American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Controlling Tuberculosis in the United States
During 1993–2003, incidence of tuberculosis (TB) in theUnited States decreased 44% and is now occurring at a historiclow level (14,874 cases in 2003). The Advisory Council for theElimination of Tuberculosis has called for a renewed commitmentto eliminating TB in the United States, and the Institute ofMedicine has published a detailed plan for achieving that goal.In this statement, the American Thoracic Society (ATS), Centersfor Disease Control and Prevention (CDC), and the InfectiousDiseases Society of America (IDSA) propose recommendations toimprove the control and prevention of TB in the United Statesand to progress toward its elimination.
This statement is one in a series issued periodically by thesponsoring organizations to guide the diagnosis, treatment,control, and prevention of TB. This statement supersedes theprevious statement by ATS and CDC, which was also supportedby IDSA and the American Academy of Pediatrics (AAP). This statementwas drafted, after an evidence-based review of the subject,by a panel of representatives of the three sponsoring organizations.AAP, the National Tuberculosis Controllers Association, andthe Canadian Thoracic Society were also represented on the panel.
This statement integrates recent scientific advances with currentepidemiologic data, other recent guidelines from this series,and other sources into a coherent and practical approach tothe control of TB in the United States. Although drafted toapply to TB-control activities in the United States, this statementmight be of use in other countries in which persons with TBgenerally have access to medical and public health servicesand resources necessary to make a precise diagnosis of the disease;achieve curative medical treatment; and otherwise provide substantialscience-based protection of the population against TB.
This statement is aimed at all persons who advocate, plan, andwork at controlling and preventing TB in the United States,including persons who formulate public health policy and makedecisions about allocation of resources for disease controland health maintenance and directors and staff members of state,county, and local public health agencies throughout the UnitedStates charged with control of TB. The audience also includesthe full range of medical practitioners, organizations, andinstitutions involved in the health care of persons in the UnitedStates who are at risk for TB.
During 1993–2003, incidence of tuberculosis (TB) in theUnited States decreased 44% and is now occurring at a historiclow level (14,874 cases in 2003). The Advisory Council for theElimination of Tuberculosis (ACET) (1) has called for a renewedcommitment to eliminating TB in the United States, and the Instituteof Medicine (IOM) (2) has published a detailed plan for achievingthat goal. In this statement, the American Thoracic Society(ATS), Centers for Disease Control and Prevention (CDC), andthe Infectious Diseases Society of America (IDSA) propose recommendationsto improve the control and prevention of TB in the United Statesand to progress toward its elimination.
This statement is one in a series issued periodically by thesponsoring organizations to guide the diagnosis, treatment,control, and prevention of TB (3–5). This statement supersedesone published in 1992 by ATS and CDC, which also was supportedby IDSA and the American Academy of Pediatrics (AAP) (6). Thisstatement was drafted, after an evidence-based review of thesubject, by a panel of representatives of the three sponsoringorganizations. AAP, the National Tuberculosis Controllers Association(NTCA), and the Canadian Thoracic Society were also representedon the panel. The recommendations contained in this statement(see GRADED RECOMMENDATIONS FOR THE CONTROL AND PREVENTION OFTB) were rated for their strength by use of a letter grade andfor the quality of the evidence on which they were based byuse of a Roman numeral (Table 1) (7). No rating was assignedto recommendations that are considered to be standard practice(i.e., medical or administrative practices conducted routinelyby qualified persons who are experienced in their fields).
TABLE 1. Grading system for ranking recommendations in this statement
This statement integrates recent scientific advances with currentepidemiologic data, other recent guidelines from this series(3–5), and other sources (2, 8–10) into a coherentand practical approach to the control of TB in the United States.Although drafted to apply to TB control activities in the UnitedStates, this statement might be of use in other countries inwhich persons with TB generally have access to medical and publichealth services and resources necessary to make a precise diagnosisof the disease, achieve curative medical treatment, and otherwiseprovide substantial science-based protection of the populationagainst TB.
This statement is aimed at all persons who advocate, plan, andwork at controlling and preventing TB in the United States,including persons who formulate public health policy and makedecisions about allocation of resources for disease controland health maintenance and directors and staff members of state,county, and local public health agencies throughout the UnitedStates charged with control of TB. The audience also includesthe full range of medical practitioners, organizations, andinstitutions involved in the health care of persons in the UnitedStates who are at risk for TB.
Throughout this document, the terms latent TB infection (LTBI),TB, TB disease, and infectious TB disease are used. LTBI isused to designate a condition in which an individual is infectedwith Mycobacterium tuberculosis but does not currently haveactive disease. Such patients are at risk for progressing toTB disease. Treatment of LTBI (previously called preventivetherapy or chemoprophylaxis) is indicated for those at increasedrisk for progression as described in the text. Persons withLTBI are asymptomatic and have a negative chest radiograph.TB, TB disease, and infectious TB indicate that the diseasecaused by M. tuberculosis is clinically active; patients withTB are generally symptomatic for disease. Positive culture resultsfor M. tuberculosis complex are an indication of TB disease.Infectious TB refers to TB disease of the lungs or larynx; personswith infectious TB have the potential to transmit M. tuberculosisto other persons.
Progress toward TB Elimination
A strategic plan for the elimination of TB in the United Stateswas published in 1989 (11), when the United States was experiencinga resurgence of TB (Figure 1). The TB resurgence was attributableto the expansion of HIV infection, nosocomial transmission ofM. tuberculosis, multidrug-resistant TB, and increasing immigrationfrom counties with a high incidence of TB. Decision makers alsorealized that the U.S. infrastructure for TB control had deteriorated(12); this problem was corrected by a substantial infusion ofresources at the national, state, and local levels (13). Asa result, the increasing incidence of TB was arrested; during1993–2003, an uninterrupted 44% decline in incidence occurred,and in 2003, TB incidence reached a historic low level. Thissuccess in responding to the first resurgence of TB in decadesindicates that a coherent national strategy; coordination oflocal, state, and federal action; and availability of adequateresources can result in dramatic declines in TB incidence. Thissuccess also raised again the possible elimination of TB, andin 1999, ACET reaffirmed the goal of TB elimination in the UnitedStates (1).
Figure 1. Number of reported cases of tuberculosis, by year or diagnosis—United States, 1982–2003.
The prospect of eliminating TB was critically analyzed in anindependent study published by IOM in 2000 (2). The IOM studyconcluded that TB could ultimately be eliminated but that atthe present rate of decline, elimination would take 70 yearsor more. Calling for greater levels of effort and resourcesthan were then available, the IOM report proposed a comprehensiveplan to (1) adjust control measures to the declining incidenceof disease; (2) accelerate the decline in incidence by increasingtargeted testing and treatment of LTBI; (3) develop new toolsfor diagnosis, treatment, and prevention; (4) increase U.S.involvement in global control of TB; and (5) mobilize and sustainpublic support for TB elimination. The report also noted thecyclical nature of the U.S. response to TB and warned againstallowing another "cycle of neglect" to occur, similar to thatwhich caused the 1985–1992 resurgence.
As noted, the 44% decrease in incidence of TB in the UnitedStates during 1993–2003 (14, 15) has been attributed tothe development of effective interventions enabled by increasedresources at the national, state, and local levels (1, 2, 16).Whereas institutional resources targeted specific problems suchas transmission of TB in health care facilities, public resourceswere earmarked largely for public health agencies, which usedthem to rebuild the TB-control infrastructure (13, 17). A primaryobjective of these efforts was to increase the rate of completionof therapy among persons with TB, which was achieved by innovativecase-management strategies, including greater use of directlyobserved therapy (DOT). During 1993–2000, the percentageof persons with reported TB who received DOT alone or in combinationwith self-supervised treatment increased from 38 to 78%, andthe proportion of persons who completed therapy in less than1 year after receiving a diagnosis increased from 63 to 80%(14). Continued progress in the control of TB in the UnitedStates will require consolidation of the gains made throughimproved cure rates and implementation of new strategies tofurther reduce incidence of TB.
Challenges to Progress toward TB Elimination
The development of optimal strategies to guide continuing effortsin TB control depends on understanding the challenges confrontingthe effort. The five most important challenges to successfulcontrol of TB in the United States are as follows: (1) prevalenceof TB among foreign-born persons residing in the United States,(2) delays in detecting and reporting cases of pulmonary TB,(3) deficiencies in protecting contacts of persons with infectiousTB and in preventing and responding to TB outbreaks, (4) persistenceof a substantial population of persons living in the UnitedStates with LTBI who are at risk for progression to TB disease,and (5) maintaining clinical and public health expertise inan era of declining TB incidence. These five concerns (Box 1)serve as the focal point for the recommendations made in thisstatement to control and prevent TB in the United States.
BOX 1. MAJOR CHALLENGES TO SUCCESSFUL CONTROL OF TB
TB amongforeign-born persons residing in the United States
Delays indetection and reporting of cases of pulmonary TB
Deficienciesin protecting contacts of persons with infectious cases of TBand in preventing and responding to TB outbreaks
Presence ofa large reservoir of persons living in the United States withlatent TB infection who are at risk for progression to TB disease
Maintainingclinical and public health expertise in an era of decliningTB incidence
Prevalence of TB among Foreign-born Persons Residing in the United States.
