6.1 Tuberculosis6. Infectious Diseases | 6.2 Anthrax
TB is a disease caused by inhalation of the mycobacterial pathogen Mycobacterium tuberculosis. After inhalation, infection can occur quickly, but most infected people control the infection for months to years, resulting in a condition called latent TB infection. People with latent TB infection are not contagious. However, between five and 10 percent of those with latent TB infection will eventually become unable to control the infection and develop active disease in the lung and other sites. This percentage is much higher in those with impaired cellular immunity, such as those taking immunosuppressive medications or with immunosuppressive conditions such as HIV infection. People with active pulmonary TB, especially cavitary TB, can be highly infectious and spread infection via the airborne route, especially by coughing. Latent TB infection can be detected by assessing for specific cell-mediated immunity to TB as a biomarker of infection. This can be done by tuberculin skin test or a newly licensed blood test measuring interferon gamma secretion by tuberculin-stimulated cells in anticoagulated whole blood (Quantiferon Gold). Detection of latent TB infection is important, because timely antimicrobial treatment can prevent development of active disease, benefiting both the infected individual and contacts at risk for disease transmission.
TB is a massive worldwide problem. It is estimated that more than one third of the world’s population is infected and that about 1.8 million people die of the disease each year. Fortunately, the U.S. has a much lower prevalence of infection. It was estimated in 2002 that between 9.6 and 14.9 million people in the U.S. had latent TB infection.
Following decades of TB decline, active TB cases in the U.S. increased by 20 percent between 1985 and 1992. Several factors contributed to this crisis: a large immune-suppressed population associated with the HIV epidemic; increased immigration from countries with high prevalence of TB; emergence of multi-drug resistant TB; outbreaks of TB in high-risk settings, such as hospitals and correctional facilities; and decreased funding resulting in a general decline in TB services and infrastructure (A6-1).155 Outbreaks of TB have been documented in hospitals, nursing homes, prisons, homeless shelters, and other congregate settings.
RDRP has worked to prevent and reduce occupationally-related TB within the context of the broader CDC response to eliminate TB in the U.S. This response to TB elimination has been formulated with extensive input from extramural experts. In 1989, the Advisory Committee to Eliminate TB, a Federal Advisory Committee to CDC, developed “A Strategic Plan for the Elimination of TB in the U.S,” which was published by CDC (A6-2). This plan proposed a national strategy for TB elimination. A Federal TB Task Force drawn from a broad range of agencies committed to the elimination of TB, including NIOSH/RDRP, was established in1991. The TB Task force sought to implement the strategic plan, and complemented the plan by developing a “National Action Plan to Combat Multidrug-Resistant TB in the U.S.” in 1992 (A6-3).
More recently, in 2000, the IOM issued a report, “Ending Neglect: the Elimination of TB in the U.S.,” which detailed recommendations for maintaining control of TB and accelerating the rate of its decline, aimed at eliminating the disease (A6-4, A6-5).156,157 To help implement these IOM recommendations, two reports providing guidance for future prevention of TB were issued by CDC, with NIOSH/RDRP participation (one on behalf of the Federal TB Task Force) (A6-6, A6-7). RDRP staff developed strategies for inclusion in both of these reports. Efforts by NIOSH/RDRP and CDC in general have also been guided by a report developed by IOM in response to a Congressional request “TB in the Workplace,” that was issued in 2001. It outlined criteria that could be used to develop an effective and acceptable OSHA standard on occupational TB (A6-8).158
To contribute to the prevention of TB in the workplace, RDRP has focused efforts in its unique areas of strength. These have included administrative controls (including training, education, and participation in development and implementation of guidelines and recommendations); environmental controls, such as ventilation and filtration systems and ultraviolet (UV) germicidal radiation; respiratory protection; exposure assessment; field studies in workplaces where TB transmission was a concern; and surveillance.
Outputs and Transfer
In the last 10 years, RDRP has produced 79 papers published in peer-reviewed journals, 32 abstracts and presentations at professional conferences, eight book chapters, six NIOSH numbered documents and NIOSH videos on TB, and 10 other reports (A6-9).
The NIOSH numbered documents are:
Outputs and Transfer activities divided by subject area are described below:
Administrative Controls and Training
In 1990, CDC released “Guidelines for Preventing the Transmission of Tuberculosis in Health-Care Settings, with Special Focus on HIV-Related Issues” (A6-13). These were expanded and revised in 1994 as “Guidelines for Preventing the transmission of Mycobacterium tuberculosis in Health-Care Facilities, 1994” (1, A6-14) and 2005 as the “Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings” (2, A6-15). RDRP researchers were key members of the working group that wrote the latter guidelines, which recommend a comprehensive approach based on a hierarchy of controls that specifies varying levels of preventive action depending on level of risk.
