Controlling Tuberculosis in the United States

Because of their essential role in developing new diagnostics, drugs, and vaccines, the pharmaceutical and biotechnology industries are partners in TB control. Although development of new tools for diagnosis, treatment, and prevention of TB has been deemed essential to the effort to combat the disease globally and to continue to make progress toward its elimination in the United States and other developed countries (1,2,45,259), progress in these fields has been slow. Slow progress in this field has been attributed to private industry's perception that such products are not needed in developed countries and do not offer profit opportunities in resource-poor countries (246,260). However, new public-private partnerships are emerging to facilitate the development of essential new tools (261), including three partnerships established with support from the Bill and Melinda Gates Foundation: the Global Alliance for Tuberculosis Drug Development (http://www.tballiance.org), the Aeras Global Tuberculosis Vaccine Foundation (http://www.aeras.org), and the Foundation for Innovative New Diagnostics (http://www.finddiagnostics.org). These organizations have provided venues to identify and address obstacles to developing new tools for TB among private industry, public and academic researchers, and philanthropic organizations. These organizations also receive support from the private sector.

The pharmaceutical industry has also contributed to the global TB control effort by assisting in making drugs for TB, including second-line drugs for patients with multidrug-resistant TB, more affordable (262,263). Such actions can enable pharmaceutical companies to become leaders in efforts to improve TB control and prevention.

Roles and Responsibilities of the Pharmaceutical and Biotechnology Industries

• The pharmaceutical and biotechnology industries should
  --- understand the dimensions of the global TB epidemic and realize their key role in developing the necessary tools for diagnosis, treatment, and prevention of TB;
  --- respond to the current surge of interest in TB globally by reexamining the costs of new product development and by considering potential new public and private funding and the markets for such      products in developing countries;
  --- contribute their perspectives and become involved in coalitions such as NCET, the Global Partnership to Stop Tuberculosis, the Global Alliance for Tuberculosis Drug Development, and the Foundation for Innovative New Diagnostics; and
  --- work with other stakeholders to ensure access of essential products to those whose lives are at stake.

Essential Components of TB Control in the United States

Case Detection and Management

Case detection and case management include the range of activities that begin when a diagnosis of TB is first suspected and end with the completion of a course of treatment for the illness. TB case management describes the activities undertaken by the jurisdictional public health agency and its partners to ensure successful completion of TB treatment and cure of the patient. The rationale and methodology of TB case management have been described previously (5). Organizational aspects of case management from the viewpoint of the jurisdictional public health agency are also discussed in this statement.

Case detection includes the processes that lead to the presentation, evaluation, receipt of diagnosis, and reporting of persons with active TB. Case detection involves patients with active TB who seek medical care for symptoms associated with TB, their access to health care, their health-care providers, the consultants and clinical laboratories used by those health-care providers, and the responsible public health agency. Although steadily increasing treatment completion rates (14) indicate that progress has been made in the management of TB patients, TB case detection is still problematic. Delays in diagnosis and report of TB cases continue to be common. Also, despite the 44% reduction in TB incidence in the United States since 1992, the proportion of pulmonary cases that are sputum smear-positive at diagnosis has changed little, accounting for >60% of all reported cases (14). The majority of pulmonary TB cases continue to be diagnosed at an advanced stage. Earlier diagnosis would result in less individual morbidity and death, greater success in treatment, less transmission to contacts, and fewer outbreaks of TB. Improvement in the detection of TB cases is essential to progress toward elimination of TB in the United States (Box 1).

The first step in improving TB case detection is to remove barriers in access to medical services that are often encountered by persons in high-risk categories. Such barriers might be patient-related, such as cultural stigmas associated with the diagnosis of TB, which might lead foreign-born persons to deny or hide symptoms (264,265), or fear of being reported to immigration authorities if medical care is accessed (19). Foreign-born persons, particularly recently arrived immigrants, refugees, and other persons of low SES might not have access to primary health services because they do not have health insurance or they are not familiar with the U.S. medical care system (20,118,266).

Removing patient-related barriers to health care is particularly difficult. Improved patient education about TB is needed (18). Continuing immigration from countries at high risk, often including persons with strong cultural views about TB, underscores the need for patient education. As with other interventions to enhance TB control and prevention, local public health action should be based on the local pattern of disease. In developing education messages and outreach strategies, public health authorities should work with organizations that serve communities at high risk to gain community input (203). This statement provides recommendations on working with community-based organizations, key informants, and academic institutions to gain ethnographic information, learn about the health beliefs and values of populations at high risk within the community, and develop targeted interventions that will be most effective.

The majority of TB cases are detected during the medical evaluation of symptomatic illnesses (19,267). Persons experiencing symptoms ultimately attributable to TB usually seek care not at a public health TB clinic but rather from other medical practitioners and health-care settings. In 18 California counties with the highest TB morbidity of persons during 1996--1997, initial points of entry into the health-care system for persons who received a diagnosis of TB were hospital inpatient evaluations (45%), private outpatient offices or clinic evaluations (32%), TB clinic evaluations (12%), and other sites (11%), including a non-TB clinic in a health department and correctional facilities (California Tuberculosis Controllers Association, unpublished data, 2003). A similar pattern was observed in Washington state. In Seattle and its suburban areas in 1997, primary care practitioners or clinics reported 48% of TB cases during evaluations of outpatients with symptoms and 32% during hospital evaluations; only 2% of cases were diagnosed during a public health TB clinic evaluation for a symptomatic illness (Seattle-King County Department of Public Health, unpublished data, 1998).

These data indicate that the professionals in the primary health-care sector, including hospital and ED clinicians, should be trained to recognize patients with symptoms consistent with TB. Dramatic reductions in TB were recorded in NYC (13) and Baltimore (195) in association with extensive education campaigns for health-care providers in the community. These studies indicate the need to maintain clinical expertise for the diagnosis and treatment of TB (24,41).

Because pulmonary disease among adults is most frequently associated with the spread of TB, the following discussion and recommendations regarding TB case detection are limited to considerations of pulmonary TB among adults. A classic set of historic features, signs, symptoms, and radiographic findings occurring among adults should raise a suspicion of pulmonary TB and prompt a diagnostic investigation (3,189,267--271). Historic features include exposure to TB, a positive test result for M. tuberculosis infection, and the presence of risk factors such as immigration from a high-prevalence area, HIV infection, homelessness, or previous incarceration. Signs and symptoms typical of TB include prolonged coughing with production of sputum that might be bloody, fever, night sweats, and weight loss. On a chest radiograph, the classical findings of TB in immunocompetent patients are upper-lobe infiltrates, frequently with evidence of contraction fibrosis and cavitation (270). However, these features are not specific for TB, and, for every person in whom pulmonary TB is diagnosed, an estimated 10--100 persons are suspected on the basis of clinical criteria and must be evaluated (272,273).

The clinical presentation of TB varies considerably as a result of the extent of disease and the host response. In addition, variation in clinical symptoms and signs of TB is associated with underlying illnesses (e.g., HIV infection, chronic renal failure, alcoholism, drug abuse, and diabetes mellitus). The signs of TB are also associated with race and ethnicity and are attributed to unknown factors (3,267,270). The chest radiograph among persons with advanced HIV infection and pulmonary TB, for example, might have lower-lobe and lobar infiltrates, hilar adenopathy, or interstitial infiltrates (274). TB should be suspected in any patient who has persistent cough for >2--3 weeks or other compatible signs and symptoms as noted previously (10,267,275).

In the drive toward TB elimination in the United States, effective TB case detection is essential, and medical practitioners should recognize patients in their practice who are at increased risk for TB and be aware of the possibility of diagnosing TB if they observe compatible symptoms. Guidelines have been provided for the initial steps of TB case detection in five clinical scenarios encountered by providers of primary health care, including those serving in medical EDs (Table 5). In these settings, evidence exists to support proceeding with a diagnostic evaluation for pulmonary TB. The subsequent management of suspected cases in these scenarios depends on the judgment of the medical practitioner, in consultation with specialists in internal medicine, pulmonary diseases, or infectious diseases if necessary (5). These recommendations do not cover the spectrum of clinical presentations of pulmonary TB in adults and are not meant to substitute for sound clinical judgment.

Cases of pulmonary TB also are detected through directed public health activities designed to detect TB disease among certain persons who have not sought medical care. Compared with persons whose cases were detected passively by medical practitioners among patients who have sought medical care, persons whose cases are detected actively are usually in a less advanced stage of pulmonary disease, as manifested by the absence of symptoms and by negative sputum AFB smear results. Although no supporting literature exists, cases detected in that stage of disease might be less advanced and easier to cure.

Active efforts to detect cases of TB among persons who have not sought medical care are routinely made during evaluation of contacts of patients with pulmonary TB (30,31,276) and of other persons with newly diagnosed infection with M. tuberculosis (4). Screening for TB also is performed during evaluation of immigrants and refugees with Class B1 or Class B2 TB notification status (277--279), during evaluations of persons involved in TB outbreaks (34,35,136,172,280,281), and occasionally in working with populations with a known high incidence of TB (167,185). Screening for TB disease is indicated when the risk for TB in the population is high and when the consequences of an undiagnosed case of TB are severe (282), such as in jails and prisons (253,283).

Screening for TB disease (i.e., active case finding) might contribute substantially to overall TB case detection. A population-based study from Los Angeles indicated that 30% of reported TB cases during the period of study were detected through screening activities (267). During 1998--2001, of 356 TB cases reported by the Seattle-King County TB Program, 40 (11%) were detected through active case detection in contact investigation and evaluations of immigrants and refugees with Class B1 and B2 TB notification status.

The clinical settings in which TB has been effectively detected among persons without symptoms, the methodology of testing, and outcomes of the screening process have been described (Table 6). On the basis of its very high yield of detecting TB cases, domestic follow-up evaluation of immigrants and refugees with Class B1 and B2 TB notification status should be given highest priority by all TB-control programs. The yield of detecting TB cases during screening at homeless shelters increased sharply in an outbreak setting (Table 6). Although prevalence data from individual studies are not available, investigations undertaken to control TB outbreaks that involved diverse settings and groups of immunocompetent and immunocompromised persons have consistently been productive in detecting TB cases and high rates of LTBI among exposed persons (34,35,136,173,280,281). Outbreak investigations should be counted among the settings in which screening for active TB is recommended.

Contact Investigation and Outbreak Control

Contact investigation is an essential function of TB control in the United States (Box 4) (1,17). The investigation of a case of TB results in identifying approximately 10 contacts (284). Among close contacts, approximately 30% have LTBI, and 1%--3% have progressed to TB disease (30,284). Without intervention, approximately 5% of contacts with newly acquired LTBI progress to TB disease within 2 years of the exposure (285). The prevalence of TB among close contacts is approximately 1,000/100,000 population (>100-fold higher than in the general population) (285). Examination of contacts is therefore one of the most important activities for identifying persons with disease and those with LTBI who have a high risk for acquiring TB disease.

Transmission of M. tuberculosis has occurred in health-care facilities (286,287), bars (134,288), doctors' offices (289), airplanes (290), crack houses (291), respite facilities that provide care for HIV-infected persons (136), drug rehabilitation methadone centers (36), navy ships (292), homeless shelters (120), schools (173), church choirs (140), and renal transplant units (141). The utility and importance of contact investigations in those settings and also for populations at high risk (e.g., foreign-born persons [293], children [294--297], and persons exposed to multidrug-resistant TB cases [91,298]) has also been documented.

In the United States, state and local public health agencies perform 90% of contact investigations as part of the public health mandate for TB control (Box 5) (2). Public health TB-control programs are responsible for ensuring that contact investigations are conducted effectively and that all exposed contacts are identified, provided with access to adequate care, and followed to completion of therapy. For health agencies to fully discharge this responsibility, adequate funding and political commitment are required.

Health agencies use a general epidemiologic framework for contact investigations (299). However, this approach alone might have limited effectiveness because of factors such as initial diagnostic delays and failure to ensure completion of therapy for LTBI. Consequently, programs have recognized the necessity of widening traditional contact investigation sites to include nonhousehold locations (e.g., homeless shelters, correctional facilities, nursing homes, and hospices that serve HIV-infected persons) and households. Genotyping studies have documented that traditional contact investigation methods have failed to identify contacts or detect transmission of M. tuberculosis (28,33,34,151,172). As a result, IOM (2) and ACET (1) have called for the development and implementation of enhanced techniques for contact investigation.

The primary goal of a contact investigation is to identify persons who were exposed to infectious M. tuberculosis and ensure that they are tested for M. tuberculosis infection, screened for TB disease, are followed up, and complete a standard course of treatment, if indicated. Secondary goals are to stop transmission of M. tuberculosis by identifying undetected patients with infectious TB and to determine whether a TB outbreak has occurred. In that case, an expanded outbreak investigation should ensue.

Steps of a Contact Investigation

State and local public health agencies, often represented by TB-control programs, are responsible for initiating and conducting contact investigations and evaluating their outcomes to ensure their effectiveness. A contact investigation has 14 steps, as follows:

1. Setting priorities. A contact investigation is considered once a suspected or confirmed case of TB comes to the attention of the jurisdictional TB-control program. At that time, a decision should be made about the priority of that investigation among other TB-control activities. Not all cases of TB require a contact investigation, and certain investigations will have greater priority than others. Priorities should be decided on the basis of the characteristics of the source-case, of the environment of the place(s) of exposure, and of the contacts. The three most important categories of information used to establish priorities for cases for contact investigations are 1) the site of disease, 2) the results of sputum AFB smears and NAA testing, and 3) the findings on the chest radiograph. In general, patients with pulmonary TB, positive sputum AFB smear results, and cavitation noted on a chest radiograph are more infectious and therefore have a higher priority for contact investigation. The use of an NAA test is helpful in rapidly differentiating between pulmonary disease caused by M. tuberculosis and nontuberculous mycobacteria, thus avoiding unnecessary contact investigations. Persons with pulmonary TB who have negative sputum AFB smear results tend to be less infectious, and their contacts should be investigated, but with lower priority.  Contacts of patients with extrapulmonary TB should be evaluated if the patient has concurrent pulmonary or laryngeal disease, the contacts are at increased risk for acquiring TB disease (e.g., children aged <5 years and HIV-infected persons), or the patient has pleural TB (300). Pleural TB is a manifestation of primary TB and often occurs among persons who have been recently infected. In addition, persons with pleural TB can have positive sputum AFB smear results. Children aged <5 years with TB, regardless of the site of disease, should have a contact investigation to identify the source-case.
2. Defining the beginning and end of the period of infectiousness. Before a contact investigation can be started, the period of infectiousness of the index case should be determined. This period sets the limits for the investigation, allows for setting priorities for contacts within the designated timeframe, and determines the scheduling for follow-up tests. Exactly when a patient becomes infectious is unknown; the usual assumption is that the patient becomes infectious approximately 3 months before diagnosis; however, it might be longer, depending on the history of signs and symptoms, particularly cough and the extent of disease. The end of the period is defined as the time when contact with the index case is broken or when all of the criteria for determining when during therapy a patient with pulmonary TB has become noninfectious (Box 3) are met. Patients with multidrug-resistant TB who are on inadequate therapy or who have persistently positive sputum AFB smear or culture results might remain infectious for a prolonged period of time. Those patients, if not in effective isolation, should be reassessed for new contacts as long as they remain infectious.
3. Medical record review. For potential transmission risk and infectiousness of a case to be assessed, all currently available information about the reported case or suspect is obtained through case medical record reviews, conversations with the health-care provider or other reporting source, and laboratory report reviews. This information can be disclosed by covered entities for public health activities as provided by the Privacy Rule of HIPAA (217).
4. Case interview and reinterview. The patient interview may be conducted in the hospital, at the patient's home, or wherever convenient and conducive to establishing trust and rapport. The ability to conduct an effective interview might determine the success or failure of the contact investigation. All persons with whom the patient has been in close contact and the locations that the patient commonly frequents should be identified. Good interviewing skills can elicit vital information that otherwise might not be forthcoming. For different reasons (e.g., stigmatization, embarrassment, or involvement in illegal activities), patients might be reluctant to identify contacts or places they frequent. Developing an ability to interview patients effectively so as to elicit contacts requires training and periodic review by supervisors, and only trained personnel should interview patients. A patient should be interviewed as soon as possible after notification and reinterviewed 1--2 weeks later to clarify data or obtain missing data. When possible, the second interview should be conducted at the patient's primary residence. Also, all interviews should be conducted in the patient's primary language and with sensitivity to the patient's culture.
5. Field investigation. Field investigations enable investigators to 1) interview or reinterview identified contacts and obtain an adequate medical history to evaluate previous exposure to TB, existence of prior M. tuberculosis infection, existence of disease and treatment, risk factors for acquiring TB, and symptoms; 2) obtain locator information; 3) apply a tuberculin skin test to identified contacts (the role of QFT-G in the assessment of contacts has not been determined); 4) observe contacts for any signs or symptoms suggestive of TB; 5) schedule subsequent medical evaluations and collect sputum samples from any contact who is symptomatic; 6) identify sources of health care and make referrals; 7) identify additional contacts who might also need follow-up; 8) educate contacts about the purpose of the investigation and the basics of TB pathogenesis and transmission; 9) observe the contact's environment for possible transmission factors (e.g., crowding and poor ventilation); 10) assess contacts' psychosocial needs and other factors that might influence compliance with medical recommendations; and 11) reinforce confidentiality. Visits to the exposure site(s) should be conducted as soon as possible. Contacts at higher risk for disease progression and more severe disease (e.g., young children and HIV-infected persons) require the most rapid follow-up.  Transmission sites might involve social networks not customarily considered in traditional contact investigations. For example, in certain TB cases reported separately in different communities, participation in a church choir was identified as a common factor (140). The contact investigation failed to identify the source-patient's choir contacts, resulting in secondary cases of TB. In an outbreak associated with a floating card game, the outbreak was propagated because a network of persons engaged in illegal activities was not identified (172). These examples demonstrate the importance of congregate activities beyond work and socially defined high-risk contacts.
6. Clinical evaluation of contacts. All close contacts of patients with pulmonary or laryngeal TB and a positive culture result for M. tuberculosis or a positive sputum AFB smear result should receive a tuberculin skin test unless they have documentation of a previously positive test. Highest priority for tuberculin skin testing and follow-up evaluation should be given to 1) contacts identified as being at highest risk for recent infection on the basis of their history of exposure to the case-patient and risk for transmission and 2) those at high risk for progression from M. tuberculosis infection to TB disease (e.g., infants, young children, HIV-infected persons, and other persons whose medical conditions predispose them to progress from infection to disease). Among children and infants, children aged <3 years are at greatest risk for rapid progression and should receive the highest priority for all preventive interventions for contacts. For the greatest level of protection of children exposed to TB to be ensured, all children aged <5 years should be considered to be high-risk contacts. 
   