Once a disease that predominately affected U.S.-born persons,TB now affects a comparable number of foreign-born persons whoreside in the United States permanently or temporarily, althoughsuch persons make up only 11% of the U.S. population (14). During1993–2003, as TB incidence in the United States declinedsharply, incidence among foreign-born persons changed little(14). Lack of access to medical services because of cultural,linguistic, financial, or legal barriers results in delays indiagnosis and treatment of TB among foreign-born persons andin ongoing transmission of the disease (18–21). Successfulcontrol of TB in the United States and progress toward its eliminationdepend on the development of effective strategies to controland prevent the disease among foreign-born persons.
Delays in Detection and Reporting of Cases of Pulmonary TB.
New cases of infectious TB should be diagnosed and reportedas early as possible in the course of the illness so curativetreatment can be initiated, transmission interrupted, and publichealth responses (e.g., contact investigation and case-managementservices) promptly arranged. However, delays in case detectionand reporting continue to occur; these delays are attributedto medical errors (22–26) and to patient factors (e.g.,lack of understanding about TB, fear of the authorities, andlack of access to medical services) (18–20). In addition,genotyping studies have revealed evidence of persistent transmissionof M. tuberculosis in communities that have implemented highlysuccessful control measures (27–29), suggesting that suchtransmission occurred before a diagnosis was received. Improvementsin the detection of TB cases, leading to earlier diagnosis andtreatment, would bring substantial benefits to affected patientsand their contacts, decrease TB among children, and preventoutbreaks.
Deficiencies in Protecting Contacts of Person with Infectious TB and in Preventing and Responding to TB Outbreaks.
Although following up contacts is among the highest public healthpriorities in responding to a case of TB, problems in conductingcontact investigations have been reported (30–32). Approachesto contact investigations vary widely from program to program,and traditional investigative methods are not well adapted tocertain populations at high risk. Only half of at-risk contactscomplete a course of treatment for LTBI (32). Reducing the riskof TB among contacts through the development of better methodsof identification, evaluation, and management would lead tosubstantial personal and public health benefits and facilitateprogress toward eliminating TB in the United States.
Delayed detection of TB cases and suboptimal contact investigationcan lead to TB outbreaks, which are increasingly reported (26,33–38). Persistent social problems, such as crowding inhomeless shelters and detention facilities, are contributingfactors to the upsurge in TB outbreaks. The majority of jurisdictionslack the expertise and resources needed to conduct surveillancefor TB outbreaks and to respond effectively when they occur.Outbreaks have become an important element in the epidemiologyof TB, and measures to detect, manage, and prevent them areneeded.
Persistence of a Substantial Population of Persons Living in the United States with LTBI Who Are at Risk for Progression to TB Disease.
An estimated 9.6 to 14.9 million persons residing in the UnitedStates have LTBI (39). This pool of persons with latent infectionis continually supplemented by immigration from areas of theworld with a high incidence of TB and by ongoing person-to-persontransmission among certain populations at high risk. For TBdisease to be prevented among persons with LTBI, those at highestrisk must be identified and receive curative treatment (4).Progress toward the elimination of TB in the United States requiresthe development of new cost-effective strategies for targetedtesting and treatment of persons with LTBI (17, 40).
Maintaining Clinical and Public Health Expertise in an Era of Declining TB Incidence.
Detecting a TB case, curing a person with TB, and protectingcontacts of such persons require that clinicians and the staffmembers of public health agencies responsible for TB have specificexpertise. However, as TB becomes less common, maintaining suchexpertise throughout the loosely coordinated TB-control systemis challenging. As noted previously, medical errors associatedwith the detection of TB cases are common, and deficienciesexist in important public health responsibilities, such as contactinvestigations and outbreak response. Errors in the treatmentand management of patients with TB continue to occur (41, 42).Innovative approaches to education of medical practitioners,new models for organizing TB services (2), and a clear understandingand acceptance of roles and responsibilities by an expandedgroup of participants in TB control will be needed to ensurethat the clinical and public health expertise necessary to progresstoward the elimination of TB are maintained.
Meeting the Challenges to TB Elimination
Further improvements in the control and prevention of TB inthe United States will require a continued strong public healthinfrastructure and involvement of a range of health professionalsoutside the public health sector. The traditional model of TBcontrol in the United States, in which planning and executionreside almost exclusively with the public health sector (17),is no longer the optimal approach during a sustained drive towardthe elimination of TB. This statement emphasizes that successin controlling TB and progressing toward its elimination inthe United States will depend on the integrated activities ofprofessionals from different fields in the health sciences.This statement proposes specific measures to enhance TB controlso as to meet the most important challenges; affirms the essentialrole of the public health sector in planning, coordinating,and evaluating the effort (43); proposes roles and responsibilitiesfor the full range of participants; and introduces new approachesto the detection of TB cases, contact investigations, and targetedtesting and treatment of persons with LTBI.
The plan to reduce the incidence of TB in the United Statesmust be viewed in the larger context of the global effort tocontrol TB. The global TB burden is substantial and increasing.In 2000, an estimated 8.3 million (7.9–9.2 million) newcases of TB occurred, and 1.84 million (1.59–2.22 million)persons died of TB; during 1997–2000, the worldwide TBcase rate increased 1.8%/year (44). TB is increasing worldwideas a result of inadequate local resources and the global epidemicof HIV infection. In sub-Saharan Africa, the rate of TB casesis increasing 6.4%/year (44). ACET (1), IOM (2), and other publichealth authorities (45, 46) have acknowledged that TB will notbe eliminated in the United States until the global epidemicis brought under control, and they have called for greater U.S.involvement in global control efforts. In response, CDC andATS have become active participants in a multinational partnership(Stop TB Partnership) that was formed to guide the global effortsagainst TB. U.S. public and private entities also have providedassistance to countries with a high burden of TB and fundingfor research to develop new, improved tools for diagnosis, treatment,and prevention, including an effective vaccine.
Despite the global TB epidemic, substantial gains can be madetoward elimination of TB in the United States by focusing onimprovements in existing clinical and public health practices(47–49). However, the drive toward TB elimination in theUnited States will be resource-intensive (1, 12). Public healthagencies that plan and coordinate TB-control efforts in statesand communities need sufficient strength in terms of personnel,facilities, and training to discharge their responsibilitiessuccessfully, and the growing number of nonpublic health contributorsto TB control, all pursuing diverse individual and institutionalgoals, should receive value for their contributions. Continuedprogress toward TB elimination in the United States will requirestrengthening the nation's public health infrastructure ratherthan reducing it (1, 50).
Basic Principles of TB Control in the United States
Four prioritized strategies exist to prevent and control TBin the United States (17), as follows:
The first strategy isto promptly detect and report personswho have contracted TB.Because the majority of persons withTB receive a diagnosiswhen they seek medical care for symptomscaused by progressionof the disease, health care providers,particularly those providingprimary health care to populationsat high risk, are key contributorsto the detection of TB casesand to case reporting to the jurisdictionalpublic health agencyfor surveillance purposes and for facilitatinga treatment planand case-management services.
The secondstrategy is to protect close contacts of patientswith contagiousTB from contracting TB infection and disease.Contact evaluationnot only identifies persons in the earlystages of LTBI, whenthe risk for disease is greatest (30–32),but is alsoan important tool to detect further cases of TBdisease.
Thethird strategy is to take concerted action to prevent TBamongthe substantial population of U.S. residents with LTBI.Thisis accomplished by identifying those at highest risk forprogressionfrom latent infection to active TB through targetedtestingand administration of a curative course of treatment(4). Twoapproaches exist for increasing targeted testing andtreatmentof LTBI. The first approach is to encourage clinic-basedtestingof persons who are under a clinician's care for a medicalcondition,such as HIV infection or diabetes mellitus, who areat riskfor progressing from LTBI to active TB (4). The secondapproachis to establish specific programs to reach personswho havean increased prevalence of LTBI, an increased riskfor developingactive disease if LTBI is present, or both (51).
The fourthstrategy is to reduce the rising burden of TB fromrecent transmissionof M. tuberculosis by identifying settingsat high risk fortransmission and applying effective infection-controlmeasuresto reduce the risk. This strategy was used during the1985–1992TB resurgence, when disease attributable torecent transmissionwas an important component of the increasein TB incidence (52–54).TB morbidity attributable torecent spread of M. tuberculosiscontinues to be a prominentpart of the epidemiology of thedisease in the United States.Data collected by CDC's NationalTuberculosis Genotyping andSurveillance Network at seven sentinelsurveillance sites indicatethat 44% of M. tuberculosis isolatesfrom persons with newlydiagnosed cases of TB were clusteredwith at least one otherintrasite isolate, often representingTB disease associatedwith recent spread of M. tuberculosis(55). TB outbreaks arealso being reported with greater frequencyin correctional facilities(37), homeless shelters (33), bars(27), and newly recognizedsocial settings (e.g., among personsin an East Coast networkof gay, transvestite, and transsexualHIV-infected men [34];persons frequenting an abandoned junkyardbuilding used forillicit drug use and prostitution [26]; anddancers in adultentertainment clubs and their contacts, includingchildren [38]).Institutional infection-control measures developedin the 1990sin response to the 1985–1992 resurgence intransmissionof M. tuberculosis in the United States (10) havebeen highlysuccessful in health care facilities (56). However,newly recognizedhigh-risk environments (26, 27, 33, 34, 37,38) present challengesto the implementation of effective infection-controlmeasures.Further attention is required to control the transmissionofM. tuberculosis in these environments.
