 |
  |
 |
 |
| |
 |
 |
| ||||||||||
|
|
|
|
|
|
|
||||
| ||||||||||
 |
|
|
|
|
Controlling Tuberculosis in the United StatesRecommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of AmericaPlease note: An erratum has been published for this article. To view the erratum, please click here. Corresponding preparers: Zachary Taylor, MD, National Center for HIV, STD, and TB Prevention, CDC; Charles M. Nolan, MD, Seattle-King County Department of Public Health, Seattle, Washington; Henry M. Blumberg, MD, Emory University School of Medicine, Atlanta, Georgia. SummaryDuring 1993--2003, incidence of tuberculosis (TB) in the United States decreased 44% and is now occurring at a historic low level (14,874 cases in 2003). The Advisory Council for the Elimination of Tuberculosis has called for a renewed commitment to eliminating TB in the United States, and the Institute of Medicine has published a detailed plan for achieving that goal. In this statement, the American Thoracic Society (ATS), CDC, and the Infectious Diseases Society of America (IDSA) propose recommendations to improve the control and prevention of TB in the United States and to progress toward its elimination. This statement is one in a series issued periodically by the sponsoring organizations to guide the diagnosis, treatment, control, and prevention of TB. This statement supersedes the previous statement by ATS and CDC, which was also supported by IDSA and the American Academy of Pediatrics (AAP). This statement was drafted, after an evidence-based review of the subject, by a panel of representatives of the three sponsoring organizations. AAP, the National Tuberculosis Controllers Association, and the Canadian Thoracic Society were also represented on the panel. This statement integrates recent scientific advances with current epidemiologic data, other recent guidelines from this series, and other sources into a coherent and practical approach to the control of TB in the United States. Although drafted to apply to TB control activities in the United States, this statement might be of use in other countries in which persons with TB generally have access to medical and public health services and resources necessary to make a precise diagnosis of the disease; achieve curative medical treatment; and otherwise provide substantial science-based protection of the population against TB. This statement is aimed at all persons who advocate, plan, and work at controlling and preventing TB in the United States, including persons who formulate public health policy and make decisions about allocation of resources for disease control and health maintenance and directors and staff members of state, county, and local public health agencies throughout the United States charged with control of TB. The audience also includes the full range of medical practitioners, organizations, and institutions involved in the health care of persons in the United States who are at risk for TB. IntroductionDuring 1993--2003, incidence of tuberculosis (TB) in the United States decreased 44% and is now occurring at a historic low level (14,874 cases in 2003). The Advisory Council for the Elimination of Tuberculosis (ACET) (1) has called for a renewed commitment to eliminating TB in the United States, and the Institute of Medicine (IOM) (2) has published a detailed plan for achieving that goal. In this statement, the American Thoracic Society (ATS), CDC, and the Infectious Diseases Society of America (IDSA) propose recommendations to improve the control and prevention of TB in the United States and to progress toward its elimination. This statement is one in a series issued periodically by the sponsoring organizations to guide the diagnosis, treatment, control, and prevention of TB (3--5). This statement supersedes one published in 1992 by ATS and CDC, which also was supported by IDSA and the American Academy of Pediatrics (AAP) (6). This statement was drafted, after an evidence-based review of the subject, by a panel of representatives of the three sponsoring organizations. AAP, the National Tuberculosis Controllers Association (NTCA), and the Canadian Thoracic Society were also represented on the panel. The recommendations contained in this statement (see Graded Recommendations for the Control and Prevention of Tuberculosis) were rated for their strength by use of a letter grade and for the quality of the evidence on which they were based by use of a Roman numeral (Table 1) (7). No rating was assigned to recommendations that are considered to be standard practice (i.e., medical or administrative practices conducted routinely by qualified persons who are experienced in their fields). This statement integrates recent scientific advances with current epidemiologic data, other recent guidelines from this series (3--5), and other sources (2,8--10) into a coherent and practical approach to the control of TB in the United States. Although drafted to apply to TB control activities in the United States, this statement might be of use in other countries in which persons with TB generally have access to medical and public health services and resources necessary to make a precise diagnosis of the disease; achieve curative medical treatment; and otherwise provide substantial science-based protection of the population against TB. This statement is aimed at all persons who advocate, plan, and work at controlling and preventing TB in the United States, including persons who formulate public health policy and make decisions about allocation of resources for disease control and health maintenance and directors and staff members of state, county, and local public health agencies throughout the United States charged with control of TB. The audience also includes the full range of medical practitioners, organizations, and institutions involved in the health care of persons in the United States who are at risk for TB. Throughout this document, the terms latent TB infection (LTBI), TB, TB disease, and infectious TB disease are used. LTBI is used to designate a condition in which an individual is infected with Mycobacterium tuberculosis but does not currently have active disease. Such patients are at risk for progressing to tuberculosis disease. Treatment of LTBI (previously called preventive therapy or chemoprophylaxis) is indicated for those at increased risk for progression as described in the text. Persons with LTBI are asymptomatic and have a negative chest radiograph. TB, TB disease, and infectious TB indicate that the disease caused by M. tuberculosis is clinically active; patients with TB are generally symptomatic for disease. Positive culture results for M. tuberculosis complex are an indication of TB disease. Infectious TB refers to TB disease of the lungs or larynx; persons with infectious TB have the potential to transmit M. tuberculosis to other persons. Progress Toward TB EliminationA strategic plan for the elimination of TB in the United States was published in 1989 (11), when the United States was experiencing a resurgence of TB (Figure 1). The TB resurgence was attributable to the expansion of HIV infection, nosocomial transmission of M. tuberculosis, multidrug-resistant TB, and increasing immigration from counties with a high incidence of TB. Decision makers also realized that the U.S. infrastructure for TB control had deteriorated (12); this problem was corrected by a substantial infusion of resources at the national, state, and local levels (13). As a result, the increasing incidence of TB was arrested; during 1993--2003, an uninterrupted 44% decline in incidence occurred, and in 2003, TB incidence reached a historic low level. This success in responding to the first resurgence of TB in decades indicates that a coherent national strategy; coordination of local, state, and federal action; and availability of adequate resources can result in dramatic declines in TB incidence. This success also raised again the possible elimination of TB, and in 1999, ACET reaffirmed the goal of tuberculosis elimination in the United States (1). The prospect of eliminating tuberculosis was critically analyzed in an independent study published by IOM in 2000 (2). The IOM study concluded that TB could ultimately be eliminated but that at the present rate of decline, elimination would take >70 years. Calling for greater levels of effort and resources than were then available, the IOM report proposed a comprehensive plan to 1) adjust control measures to the declining incidence of disease; 2) accelerate the decline in incidence by increasing targeted testing and treatment of LTBI; 3) develop new tools for diagnosis, treatment, and prevention; 4) increase U.S. involvement in global control of TB; and 5) mobilize and sustain public support for TB elimination. The report also noted the cyclical nature of the U.S. response to TB and warned against allowing another "cycle of neglect" to occur, similar to that which caused the 1985--1992 resurgence. As noted, the 44% decrease in incidence of TB in the United States during 1993--2003 (14,15) has been attributed to the development of effective interventions enabled by increased resources at the national, state, and local levels (1,2,16). Whereas institutional resources targeted specific problems such as transmission of TB in health-care facilities, public resources were earmarked largely for public health agencies, which used them to rebuild the TB-control infrastructure (13,17). A primary objective of these efforts was to increase the rate of completion of therapy among persons with TB, which was achieved by innovative case-management strategies, including greater use of directly observed therapy (DOT). During 1993--2000, the percentage of persons with reported TB who received DOT alone or in combination with self-supervised treatment increased from 38% to 78%, and the proportion of persons who completed therapy in <1 year after receiving a diagnosis increased from 63% to 80% (14). Continued progress in the control of TB in the United States will require consolidation of the gains made through improved cure rates and implementation of new strategies to further reduce incidence of TB. Challenges to Progress Toward TB EliminationThe development of optimal strategies to guide continuing efforts in TB control depends on understanding the challenges confronting the effort. The five most important challenges to successful control of TB in the United States are 1) prevalence of TB among foreign-born persons residing in the United States; 2) delays in detecting and reporting cases of pulmonary TB; 3) deficiencies in protecting contacts of persons with infectious TB and in preventing and responding to TB outbreaks; 4) persistence of a substantial population of persons living in the United States with LTBI who are at risk for progression to TB disease; and 5) maintaining clinical and public health expertise in an era of declining TB incidence. These five concerns (Box 1) serve as the focal point for the recommendations made in this statement to control and prevent TB in the United States. Prevalence of TB Among Foreign-Born Persons Residing in the United States Once a disease that predominately affected U.S.