthcare workers in their work- place against the novel influenza A (nH1N1) virus. Issues to be addressed to the extent feasible given available evidence and within the timeline for this letter report include: the potential for exposure to the nH1N1 virus among healthcare workers, which groups of workers are at risk, which patient care activities pose a risk of exposure and what degree of risk, and what is known and what is unknown about transmissibility, severity and virulence of the cur- rent virus and how transmissibility might change. The committee will base its recommendations on the available current state of scientific and empirical evidence about nH1N1 virus, as well as its expert judgment. Economic and logistical considerations regarding PPE equipment will not be addressed in this letter report. In determining the appropriate respiratory protection for the U.S. healthcare workforce, attention will be given to the current PPE guid- ance documents offered by the CDC and by the World Health Organization for novel H1N1 influenza and for seasonal influenza. reports (IOM, 2005a,b, 2006, 2007, 2008a), served as a basis for this let- ter report, and the committee built on these efforts with information pro- vided at the workshop as well as from recent published literature and the committee’s expert judgment. Healthcare Workers: Defining the Scope of the Term More than 13.6 million workers in the United States were employed in the healthcare field in 2006 with approximately 35 percent employed in hospitals, 23 percent in nursing and residential care facilities; and 17 percent in offices of physicians (BLS, 2009). The 2008 IOM report de- fined healthcare workers to encompass all workers employed by private and public healthcare offices and facilities as well as those working in home healthcare and emergency medical services (IOM, 2008b). The definition also included health professional students who are working at or receiving instruction in healthcare facilities. For this letter report, the committee expanded on that definition to include individuals in profes- 

8 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS sional and support services (e.g., clinical laboratories); individuals in- volved in administration, patient care, and facilities management; and individuals working for private- and public-sector employers, those who are self-employed, and volunteers trained to provide systematic, regu- lated, and licensed healthcare services (including medical emergency responders). PPE in Perspective In the continuum of safety and infection prevention efforts in health- care facilities, PPE is one of many important components. Occupational safety and health measures have traditionally followed a hierarchy of controls—engineering controls, administrative and work practice con- trols, and PPE. Engineering and environmental controls (e.g., ventilation, negative-pressure rooms, isolation rooms) are considered the first line of defense as they are measures that protect or affect multiple workers and patients and do not rely on individual compliance. Administrative and work practice controls include the policies, standards, procedures, and practices established within an organization to limit hazardous exposures and improve worker safety (e.g., cohorting or isolating patients, hand hygiene, cough etiquette, worker immunization policies, training and education, and organizational commitment to creating and sustaining a culture of worker safety). Personal protective equipment includes respi- rators, gowns, gloves, eye protection, and hearing protection. All relevant work situations with the potential for infection risk (such as cleaning pa- tient rooms and delivery of food) must be considered in addition to direct care of the patients. The infection prevention and control precautions outlined by CDC’s Healthcare Infection Control Practices Advisory Committee provide a tiered approach based on routes of transmission (Siegel et al., 2007). The guidelines for airborne precautions call for a range of measures in addi- tion to standard precautions (gloves, gown, hand hygiene, etc.) including patient placement, personnel restrictions, exposure management, and individual respiratory protection measures of a fit-tested N95 or higher- level respirator. During its workshop, the committee heard about many potential en- vironmental and administrative controls that could be effective in reduc- ing the number of healthcare workers exposed to nH1N1. These would include such activities as innovative triage mechanisms for individuals 

LETTER REPORT 9 with influenza-like illnesses, separate waiting areas for such patients, and single patient rooms. At the individual level, responsibilities incumbent on the healthcare worker include the use of proper hand hygiene practices, appropriate use of PPE, and obtaining relevant immunizations offered by the employer, as well as adherence to work safety practices. Hand and respiratory hy- giene are examples of proven interventions that decrease the spread of infections. Unfortunately, evidence for compliance of healthcare workers with these measures indicates that these effective measures are signifi- cantly underused, as are most types of PPE (IOM, 2008b). Many factors have been identified as reasons for this underuse including lack of time, lack of ready access to equipment, concerns about interference with pa- tient care, and problems with comfort. The committee emphasizes that PPE needs to be viewed as one part of a continuum of controls to ensure worker and patient safety that range from engineering controls and administrative approaches to pharmaceu- tical measures (e.g., vaccines and antivirals) and personal protective equipment. Further, PPE components (e.g., eye protection, respirators) need to be seamlessly integrated into protective ensembles that effec- tively provide hazard protection for multiple routes of transmission (IOM, 2008a). Current Guidelines Regarding nH1N1 and Use of PPE by Healthcare Workers The committee carefully reviewed the current CDC and WHO infec- tion control guidelines (as well as other relevant guidelines) for health- care workers caring for patients with known or suspected nH1N1 (see Table 1) (CDC, 2009f; WHO, 2009a). These guidelines both recommend the use of hand hygiene, gloves, gowns, and eye protection, but most notably differ in the respiratory protection recommendations. CDC rec- ommends a fit-tested disposable N95 respirator or better for “all health- care personnel who enter the rooms of patients in isolation with confirmed, suspected, or probable novel H1N1 influenza” (CDC, 2009f). For emergency medical responders, the CDC recommends a fit-tested disposable N95 respirator for those workers “who are in close contact” with patients with confirmed or suspected nH1N1, for personnel 

10 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS TABLE 1 Summary of PPE Guidelines for Care of Patients with Novel H1N1 Influenza A Type of PPE—Guidelines Medical Eye Masks Gloves Gowns Protection Respirators Centers for Disease Control and Prevention Isolation precautions1: Stan- X X X X dard and contact precau- tions plus eye protection (N95) should be used for all pa- tient care activities for patients being evaluated or in isolation for novel H1N1 Respiratory protection: All healthcare personnel who enter the rooms of pa- tients in isolation with confirmed, suspected, or probable novel H1N1 in- fluenza should wear a fit- tested disposable N95 respirator or better World Health Organization Per droplet precautions, X when in direct contact with patients Per standard precautions, X3 X X X3 for procedures with a risk for splashes onto the face and body When performing aerosol- X X X X2 generating procedures When completing a nasal X3 X X X3 swab and nasal wash When collecting blood X X NOTE: Hand hygiene should be practiced consistently in all situations. 1 CDC guidelines recommend that patients with confirmed, probable or suspected cases of nH1N1 who present for care at healthcare facilities be placed into individual rooms with closed doors. 2 Types include EU FFP2 and U.S. NIOSH-certified N95 respirators. 3 Guidelines call for using face protection (either a medical mask and eye-visor or gog- gles, or a face shield). SOURCE: CDC, 2009f; WHO, 2009a. 