Structure of this Statement
This statement provides comprehensive guidelines for the fullspectrum of activities involved in controlling and preventingTB in the United States. The remainder of this statement isstructured in eight sections, as follows:
Scientific Basis ofTB Control. This section reviews the baseof knowledge of howTB is transmitted and how the disease isdistributed in theU.S. population, including new informationbased on genotypingstudies. It provides basic background informationas a reviewfor current workers in the field and orients healthcare professionalswho become new participants in TB-controlefforts.
Principlesand Practice of TB Control. This section makes thetransitionfrom the scientific knowledge base to clinical andpublic healthpractice by discussing the goal of TB controlin the UnitedStates, which is to reduce the morbidity and mortalitycausedby TB by preventing transmission of M. tuberculosis frompersonswith contagious forms of the disease to uninfected personsandpreventing progression from LTBI to TB disease among personswho have contracted M. tuberculosis infection. This sectionalso provides basic background information as a review for currentworkers in the field and serves as an orientation for healthcare professionals who become new participants in TB-controlefforts.
Recommended Roles and Responsibilities for TB Control.Thissection outlines roles and responsibilities for the spectrumof participants in the diverse clinical and public health activitiesthat lead to the control and prevention of TB. The paramountrole of the public health sector is reviewed, followed by proposedresponsibilities for nine prominent nonpublic health partnersin TB control: medical practitioners, civil surgeons, communityhealth centers, hospitals, academic institutions, medical professionalorganizations, community-based organizations, correctional facilities,and the pharmaceutical and biotechnology industries. Becauseresponsibilities for the nonpublic health sector have not beenspecified previously, this information also should be usefulto policy makers and advocates for strengthened TB control.
Essential Components of TB Control in the United States. Thissection gives detailed recommendations for enhancing the coreelements of TB control: case detection and management, contactinvestigations, and targeted testing and treatment of LTBI.Recommendations are provided for targeted public education toneutralize the stigma of TB and facilitate earlier care-seekingbehavior among patients and for education of health care professionalsfrom whom patients with TB seek care. A set of five clinicalscenarios is presented in which a diagnosis of TB should beundertaken in primary medical practice, and guidelines are presentedfor activities among certain populations to detect TB amongpersons who have not sought medical care. Guidelines are providedfor a conducting a systematic, step-by-step contact investigation.All jurisdictional TB-control programs are urged to developwritten policies and procedures on the basis of these guidelines.Recommended procedures are also outlined for conducting surveillancefor TB outbreaks and for developing an outbreak response plan.In addition, a framework is presented for identifying and prioritizingsubpopulations and settings within a community that are at highrisk for TB and that should receive targeted testing and treatmentfor LTBI. Priorities for high-risk populations should be establishedon the basis of the expected impact and efficacy of the intervention.Persons who are readily accessible and have preexisting accessto health care services (e.g., prisoners, patients receivingongoing clinic-based care for HIV infection, and immigrantsand refugees with abnormalities on preimmigration chest radiographs)should receive the highest priority. An approach is also presentedto reach members of new immigrant and refugee communities, whooften exist on the margin of U.S. society.
Control of TB amongPopulations at High Risk. On the basis ofthe epidemiology ofTB in the United States, this section providesspecific recommendationsfor controlling and preventing TB amongfive populations: (1)children, (2) foreign-born persons, (3)HIV-infected persons,(4) homeless persons, and (5) detaineesand prisoners in correctionalfacilities. Each population isreadily identifiable and hasbeen demonstrated to be at riskfor TB exposure or progressionfrom exposure to disease, orboth. Surveillance and surveysfrom throughout the United Statesindicate that certain epidemiologicpatterns of TB are consistentlyobserved among these populations,suggesting that the recommendedcontrol measures are generalizable.
Control of TB in Health Care Facilities and Other High-RiskEnvironments. This section recommends infection-control measuresto prevent the transmission of M. tuberculosis in high-risksettings. The approach to control of TB that was developed forhealth care facilities continues to be the most successful modeland is discussed in detail. The recommendations in this sectionhave been updated with respect to the assessment of institutionalrisk for TB. Three levels of risk (low, medium, and potentialongoing transmission) are outlined on the basis of communityand institutional experience with TB. An associated recommendationis that the frequency of testing of employees for LTBI shouldbe based on the institution's risk category. Recommendationsalso are provided for control of transmission of M. tuberculosisin correctional facilities, homeless shelters, and other newlyidentified high-risk environments.
Research Needs to EnhanceTB Control. This section defines gapsin knowledge and deficienciesin technology that limit currentefforts to control and preventTB. Additional research is neededin these areas to producethe evidence base and the tools foroptimal diagnosis, treatment,and prevention of TB. This sectionshould be useful to personswho formulate U.S. public healthpolicy and research prioritiesand members of academic professionsinterested in contributingto enhanced TB control, both in theUnited States and throughoutthe world.
Graded Recommendations for Control and Preventionof TB. Thissection groups detailed graded recommendations foreach areadiscussed in this report.
Transmission of TB M. tuberculosis is nearly always transmitted through an airborneroute, with the infecting organisms being carried in dropletsof secretions (droplet nuclei) that are expelled into the surroundingair when a person with pulmonary TB coughs, talks, sings, orsneezes. Person-to-person transmission of M. tuberculosis isdetermined by certain characteristics of the source-case andof the person exposed to the source-person and by the environmentin which the exposure takes place (Box 2). The virulence ofthe infecting strain of M. tuberculosis might also be a determiningfactor for transmission.
BOX 2. FACTORS DETERMINING TRANSMISSION OF M. TUBERCULOSIS
Characteristicsof the source-case
Concentration of organisms in sputum
Presenceof cavitary disease on chest radiograph
Frequency and strengthof cough
Characteristics of the exposed person
PreviousM. tuberculosis infection
Innate resistance to M. tuberculosisinfection
Genetic susceptibility to M. tuberculosis infectionor disease or both
Characteristics of the exposure
Frequencyand duration of exposure
Dilution effect (i.e., the volumeof air containing infectious droplet nuclei)
Ventilation (i.e.,the turnover of air in a space)
Exposure to ultraviolet light,including sunlight
Virulence of the infecting strain of M.tuberculosis
Characteristics of the Source-Case.
By the time persons with pulmonary TB come to medical attention,30 to 40% of persons identified as their close personal contactshave evidence of LTBI (30). The highest rate of infection amongcontacts follows intense exposure to patients whose sputum smearsare positive for acid-fast bacilli (AFB; Figure 2) (31, 57–59).Because patients with cavitary pulmonary TB are more likelythan those without pulmonary cavities to be sputum AFB smear–positive(60), patients with cavitary pulmonary disease have greaterpotential to transmit TB. Such persons also have a greater frequencyof cough, so the triad of cavitary pulmonary disease, sputumAFB smear positivity, and frequency of cough are likely relatedcausal factors for infectivity. AFB smear–negative patientswith TB also transmit TB, but with lower potential than smear-positivepatients. Patients with sputum AFB smear–negative pulmonaryTB account for approximately 17% of TB transmission (61).
Figure 2. Percentage of persons infected with Mycobacterium tuberculosis, by bacteriologic status of and proximity to the source case—British Columbia and Saskatchewan, 1966–1971. Source: Reference 57.
Characteristics of the Exposed Person.
A study of elderly nursing home residents indicated that personswith initially positive tuberculin skin test results duringperiods of endemic exposure to TB had a much lower risk forTB than those whose skin test results were initially negative(62, 63). This finding suggests that preexisting LTBI confersprotection against becoming infected on subsequent exposureand progression to active disease. Similarly, having prior diseasecaused by M. tuberculosis had been assumed to confer protectionagainst reinfection with a new strain of M. tuberculosis. However,molecular typing of paired isolates of M. tuberculosis frompatients with recurrent episodes of TB disease has demonstratedthat reinfection does occur among immunocompetent and immunocompromisedpersons (64, 65).
The classic means of protecting persons exposed to infectiousdiseases is vaccination. Because of its proven efficacy in protectinginfants and young children from meningeal and miliary TB (66),vaccination against TB with Mycobacterium bovis bacillus Calmette-Guérin(BCG) is used worldwide (although not in the U.S.). This protectiveeffect against the disseminated forms of TB in infants and childrenis likely based on the ability of BCG to prevent progressionof the primary infection when administered at that stage oflife (67). Epidemiologic evidence suggests that BCG immunizationdoes not protect against the development of infection with M.tuberculosis on exposure (68) and use of BCG has not had animpact on the global epidemiology of tuberculosis. One recentretrospective study found that BCG protective efficacy can persistfor 50 to 60 years, indicating that a single dose might havea long duration of effect (69). A meta-analysis indicated that,overall, BCG reduced the risk for TB 50% (66); however, anothermeta-analysis that examined protection over time demonstrateda decrease in efficacy of 5 to 14% in seven randomized controlledtrials and an increase of 18% in three others (70). An effectivevaccine against M. tuberculosis is needed for global TB controlto be achieved.