-born persons, TB now affects a comparable number of foreign-born persons who reside in the United States permanently or temporarily, although such persons make up only 11% of the U.S. population (14). During 1993--2003, as TB incidence in the United States declined sharply, incidence among foreign-born persons changed little (14). Lack of access to medical services because of cultural, linguistic, financial, or legal barriers results in delays in diagnosis and treatment of TB among foreign-born persons and in ongoing transmission of the disease (18--21). Successful control of TB in the United States and progress toward its elimination depend on the development of effective strategies to control and prevent the disease among foreign-born persons. Delays in Detection and Reporting of Cases of Pulmonary TB New cases of infectious TB should be diagnosed and reported as early as possible in the course of the illness so curative treatment can be initiated, transmission interrupted, and public health responses (e.g., contact investigation and case-management services) promptly arranged. However, delays in case detection and reporting continue to occur; these delays are attributed to medical errors (22--26) and to patient factors (e.g., lack of understanding about TB, fear of the authorities, and lack of access to medical services) (18--20). In addition, genotyping studies have revealed evidence of persistent transmission of M. tuberculosis in communities that have implemented highly successful control measures (27--29), suggesting that such transmission occurred before a diagnosis was received. Improvements in the detection of TB cases, leading to earlier diagnosis and treatment, would bring substantial benefits to affected patients and their contacts, decrease TB among children, and prevent outbreaks. Deficiencies in Protecting Contacts of Person with Infectious TB and in Preventing and Responding to TB Outbreaks Although following up contacts is among the highest public health priorities in responding to a case of TB, problems in conducting contact investigations have been reported (30--32). Approaches to contact investigations vary widely from program to program, and traditional investigative methods are not well adapted to certain populations at high risk. Only half of at-risk contacts complete a course of treatment for LTBI (32). Reducing the risk of TB among contacts through the development of better methods of identification, evaluation, and management would lead to substantial personal and public health benefits and facilitate progress toward eliminating TB in the United States. Delayed detection of TB cases and suboptimal contact investigation can lead to TB outbreaks, which are increasingly reported (26,33--38). Persistent social problems such as crowding in homeless shelters and detention facilities are contributing factors to the upsurge in TB outbreaks. The majority of jurisdictions lack the expertise and resources needed to conduct surveillance for TB outbreaks and to respond effectively when they occur. Outbreaks have become an important element in the epidemiology of TB, and measures to detect, manage, and prevent them are needed. Persistence of a Substantial Population of Persons Living in the United States with LTBI Who Are at Risk for Progression to TB Disease An estimated 9.6--14.9 million persons residing in the United States have LTBI (39). This pool of persons with latent infection is continually supplemented by immigration from areas of the world with a high incidence of TB and by ongoing person-to-person transmission among certain populations at high risk. For TB disease to be prevented among persons with LTBI, those at highest risk must be identified and receive curative treatment (4). Progress toward the elimination of TB in the United States requires the development of new cost-effective strategies for targeted testing and treatment of persons with LTBI (17,40). Maintaining Clinical and Public Health Expertise in an Era of Declining TB Incidence Detecting a TB case, curing a person with TB, and protecting contacts of such persons requires that clinicians and the staff members of public health agencies responsible for TB have specific expertise. However, as TB becomes less common, maintaining such expertise throughout the loosely coordinated TB-control system is challenging. As noted previously, medical errors associated with the detection of TB cases are common, and deficiencies exist in important public health responsibilities such as contact investigations and outbreak response. Errors in the treatment and management of TB patients continue to occur (41,42). Innovative approaches to education of medical practitioners, new models for organizing TB services (2), and a clear understanding and acceptance of roles and responsibilities by an expanded group of participants in TB control will be needed to ensure that the clinical and public health expertise necessary to progress toward the elimination of TB are maintained. Meeting the Challenges to TB EliminationFurther improvements in the control and prevention of TB in the United States will require a continued strong public health infrastructure and involvement of a range of health professionals outside the public health sector. The traditional model of TB control in the United States, in which planning and execution reside almost exclusively with the public health sector (17), is no longer the optimal approach during a sustained drive toward the elimination of TB. This statement emphasizes that success in controlling TB and progressing toward its elimination in the United States will depend on the integrated activities of professionals from different fields in the health sciences. This statement proposes specific measures to enhance TB control so as to meet the most important challenges; affirms the essential role of the public health sector in planning, coordinating, and evaluating the effort (43); proposes roles and responsibilities for the full range of participants; and introduces new approaches to the detection of TB cases, contact investigations, and targeted testing and treatment of persons with LTBI. The plan to reduce the incidence of TB in the United States must be viewed in the larger context of the global effort to control TB. The global TB burden is substantial and increasing. In 2000, an estimated 8.3 million (7.9--9.2 million) new cases of TB occurred, and 1.84 million (1.59--2.22 million) persons died from TB; during 1997--2000, the worldwide TB case rate increased 1.8%/year (44). TB is increasing worldwide as a result of inadequate local resources and the global epidemic of HIV infection. In sub-Saharan Africa, the rate of TB cases is increasing 6.4%/year (44). ACET (1), IOM (2), and other public health authorities (45,46) have acknowledged that TB will not be eliminated in the United States until the global epidemic is brought under control, and they have called for greater U.S. involvement in global control efforts. In response, CDC and ATS have become active participants in a multinational partnership (Stop TB Partnership) that was formed to guide the global efforts against TB. U.S. public and private entities also have provided assistance to countries with a high burden of TB and funding for research to develop new, improved tools for diagnosis, treatment, and prevention, including an effective vaccine. Despite the global TB epidemic, substantial gains can be made toward elimination of TB in the United States by focusing on improvements in existing clinical and public health practices (47--49). However, the drive toward TB elimination in the United States will be resource-intensive (1,12). Public health agencies that plan and coordinate TB- control efforts in states and communities need sufficient strength in terms of personnel, facilities, and training to discharge their responsibilities successfully, and the growing number of nonpublic health contributors to TB control, all pursuing diverse individual and institutional goals, should receive value for their contributions. Continued progress toward TB elimination in the United States will require strengthening the nation's public health infrastructure rather than reducing it (1,50). Basic Principles of TB Control in the United StatesFour prioritized strategies exist to prevent and control TB in the United States (17), as follows:
Structure of this StatementThis statement provides comprehensive guidelines for the full spectrum of activities involved in controlling and preventing TB in the United States. The remainder of this statement is structured in eight sections, as follows:
Scientific Basis of TB Control Transmission of TBM. tuberculosis is nearly always transmitted through an airborne route, with the infecting organisms being carried in droplets of secretions (droplet nuclei) that are expelled into the surrounding air when a person with pulmonary TB coughs, talks, sings, or sneezes. Person-to-person transmission of M. tuberculosis is determined by certain characteristics of the source-case and of the person exposed to the source-person and by the environment in which the exposure takes place (Box 2). The virulence of the infecting strain of M. tuberculosis might also be a determining factor for transmission. Characteristics of the Source-Case By the time persons with pulmonary TB come to medical attention, 30%--40% of persons identified as their close personal contacts have evidence of LTBI (30). The highest rate of infection among contacts follows intense exposure to patients whose sputum smears are positive for acid-fast bacilli (AFB) (31,57--59) (Figure 2). Because patients with cavitary pulmonary TB are more likely than those without pulmonary cavities to be sputum AFB smear-positive (60), patients with cavitary pulmonary disease have greater potential to transmit TB. Such persons also have a greater frequency of cough, so the triad of cavitary pulmonary disease, sputum AFB smear-positivity, and frequency of cough are likely related causal factors for infectivity. AFB smear-negative TB patients also transmit TB, but with lower potential than smear-positive patients. Patients with sputum AFB smear-negative pulmonary TB account for approximately 17% of TB transmission (61). Characteristics of the Exposed Person A study of elderly nursing home residents indicated that persons with initially positive tuberculin skin test results during periods of endemic exposure to TB had a much lower risk for TB than those whose skin test results were initially negative (62,63). This finding suggests that preexisting LTBI confers protection against becoming infected upon subsequent exposure and progression to active disease. Similarly, having prior disease caused by M. tuberculosis had been assumed to confer protection against reinfection with a new strain of M. tuberculosis. However, molecular typing of paired isolates of M. tuberculosis from patients with recurrent episodes of TB disease has demonstrated that reinfection does occur among immunocompetent and immunocompromised persons (64,65). The classic means of protecting persons exposed to infectious diseases is vaccination. Because of its proven efficacy in protecting infants and young children from meningeal and miliary TB (66), vaccination against TB with Mycobacterium bovis bacillus Calmette-Guerín (BCG) is used worldwide (although not in the United States). This protective effect against the disseminated forms of TB in infants and children is likely based on the ability of BCG to prevent progression of the primary infection when administered at that stage of life (67). Epidemiologic evidence suggests that BCG immunization does not protect against the development of infection with M. tuberculosis upon exposure (68), and use of BCG has not had an impact on the global epidemiology of TB. One recent retrospective study found that BCG protective efficacy can persist for 50--60 years, indicating that a single