LETTER REPORT 11 “engaged in aerosol generating activities,” and for personnel involved in the “interfacility transfer” of patients with suspected or confirmed nH1N1 (CDC, 2009e). WHO recommends standard and droplet precau- tions (including a medical mask, gown, gloves, eye protection, hand hy- giene) for those working in direct contact with patients and additional precautions for aerosol-generating procedures including wearing a facial particulate respirator (WHO, 2009a). The WHO recommendations take into account the need for sustainability in a variety of countries and allow each country to put forward its own guidelines on the recommended level of protection based on a variety of factors. The recently released Canadian guidelines also provide a tiered ap- proach based on the current behavior of the virus, recommending N95 use for aerosol-generating procedures with direct patient contact only (PHAC, 2009a,b,c,d). The guidelines note an anticipation that only a mi- nority of the patients will need to be cared for at this level, recommend- ing the use of medical masks for direct patient interactions that do not include the potential for procedure-induced aerosol generation. Routine practices are recommended for indirect contact with nH1N1 influenza patients. The guidelines note that hand hygiene and respiratory hygiene should be practiced consistently in all situations. INFLUENZA A Overview of Influenza A Influenza is a serious respiratory illness caused by infection with in- fluenza type A or type B virus. Influenza infections peak during the win- ter months in each hemisphere. In addition to seasonal occurrences of influenza, outbreaks of influenza may result in a global pandemic. The risk of serious illness and death from seasonal influenza is highest at the extremes of age (e.g., among persons 65 years and older and children under 2 years of age) and persons with certain medical conditions. In the United States, an average epidemic season of influenza results in more than 36,000 deaths and 200,000 hospitalizations due to influenza-related causes (CDC, 2009c). Among influenza-related deaths, most of the ex- cess mortality occurs in persons 65 years and older, often from pneumo- nia (Lewis, 2006). 

12 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS Influenza viruses are RNA viruses with a segmented genome. Two influenza A virus subtypes and one influenza B virus have been circulat- ing since 1977, and winter peaks are typically seen. Seasonal influenza viruses mutate frequently and this antigenic drift is the reason why vac- cine formulations are changed annually. Current seasonal influenza vi- ruses consist of an H1N1 and an H3N2 subtype (subtypes are classified by the surface proteins of the virus called hemagglutinin [H] and neura- minidase [N]). In addition, a novel H1N1 influenza A virus (nH1N1) appeared in 2009. Thus, four different influenza virus strains (two H1N1, one H3N2, and one B virus) are currently circulating (CDC, 2009b; Fiore et al., 2009). Over the past 400 years at least 31 pandemics have been described; during the 20th century, pandemics occurred in 1918 (H1N1), in 1957 (H2N2) and in 1968 (H3N2) (Lazzari and Stohr, 2004). In contrast to influenza epidemics, pandemics occur more rarely, every 10 to 50 years (Kamps and Reyes-Terán, 2006). Of the three recent pandemics, the 1918 pandemic resulted in the highest mortality, causing an estimated 675,000 deaths in the United States and a total of 50 million or more deaths worldwide (HHS, 2009). In 1977, an H1N1 virus reappeared after a hiatus of 20 years without displacing the H2N2 strain. At that time, many young people under 23 years of age had no immunity to H1N1 vi- ruses and that age group was preferentially affected by influenza virus infections with strains of that subtype (HHS, 2009). Overview of Novel H1N1 Influenza A Geographic Spread In 2009, a novel influenza A (nH1N1) virus was detected among humans in Mexico in March 2009 and the first two cases of nH1N1 were identified in the United States in April 2009 (CDC, 2009j). The virus is a triple-reassortant influenza A (H1) of human, swine, and fowl origins from North America (Shinde et al., 2009). Since then the virus has spread worldwide and 71 percent of the circulating influenza is attribut- able to this strain (Olsen, 2009). The WHO declared an nH1N1 pan- demic on June 11, 2009. As of August 13, 2009, 177 countries and overseas territories and communities have reported over 180,000 labora- tory confirmed cases of nH1N1, with the majority of cases occurring in the Americas (WHO, 2009b). Over 1,799 deaths have been reported 

LETTER REPORT 13 worldwide. In the United States, 7,983 hospitalizations and 522 deaths associated with nH1N1 were reported to CDC as of August 21, 2009 (CDC, 2009a). Because relatively few people with respiratory illnesses are tested for nH1N1 infection and countries are no longer required to test and report individual cases, these numbers likely underestimate the true impact of this pandemic. This is particularly the case in determining the overall prevalence of infection and therefore determining the de- nominator for any calculation of mortality and morbidity rates. Novel H1N1 has emerged as the primary influenza virus in the Southern Hemisphere and in countries such as Australia, certain prov- inces have reported increased numbers of cases, increased emergency department volume, and increased illness severity (Australian Depart- ment of Health and Ageing, 2009). Summary data from earlier in the outbreak show the crude hospitalization ratios ranging from 3.4 to 8.9, and adjusted case fatality ratios ranging from 0.20 to 1.23 (Garske et al., 2009). Spectrum of Illness The spectrum of illness associated with nH1N1 is similar to that re- ported with seasonal influenza infection varying from asymptomatic to mildly symptomatic to severely ill. Most infected individuals exhibit mild, self-limiting influenza-like symptoms including fever, lethargy, and loss of appetite (see Table 2). Of note, diarrhea is reported as com- mon to nH1N1 infection while it is uncommon to seasonal influenza (Levine, 2009). Severe complications of influenza that have been re- ported in patients with nH1N1 include primary influenza pneumonia, secondary bacterial pneumonias, adult respiratory distress syndrome, and encephalopathy (children) (CDC, 2009g). To date, a small number of cases of viral resistance to oseltamivir (Tamiflu) have been reported and the virus appears to remain sensitive to zanamivir (Relenza) at this time (WHO, 2009b). 

14 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS TABLE 2 Comparison of Viral Signs and Symptoms Common Seasonal Cold Influenza Avian Influenza (coryza) (e.g., H3N2) (e.g., H5N1) nH1N1 Fever No/rare Common/high Common/high Common/high Malaise No Yes Yes Yes Myalgias No Yes Yes Yes Rhinorrhea Copious Mild Mild Mild Cough No Common Common Common Sore throat Mild Moderate to Moderate to Moderate to severe severe severe Diarrhea No Uncommon Common Common Morbidity Rarely Common Common Common (bed rest) Fatalities No Elderly, very All groups but Ages 25–49 young, those with predominance in underlying illness < 50 years SOURCE: Levine, 2009; Perez-Padilla et al., 2009. Populations at Risk Specific populations seemingly at higher risk for nH1N1 inflection include children and young adults, pregnant women, and those with chronic illnesses and immunocompromised states (CDC, 2009d; Fiore, 2009). nH1N1 influenza differs from seasonal influenza most notably in terms of the ages of the populations at highest risk. Case rates are highest in individuals less than 49 years old (see Table 3). For seasonal influ- enza, persons 65 years and older account for 60 percent of influenza- related hospitalizations as compared to 5 percent of nH1N1 related hos- pitalizations. In addition, 8 percent of nH1N1-related deaths occurred among persons 65 years and older compared to 90 percent of seasonal influenza-related deaths (National Center for Immunization and Respira- tory Diseases, 2009). As of July 2009, the median age for individuals hospitalized with laboratory-confirmed nH1N1 was 20 years and the me- dian age of individuals who died with nH1N1 infection was 37 years. 