Because only 30 to 40% of persons with close exposure to a patientwith pulmonary TB become infected (30, 31), innate immunitymight protect certain persons from infection (71). The innatemechanisms that protect against the development of infectionare largely uncharacterized (71). Although immunocompromisedpersons (e.g., those with HIV infection) are at increased riskfor progression to TB disease after infection with M. tuberculosis,no definitive evidence exists that immunocompromised persons,including those with HIV infection, have increased susceptibilityto infection on exposure.
Observational studies suggest that population-based variabilityin susceptibility to TB might be related to the length of timea population has lived in the presence of M. tuberculosis andhas thus developed resistance to infection through natural selection(72–74). However, the genetic basis for susceptibilityor resistance to TB is not well understood (72, 75).
Characteristics of the Exposure.
Studies that have stratified contacts of persons with pulmonaryTB according to time spent with the infected person indicatethat the risk for becoming infected with M. tuberculosis isin part determined by the frequency and duration of exposure(60). In a given environment shared by a patient with pulmonaryTB and a contact, the risk for transmitting the infection varieswith the density of infectious droplet nuclei in the air andhow long the air is inhaled. Indoors, tubercle bacilli are expelledinto a finite volume of air, and, unless effective ventilationexists, droplet nuclei containing M. tuberculosis might remainsuspended in ambient air (76). Exposures in confined air systemswith little or no ventilation pose a major risk for transmissionof TB; this has been demonstrated in homes, ships, trains, officebuildings, and health care institutions (77–80). Whencontact occurs outdoors, TB bacilli expelled from the respiratorytract of an infectious person are rapidly dispersed and arequickly rendered nonviable by sunlight (77). The risk for transmissionduring such encounters is very limited.
Considerable attention has been given to transmission of M.tuberculosis during air travel. Investigations have demonstratedthat the risk for transmission from an infectious person toothers on an airplane is greater on long flights (> 8 hours)and that the risk for contracting M. tuberculosis infectionis highest for passengers and flight crew members sitting orworking near an infectious person (81, 82). However, the overallpublic health importance of such events is negligible (77, 81).
Virulence of the Infecting Strain ofM. TUBERCULOSIS.
Although much is known about factors that contribute to therisk for transmission of M. tuberculosis from person to person,the role of the organism itself is only beginning to be understood(83). Genetic variability is believed to affect the capabilityof M. tuberculosis strains to be transmitted or to cause diseaseonce transmitted, or both. The M. tuberculosis W-strain family,a member of the globally spread Beijing family (84), is a groupof clonally related multidrug-resistant organisms of M. tuberculosisthat caused nosocomial outbreaks involving HIV-infected personsin New York City during 1991–1994 (85, 86). W-family organisms,which have also been associated with TB outbreaks worldwide,are believed to have evolved from a single strain of M. tuberculosisthat developed resistance-conferring mutations in multiple genes.The growth of W-family organisms in human macrophages is four-to eightfold higher than that of strains that cause few or nosecondary cases of TB; this enhanced ability to replicate inhuman macrophages might contribute to the organism's potentialfor enhanced transmission (87).
Whether M. tuberculosis loses pathogenicity as it acquires resistanceto drugs is not known. Isoniazid-resistant M. tuberculosis strainsare less virulent than drug-susceptible isolates in guinea pigs(88), and genotyping studies from San Francisco, California,and from the Netherlands indicated that isoniazid-resistantstrains are much less likely to be associated with clustersof TB cases than drug-susceptible strains (89, 90). Nevertheless,because person-to-person spread has been demonstrated repeatedly,persons with TB with drug-resistant isolates should receivethe same public health attention at the programmatic level asthose with drug-susceptible isolates (91, 92).
Effect of Chemotherapy on Infectiousness.
Patients with drug-susceptible pulmonary and other forms ofinfectious TB rapidly become noninfectious after institutionof effective multiple-drug chemotherapy. This principle hasbeen established by studies demonstrating that household contactsof persons with infectious pulmonary TB who were treated athome after a brief period of hospitalization for institutionof therapy developed LTBI at a frequency no greater than thatof persons with pulmonary TB who were hospitalized for 1 year(93) or until sputum cultures became negative (94). This potenteffect of chemotherapy on infectiousness is likely attributable,at least in part, to the rapid elimination of viable M. tuberculosisfrom sputum (95) and to reduction in cough frequency (96). Theability of chemotherapy to eliminate infectivity is one reasonwhy detecting infectious cases and promptly instituting multiple-drugtherapy is the primary means of interrupting the spread of TBin the United States.
The effect of chemotherapy to eliminate infectiousness was oncebelieved to occur rapidly, and patients on chemotherapy werebelieved not to be infectious (97, 98). However, no ideal testexists to assess the infective potential of a patient with TBon treatment, and infectivity is unlikely to disappear immediatelyafter multidrug therapy is started. Quantitative bacteriologicstudies indicate that the concentration of viable M. tuberculosisin sputum of persons with cavitary sputum AFB smear–positivepulmonary TB at the time of diagnosis, which averaged 106–107organisms/ml, decreased by more than 90% (10-fold) during thefirst 2 days of treatment, an effect attributable primarilyto administration of isoniazid (99), and by more than 99% (100-fold)by Days 14–21, an effect attributable primarily to administrationof rifampin and pyrazinamide (100). Thus, if no factor otherthan the elimination of viable M. tuberculosis from sputum wereto account for the loss of infectivity during treatment, themajority of patients (at least those with infection attributableto isolates susceptible to isoniazid) who have received treatmentfor as few as 2 days with the standard regimen (i.e., isoniazid,rifampin, ethambutol, and pyrazinamide) could be assumed tohave an infective potential that averages 10% of that at thetime of diagnosis. After 14 to 21 days of treatment, infectiousnessaverages less than 1% of the pretreatment level.
This statement presents general guidelines on elimination ofinfectivity with treatment (Box 3). However, decisions aboutinfectiousness of a person on treatment for TB should alwaysbe individualized on the basis of the following: (1) the extentof illness, (2) the presence of cavitary pulmonary disease,(3) the degree of positivity of sputum AFB smear results, (4)the frequency and strength of cough, (5) the likelihood of infectionwith multidrug-resistant organisms, and (6) the nature and circumstancesof the contact between the infected person and exposed contacts(101). Patients who remain in hospitals or reside either temporarilyor permanently in congregate settings (e.g., shelters and correctionalfacilities) are subject to different criteria for infectiousness.In such congregate settings, identification and protection ofclose contacts are not possible during the early phase of treatment,and more stringent criteria for determining absence of infectivity(i.e., three consecutive AFB-negative sputum smears) shouldbe followed (10). All patients with suspected or proven multidrug-resistantTB should be subjected to these more stringent criteria forabsence of infectivity (10).
BOX 3. CRITERIA FOR DETERMINING WHEN DURING THERAPY A PATIENTWITH PULMONARY TB HAS BECOME NONINFECTIOUS*
Patient has negligiblelikelihood of multidrug-resistant TB (no known exposure to multidrug-resistantTB and no history of prior episodes of TB with poor complianceduring treatment).
Patient has received standard multidruganti-TB therapy for 2–3 weeks. (For patients with sputumAFB smear results that are negative or rarely positive, thresholdfor treatment is 5–7 days.)
Patient has demonstratedcomplete adherence to treatment (e.g., is receiving directlyobserved therapy).
Patient has demonstrated evidence of clinicalimprovement (e.g., reduction in the frequency of cough or reductionof the grade of the sputum AFB smear result).
All close contactsof patient have been identified, evaluated, advised, and, ifindicated, started on treatment for latent TB infection. Thiscriterion is critical, especially for close contacts who arechildren younger than 4 years and those of any age with immunocompromisinghealth conditions (e.g., HIV infection).
While in hospitalfor any reason, patients with pulmonary TB should remain inairborne-infection isolation until they (1) are receiving standardmultidrug anti-TB therapy; (2) have demonstrated clinical improvement;and (3) have had three consecutive AFB-negative smear resultsof sputum specimens collected 8–24 hours apart, with atleast one being an early-morning specimen. Hospitalized patientsreturning to a congregate setting (e.g., a homeless shelteror detention facility) should have three consecutive AFB-negativesmear results of sputum specimens collected more than 8 hoursapart before being considered noninfectious.
*These six criteriafor absence of infectivity with treatment should be consideredgeneral guidelines. Decisions about infectivity of a personon treatment for TB should depend on the extent of illness andthe specific nature and circumstances of the contact betweenthe patient and exposed persons.
Progression from LTBI to TB Disease.