dose might have a long duration of effect (69). A meta-analysis indicated that overall BCG reduced the risk for TB 50% (66); however, another meta-analysis that examined protection over time demonstrated a decrease in efficacy of 5%--14% in seven randomized controlled trials and an increase of 18% in three others (70). An effective vaccine against M. tuberculosis is needed for global TB control to be achieved. Because only 30%--40% of persons with close exposure to a patient with pulmonary TB become infected (30,31), innate immunity might protect certain persons from infection (71). The innate mechanisms that protect against the development of infection are largely uncharacterized (71). Although immunocompromised persons (e.g., those with HIV infection) are at increased risk for progression to TB disease after infection with M. tuberculosis, no definitive evidence exists that immunocompromised persons, including those with HIV infection, have increased susceptibility to infection upon exposure. Observational studies suggest that population-based variability in susceptibility to TB might be related to the length of time a population has lived in the presence of M. tuberculosis and has thus developed resistance to infection through natural selection (72--74). However, the genetic basis for susceptibility or resistance to TB is not well understood (72,75). Characteristics of the Exposure Studies that have stratified contacts of persons with pulmonary TB according to time spent with the infected person indicate that the risk for becoming infected with M. tuberculosis is in part determined by the frequency and duration of exposure (60). In a given environment shared by a patient with pulmonary TB and a contact, the risk for transmitting the infection varies with the density of infectious droplet nuclei in the air and how long the air is inhaled. Indoors, tubercle bacilli are expelled into a finite volume of air, and, unless effective ventilation exists, droplet nuclei containing M. tuberculosis might remain suspended in ambient air (76). Exposures in confined air systems with little or no ventilation pose a major risk for transmission of TB; this has been demonstrated in homes, ships, trains, office buildings, and health-care institutions (77--80). When contact occurs outdoors, TB bacilli expelled from the respiratory tract of an infectious person are rapidly dispersed and are quickly rendered nonviable by sunlight (77). The risk for transmission during such encounters is very limited. Considerable attention has been given to transmission of M. tuberculosis during air travel. Investigations have demonstrated that the risk for transmission from an infectious person to others on an airplane is greater on long flights (>8 hours) and that the risk for contracting M. tuberculosis infection is highest for passengers and flight crew members sitting or working near an infectious person (81,82). However, the overall public health importance of such events is negligible (77,81). Virulence of the Infecting Strain of M. tuberculosis Although much is known about factors that contribute to the risk for transmission of M. tuberculosis from person to person, the role of the organism itself is only beginning to be understood (83). Genetic variability is believed to affect the capability of M. tuberculosis strains to be transmitted or to cause disease once transmitted, or both. The M. tuberculosis W-strain family, a member of the globally spread Beijing family (84), is a group of clonally related multidrug-resistant organisms of M. tuberculosis that caused nosocomial outbreaks involving HIV-infected persons in New York City (NYC) during 1991--1994 (85,86). W-family organisms, which have also been associated with TB outbreaks worldwide, are believed to have evolved from a single strain of M. tuberculosis that developed resistance-conferring mutations in multiple genes. The growth of W-family organisms in human macrophages is four- to eightfold higher than that of strains that cause few or no secondary cases of TB; this enhanced ability to replicate in human macrophages might contribute to the organism's potential for enhanced transmission (87). Whether M. tuberculosis loses pathogenicity as it acquires resistance to drugs is not known. Isoniazid-resistant M. tuberculosis strains are less virulent than drug-susceptible isolates in guinea pigs (88), and genotyping studies from San Francisco, California, and from the Netherlands indicated that isoniazid-resistant strains are much less likely to be associated with clusters of TB cases than drug-susceptible strains (89,90). Nevertheless, because person-to-person spread has been demonstrated repeatedly, persons with TB with drug-resistant isolates should receive the same public health attention at the programmatic level as those with drug-susceptible isolates (91,92). Effect of Chemotherapy on Infectiousness Patients with drug-susceptible pulmonary and other forms of infectious TB rapidly become noninfectious after institution of effective multiple-drug chemotherapy. This principle has been established by studies demonstrating that household contacts of persons with infectious pulmonary TB who were treated at home after a brief period of hospitalization for institution of therapy developed LTBI at a frequency no greater than that of persons with pulmonary TB who were hospitalized for 1 year (93) or until sputum cultures became negative (94). This potent effect of chemotherapy on infectiousness is likely attributable, at least in part, to the rapid elimination of viable M. tuberculosis from sputum (95) and to reduction in cough frequency (96). The ability of chemotherapy to eliminate infectivity is one reason why detecting infectious cases and promptly instituting multiple-drug therapy is the primary means of interrupting the spread of TB in the United States. The effect of chemotherapy to eliminate infectiousness was once thought to occur rapidly, and patients on chemotherapy were thought not to be infectious (97,98). However, no ideal test exists to assess the infective potential of a TB patient on treatment, and infectivity is unlikely to disappear immediately after multidrug therapy is started. Quantitative bacteriologic studies indicate that the concentration of viable M. tuberculosis in sputum of persons with cavitary sputum AFB smear-positive pulmonary TB at the time of diagnosis, which averaged 106--107 organisms/ml, decreased >90% (10-fold) during the first 2 days of treatment, an effect attributable primarily to administration of isoniazid (99), and >99% (100-fold) by day 14--21, an effect attributable primarily to administration of rifampin and pyrazinamide (100). Thus, if no factor other than the elimination of viable M. tuberculosis from sputum were to account for the loss of infectivity during treatment, the majority of patients (at least those with infection attributable to isolates susceptible to isoniazid) who have received treatment for as few as 2 days with the standard regimen (i.e., isoniazid, rifampin, ethambutol, and pyrazinamide) could be assumed to have an infective potential that averages 10% of that at the time of diagnosis. After 14--21 days of treatment, infectiousness averages <1% of the pretreatment level. This statement presents general guidelines on elimination of infectivity with treatment (Box 3). However, decisions about infectiousness of a person on treatment for TB should always be individualized on the basis of 1) the extent of illness; 2) the presence of cavitary pulmonary disease; 3) the degree of positivity of sputum AFB smear results; 4) the frequency and strength of cough; 5) the likelihood of infection with multidrug-resistant organisms; and 6) the nature and circumstances of the contact between the infected person and exposed contacts (101). Patients who remain in hospitals or reside either temporarily or permanently in congregate settings (e.g., shelters and correctional facilities) are subject to different criteria for infectiousness. In such congregate settings, identification and protection of close contacts is not possible during the early phase of treatment, and more stringent criteria for determining absence of infectivity (i.e., three consecutive AFB-negative sputum smears) should be followed (10). All patients with suspected or proven multidrug resistant TB should be subjected to these more stringent criteria for absence of infectivity (10). Progression from LTBI to TB Disease Although the human immune response is highly effective in controlling primary infection resulting from exposure to M. tuberculosis among the majority of immunocompetent persons, all viable organisms might not be eliminated. M. tuberculosis is thus able to establish latency, a period during which the infected person is asymptomatic but harbors M. tuberculosis organisms that might cause disease later (4,71). The mechanisms involved in latency and persistence are not completely understood (71,72). For the majority of persons, the only evidence of LTBI is an immune response against mycobacterial antigens, which is demonstrated by a positive test result, either a tuberculin skin test (3) or, in certain circumstances, a whole blood antigen-stimulated interferon-g release assay result (e.g., QuantiFERON®-TB Gold test [QFT-G] [Cellestis Limited, Carnegie, Victoria, Australia]). The tuberculin skin test measures delayed-type hypersensitivity; QFT-G, an ex vivo test for detecting latent M. tuberculosis infection, measures a component of cell-mediated immune response (102). QFT-G is approved by the Food and Drug Administration (FDA), and CDC will publish guidelines on its use. CDC had previously published guidelines for use of QuantiFERON®-TB, an earlier version of the test that is no longer available (103). T SPOT-TB,® an enzyme-linked immunospot assay for IFN-g, is marketed in Europe along with QFT-G but is not FDA-approved for use in the United States. Although approved by FDA, the Tine Test® is not recommended for the diagnosis of M. tuberculosis infection. Tests available in other countries to diagnose M. tuberculosis infection (e.g., T SPOT-TB and Heaf test) are not recommended for clinical use in the United States. Once a person has contracted LTBI, the risk for progression to TB disease varies. The greatest risk for progression to disease occurs within the first 2 years after infection, when approximately half of the 5%--10% lifetime risk occurs (4,104). Multiple clinical conditions also are associated with increased risk for progression from LTBI to TB disease. HIV infection is the strongest known risk factor (4). Other key risk factors because of their prevalence in the U.S. population are diabetes mellitus (105), acquisition of LTBI in infancy or early childhood, and apical fibro-nodular changes on chest radiograph (106). A recent addition to the known risk factors for progression from LTBI to TB disease is the use of therapeutic agents that antagonize the effect of cytokine tumor necrosis factor alpha (TNF-a) and have been proven to be highly effective treating autoimmune-related conditions (e.g., Crohn's disease and rheumatoid arthritis) (107). Cases of TB have been reported among patients receiving all three licensed TNF-a antagonists (i.e., infliximab, etanercept, and adalimimab) (108). CDC has published interim guidelines for preventing TB when these agents are used (109). Epidemiology of TB in the United StatesSurveillance (i.e., the systematic collection, analysis, and dissemination of data) is a critical component of successful TB control, providing essential