   Regardless of where the tuberculin skin test is performed (e.g., field visit, TB clinic, or referral site), arrangements should be made to ensure that the skin test is read within 48--72 hours. Contacts who have tuberculin skin test reactions >5 mm and who have no history of a prior positive result are considered at risk for newly acquired M. tuberculosis infection. Those persons should receive a chest radiograph and medical evaluation for TB disease. Adults and children aged >5 years should receive a single posterior-anterior radiograph (4); children aged <5 years should receive both posterior-anterior and lateral TB radiographs (4). The following contacts should have a chest radiograph regardless of skin test result: 1) persons with symptoms of TB; 2) persons who are immunosuppressed or who have other risk factors for progression from M. tuberculosis infection to TB disease; and 3) children aged <5 years.
   
   The presence of HIV coinfection might affect decisions about subsequent management of contacts (e.g., prescribing prophylactic treatment and completing treatment for LTBI regardless of results of a tuberculin skin test). An HIV-infected contact also should be effectively counseled about the substantial risk for disease progression and the need to accept and adhere to a course of treatment for LTBI. Although contacts of HIV-infected persons with TB have substantial risk for HIV infection themselves, contacts of TB cases without HIV infection have low rates of HIV infection (301), suggesting that offering HIV testing to all contacts might not be cost-effective. The decision should be based on local data demonstrating that contacts of TB cases are at high risk for HIV infection (i.e., the contacts have a prevalence of HIV infection of >1% [302]). The local epidemiology of TB, HIV infection, and TB/HIV coinfection also may be used as a basis for the decision. If resources are limited, and if local data indicate that HIV infection contributes only minimally to the TB problem (i.e., the HIV seroprevalence of contacts is likely to approach 0.1% of the general U.S. population), then the highest priority for voluntary HIV counseling and testing should be assigned to contacts of HIV-infected persons with TB and those who have identified risk factors for HIV (303).
   
   Contacts who have a documented prior positive tuberculin skin test and who are not known or likely to be immunocompromised generally do not require further evaluation unless they have symptoms suggestive of TB disease. However, candidates for treatment of LTBI on the basis of other criteria (4) should first receive a medical evaluation, including a chest radiograph, to exclude TB. Contacts with a negative tuberculin skin test should be retested approximately 8--12 weeks after the first test unless the initial skin test was performed >8 weeks after the contact's last exposure to the index patient. Every 3 months, all contacts with negative skin test results who remain in close contact with an infectious patient should receive a repeat tuberculin skin test and, if symptoms of TB disease are present, a chest radiograph. A contact whose repeated test is positive (>5mm) should receive a chest radiograph if one has not been taken recently. If the radiograph is normal, the contact should be evaluated for treatment of LTBI; if it is abnormal, the patient should be evaluated for TB disease or other cause of the abnormality.
   
   TB-control programs should find and evaluate all persons who have had sufficient contact with an infectious TB patient to become infected. Contacts at high risk (e.g., infants, young children, and HIV-infected persons) should be identified and evaluated rapidly to prevent the onset of serious, potentially life-threatening complications (e.g., TB meningitis). In certain jurisdictions, legal measures have been put in place to ensure that contact evaluation and follow-up occurs (304). The use of existing communicable disease laws should be considered for contacts that fail to comply with the examination requirements. All contacts should be assessed routinely for obstacles to their participation in the evaluation process. Any structural barrier that impedes the ability of the patient to access services (e.g., inconvenient clinic hours or location, work or family obligations, and lack of transportation) should be addressed.
7. Treatment of contacts with LTBI. Contacts with LTBI should be treated unless compelling contraindications exist. For completion of therapy to be ensured, contacts should be placed on DOT whenever possible. If resources do not allow that all infected contacts receive DOT, priority should be assigned to 1) children aged <5 years; 2) contacts with HIV infection; 3) other contacts with risk factors for progression to TB disease (4); 4) contacts with documented skin test conversion; and 5) contacts of patients with positive sputum AFB smear results and cavities on chest radiography. Contacts on self-administered therapy should be monitored monthly by personal interview for adverse effects and adherence until treatment is completed.
8. Primary prophylaxis of high-risk contacts. Because tuberculin skin test results might take 8--10 weeks to become positive after infection with M. tuberculosis, a contact's initial skin test result might be negative even if the person is infected. A second test should be placed 8--12 weeks after the contact's last exposure to the infectious patient, so the possibility of LTBI for those persons can be better evaluated. During the 8--12 week window period between a first and second skin test, the following contacts with initially negative tuberculin skin test results should receive treatment for LTBI after TB disease has been ruled out by clinical examination and chest radiograph: 1) contacts aged <5 years (with highest priority given to those aged <3 years) and 2) contacts with HIV infection or who are otherwise immunocompromised (4). If the second skin test result is negative (<5 mm), the contact is immunocompetent (including immunocompetent young children) and no longer exposed to infectious TB, treatment for LTBI may be discontinued, and further follow-up is unnecessary. If the second skin test is negative but the contact is immunocompromised (e.g., with HIV infection), a course of therapy for LTBI should be completed. If the second skin test result is negative but the person remains in close contact with an infectious patient, treatment for LTBI should be continued if the contact is 1) aged <5 years; 2) aged 5--15 years, at the clinician's discretion; or 3) HIV-seropositive or otherwise immunocompromised.
9. Expanding the contact investigation. Defining the extent of the contact investigation is the responsibility of the investigating TB-control program. Once testing of high-priority contacts is completed, the extent of transmission of M. tuberculosis should be evaluated. Consideration can then be given to expanding the investigation to include contacts at lower risk for infection. In general, the contact investigation need be expanded only if excessive transmission is detected, on the basis of the following criteria: 1) secondary cases of TB are identified in contacts; 2) documented skin test conversions exist; and 3) comparison of skin test positivity among contacts with available data on the baseline prevalence of skin test positivity in the population indicates the probability of transmission. When a contact investigation is expanded, resources should continue to be directed to persons identified as being at greatest risk. In any case, the total contact-tracing process should be completed <3 months after initiation of the investigation, unless evidence of transmission requires further expansion of testing.
10. Data management and use in decision-making. Maintenance of data is crucial to all aspects of the contact investigation. Protocols should be developed to maximize the efficiency of the process, given available resources. Data should be collected for cases and contacts by using standardized forms (paper or electronic) with standard definitions and formats, according to national guidelines (305). Data elements should mirror those collected by the states and CDC, but individual jurisdictions may elect to expand the data elements.
11. Evaluation. Contact investigation steps should be adequately documented, so the process can be monitored and evaluated. National performance measures for TB control stipulate that programs should complete treatment of LTBI among 61% of contacts of infectious TB cases (Table 4). Additional parameters should also be tracked and evaluated. Programs should determine whether the indications given previously for conducting a contact investigation are applied to all reported cases. In addition, for each TB case that is investigated, the number of contacts identified should be recorded. For each contact identified, outcomes to monitor include 1) whether the contact evaluation took place (including placing and reading the first and second tuberculin skin tests, if applicable) and was completed and 2) whether the recommended protective interventions (including screening for TB disease, treatment for LTBI, and prophylaxis within the window period) were offered, accepted, started, and completed. Results of the evaluation should be aggregated and recorded for stipulated intervals of time, as follows: 1) among identified contacts, the number and percentage that were referred for evaluation; 2) among those referred, the number and percentage that completed evaluation; 3) among those evaluated, the number and percentage eligible for treatment of LTBI; and 4) among those eligible, the number and percentage that started and completed treatment.
    
    Surveillance of individual contacts is not conducted routinely in the United States. However, CDC collects aggregate data on the outcomes of contact investigations from state and local TB control programs through the Aggregate Report for Program Evaluation. Routine collection and review of these data can provide the basis for evaluation of contact investigations for TB control programs.
12. Education and training for contact investigations. The education needs for all aspects of the investigation process (including medical abstraction, patient interviewing, cultural competency, maintaining patient confidentiality, and how to perform tuberculin skin testing) should be continuously assessed. All involved staff should receive ongoing training. CDC-funded regional training centers offer training courses in contact investigation and interviewing skills.
13. Confidentiality. Maintaining confidentiality is a critical component of the contact investigation process. Guidelines for release of confidential information related to conducting contact investigations should be developed. An example of appropriate release of confidential medical information is the release of an index case patient's drug susceptibility test results to a clinician caring for a contact with LTBI or one who has progressed to active TB.
14. Contact investigations among special populations. Contact investigations often are conducted among special populations or locations (e.g., homeless shelters, correctional facilities, HIV residential facilities, schools, worksites, health-care facilities, active drug users, and living along the U.S.--Mexico border). Guidelines offering specific recommendations for contact investigations under these circumstances have been published (305).

Outbreak Investigations

Failure to recognize an increase in the occurrence of TB (162) or to expand a contact investigation when needed can result in continued transmission of TB. Missed epidemiologic links among patients with TB can have severe consequences as evidenced in an outbreak associated with a floating card game in the rural south (172) and an outbreak in Kansas among exotic dancers and their close contacts that occurred during a 7-year period (38).

When TB occurs with high incidence, clusters of cases that have epidemiologic links likely occur constantly but tend to blend into the generally high morbidity (306). In a low-incidence setting, however, clusters of linked TB cases can be identified more readily. Three criteria have been established to determine that a TB outbreak is occurring (162): 1) an increase has occurred above the expected number of TB cases; 2) transmission is continuing despite adequate control efforts by the TB-control program; and 3) contact investigations associated with the increased cases require additional outside help.

TB outbreaks have occurred in low-incidence areas in which expertise and experience in dealing with such outbreaks might be lacking. Such outbreaks have occurred among different populations and settings, including a young foreign-born child in North Dakota (25); exotic dancers and their contacts in Kansas (38), homeless persons in Syracuse, New York (120); factory workers in Maine (188); and limited, seemingly unrelated clusters of cases that were the cause over time of perpetuating transmission in Alabama (307).

For an increase in the expected number of TB cases (the first criterion of an outbreak) to be identified, the local epidemiology of TB should be understood. Detection of a TB outbreak in an area in which prevalence is low might depend on a combination of factors, including recognition of sentinel events, routine genotype cluster analysis of surveillance data, and analysis of M. tuberculosis drug-resistance and genotyping patterns.

When an outbreak is identified, short-term investigation activities should follow the same principles as those for the epidemiologic part of the contact investigation (i.e., defining the infectious period, settings, risk groups, mode of transmission, contact identification, and follow-up). However, long-term activities require continued active surveillance, M. tuberculosis genotyping, additional contact investigations and related follow-up for additional cases, and continuing education of providers, staff, and patients. Consequently, a plan for long-term support should exist from the outset of the investigation.

A written protocol should be developed. At a minimum, the protocol should outline the outbreak response plan, including indications for initiating the plan, notification procedures, composition of the response team, sources of staffing, plan for follow-up and treatment of contacts, indications for requesting CDC assistance, and a process for evaluation of the outbreak response. The outbreak response plan should also include information on how to work strategically with the media during the public health emergency. CDC offers training packages to assist public HCWs in media communications, including emergency and crisis communication. This training emphasizes prevent planning, event response activities, and post-event follow-up. Information on public health communication programs is available at http://www.cdc.gov/communication/cdcynergy.htm.

Targeted Testing and Treatment of LTBI

An estimated 9.5--14.7 million persons in the United States have LTBI (39). Continued progress toward eliminating TB in the United States and reducing TB among foreign-born persons will be impossible without devising effective strategies to meet this challenge. Guidelines on targeted testing and treatment of LTBI have been published (4) and revised (308). Those guidelines include recommendations for diagnosing LTBI and treating infected persons, limiting the possibility of treatment-associated hepatotoxicity, and identifying persons and populations to target for testing. A new diagnostic test for LTBI, QFT-G, has been approved by FDA, and guidelines for its use will be published by CDC. This section outlines a recommended approach to planning and implementing programs for targeted testing and treatment of LTBI to create an effective public health tool for communitywide prevention of TB.

Targeted testing and treatment of persons with LTBI is not a new concept for the prevention of TB in the United States (309). The effectiveness of treating LTBI among populations at high risk has been established in clinical trials (285), but this intervention has not been proven to have an impact on the incidence of TB in the United States. Theoretically, the epidemiologic impact would be considerable if cases of TB in a population were largely the result of progression of LTBI and if all persons at high risk with latent infection could be identified and treated successfully. Practically, those circumstances rarely exist. In the United States, the effectiveness of targeted testing and treatment of LTBI as a public health measure has been limited by concern for the side effects of treatment (notably hepatotoxocity) (310), poor acceptance of the intervention among health professionals (311), and poor adherence among patients to the lengthy course of treatment (45,312).

Two approaches exist to increasing targeted testing and treatment of LTBI. One is to promote clinic-based testing of persons who are under a clinician's care for a medical condition (e.g., HIV infection or diabetes mellitus) that also confers a risk for acquiring TB. This approach, which depends on a person's risk profile for TB and not on the local epidemiology of the disease, requires education of health-care providers and depends ultimately on their initiative. Although difficulties exist in quantifying and evaluating its effectiveness, this approach could conceivably become a useful tool to reduce the incidence of TB among foreign-born and other persons at high risk because they can be accessed conveniently where they receive primary health-care services. The other approach is to establish specific programs that target a subpopulation of persons who have a high prevalence of LTBI or who are at high risk for acquiring TB disease if they have LTBI, or both. This approach presumes that the jurisdictional TB-control agency has identified the pockets of high TB risk within its jurisdiction through epidemiologic analysis and profiling (313--316). Those high-risk pockets might consist of foreign-born, homeless, or HIV-infected persons, or they might be geographic regions (e.g., a neighborhood within a city or town) or specific sites (e.g., a homeless shelter or an HIV-housing facility).

The epidemiologic profile should include an assessment of the risk for TB in the population or at the site, the ease of access to the population or site, and the likelihood of acceptance of and adherence to targeted testing and treatment. For this assessment to be facilitated, populations at high risk may be separated into three tiers (Box 6). Assignment of groups to these three tiers is based on six criteria: 1) incidence of TB; 2) prevalence of LTBI; 3) risk for acquiring TB disease if the person is infected with M. tuberculosis; 4) likelihood of accepting treatment for LTBI and adhering to it; 5) ease of access to the population; and 6) in a congregate setting, the consequence of transmission of M. tuberculosis.

Tier 1 is made up of well-defined populations at high risk that can also be conveniently accessed and followed, either in locations such as clinics or community health centers, prisons, or other congregate living sites or through mandatory registration. Persons in this tier often have a high prevalence of TB and LTBI (immigrants and refugees with Class B TB notification status), an increased risk for TB disease if infected with M. tuberculosis (persons with HIV infection), or both (certain homeless and detained populations). The consequences of the spread of TB in congregate settings increase the necessity of preventive action. Location-based, high-risk communities in Tier 1 are, for the most part, readily identifiable and easily accessible; often have their own resources; and generally include the probability of access for a long enough period to permit completion of treatment for LTBI. These populations should be the first priority for targeted testing programs.

Persons enrolled in substance-abuse treatment centers may be considered transitional between Tier 1 and Tier 2, depending on local epidemiologic and demographic factors. Substance abusers might have a high prevalence of LTBI. Injection drug users also might have an increased risk for acquiring TB if they are infected with M. tuberculosis and at increased risk for HIV infection (317). Access and factors related to acceptance and completion of therapy also might vary by location. Typically, substance abuse treatment centers that include long-term inpatient treatment or regularly scheduled appointments (e.g., methadone treatment centers) are the best choices for intervention because ease of ongoing access allows sufficient time for completion of therapy. Voluntary HIV counseling and testing should be offered routinely as part of any targeted testing program among this population.

Populations in Tier 2 also include identifiable and accessible populations made up of persons at high risk, but the distinguishing characteristic is that obtaining satisfactory rates of completion of treatment for LTBI might be difficult because of dispersal of the population throughout a larger community or a brief duration of residency in congregate settings. For example, in Atlanta, Georgia, after local epidemiology of TB was analyzed, community sites for targeted testing and treatment of LTBI of residents of high-risk inner-city areas were identified (184). Sites of access included outpatient areas of the public hospital, the city jail, clinics serving homeless persons, and neighborhoods frequented by substance abusers. Although 65% of the targeted population that had a tuberculin skin test placed returned to have the skin test read, only 20% of those with an indication for treatment of LTBI completed a course of therapy; this represented 1% of persons who underwent targeted testing.

Tier 3 consists of persons born in countries with a high incidence of TB or U.S.-born persons in racial/ethnic minority populations with high prevalence of LTBI who do not necessarily have an increased risk for progressing to TB disease. Eventually, the control of TB among foreign-born persons and progress toward elimination of TB in the United States depends on achieving greater success in preventing TB among populations at high risk by widespread targeted testing and treatment of LTBI in the public and private medical sectors. However, establishing successful targeted testing and treatment programs for foreign-born persons who are not found in Tier 1 or Tier 2 settings is challenging. Obstacles include the limitations of the tuberculin skin test to differentiate between reactions attributable to BCG or infection with M. tuberculosis, the prevalent belief among a substantial number of foreign-born persons that BCG vaccination is the cause of a positive test for M. tuberculosis infection and is also protective against TB disease, language and cultural barriers, barriers in access to medical care, and difficulties in providing outreach and education.