LETTER REPORT 15 TABLE 3 Case Rate and Hospitalization Rate per 100,000 Population by Age Group of Laboratory-Confirmed nH1N1 in the United States Age (years) Case Rate Hospitalization Rate 0–4 22.9 4.5 5–24 26.7 2.1 25–49 6.97 1.1 50–64 3.92 1.2 ≥ 65 1.3 1.7 SOURCE: Fiore, 2009. Conclusions Review of data regarding the epidemiology of nH1N1 influenza in the United States and in countries in the Southern Hemisphere indicates no antigenic change thus far in the virus and does not suggest any major change in virulence. The committee heard testimony about specific popu- lations in intensive care units with high mortality in both the United States and Australia. However, the aggregate data at this time do not demonstrate mortality more excessive than with seasonal influenza. The interpretation of the data however is subject to variability dependent upon the ascertainment of the total number of infected individuals and deaths. The U.S. experience at the present time is limited to a spring and summer outbreak, not the usual time for influenza, and therefore does not provide the complete view of the potential impact of nH1N1. It is impor- tant to note that CDC has stopped collecting information on individual nH1N1 cases. Current evidence indicates that the nH1N1 virus does not contain specific genes thought to contribute to virulence in humans that have been present in some other pandemic strains. However, it is a novel virus that enters populations in which many members, particularly younger people and children, have no previous immunity to its antigens. It is this lack of immunity that makes the younger population so susceptible to infection, morbidity, and mortality. This is in contrast to other seasonal influenza strains that have particularly affected elderly and very young individuals. Younger healthcare workers will be particularly susceptible 

16 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS to infection from the nH1N1 virus until an effective vaccine becomes available. INFLUENZA TRANSMISSION Human transmission of influenza virus is thought to primarily occur by three routes: (1) contact exposure in which the virus is transferred by direct physical contact between an infected and uninfected individual or indirectly through fomites (contaminated objects or surfaces) and subse- quent hand to face contact; (2) droplet spray exposure through the direct projection by coughing or sneezing of respiratory fluid particles with diameters greater than 100 μm; and (3) airborne (inhalation) exposure. Because large droplets settle rapidly from air, exposure to droplet spray requires close contact with the influenza patient; for airborne exposure the virus is carried both on smaller respirable 4,5 particles that can pene- trate to and deposit in the alveolar region and inhalable particles that de- posit in the tracheobronchial and nasopharyngeal airway regions. With most respiratory pathogens, including influenza, the relative contribution of each of these types of transmission has not been adequately ascer- tained. Adding to the uncertainty, the respective proportions may vary with the setting, with the temperature and humidity, with the intensity of virus emission, and with infectivity of the virus (the probability of infec- tion per virus) when received via different exposure routes (Nicas and Jones, 2009). Data are limited on the distances that respiratory fluid par- ticles of various sizes travel through the air before settling. Further, even for a single particle size, the distance traveled is expected to vary with the force of the expiratory event, the angle of emission relative to the floor, and air turbulence conditions. Future studies may have difficulty quantifying the relative impor- tance of each potential route of transmission, especially due to limita- tions with controlled human experiments. Consequently, mathematical modeling and analysis have the potential to improve knowledge of hu- man-to-human transmission of influenza virus. In this vein, mathematical 4 Respirable particles include both the small particles associated with coughing, sneez- ing, and breathing as well as the larger particles which dessicate into smaller particles known as droplet nuclei. 5 The committee used the standardized categorization regarding particle size and depo- sition: inhalable (particles inhaled through the nose and/or mouth during breathing), tho- racic (the subfraction of inhalable which penetrates into the lung below the larynx), and respirable (the subfraction of inhalable which penetrates down to the alveolar region). 

LETTER REPORT 17 models have been developed to help estimate the relative contribution of each exposure pathway. These models consider the existing knowledge base regarding virus concentrations, frequency and size of particles gen- erated in coughs and sneezes, gravitational and decay characteristics of these particles, and role of humidity and ventilation. Nicas and Jones found “influenza A transmission in natural settings may involve multiple exposure pathways, although the relative contribution of each pathway is situation-specific and depends on a set of factors that will be unknown a priori” (Nicas and Jones, 2009). They therefore concluded that non- pharmaceutical interventions for pandemic virus must address all poten- tial routes of exposure. In contrast, Atkinson and Wein found aerosol transmission to be more dominant than contact transmission (Atkinson and Wein, 2009). This letter report is focused solely on airborne exposures that would require respiratory protection. Respirable particles settle slowly from air and are able to disperse throughout the room. Thus, inhalation exposure to respirable particles does not require close contact with an influenza patient, although exposure intensity is higher close to the patient. Large droplet particles settle more rapidly from air and do not disperse throughout the room. Thus, exposure to these particles tends to require close contact with the influenza patient, although there is a continuum of distances traveled from the point of emission depending on particle size. Evidence from environmental and animal studies has supported the role of airborne exposure in the transmission of influenza virus. The 2008 IOM report reviewed research on airborne transmission including animal studies on influenza transmission and observational studies on the effects of ultraviolet light and air circulation (IOM, 2008b). Newer stud- ies published since the 2008 IOM report provide additional evidence re- garding airborne transmission. For example, Fabian and colleagues (2008) showed that persons ill with influenza A (and B) emit the virus as respirable-size particles in exhaled breath and in coughs. In a study using stationary and personal sampling and measurement in a healthcare clinic attended by patients with influenza A (and B), researchers confirmed the presence of the airborne influenza virus in various clinic locations and in the breathing zones of healthcare workers, with more than fifty percent of detectable virus particles in the respirable range (Blachere et al., 2009). Mubareka and colleagues (2009) found that guinea pigs infected with the influenza A virus (H3N2) can efficiently transmit the infection to susceptible guinea pigs via inhalation, presumably by virus carried on respirable particles (Mubareka et al., 2009). Other recent studies show 

18 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS that ferrets infected with nH1N1 virus transmitted the infection to sus- ceptible animals via inhalation. Inhalation transmission was less efficient compared to a seasonal H1N1 virus in the study by Maines and col- leagues (2009) but was found to be efficient in the second study (Mun- ster et al., 2009). Current evidence supports airborne exposure as likely being one of the routes of nH1N1 virus transmission in healthcare settings absent ap- propriate exposure control measures. This does not preclude transmission by the droplet spray and contact routes absent appropriate control meas- ures. Therefore, the committee concluded that recent animal and envi- ronmental studies have demonstrated the importance of airborne transmission of nH1N1 virus; however, the relative contribution of each of the possible routes of transmission is yet to be determined. Without knowing the contributions of each of the possible route(s) of transmis- sion, all routes must be considered probable and consequential. TRANSMISSION RISKS FOR HEALTHCARE WORKERS Although much remains to be learned about the routes of nH1N1 transmission and about which medical procedures and types of interac- tions will result in high-risk exposures to healthcare workers, the virus is known to pose hazards in healthcare facilities and to healthcare workers because of its short incubation period, patient infectivity prior to clinical symptoms, variability of viral shedding among different hosts, multiple routes of transmission, and efficient spread from person to person. While it is widely assumed that aerosol-generating procedures increase the ex- posure risk to healthcare workers, data about procedural risks are cur- rently lacking. Nevertheless, there is evidence that work-related exposures to patients infected with nH1N1 virus result in healthcare workers becoming infected (CDC, 2009h; Perez-Padilla et al., 2009). More needs to be learned about the significance and impact of transmis- sion of influenza in a variety of healthcare settings. Several patient populations would be of particular concern during an nH1N1pandemic, and their care may pose increased risk of exposure to healthcare workers. Prevalence appears highest in children, youth, and young adults, the latter group being part of the healthcare workforce. Healthcare workers may be hesitant to come to work during a pandemic 