To assist in implementation of CDC guidelines in workplaces, RDRP developed training and education materials for workers appropriate to varied educational backgrounds. These materials addressed TB control measures relevant to a variety of work settings and responsibilities. A guide for healthcare workers, “Protect Yourself Against TB – A Respiratory Protection Guide for Healthcare Workers,” (A6-12) was distributed (a total of 94,935 copies) to healthcare workers and to the CDC Division of Global Migration and Quarantine, which redistributed the document to workers in primate quarantine facilities. The document was also posted on the NIOSH Web site and available in a video version. A manual, “TB Respiratory Protection Program in Healthcare Facilities–Administrators Guide,” (A6-11) was also developed and distributed to serve as a practical guide for individuals responsible for initiating and running TB respiratory protection programs in healthcare facilities. Both guides are available in hard copy and video. A total of 12,839 copies of the video (VHS and DVD) and 55,413 printed copies of the document were distributed.
To develop practical approaches for implementation of guidelines in workplaces, RDRP entered into cooperative agreements with the California Department of Health Services (A6-16), Washington University School of Medicine (A6-17), National Jewish Medical and Research Center (A6-18), and the State of New Jersey Department of Health and Senior Services (A6-19). The grantees assisted in the development of recommendations to maximize compliance with the 1994 CDC guidelines on the prevention of TB transmission in health-care facilities.
In cooperation with NCID, the National Center for HIV, STD, and TB Prevention, and the NIOSH International Activities office, RDRP scientists taught in a three-day training course, “Preventing the Institutional Transmission of TB and Multidrug-Resistant TB (MDR TB),” in Riga, Latvia and Chuvashia, Russia. RDRP scientists also participated in respirator fit-testing for health workers and reviewed infection control activities in Latvia and Russia. RDRP and other CDC scientists surveyed the state-of-practice of TB control in five developing countries (Thailand, Brazil, Malawi, Ivory Coast, and Latvia). RDRP participation included providing recommendations for eliminating congested indoor waiting areas, where possible, modifying patient flow through various facilities, installing cost-effective engineering controls, and using respiratory protection. In Thailand and Brazil RDRP worked with the government and healthcare professionals to tailor Ultraviolet Germicidal Irradiation (UVGI) and/or ventilation controls to specific hospitals.
RDRP scientists contributed to the writing of the “Guidelines for the Prevention of TB in Health Care Facilities in Resource-Limited Settings,” (WHO/CDC Collaborative Guidelines [A6-20]).
RDRP scientists helped to develop environmental controls to prevent the spread and reduce the concentration of infectious droplet nuclei. RDRP conducted research on ventilation and UVGI systems to optimize how these measures can be used to effectively prevent the transmission of TB.
Environmental control solutions developed by RDRP scientists include portable air cleaners, isolation room models, and UVGI devices fixed in-room and installed in ventilation systems. RDRP research showed that UVGI is effective for inactivation of bacteria and bacterial spores (3, 4, A6-21, A6-22; A6-23). RDRP research has also demonstrated that, when used properly, portable air cleaners can help remove airborne infectious aerosols and provide better overall air mixing in rooms used to house infectious TB patients (final report A6-24). RDRP scientists did research to model air flow and leakage from an airborne infection isolation room. An empirical model was developed that is an effective and economical tool that engineers and designers can use when designing and constructing airborne infection isolation rooms (5, A6-25).
RDRP sponsored a workshop to develop a national research strategy on engineering controls for prevention of airborne infections in workers at health-care and related facilities (A6-26).
RDRP scientists have conducted research relevant to the use of personal respiratory protective equipment in areas where there is still a risk for exposure to M. tuberculosis. Specifically, this research has focused on bioaerosol filter efficiency, filter reuse, and fit testing.
RDRP contracted with the University of Minnesota to test filtration efficiency of surgical masks and all three types of NIOSH-certified (Part 11) respirators (dust/mist respirators, dust/fume/mist respirators, and High-Efficiency Particulate Aerosol [HEPA] respirators) against polystyrene latex spheres and three bioaerosols (M. abscessus and Bacillus subtilis [both rods] and Staphylococcus epidermidis [spherical]). The HEPA respirators had the highest filter efficiency against all four challenge aerosols (A6-27, A6-28, A6-29).