information needed to 1) determine patterns and trends of the disease; 2) identify populations and settings at high risk; and 3) establish priorities for control and prevention activities. Surveillance is also essential for quality-assurance purposes, program evaluation, and measurement of progress toward TB elimination. In addition to providing the epidemiologic profile of TB in a given jurisdiction, state and local surveillance are essential to national TB surveillance. CDC's national TB surveillance system publishes epidemiologic analyses of reported TB cases in the United States (110). Data for the national TB surveillance system are reported by state health departments in accordance with standard TB case-definition and case-report formats (110,111). The system tracked the reversal of the declining trend in TB incidence in the United States in the mid-1980s, the peak of the resurgence in 1992 (with a 20% increase in cases reported during 1985--1992), and the subsequent 44% decline to an all-time low number (14,871) and rate (5.1 cases/100,000 population) of TB cases in 2003 (14,15) (Figure 1). Geographic Distribution of TB Wide disparities exist in the geographic distribution of TB cases in the United States. In 2003, six states (California, Florida, Georgia, Illinois, New York, and Texas) each reported >500 cases and accounted for 57% of the national total (14). These states along with New Jersey accounted for approximately 75% of the overall decrease in cases since 1992. The highest rates and numbers of TB cases are reported from urban areas; >75% of cases reported in 2003 were from areas with >500,000 population (14). In 2003, a total of 24 states (48%) had incidence of <3.5 cases of TB/100,000 population, the rate established as the year 2000 interim target for the United States in the 1989 strategic plan for eliminating TB (11). Demographic Distribution of TB In 2003, adults aged 15--64 years accounted for 73.6% of reported TB cases. Incidence of TB was highest (8.4 cases/100,000 population) among adults aged >65 years, who accounted for 20.2% of cases. Children aged <14 years accounted for 6.2% of reported cases and had the lowest incidence of TB; 61.3% of reported cases occurred among men, and case rates among men were at least double those of women in mid- and older-adult age groups. In 2003, the white, non-Hispanic population accounted for only 19% of reported cases of TB, and TB incidence among the four other racial/ethnic populations for which data were available was 5.7--21.0 times that of non-Hispanic whites (Table 2). Foreign-born persons accounted for 94% of TB cases among Asians and 74% of cases among Hispanics, whereas 74% of cases among non-Hispanic blacks occurred among persons born in the United States (15). Distribution of TB by Socioeconomic and Employment Status Socioeconomic status (SES). Low SES is associated with an increased risk for TB. An analysis of national surveillance data that assigned socioeconomic indicator values on the basis of residence zip code indicated that the risk for TB increased with lower SES for six indicators (crowding, education, income, poverty, public assistance, and unemployment), with crowding having the greatest impact (112). Risk for TB increased uniformly between socioeconomic quartile for each indicator, similar to other socioeconomic health gradients for other chronic diseases, except for crowding, for which risk was concentrated in the lowest quartile. Adjusting for SES accounted for approximately half of the increased risk for TB associated with race/ethnicity among U.S.-born blacks, Hispanics, and American Indians (112). Occupation. Increased incidence of TB among persons with certain occupations is attributable to exposure in the work environment and to an increased likelihood that workers will have other risk factors unrelated to occupation, such as foreign birth. A 29-state study of patients with clinically active TB reported during 1984--1985 indicated that increased incidence was independent of occupation. An association between general SES groupings of occupations and risk for TB also was demonstrated in that study (113). Chronically unemployed persons had high incidence of TB; this finding is consistent with surveillance data indicating that >50% of TB patients were unemployed during the 2 years before diagnosis (14). TB among health-care workers (HCWs). Because transmission of M. tuberculosis in health-care institutions was a contributing factor to the resurgence of TB during 1985--1992, recommendations were developed to prevent transmission in these settings (10). In 2003, persons reported to have been HCWs in the 2 years before receiving their diagnoses accounted for 3.1% of reported TB cases nationwide (14). However, the elevated risk among HCWs might be attributable to other factors (e.g., birth in a country with a high incidence of TB) (114). A multistate occupational survey indicated that the majority of HCWs did not have a higher risk for TB than the general population; respiratory therapists, however, did appear to be at greater risk (113). Identification of Populations at High Risk for TB Contacts of infectious persons. A high prevalence of TB disease and LTBI has been documented among close contacts of persons with infectious pulmonary TB (31). A study of approximately 1,000 persons from urban sites with pulmonary AFB sputum smear-positive TB indicated that more than one third of their contacts had positive tuberculin skin tests and that 2% of all close contacts had active TB. Contacts identified with TB disease were more likely to be household members or children aged <6 years (31). Foreign-born persons. The proportion of TB cases in the United States occurring among foreign-born persons increased progressively during the 1990s; in 2003, persons born outside the United States accounted for 53% of reported cases (14) (Figure 3). Although foreign-born persons who received a diagnosis of TB in 2002 were born in >150 countries worldwide, as in each of the 6 previous years, five countries of origin accounted for the greatest number of foreign-born persons with TB: China (5%), India (8%), Mexico (26%), the Philippines (12%), and Vietnam (8%). During 1992--2003, the number of states in which >50% of the total reported cases occurred among foreign-born persons increased from four (8%) in 1992 to 24 (48%) in 2003 (15). Among states and cities, however, this profile can change rapidly, reflecting changes in patterns of immigration and refugee settlement (21). Surveillance data indicate that incidence of TB among foreign-born persons is approximately 23 cases/100,000 population (14). Incidence varied by county of origin, appearing to reflect incidence of TB in the country of birth (21,115,116). In 2003, approximately 47% of foreign-born persons with TB received their diagnoses within 5 years of their arrival in the United States, and 19% received their diagnoses within 1 year of arrival. Among foreign-born persons, TB case rates decreased with longer duration of residence in the United States. TB rates were nearly four times higher among persons residing in the United States for <5 years than in those who were residents for >5 years (115,116). HIV-infected persons. Because reporting of HIV infection among persons with TB is not complete, the exact prevalence of HIV infection among such persons is unknown. During 1993--2001, the prevalence of reported HIV infection occurring among persons also reported with TB decreased from 15% to 8% (14); this decrease has been attributed, in part, to reduced transmission of TB among HIV-infected persons (16). According to a recent worldwide epidemiologic assessment, however, 26% of adult TB cases in the United States are attributable to HIV infection (44). Homeless persons. In 2003, persons known to have been homeless in the year before receiving a diagnosis accounted for 6.3% of cases of TB nationwide. On the basis of available population estimates (117), incidence of TB among homeless persons is approximately 30--40/100,000 population, more than five times the national case rate. However, a prospective study of a cohort of approximately 3,000 homeless persons in San Francisco documented an annual incidence of >250 cases/100,000 population (118). In addition, outbreaks of TB linked to overnight shelters continue to occur among homeless persons and likely contribute to the increased incidence of TB among that population (119,120). Other populations at high risk. In 2003, persons known to have injected drugs in the year before receiving a diagnosis accounted for 2.2% of reported cases of TB, and noninjection drug use was reported by 7.3% of persons with TB. In certain U.S. communities, injection drug use is sufficiently prevalent so as to constitute a high risk for epidemiologic importance rather than simply an individual risk factor, especially when overlap exists between injection drug use and HIV infection (121,122). TB Among Detainees and Prisoners in Correctional Facilities The proportion of cases of TB occurring among inmates of prisons and jails has remained stable at approximately 3%--4% since data began to be collected in 1993; it was 3.2% in 2003 (14). Inmates also have high incidence of TB, with rates often >200/100,000 population (123), and they have a disproportionately greater number of risk factors for TB (e.g., low SES, HIV infection, and substance abuse) compared with the general population (124,125). TB transmission in correctional facilities contributes to the greater risk among those populations, presumably because of the difficulties in detecting cases of infectious TB and in identifying, evaluating, and treating contacts in these settings (37,126). TB outbreaks occur in both prison and jail settings. Dedicated housing units for prison inmates with HIV infection were sites of transmission in California in 1995 (126) and South Carolina in 1999 and in South Carolina in 1999 (37). In the South Carolina outbreak, delayed diagnosis and isolation of an inmate who apparently had active TB after entering the facility led to >15 outbreak cases. Transmission leading to TB infection in the community also was documented in an outbreak that occurred in a jail in Tennessee during 1995--1997 (127,128) that involved approximately 40 inmates; contact investigations were incomplete because of brief jail terms and frequent movement of inmates. During the same period, 43% of patients with TB in the surrounding community had previously been incarcerated in that jail (127), and, after 2 years, the jail outbreak strain was more prevalent in the community than it was during the jail outbreak. Genotyping studies indicated that the outbreak strain accounted for approximately 25% of TB cases in the community, including those among patients with no history of incarceration (128). Contributions of Genotyping of M. tuberculosisM. tuberculosis genotyping refers to procedures developed to identify M. tuberculosis isolates that are identical in specific parts of the genome (83). To date, M. tuberculosis genotyping has been based on polymorphisms in the number and genomic location of mycobacterial repetitive elements. The most widely used genotyping test for M. tuberculosis is restriction fragment length polymorphism (RFLP) analysis of the distribution of the insertion sequence IS6110 (129). However, genotyping tests based on polymorphisms in three additional mycobacterial repetitive elements (i.e., polymorphic guanine cytosine--rich repetitive sequences, direct repeats [e.g., spoligotyping], and mycobacterial interspersed