LETTER REPORT 19 if they do not feel adequately protected and confident in the facility’s ability to safely meet demands for patient care (Irvin et al., 2008). Under the Occupational Safety and Health Act, employers are re- quired to provide a workplace free from recognized hazards and to take feasible steps to protect workers from those hazards (Public Law 91- 596). Healthcare organizations and workers need consistent and clear nH1N1 guidelines that can be implemented across all healthcare facili- ties. In addition, employers must devote significant effort to assessing risk in their organization and to fully implementing those guidelines so needed practices are widely adopted. This should include ongoing educa- tion and training of healthcare workers. Employers should make special efforts to provide a place where workers can get questions answered and concerns addressed. Worker adherence and protection can be enhanced if individuals believe that the guidelines are derived from the best available evidence. Although workers are aware of expert guidance and the risk they face, they often do not wear PPE when faced with conditions requiring its use. Such noncompliance is also seen in low rates of hand hygiene and use of gloves, respirators, and eye protection. To improve the com- pliance rates and thereby improve worker protection, a “culture of safety” for workers must be established in all healthcare organizations evidenced by senior leadership commitment. America’s healthcare insti- tutions need to create, foster, and act as a role model of a culture of worker safety that is akin to the commitment made to patient safety. This culture of worker safety will require an emphasis on planning, education, equipment, materials, organization, bed spacing, patient isolation, and many other factors that focus on maximizing worker and patient safety. Employees should feel uncomfortable when not wearing PPE during ap- propriate situations, and supervisors should reinforce the importance of PPE and enforce policies so that noncompliance is a rare exception rather than the rule (IOM, 2008b). The committee heard testimony that strong institutional commit- ments to safety may minimize absenteeism, particularly during a pan- demic, although available data, particularly from the SARS (severe acute respiratory syndrome) experience suggest that healthcare workers are highly motivated to come to work in the face of uncertain risk when they believe that their contributions to patient care are critical and that they will be protected. It is recognized that such actions will not prevent healthcare workers from becoming infected in the community through activities unrelated to their jobs. 

20 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS EFFICACY OF RESPIRATORS AND MEDICAL MASKS The two major issues with regard to assessing the efficacy of respira- tory protection measures are the effectiveness of the filter and the extent to which the respirator has a tight seal with the wearer’s face that re- stricts inward leakage. Respirators are personal protective devices that cover the nose and mouth (or in some cases, more of the face and head) and operate either by purifying the air inhaled by the wearer through fil- tering materials or by independently supplying breathable air to the wearer. To be optimally effective, most types of respirators require a tight facial seal, thus individual fit testing is required. In the healthcare setting, medical masks are loose-fitting facial cov- erings that are designed to prevent wound contamination in the patient from the cough or exhaled secretions of the physician, nurse, or other healthcare worker. As noted in the 2008 IOM report, medical masks are not designed or certified to protect the wearer from exposure to airborne hazards (IOM, 2008b). They may offer some limited, as yet largely unde- fined, protection as a barrier to splashes and droplet spray. However, be- cause of the loose-fitting design of medical masks (and consequent leakage around the sides) and their lack of protective engineering, medi- cal masks are not considered personal respiratory protective equipment. Both respirators and medical masks may act as a barrier to the spread of droplets and to contact transmission that might occur when hands touch the nose or mouth, but the committee did not examine these routes of exposure. The National Institute for Occupational Safety and Health (NIOSH) certifies the filtering performance of respirators, 6 but the Food and Drug Administration (FDA) has no similar certification process for medical masks. Healthcare facilities are required to purchase NIOSH-certified respirators to comply with OSHA regulations when protecting workers against inhalation of airborne hazards. FDA examines submissions of data on medical masks and can provide market clearance for medical masks. There are no regulatory requirements for healthcare facilities ne- cessitating purchase of FDA-cleared medical masks. Recent studies have strengthened the evidence that respirators afford greater protection against respirable particles than medical masks. Stud- ies comparing the filtering efficacy of medical masks and certified N95 6 N95 respirators cleared by FDA for use in the healthcare setting are called surgical N95 respirators. These devices are also NIOSH certified to meet the N95 respirator per- formance requirements (FDA, 2009). 

LETTER REPORT 21 respirators have found consistently high filtering capacity of N95 respira- tors and a wide range of filtering performance by medical masks (Qian et al., 1998; Oberg and Brosseau, 2008; Rengasamy et al., 2008, 2009). N95 respirators are tested as part of the NIOSH certification process to determine if they meet the criteria to filter out at least 95 percent of parti- cles that are 0.3 µm in size (42 CFR Part 84). Studies by Lee and col- leagues (2008) and Balazy and colleagues (2006) used aerosols of similar particle size range to bacteria and viruses (0.04–1.3 µm) and found that while some N95 respirators allowed slightly greater than 5 percent parti- cle penetration, they had protection factors that were 8 to 12 times greater than those of medical masks. A recent study of nine types of medical masks by Oberg and Brosseau (2008) found wide variations in particle penetration (4 percent to 90 percent) through medical mask fil- ters. The study also found that the majority of the medical masks failed the qualitative fit tests and all failed the quantitative fit tests. At the workshop, discussion focused on filtration principles that show that the aerodynamic behavior of an aerosol particle is based on its size, density, and shape (i.e., a 0.3 µm latex sphere behaves in a similar manner to a particle of the same size, density, and shape that may carry a virus). Using particles less than 1 µm, a study of total leakage through medical masks worn by 25 subjects found that the contribution to total leakage into the medical mask was 5 percent to 8 percent from filter leakage and 25 to 38 percent from faceseal leakage (Grinshpun et al., 2009). In that study, N95 respirator contribution to total leakage was less than 1 percent from filter leakage and 3 to 5 percent from faceseal leakage. One of the important issues in the discussion of medical masks ver- sus respirators has been the issue of comfort and wearability. A study on worker tolerance for wearing respiratory protective devices over the course of an 8-hour work shift demonstrated that a variety of medical masks and respirators (N95 filtering facepiece, elastomerics, and pow- ered air-purifying respirators) were all poorly tolerated (Radonovich et al., 2009b). The study noted the progressive decline over the workday in the utilization of medical masks, N95 respirators, and powered air- purifying respirators with not more than 30 percent of workers wearing these devices throughout the 8-hour working day. A range of issues was reported including discomfort, difficulty speaking and communicating, and a number of physical complaints. A federal interagency effort (Pro- ject BREATHE—Better Respirator Equipment Using Advanced Technologies for Healthcare Employees) is focused on specifying per- 

22 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS formance criteria for improvements in respirators for healthcare workers (Radonovich et al., 2009a). Data are quite limited that could inform decisions regarding other types of respirators that healthcare workers should be provided. Despite the apparent differences in filtering efficiency (95 percent, 99 percent, and 100 percent), all tight fitting half-face negative pressure air purifying respirators (including filtering facepiece respirators like N95s, N99s and P100s, along with all half-mask elastomeric respirators equipped with either N95, N99, and P100 filter cartridges) are assigned the same pro- tection factor 7 by OSHA. NIOSH-certified respirators with N95 filters will filter between 95 and 99 percent of the most penetrating aerosols (0.3 µm). Further, as with N95 respirators, the majority of particle pene- tration in the N99 and P100 respirators comes from facepiece leakage. The committee did not identify any data from clinical trials comparing the efficacy of N95 respirators to that of N99 or other respirators with superior filtering efficacy and similarly did not find comparisons of res- pirator protection during various clinical procedures including aerosol- generating procedures. Some healthcare facilities have used respiratory protection devices with higher levels of protection, such as powered air purifying respirators, during aerosol generating procedures. Current CDC guidelines and OSHA requirements both indicate that fit testing is required when using an N95 respirator. The committee re- viewed evidence that while some medical masks have filter efficiencies that approach N95 respirators, the major difference is that they do not make a tight seal to the face. The purposes of fit testing are to ensure a properly fitted respirator that minimizes facepiece leakage and to provide the user with education on how to maintain a tight seal of a respirator essential for efficacious function. As discussed in the 2008 IOM report, ongoing research is needed to standardize fit test methodologies and to develop technologies for the production of more effective and consistent faceseals for respirators (IOM, 2008b). Ongoing efforts are exploring a number of design and reusability is- sues associated with the use of medical masks and respirators. NIOSH is proposing the addition of tests of total inward leakage for filtering facepiece respirators to the respirator certification process. An additional issue noted by the committee was the need for clear and consumer- friendly measures to permit comparison of the characteristics and testing 7 For this type of respirator, the assigned protection factor is 10, a measure of the ratio of the concentration of the contaminant outside the respirator to the concentration of the contaminant inside the respirator. 