Other RDRP extramural research with the University of Cincinnati demonstrated that N95 respirators filter bioaerosols as well as they filter most industrial aerosols. This research also found that reaerosolization of bacteria from N95 respirators was insignificant during respirator wear (6, A6-30; A6-31)
RDRP also entered into two interagency agreements with the U.S. Army’s Dugway Proving Ground. The first evaluated the protective efficacy of surgical masks and dust/mist, dust/fume/mist, and HEPA (both powered and non-powered) respirators against Bacillus subtilis var. niger and sodium chloride aerosol. It was shown that HEPA respirators were effective in removing bioaerosols and there was no significant difference in penetration between bioaerosols and non-bioaerosols. The second tested N95 and P100 (Part 84) respirators against M. tuberculosis (H37Ra strain) to assess the acceptability of reusing Part 84 respirators. Parameters tested included filter efficiency, microorganism survival, mold and fungal contamination, and contamination due to handling. The study determined that Part 84 filters removed M. tuberculosis effectively and could be reused with little risk of internal contamination if properly handled and stored (7, A6-32).
RDRP scientists conducted fit-testing research on N95 respirators that demonstrated all N95 filtering facepiece respirators did not have the same fitting characteristics during a simulated workplace test. RDRP scientists have also shown that passing some of the fit tests listed in the OSHA respirator standard (29 CFR 1910.134) with N95 filtering facepieces does not guarantee an acceptable level of protection in the workplace (8, 9, A6-33, A6-34). RDRP disseminated results of this and related research to OSHA in comments to the docket on the proposed OSHA rule on occupational exposure to TB (A6-35, A6-36, A6-37).
RDRP scientists have worked to develop improved approaches to assessing exposure to TB. These improved approaches to exposure assessment are a much needed research tool. A sampling and detection method based on PCR to monitor for the presence of M. tuberculosis in air filter samples was developed and disseminated in the NMAM (A6-38). This method was modified to allow determination of concentration and aerodynamic size range of airborne mycobacteria.159 Because PCR-based methods will measure both viable mycobacteria with the potential to transmit infection and nonviable mycobacteria that cannot, extramural investigators funded via RDRP developed methods to document concentration and size distribution of viable cough-generated airborne M. tuberculosis from patients with TB.160
RDRP investigators were the first to apply proteomic profiling of mycobacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to the identification of TB and differentiation of TB from other mycobacterial species.161 This work was awarded the prestigious Charles C. Shepard Science Award as best CDC laboratory and methods paper of 2004. The usefulness of proteomic profiling is probably not so much for the identification of TB as for the identification of unique molecular constituents that could be used as targets of other detection methods (such as immunoassays) or as antigens in immunodiagnostic tests or vaccines. RDRP investigators in collaboration with investigators from the Lawrence Livermore Laboratory also used bioaerosol mass spectrometry as the analytical basis for a prototype real-time sampler for rapid detection of individual airborne Mycobacterium tuberculosis H37Ra particles.162
RDRP scientists have responded to more than 100 requests (including 43 HHEs) from employers, employees, employee representatives, and governmental agencies for assistance in evaluating workplace TB risk in particular work settings and to make recommendations for reducing worker exposure to TB. These requests came from a variety of work settings, including hospitals, neighborhood health centers, TB clinics, homeless shelters, drug treatment centers, correctional facilities, social service facilities, laboratories, medical waste treatment facilities, and an inspection station for imported non-human primates. Reports describing findings and presenting recommendations of HHEs are developed and distributed to the employer, employees, and relevant governmental agencies. Findings from selected investigations have been disseminated in nine papers in the peer-reviewed literature and at 12 presentations at technical meetings and conferences.
RDRP field studies have important, practical benefits for requestors. In one example, RDRP investigators worked together with other elements of CDC to evaluate and improve environmental controls at the largest homeless shelter in St. Louis, Missouri. Conditions in the shelter were implicated as underlying an outbreak of 19 cases of active TB between February 2001 and August 2003. RDRP engineers assessed the facility and recommended a combination of upper-air and in-duct UVGI in the high-risk areas of the shelter, in conjunction with improved ventilation system filtration, increased fresh air, and improved maintenance practices. The recommendations were implemented and no new cases of TB have been identified at the shelter to date (A6-39).
RDRP provided additional funding to SENSOR, a state-based occupational surveillance program, to build capacity for the surveillance of occupationally related TB in state programs (A6-40). The grantees developed state-based sentinel surveillance programs to assess the risk of TB infection and TB in high-risk occupational settings.
The American Institute of Architects included information from the 1994 CDC TB guidelines in their 2001 version of the "Guidelines for Design and Construction of Hospital and Healthcare Facilities." For airborne infection isolation rooms, these guidelines adopted recommendations for room air exchange rates and directional air flow, as well as limitations on the use of portable in-room air cleaners, as written by RDRP scientists. A 2006 update of these American Institute of Architects guidelines retains RDRP-generated recommendations (A6-41).163
Two recently published CDC documents provide updated guidance on the prevention of the transmission of TB—“Guidelines for Preventing the Transmission of Mycobacterium TB in Health-Care Settings,” published in 2005 (A6-15), and “Prevention and Control of TB in Correctional and Detention Facilities: Recommendations from CDC,” published in 2006 (10, A6-42). Both guidelines update TB control recommendations, reflecting shifts in the epidemiology of TB, advances in scientific understanding, and changes in health care. RDRP scientists wrote the engineering controls and respiratory protection sections of these guidelines and also provided input into the other sections of the document. The Joint Commission on Accreditation of Healthcare Organizations (http://www.jointcommission.org ) has used the CDC guidelines as a basis for their standards for reviewing of health-care organizations (A6-43).164 OSHA uses the guidelines in citing employers under the general duty clause regarding TB issues.