repetitive units [MIRU]) have also been developed (83). M. tuberculosis isolates with identical DNA patterns in an established genotyping test often have been linked through recent transmission among the persons from whom they were isolated. When coupled with traditional epidemiologic investigations, analyses of the genotype of M. tuberculosis strains have confirmed suspected transmission and identified unsuspected transmission of M. tuberculosis. These analyses have also identified risk factors for recent infection with rapid progression to disease, demonstrated exogenous reinfection with different strains, identified weaknesses in conventional contact investigations, and documented the existence of laboratory cross-contamination. Genotyping has become an increasingly useful tool for studying the pathogenesis, epidemiology, and transmission of TB. Epidemiology of TB Among Contacts in Outbreak Settings Conventional contact investigations have used the concentric circles approach to collect information and screen household contacts, coworkers, and increasingly distant contacts for TB infection and disease (17). The concentric circles model has been described previously (130). However, this method might not always be adequate in out-of-household settings. In community-based studies from San Francisco (131), Zurich (132), and Amsterdam (133), only 5%--10% of persons with clustered IS6110-based genotyping patterns were identified as contacts by the source-person in the cluster. This finding indicates that either 1) transmission of M. tuberculosis might occur more commonly than suspected and is not easily detected by conventional contact tracing investigations or 2) genotype clustering does not necessarily represent recent transmission (55). Because genotyping studies discover only missed or mismanaged contacts (i.e., those that subsequently receive a diagnosis of TB), such studies cannot explain the successes of the process or the number of cases that were prevented. Certain populations (e.g., the urban homeless) present specific challenges to conducting conventional contact investigations. Genotyping studies have provided information about chains of transmission in these populations (118,119). In a prospective study of TB transmission in Los Angeles, the degree of homelessness and use of daytime services at three shelters were factors that were independently associated with genotype clustering (119). Additional studies support the idea that specific locations can be associated with recent or ongoing transmission of M. tuberculosis among homeless persons. Two studies among predominantly HIV-infected men have demonstrated evidence of transmission at specific bars in the community (134,135). Genotyping techniques have confirmed TB transmission in HIV residential facilities (136), crack houses (i.e., settings in which crack cocaine is sold or used) (137), hospitals and clinics (54), and prisons (138,139). TB transmission also has been demonstrated among church choirs (140) and renal transplant patients (141) and in association with processing of contaminated medical waste (142) and with bronchoscopy (143,144). Communitywide Epidemiology of TB TB might arise because of rapid progression from a recently acquired M. tuberculosis infection, from progression of LTBI to TB disease, or occasionally from exogenous reinfection (145). The majority of genotyping studies have assumed that clustered isolates in a population-based survey reflect recent transmission of M. tuberculosis. Certain studies have identified epidemiologic links between clustered TB cases, inferring that the clustered cases are part of a chain of transmission from a single common source or from multiple common sources (131,146). The number and proportion of population-based cases of TB that occur in clusters representing recent or ongoing transmission of M. tuberculosis have varied from study to study; frequency of clustering has varied from 17%--18% (in Vancouver, Canada) to 30%--40% (in U.S. urban areas) (131,147,148). Youth, being a member of a racial or ethnic minority population, homelessness, substance abuse, and HIV infection have been associated with clustering (131,133, 148,149). The increasing incidence of TB among foreign-born persons underscores the need to understand transmission dynamics among this population. In San Francisco, two parallel TB epidemics have been described (150,151), one among foreign-born persons that was characterized by a low rate of genotype clustering and the other among U.S-born persons that was characterized by a high rate of genotype clustering. In a recent study from NYC, being born outside the United States, being aged >60 years, and receiving a diagnosis after 1993 were factors independently associated with being infected with a strain not matched with any other, whereas homelessness was associated with genotype clustering and recent transmission (152). Among foreign-born persons, clustered strains were more likely to be found among patients with HIV infection (152). Other Contributions of Genotyping Genotyping can determine whether a patient with a recurrent episode of TB has relapsed with the original strain of M. tuberculosis or has developed exogenous reinfection with a new strain (64,153). In Cape Town, South Africa, where incidence of TB is high and considerable ongoing transmission exists, 16 (2.3%) of 698 patients had more than one episode of TB disease. In 12 (75%) of the 16 recurrent cases, the pairs of M. tuberculosis isolates had different IS6110-based genotyping patterns, indicating exogenous reinfection (154). However, in areas with a low incidence of TB, episodes of exogenous reinfection are uncommon (153). Because TB incidence in the majority of areas of the United States is low and decreasing, reinfection is unlikely to be a major cause of TB recurrence. Genotyping has greatly facilitated the identification of false-positive cultures for M. tuberculosis resulting from laboratory cross-contamination of specimens. Previously, false-positive cultures (which might lead to unnecessary treatment for patients, unnecessary work for public health programs in investigating cases and pseudo-outbreaks, and unnecessary costs to the health-care system) were difficult to substantiate (155). Because of its capability to determine clonality among M. tuberculosis strains, genotyping has been applied extensively to verify suspected false-positive cultures (156--158) and to study the causes and prevalence of laboratory cross-contamination (159,160). The Role of Genotyping of M. tuberculosis in TB-Control Programs In 2004, CDC established the Tuberculosis Genotyping Program (TBGP) to enable rapid genotyping of isolates from every patient in the United States with culture-positive TB (161). State TB programs may submit one M. tuberculosis isolate from each culture-positive case within their jurisdictions to a contracted genotyping laboratory. A detailed manual describing this program, including information on how to interpret genotyping test results and how to integrate genotyping into TB-control activities, has been published (162). Genotyping information is essential to optimal TB control in two settings. First, genotyping is integral to the detection and control of TB outbreaks, including ruling a suspected outbreak in or out and pinpointing involved cases and the site or sites of transmission (54,136--144). Second, genotyping is essential to detect errors in handling and processing of M. tuberculosis isolates (including laboratory cross-contamination) that lead to reports of false-positive cultures for M. tuberculosis (156,158--160,163). More extensive use of M. tuberculosis genotyping for TB control depends on the availability of sufficient program resources to compare results with information from traditional epidemiologic investigative techniques. Time-framed genotyping surveys and good fieldwork can unravel uncertainties in the epidemiology of TB in problematic populations at high risk (150--152,164). Genotyping surveys and epidemiologic investigations also can be used as a program monitoring tool to determine the adequacy of contact investigations (29,119,132--134,164--166) and evaluate the success of control measures designed to interrupt transmission of M. tuberculosis among certain populations or settings (167). Programs that use genotyping for surveillance of all of the jurisdiction's M. tuberculosis isolates should work closely on an ongoing basis with the genotyping laboratory and commit sufficient resources to compare genotyping results with those of traditional epidemiologic investigations. Information from both sources is needed for optimum interpretation of the complex epidemiologic patterns of TB in the United States (84,168). Principles and Practice of TB ControlBasic Principles of TB ControlThe goal of TB control in the United States is to reduce morbidity and mortality caused by TB by 1) preventing transmission of M. tuberculosis from persons with contagious forms of the disease to uninfected persons and 2) preventing progression from LTBI to TB disease among persons who have contracted M. tuberculosis infection. Four fundamental strategies are used to achieve this goal (Box 4) (17,169), as follows:
Vaccination with BCG is not recommended as a means to control TB in the United States because of the unproved efficacy of the vaccine in the U.S. population (174,175), its effect of confounding the results of tuberculin skin testing (176) and the success of other measures in reducing incidence of TB (16). During the 1985--1992 TB resurgence, the documented spread of TB, including multidrug-resistant TB, in health-care institutions and in the community (52--54,177,178) stimulated interest in the potential use of BCG to protect HCWs and others from exposure to M. tuberculosis. In 1996, a statement from ACET and the Advisory Committee on Immunization Practices (179) recommended vaccination with BCG for 1) infants and children with exposure to M. tuberculosis in settings in which other protective measures are either inaccessible or proven to be ineffective and 2) HCWs when likelihood of exposure to multidrug-resistant TB is high and recommended control measures have not been successful. With improved TB control in the United States and the decline of multidrug-resistant TB (13), use of BCG for protection against TB has declined. An improved vaccine, particularly one that protects adults with LTBI against acquiring TB disease, would accelerate progress toward TB elimination in the United States (180). Deficiencies in TB ControlBecause TB control is a complex undertaking that involves multiple participants and processes, mistakes often occur, with adverse consequences. Common errors include 1) delays among persons with active TB obtaining health care; 2) delayed detection and diagnosis of active TB; 3) failed or delayed reporting of TB; 4) failure to complete an effective course of treatment for TB; 5) missed opportunities to prevent TB among children; and 6) deficiencies in conducting contact investigations and in recognizing and responding to outbreaks. Delays in Obtaining Health Care Homeless patients with TB symptoms often delay seeking care or experience delays in gaining access to care (181), and fear of immigration authorities has been associated with patient delay among foreign-born persons (19). Patients who speak languages other than English or who are aged 55--64 years are more likely than others to delay seeking care (20). Cultural factors that might affect health-seeking behavior by foreign-born