LETTER REPORT 23 data on respirators. If testing data of a similar rigorous nature becomes available for medical masks, then consumer-oriented approaches to dis- seminating that data would also be beneficial. Although this report is focused on studies relevant to healthy health- care workers wearing a medical mask or respirator to prevent the devel- opment of influenza, it is important to note that there are data in a small number of studies that support the effectiveness of medical masks and respirators as source control (i.e., worn by patients) to prevent transmis- sion from ill patients to healthcare workers or other patients (Inouye et al., 2006; Johnson et al., 2009). Medical masks for source control may decrease transmission occurring through droplets and other larger parti- cles or materials, although not significantly decreasing airborne trans- mission. Further research on their use in patients is needed. CLINICAL STUDIES OF MEDICAL MASKS AND RESPIRATOR USE IN PREVENTING RESPIRATORY DISEASE Few data are available on the clinical effectiveness of medical masks and respirators in preventing the transmission of respiratory disease vi- ruses; thus, this is an area needing further research. The 2008 IOM study examined studies on the use of respirators and medical masks in prevent- ing respiratory syncytial virus transmission and transmission of SARS (severe acute respiratory syndrome) and found mixed results (IOM, 2008b). Recent reviews of physical interventions to prevent or slow the spread of respiratory viruses have noted the limited state of clinical evi- dence on comparison of medical masks and N95 respirators and the ab- sence of randomized controlled clinical trials (Jefferson et al., 2008; Lee and Umscheid, 2009). Observational studies on the use of medical masks have noted reductions in respiratory disease outbreaks in which medical masks were used as one part of a set of interventions (Weinstock et al., 2000; Jefferson et al., 2008); however, conclusions cannot be drawn as the effects of PPE cannot be separated from the confounding effects of other infection control measures. A recent study of the 2009 outbreak of nH1N1 in Mexico reported that after the strict enforcement of infection control measures (e.g., patient isolation; use of N95 respirators, goggles, gowns, and gloves; liberal use of hand sanitizer) in hospitals treating pa- tients with the nH1N1 virus, no additional healthcare workers contracted influenza-like illness (Perez-Padilla et al., 2009) . 

24 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS The committee found that several studies are being reviewed that might provide additional insights into questions regarding respiratory protection and influenza transmission. Information on these studies was available through conference abstracts or presentations at the workshop. A community study by Aiello and colleagues focused on college students living in dormitories who were randomized to wear medical masks only or to use hand hygiene plus medical masks during two winter seasonal influenza seasons. In year 1, both intervention groups showed reduced influenza-like illness versus controls. In year 2, the group using medical masks and hand hygiene had reductions in PCR-positive influenza (Aiello and Monto, 2009). Cowling and colleagues in a recently pub- lished paper described a randomized trial that assessed secondary infec- tions in families with a single index child ill with influenza (Cowling et al., 2009). In a subset of the households, those where the intervention was started within 36 hours of initial symptoms in the index patient, a reduction in infections for those using medical masks and hand hygiene was noted. However, because the index case was also encouraged to wear a medical mask, one cannot discern a protective effect of the medi- cal mask as a personal protective device versus its role in source control. A cluster-randomized clinical trial in a community setting examined use of P2 respirators (similar to N95 respirators) and medical masks worn by well parents of a child sick with an influenza-like illness (MacIntyre et al., 2009a). This study showed no effect by intention-to-treat analysis but a reduction in risk of infection by 60 to 80 percent in subjects with either medical mask or respirator use was noted. The study was not powered to examine the difference between medical masks and P2 respirators and the effect was seen for all devices combined. Two studies in healthcare workers are submitted for publication. MacIntyre and colleagues (2009b) conducted a cluster randomized clini- cal trial to compare the clinical efficacy of medical masks versus N95 respirators with and without fit testing, versus control in influenza trans- mission in 1,936 healthcare workers in China. N95 respirators were found to have statistically significant efficacy of 60 percent against clini- cal respiratory illness, 75 percent against influenza-like illness, 56 per- cent against laboratory-confirmed respiratory viral infection, and 75 percent against confirmed influenza. Medical masks showed no efficacy. In a randomized trial in Canada of 446 individual nurses working in acute care institutions randomized to fit tested N95 respirators versus masks during the 2008–2009 influenza season, medical masks were 

LETTER REPORT 25 found to be noninferior to the respirators. 8 However, without having the full details of the studies the committee could not draw conclusions from either study. Clinical effectiveness data are thus quite limited and con- flicting at this time, and the committee in its recommendations urges fur- ther randomized clinical trials be conducted to explore the types and combinations of PPE that will be effective as one component of strate- gies to prevent influenza transmission in healthcare workers. FACTORS IN DECISIONS ON RESPIRATORY PROTECTION At its workshop the committee heard several perspectives on deci- sion-making strategies all of which emphasized the importance of focus- ing on the hierarchy of controls in ensuring a safe work environment. Rather than focusing to such a large extent on PPE that is subject to variations in individual use, the speakers urged environmental and ad- ministrative strategies to minimize the number of healthcare workers (and patients) potentially exposed to nH1N1, such as innovative triage approaches and cohorting. In general, a risk management approach is used in infection control that focuses on identifying the hazard, assessing the risk, mitigating the risk through appropriate interventions, and subse- quently monitoring and reviewing the effect of the interventions in two constituent groups—patients and healthcare workers. The degree of pro- tection or the choice of PPE is determined by the degree of risk to the healthcare worker (OSHA, 2009). Based on its expert judgment, the committee identified a number of factors that affect the degree of risk including the characteristics of the virus, the healthcare worker’s condi- tion, the work environment, the patient’s condition, and the patient– worker encounter (see Box 2). In examining the many issues regarding selecting the appropriate personal protection for healthcare workers exposed to nH1N1, the com- mittee recognized the breadth and importance of issues that factor into these decisions and the many questions that remain largely unknown. The committee was tasked with examining the factors related to the 8 Personal communication with M. Loeb, McMaster University, August 20, 2009. 