Although the human immune response is highly effective in controllingprimary infection resulting from exposure to M. tuberculosisamong the majority of immunocompetent persons, all viable organismsmight not be eliminated. M. tuberculosis is thus able to establishlatency, a period during which the infected person is asymptomaticbut harbors M. tuberculosis organisms that might cause diseaselater (4, 71). The mechanisms involved in latency and persistenceare not completely understood (71, 72).
For the majority of persons, the only evidence of LTBI is animmune response against mycobacterial antigens, which is demonstratedby a positive test result: either a tuberculin skin test (3)or, in certain circumstances, a whole blood antigen–stimulatedIFN- release assay result (e.g., QuantiFERON-TB Gold test [QFT-G];Cellestis Limited, Carnegie, Victoria, Australia). The tuberculinskin test measures delayed-type hypersensitivity; QFT-G, anex vivo test for detecting latent M. tuberculosis infection,measures a component of cell-mediated immune response (102).QFT-G is approved by the U.S. Food and Drug Administration,and CDC will publish guidelines on its use. CDC had previouslypublished guidelines for use of QuantiFERON-TB, an earlier versionof the test that is no longer available (103). T SPOT-TB, anenzyme-linked immunospot assay for IFN-, is marketed in Europealong with QFT-G but is not FDA-approved for use in the U.S.Although approved by the Food and Drug Administration, the Tinetest is not recommended for the diagnosis of M. tuberculosisinfection. Tests available in other countries to diagnose M.tuberculosis infection (e.g., T SPOT-TB and Heaf test) are notrecommended for clinical use in the United States.
Once a person has contracted LTBI, the risk for progressionto TB disease varies. The greatest risk for progression to diseaseoccurs within the first 2 years after infection, when approximatelyhalf of the 5 to 10% lifetime risk occurs (4, 104). Multipleclinical conditions also are associated with increased riskfor progression from LTBI to TB disease. HIV infection is thestrongest known risk factor (4). Other key risk factors becauseof their prevalence in the U.S. population are diabetes mellitus(105), acquisition of LTBI in infancy or early childhood, andapical fibronodular changes on chest radiograph (106).
A recent addition to the known risk factors for progressionfrom LTBI to TB disease is the use of therapeutic agents thatantagonize the effect of cytokine tumor necrosis factor (TNF-)and have been proven to be highly effective treating autoimmune-relatedconditions (e.g., Crohn's disease and rheumatoid arthritis)(107). Cases of TB have been reported among patients receivingall three licensed TNF- antagonists (i.e., infliximab, etanercept,and adalimimab) (108). CDC has published interim guidelinesfor preventing TB when these agents are used (109).
Epidemiology of TB in the United States
Surveillance (i.e., the systematic collection, analysis, anddissemination of data) is a critical component of successfulTB control, providing essential information needed to (1) determinepatterns and trends of the disease, (2) identify populationsand settings at high risk, and (3) establish priorities forcontrol and prevention activities. Surveillance is also essentialfor quality-assurance purposes, program evaluation, and measurementof progress toward TB elimination. In addition to providingthe epidemiologic profile of TB in a given jurisdiction, stateand local surveillance are essential to national TB surveillance.
CDC's national TB surveillance system publishes epidemiologicanalyses of reported TB cases in the United States (110). Datafor the national TB surveillance system are reported by statehealth departments in accordance with standard TB case-definitionand case-report formats (110, 111). The system tracked the reversalof the declining trend in TB incidence in the United Statesin the mid-1980s, the peak of the resurgence in 1992 (with a20% increase in cases reported during 1985–1992), andthe subsequent 44% decline to an all-time low number (14,871)and rate (5.1 cases/100,000 population) of TB cases in 2003(Figure 1) (14, 15).
Geographic Distribution of TB.
Wide disparities exist in the geographic distribution of TBcases in the United States. In 2003, six states (California,Florida, Georgia, Illinois, New York, and Texas) each reported500 or more cases and accounted for 57% of the national total(14). These states along with New Jersey accounted for approximately75% of the overall decrease in cases since 1992. The highestrates and numbers of TB cases are reported from urban areas:more than 75% of cases reported in 2003 were from areas witha population of 500,000 or greater (14). In 2003, 24 states(48%) had an incidence of 3.5 or fewer cases of TB/100,000 population,the rate established as the Year 2000 interim target for theUnited States in the 1989 strategic plan for eliminating TB(11).
Demographic Distribution of TB.
In 2003, adults aged 15 to 64 years accounted for 73.6% of reportedTB cases. Incidence of TB was highest (8.4 cases/100,000 population)among adults older than 65 years, who accounted for 20.2% ofcases. Children younger than 14 years accounted for 6.2% ofreported cases and had the lowest incidence of TB; 61.3% ofreported cases occurred among men, and case rates among menwere at least double those of women in mid- and older-adultage groups. In 2003, the white, non-Hispanic population accountedfor only 19% of reported cases of TB, and TB incidence amongthe four other racial/ethnic populations for which data wereavailable was 5.7 to 21.0 times that of non-Hispanic whites(Table 2). Foreign-born persons accounted for 94% of TB casesamong Asians and 74% of cases among Hispanics, whereas 74% ofcases among non-Hispanic blacks occurred among persons bornin the United States (15).
TABLE 2. Tuberculosis rates* among five racial/ethnic populations—united states, 2003
Distribution of TB by Socioeconomic and Employment Status. SOCIOECONOMIC STATUS.
Low socioeconomic status (SES) is associated with an increasedrisk for TB. An analysis of national surveillance data thatassigned socioeconomic indicator values on the basis of residencezip code indicated that the risk for TB increased with lowerSES for six indicators (crowding, education, income, poverty,public assistance, and unemployment), with crowding having thegreatest impact (112). Risk for TB increased uniformly betweensocioeconomic quartile for each indicator, similar to othersocioeconomic health gradients for other chronic diseases, exceptfor crowding, for which risk was concentrated in the lowestquartile. Adjusting for SES accounted for approximately halfof the increased risk for TB associated with race/ethnicityamong U.S.-born blacks, Hispanics, and American Indians (112).
OCCUPATION.
Increased incidence of TB among persons with certain occupationsis attributable to exposure in the work environment and to anincreased likelihood that workers will have other risk factorsunrelated to occupation, such as foreign birth. A 29-state studyof patients with clinically active TB reported during 1984–1985indicated that increased incidence was independent of occupation.An association between general SES groupings of occupationsand risk for TB also was demonstrated in that study (113). Chronicallyunemployed persons had high incidence of TB; this finding isconsistent with surveillance data indicating that more than50% of patients with TB were unemployed during the 2 years beforediagnosis (14).
TB AMONG HEALTH CARE WORKERS.
Because transmission of M. tuberculosis in health care institutionswas a contributing factor to the resurgence of TB during 1985–1992,recommendations were developed to prevent transmission in thesesettings (10). In 2003, persons reported to have been healthcare workers (HCWs) in the 2 years before receiving their diagnosesaccounted for 3.1% of reported TB cases nationwide (14). However,the elevated risk among HCWs might be attributable to otherfactors (e.g., birth in a country with a high incidence of TB)(114). A multistate occupational survey indicated that the majorityof HCWs did not have a higher risk for TB than the general population;respiratory therapists, however, did appear to be at greaterrisk (113).
Identification of Populations at High Risk for TB. CONTACTS OF INFECTIOUS PERSONS.
A high prevalence of TB disease and LTBI has been documentedamong close contacts of persons with infectious pulmonary TB(31). A study of approximately 1,000 persons from urban siteswith pulmonary AFB sputum smear–positive TB indicatedthat more than one-third of their contacts had positive tuberculinskin tests and that 2% of all close contacts had active TB.Contacts identified with TB disease were more likely to be householdmembers or children younger than 6 years (31).
FOREIGN-BORN PERSONS.
The proportion of TB cases in the United States occurring amongforeign-born persons increased progressively during the 1990s;in 2003, persons born outside the United States accounted for53% of reported cases (Figure 3) (14). Although foreign-bornpersons who received a diagnosis of TB in 2002 were born inmore than 150 countries worldwide, as in each of the previous6 years, five countries of origin accounted for the greatestnumber of foreign-born persons with TB: China (5%), India (8%),Mexico (26%), the Philippines (12%), and Vietnam (8%). During1992–2003, the number of states in which 50% or more ofthe total reported cases occurred among foreign-born personsincreased from four (8%) in 1992 to 24 (48%) in 2003 (15). Amongstates and cities, however, this profile can change rapidly,reflecting changes in patterns of immigration and refugee settlement(21).
Figure 3. Number and percentage of cases of tuberculosis among foreign-born persons, by year of diagnosis—United States, 1986–2003.
Surveillance data indicate that incidence of TB among foreign-bornpersons is approximately 23 cases/100,000 population (14). Incidencevaried by county of origin, appearing to reflect incidence ofTB in the country of birth (21, 115, 116). In 2003, approximately47% of foreign-born persons with TB received their diagnoseswithin 5 years of their arrival in the United States, and 19%received their diagnoses within 1 year of arrival. Among foreign-bornpersons, TB case rates decreased with longer duration of residencein the United States. TB rates were nearly four times higheramong persons residing in the United States for fewer than 5years than in those who were residents for 5 years or more (115,116).