Typical Tier 3 populations are new refugee and immigrant groups that are not yet assimilated into U.S. society. Such populations might be ignorant of their TB risk, usually lack ready access to health-care services, and might have strong cultural understandings about TB that are at variance with those that guide TB-control activities in the United States. TB-prevention activities in this kind of community are highly cost-intensive (221). Engaging such communities is a challenging task.

Community-based TB prevention for Tier 3 populations requires a partnership between the jurisdictional health department and the affected community. The community should gain an understanding of the TB problem as it relates to them and should participate in the design of the intervention. Community education is essential for this approach to succeed. The target population should be involved in the design and implementation phases of the intervention, interventions should be developed within the cultural context of the targeted population, and intermediate goals or benchmarks should show the population that program activities are achieving success. For example, in Los Angeles, California, the public health TB program contracted with community-based organizations to screen and provide treatment for LTBI to persons at risk in Latino and Asian neighborhoods and at schools teaching English as a second language (249). In Cambridge, Massachusetts, a coalition of Haitian community groups identified TB education as an issue for their community; strategies to achieve this goal included development of a videotape written and produced for viewing in Haitian barbershops and beauty salons in the community, a lottery, and measures for evaluation in terms of knowledge and future access to care (S. Etkind, Massachusetts Department of Health, personal communication, 2002).

For communities in Tier 3, TB is only one (and often not the most important) of multiple medical and public health needs. A broad approach should be adopted that includes TB prevention with other activities to improve health status. Certain Tier 3 populations have achieved sufficient self-identity and development to establish access to health care through a community health center, individual medical providers, or clinics. Those communities that have an already established route of access to health care have an infrastructure in place to establish programs for targeted testing and treatment of LTBI. Obstacles to overcome often include lack of medications and chest radiographs, the need for a system to track patients who do not return for monthly appointments, and the capacity to evaluate the program.

Programs for population-based targeted testing and treatment for LTBI often have been conducted by public health agencies through TB-control programs. However, recent studies have also described the establishment of such programs in nonpublic health venues. Promising results, in terms of access to persons at high risk and completion of treatment of LTBI, have been achieved from nontraditional sites, including syringe exchanges (318), jails (256), neighborhood health clinics (319), homeless shelters (320), and schools (321,322). This trend indicates a widening interest in this means of preventing TB and is possibly influenced by the emergence of community-oriented primary care (241,323), which places primacy on interventions for specific patients that help prevent disease and preserve the health of the entire population from which these patients are drawn.

As programs move from Tier 1 to Tier 2 and Tier 3 populations, the complexity of the effort and the cost of the program will increase. Also, because persons in Tier 3 populations generally have a lower risk for progression from LTBI to TB disease, the effectiveness and impact of a program will be less than efforts directed to Tier 1 and Tier 2 populations. Whatever population is selected or strategy is employed for the targeted testing project, programs should systematically evaluate the activity to ensure the efficient use of resources. Process, outcome, and impact indicators should be selected and routinely monitored by the program.

For purposes of monitoring and evaluation, activities associated with targeted testing and treatment for M. tuberculosis infection can be divided into three phases: the testing itself, the medical evaluation of persons with positive test results, and the treatment of those persons with LTBI. Performance indicators should be selected for each phase. For the testing phase, indicators include the number of persons at high risk identified and the number and proportion of those that were actually tested. Among those tested, the number and proportion that had a positive result for M. tuberculosis infection should be tracked. Useful indicators for the medical evaluation phase include the proportion of persons with a positive test result who completed a medical evaluation and the number and proportion that were determined to have TB disease. Indicators for the treatment phase include the proportion of eligible persons starting treatment for LTBI and the number and proportion that completed treatment. Reasons for failure to complete treatment (e.g., adverse drug effects, loss of interest, and loss to follow-up) should be monitored. Costs should be measured for each phase of the project. The cost per person with LTBI completing treatment provides a measure of the relative efficiency of the program. Finally, the impact of the program can be estimated by estimating the number of cases of TB prevented, which is dependent on the number of persons completing treatment and the estimated risk for progressing to TB disease.

Surveillance of persons with LTBI does not routinely occur in the United States. However, CDC has recently developed a national surveillance system to record serious adverse events (i.e., hospitalization or death) associated with treatment of LTBI. Surveillance of these events will provide data to evaluate the safety of treatment regimens recommended in current guidelines (4,324).

Control of TB Among Populations at Risk

This section contains recommendations for measures to control and prevent TB in five populations (children, foreign-born persons, HIV-infected persons, homeless persons, and detainees and prisoners in correctional facilities). Each of these populations occupies an important niche in the epidemiology of TB in the United States. Individual members of each population have been demonstrated, on the basis of their membership in the population, to be at higher risk for exposure to M. tuberculosis or for progression from exposure to disease, or both. Furthermore, nationwide surveillance and surveys (27,118--120,127,136,139,150,198,295,315,325,326 ) indicate that the epidemiology of TB in these populations is similar from community to community, which suggests that the recommended control measures are subject to generalization and can be applied more or less uniformly throughout the United States.

Children, foreign-born persons, HIV-infected persons, homeless persons, and detainees and prisoners should not be assumed to be the only populations at high risk for TB, nor are homeless shelters and detention facilities the only settings in need of enhanced TB-control strategies. Local surveillance and surveys frequently have identified populations and settings of high TB risk and transmission that required the formulation of specific control measures (122,137,152,313,315,316,327,328). This is the primary reason why state and local surveillance should be conducted to develop a clear understanding of the epidemiology of TB at the jurisdictional level.

Most important, the concept of identifying and targeting populations and settings at high risk should be viewed as a dynamic rather than as a static process. Such populations emerge and recede in importance at the local, state, and national levels. For example, foreign-born persons received little attention in the 1992 edition of this statement (6). A population whose risk for TB is now being recognized and delineated is U.S.-born non-Hispanic blacks, who account for approximately 25% of TB morbidity in the United States and who have TB rates approximately eight times those of whites (329,330) (Table 2). CDC and collaborating public health agencies in Chicago, Illinois and the states of Georgia and South Carolina are exploring new strategies to address this problem (331).

Control of TB Among Children and Adolescents

The occurrence of TB among infants and young children indicates recent transmission of M. tuberculosis and often the presence in the community of an unidentified adult with infectious TB. Thus, a case of TB in a child is a sentinel health event that signals a public health breakdown (197). Also, certain features of TB among children mandate special considerations in case detection and case management, contact investigations, and targeted testing and treatment of LTBI. For example, if LTBI results from exposure to TB in infancy and early childhood, a substantial risk exists for rapid progression to TB disease, including the development of potentially lethal forms of TB (198,294,325). The recommendations in this statement for control of TB among children and adolescents should receive high priority in all state and community TB-control plans.

Basis for Recommendations for TB Control Among Children and Adolescents

Case detection and primary prevention strategy: contact investigation of adults with pulmonary TB. The majority of infants and children who acquire TB disease do so within 3--12 months of contracting M. tuberculosis infection. Infants and toddlers aged <3 years are especially prone to the rapid progression from infection to disease, and they often acquire severe forms of TB, including meningitis and disseminated disease. The most important step to detect and prevent TB among children is the timely identification and effective treatment of adults with active TB. The cornerstone of TB prevention among children is high-quality contact investigations of suspected cases of pulmonary TB in adults, because 20%--40% of pediatric cases of TB could have been prevented if contact investigation had been more timely and thorough (198,293,325).

Contact investigation of adult pulmonary TB cases is crucial to the detection, control, and prevention of pediatric TB and its complications (332,333). The yield of detection of TB and LTBI is high, with an average of 50% of childhood household contacts having LTBI or TB disease (31,60). Because <50% of cases of TB among children are asymptomatic despite abnormal radiographic findings, contact investigation leads to earlier discovery of TB among children, better treatment outcomes, and fewer complications (326). Also, children with LTBI or TB disease identified through contact investigation are more likely to receive DOT at the same time as the source-case, which increases adherence to therapy.

Another benefit of contact investigations is the ability to identify and treat infants and young children who have been exposed to a person with a contagious case of TB and who might be infected but nevertheless have a negative tuberculin skin test (the role of QFT-G for diagnosis of LTBI in children aged <17 years has not been determined). A tuberculin skin test might take 2--3 months after infection to become positive in an infant or toddler. However, the incubation period for severe TB, including meningitis and disseminated disease, might be only 4--6 weeks. Failure to give empiric treatment for LTBI to exposed infants and young children with negative tuberculin skin test results, particularly those aged <3 years, might therefore result in rapid acquisition of disease (295,325).

Case management. The record for adherence to treatment for TB is no better for children than it is for adults (333). Children with TB might live in socially disorganized or disadvantaged homes and receive care from multiple adults. A chaotic environment can lead to a poor understanding of TB and its treatment and decreased adherence. DOT is effective in TB treatment for children and adolescents. However, almost 10% of children receiving DOT experience gaps in treatment that require extensions of therapy (326). Intensive-case management, including use of incentives and enablers, is a crucial element of a TB-treatment plan for children.

Contact investigation of cases of TB among children and adolescents. Contact investigations for children with suspected TB are generally conducted to identify the adult source-case. Identifying a source-case serves to establish the diagnosis of TB in the majority of children and, if the source-case is culture-positive for M. tuberculosis, to determine the likely drug susceptibility pattern of the infecting strain of M. tuberculosis in the child.

Even with optimal medical evaluation, M. tuberculosis can be isolated from <50% of children with clinically suspected TB. While microbiologic testing determines the diagnosis of TB for the majority of adults, positive culture results often are lacking for children. In the majority of cases, the diagnosis of pediatric TB is established by the triad of 1) a positive tuberculin skin test result, 2) either an abnormal chest radiograph or physical examination or both, and 3) discovery of a link to a known or suspected case of contagious pulmonary TB. Because culture yields from children with TB are low, determining the drug susceptibility pattern from the source-case isolate often is the only way to determine optimal treatment for children with either LTBI or TB disease (334,335).

Because TB among infants and young children usually occurs within weeks to months of contracting infection with M. tuberculosis, having a child with disease is a marker of recent transmission from someone in the child's environment. The source-case, often a parent or other caregiver (336--338), might not have been identified as having TB by the time the child becomes ill. Consequently, parents and other adults who are close contacts of children hospitalized with TB should be evaluated themselves for TB disease as soon as possible to serve as a case-detection tool and to prevent nosocomial transmission of M. tuberculosis (339). A chest radiograph should be performed on these family members to exclude pulmonary TB; certain centers have implemented this recommendation by requiring that adults who accompany a child have a chest radiograph performed and interpreted immediately while at the health-care facility (339). Other adult family members or friends also should be required to show evidence of a normal chest radiograph, performed by the health department or other provider, before being allowed to visit the child. Because TB in the child, not LTBI, is the reliable marker of recent infection, chest radiograph screening of accompanying adults is not necessary if the child has LTBI without TB disease.

Associate investigations (i.e., efforts to identify and evaluate household contacts of a child with LTBI to identify the infectious person responsible for the child's infection) are often performed as part of the evaluation of a child with LTBI (5,17,340--343). The usefulness of this approach depends on the criteria for placing skin tests on children. If testing of children at low risk is undertaken, associate investigations will be costly, have a low yield, and divert TB-control resources from more important activities. Associate investigations of children at high risk, however, usually detect a limited number of persons with TB but do identify substantial numbers of other persons with LTBI who are candidates for treatment (341--343).

Targeted testing and treatment of LTBI. In the 1950s and 1960s, child-centered TB control activities were based on periodic testing of all children for LTBI (344). However, as the number of TB cases dropped, the disease became concentrated among persons at high risk in particular subpopulations. Consequently, the majority of U.S. children have negligible risk for acquiring LTBI. Among children at low risk, the majority of positive tuberculin skin test results are false positives caused by nonspecific reactivity or exposure to nontuberculous mycobacteria in the environment (344). False-positive results lead to unnecessary health-care expenditures and anxiety for the child, family, school, and HCWs (345). Thus, while the testing of children with an expected high prevalence of LTBI is desirable, mass testing of children with a low prevalence of LTBI is counterproductive and should not be undertaken.

The optimal approach is to perform tuberculin skin testing only on those children with specific risk factors for LTBI. A questionnaire that assesses risk factors for TB can be used successfully in clinics and private offices to identify children at risk for LTBI (237,346--348); this approach can also be used to identify at-risk college students (349). The screening tool is the questionnaire; only those children whose answers indicate that they are at risk for LTBI should receive a tuberculin skin test. Use of a questionnaire can also address issues related to discrimination; all children in a setting such as a school or child-care center can be screened easily, but only those with identified risk factors for LTBI should receive a tuberculin skin test, thereby diminishing the number of false-positive results.

No single questionnaire has been validated for use in all settings and for all ages of children. Factors that have correlated highly with risk for LTBI among children in more than one study include 1) previous positive tuberculin skin test result; 2) birth in a foreign country with high prevalence; 3) nontourist travel to a high-prevalence country for >1 week; 4) contact with person with TB; and 5) presence in the household of another person with LTBI. Questions pertaining to a locally identified population with a high rate of TB should be included in a questionnaire, but validation of these questions is difficult.

In certain treatment programs for LTBI among children in the United States, the completion rate associated with 6--9 months of self-supervised isoniazid therapy is only 30%--50%. As LTBI among young children might progress rapidly to TB disease, DOT is recommended. Children with LTBI, who are most likely to benefit from DOT because of their high risk for rapid progression of infection to disease, include contacts of persons with recently diagnosed cases of pulmonary TB, infants and young children, and children with immunologic deficiencies, especially HIV infection.

Control of TB Among Foreign-Born Persons

TB among foreign-born persons is of increasing importance. During 1992--2003, the number of TB cases decreased 64% among U.S.-born persons but increased 8% among persons born outside the United States (14,15). During 1992--2003, the percentage of TB cases in the United States that occurred among foreign-born persons increased from 27% in 1992 to 53.3% in 2003 (15), and the number of states in which >50% of reported cases of TB occurred among foreign-born persons increased from four (8%) in 1992 to 25 (50%) in 2003 (15). In 2003, eight states (California, Florida, Illinois, Massachusetts, New Jersey, New York, Texas, and Virginia) accounted for 71% of cases among foreign-born persons. Foreign-born persons with TB have been more likely than U.S.-born persons to harbor drug-resistant strains of M. tuberculosis; in 2003, 10.6% of foreign-born persons with TB had TB with primary isoniazid resistance, compared with 4.6% of U.S.-born persons with TB (14).

The increase in cases of TB among foreign-born persons has been attributed to at least three factors (350). First, the number of persons entering the United States from other countries in which TB occurs with high incidence (44) now accounts for >75% of the immigrant flow (116,278); during 1994--2003, an estimated 80%--86% of immigrants admitted to the United States came from high-incidence countries (351). Second, foreign-born persons are subject to cultural and linguistic barriers that might affect health-seeking behavior and access to medical care, resulting in delays in diagnosis and difficulty in understanding and completing treatment (18,19,194,325). Third, these barriers, which have implications for the treatment, control, and prevention of TB among foreign-born persons, have not been sufficiently appreciated and addressed in TB-control program planning in the United States.

Precise information is lacking to assist in the identification of foreign-born persons who have an elevated risk for acquiring TB during residence in the United States. Immigrants entering either Canada or the United States have a risk for TB during their early years of residence that approximates that of residents of the country of birth (115,352,353). Over time, the risk declines and approaches that of residents of the host country. Consequently, recent guidelines have designated immigrants from countries with a high prevalence of TB who have resided in the United States <5 years as foreign-born persons at high risk (4).

Criteria for characterizing countries as having a high prevalence of TB have not been developed, and no consensus exists on which countries should be designated as having a high prevalence of TB. In rank order, the 14 countries listed most frequently as country of origin of foreign-born persons with reported TB in the United States are Mexico, the Philippines, Vietnam, India, China, Haiti, South Korea, Somalia, Guatemala, Ecuador, Ethiopia, Peru, El Salvador, and Honduras), and these 14 countries accounted for 76% of cases among foreign-born persons during 1999--2002 (14). Estimated incidence rates of TB in these countries in 2002 ranged from 33/100,000 population (Mexico) to 406/100,000 population (Somalia) (354). However, the country of origin of foreign-born persons with TB can vary substantially among localities within a state and between states and regions across the United States.

State and local TB control programs should develop their own profiles of risk for TB among foreign-born persons as part of the jurisdiction's overall epidemiologic analysis of TB and then define which immigrant and foreign-born populations in their areas should be considered as being at high risk for TB. Data sources for TB programs to use in making this determination include 1) WHO data on the estimated incidence of TB in countries of origin (354); 2) local epidemiologic and surveillance data (151,152,313--316,355); 3) published guidelines (4,279), and other sources of data (115,116); 4) qualitative information on refugee and immigrant movement into the jurisdiction; and 5) availability of resources to establish control and prevention measures targeted toward the foreign-born population. The principles and priorities of TB control among foreign-born persons at high risk are not different from those for control of TB among U.S.-born persons (Box 4). However, for the reasons given previously, TB control among foreign-born persons at high risk might present challenges requiring targeted strategies specific to that population (152,356).

How Foreign-Born Persons Enter the United States

Foreign-born persons enter the United States legally through different official channels (Table 7). As a condition of entry, persons migrating as immigrants, refugees, and asylees are required to be screened for diseases of public health significance, including TB. Persons entering in the nonimmigrant category do not require preentry screening. Persons who enter the country without legal documentation are referred to as unauthorized aliens.

During 1992--2002, an estimated 380,000--536,000 persons entered the United States annually as immigrants, refugees, or asylees (Table 8). In 2002, among the estimated 516,000 persons in those categories, 86.6% were from countries with high incidence of TB. Immigrants, refugees, and asylees constitute only a fraction of foreign-born persons who enter the United States each year; the majority (20--35 million persons) enter in one of the nonimmigrant subcategories (Table 8). The majority of entering nonimmigrants are tourists or business travelers who spend only a short time in the United States. However, an estimated 850,000--1.9 million workers, students, and other visitors and their families might reside in the United States for multiple years (Table 8).