26 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS transmission of the virus and the efficacy of personal respiratory protec- tive technologies, but it was not tasked with considering the economic and logistical implications, the extent of healthcare workers’ individual factors (e.g., age, immunization status), or compliance issues. BOX 2 Risk Factors and Issues That Affect PPE Decisions Virus Characteristics: • Nature of the hazard—virulence, disease severity, lethality, life (longevity) • Routes of transmission • Ease of transmission The Healthcare Worker: • Natural immunity and immunization status • Age • Underlying health conditions • Personal risk factors (e.g., chronic diseases and personal habits) • Immunoprophylaxis • Compliance with PPE Work Environment: • Setting (e.g., hospital, emergency medical services, direct care) • Volume of patients • Source control • Ambient conditions • Virus load profile • PPE comfort and wearability • Isolation, cohorting, and other environmental and administrative controls The Patient: • Age • Super-shedder, super-spreader • Underlying health conditions/symptoms • Personal risk factors (e.g., chronic diseases and habits) 

LETTER REPORT 27 RECOMMENDATIONS On the basis of input from the IOM workshop, previous IOM reports, the expert judgment of the committee members, and review of the litera- ture, the committee provides the following recommendations. Respiratory Protection The committee’s task focused solely on personal respiratory protec- tion. Studies on influenza transmission show that airborne transmission is one of the potential routes of transmission. Research is needed to deter- mine the relative contribution of the transmission pathways. Given the limited information on routes of transmission, the committee found that respiratory protection is indicated at this time. Evidence from NIOSH staff and other researchers provide convinc- ing data on the ability of N95 respirators to filter out 95 to 99 percent of relevant particles and these devices have their maximum effectiveness when properly fitted to the face of users. Research results on the filtra- tion and fit of medical masks show wide variation in penetration of aero- sol particles (4 percent to 90 percent) suggesting that the use of many of these masks is unlikely to be effective to protect against airborne trans- mission. Additionally, there was considerable evidence in laboratory studies of an order of magnitude higher leakage of particles under and around the medical mask from the unfitted margins than respirators. However, it is important to note that controversy exists regarding clinical guideline decision making in regards to the clinical effectiveness of medical masks. That is, some experts assert that factors including worker compliance may significantly affect the clinical effectiveness of various personal respiratory protection technologies and therefore have implica- tions for appropriate clinical guidelines. The committee found a paucity of studies on the clinical effectiveness of respirators versus medical masks for influenza. Several studies are underway or in publication. The few studies available in abstract form or presented at the conference showed mixed results. The committee bases its recommendation on the evidence of airborne transmission and the filtering and fit characteristics of N95 respirators compared to that of medical masks. 

28 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS Recommendation 1: Use Fit-Tested N95 Respirators Healthcare workers (including those in non-hospital settings) who are in close contact with individuals with nH1N1 influ- enza or influenza-like illnesses should use fit-tested N95 respi- rators or respirators that are demonstrably more effective as one measure in the continuum of safety and infection control efforts to reduce the risk of infection. • The committee endorses the current CDC guidelines and recommends that these guidelines should be con- tinued until or unless further evidence can be provided to the effect that other forms of protection or other guidelines are equally or more effective. • Employers should ensure that the use and fit testing of N95 respirators be in accordance with OSHA regula- tions, and healthcare workers should use the equip- ment as required by regulations and employer policies. The committee acknowledges that many issues factor into the policy decision-making process and notes in the recommendation that the guidelines will need to be subsequently reexamined as is generally done for many forms of clinical guidance. It is not the intention of the commit- tee to recommend that all healthcare workers use N95 respirators, rather the use of respirators should be for those in initial contact with individu- als presenting with undetermined febrile respiratory illnesses or those with close contact with individuals with confirmed or suspected nH1N1. The term close contact has generally been defined as being within 6 feet of a patient (CDC, 2009i). In addition, the entrance of a healthcare worker into an enclosed space with a patient (e.g., isolation rooms) has also been identified to pose a higher risk for infection of healthcare workers. However, the committee concluded that there was insufficient evidence at this time to fully define close contact for all settings and situations. As noted throughout this report, respiratory protection is one part of a systematic multipronged infection prevention and control strategy. The goal is to minimize risk and decrease the number of healthcare workers with potential exposure to undetermined febrile respiratory ill- nesses and to accurately and rapidly diagnose patients who necessitate antivirals, antimicrobials, and other essential medical and public health interventions. 

LETTER REPORT 29 Future Research It is still unclear what proportion of the spread of influenza virus oc- curs through each of the potential routes of transmission (contact, droplet spray, airborne), as well as the role of respiratory protection devices for each of these routes of transmission. Because of the lack of a strong and conclusive evidence base, the committee noted that determination of the relative contribution of each route of transmission is essential for long- term preparedness planning. Secondly, the committee concluded that a stronger evidence base is needed regarding the effectiveness of personal respiratory protection technologies in clinical settings. As described pre- viously, while some data are available, more research is needed to under- stand the clinical implementation of efficacious technologies, such as how compliance with various technologies can affect their use. Finally, as suggested in the IOM 2008 report (IOM, 2008b), continued collabora- tion and integration between the relevant agencies (e.g., FDA, CDC) are essential to assure the clinical implementation of newer technologies that are both efficacious as well as effective in the clinical setting. The com- mittee bases the following recommendation on its examination of the evidence base, workshop presentations on the newest studies available, previous IOM studies, and its expert judgment. Recommendation 2: Increase Research on Influenza Trans- mission and Personal Respiratory Protection CDC centers (e.g., National Institute for Occupational Safety and Health; National Center for Immunization and Respira- tory Diseases; National Center for Preparedness, Detection, and Control of Infectious Diseases), the National Institutes of Health, and other relevant federal agencies and private insti- tutions should fund and undertake additional research to • resolve the unanswered questions regarding the rela- tive contribution of various routes of influenza trans- mission, • fully explore the effectiveness of personal respiratory protection technologies in a variety of clinical settings through randomized clinical trials, and • design and develop the next generation of personal respiratory protection technologies for healthcare workers to enhance safety, comfort, and ability to per- form work-related tasks. 

30 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS REFERENCES Aiello, A. E., and A. S. Monto. 2009. Reducing transmission of influenza by face masks and hand hygiene. Presentation to the IOM Committee on Respiratory Protection for Healthcare Workers in the Workplace Against Novel H1N1 Influenza A, August 12, 2009. Washington, DC. Atkinson, M., and L. Wein. 2008. Quantifying the routes of transmission for pandemic influenza. Bulletin of Mathematical Biology 70(3):820- 867. Australian Department of Health and Ageing. 2009. Australian influenza surveillance report. No.12, 2009, reporting period: 25 July 2009-31 July 2009. Canberra, Australia: Department of Health and Ageing, Australian Government. Balazy, A., M. Toivola, A. Adhikari, S. K. Sivasubramani, T. Reponen, and S. A. Grinshpun. 2006. Do N95 respirators provide 95% protec- tion level against airborne viruses, and how adequate are surgical masks? American Journal of Infection Control 34(2):51-57. Blachere, F. M., W. G. Lindsley, T. A. Pearce, S. E. Anderson, M. Fisher, R. Khakoo, B. J. Meade, O. Lander, S. Davis, R. E. Thewlis, I. Celik, B. T. Chen, and D. H. Beezhold. 2009. Measurement of air- borne influenza virus in a hospital emergency department. Clinical Infectious Diseases 48(4):438-440. BLS (Bureau of Labor Statistics). 2009. Career guide to industries: Health care. http://www.bls.gov/oco/cg/cgs035.htm (accessed Au- gust 10, 2009). Blumenfeld, H. L., E. D. Kilbourne, D. B. Louria, and D. E. Rogers. 1959. Studies on influenza in the pandemic of 1957-1958. I. An epi- demiologic, clinical and serologic investigation of an intrahospital epidemic, with a note on vaccination efficacy. Journal of Clinical Investigation 38(1 Part 2):199-212. CDC (Centers for Disease Control and Prevention). 2009a. 2008-2009 influenza season week 32 ending August 15, 2009. http://cdc.gov/flu/weekly/index.htm (accessed August 26, 2009). ———. 2009b. 2009-10 influenza prevention & control recommenda- tions. ACIP recommendations: Introduction and biology of influenza. http://www.cdc.gov/flu/professionals/acip/background.htm (accessed August 19, 2009). ———. 2009c. Flu symptoms & severity: Influenza symptoms. http://www.cdc.gov/flu/about/disease/symptoms.htm (accessed Au- gust 19, 2009). 