HIV-INFECTED PERSONS.
Because reporting of HIV infection among persons with TB isnot complete, the exact prevalence of HIV infection among suchpersons is unknown. During 1993–2001, the prevalence ofreported HIV infection occurring among persons also reportedwith TB decreased from 15 to 8% (14); this decrease has beenattributed, in part, to reduced transmission of TB among HIV-infectedpersons (16). According to a recent worldwide epidemiologicassessment, however, 26% of adult TB cases in the United Statesare attributable to HIV infection (44).
HOMELESS PERSONS.
In 2003, persons known to have been homeless in the year beforereceiving a diagnosis accounted for 6.3% of cases of TB nationwide.On the basis of available population estimates (117), incidenceof TB among homeless persons is approximately 30–40/100,000population, more than five times the national case rate. However,a prospective study of a cohort of approximately 3,000 homelesspersons in San Francisco documented an annual incidence of morethan 250 cases/100,000 population (118). In addition, outbreaksof TB linked to overnight shelters continue to occur among homelesspersons and likely contribute to the increased incidence ofTB among that population (119, 120).
OTHER POPULATIONS AT HIGH RISK.
In 2003, persons known to have injected drugs in the year beforereceiving a diagnosis accounted for 2.2% of reported cases ofTB, and noninjection drug use was reported by 7.3% of personswith TB. In certain U.S. communities, injection drug use issufficiently prevalent so as to constitute a high risk for epidemiologicimportance rather than simply an individual risk factor, especiallywhen overlap exists between injection drug use and HIV infection(121, 122).
TB among Detainees and Prisoners in Correctional Facilities.
The proportion of cases of TB occurring among inmates of prisonsand jails has remained stable at approximately 3 to 4% sincedata began to be collected in 1993; it was 3.2% in 2003 (14).Inmates also have high incidence of TB, with rates often morethan 200/100,000 population (123), and they have a disproportionatelygreater number of risk factors for TB (e.g., low SES, HIV infection,and substance abuse) compared with the general population (124,125). TB transmission in correctional facilities contributesto the greater risk among those populations, presumably becauseof the difficulties in detecting cases of infectious TB andin identifying, evaluating, and treating contacts in these settings(37, 126).
TB outbreaks occur in both prison and jail settings. Dedicatedhousing units for prison inmates with HIV infection were sitesof transmission in California in 1995 (126) and in South Carolinain 1999 (37). In the South Carolina outbreak, delayed diagnosisand isolation of an inmate who apparently had active TB afterentering the facility led to more than 15 outbreak cases. Transmissionleading to TB infection in the community also was documentedin an outbreak that occurred in a jail in Tennessee during 1995–1997(127, 128) that involved approximately 40 inmates; contact investigationswere incomplete because of brief jail terms and frequent movementof inmates. During the same period, 43% of patients with TBin the surrounding community had previously been incarceratedin that jail (127), and, after 2 years, the jail outbreak strainwas more prevalent in the community than it was during the jailoutbreak. Genotyping studies indicated that the outbreak strainaccounted for approximately 25% of TB cases in the community,including those among patients with no history of incarceration(128).
Contributions of Genotyping of M. tuberculosis M. tuberculosis genotyping refers to procedures developed toidentify M. tuberculosis isolates that are identical in specificparts of the genome (83). To date, M. tuberculosis genotypinghas been based on polymorphisms in the number and genomic locationof mycobacterial repetitive elements. The most widely used genotypingtest for M. tuberculosis is restriction fragment length polymorphism(RFLP) analysis of the distribution of the insertion sequenceIS6110 (129). However, genotyping tests based on polymorphismsin three additional mycobacterial repetitive elements (i.e.,polymorphic guanine cytosine–rich repetitive sequences,direct repeats [spoligotyping], and mycobacterial interspersedrepetitive units [MIRU]) have also been developed (83). M. tuberculosisisolates with identical DNA patterns in an established genotypingtest often have been linked through recent transmission amongthe persons from whom they were isolated.
When coupled with traditional epidemiologic investigations,analyses of the genotype of M. tuberculosis strains have confirmedsuspected transmission and identified unsuspected transmissionof M. tuberculosis. These analyses have also identified riskfactors for recent infection with rapid progression to disease,demonstrated exogenous reinfection with different strains, identifiedweaknesses in conventional contact investigations, and documentedthe existence of laboratory cross-contamination. Genotypinghas become an increasingly useful tool for studying the pathogenesis,epidemiology, and transmission of TB.
Epidemiology of TB among Contacts in Outbreak Settings.
Conventional contact investigations have used the concentriccircles approach to collect information and screen householdcontacts, coworkers, and increasingly distant contacts for TBinfection and disease (17). The concentric circles model hasbeen described previously (130). However, this method mightnot always be adequate in out-of-household settings. In community-basedstudies from San Francisco (131), Zurich (132), and Amsterdam(133), only 5 to 10% of persons with clustered IS6110-basedgenotyping patterns were identified as contacts by the source-personin the cluster. This finding indicates that either (1) transmissionof M. tuberculosis might occur more commonly than suspectedand is not easily detected by conventional contact tracing investigationsor (2) genotype clustering does not necessarily represent recenttransmission (55). Because genotyping studies discover onlymissed or mismanaged contacts (i.e., those that subsequentlyreceive a diagnosis of TB), such studies cannot explain thesuccesses of the process or the number of cases that were prevented.
Certain populations (e.g., the urban homeless) present specificchallenges to conducting conventional contact investigations.Genotyping studies have provided information about chains oftransmission in these populations (118, 119). In a prospectivestudy of TB transmission in Los Angeles, the degree of homelessnessand use of daytime services at three shelters were factors thatwere independently associated with genotype clustering (119).Additional studies support the idea that specific locationscan be associated with recent or ongoing transmission of M.tuberculosis among homeless persons. Two studies among predominantlyHIV-infected men have demonstrated evidence of transmissionat specific bars in the community (134, 135).
Genotyping techniques have confirmed TB transmission in HIVresidential facilities (136), crack houses (i.e., settings inwhich crack cocaine is sold or used) (137), hospitals and clinics(54), and prisons (138, 139). TB transmission also has beendemonstrated among church choirs (140) and renal transplantpatients (141) and in association with processing of contaminatedmedical waste (142) and with bronchoscopy (143, 144).
Communitywide Epidemiology of TB.
TB might arise because of rapid progression from a recentlyacquired M. tuberculosis infection, from progression of LTBIto TB disease, or occasionally from exogenous reinfection (145).The majority of genotyping studies have assumed that clusteredisolates in a population-based survey reflect recent transmissionof M. tuberculosis. Certain studies have identified epidemiologiclinks between clustered TB cases, inferring that the clusteredcases are part of a chain of transmission from a single commonsource or from multiple common sources (131, 146).
The number and proportion of population-based cases of TB thatoccur in clusters representing recent or ongoing transmissionof M. tuberculosis have varied from study to study; frequencyof clustering has varied from 17 to 18% (in Vancouver, Canada)to 30 to 40% (in U.S. urban areas) (131, 147, 148). Youth, beinga member of a racial or ethnic minority population, homelessness,substance abuse, and HIV infection have been associated withclustering (131, 133, 148, 149).
The increasing incidence of TB among foreign-born persons underscoresthe need to understand transmission dynamics among this population.In San Francisco, two parallel TB epidemics have been described(150, 151): one among foreign-born persons, which was characterizedby a low rate of genotype clustering, and the other among U.S.-bornpersons, which was characterized by a high rate of genotypeclustering. In a recent study from New York City, being bornoutside the United States, being aged 60 years or older, andreceiving a diagnosis after 1993 were factors independentlyassociated with being infected with a strain not matched withany other, whereas homelessness was associated with genotypeclustering and recent transmission (152). Among foreign-bornpersons, clustered strains were more likely to be found amongpatients with HIV infection (152).
Other Contributions of Genotyping.
Genotyping can determine whether a patient with a recurrentepisode of TB has relapsed with the original strain of M. tuberculosisor has developed exogenous reinfection with a new strain (64,153). In Cape Town, South Africa, where incidence of TB is highand considerable ongoing transmission exists, 16 (2.3%) of 698patients had more than one episode of TB disease. In 12 (75%)of the 16 recurrent cases, the pairs of M. tuberculosis isolateshad different IS6110-based genotyping patterns, indicating exogenousreinfection (154). However, in areas with a low incidence ofTB, episodes of exogenous reinfection are uncommon (153). BecauseTB incidence in the majority of areas of the United States islow and decreasing, reinfection is unlikely to be a major causeof TB recurrence.
Genotyping has greatly facilitated the identification of false-positivecultures for M. tuberculosis resulting from laboratory cross-contaminationof specimens. Previously, false-positive cultures (which mightlead to unnecessary treatment for patients, unnecessary workfor public health programs in investigating cases and pseudo-outbreaks,and unnecessary costs to the health care system) were difficultto substantiate (155). Because of its capability to determineclonality among M. tuberculosis strains, genotyping has beenapplied extensively to verify suspected false-positive cultures(156–158) and to study the causes and prevalence of laboratorycross-contamination (159, 160).