A nonimmigrant, refugee, or asylee residing in the United States who meets the eligibility requirements and applies for a change in visa status to that of a lawful permanent resident should undergo required health screening assessment by a civil surgeon. During 2002, of the 679,305 persons who adjusted their immigration status under this program, 536,995 (79%) were from countries with high incidence of TB (238). In addition, an estimated 7 million unauthorized aliens resided in the United States in January 2000, and during 1990--1999, the unauthorized alien population increased annually by approximately 350,000 persons (357).

Current Requirements for TB Screening of Immigrants

U.S. immigration law mandates screening outside the United States for applicants designated as immigrants who are applying for permanent residence status and for applicants designated as refugees or asylees (Table 7). The purpose of mandated screening is to deny entry to persons who have either communicable diseases of public health import or physical or mental disorders associated with harmful behavior, abuse drugs or are addicted to drugs, or are likely to become wards of the state. The current list of infectious diseases of public health significance that are grounds for exclusion include infectious TB, HIV infection, leprosy, and certain sexually transmitted diseases (358). Worldwide, approximately 400 licensed local physicians, designated as "panel physicians," perform these medical examinations. Panel physicians are appointed by U.S. embassies and consulates that issue visas. CDC is responsible for monitoring the quality of these examinations and for providing technical guidance and consultation for TB diagnosis and treatment.

The TB screening process is a program for active TB case detection designed to deny entry to persons with infectious pulmonary TB (identified by positive sputum AFB smear results). For persons aged >15 years, a brief medical history and a chest radiograph are obtained (Figure 4). If the chest radiograph is considered compatible with pulmonary TB, three sputum specimens are obtained and examined for AFB. Although procedures vary from site to site, smears are usually performed by Ziehl-Neelsen staining and examined with light microscopy. Cultures for M. tuberculosis are not required and are not routinely performed. Persons aged <15 years are evaluated only if they have symptoms that are consistent with TB or are a contact of person with infectious TB. A test for M. tuberculosis infection is performed, and a chest radiograph is obtained if the test is positive or if the child is suspected to have TB.

Persons with abnormal chest radiographs suggestive of TB and with AFB-positive sputum smear results are classified as having Class A TB, which is an excludable condition for entry into the United States (358). Persons so designated have two options: 1) to complete a course of treatment for TB, including documented negative sputum AFB smears at the end of treatment, at which point they are classified according to their chest radiograph results and may enter the United States; or 2) to receive TB treatment until sputum smear results for AFB convert from positive to negative and then apply for an immigration waiver. A U.S. health-care provider who agrees to assume responsibility for the completion of TB treatment after a person's arrival in the United States should sign the waiver. The waiver is countersigned by a representative of the jurisdictional public health agency of the person's intended U.S. destination. An applicant whose chest radiograph is compatible with active TB but whose sputum AFB smear results are negative is classified as having Class B1 status and may enter the United States. If the chest radiograph is compatible with inactive TB, no sputum specimens are required, and the applicant enters the country with Class B2 status (358).

Immigrants with a Class A waiver or with Class B1 or B2 status are identified at ports of entry to the United States by CIS on entry to the United States and reported to CDC's Division of Global Migration and Quarantine (DGMQ). DGMQ notifies state and local health departments of refugees and immigrants with TB classifications who are moving to their jurisdiction and need follow-up evaluations. Persons with a Class A waiver are required to report to the jurisdictional public health agency for evaluation or risk deportation. For persons with Class B1 and B2 status, however, the stipulated evaluation visits to the health agency are voluntary.

Persons Seeking Adjustment of Status After Arrival

Persons seeking to adjust their immigration status after residing in the United States with nonimmigrant visa status should undergo a medical evaluation by one of the approximately 3,000 U.S. medical practitioners designated by DGMQ as civil surgeons. TB screening by civil surgeons is based on tuberculin skin testing; QFT-G is also approved for detecting LTBI. If an applicant seeking adjustment of status has a tuberculin skin test reading of >5 mm, a chest radiograph is required. If the radiograph is compatible with active TB, the person is referred to the jurisdictional public health agency for further evaluation (358). Civil surgeons are also advised that persons with a positive tuberculin test result and no signs or symptoms of TB disease should be referred to public health agencies for evaluation for treatment of LTBI, following ATS/CDC/IDSA guidelines (4,324).

Because data on the outcomes of TB screening of persons seeking to adjust their immigration status are not aggregated or analyzed, only limited information is available. In an evaluation of the screening practices in five U.S. Immigration and Naturalization Service jurisdictions, among 5,739 applicants eligible for screening through tuberculin skin testing, 4,290 (75%) were considered to have been screened appropriately (240). In Denver, Colorado, where health department physicians serve as civil surgeons, 7,573 persons were evaluated for adjustment of status during May 1987--December 1988 (239). Applicants were screened with tuberculin skin testing, chest radiographs, or both. Among 4,840 applicants that had a tuberculin skin test placed, 2,039 (42%) had a reaction >10 mm. Sixteen persons (0.7%) were sputum culture-positive for M. tuberculosis. Therapy with isoniazid was recommended for 1,029 applicants, of whom 716 (70%) completed 6 months of treatment.

Immigration Status of Foreign-Born Persons with TB

Studies have sought to identify the initial immigration status of foreign-born persons with reported TB. During 1992--1993 in Hawaii, 78% of TB cases occurred among immigrants, 4% among student nonimmigrants, and 4% among nonimmigrant tourists (350); in 14% of cases, the immigration status could not be determined. During 1992--1994 in Seattle, Washington, 58% of TB cases among foreign-born persons who had resided in the United States for <1 year occurred among immigrants or refugees (293); immigration status was not determined among the remaining foreign-born persons. During 1998--2000, a total of 59% of foreign-born persons with TB in Tarrant County, Texas, were immigrants or refugees, 24% were unauthorized immigrants, and 17% were nonimmigrant students and workers (316).

Assessment of TB Screening Requirements for Immigrants

The priority for immigration screening efforts is to detect cases of pulmonary TB among persons applying for permanent residence in the United States and to prevent the most infectious persons from entering the United States. However, requirements for screening outside the United States do not apply to the majority of foreign-born persons entering the United States because those classified as nonimmigrants and unauthorized immigrants do not undergo screening (Table 7) (277).

Furthermore, a significant proportion of immigrants with Class B1 (4%--14%) and B2 (0.4%--4%) status allowed to enter the United States with abnormal chest radiographs because of having AFB-negative sputum smears on screening outside the United States are later discovered (on the basis of follow-up evaluations by U.S. public health agencies) to have active TB at the time of entry (350). This finding has great importance for TB-control activities in certain U.S. jurisdictions.

IOM, NTCA, and CDC have suggested changes in the screening procedures for immigrants, as follows:

• IOM has recommended that testing for M. tuberculosis infection be added as a requirement to the medical evaluation for immigrant visa applicants from countries with high incidence of TB (2).
• IOM has recommended that 1) a Class B4 TB designation be created for persons with normal chest radiographs and positive tuberculin skin tests and that 2) immigrants with B4 status be required to undergo an evaluation for TB and, when indicated, complete an approved course of treatment for LTBI before receiving a permanent residency card.
• CDC has proposed enhancing training and oversight of panel physicians outside the United States and of civil surgeons in the United States to improve the quality of immigration screening (359). CDC is also working to develop an electronic system for notifying jurisdictional public health agencies about the arrival of Class B immigrants.
• NTCA has called for 1) clarification of legal and fiscal issues associated with domestic evaluation and treatment of immigrants; 2) efforts to educate immigrants with Class B1 and B2 status about their responsibilities for follow-up; and 3) operational research to address the cost effectiveness of screening additional categories of immigrants.
• Consideration also should be given to broadening the scope of medical evaluations for immigrants. The costs and benefits of extending the requirement for screening to all visa applicants planning to reside in the United States for >6 months should be examined. Consideration is being given to adding sputum cultures to the sputum AFB smear evaluation of visa applicants who, on the basis of an abnormal chest radiograph, are suspected to have pulmonary TB or who, at least for persons with smear-positive TB cases, are from countries with known high rates of drug resistance.

TB Control at the U.S.-Mexican Border

The U.S.-Mexican border presents specific challenges to TB control. Four U.S. states (California, Arizona, New Mexico, and Texas) and six Mexican states (Baja California Norte, Sonora, Chihuahua, Coahuila, Nuevo León, and Tamaulipas) comprise the U.S.-Mexican border, and an estimated 1 million persons cross the border daily. In the six Mexican border states, estimated annual TB incidence is 27.1 cases/100,000 population, compared with 5.1 cases/100,000 population in the United States (359). In 1999, Mexico was the country of origin for 23% of foreign-born persons in the United States with reported TB, and 75% of those cases were reported from the four U.S. border states. In 1996, those same states reported 83% of TB cases among foreign-born Hispanics (360). The high rate of TB at the border, the substantial number of border crossings, the substantial geographic area involved, and the prevalent cultural and linguistic barriers make TB control a challenge in this region.

Recommendations to improve TB control at the U.S.-Mexican border have been published (361). These recommendations include use of a binational case definition and development of a binational registry of TB cases, improvements in clinical care of binational TB patients and close contacts by cross-border case-management strategies, development of performance indicators for these activities, and setting research priorities (361).

Basis for Recommendations on TB Control Among Foreign-Born Persons

Surveillance. The inability to distinguish imported TB present at the time of entry of foreign-born persons into the United States from domestically occurring disease obscures the progress that certain states and cities have made in TB control. Standardized reporting of new TB cases does not allow separating TB among foreign-born persons that is present at the time of entry from cases that arise during residence in the United States. This is more than a semantic distinction because cases of TB that occur among short-term visitors and workers, students, and unauthorized aliens are counted as U.S. incident cases even though a substantial number are imported (115). Surveys using sputum cultures indicate that 4%--13% of immigrants and refugees with Class B1 status have TB disease at the time of entry (279). TB present at the time of entry is likely to contribute to the higher incidence rates of TB noted among foreign-born persons in the first 2 years after arrival (115). The importance of imported cases and the need to distinguish them from domestic cases has also been demonstrated in the smallpox, polio, and measles eradication efforts in North America.

Case detection. Multiple factors common to the experience of foreign-born persons in the United States might lead to delays in the detection of TB. Preexisting culturally derived beliefs about TB might serve as a disincentive to seek health care when symptoms of TB are experienced (18,279). Also, foreign-born persons wishing to receive a medical evaluation might encounter financial, linguistic, or other barriers to access (19). Once medical services are sought, foreign-born persons are likely to receive their evaluation from certain kinds of health-care providers (e.g., foreign-born physicians or those working in community health centers or hospital EDs) rather than from TB clinics conducted by public health agencies. These challenges to optimal case detection among foreign-born persons will require 1) targeted public education for foreign-born populations at high risk to explain that TB is a treatable, curable disease; 2) better access to medical services, especially for recently arrived immigrants and refugees; and 3) maintenance of clinical expertise in the diagnosis and management of TB among medical practitioners (Box 1).

The TB-screening process for visa applicants (i.e., identification of persons with abnormal chest radiographs) has provided opportunities for active case detection in follow-up evaluations in the United States. Data derived from programs that have sought to identify active TB cases on the basis of positive sputum cultures for M. tuberculosis among immigrants with Class B notification status indicate that 3%--14% of the approximately 6,000 immigrants with Class B1 status who enter the United States each year and 0.4%--4.5% of the 12,000 immigrants with Class B2 status have TB at the time of entry (279). In San Francisco, California, during July 1992--December 1993, of 182 immigrants with Class B1 status who received follow-up evaluations, 27 (14.8%) had active TB, and 134 (73.3%) had inactive TB (362). Among 547 immigrants with Class B2 status, 24 (4.3%) had active TB, and 301 (54.5%) had inactive TB. In California, 3.5% of all persons with a Class B notification status who arrived during January 1992--September 1995 were reported to have active TB <1 year of arrival (277). Recent arrivals with Class B notification status accounted for 38% of all foreign-born persons with TB reported <1 year of arrival. Among 124 immigrants and refugees in Hawaii who were reported during 1992--1993 to have TB <1 year of arrival, 78 (63%) had been classified as having Class B1 status and 17 (14%) as having Class B2 status (350). However, a study from Los Angeles suggested that the visa application process was more effective in identifying cases among persons recently arrived from Southeast Asia than among those from Mexico and Central America (363).

An active Class B1/B2 follow-up program can be relatively cost effective. During October 1995--June 1996, in Santa Clara County, California, 87% of immigrants with Class B status responded to letters inviting them to receive a follow-up evaluation, resulting in a cost of $9.90 to locate one immigrant with Class B1/B2 status and $175.88 to locate one person with TB (364).

Case management. As with case detection, cultural and linguistic differences might impede successful treatment outcomes among foreign-born persons. Case management of persons whose primary language is not English depends on reliable and competent medical translation. Providers and agencies that work with foreign-born patients at high risk should ensure that adequate translation and interpretation services are available. In jurisdictions in which the majority of the cases occur among foreign-born person, providing these services can be costly. For example, in 2000, the Tarrant County Health Department TB Program (Fort Worth, Texas), spent approximately $24,000 on professional translation services (365). Ideally, professional services should be used for translation rather than relatives or family friends (365).

Culturally derived attitudes and beliefs about TB and its treatment can also be impediments to the management of TB among foreign-born persons. Each culture has its own knowledge, attitudes, and beliefs about TB and how it should be treated. For example, in a study that used focus groups to evaluate attitudes regarding TB among Filipino immigrants, participants expressed a belief that TB was extremely contagious (264) and mentioned the associated social stigma and isolation. Although all participants agreed that medical therapy was necessary, participants also trusted the effectiveness of traditional treatments. As more of the burden of TB in the United States is borne by foreign-born persons, the need for health-care providers to understand cultural attitudes toward TB will increase.

Case management is particularly difficult at the U.S.-Mexico border where, until recently, tracking systems for persons who migrated between the two countries were not in place. A new binational system has been established to ensure continuity of care and completion of TB treatment for patients who migrate between the United States and Mexico and to coordinate the referral of patients between the health systems of both countries. The project is now being tested in four U.S.-Mexican jurisdictions (San Diego, California, and Tijuana, Baja California; El Paso, Texas--Las Cruces, New Mexico, and Ciudad Juarez, Chihuahua; Webb and Cameron Counties, Texas, and Matamoros, Tamaulipas; and Arizona and Sonora). If the pilot project proves successful, this binational TB patient referral and information system will likely be expanded to other parts of the United States and Mexico.

Contact investigation. Contact investigations have a particularly high yield when conducted on foreign-born patients. In Seattle, for example, contacts of foreign-born persons with TB were more numerous (6.0 versus 3.4 per case) and substantially more likely to be have positive tuberculin skin test results (50% versus 18%) and to be started on treatment for LTBI (40% versus 23%) than were contacts of U.S.-born persons with TB (293). A multicenter survey from around the United States demonstrated that the tuberculin skin test was positive among 71% of foreign-born contacts compared with 32% of all close contacts (31). Although not all foreign-born contacts identified during a contact investigation are recently infected, the majority would nevertheless be considered candidates for treatment of LTBI under current guidelines (4). In addition, a Canadian study indicated that contact investigations were more cost effective than preimmigration screening and postarrival surveillance (276).

Targeted testing and treatment of LTBI. Surveys using molecular epidemiologic methods have consistently demonstrated that less clustering of M. tuberculosis isolates occurs from foreign-born patients than from U.S.-born patients; this has been interpreted as evidence that less person-to-person spread of TB occurs among foreign-born persons in the United States and that the majority of cases of TB among foreign-born persons occur as a result of activation of a latent infection (150--152,356). In fact, one reason for the lack of progress in reducing TB among foreign-born persons might be that insufficient attention has been given to targeted testing and treatment (152), which should be the most applicable prevention strategy for this population, in which TB disease occurs mainly by progression from LTBI.

The success of programs for targeted testing and treatment of LTBI among populations at high risk in the United States has been thwarted by poor interest in the intervention on the part of medical practitioners and poor adherence by patients (51). Among foreign-born persons, these problems are magnified by the lack of access to care and by cultural and linguistic obstacles. Successful models for administering targeted testing and treatment of LTBI among refugees have been published; these models are resource-intensive and require a commitment to working within the population's cultural contexts (202,221). In addition, the use of DOT increases treatment completion rates (366).

Other opportunities to conveniently access foreign-born persons for targeted testing programs include school-based testing of foreign-born students. The majority of persons residing as students in the United States remain long enough to receive targeted testing for LTBI and, if TB is diagnosed, to complete a course of treatment. Screening for TB is required by 61% of colleges and universities: for all students in 26%, for all international students in 8%, and for students in specific academic programs in 47% (367). School-based screening also has been evaluated among younger students (150,322,345). In California, widespread TB screening of kindergarten and high school students yielded a low prevalence of skin test reactors and a limited number of cases of TB, but foreign-born students were >30 times more likely than U.S.-born students to have the infection (345). In a cost-benefit analysis, screening all students would be expected to prevent 14.9 cases/10,000 children screened, whereas targeted testing would prevent 84.9 cases/10,000 screened and would be less costly (345).

Control of TB Among Persons with HIV Infection

HIV and M. tuberculosis interact in ways that tend to worsen both diseases among coinfected persons (368). When a person with HIV infection is exposed to a patient with infectious TB, the risk for acquiring TB disease soon after that exposure is markedly increased (369). In outbreaks in which the start of exposure could be determined, HIV-infected persons acquired active TB in as little as a month after exposure to a person with infectious TB (136). HIV coinfection is also a highly potent risk factor for progression from LTBI to TB (44,46,370). Persons with LTBI and HIV coinfection have a risk for progressing to TB disease of approximately 10%/year (317,371,372), which is 113--170 times greater than the risk for a person with LTBI who is HIV-seronegative and has no other risk factors (4,44).

On a global level, HIV infection has had a substantial effect on the epidemiology of TB. Areas of the world most heavily affected by the global epidemic of HIV/AIDS (e.g., sub-Saharan Africa) have also sustained increases in the incidence of TB (44,46,373). TB is the most common infectious complication and the most common cause of death among persons with HIV/AIDS in places where the incidence of both diseases is high (374). In the United States, HIV infection has been associated with TB outbreaks in institutional settings, including health-care facilities (53), correctional facilities (37), and homeless shelters (33).