LETTER REPORT 31 ———. 2009d. Interim guidance on antiviral recommendations for pa- tients with novel influenza A (H1N1) virus infection and their close contacts. http://www.cdc.gov/h1n1flu/recommendations.htm (ac- cessed August 26, 2009). ———. 2009e. Interim guidance for emergency medical services (EMS) systems and 9-1-1 public safety answering points (PSAPs) for man- agement of patients with confirmed or suspected swine-origin Influ- enza A (H1N1) infection. http://www.cdc.gov/h1n1flu/guidance_ ems.htm (accessed August 19, 2009). ———. 2009f. Interim guidance for infection control for care of patients with confirmed or suspected novel influenza A (H1N1) virus infection in a healthcare setting. May 13, 2009. http://www.cdc.gov/h1n1 flu/guidelines_infection_control.htm (accessed August 28, 2009). ———. 2009g. Neurologic complications associated with novel influ- enza A (H1N1) virus infection in children—Dallas, Texas, May 2009. Morbidity & Mortality Weekly Report 58(28):773-778. ———. 2009h. Novel Influenza A (H1N1) virus infections among health-care personnel—United States, April-May 2009. Morbidity & Mortality Weekly Report 58(23):641-645. ———. 2009i. Interim recommendations for facemask and respirator use to reduce novel influenza A (H1N1) virus transmission. http://www.cdc.gov/h1n1flu/masks.htm (accessed August 26, 2009). ———. 2009j. Update: Novel influenza A (H1N1) virus infection— Mexico, March-May, 2009. Morbidity & Mortality Weekly Report 58(21):585-589. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm 5821a2.htm (accessed August 25, 2009). Cowling, B. J., K.-H. Chan, V. J. Fang, C. K. Y. Cheng, R. O. P. Fung, W. Wai, J. Sin, W. H. Seto, R. Yung, D. W. S. Chu, B. C. F. Chiu, P. W. Y. Lee, M. C. Chiu, H. C. Lee, T. M. Uyeki, P. M. Houck, J. S. M. Peiris, and G. M. Leung. 2009. Facemasks and hand hygiene to prevent influenza transmission in households: A randomized trial. Annals of Internal Medicine August 3 Epub. Fabian, P., J. J. McDe- vitt, W. H. DeHaan, R. O. P. Fung, B. J. Cowling, K. H. Chan, G. M. Leung, and D. K. Milton. 2008. Influenza virus in human exhaled breath: An observational study. PLoS ONE 3(7):e2691. FDA (Food and Drug Administration). 2009. Masks and N95 respira- tors.http://www.fda.gov/MedicalDevices/ProductsandMedicalProced ures/MedicalToolsandSupplies/PersonalProtectiveEquipment/ucm05 5977.htm (accessed August 27, 2009). 

32 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS Fiore, A. E. 2009. Novel influenza A (H1N1) epidemiology update. Pres- entation at Advisory Committee on Immunization Practices meeting, July 29, 2009. PowerPoint Presentation. Fiore, A. E., D. K. Shay, K. Broder, J. K. Iskander, T. M. Uyeki, G. Mootrey, J. S. Bresee, N. J. Cox. 2009. Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. Morbidity & Mortality Weekly Report. Recommendations & Reports 58(RR-8):1- 52. Garske, T., J. Legrand, C. A. Donnelly, H. Ward, S. Cauchemez, C. Fra- ser, N. M. Ferguson, and A. C. Ghani. 2009. Assessing the severity of the novel influenza A/H1N1 pandemic. British Medical Journal 339:b2840. Grinshpun, S. A., H. Haruta, R. M. Eninger, T. Reponen, R. T. McKay, and S.-A. Lee. 2009. Performance of an N95 filtering facepiece par- ticulate respirator and a surgical mask during human breathing: Two pathways for particle penetration. Journal of Occupational and Envi- ronmental Hygiene 6(10):593-603. HHS (U.S. Department of Health and Human Services). 2009. Pandem- ics and pandemic threats since 1900. http://www.pandemicflu.gov/ general/historicaloverview.html (accessed August 19, 2009). Inouye, S., Y. Matsudaira, and Y. Sugihara. 2006. Masks for influenza patients: Measurement of airflow from the mouth. Japanese Journal of Infectious Diseases 59(3):179-181. IOM (Institute of Medicine). 2005a. Microbial threats to health: The threat of pandemic influenza. Washington, DC: The National Acad- emies Press. ———. 2005b. The threat of pandemic influenza: Are we ready? Work- shop summary. Washington, DC: The National Academies Press. ———. 2006. Reusability of facemasks during an influenza pandemic: Facing the flu. Washington, DC: The National Academies Press. ———. 2007. Ethical and legal considerations in mitigating pandemic disease: Workshop summary. Washington, DC: The National Acad- emies Press. ———. 2008a. The Personal Protective Technology Program at NIOSH. Washington, DC: The National Academies Press. ———. 2008b. Preparing for an influenza pandemic: Personal protec- tive equipment for healthcare workers. Washington, DC: The Na- tional Academies Press. 

LETTER REPORT 33 Irvin, C. B., L. Cindrich, W. Patterson, and A. Southall. 2008. Survey of hospital healthcare personnel response during a potential avian influ- enza pandemic: Will they come to work? Prehospital & Disaster Medicine 23(4):328-335. Jefferson, T., R. Foxlee, C. D. Mar, L. Dooley, E. Ferroni, B. Hewak, A. Prabhala, S. Nair, and A. Rivetti. 2008. Physical interventions to in- terrupt or reduce the spread of respiratory viruses: Systematic re- view. British Medical Journal 336(7635):77-80. Johnson, D. F., J. D. Druce, C. Birch, and M. L. Grayson. 2009. A quan- titative assessment of the efficacy of surgical and N95 masks to filter influenza virus in patients with acute influenza infection. Clinical In- fectious Diseases 29(2):275-277. Kamps, B. S., and G. Reyes-Terán. 2006. Introduction. In Influenza re- port 2006, edited by B. S. Kamps, C. Hoffman and W. Preiser. Paris: Flying Publisher. Lazzari, S., and K. Stohr. 2004. Avian influenza and influenza pandem- ics. Bulletin of the World Health Organization 82(4):242. Lee, I., and C. A. Umscheid. 2009. Respiratory protection devices for pandemic influenza (H1N1): A systematic review from the University of Pennsylvania Health System for Evidence-based Practice. Phila- delphia, PA: Trustees of the University of Pennsylvania. Lee, S.-A., S. A. Grinshpun, and T. Reponen. 2008. Respiratory per- formance offered by N95 respirators and surgical masks: Human subject evaluation with NaCl aerosol representing bacterial and viral particle size range. Annals of Occupational Hygiene 52(3):177-185. Levine, M. M. 2009. Overview of novel swine-origin H1N1 influenza. Presentation to the IOM Committee on Respiratory Protection for Healthcare Workers in the Workplace Against Novel H1N1 Influenza A, August 12, 2009. Washington, DC. Lewis, D. B. 2006. Avian flu to human influenza. Annual Review of Medicine 57:139-154. MacIntyre, C. R., S. Cauchemez, D. E. Dwyer, H. Seale, P. Cheung, G. Browne, M. Fasher, J. Wood, Z. Gao, R. Booy, and N. Ferguson. 2009a. Face mask use and control of respiratory virus transmission in households. Emerging Infectious Diseases 15(2):233-241. MacIntyre, C. R., Q. Wang, S. Cauchemez, H. Seale, D. E. Dwyer, Y. Peng, S. Weixian, and N. M. Ferguson. 2009b. The first randomised, controlled clinical trial of surgical masks compared to fit-tested and non-fit tested N95 masks in the prevention of respiratory virus infec- tion in hospital health care workers in Beijing, China. Abstract to be 