A marked improvement in TB control measures by health care facilities was noted in a comparison of responses to national surveys of hospitals done in 1992 and 1996, two years before and two years after CDC’s release of the1994 guidelines on preventing TB transmission in health care facilities.165
The effectiveness of the broad approach to TB prevention is reflected in the 46 percent decline in the total number of TB cases in the U.S. decreases from 1992 to 2004 (A6-44).
From 1994 to 1998, the incidence of active TB among health care workers declined from 5.6 per 100,000 to 4.6 per 100,000, while rates for all other workers remained at 5.2 per 100,000.165
RDRP will continue efforts to prevent occupational TB, focusing on areas identified in the CDC and the Federal TB Task Force’s responses to the IOM report “Ending Neglect: The Elimination of TB from the U.S.”
Respirator research is a major focus of the RDRP role within the broader CDC response to TB. RDRP is developing a panel of subjects for fit-testing studies which will better represent the diversity found in today's U.S. workforce than the traditionally used (Los Alamos) panel. Respirators designed to fit such a panel would fit today’s workforce better than those designed for the older Los Alamos panel. RDRP researchers are also developing a total inward leakage test, intended to quantify the general ability of each respirator model to fit individuals. A requirement to pass total inward leakage testing as a part of respirator certification will hopefully result in respirators with better inherent fitting characteristics. This will provide an additional margin of safety over current testing criteria and will motivate manufacturers to modify respirator design for improved performance.
See also “What’s Ahead” in chapter 6.3b, which addresses RDRP’s role in the CDC initiative in environmental microbiology. This initiative is relevant to all occupational infectious diseases that can be transmitted via the airborne route.
155. “Self-Study Modules on Tuberculosis developed by the Centers for Disease Control and Prevention, National Center for HIV, STD, and TB Prevention, Division of Tuberculosis Elimination, Public Health Practice Program Office, Division of Media and Training Services.” [http://www.phppo.cdc.gov/phtn/tbmodules/Default.htm]. Accessed September 5, 2006.
156. Institute of Medicine, Ending Neglect: the Elimination of TB in the United States, Executive Summary. [newton.nap.edu/execsumm_pdf/9837.pdf]. Accessed September 6, 2006.
157. Institute of Medicine, Ending Neglect: the Elimination of TB in the United States, Report in Brief. [newton.nap.edu/html/ending_neglect/reportbrief.pdf]. Accessed September 6, 2006.
158. Institute of Medicine, Tuberculosis in the Workplaces, Report in Brief. [newton.nap.edu/html/tuberculosis/reportbrief.pdf]. Accessed September 5, 2006.
159. Schafer MP, Martinez KF, Mathews ES . Rapid detection and determination of the aerodynamic size range of airborne mycobacteria associated with whirlpools. Appl Occup Environ Hyg 18(1):41-50.
160. Fennelly KP, Martyny JW, Fulton KE, Orme IM, Cave DM, Heifets LB . Cough-generated aerosols of Mycobacterium tuberculosis: a new method to study infectiousness. Am J Respir Crit Care Med 1;169(5):604-9.
161. Hettick JM, Kashon ML, Simpson JP, Siegel PD, Mazurek GH, Weissman DN . Proteomic profiling of intact mycobacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anal Chem 1;76(19):5769-76.
162. Tobias HJ, Schafer MP, Pitesky M, Fergenson DP, Horn J, Frank M, Gard EE . Bioaerosol mass spectrometry for rapid detection of individual airborne Mycobacterium tuberculosis H37Ra particles. Appl Environ Microbiol 71(10):6086-95.
163. American Institute of Architects . Guidelines for design and construction of hospital and health care facilities. Washington, DC: American Institute of Architects. [https://aia-timssnet.uapps.net/Timssnet/Common/TNT_ShowDetail.cfm]. Accessed on September 5, 2006.
164. Kuhny L . Standards Interpretation Joint Commission on Accreditation of Healthcare Organizations 630-792-5900: JCAHO Standards Submission.” [Private email]. Joint Commission on Accreditation of Healthcare Organizations, 601 13th Street, NW, Suite 1150N, Washington, DC 20005.
165. Institute of Medicine  Tuberculosis in the Workplace. National Academies of Science. Washington, DC [darwin.nap.edu/books/0309070287/html].