Before the advent of highly active antiretroviral therapy (HAART) in the early 1990s, HIV infection caused a progressive decline in immune competence and death. However, the use of HAART using combination therapy plus protease inhibitors has prolonged the survival among persons with HIV infection (375--377). The introduction of HAART has also decreased the incidence of TB among HIV-infected persons: an 80% decrease in risk for TB has been demonstrated among HIV-infected persons receiving HAART (378).

With the declining incidence of TB in the United States since 1992, the incidence of HIV infection among persons with TB also has decreased. This is likely attributable to increased understanding of the biologic interactions between the two pathogens, leading to more targeted TB-control efforts and to the introduction of HAART. Another factor is improved TB infection control in health-care facilities, because HIV- infected persons were particularly affected by health-care--associated transmission of M. tuberculosis (53).

HIV infection was a prominent cause of the 1985--1992 TB resurgence in the United States, especially the incursion of health-care--associated TB (including multidrug-resistant disease). That fact, along with the knowledge that the global epidemics of HIV infection and TB are continuing unabated (44), dictates a high degree of respect and vigilance for the adverse consequences that HIV infection could impose on the epidemiology of TB in the United States.

Basis for Recommendations of Control of TB Among Persons with HIV Infection

HIV counseling and testing. Knowledge of the presence of HIV infection among patients with TB is useful for surveillance purposes to ensure that an optimal drug regimen is chosen for treatment (5), refer persons for HIV primary care if the case is newly detected, and guide decisions about contact investigations. TB is frequently the first illness that brings a person who has not previously received a diagnosis of HIV infection into the health-care system.

Voluntary counseling and testing for HIV is recommended for all patients with TB (5), but this recommendation has not been fully implemented, and reporting of HIV among persons with TB is incomplete (14). In 2003, HIV testing was performed for <50% of patients reported with TB in the United States, and only 63% of persons in the age group at greatest risk (persons aged 25--44 years) were tested (14). HIV counseling and testing has also been recommended for contacts of persons with TB (302). However, recent data indicate that contacts of HIV-infected persons with TB have a high rate of HIV infection but that contacts of persons with TB without HIV infection do not (301). HIV testing for other persons with LTBI should be limited to those who have clinical or behavioral risk factors for HIV infection.

Case detection. HIV coinfection affects the clinical and radiographic manifestations of TB. HIV-infected patients are more likely than persons without HIV infection to have extrapulmonary and miliary TB (379,380), and those who have pulmonary TB tend to have atypical findings (e.g., they are less likely to have apical cavities and are more likely to have lower lobe or instititial infiltrates and mediastinal or paratracheal lymphadenopathy). These atypical features are heavily dependent on the patient's CD4 cell count; those with CD4 cell counts >300 cells/µL usually have manifestations, such as upper lobe cavitary infiltrates (274). Persons with HIV infection might also have pulmonary TB despite a normal chest radiograph (274,379).

HIV-infected patients are also vulnerable to other pulmonary and systemic infections such as Pneumocystis carinii and pneumococcal pneumonias and disseminated M. avium complex disease. Although the symptoms and signs of TB are usually different to the trained clinician from those caused by other prevalent invasive pathogens (273,381), HIV co-infection often results in delay in the diagnosis of TB as a result of altered clinical and radiographic manifestations (23).

Undetected transmission of M. tuberculosis to HIV-infected persons can have serious sequelae (136). A substantial outbreak of TB in a prison in South Carolina in 1999 demonstrated the widespread consequences of an unrecognized TB case in a congregate setting with a substantial number of HIV-infected persons (37). In that outbreak, 32 TB cases and 96 tuberculin skin test conversions resulted from a single unrecognized case. Similar outbreaks have occurred in hospitals (53,244), HIV-living facilities and day-treatment programs (136), and homeless shelters (33). Such outbreaks underscore the importance of aggressive TB screening and treatment in settings in which HIV-infected persons congregate. Screening for TB in those settings has been successfully conducted by using symptom checklists, tuberculin skin testing, and chest radiographs (37,118,136).

Case management. Management of TB among persons with HIV infection is complex. Drugs used to treat TB and those employed in combination antiretroviral therapy have overlapping toxicities and potentially dangerous drug interactions (382). Paradoxical responses to TB therapy are more common among HIV-infected persons (383). Use of multiple potentially toxic medications also provides further challenge to adherence with TB treatment. Therefore, integration of management of both HIV infection and TB is critical to the success of management of both. Comprehensive case management, including DOT, is particularly important (5). Among HIV-infected TB patients, more favorable outcomes and survival have been associated with DOT than with self-administered therapy (384). ATS/CDC/IDSA guidelines should be consulted for recommendations on length and mode of treatment and selection of drug regimens (5). Finally, patients with HIV and TB bear the brunt of two conditions that are associated with clinical and social complexities that can be personally overwhelming. Both HIV infection and TB are associated with stigmatization, and patients with these concomitant conditions often suffer from isolation and a lack of social support.

Contact investigation. Despite controversy as to whether HIV-coinfected patients with TB are more or less infectious than HIV-seronegative patients (385,386), they are clearly capable of transmitting M. tuberculosis; contacts of the two populations of patients have comparable rates of LTBI (369,387). The higher risk for progressing rapidly from exposure to M. tuberculosis to TB disease means that all of the medical and public health interventions (case detection and reporting, initiation of an effective drug regimen, and identification and evaluation of contacts) are more urgent when working to control HIV-associated TB (388).

Although offering HIV counseling and testing to all contacts of persons with infectious TB has been recommended (302), this undertaking would be resource-intensive. Whereas prevalence of HIV infection among contacts of HIV-infected persons is high, prevalence among contacts of persons with TB without HIV infection or with undetermined status is negligible (301).

Targeted testing and treatment of LTBI. HIV coinfection is the most important known risk factor for persons with LTBI acquiring active TB (317,371,372). Treatment of LTBI is effective in reducing the risk for progression to TB disease among HIV coinfected persons (372,389). Thus, all possible efforts should be made to ensure that HIV-infected persons are tested for M. tuberculosis infection and that those found to have latent infection receive and complete a course of treatment. In addition, knowledge of the HIV status of persons being evaluated for LTBI is desirable 1) in interpreting the tuberculin skin test result (e.g., >5 mm of induration is considered a positive test among persons with HIV infection [4]) and 2) in counseling persons with positive skin test results about the risks and benefits of treatment for LTBI (the role of QFT-G for testing persons with HIV infection for LTBI has not been determined). According to current guidelines (302), persons being evaluated for LTBI should also be screened for HIV infection by using self-reported clinical and behavioral risk factors.

Institutional infection control. Infection-control measures recommended to prevent transmission of M. tuberculosis have been effective in limiting exposure of HIV-infected persons, including patients, visitors, and staff members, to M. tuberculosis in hospitals, extended care facilities, and correctional facilities (9,244). Nevertheless, the risk for rapid progression from exposure to TB disease means that HIV-infected persons should continue to be advised of any potential sites of institutional exposure so an informed choice regarding employment or volunteering can be made.

Control of TB Among Homeless Persons

The persistence of TB among homeless persons in the United States is a major public health problem. The homeless population is not insubstantial; in 1995, an estimated 5 million persons (2.5% of adult U.S. residents) either were or had recently been homeless, living in streets or shelters, or marginally housed (e.g., living on public support in residential hotels) (390). TB incidence is high among homeless persons, and evidence exists of considerable transmission of M. tuberculosis. Among 2,774 homeless persons enrolled during 1990--1994 in San Francisco, California, 25 incident cases were identified for 1992--1996, for an annual rate of 270 cases/100,00 population (118). Among 20 M. tuberculosis isolates from incident cases that were subjected to genotyping study, 15 (75%) were clustered, indicating chains of transmission in the population. Other molecular epidemiology studies also have identified homelessness as an important risk factor for clustering of M. tuberculosis isolates (33,119,391,392).

Shelters are key sites of TB transmission among homeless persons throughout the United States (27,33,118--120,166, 391--393). In Los Angeles, California during March 1994--May 1997, three homeless shelters were sites of TB transmission for 55 (70%) of 79 homeless patients (33). In Fort Worth, Texas during 1995--1996, clusters of cases among homeless persons occurred simultaneously in four homeless shelters (27). In Alabama, genotyping of isolates from TB cases reported in 1994-98 revealed an undetected statewide outbreak of TB that was traced to transmission in a correctional facility and in two homeless shelters (166). In an outbreak in a shelter in Syracuse, New York, during 1997--1998, a shelter resident was probably infectious for 10 months before receiving a diagnosis; ventilation in the shelter was poor, and the population included vulnerable persons with risk factors that included HIV infection, substance abuse, and malnutrition (120).

Multiple barriers to the control of TB among homeless persons have been identified. Delays in detection of infectious cases have been reported (20); in a computer simulation study that modeled multiple strategies for TB control among homeless persons, a 10% improvement in access to treatment led to greater declines in disease and death after 10 years than comparable improvements in treatment programs (394). Traditional methods of conducting contact investigations often fail to identify contacts of homeless persons with TB (30,119,120). Difficulties also have been encountered in completing treatment for homeless patients with active TB (395) and LTBI (167,184).

Basis for Recommendations for Control of TB Among Homeless Persons

Surveillance and case detection. Delays in diagnosis and treatment of TB among homeless persons might occur as a result of delays in seeking medical care (181) and to the failure of medical providers to detect TB among those seeking care (20). Homeless persons with TB are disproportionately likely to receive care in hospital EDs and other urgent care clinics (232). For example, during 1994--1996, homeless persons in Atlanta, Georgia, were more likely than other patients to receive a diagnosis in a hospital ED (184). On the basis of sputum AFB smear results and radiologic findings, homeless persons had more advanced disease at the time of diagnosis, another indication that they received diagnoses later in the course of their disease (184).

Shelters have proved to be effective sites for case detection by use of screening procedures among homeless persons. During May 1996--February 1997, among 127 homeless persons in Alabama for whom shelter-based screening was conducted by using symptom evaluation, sputum culture, and chest radiographs as the screening package, four (3.1%) persons had TB disease (281). Symptom evaluation alone was not proven to be useful. In a similar study from London, United Kingdom, that employed symptom evaluation, tuberculin skin testing, and chest radiography, 1.5% of homeless persons were determined to have TB (396).

On the basis of findings of a high prevalence of TB in shelter-using homeless populations, certain communities have implemented compulsory screening of shelter residents based on symptom evaluation or tuberculin skin testing with radiographs for those with positive tests. One such program in Portland, Oregon, initiated in 1985, was associated with an 89% reduction in TB morbidity in the geographic area served by participating shelters during 1980--1995 (397). The implementation of a similar screening program in shelters in Denver, Colorado, in 1995 led to lower rates of active TB and reduced transmission of TB disease, as demonstrated by less genotype clustering by DNA fingerprinting (167). Both screening programs were based on symptom evaluation, tuberculin skin testing, and chest radiography. The decrease in TB morbidity in both these studies was attributed to shelter-based case detection through screening activities.

Case management. Completion of treatment for active TB is more difficult for homeless persons, particularly those who report substance abuse, including alcohol abuse (395). Homeless persons with active TB are at high risk for poor adherence even with enhanced DOT and are more likely to default and move from the area of initial diagnosis. They are also more likely to have legal action taken in the form of court-ordered treatment or detention. Comprehensive case management that includes a variety of incentives and enablers, including food, temporary housing, transportation vouchers, and treatment for substance abuse and mental illness has improved rates of treatment completion in this population.

Costs for homeless persons who are hospitalized for initial treatment of active TB have been $2,000 more than costs for persons who were not homeless (398). Excess hospital utilization could be attributable to social considerations, clinical indications (especially the need to render a patient noninfectious before discharge to a congregate living setting), or concerns about adherence to the plan of treatment. In San Diego, California, a novel housing program that used hostels facilitated the completion of treatment of TB in homeless persons (399). Completion rates of 84%--100% were achieved for persons housed at a designated hostel in 1995. Certain TB-control programs in cities with substantial homeless populations routinely provide temporary or longer-term housing in attempts to improve completion of treatment. The California Department of Health allots funds for temporary housing of persons with TB to each of its county and local jurisdictions. The U.S. Department of Housing and Urban Development also provides funding for housing patients with TB.

The beneficial impact on treatment outcomes of an integrated approach to managing homeless patients with TB has been emphasized (394). For example, a social care and health follow-up program among homeless patients in Spain was associated with a decrease in TB rates from 32.4/100,000 in 1987 to 19.8 cases/100,000 in 1992, and better completion rates and reduced costs for hospitalizations were also documented (400). In Massachusetts, 58 (34.5%) of 214 persons hospitalized in a dedicated inpatient unit for difficult TB patients during 1990--1995 were homeless (401). Regardless of the case-management plan that is chosen, all such interventions should take into consideration the importance of addressing major gaps in knowledge, attitudes, and beliefs about TB among homeless persons (181).

Contact investigation. Contact investigations for cases of TB among homeless persons are particularly challenging. Homeless patients with TB often fail to identify contacts during routine investigation (30). Completing a contact evaluation in identified contacts and completing treatment for LTBI among contacts that are homeless are often difficult (320,391,402). Interpretation of the results of tuberculin skin testing of contacts of homeless cases is problematic because the background prevalence of positive tuberculin skin tests in the population is usually higher than that of the general population. As with contact investigations among other populations at high risk, discerning when a contact investigation has become a targeted testing program is often difficult. A proposed alternative approach to conducting contact investigations of homeless persons is to focus on possible sites or locations of exposure, such as shelters (391,393).

Targeted testing for and treatment of LTBI. When homeless persons are identified as a population at high risk on the basis of the local epidemiology of TB, targeted testing and treatment protocols tailored to local circumstances should be developed. However, low rates of completion of therapy for LTBI are commonly observed (167,184,402). For example, among 7,232 inner city residents (including homeless persons) screened for LTBI during 1994--1996 in Atlanta, Georgia, 4,701 (65%) completed tuberculin skin testing; of 809 (17%) who had a positive test, 409 (50%) were candidates for isoniazid therapy, and 84 (20%) completed treatment (184). In another study conducted in San Francisco, California, during 1991--1994 that was designed to improve adherence, two novel interventions (biweekly preventive DOT with either a $5 incentive or a peer health adviser) were compared with the usual method of self-supervised treatment (402). Even though completion of treatment was not high for any of the three groups, multivariate analysis indicated that independent predictors of completion were being offered the monetary incentive and residence in a hotel or other stable housing at entry into the study. That report confirmed an earlier finding that advocated offering monetary incentives (320).

Institutional and environmental controls. Efforts have been made to reduce transmission of TB in shelters for homeless persons by enhancing institutional control measures. These efforts have included reducing shelter size (13), improving ventilation systems, and using germicidal ultraviolet light (280).

Control of TB Among Detainees and Prisoners

Correctional facilities in the United States include jails and prisons, which serve different but complementary functions. Jails serve as pretrial detention centers and house persons (detainees) awaiting trial and those sentenced to <1 year of incarceration. Local and county governments operate the majority of jails. Jails are characterized by rapid turnover of detainees with short lengths of stay. Prisons serve as sites of detention for persons (prisoners) who have been sentenced and will be incarcerated for a known length of time, generally >1 year. State governments, the federal government, and the military all operate prison systems. On any given day, approximately 2 million persons in the United States are incarcerated; 1.4 million of those are imprisoned, and the remainder are detained in jails. Approximately 6 million persons are incarcerated in jails or prisons each year for variable lengths of time (124,125).

Detainees and prisoners represent the poorest and most medically underserved segments of the U.S. population, the same population segments at risk for LTBI and TB disease (124,252,253). Persons entering prisons have usually spent time in jail, and detainees and prisoners eventually reenter the community. Consequently, TB outbreaks among detainees, prisoners, and the general population of a geographic area are interrelated (127,403), and close coordination of TB-control activities is needed between health programs in correctional facilities and jurisdictional public health agencies.

Prisons have long been identified as sites of transmission of M. tuberculosis to other inmates and workers (38,139,404--408), including those with HIV infection (38,139,405,408). In addition, time spent in jail is a risk factor for subsequent acquisition of TB (127,250,256), an indication that jails often are also sites of transmission. Correctional facilities are among the most important sites of transmission of M. tuberculosis in the United States.

Failure to detect TB in correctional facilities results in TB outbreaks, which have been well documented (37,139,404--408). Outbreaks of multidrug-resistant TB involving inmates and staff, including HIV-infected persons, were a prominent component of the 1985--1992 TB resurgence in the United States (404,405,409--411). However, outbreaks have continued to occur (37,139), even though TB control, including control of M. tuberculosis transmission, in the United States has improved.

Basis for Recommendations on Control of TB Among Detainees and Prisoners

Case detection and case management. Despite the importance of jails and prisons in sustaining and amplifying the reservoir of TB in the United States (127,405,407), little is known about the optimal means of case detection of TB among detainees and prisoners. The majority of prisons have adopted a case-detection strategy that is based on a survey of TB symptoms obtained on admission, in which all entrants are tested for M. tuberculosis infection <14 days of admission; universal chest radiographs of all entrants are rarely offered (410). No data have been published supporting the effectiveness of symptom surveys and testing for M. tuberculosis infection for detecting cases of TB and preventing transmission within jail systems, although screening by tuberculin skin testing was effective in controlling TB in one prison system (411). Certain substantial urban jails perform chest radiographs on all persons entering the institution in an attempt to minimize transmission of TB (283,412), and data indicate that this approach is cost effective (412). Because nearly all prison entrants have first been detained in a jail system, effective TB case-detection programs in jails will substantially decrease the probability that persons with undetected active TB will be admitted to prison.

Once cases are detected, strategies similar to those used in the community have led to high rates of successful treatment completion (413). A particular problem for case management in a jail setting is the unanticipated release of detainees, which often precludes the development of an effective discharge plan. Strategies to better coordinate discharges with public health authorities should be promoted.