persons include misinterpretation or minimization of symptoms, self-care by using over-the-counter or folk medicines, and the social stigma associated with TB (18). In certain societies, women with TB are less likely to take advantage of health-care services, perhaps because of stigma associated with the diagnosis, including a lower likelihood of marriage (182,183). Even in areas with open access to public health clinical services, persons at risk for TB might not seek evaluation and treatment because they are not aware that these resources are available for persons with limited financial means (118,184--186). Delayed Detection and Diagnosis of Active TB Delayed detection of a case of TB and resulting delays in initiation of treatment can occur if the clinician does not suspect the diagnosis. A survey conducted in NYC in 1994 found that the median delay within the health-care system (defined as the time from first contact to initiation of treatment for active TB) was 15 days (range: 0--430 days) (20). Asians and homeless persons were more likely to encounter delays in receiving a diagnosis than non-Asians and persons with stable housing. Persons without cough who had AFB smear-negative TB or who did not have a chest radiograph at their initial visit also experienced delays. In London, England, delays in diagnosis occurred among whites and among women of all racial/ethnic populations (187). Regardless of the reason, the consequences of delays in diagnosis and initiation of effective therapy can be serious. In Maine, a shipyard worker aged 32 years who was a TB contact and who was untreated despite having symptoms of active TB, repeated medical visits, and a chest radiograph consistent with active TB did not receive a diagnosis of TB until 8 months after he became ill (188), and 21 additional cases of TB occurred among his contacts. Of 9,898 persons who were investigated as contacts, 697 (7.0%) persons received diagnoses of new LTBIs. A high school student in California was symptomatic for >1 year before TB was diagnosed (177). Subsequently, 12 additional TB cases among fellow students were linked to the source-case, and 292 (23%) of 1,263 students tested had positive tuberculin skin tests. Other instances of delayed or missed diagnoses of TB have been reported that have resulted in extended periods of infectiousness and deaths (22,24,178). These problems reflect the increasing difficulty in maintaining clinical expertise in the recognition of TB in the face of declining disease incidence (41). Recognition of TB among patients with AFB-negative sputum smear results is a challenge for practitioners and has been associated with delays in reporting and treatment (22,189,190). Delayed Reporting of TB Failure to promptly report a new TB case delays public health responses (e.g., institution of a treatment plan, case-management services, and protection of contacts). Although TB cases in the United States rarely remain unreported, timeliness of reporting varies (median: 7--38 days) (190). Failure to Receive and Complete a Standard Course of Treatment for Active TB Failure to receive and complete a standard course of treatment for TB has adverse consequences, including treatment failure, relapse, increased TB transmission, and the emergence of drug-resistant TB (191--193). At least two reasons exist for failure to complete standard treatment. Patients frequently fail to adhere to the lengthy course of treatment (188). Poor adherence to treatment regimens might result from difficulties with access to the health-care system, cultural factors, homelessness, substance abuse, lack of social support, rapid clearing of symptoms, or forgetfulness (18,194). Also, as TB has become less common, clinicians might fail to use current treatment regimens (48). These adverse outcomes are preventable by case-management strategies provided by TB-control programs, including use of DOT (13,195,196). Missed Opportunities To Prevent TB Among Children The absence of TB infection and disease among children is a key indicator of a community's success in interrupting the transmission of TB (197). The 1985--1992 TB resurgence included a reversal of the long-term decline in the incidence of TB among children, which indicated a failure of the public health system to prevent disease transmission (197). A study of 165 children reported with TB in California in 1994 found that for 59 (37%), an adult source-case was identified (198). Factors that contributed to transmission to children included delayed reporting, delayed initiation of contact investigations, and poor management of adult source-cases. Improvements in contact investigations might have prevented 17 (10%) of those cases (198). Deficiencies in Conducting Contact Investigations and in Recognizing and Responding to Outbreaks Deficiencies in contact investigations and failure to recognize and respond to TB outbreaks are among the most important challenges to optimal control of TB in the United States. These topics are discussed in detail in this statement along with the other essential components of TB control. Importance of TB Training and EducationThe 1985--1992 TB resurgence led ACET to call for a renewed focus on training and education as an integral part of strategies for TB control, prevention, and elimination (1). Factors indicating a need for this focus include the following:
Educating Patients and Communities at High Risk Education of patients by clinicians, TB program staff, and trusted community members promotes acceptance and adherence to authoritative advice about controlling and preventing TB. Such education can influence patients' decision-making about whether to accept and complete treatment for LTBI (202). Because cultural and health beliefs might act as barriers to effective control of TB (18,19), an increasing need exists for education targeted at populations at high risk (19). TB-control programs should enlist community-based organizations and other key informants to discover the health beliefs, norms, and values of communities at high risk in their jurisdictions (202,203). Professional associations and academic institutions (including schools of medicine, public health, and nursing) will be valuable partners in developing an understanding of the health perceptions of these populations. Education materials should be developed with input from the target audience to ensure that they are culturally and linguistically appropriate (203,204). The Strategic Plan for TB Training and Education In 1997, CDC funded a project to develop a Strategic Plan for Tuberculosis Training and Education (the Strategic Plan) that provided guidance to agencies and organizations in the United States that offer TB training and education for public- and private-sector providers. The Strategic Plan specified critical areas requiring attention, including 1) the need for culturally competent programs and materials, 2) effective methods and technologies, 3) collaboration and cooperation among training and education partners outside TB-control programs, and 4) adequate funding for training and education efforts. Other Resources for TB Training and Education Substantial progress has been made in developing and disseminating resources for TB training and education. CDC and national TB centers, NTCA, regional controllers associations (e.g., the Northeast Tuberculosis Training Consortium), state and local health departments, and the National Laboratory Training Network have all conducted education programs or developed training and education materials. In 2001, as stipulated by the Strategic Plan, the Tuberculosis Education and Training Network was established. The network is coordinated by CDC and includes educators in local, state, and territorial health agencies. CDC has also developed the Tuberculosis Information CD-ROM, Version 3, and the Tuberculosis Education and Training Resource Guide; these products are designed to enhance awareness and accessibility of resources (available at http://www.cdc.gov/nchstp/tb/default.htm) for TB education and training. The establishment in 2004 of the National Tuberculosis Curriculum Coordinating Center at the University of California at San Diego by the National Heart Lung and Blood Institute signals a commitment by the National Institutes of Health (NIH) to provide basic TB education for health-care students and providers. Professional societies and specialty boards are means for reaching private medical providers. Including TB as a subject in state medical society programs, hospital grand rounds, and medical specialty board examinations would be a valuable resource for providers serving populations at low risk. New linkages should be established to reach providers serving populations at high risk (e.g., foreign-born, homeless, and HIV-infected persons). For example, the AIDS Education and Training Centers funded by the Health Resources and Services Administration are a resource for reaching HIV/AIDS providers, and foreign physicians' associations and community-based organizations are potential partners for reaching international medical graduates and health-care providers of foreign-born persons. Laboratory Services for Optimal TB ControlThe diagnosis of TB, management of patients with the disease, and public health control services rely on accurate laboratory tests. Laboratory services are an essential component of effective TB control, providing key information to clinicians (for patient care) and public health agencies (for control services). Up to 80% of all initial TB-related laboratory work (e.g., smear and culture inoculation) is performed in hospitals, clinics, and independent laboratories outside the public health system, whereas >50% of species identification and drug susceptibility testing is performed in public health laboratories (205). Thus, effective TB control requires a network of public and private laboratories to optimize laboratory testing and the flow of information. Public health laboratorians, as a component of the public health sector with a mandate for TB control, should take a leadership role in developing laboratory networks and in facilitating communication among laboratorians, clinicians, and TB controllers. Role of Public Health Laboratories Public health laboratories should ensure that clinicians and public health agencies within their jurisdictions have ready access to reliable laboratory tests for diagnosis and treatment of TB (206). Specific tasks to ensure the availability, accessibility, and quality of essential laboratory services are 1) assessment of the cost and availability of TB laboratory services and 2) development of strategic plans to implement and maintain a systems approach to TB testing (207). In this process, public health laboratories should assess and monitor the competence of laboratories that perform any testing related to the diagnosis, management, and control of TB within their jurisdictions; develop guidelines for reporting and tracking of laboratory results; and educate laboratory staff members, health-care providers, and public health officials about available laboratory tests, new technologies, and indications for their use. For example, public health laboratories should lead the discussion on the costs, logistics requirements (e.g., collection and transport of clinical specimens within the required time), and quality assurance issues associated with the use of QFT-G, the new test for latent M. tuberculosis infection (103). The process of coordinating TB laboratory services is usually best organized at the state