The Role of Genotyping ofM. TUBERCULOSISIN TB-CONTROL PROGRAMS.
In 2004, CDC established the Tuberculosis Genotyping Programto enable rapid genotyping of isolates from every patient inthe United States with culture-positive TB (161). State TB programsmay submit one M. tuberculosis isolate from each culture-positivecase within their jurisdictions to a contracted genotyping laboratory.A detailed manual describing this program, including informationon how to interpret genotyping test results and how to integrategenotyping into TB-control activities, has been published (162).
Genotyping information is essential to optimal TB control intwo settings. First, genotyping is integral to the detectionand control of TB outbreaks, including ruling a suspected outbreakin or out and pinpointing involved cases and the site or sitesof transmission (54, 136–144). Second, genotyping is essentialto detect errors in handling and processing of M. tuberculosisisolates (including laboratory cross-contamination) that leadto reports of false-positive cultures for M. tuberculosis (156,158–160, 163).
More extensive use of M. tuberculosis genotyping for TB controldepends on the availability of sufficient program resourcesto compare results with information from traditional epidemiologicinvestigative techniques. Time-framed genotyping surveys andgood fieldwork can unravel uncertainties in the epidemiologyof TB in problematic populations at high risk (150–152,164). Genotyping surveys and epidemiologic investigations alsocan be used as a program monitoring tool to determine the adequacyof contact investigations (29, 119, 132–134, 164–166)and evaluate the success of control measures designed to interrupttransmission of M. tuberculosis among certain populations orsettings (167).
Programs that use genotyping for surveillance of all of thejurisdiction's M. tuberculosis isolates should work closelyon an ongoing basis with the genotyping laboratory and commitsufficient resources to compare genotyping results with thoseof traditional epidemiologic investigations. Information fromboth sources is needed for optimum interpretation of the complexepidemiologic patterns of TB in the United States (84, 168).
Basic Principles of TB Control
The goal of TB control in the United States is to reduce morbidityand mortality caused by TB by (1) preventing transmission ofM. tuberculosis from persons with contagious forms of the diseaseto uninfected persons and (2) preventing progression from LTBIto TB disease among persons who have contracted M. tuberculosisinfection. Four fundamental strategies are used to achieve thisgoal (Box 4) (17, 169), as follows:
Early and accurate detection,diagnosis, and reporting of TBcases leading to initiation andcompletion of treatment. Detectingand reporting suspected casesof TB is the key step in stoppingtransmission of M. tuberculosisbecause it leads to prompt initiationof effective multiple-drugtreatment, which rapidly reducesinfectiousness (seeBox 3).Completion of a full course of standardtherapy is essentialto prevent treatment failure, relapse,and the acquisition ofdrug resistance (5). TB is commonly diagnosedwhen a personseeks medical attention for symptoms caused bythe disease ora concomitant medical condition. Thus, healthcare providers,particularly those providing primary healthcare to populationsat high risk, are key contributors to TBcase detection. A suspectedor confirmed case of TB should bereported immediately to thejurisdictional public health agency.Reporting of new casesis essential to initiate public healthresponses, includinginstitution of a treatment plan, case-managementservices, andevaluation of contacts, and for surveillance purposes.Thisstatement contains detailed recommendations for improvingdetectionof TB cases. Treatment of TB is the subject of anotherstatementin this series from ATS, CDC, and IDSA (5).
Identificationof contacts of patients with infectious TB andtreatment ofthose at risk with an effective drug regimen. Theevaluationof contacts of cases of infectious TB is one of themost productivemethods of identifying adults and children withLTBI at highrisk for progression to TB disease and personsin the earlystages of TB disease (30, 31). Contact investigationsthereforeserve as an important means of detecting TB casesand at thesame time identify persons in the early stage ofLTBI, whenthe risk for progression to TB disease is high andthe benefitof treatment is greatest (4).
Identification of other personswith LTBI at risk for progressionto TB disease and treatmentof those persons with an effectivedrug regimen. Targeted testingis intended to identify personsother than TB contacts who havean increased risk for acquiringTB and to offer such personsdiagnostic testing for M. tuberculosisinfection and treatment,if indicated, to prevent subsequentprogression to TB disease(4). This approach is critical tothe eventual elimination ofTB in the United States, becauseit is the only means of preventingTB in the substantial poolof persons with LTBI at high riskfor progression to TB disease.Targeted testing and treatmentof LTBI is also a primary meansof controlling TB among foreign-bornpersons at high risk residingin the United States because genotypingsurveys have consistentlydemonstrated that the majority ofTB cases in that populationare attributable to progressionfrom LTBI (150–152). Targetedtesting and treatment ofLTBI is best accomplished through cost-effectiveprograms aimedat patients and populations identified on thebasis of localsurveillance data as being at increased riskfor TB (51). Guidelinesfor this activity have been published(4). This statement includesrecommendations for organizingand conducting programs for targetedtesting and treatment ofLTBI.
Identification of settingsin which a high risk exists for transmissionof M. tuberculosisand application of effective infection-controlmeasures. Forthe rising burden of TB from recent transmissionof M. tuberculosisto be reduced, settings at high risk fortransmission shouldbe identified, and effective infection-controlmeasures shouldbe taken to reduce the risk. In the 1980s, themajority of casesof TB in the United States were believed toarise through activationof LTBI, and few cases were believedto occur as a consequenceof recent transmission of M. tuberculosis(6). During the 1985–1992TB resurgence, however, diseasecaused by recent transmissionwas a critical component of theincrease in TB incidence. TBoutbreaks associated with person-to-personspread occurred indifferent venues, most prominently in healthcare facilities(52–54, 170). TB morbidity caused by recentspread ofM. tuberculosis has continued to be a prominent partof theepidemiology of the disease in the United States. During1996–2000,when incidence of TB was in constant decline,a survey involving10,883 M. tuberculosis isolates collectedfrom persons withnewly diagnosed cases from seven NationalTuberculosis Genotypingand Surveillance Network sentinel surveillancesites indicatedthat 52% were clustered with at least one otherisolate (averagegenotype cluster size: six isolates), frequentlyrepresentingcases of TB disease associated with recent spreadof M. tuberculosis(171). Outbreaks of TB are also being reportedwith greaterfrequency (33, 34, 172, 173). Institutional infection-controlmeasures have been highly successful in health care facilities(56), but other high-risk settings (e.g., correctional facilities[37], homeless shelters [33], bars [27], and social settingsthat extend beyond single venues [26, 34, 38, 172]) presentchallenges to effective infection control (172).
BOX 4. STRATEGIES TO ACHIEVE THE GOAL OF REDUCTION OF TB MORBIDITYAND MORTALITY
Early and accurate detection, diagnosis, and reportingof TB cases
Prompt initiation of effective treatment and completionof a full course of therapy for patients with TB
Identificationof contacts of patients with infectious TB and other personswith latent TB infection who are at substantial risk for progressingto TB disease and treatment of those persons with a standardregimen
Identification of settings in which a high risk existsfor transmission of M. tuberculosis and application of effectiveinfection-control measures
Vaccination with BCG is not recommended as a means to controlTB in the United States because of the unproved efficacy ofthe vaccine in the U.S. population (174, 175), its effect ofconfounding the results of tuberculin skin testing (176), andthe success of other measures in reducing incidence of TB (16).During the 1985–1992 TB resurgence, the documented spreadof TB, including multidrug-resistant TB, in health care institutionsand in the community (52–54, 177, 178) stimulated interestin the potential use of BCG to protect HCWs and others fromexposure to M. tuberculosis. In 1996, a statement from ACETand the Advisory Committee on Immunization Practices (179) recommendedvaccination with BCG for (1) infants and children with exposureto M. tuberculosis in settings in which other protective measuresare either inaccessible or proven to be ineffective and (2)HCWs when likelihood of exposure to multidrug-resistant TB ishigh and recommended control measures have not been successful.With improved TB control in the United States and the declineof multidrug-resistant TB (13), use of BCG for protection againstTB has declined. An improved vaccine, particularly one thatprotects adults with LTBI against acquiring TB disease, wouldaccelerate progress toward TB elimination in the United States(180).
Deficiencies in TB Control
Because TB control is a complex undertaking that involves multipleparticipants and processes, mistakes often occur, with adverseconsequences. Common errors include the following: (1) delaysamong persons with active TB obtaining health care, (2) delayeddetection and diagnosis of active TB, (3) failed or delayedreporting of TB, (4) failure to complete an effective courseof treatment for TB, (5) missed opportunities to prevent TBamong children, and (6) deficiencies in conducting contact investigationsand in recognizing and responding to outbreaks.
Delays in Obtaining Health Care.
Homeless patients with TB symptoms often delay seeking careor experience delays in gaining access to care (181), and fearof immigration authorities has been associated with patientdelay among foreign-born persons (19). Patients who speak languagesother than English or who are aged 55 to 64 years are more likelythan others to delay seeking care (20).