Contact investigation. Continuing outbreaks of TB in correctional facilities (37,139) underscore the importance of prompt and thorough contact investigations in jails and prisons. Contact investigations in correctional facilities involve two steps: 1) identifying and evaluating persons exposed before the source-case was incarcerated, and 2) identifying and evaluating persons exposed during incarceration of the source-case. Effective case detection is important to limit the size of the latter group. Contact investigations often need to be conducted broadly, among more than one facility, because of the movement of detainees within the correctional system (414).

Conducting contact investigations based on the concentric circle method is difficult in correctional institutions. Frequently, a single infected person can expose up to several hundred persons both before and after incarceration. Cases involving persons who were exposed before incarceration should be managed by the jurisdictional public health agency for the community in which the person lived before arrest. For the jurisdictional public health agency to carry out those contact investigations effectively, prompt notification and case reporting by the detention facility is necessary. Guidelines for conducting contact investigations in jails have been published (258).

Targeted testing and treatment of LTBI. Targeted testing and treatment of latent TB among detainees and prisoners has been described in detail (415--417). Because of the high risk for transmission of M. tuberculosis in correctional facilities, inmates incarcerated for >14 days usually receive a test for M. tuberculosis infection as part of TB case detection. Detainees and prisoners with LTBI often are considered to be candidates for treatment of latent TB (124,252,253). Prisons often are an ideal setting for effective treatment of LTBI because of known location of the patient, length of stay, prohibition of illicit drugs and alcohol, and a predictable diet. Nevertheless, achieving high rates of completion of treatment for LTBI in prisons or jails has been difficult (257,416,417).

The majority of jail detainees are released in <14 days of entry. If treatment for LTBI is started in the jail setting, community follow-up after release from jail is essential. Without specific interventions to assure such follow-up, the probability of completion of treatment might be <10% (256,257,418). Recent developments in short-course treatment of latent TB with a combination of rifampin and pyrazinamide for 2 months offered promise in improving treatment completion rates (419). However, the toxicity of this regimen precludes its routine use (324), and this combination should generally not be used for the treatment of LTBI in correctional settings because the rates of toxicity have been similar to those observed in the wider community. In addition, detainees and prisoners have high rates of hepatitis C infection, making them especially prone to serious hepatotoxicity.

Institutional infection control. Correctional institutions have been sites of virulent outbreaks of TB, including multidrug-resistant TB, that have involved HIV-infected inmates and staff (37,139,405,408). Common findings in these outbreaks have included the failure to isolate persons with active TB quickly. Another common finding has been disease associated with rapid transmission of M. tuberculosis when immunosuppressed detainees and prisoners are housed together. An effective infection-control program can decrease the likelihood of TB transmission in correctional institutions (420). Guidelines to assist correctional institutions in developing effective infection-control programs have been published (258).

Control of TB in Health-Care Facilities and Other High-Risk Environments

During the 1985--1992 TB resurgence in the United States, TB cases resulted from transmission of M. tuberculosis in settings where patients with infectious TB congregated closely with susceptible persons (52--54,170,421). This epidemiologic disease pattern had not been recognized in the United States since the development of effective drugs against TB starting in the 1950s. Hospitals and other health-care facilities were the primary, but not the only, sites of transmission (405,406,408), and HIV-infected persons were prominent among those who contracted M. tuberculosis infection and rapidly acquired TB disease (52--54,170,406,408). Although incidence of TB in health-care facilities has been markedly reduced because of the development and deployment of effective infection-control measures (56,422--424) and decreasing incidence of TB in different communities, TB disease attributable to recent transmission of M. tuberculosis in other settings has not only persisted but has been recognized in a wide variety of sites and settings and become an established epidemiologic pattern.

As a consequence of the changed epidemiology of TB in the United States, the primary strategies now required to control the disease include measures for its prevention in settings in which a risk for transmission of M. tuberculosis exists (Box 4). Recommendations for infection-control measures in high-risk settings are provided in this statement. The approach to control of TB and other airborne infections that was developed for health-care facilities (10) is the most successful model and is outlined in detail in this statement. Recommendations are also provided for control of transmission of M. tuberculosis in extended care facilities, correctional facilities, homeless shelters and other high-risk settings.

Control of TB in Health-Care Facilities

Strategies for control of TB in health-care facilities, which also are applicable for other settings in which high-risk persons congregate, are based on comprehensive guidelines issued by CDC in 1994 (10). New CDC guidelines for preventing transmission of M. tuberculosis in health-care facilities will be published in 2005. A draft^† of these guidelines has been published in the Federal Register. In the assessment of institutional risk for TB, three levels of risk (low, medium, and potential ongoing transmission) are recommended, based on the recent experience with TB in the institution and in the community it serves. The recommended frequency of testing of employees for M. tuberculosis infection varies, depending on the institution's level of risk. The tuberculin skin test is recommended for testing HCWs and other employees with a risk for exposure to M. tuberculosis. QFT-G is also approved for detecting LTBI; guidelines for the use of QFT-G will be published in the MMWR.

The risk for TB associated with health-care facilities is related to the incidence of TB in the community served by the facility and to the efficacy of infection-control measures (422). Implementation of infection-control guidelines (10) has markedly reduced risk for exposure to TB in health-care facilities during the past decade (56,422--424) and has also contributed to the decreasing numbers of TB cases. Implementation of effective infection-control measures in the medical workplace is thus an important element of broader national and international strategies to prevent transmission of TB (244).

Epidemiologic investigations of the early outbreaks of TB in health-care facilities, including those involving multidrug-resistant cases, indicated that transmission usually occurred because of failure to identify and isolate patients with infectious forms of TB. In certain instances, diagnosis of TB was delayed as a result of the atypical presentation of TB among patients with HIV infection, especially those with low CD4 counts. Transmission was also facilitated by 1) the intermingling of patients with undiagnosed TB with patients who were highly susceptible; 2) inadequate laboratory facilities or delayed laboratory reporting; and 3) delayed institution of effective therapy. Other factors facilitating transmission included a lack of negative pressure respiratory isolation rooms, recirculation of air from respiratory isolation rooms to other parts of the hospital, failure to isolate patients until they were no longer infectious, allowing isolated patients to leave their rooms without wearing a mask, and leaving respiratory isolation room doors open (52--54,170,421,425,426).

CDC guidelines recommend a hierarchy of TB infection-control measures (10). In order of importance, these measures are administrative controls, engineering controls, and personal respiratory protection (PRP) (Box 7). Administrative controls consist of measures to reduce the risk for exposure to persons with infectious TB, including screening of patients for symptoms and signs of TB at the time of admission, isolating those with suspected disease, establishing a diagnosis, and promptly initiating standard therapy (5). Engineering control measures are designed to reduce dissemination of droplet nuclei containing M. tuberculosis from infectious patients and include the use of airborne infection isolation rooms. The third level (and the lowest on the hierarchy of controls) is the use of PRP devices such as N-95 respirators. Respirator usage for the prevention of TB is regulated by the Occupational and Health Safety Administration under the general industry standard for respiratory protection^§.

In implementing a comprehensive infection control program for TB, institutions should first conduct a risk assessment to determine what measures are applicable. Risk for transmission of M. tuberculosis varies widely, and procedures that are appropriate for an institution in an area of high TB incidence (e.g., an inner-city hospital or homeless shelter in a metropolitan high-incidence area) differ from those applicable to an institution located in a low incidence area that is rarely used by patients with TB. The jurisdictional public health TB-control program should assist in the development of the assessment, which should include data on the epidemiology of TB in the community served by the institution and the number of TB patients receiving evaluation and care.

The institutional risk for TB can be stratified according to the size of the institution and the number of patients with TB as low risk, medium risk, or potential ongoing transmission. Hospitals with >200 beds that provided care for fewer than six patients with TB during the previous year are categorized as low risk whereas those that cared for six or more patients are categorized as medium risk. For hospitals with <200 beds, those with fewer than three TB patients in the previous year are considered low risk, and those with three or more cases are considered medium risk. Outpatient clinics, outreach programs, or home health settings that provide care for fewer than three patients with TB per year are considered low risk, and those that care for three or more patients are considered medium risk. TB clinics, outreach programs, and other settings in which HCWs are responsible for the care of persons with TB are classified as medium risk. Any institution, clinic, or setting with evidence of recent patient-to-patient or patient-to-employee transmission of M. tuberculosis or of ongoing or unresolved transmission should be classified as having potential ongoing transmission until effective control measures have been implemented and transmission is interrupted. Potential ongoing transmission is a temporary classification.

When transmission of M. tuberculosis is suspected at a facility, an immediate investigation should be undertaken that includes consultation with public health officials or experts in hospital epidemiology and infection control. Evidence of potential transmission of M. tuberculosis includes clusters of conversions of tests for M. tuberculosis infection among employees from negative to positive, increased rates of positive tests for M. tuberculosis infection among employees, an employee with potentially infectious TB, unrecognized TB among patients or employees, and recognition of identical strains on genotyping of M. tuberculosis isolates from patients or employees.

How often employees at health-care facilities and other at-risk sites for M. tuberculosis infection are tested depends on the risk assessment. The positive predictive value of the tuberculin skin test is low when populations with a low prevalence of infection with M. tuberculosis are tested (424,427). Consequently, frequent testing by using that method in low-incidence, low-risk settings is discouraged. In addition, false-positive tests have been reported when institutions changed brands of Purified Protein Derivative (PPD) reagent, for example from Tubersol^® to Aplisol^® (427).

At the time of employment, all HCWs should undergo baseline testing (with two-step testing if the tuberculin skin test is used and no testing was performed during the preceding year) (10). Those in medium-risk settings should be tested annually. Follow-up testing is recommended for workers in low-risk settings only if exposure to a patient with infectious TB (i.e., a patient not initially isolated but later found to have laryngeal or pulmonary TB) has occurred. Institutions in which ongoing transmission of M. tuberculosis is documented should carry out testing for M. tuberculosis infection of HCWs at risk every 3 months until transmission has been terminated.

Employees testing positive for M. tuberculosis infection should receive a chest radiograph to exclude TB disease and should be evaluated for the treatment of LTBI based on current recommendations (4,324). Compliance with therapy for LTBI among HCWs, including clinicians, has historically been poor (428--430). Employee health clinics and infection-control departments should emphasize to HCWs the importance of completion of therapy for LTBI. In a comprehensive infection-control program that encourages HCWs to complete treatment for LTBI, higher completion rates have been reported (431,432).

Control of Transmission of M. tuberculosis in Other High-Risk Settings

Extended Care facilities. Elderly persons residing in a nursing home are almost twice as likely to acquire TB as those living in the community (252,433,434). Certain considerations for control of TB in hospitals apply also to extended care facilities, including 1) maintaining a high index of suspicion for the disease; 2) promptly detecting cases and diagnosing disease; 3) isolating infectious persons and initiating standard therapy; 4) identifying and evaluating contacts; and 5) conducting contact investigations when indicated. The value of treating LTBI in elderly residents of nursing homes so as to prevent future outbreaks has been documented (435).

In 1990, CDC published recommendations for TB control in extended care facilities (433). Those long-term care facilities that do not have airborne-infection-isolation rooms should transfer patients suspected to have infectious TB to other facilities (including acute-care hospitals) until the disease is ruled in or out and treatment is started if indicated and continued until the patient is noninfectious (10). The risk assessment and frequency of testing for LTBI for employees at long-term care facilities are similar to those described previously. Residents should be tested on admission to the facility and should provide a history and undergo physical examination to identify symptoms and signs of TB. Residents with LTBI should be offered treatment according to current recommendations (4,324), with careful monitoring for drug toxicity.

Correctional facilities. Common findings in outbreaks of TB in correctional facilities were the failure to recognize and isolate patients with TB and rapid progression of outbreaks when immunosuppressed detainees were housed together (405,406,408). Because of the substantial numbers of cases of TB infection and disease that might result from outbreaks at correctional facilities and the natural movement of inmates from incarceration to the general population, correctional facilities should be viewed as being among the most important sites of transmission of M. tuberculosis in the United States (128,436).

Guidelines for control of TB transmission in correctional facilities (123) have emphasized that the infection-control principles developed for health-care facilities (10) are also applicable to correctional facilities. In prisons and jails, the most important activity in TB infection control is efficient detection of infectious TB cases, including those that are prevalent among persons entering the facility and those that arise during detention. A prompt diagnostic evaluation, respiratory isolation (including transfer out of the facility if airborne-infection-isolation rooms are not available), and institution of a standard treatment regimen are urgent priorities when suspected cases are encountered. If this process is delayed, a substantial number of persons might be exposed as a result of the congregate living arrangements that characterize correctional facilities.

Because of crowded conditions that favor the spread of M. tuberculosis (420) and the high prevalence of HIV infection among prisoners (255), contact investigations should be undertaken immediately once a case of TB has occurred at a facility. In a study conducted in the Maryland state correctional system, prisons that conducted programs for targeted testing and treatment of LTBI among inmates experienced lower rates of tuberculin skin test conversions, an indication that this measure can contribute to successful infection control (420). A template is now available to assist jails in instituting an effective infection-control program (258).

Shelters for homeless persons. As with correctional facilities, homeless shelters are important sites of transmission of M. tuberculosis and an important cause of the continuing high incidence of TB among the homeless population (33,118). Effective infection-control strategies in those venues are use of M. tuberculosis genotyping for rapid identification of clustered cases and sites of transmission (27,33), screening shelter users for TB disease, wide-ranging contact investigations, and engineering controls, including ultraviolet germicidal irradiation (437). A systematic shelter- based program for targeted testing and treatment of LTBI in Denver was also demonstrated to decrease incidence of TB in the homeless population (167).

Because crowding and poor ventilation are often prevalent in shelters, infection-control efforts should also include engineering modifications to decrease exposure to M. tuberculosis. A guide to assist shelters in improving the safety of their environment through modifications in ventilation, air filtration, and the introduction of ultraviolet germicidal irradiation has been published (438).

Other high-risk settings. As the incidence of TB has receded in recent years, new patterns of transmission have become evident. Epidemiologic investigations prompted by an increase in the incidence in TB in a community or state or by the identification of clusters of cases with identical M. tuberculosis genotype patterns have detected transmission in such venues as crack houses (137) and bars (27). In addition, transmission has been identified in association with certain social activities that are not typically considered in routine contact investigations; a church choir (140), a floating card game (172), exotic dancers and their contacts (38), a transgender social network (34), and persons who drink together in multiple drinking establishments (439).

Although special techniques have been developed for exploring chains of transmission of M. tuberculosis in complex social networks (439), transmission of M. tuberculosis in such settings is not amenable to prevention by available infection-control strategies. These newly identified patterns of transmission of M. tuberculosis might be too complex to be detected and controlled by traditional approaches, and real-time M. tuberculosis genotyping capable of identifying unsuspected linkages among incident cases might be increasingly useful (131).

This new TB threat, transmission in previously unknown settings, has emerged at a time when local TB-control programs often are not prepared to respond. As TB morbidity decreases in the United States and TB-control programs necessarily contract, new approaches will emerge, particularly in low-incidence areas. One model envisions that local public HCWs who do not work exclusively on TB are served by regional TB supervisors, who in turn are supported by statewide consultants and CDC specialists (172).

Research Needs to Enhance TB Control

Implementation of the recommendations contained in this statement will likely improve TB control and allow progress to be made toward eliminating TB in the United States. However, achieving TB elimination as defined by ACET (i.e., one annual case of TB per one million population [11]) will require substantial advancements in the technology of diagnosis, treatment, and prevention of the disease. IOM has estimated that at the current rate of decline, approximately 6% annually, eliminating TB in the United States would take >70 years (2). New tools are needed for the diagnosis, treatment, and prevention of TB to accelerate the decline in TB incidence and reach the elimination threshold sooner (1,2,45). In addition, improved tests for the diagnosis of TB and LTBI and more effective drugs to treat them are needed to reduce the substantial worldwide burden of disease and death resulting from TB (44).

AFB smear microscopy and the tuberculin skin test, the most commonly used tests for the diagnosis of TB and latent infection respectively, derive from technology developed in the 19th Century; the only available vaccine against TB, BCG, dates from the early 20th Century; and rifampin, the most recent novel compound for treatment of TB, was introduced in 1963. In the long term, the development of a new and effective vaccine would have the greatest impact on the global epidemic of TB, and the United States should lead the research and advocacy efforts to develop such a vaccine (180,440). However, other advances in TB diagnosis and treatment might substantially improve the control of TB in the United States. Better means to diagnose and treat LTBI are needed immediately. Breakthrough diagnostics and drugs that would facilitate the more effective usage of this therapeutic intervention to prevent TB would have an immediate and lasting effect on the incidence of the disease in the United States by affecting at least three of the major challenges to TB control in the United States: the substantial pool of persons with LTBI, TB among foreign-born persons, and TB among contacts of persons with infectious TB (Box 1).

Public health interventions to control TB should be based on practices that have been demonstrated to be effective. Because an established scientific basis is lacking for certain fundamental principles of TB control, including certain recommendations contained in this statement, logic, experience, and expert opinion have been used to guide clinical and public health practice to control TB. In the preparation of these recommendations for TB control, deficiencies in evidence were frequently noted. Better understanding is needed of which persons among the millions of foreign-born persons that enter the United States each year (Table 8) are at sufficient additional risk for TB to warrant public health intervention. The approaches recommended for the development of programs for targeted testing of LTBI need additional verification. The new concepts of identifying contacts of infectious TB cases (439) require refinement. The optimal method of reducing the concentration of M. tuberculosis in ambient air in venues such as homeless shelters is not yet defined (438). Methods to monitor and evaluate TB control programs, and in particular, new activities such outbreak surveillance and response (441), should be delineated and standardized.

The epidemiology of TB in the United States is constantly changing. Recent examples, as noted throughout this statement, are the increase in TB among foreign-born persons, the upsurge in reports of TB outbreaks, and the persistent high incidence of the disease among U.S.-born non-Hispanic blacks. Epidemiologic studies, including economic analyses, are needed to augment surveillance data and facilitate decisions about allocation of effort and resources to address newly identified facets of the epidemiology of TB.