level (208), and the Association of Public Health Laboratories has compiled descriptions of successful organizational models for integrated laboratory services (207). Role of Clinical Laboratories Because the majority of initial TB laboratory work related to diagnosis of TB is conducted in hospitals, clinics, and independent laboratories (205), clinicians and public health agencies are increasingly dependent on the laboratory sector for the confirmation of reported cases, and public health laboratories are similarly dependent for referral of specimens for confirmatory testing and archiving. However, as a result of laboratory consolidation at the regional or national level (206), private laboratories are experiencing more difficulties in fulfilling this function. In certain instances, consolidation has resulted in poor communication among laboratory personnel, clinicians, and public health agencies (206,209). Problems also have been identified in specimen transport, test result reporting, and quality control (206,209,210). In response, certain states (e.g., Wisconsin*) have adopted laws and regulations that mandate essential clinical laboratory services for TB control (e.g., drug susceptibility testing and reporting of the first M. tuberculosis isolate from each patient and submission of isolates to the state public health laboratory). The clinical laboratory sector should accept the responsibilities that accompany its emergence as a provider of essential TB testing (209). This statement provides recommendations to guide turnaround times for essential tests, reporting to clinicians and jurisdictional public health agencies, and referral of specimens to public health laboratories or their designees. Essential Laboratory Tests Six tests performed in clinical microbiologic laboratories are recommended for optimal TB control services (Table 3). These laboratory tests should be available to every clinician involved in TB diagnosis and management and to jurisdictional public health agencies charged with TB control. In addition, other tests that are useful in the diagnosis and management of selected patients and for specific TB control activities include M. tuberculosis genotyping, serum drug levels, tests used for monitoring for drug toxicity, and QFT-G for diagnosis of latent M. tuberculosis infection (5,103,162). Access to these specialized tests should be provided as needed. For suspected cases of pulmonary TB, sputum smears for AFB provide a reliable indication of potential infectiousness; and for AFB smear-positive pulmonary cases, a nucleic acid amplification assay (NAA) provides rapid confirmation that the infecting mycobacteria are from the M. tuberculosis complex. These two tests, which should be available with rapid turnaround times from specimen collection, facilitate decisions about initiating treatment for TB or a non-TB pulmonary infection, and, if TB is diagnosed, for reporting the case and establishing priority to the contact investigation. Growth detection and identification of M. tuberculosis by culture of sputum and other affected tissue is essential for confirmation of the identity of the organism and for subsequent drug susceptibility testing, which is recommended on all initial isolates for each patient. Cultures also remain the cornerstone for the diagnosis of TB in smear-negative pulmonary and extrapulmonary cases and, along with sputum smears for AFB, provide the basis for monitoring a patient's response to treatment, for release from isolation, and for diagnosing treatment failure and relapse (5). The use of liquid media systems, which can provide information in less time than solid media (in certain cases, 7 days), should be available in all laboratories that perform culture for mycobacteria. Detailed descriptions of these recommended laboratory tests; recommendations for their correct use; and methods for collecting, handling, and transporting specimens have been published (3,211). Recommended Roles and Responsibilities for TB ControlThis section delineates organizational and operational responsibilities of the public health sector that are essential to achieve the goals of TB control in the United States. However, a central premise of this statement is that continuing progress toward elimination of TB in the United States will require the collaborative efforts of a broad range of persons, organizations, and institutions in addition to the public health sector, which has responsibility for the enterprise. For example, clinicians who provide primary health care and other specialized health services to patients at high risk for TB, academic medical centers that educate and train them, hospitals in which they practice, and professional organizations that serve their interests can all make meaningful contributions to improve the detection of TB cases, one of the most important obstacles to continuing progress (Box 1). Similarly, important roles exist for such entities as community-based organizations representing populations at risk for TB and the pharmaceutical industry, which takes academic advances and develops the tools for diagnosis, treatment, and prevention of TB. This section discusses the importance to the TB elimination effort of participants outside the public health sector and proposes specific roles and responsibilities that each could fulfill toward that goal. The sponsoring organizations intend for these proposals to serve as the basis for discussion and consensus building on the important roles and responsibilities of the nonpublic health sector in continuing progress toward the elimination of TB in the United States. Public Health SectorThe infrastructure for TB control has been discussed extensively in recent years. An analysis of contributing factors to the rise in the number of TB cases during 1985--1992 concluded that the resurgence never would have occurred had the public health infrastructure been left in place and supported appropriately (212). The need to maintain the TB-control infrastructure has been expressed repeatedly (1,2,13,213,214). Public health activities have been described as consisting of four interrelated components: mission/purpose, structural capacity, processes, and outcomes (215). Among these four components, structural capacity (i.e., persons who do the work of public health, their skills and capacities, the places where they work, the way they are organized, the equipment and systems available to them, and the fiscal resources they command) represents the public health infrastructure for TB control. The responsibility for TB control and prevention in the United States rests with the public health system through federal, state, county, and local public health agencies. Programs conducted by these agencies were critical to the progress that has been made in TB control, and the deterioration of those programs following the loss of categoric federal funding contributed to the resurgence of TB in the United States during 1985--1992 (1,2,13,212--214). Since 1992, as a result of increased funding for TB-control programs, national incidence of TB disease has declined. In 2004, $147 million in federal funds were dedicated to domestic TB control, compared with $6.6 million in 1989, during the resurgence. These funds have been used to rebuild public health--based TB-control systems, and the success achieved highlights the critical role of the public health system in TB control. TB control in the United States has traditionally been conducted through categoric programs established to address the medical aspects of the disease and the specific interventions required for its successful prevention and management (17,216). CDC's Division of TB Elimination, in partnership with other CDC entities that conduct TB-related work, provides guidance and oversight to state and local jurisdictions by conducting nationwide surveillance; developing national policies, priorities, and guidelines; and providing funding, direct assistance, education, and program evaluation. Setting the national agenda for support of basic and clinical research is also a critical function of federal health agencies, including NIH and CDC, with support from nongovernment organizations such as ATS and IDSA. To meet the priorities of basic TB control (Box 4), state and local public health agencies with responsibility for TB control should provide or ensure the provision of a core group of functions (Box 5). Jurisdictional public health agencies should ensure that competent services providing these core elements function adequately within their jurisdictions and are available with minimal barriers to all residents. How the core components of TB control are organized differs among jurisdictions, depending on the local burden of disease, the overall approach to public health services within the jurisdiction, budgetary considerations, the availability of services within and outside the public health sector, and the relationships among potential participants. Certain jurisdictions provide core program components themselves, whereas other jurisdictions contract with others to provide them. In the majority of cases, the organization includes a mix in which the public health agency provides certain services, contracts for others, and works collaboratively with partners and stakeholders to accomplish the remainder (48). Sharing of direct services, including patient management, increases the importance of the public health sector, which retains responsibility for success of the process. This evolving role of the public health sector in TB control is consistent with the widely accepted concept of the three core functions of public health that IOM proposed in 1988: assessment, policy development, and assurance (43). Health Insurance Portability and Accountability ActThe Health Insurance Portability and Accountability Act (HIPAA) of 1996 included provisions to protect the privacy of individually identifiable health information. To implement these privacy protections, the U.S. Department of Health and Human Services has issued a ruling on how health-care providers may use and disclose personally identifiable health information about their patients; these regulations provide the first national standards for requirements regarding the privacy of health information (217). HIPAA also recognizes the legitimate need for public health authorities and others responsible for ensuring the public's health and safety to have access to personal health information to conduct their missions and the importance of public health disease reporting by health-care providers. HIPAA permits disclosure of personal health information to public health authorities legally authorized to collect and receive the information for specified public health purposes. Such information may be disclosed without written authorization from the patient. Disclosures required by state and local public health or other laws are also permitted. Thus, HIPAA should not be a barrier to the reporting of suspected and verified TB cases by health-care providers, including health-care institutions. Additional information about HIPAA is available at http://www.hhs.gov/ocr/hipaa. Roles and Responsibilities of Federal Public Health Agencies