34 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS presented at the Interscience Conference on Antimicrobial Chemo- therapy (ICAAC), September 15, 2009, San Francisco, CA. Maines, T. R., A. Jayaraman, J. A. Belser, D. A. Wadford, C. Pappas, H. Zeng, K. M. Gustin, M. B. Pearce, K. Viswanathan, Z. H. Shriver, R. Raman, N. J. Cox, R. Sasisekharan, J. M. Katz, and T. M. Tumpey. 2009. Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science 1177238. Mubareka, S., A. C. Lowen, J. Steel, A. L. Coates, A. Garcia-Sastre, and P. Palese. 2009. Transmission of influenza virus via aerosols and fomites in the guinea pig model. Journal of Infectious Diseases 199(6):858-865. Munster, V. J., E. de Wit, J. M. A. van den Brand, S. Herfst, E. J. A. Schrauwen, T. M. Bestebroer, D. van de Vijver, C. A. Boucher, M. Koopmans, G. F. Rimmelzwaan, T. Kuiken, A. D. M. E. Osterhaus, and R. A. M. Fouchier. 2009. Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 1177127. National Center for Immunization and Respiratory Diseases. 2009. Use of Influenza A (H1N1) 2009 monovalent vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. Morbidity & Mortality Weekly Report 58(Early release):1-8. Nicas, M., and R. M. Jones. 2009. Relative contributions of four expo- sure pathways to influenza infection risk. Risk Analysis 29(9):1292- 1303. Oberg, T., and L. M. Brosseau. 2008. Surgical mask filter and fit per- formance. American Journal of Infection Control 36(4):276-282. Olsen, S. J. 2009. Current clinical and epidemiological picture of novel influenza A (H1N1) in the southern hemisphere. Presentation to the Committee on Respiratory Protection for Healthcare Workers in the Workplace Against Novel H1N1 Influenza A, August 12, 2009. Washington, DC. OSHA (Occupational Safety and Health Administration). 2009. Guid- ance on Preparing Workplaces for an Influenza Pandemic. Washing- ton, DC: Occupational Safety and Health Administration. PDR (Physicians’ Desk Reference). 1995. The physicians’ desk reference medical dictionary. Montrale, NJ: Medical Economics. Perez-Padilla, R., D. de la Rosa-Zamboni, S. Ponce de Leon, M. Hernan- dez, F. Quinones-Falconi, E. Bautista, A. Ramirez-Venegas, J. Rojas-Serrano, C. E. Ormsby, A. Corrales, A. Higuera, E. Mondragon, and J. A. Cordova-Villalobos for the INER Working 

LETTER REPORT 35 Group on Influenza. 2009. Pneumonia and respiratory failure from swine-origin Influenza A(H1N1) in Mexico. New England Journal of Medicine 361(7):680-689. PHAC (Public Health Agency of Canada). 2009a. Interim guidance: In- fection prevention and control measures for health care workers in acute care facilities. http://www.phac-aspc.gc.ca/alert-alerte/swine- porcine/hp-ps/ig_acf-ld_esa-eng.php (accessed August 3, 2009). ———. 2009b. Interim guidance: Infection prevention and control measures for health care workers in long-term care facilities. http://www.phac-aspc.gc.ca/alert-alerte/swine-porcine/hp-ps/prevent ion-eng.php (accessed August 3, 2009). ———. 2009c. Interim guidance: Infection prevention and control measures for prehospital care. http://www.phac-aspc.gc.ca/alert- alerte/swine-porcine/hp-ps/pc-sp-eng.php (accessed August 3, 2009). ———. 2009d. Point of care risk assessment tool for pandemic (H1N1) 2009 flu virus. http://www.phac-aspc.gc.ca/alert-alerte/swine- porcine/hp-ps/a1-eng.php#app1 (accessed August 3, 2009). Qian, Y., K. Willeke, S. A. Grinshpun, J. Donnelly, and C. C. Coffey. 1998. Performance of N95 respirators: Filtration efficiency for air- borne microbial and inert particles. American Industrial Hygiene As- sociation Journal 59(2):128-132. Radonovich, L. J., Jr., R. Roberge, A. Baig, A. Levinson, R. E. Shaffer, D. F. Doerr, and V. Davey. 2009a. Better respirator equipment using advanced technologies for healthcare employees (Project B.R.E.A.T.H.E.): An interagency working group of the U.S. federal government. Washington, DC: Office of Public Health and Environ- mental Hazards, Veterans Health Administration, U.S. Department of Veterans Affairs. Radonovich, L. J., Jr., J. Cheng, B. V. Shenal, M. Hodgson, and B. S. Bender. 2009b. Respirator tolerance in health care workers. Journal of the American Medical Association 301(1):36-38. Rengasamy, S., W. P. King, B. C. Eimer, and R. E. Shaffer. 2008. Filtra- tion performance of NIOSH-approved N95 and P100 filtering facepiece respirators against 4 to 30 nanometer-size nanoparticles. Journal of Occupational and Environmental Hygiene 5(9):556-564. Rengasamy, S., B. C. Eimer, and R. E. Shaffer. 2009. Comparison of nanoparticle filtration performance of NIOSH-approved and CE- marked particulate filtering facepiece respirators. Annals of Occupa- tional Hygiene 53(2):117-128. 

36 RESPIRATORY PROTECTION FOR HEALTHCARE WORKERS Shinde, V., C. B. Bridges, T. M. Uyeki, B. Shu, A. Balish, X. Xu, S. Lindstrom, L. V. Gubareva, V. Deyde, R. J. Garten, M. Harris, S. Gerber, S. Vagasky, F. Smith, N. Pascoe, K. Martin, D. Dufficy, K. Ritger, C. Conover, P. Quinlisk, A. Klimov, J. S. Bresee, and L. Fi- nelli. 2009. Triple-reassortant swine influenza A (h1) in humans in the United States, 2005-2009. New England Journal of Medicine 360(25):2616-2625. Siegel, J. D., E. Rhinehart, M. Jackson, L. Chiarello, and Healthcare In- fection Control Practices Advisory Committee. 2007. 2007 guideline for isolation precautions: Preventing transmission of infectious agents in healthcare settings. Atlanta, GA: Centers for Disease Con- trol and Prevention. Weinstock, D. M., J. Eagan, S. A. Malak, M. Rogers, H. Wallace, T. E. Kiehn, and K. A. Sepkowitz. 2000. Control of influenza A on a bone marrow transplant unit. Infection Control & Hospital Epidemiology 21(11):730-732. WHO (World Health Organization). 2009a. Infection prevention and control in health care for confirmed or suspected cases of pandemic (H1N1) 2009 and influenza-like illnesses. http://www.who.int/csr/ resources/publications/20090429_infection_control_en.pdf (accessed July 21, 2009). ———. 2009b. Pandemic (H1N1) 2009 - update 62 (revised 21 August 2009). http://www.who.int/csr/don/2009_08_21/en/index.html (ac- cessed August 21, 2009).