As new diagnostics are introduced to TB control, operational, economic, and behavioral studies will be needed to determine their most effective use. For example, QFT, a new diagnostic test for LTBI, was licensed in 2001, and early research indicated that this new test might have advantages over the tuberculin skin test in distinguishing between latent M. tuberculosis infection and infection with nontuberculous mycobacteria or vaccination with BCG (102). However, guidelines on testing for LTBI recommended that QFT should not be used in the evaluation of contacts of infectious cases of TB, for children aged <17 years, for pregnant women, or for patients with immunocompromising conditions, including HIV infection, because of a lack of data from studies in those populations (103). A newer version of the test, QFT-G, was licensed in 2004. The role of this new test in these populations has not been determined Thus, considerable research remains to be done to delineate the advantages this new test can bring to TB control.

Despite the best efforts of national, state, and local TB programs, nonadherence to prescribed treatment for TB and latent infection remains a major barrier to TB elimination. As evidence of the importance of that intervention, completion of a course of treatment is the first national performance standard for TB (Table 4). For the outcome of TB treatment to be improved, both patient and health-care provider behaviors related to adherence to TB treatment must be understood, and that understanding should be used to design and implement methods for improving adherence. Although considerable research has been conducted in this field, no comprehensive effort has been undertaken to examine and compile the results and identify best practices. Gaps in knowledge remain, and the need exists to develop and implement a comprehensive behavioral and social science research agenda to address these deficiencies.

Graded Recommendations for the Control and Prevention of Tuberculosis (TB)

Recommendations for TB Laboratory Services

• Laboratorians, clinicians, and public health officials should work together to develop an integrated system that ensures timely laboratory testing and flow of information among laboratorians, clinicians, and TB controllers (AIII).
• Public health laboratorians should take a leadership role to develop the laboratory system and assure that essential laboratory tests for TB control are available, accessible, standardized, reproducible, and with high sensitivity and specificity (AII).
• Public health laboratories should educate laboratory staffs, health-care providers, and public health officials about the most effective uses of clinical microbiologic laboratory services. Such activities might include education programs, development of web-based or written materials, or direct consultation (standard practice [SP]).
• All microbiology laboratories should subscribe to specified turnaround times (Box 2) from date of specimen collection to date when the following results are reported:
  --- acid-fast microscopy: <24 hours;
  --- growth detection of mycobacteria in culture: <14 days;
  --- identification of M. tuberculosis complex: <21 days; and
  --- drug susceptibility testing: <30 days (AII).
• The following laboratory results should be reported immediately (preferably by electronic or fax transmission) by the testing laboratory to the responsible clinician and to the jurisdictional TB control program:
  --- a positive smear for AFB and the subsequent growth detection (culture) result of that specimen;
  --- identification of M. tuberculosis complex in any specimen; and
  --- drug susceptibility test results, especially when isolates are drug resistant (AII); and
• Clinical microbiologic laboratories should include, as part of quality improvement, a plan for identification and review of possible false-positive results. Any false-positive result should trigger an inquiry and a plan of correction (155) (SP).

Recommendations for TB Case Detection

• Steps recommended by IOM (2) to improve public knowledge and awareness about the risk factors for TB, symptoms of TB, and the implications of the diagnosis of latent infection should be undertaken by TB-control programs, community-based organizations representing populations at high risk, and academic health sciences institutions. Targeted education of populations at high risk might be particularly effective in neutralizing the stigma associated with TB among foreign-born populations on the basis of cultural beliefs in their country of origin. Programs for patient education should always be designed with input from the targeted community (AII).
• Because nonpublic health medical practitioners most often conduct the initial evaluation on persons who have symptoms related to TB, health departments, academic institutions, and medical professional organizations should provide continuing education about TB to their constituent health-care providers. These efforts should be focused on clinicians serving populations at high risk for TB on the basis of local or regional trends in TB epidemiology (AIII).
• Jurisdictional public health agencies should ensure that clinicians who evaluate persons with suspected TB have access to current, accurate, and timely diagnostic services (SP).
• Guidelines for detection of TB cases in clinical settings should be followed by primary care, ED, and hospital-based practitioners (Table 5).
• Screening for TB cases during contact and outbreak investigations and during the evaluation of immigrants and refugees with Class A/B1/B2 TB notification status has a high yield of finding cases (Table 6) and should be given high priority as a method for TB case detection (AII).
• Public health programs should identify other opportunities for screening for TB disease on the basis of the local epidemiology of TB, such as in congregate settings, homeless shelters, and correctional facilities in which the consequences of an undiagnosed case are severe. All case detection activities should be evaluated periodically to determine their usefulness (AII).

Recommendations for Contact Investigations and for Outbreak Prevention and Response

• Contact investigations are a critical component of TB control, following only TB case detection and treatment in priority (AIII).
• State and local health departments should establish a comprehensive contact investigation program to ensure that contacts of infectious TB cases are identified, access to adequate care is provided, and therapy is completed (AIII).
• TB-control programs should develop a protocol for conducting contact investigations that identifies persons responsible for each step of the investigation and outline processes to maximize the efficiency of the process within the framework of available resources (AIII).
• TB-control programs should have procedures for voluntary HIV counseling and testing of contacts. Those procedures should set priorities for HIV counseling and testing of contacts on the basis of locally derived data on the risk for HIV infection among contacts or, alternatively, on the local epidemiology of TB and HIV infection (BIII).
• Tuberculin skin testing of contacts should establish as first priorities those contacts who are at highest risk for progressing from LTBI to TB disease on the basis of transmission risk assessment and the presence in contacts of risk factors for progression (e.g., age <5 years, HIV infection, and other immunocompromising conditions (4) (AII).
• DOT for LTBI should be considered for all contacts. High risk contacts should receive highest priority for directly observed treatment (AIII).
• TB-control programs should apply existing communicable disease laws that protect the health of the community to contacts who fail to comply with the examination requirements (BIII).
• TB-control programs should develop guidelines, in conjunction with the program legal office and in compliance with HIPAA rule, for release of confidential information related to conducting contact investigations (BIII).
• TB-control programs should evaluate the effectiveness and impact of contact investigations and develop interventions to improve performance when indicated (BIII).
• TB-control programs should develop outbreak response plans for their jurisdictions. These plans should include indications for initiating the plan, notification procedures, composition of the response team, source of staffing, plan for follow-up and treatment of contacts, indications for requesting assistance from CDC, and a plan for evaluating the outbreak response (BIII).

Recommendations for the Public Health Aspects of Targeted Testing and Treatment of LTBI

• When a TB-control program is prepared to develop strategies for targeted testing and treatment of LTBI (i.e., the program satisfies national objectives for management of TB cases and contacts [Table 4]), it should begin by identifying populations and communities at high risk for LTBI within its jurisdiction and establish priorities for intervention (AIII).
• Populations and communities should be categorized on the basis of the expected impact and efficacy of targeted testing in the setting. Tier 1 groups (Box 6) should receive the highest priority, followed by groups in Tier 2 and Tier 3 (AII).
• Once the targeted population or community has been identified, strategic and operational decisions should be made on how best to establish the targeted testing and treatment program. Questions to decide include where to locate the program, how to identify and allocate resources, what training is needed for practitioners and patients, and what data-management needs exist. Focus groups, influential community leaders, associations and community action agencies, religious organizations, coalitions, block organizations, and informal community groups all can contribute to these decisions (AII).
• Public health agencies that establish targeted testing and treatment programs should maximize patient convenience and acceptance through strategies such as employing, when possible, staff members from the populations being served, medical translation, cultural awareness and sensitivity, flexible clinic hours, outreach services for patient transport, and the use of incentives and enablers. All services should be free of cost to patients (AII).
• Targeted testing programs established in the community (e.g., at community health centers, schools, prisons, jails, substance abuse centers, and homeless shelters) should receive full support from the jurisdictional public health agency. Such support might be decisive in the success of nonpublic health targeted testing and treatment programs. Types of support should include training and education of providers, patient education materials, provisions of medication, radiographs and other laboratory services, clinical consultation, and design of tracking and data management systems (AII).
• Targeted testing programs should be routinely and systematically evaluated for their effectiveness, efficiency and impact. Programs that are not effective should be improved or discontinued (AIII).

Recommendations for TB Control Among Children and Adolescents

Case Detection and Primary Prevention Strategy

• Timely reporting of suspected cases of infectious TB is crucial to the prevention of TB among children (AII).
• Contact investigation of adults with infectious TB is the most important activity for early detection of TB among children, identification of children with LTBI who are at high risk for progressing to primary TB and its sequellae, and determination of the drug susceptibility pattern of the M. tuberculosis isolate causing TB disease or LTBI in a child. Contact investigations should be timely and thorough, and adequate resources for them should be made available. This should be one of the highest priority goals of any TB-control program (AII).
•  Children aged <5 years who have been identified as contacts of persons with infectious TB should receive a clinical evaluation, including a tuberculin skin test and chest radiograph, to rule out active TB. Once active TB has been ruled out, children with positive tuberculin skin test results should receive a full course of treatment for LTBI. Those who have negative skin test results should also receive treatment for presumed LTBI. This intervention is especially critical for infants and toddlers aged <3 years but is recommended for all children aged <5 years. A second tuberculin test is then placed at least 3 months after exposure to infectious TB has ended. If the second test result is positive, treatment should be continued for a full course of treatment for LTBI. If the second test result is negative, treatment may be stopped (AII).

Case Management

• DOT should be the standard of care for treatment of TB disease among children and adolescents (AII).
• As adherence to treatment is no better for children than for adults, all efforts should be made to support children and families through treatment of TB through comprehensive case management (AIII).

Contact Investigation

• Infants and younger children with primary TB disease are rarely if ever contagious. They do not need to be excluded from activities or isolated in health-care settings (AII).
• Children and adolescents of any age with characteristics of adult-type TB (i.e., productive cough and cavitary or extensive upper lobe lesions on chest radiograph) should be considered potentially contagious at the time of diagnosis (AII).
• Infants with suspected or proven congenital pulmonary TB should be considered contagious and effective infection-control measures should be undertaken (AII).
• Adults who accompany and visit children with TB in health-care settings should be evaluated for TB disease as soon as possible to exclude the possibility that they are the source case for the child. These adults should have a chest radiograph to rule out pulmonary TB and to prevent the possibility of transmission within the health-care setting (AII).
• Testing of the contacts of children aged <4 years with LTBI is recommended for persons sharing a residence with the child or those with equally close contact. Such investigations may be performed by public health agencies or primary health-care providers (BII).

Targeted Testing and Treatment of LTBI

• Contact investigations of adults with TB and targeted tuberculin skin testing of foreign-born children from countries with a high incidence of TB are the best and most efficient methods for finding children with LTBI (AII).
• Because foreign birth in a country with a high prevalence of TB is the greatest attributable risk factor for LTBI, children born in or with extensive travel to such countries should be targeted for testing for LTBI. This includes foreign-born adopted children. Testing for LTBI among children with low risk for infection should be avoided (AII).
• A risk assessment questionnaire can be used to identify children with risk factors for LTBI who should undergo a tuberculin skin test (AI).
• A decision to place a tuberculin skin test is a commitment to arrange evaluation and treatment for LTBI (SP).
• A tuberculin skin test should always be placed, read, and interpreted by specifically trained persons (SP).
• In general, foreign-born children with LTBI should be treated with isoniazid unless information exists linking them to a specific case of isoniazid-resistant TB (AIII).
• DOT should be considered strongly as the means of treatment for newborns and infants, contacts of persons with recent cases, and immune-compromised children and adolescents with LTBI because they are at greatest risk for progression to TB disease (AIII).

Recommendations for TB Control Among Foreign-Born Persons

Surveillance

• Public health agencies in states and communities with a substantial number of TB cases among foreign-born persons should develop enhanced surveillance methods in order to gain a detailed understanding of the local epidemiology of TB among foreign-born persons. This is important for program planning and to ensure that recently arrived immigrants, refugees, and other foreign-born persons at high risk have access to medical and public health services (AIII).
• Imported cases of TB present at the time of entry should be distinguished from incident cases, i.e., those that arise during residence in the United States (AIII).
• Cases of TB among persons granted temporary entry to the United States as visitors, students, and temporary workers and unauthorized aliens (Table 7) should be distinguished from those among foreign-born permanent residents (AIII).
• Cases identified as a result of targeted testing activities should be distinguished from those identified by noting symptoms of active TB (AIII).
• For TB control along the U.S.-Mexico border to be facilitated, a binational TB case definition and TB registry system should be adopted and evaluated (AIII).

Case Detection

• Jurisdictional public health agencies responsible for TB control should undertake or engage community groups to undertake education campaigns for foreign-born persons at high risk. These campaigns should communicate the importance of TB as a personal and public health threat, the symptoms to look for, how to access diagnostic and targeted testing services in the community, and the concept of LTBI. The purpose of this education is to destigmatize the infection, acquaint the population with available medical and public health services, and explain the approaches used to treat, prevent, and control TB (AIII).
• Public health agencies conducting TB-control programs should establish liaisons with primary care physicians, community health centers, hospital EDs, and other organizations that provide health care for foreign-born populations at high risk to provide TB publications and guidelines and education about the local epidemiology of TB (AIII).
• Public health agencies conducting TB-control programs should establish liaisons with civil surgeons within their jurisdictions. They should also ensure that civil surgeons have access to recent TB publications and guidelines and that they promptly report all suspected cases of TB (AIII).
• CDC should provide standardized education and training programs with a formal certification process for panel physicians and civil surgeons. As part of the certification, continuing education programs should be required (AIII).
• Federal, state and local public health agencies should assign high priority to the follow-up of immigrants with a Class A TB waiver and Class B1 and B2 TB notification status (AII).

Case Management

• Culturally appropriate case management should be instituted, including readily available professional translation and interpretation services, for all foreign-born persons. If possible, outreach workers should be from the patient's own cultural background (AII).

Contact Investigation

• Local and state jurisdictions should assign high priority to contact investigations of foreign-born persons with TB because of the high likelihood of identifying persons with LTBI as well as secondary TB cases (AII).
• Culturally sensitive and appropriate contact investigation protocols should be established (AIII).

Targeted Testing and Treatment of LTBI

• In jurisdictions where foreign-born persons constitute a major proportion of the TB burden, targeted testing and treatment of LTBI for foreign-born persons at high risk (4) should be implemented as a primary means of preventing TB in the community. The tiered approach (Box 6), which is based on access to the target populations and likelihood of implementing a successful program, should be employed (AII).
• In developing the plan for targeted testing and treatment of LTBI among foreign-born persons at high risk, TB-control programs should collaborate with health-care providers, neighborhood health centers, and community advocacy groups that serve and work with the target populations (AII).
• The testing of immigrants and refugees with a Class A TB waiver and Class B1 and B2 TB notification status for LTBI as well as for active TB should always be prioritized (AII).
• Targeted testing and treatment of foreign-born children at high risk aged <15 years should be a priority (SP).
• When resources permit, DOT for LTBI should be used to ensure high completion rates (BII).
• Jurisdictional public health agencies should work with local colleges and universities to develop targeted testing protocols for foreign-born students at high risk and assist with treatment of LTBI (BIII).

Recommendations for TB Control Among HIV-Infected Persons

HIV Counseling and Testing

• Voluntary HIV counseling and testing is recommended for all patients with TB and should be considered the standard of care. In extreme circumstances, if establishing priorities is necessary as a result of resource constraints, patients aged 25--44 years should receive highest priority (SP).
• Clinic staff members at sites where patients with TB are followed should receive up-to-date education and training on the most current concepts and methodology of voluntary HIV counseling, testing, and referral. If on-site HIV testing is not feasible, TB facilities should have well-established arrangements for referral to other testing sites (SP).
• Voluntary HIV counseling and testing should be offered routinely to contacts of HIV-infected TB cases (AII).
• Voluntary HIV counseling and testing should be offered to all contacts that are members of populations with a prevalence of HIV infection >1% (302). In other communities and settings, the decision of whether to routinely offer voluntary HIV counseling and testing to contacts of persons with infectious TB should be based on the local epidemiology of HIV infection and TB. In communities or settings where populations at risk for TB are also known to have high rates of HIV infection (e.g., injection drug users (IDUs) in inner cities [317]), all contacts should be routinely offered voluntary HIV counseling and testing. In communities and settings in which the HIV seroprevalence likely approaches that of the general U.S. population (<0.1%), a risk-factor assessment for HIV infection should be included in the evaluation of contacts of infectious cases, and contacts with clinical or behavioral risk factors for HIV infection (302) should receive voluntary HIV counseling and testing (AII).
• Persons with LTBI who are members of populations with a prevalence of HIV infection >1% should be routinely offered voluntary HIV counseling and testing (302). Otherwise the decision of whether to routinely offer HIV counseling and testing to persons with LTBI should based on the local epidemiology of HIV infection and TB. In communities or settings where populations at risk for TB are also known to have high rates of HIV infection (e.g., IDUs in inner cities [317]), routine counseling and testing among patients with LTBI is indicated. In other communities and settings the HIV seroprevalence is likely to approach that of the general U.S. population (<0.1%), a risk-factor assessment for HIV infection should be included as a standard part of the initial evaluation for all persons diagnosed with LTBI. Persons with clinical or behavioral risk factors (302) should receive HIV counseling and testing (AII).
• Routine periodic cross-matches of jurisdictional HIV and TB case registries should be conducted to ensure completeness of reporting of both diseases (SP).