Roles and Responsibilities of Jurisdictional Public Health Agencies Planning and policy development. The blueprint for TB control for a given area is a responsibility of the jurisdictional public health agency. Policies and plans should be based on a thorough understanding of local epidemiologic data and on the capabilities and capacities of clinical and support services for clients, the fiscal resources available for TB control, and ongoing indicators of program performance. Open collaboration is essential among public health officials and community stakeholders, experts in medical and nonmedical TB management, laboratory directors, and professional organizations, all of whom provide practical perspectives to the content of state and local TB-control policy. Policies and procedures should reflect national and local standards of care and should offer guidance in the management of TB disease and LTBI. A written TB control plan that is updated regularly should be distributed widely to all interested and involved parties. The plan should assign specific roles and responsibilities; define essential pathways of communication between providers, laboratories, and the public health system; and assign sufficient resources, both human and financial, to ensure its implementation, including a responsible case manager for each suspected and verified case of TB. The plan should include the provision of expert consultation and oversight for TB-related matters to clinicians, institutions, and communities. It should provide special guidance to local laboratories that process TB-related samples, assist local authorities in conducting contact or outbreak investigations and DOT, and provide culturally appropriate information to the community. Systems to minimize or eliminate financial and cultural barriers to TB control should be integral to the plan, and persons with TB and persons at high risk with TB infection should receive culturally appropriate education about TB and clinical services, including treatment, with no consideration for their ability to pay. Finally, the plan should be consistent with current legal statutes related to TB control. Relevant laws and regulations should be reviewed periodically and updated as necessary to ensure consistency with currently recommended clinical and public health practice (e.g., mandatory reporting laws, institutional infection-control procedures, hospital and correctional system discharge planning, and involuntary confinement laws) (218). Collection and analysis of epidemiologic and other data. The development of policies and plans for the control of TB within a jurisdiction requires a detailed understanding of the epidemiology of TB within the jurisdiction. Mandatory and timely case reporting from community sources (e.g., providers, laboratories, hospitals, and pharmacies) should be enforced and evaluated regularly. To facilitate the reporting process and data analyses, jurisdictions should modify systems as necessary to accommodate local needs and evolving technologies. State and local TB-control programs should have the capability to monitor trends in TB disease and LTBI in populations at high risk and to detect new patterns of disease and possible outbreaks. Populations at high risk should be identified and targeted for active surveillance and prevention, including targeted testing and treatment of LTBI (4). Timely and accurate reporting of suspected and confirmed TB cases is essential for public health planning and assessment at all levels. Analyses of these data should be performed at least annually to determine morbidity, demographic characteristics, and trends so that opportunities for targeted screening for disease or infection can be identified. Regular reviews of clinical data (e.g., collaborative formal case presentations and cohort analyses of treatment outcomes; completeness, timeliness and effectiveness of contact investigations; and treatment of LTBI) may be used as indicators of program performance. Data should be collected and maintained in a secure, computerized data system that contains up-to-date clinical information on persons with suspected and confirmed cases and on other persons at high risk. Each case should be reviewed at least once monthly by the case manager and by field or outreach staff to identify problems that require attention. The TB-case registry should ensure that laboratory data, including data on sputum culture conversion and drug susceptibility testing of clinical isolates, are promptly reported, if applicable, to the health-care provider so any needed modifications in management can be made. This requires a communications protocol for case managers, providers, and the public health and private laboratory systems that will transmit information in a timely fashion. Aggregate program data should be available to the health-care community and to community groups and organizations with specific interests in public health to support education and advocacy and to facilitate their collaboration in the planning process. Clinical and diagnostic services for patients with TB and their contacts. TB-control programs should ensure that patients with suspected or confirmed TB have ready access to diagnostic and treatment services that meet national standards (3,5). These services are often provided by state- or city-supported TB specialty clinics and staffed by health department personnel or by contracted service providers; however, persons may seek medical care for TB infection or disease in the private medical sector. Regardless of where a person receives medical care, the primary responsibility for ensuring the quality and completeness of all TB-related services rests with the jurisdictional health agency, and health departments should develop and maintain close working relations with local laboratories, pharmacies, and health-care providers to ensure that standards of care, including those for reporting, are met. Clinical services provided by the health department, contracted vendors, or private clinicians should be competent, accessible, and acceptable to members of the community served by the jurisdiction. Hours of clinic operation should be convenient, and waiting intervals between referral and appointments should be kept to a minimum. Persons with symptoms of TB should be accommodated immediately (i.e., on a walk-in basis). Staff, including providers, should reflect the cultural and ethnic composition of the community to the extent that this is possible, and competent clinical interpreter services should be available to those patients who do not speak English. All clinical services, including diagnostic evaluation, medications, clinical monitoring, and transportation, should be available without consideration of the patient's ability to pay and without placing undue stress on the patient that might impair completion of treatment. Clinical facilities should provide diagnostic, monitoring, and screening tests, including radiology services. Health-care providers, including nurses, clinicians, pharmacists, laboratory staff members, and public health officials, should be educated about the use and interpretation of diagnostic tests for TB infection and disease. Clinics and providers should monitor patients receiving TB medications at least monthly for drug toxicity and for treatment response, according to prevailing standards of care (5). Counseling and voluntary testing for HIV infection should be offered to all persons with suspected and proven TB and to certain persons with LTBI, with referral for HIV treatment services when necessary. A case manager, usually a health department employee, should be assigned to each patient suspected or proven to have TB to ensure that adequate education is provided about TB and its management, standard therapy is administered continuously, and identified contacts are evaluated for infection and disease. A treatment plan for persons with TB should be developed immediately on report of the case. This plan should be reviewed periodically by the case manager and the treating clinician and modified as necessary as new data become available (219). The treatment plan should include details about the medical regimen used, how and where treatment is to be administered, monitoring of adherence, drug toxicity, and clinical and bacteriologic responses. Social and behavioral factors that might interfere with successful completion of treatment also should be addressed. Patient-specific strategies for promoting adherence to treatment should take into account each patient's clinical and social circumstances and needs (5). Such strategies might include the provision of incentives or enablers (e.g., monetary payment, public transportation passes, food, housing, child care, or transportation to the clinic for visits). Whether the patient's care is managed by a public health clinic or in the private sector, the initial strategy used should emphasize direct observation of medication ingestion by an HCW. Patient input into this process (e.g., regarding medications to be taken or the location of DOT) is often useful as it can minimize the burden of treatment and provide the patient a degree of control over an anticipated lengthy course of therapy. Expert medical consultation in TB should be available to the health-care community, especially for patients who have drug-resistant disease or medical diagnoses that might affect the course or the outcome of treatment. Consultants may be employees of the health department or clinicians with expertise who are under contract with the health department. Inpatient care should be available to all persons with suspected or proven TB, regardless of the person's ability to pay. Hospitalized patients with suspected proven TB should have access to expert medical and nursing care, essential diagnostic services, medications, and clinical monitoring to ensure that diagnostic and treatment standards are met. Inpatient facilities that manage persons who are at risk for TB should have infection-control policies and procedures in place to minimize the risk for nosocomial spread of infection. Facilities should report persons with suspected or confirmed TB to the health department and arrange for discharge planning as required by statute. Public health agencies should have legal authority and adequate facilities to ensure that patients with infectious TB are isolated from the community until they are no longer infectious. This authority should include the ability to enforce legal confinement of patients who are unwilling or unable to adhere to medical advice (218,220). This authority also should apply to nonadherent patients who no longer are infectious but who are at risk for becoming infectious again or becoming drug resistant. TB-control programs should serve as sources of information and expert consultation to the health-care community regarding airborne infection and appropriate infection-control practice. A TB program's presence raises overall provider awareness of TB and facilitates timely diagnosis, reporting, and treatment. Collaboration with local health-care facilities to design and assist in periodic staff education and screening is often a health department function. Expertise in airborne infections by TB-control personnel may be shared with biologic terrorism programs to assist in the design and implementation of local protocols. Contact investigation, including education and evaluation of contacts of persons with infectious TB, is a key component of the public health mandate for TB control. Often the primary responsibility of the case manager, contact investigation should proceed as quickly and as thoroughly as indicated by the characteristics of the specific case and by those of the exposed contact (e.g., young children or immunocompromised persons). This statement includes recommendations on organizing and conducting contact investigation |