Case Detection

• Physicians who provide primary care to persons with HIV infection or populations at increased risk for HIV infection should maintain a high index of suspicion for TB. Every patient in whom HIV infection has been newly diagnosed should be assessed for the presence of TB or LTBI. This should include a history for symptoms compatible with TB (e.g., cough of >2--3 weeks' duration, fever, night sweats, weight loss, or hemoptysis, or unexplained cough and fever [Table 5]) and of exposure to persons with TB. Physical examination should include examination of extrapulmonary sites such as lymph nodes, and a chest radiograph should be taken to check for findings of current or previous TB. Testing for M. tuberculosis infection by using the tuberculin skin test should be conducted, and patients with >5 mm of induration be considered to have a positive test and should receive, in addition to chest radiography, a clinical evaluation to rule out TB (4) (SP).
• Public health agencies conducting TB-control activities should maintain close contact with HIV control programs, medical practitioners and clinics, community-based organizations, homeless shelters, correctional facilities, and housing facilities that serve persons with HIV infection to ensure that a high index of awareness of TB is maintained by persons who provide services at those sites and by their HIV-infected patients (AIII).
• Health-care facilities, social service agencies, and work sites that serve patients with HIV infection should establish firm lines of referral for patients with respiratory symptoms (AIII).

Case Management

• Public health agencies conducting TB-control activities should have access to consultants with expertise in managing HIV related TB (SP).
• Management of TB and HIV infection should be effectively integrated and should include a multidisciplinary team of providers and supportive care (AIII).
• Comprehensive case management, including DOT, is strongly recommended for persons with HIV infection who have TB (AII).
• HIV-infected patients with TB and a CD4 count <100 cells/µL should receive DOT daily or three times per week (A1).

Contact Investigation

• Contact investigations of persons with TB and known or suspected HIV infection and those conducted in any circumstance in which HIV-infected persons could have been exposed to a person with infectious TB should have the highest priority and be completed without delay (AII).
• Persons with known or suspected HIV infection who have contact with a patient with infectious pulmonary TB should be offered a full course of treatment for LTBI regardless of the initial result of tuberculin skin testing once active TB has been ruled out (AII).

Targeted Testing and Treatment of LTBI

• Targeted testing and treatment for LTBI are strongly recommended at the time the diagnosis of HIV infection is established (AII).
• For HIV-infected persons whose initial tuberculin skin test is negative, repetitive testing is recommended (at least yearly) if the local epidemiologic setting indicates an ongoing risk for exposure to TB (AII).
• An HIV-infected patient who is severely immunocompromised and whose initial tuberculin skin test result is negative should be retested after the initiation of antiretroviral therapy and immune reconstitution, when CD4 cell counts are greater than 200 cells/µL) (AII).
• HIV-infected persons who receive a diagnosis of LTBI should receive high priority for DOT (BIII).

Institutional Infection Control

• HIV-infected persons should be advised that certain occupations and activities increase the likelihood of exposure to TB. These include employment and volunteer work in certain health-care facilities, correctional institutions, and shelters for the homeless, as well as in other high-risk settings identified by jurisdictional health authorities. The decision about continuing employment or volunteer activities in a high-risk setting should be made in consultation with a health-care professional and be based on factors such as the person's specific duties in the workplace, prevalence of TB in the community, and the degree to which precautions are taken to prevent TB transmission in the workplace (AIII).

Recommendations for TB Control Among Homeless Persons

Surveillance and Case Detection

• Information on whether the person is homeless should be included for each reported TB case to determine the importance of homelessness in the TB morbidity in the state or community. This is particularly important for communities that provide shelters or other congregate living facilities that are conducive to the transmission of TB (AII).
• In designing programs for control and prevention of TB in homeless persons, public health agencies should work closely with providers of shelter, housing, primary health care, treatment for alcoholism or substance abuse, and social services to ensure a comprehensive approach to improving the health and welfare of this population (AIII).
• Public health agencies should closely monitor the location, mode (i.e., screening or symptomatic presentation), and timeliness of diagnosis of TB in homeless persons in their community and use such data to develop more effective control strategies (AIII).
• Public health agencies should identify providers of medical care for homeless persons and facilities that serve homeless persons (e.g., hospital EDs and correctional institutions) to ensure that practices and procedures are implemented to readily detect and report suspected cases of TB (AIII).
• Providers of primary health care for homeless persons should be knowledgeable about how to diagnose (Table 5), isolate, and report suspected cases of TB (AIII).
• Public health agencies should have ready access to an inpatient facility for the isolation and induction phase of therapy of homeless patients with infectious TB (AII).
• Public health agencies should be prepared to conduct activities to detect TB among persons without symptoms and enhance TB case detection as part of a plan for TB control among homeless persons (Table 6). Indications for screening for TB disease include 1) a documented outbreak, 2) an increase in incidence of TB in the homeless population, and 3) evidence of current transmission of TB in the population. Shelters should always be suspected as sites of transmission (AII).

Case Management

• Case management for homeless persons with TB should be structured to encourage adherence to treatment regimens by making TB treatment a major priority for the patient. It should include provision of housing, at least on a temporary basis; an increasing number of models have demonstrated the importance of a housing incentive in successful treatment of TB in homeless persons. Case management should also include establishing linkages with providers of alcohol and substance treatment services, mental health services, and social services (AII).

Contact Investigation

• Health departments should regularly evaluate their methods for contact investigation for cases of TB among homeless persons to identify barriers and develop alternative strategies, such as shelter- or other location-based contact investigations oriented to possible sites of transmission. Factors to evaluate should include timeliness of completing contact investigations, number of contacts identified and evaluated per case, proportion of evaluated contacts with LTBI and TB disease, and completion of treatment of LTBI among contacts (AII).

Targeted Testing and Treatment of LTBI

• Targeted testing and treatment of LTBI should be a priority for homeless populations because studies from throughout the United States have demonstrated high rates of transmission of M. tuberculosis in this group. This epidemiologic situation, causing a high ongoing risk for acquiring LTBI and TB disease, might necessitate repetitive testing for M. tuberculosis infection among homeless persons (AII).
• When high rates of transmission of M. tuberculosis are documented among homeless persons, those with a positive test for M. tuberculosis infection should be presumed to be recently infected and treated for LTBI (AIII).

Institutional and Environmental Controls

• Organizations that provide shelter and other types of emergency housing for homeless persons should develop institutional TB-control plans. Guidelines to facilitate this process are available from CDC (9) and the Francis J. Curry National TB Center (403) (AII).

Recommendations for TB Control Among Detainees and Prisoners

Case Detection and Case Management

• All jails and prisons should conduct a TB case detection program for detainees and prisoners entering the facility as well as for those who become ill during incarceration to ensure prompt isolation of contagious cases of TB (AII).
• Strategies for case detection for incoming detainees and prisoners include symptom surveys (BIII), testing for M. tuberculosis infection followed by chest radiography (BIII) for those with a positive test, and universal chest radiography in jails (BII). In each setting, the adopted strategy should receive ongoing evaluation.
• Each correctional facility's health-care program for inmates and staff should ensure that training in the clinical and public health aspects of TB and other diseases of public health significance is provided in an ongoing manner (SP).
• Detainees and prisoners with signs and symptoms of TB should be placed in respiratory isolation on-site or off-site until infectious TB is ruled out (SP).
• Case-management strategies including DOT and incentives should be used to assure completion of therapy of detainees and prisoners with TB (BII).
• When detainees and prisoners receiving therapy for TB are transferred to another facility or released from detention, responsibility for continuation of the treatment plan should be transferred to the appropriate facility or agency, and the jurisdictional TB-control program should be notified (SP).

Contact Investigation

• Contact investigations of infectious TB cases in corrections facilities should receive equal priority as effective case detection as the primary means of aborting TB outbreaks. Facilities should have written procedures for contact investigations and have adequate staff to ensure prompt and thorough contact investigations. They should also consult with the jurisdictional public health TB-control program (AII).

Targeted Testing and Treatment of LTBI

• Prisons should implement a treatment program for prisoners with LTBI as part of the effort to prevent the transmission of M. tuberculosis within their walls and to contribute to the overall goal of TB elimination (AII).
• Treatment programs for LTBI in jail detainees should be undertaken only if it is possible to develop a successful plan for community follow-up of released persons on treatment (AII).
• Reducing the length of treatment for LTBI is more likely to lead to completion of treatment in correctional facilities; 4 months of rifampin is recommended as an alternative for the treatment of LTBI (4,324). Correctional health providers need to consider the costs and benefits of this regimen compared with the standard 9-month course of isoniazid in each individual case (BIII).

Institutional Infection Control

• Jails and prisons should implement effective infection-control programs including risk assessment, staff training, screening and treatment of LTBI, isolation of inmates with infectious forms of TB, treatment and discharge planning, and contact investigation (AII).
• HIV-infected detainees and prisoners should not be housed together in a separate facility unless institutional control programs following current guidelines have been established and proved to be effective in preventing the transmission of M. tuberculosis (AIII).

Recommendations for TB Control in Health-Care Facilities and Other High-Risk Settings

• All health-care institutions and other sites at high risk for transmission of M. tuberculosis should have in place a TB infection control program; they should implement and enforce procedures to promptly identify, isolate, and either manage or refer persons with suspected and confirmed infectious TB (AII).
• All health-care institutions that care for persons with TB and other sites that are at risk for transmission should implement TB infection-control measures based on a hierarchy of administrative controls, engineering controls, and respiratory protection. Administrative controls and early recognition of persons with TB are the most important parts of an airborne infection control program for TB (AII).
• Employees who have first contact with patients in settings that serve populations at high risk for TB should be trained to detect persons who could have infectious TB. Patients should be routinely asked about exposure to M. tuberculosis, previous TB infection or disease, current symptoms suggestive of TB, and medical conditions that increase the risk for TB. The medical evaluation should include an interview conducted in the patient's primary language, with the assistance of a medical interpreter if necessary (AIII).
• The index of suspicion for TB should be very high in health-care settings located in geographic areas where TB is prevalent and those serving patients at high risk for TB. Guidelines exist for conducting an evaluation for suspected pulmonary TB in adults at high risk (Table 5) (AIII).
• Among persons suspected of having TB, arrangements should be available for the diagnosis to be promptly established and standard therapy initiated (AII).
• HCWs and employees in other high-risk settings should be tested for M. tuberculosis infection upon employment. Subsequent testing should be based on risk assessment (AIII).
• Health-care facilities and other high-risk institutions should conduct a risk assessment to determine the frequency of testing for M. tuberculosis infection among employees, as a component of the proper level of TB infection control measures (AIII).
• For HCWs and employees in other high-risk settings with no other risk factors for TB, a cut-off of 15 mm of induration (rather than 10 mm) on the tuberculin skin test should be used to define a positive baseline test at the time of initial employment. An increase of >10 mm in reaction size is generally accepted as a positive test result on subsequent testing unless the worker is a contact of a TB case or has HIV infection or is otherwise immunocompromised, in which case a result of >5 mm is considered positive (AIII).
• Employees with M. tuberculosis infection should have a chest radiograph performed to exclude TB disease and should be evaluated for treatment of LTBI, based on current recommendations (AII).
• HCWs and employees in other high risk settings with an indication for treatment of LTBI should be encouraged to initiate and complete treatment (AII).
• Residents admitted to long-term care facilities should be tested for M. tuberculosis infection upon admission (with a two-step test if using tuberculin skin testing) and should receive a history and physical examination to detect symptoms and signs of TB. Residents with M. tuberculosis infection should be offered treatment if indicated (4,324), with careful monitoring for drug toxicity (BII).
• Jails and prisons should develop and implement effective infection-control programs including risk assessment, staff training, screening for TB among incoming detainees and prisoners, isolation of inmates with infectious forms of TB, treatment and discharge planning and prompt and thorough contact investigations (AII).
• In jails and prisons, HIV-infected inmates should not be housed together in a separate housing unit unless institutional control programs following current guidelines have been established and proved to be effective in preventing the transmission of M. tuberculosis (AII).
• Organizations that provide shelter and other types of emergency housing for homeless persons should develop institutional TB-control plans. Guidelines to facilitate this process are available from the Francis J. Curry National TB Center (403) (AII).
• TB-control programs should remain aware of the possibility of TB disease as a result of current transmission when conducting epidemiologic surveillance and contact investigations. M. tuberculosis genotyping should be immediately available to any program that is investigating possible transmission of M. tuberculosis (AII).
• In an era of declining rates of TB in the United States, expertise in the recognition, diagnosis and treatment of TB is likely to decline, especially in areas in which incidence is low (48). Because the risk for spread of M. tuberculosis increases when the diagnosis is not promptly made, institutional education programs for HCWs, including physicians in training, should be made a continuing priority (AIII).

Recommendations on Research for Progress Toward Elimination of TB

• A comprehensive TB research plan for the United States should be developed that identifies the major areas of need and the most effective research approaches to meet those needs. CDC and NIH should convene a broadly-based group of experts and stakeholders to develop this plan (AIII).
• The availability of improved diagnostic tests and therapies for LTBI would have an immediate and lasting impact on the incidence of TB in the United States, and research in those fields should be a priority (AIII).
• Research leading to a new and effective TB vaccine is one of the most important contributions that the United States can make to the global TB epidemic and should be a priority (AIII).
• The CDC-funded Tuberculosis Epidemiological Studies Consortium and Tuberculosis Trials Consortium represent excellent new models for bringing resources from the Federal government, public health agencies, and academia together to plan and implement research for the assessment of new diagnostics and drugs and epidemiologic and operational research on TB. These initiatives should be a priority (AIII).
• Because a substantial number of recommendations for TB control are based on logic, anecdotal experience, and expert opinion, additional research, including clinical, operational, behavioral, and economic research should focus on unanswered questions relating to the basic elements of TB control (AIII).

Acknowledgments

The following persons provided constructive and helpful insights: WJ Burman, MD, Denver Public Health, Denver, Colorado. EP Desmond, MD, California Department of Health Services, Richmond; PC Hopewell, MD, San Francisco General Hospital, University of California, San Francisco; A Green Rush, Francis J. Curry National Tuberculosis Center, San Francisco, California. RJ O'Brien, MD, Foundation for Innovative New Diagnostics, Geneva, Switzerland. T Oemig, Wisconsin Division of Public Health, Madison, Wisconsin. PM Small, MD, The Bill and Melinda Gates Foundation, Seattle; G Wang, MD, Puget Sound Neighborhood Health Centers, Seattle, Washington. KG Castro, MD, MF Iademarco, MD, L Nelson, MD, TR Navin, MD, T Shinnick, MD, Div of TB Elimination, National Center for HIV, STD, & TB Prevention, Coordinating Center for Infectious Diseases, CDC. A Lipavsky and B Nodell also assisted in the preparation of this report.

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403. Hammett TM, Harmon MP, Rhodes W. The burden of infectious disease among inmates of and releasees from US correctional facilities, 1997. Am J Public Health 2002;92:1789--94.
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407. Pelletier AR, DiFerdinando GT Jr., Greenberg AJ, et al. Tuberculosis in a correctional facility. Arch Intern Med 1993;153:2692--5.
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* Wisconsin Department of Health and Family Services. HFS 145. Control of Communicable Diseases. Available at http://www.legis.state.wi.us/rsb/code/hfs/hfs145.pdf.

^† Draft Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings. Federal Register 2004;69:70457--8.

^§ Personal Protective Equipment, 29 C.F.R. Sect. 1910.134 (2003).

Terms and Abbreviations Used in This Report

AAP	American Academy of Pediatrics
ACET	Advisory Council for the Elimination of Tuberculosis
AFB	acid-fast bacilli
ATS	American Thoracic Society
BCG	Mycobacterium bovis bacillus Calmette-Guerín
CIS	U.S. Citizenship and Immigration Service
DGMQ	CDC's Division of Global Migration and Quarantine
DOT	directly observed therapy
EDs	emergency departments
FDA	Food and Drug Administration
HAART	highly active antiretroviral therapy
HCWs	health-care workers
HIPPA	Health Insurance Portability and Accountability Act
HIV	human immunodeficiency virus
IDSA	Infectious Diseases Society of America
IOM	Institute of Medicine
LTBI	latent tuberculosis infection
NAA	nucleic acid amplification assay
NCTA	National Tuberculosis Controllers Association
NIH	National Institutes of Health
NTCA	National Tuberculosis Controllers Association
NTGSN	National Tuberculosis Genotyping and Surveillance Network
NYC	New York City
PRP	personal respiratory protection
QFT	QuantiFERON®-TB test
QFT-G	QFT gold test
RFLP	restriction fragment length polymorphism
SES	socioeconomic status
TB	tuberculosis
TBGP	Tuberculosis Genotyping Program
TNF-a	cycotine tumor necrosis factor alpha
WHO	World Health Organization

 Joint Subcommittee of the American Thoracic Society (ATS), the Infectious Diseases Society of America (ISDA), and CDC
Membership List, November 2004

Chair: Charles M. Nolan, MD, Seattle-King County Department of Public Health, Seattle, Washington (American Thoracic Society).

Co-chairs: Henry M. Blumberg, MD, Emory University School of Medicine, Atlanta, Georgia (Infectious Diseases Society of America), Zachary Taylor, MD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia.

Members: John Bernardo, MD, Boston University School of Medicine, Boston, Massachusetts; Patrick J. Brennan, MD, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Nancy E. Dunlap, MD, PhD, University of Alabama at Birmingham, Birmingham, Alabama; Charles L. Daley, MD, National Jewish Medical and Research Center, Denver, Colorado; Wafaa M. El-Sadr, MD, Harlem Hospital and Columbia University, New York City, New York; Sue Etkind, MS, Massachusetts Department of Public Health, Jamaica Plain, Massachusetts; Mark FitzGerald, MD, University of British Columbia, Vancouver, British Columbia, Canada; James B. McAuley, MD, Rush Medical College, Chicago, Illinois; Marisa Moore, MD, Centers for Disease Control and Prevention, Atlanta, Georgia; Noreen L. Qualls, DrPH, Centers for Disease Control and Prevention, Atlanta, Georgia; Randall R. Reves, MD, Denver Public Health, Denver, Colorado; Sarah E. Royce, MD, California Department of Health Services, Berkeley, California; Max Salfinger, MD, Wadsworth Center, New York State Department of Health, Albany, New York; Jeffrey R. Starke, MD, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas; Wanda Walton, PhD, Centers for Disease Control and Prevention, Atlanta, Georgia; Stephen E. Weis, DO, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas; and Jan Young, MS, California Department of Health Services, Berkeley, California.

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Date last reviewed: 10/19/2005