Cultural factors that might affect health-seeking behavior byforeign-born persons include misinterpretation or minimizationof symptoms, self-care by using over-the-counter or folk medicines,and the social stigma associated with TB (18). In certain societies,women with TB are less likely to take advantage of health careservices, perhaps because of stigma associated with the diagnosis,including a lower likelihood of marriage (182, 183). Even inareas with open access to public health clinical services, personsat risk for TB might not seek evaluation and treatment becausethey are not aware that these resources are available for personswith limited financial means (118, 184–186).
Delayed Detection and Diagnosis of Active TB.
Delayed detection of a case of TB and resulting delays in initiationof treatment can occur if the clinician does not suspect thediagnosis. A survey conducted in New York City in 1994 foundthat the median delay within the health care system (definedas the time from first contact to initiation of treatment foractive TB) was 15 days (range, 0–430 days) (20). Asiansand homeless persons were more likely to encounter delays inreceiving a diagnosis than non-Asians and persons with stablehousing. Persons without cough who had AFB smear–negativeTB or who did not have a chest radiograph at their initial visitalso experienced delays. In London, England, delays in diagnosisoccurred among whites and among women of all racial/ethnic populations(187).
Regardless of the reason, the consequences of delays in diagnosisand initiation of effective therapy can be serious. In Maine,a shipyard worker aged 32 years who was a TB contact and whowas untreated despite having symptoms of active TB, repeatedmedical visits, and a chest radiograph consistent with activeTB did not receive a diagnosis of TB until 8 months after hebecame ill (188), and 21 additional cases of TB occurred amonghis contacts. Of 9,898 persons who were investigated as contacts,697 (7.0%) persons received diagnoses of new LTBIs. A high schoolstudent in California was symptomatic for more than 1 year beforeTB was diagnosed (177). Subsequently, 12 additional TB casesamong fellow students were linked to the source-case, and 292(23%) of 1,263 students tested had positive tuberculin skintests.
Other instances of delayed or missed diagnoses of TB have beenreported that have resulted in extended periods of infectiousnessand deaths (22, 24, 178). These problems reflect the increasingdifficulty in maintaining clinical expertise in the recognitionof TB in the face of declining disease incidence (41). Recognitionof TB among patients with AFB-negative sputum smear resultsis a challenge for practitioners and has been associated withdelays in reporting and treatment (22, 189, 190).
Delayed Reporting of TB.
Failure to promptly report a new TB case delays public healthresponses (e.g., institution of a treatment plan, case-managementservices, and protection of contacts). Although TB cases inthe United States rarely remain unreported, timeliness of reportingvaries (median, 7–38 days) (190).
Failure to Receive and Complete Standard Treatment for Active TB.
Failure to receive and complete a standard course of treatmentfor TB has adverse consequences, including treatment failure,relapse, increased TB transmission, and the emergence of drug-resistantTB (191–193). At least two reasons exist for failure tocomplete standard treatment. First, patients frequently failto adhere to the lengthy course of treatment (188). Poor adherenceto treatment regimens might result from difficulties with accessto the health care system, cultural factors, homelessness, substanceabuse, lack of social support, rapid clearing of symptoms, orforgetfulness (18, 194). Second, as TB has become less common,clinicians might fail to use current treatment regimens (48).These adverse outcomes are preventable by case-management strategiesprovided by TB-control programs, including use of DOT (13, 195,196).
Missed Opportunities to Prevent TB among Children.
The absence of TB infection and disease among children is akey indicator of a community's success in interrupting the transmissionof TB (197). The 1985–1992 TB resurgence included a reversalof the long-term decline in the incidence of TB among children,which indicated a failure of the public health system to preventdisease transmission (197). A study of 165 children reportedwith TB in California in 1994 found that, for 59 children (37%),an adult source-case was identified (198). Factors that contributedto transmission to children included delayed reporting, delayedinitiation of contact investigations, and poor management ofadult source-cases. Improvements in contact investigations mighthave prevented 17 (10%) of those cases (198).
Deficiencies in Conducting Contact Investigations and in Recognizing and Responding to Outbreaks.
Deficiencies in contact investigations and failure to recognizeand respond to TB outbreaks are among the most important challengesto optimal control of TB in the United States. These topicsare discussed in detail in this statement along with the otheressential components of TB control.
Importance of TB Training and Education
The 1985–1992 TB resurgence led ACET to call for a renewedfocus on training and education as an integral part of strategiesfor TB control, prevention, and elimination (1). Factors indicatinga need for this focus include the following:
Deficiencies inclinical knowledge and practice. Errors havebeen documentedon the part of medical practitioners and TB-controlstaff inthe diagnosis, reporting, treatment, and follow-upof TB cases.These deficiencies indicate a broad need for trainingand educationthroughout the TB-control system, among both publichealth andnonpublic health participants.
Staffing and workforce concerns.Ongoing education and trainingwithin TB-control programs arerequired to inform staff membersabout programmatic and patientmanagement issues. For example,implementation of DOT for treatmentof TB disease or LTBI orthe integration of a new category ofHCWs (e.g., outreach workers)might have substantial trainingrequirements. Changes in thestate or local epidemiology ofTB and the emergence of new populationsor settings of highrisk also might necessitate additional trainingor retrainingof staff members.
New guidelines and recommendations. TB guidelinesand recommendationsare regularly published and updated (3–5).However, thepromulgation of guidelines alone does not necessarilyimproveprovider practices (42, 199). Guidelines are more effectivewhen supplemented with targeted education (42).
Educationof new contributors to TB control. TB eliminationwill requirethat new categories of health professionals, notpreviouslyidentified as contributors to TB control in the community,takeon expanded responsibilities. Education strategies forthesenew partners will be needed. For example, clinicians shouldunderstand the local epidemiology of TB sufficiently to knowif their practice includes patients at high risk. They shouldknow how to identify and treat patients at high risk who haveLTBI. They should be able to recognize the signs and symptomsof TB disease and understand how to evaluate and treat personswith suspected cases. They should understand the public healthaspects of TB, including the need for prompt reporting and thefacilitating role of the jurisdictional health agency in casemanagement. In particular, strategies are needed to maintainTB knowledge and expertise among clinicians in areas of lowTB incidence (48).
Diminished teaching about TB in medicaland nursing schools.As TB case rates declined in the UnitedStates, schools of medicineand nursing gradually reduced theiremphasis on TB education.With the resurgence of TB in the UnitedStates during 1985–1992and recognition of the extentof the global epidemic, cliniciansand public health programshave been faced with the challengesof learning to diagnose,manage, and control TB as if it werea new disease (42, 200,201). Education is essential to thefuture control of TB inthe United States and globally (2),and creating interest inTB among students of the health professionsis critical to generatingthe competent workforce needed toeliminate TB in the UnitedStates and contribute human resourcesto fighting the globalTB epidemic.
Educating Patients and Communities at High Risk.
Education of patients by clinicians, TB program staff, and trustedcommunity members promotes acceptance and adherence to authoritativeadvice about controlling and preventing TB. Such education caninfluence patients' decision making about whether to acceptand complete treatment for LTBI (202).
Because cultural and health beliefs might act as barriers toeffective control of TB (18, 19), an increasing need existsfor education targeted at populations at high risk (19). TB-controlprograms should enlist community-based organizations and otherkey informants to discover the health beliefs, norms, and valuesof communities at high risk in their jurisdictions (202, 203).Professional associations and academic institutions (includingschools of medicine, public health, and nursing) will be valuablepartners in developing an understanding of the health perceptionsof these populations. Education materials should be developedwith input from the target audience to ensure that they areculturally and linguistically appropriate (203, 204).
The Strategic Plan for TB Training and Education.
In 1997, CDC funded a project to develop a Strategic Plan forTuberculosis Training and Education (the Strategic Plan) thatprovided guidance to agencies and organizations in the UnitedStates that offer TB training and education for public- andprivate-sector providers. The Strategic Plan specified criticalareas requiring attention, including the following: (1) theneed for culturally competent programs and materials, (2) effectivemethods and technologies, (3) collaboration and cooperationamong training and education partners outside TB-control programs,and (4) adequate funding for training and education efforts.
Other Resources for TB Training and Education.
Substantial progress has been made in developing and disseminatingresources for TB training and education. CDC and national TBcenters, NTCA, regional controllers associations (e.g., theNortheast Tuberculosis Training Consortium), state and localhealth departments, and the National Laboratory Training Networkhave all conducted education programs or developed trainingand education materials. In 2001, as stipulated by the StrategicPlan, the Tuberculosis Education and Training Network was established.The network is coordinated by CDC and includes educators inlocal, state, and territorial health agencies. CDC has alsodeveloped the Tuberculosis Information CD-ROM, version 3, andthe Tuberculosis Education and Training Resource Guide; theseproducts are designed to enhance awareness and accessibilityof resources (available at http://www.cdc.gov/nchstp/tb/default.htm)for TB education and training. The establishment in 2004 ofthe National Tuberculosis Curriculum Coordinating Center atthe University of California at San Diego by the National Heart,Lung, and Blood Institute signals a commitment by the NationalInstitutes of Health (NIH) to provide basic TB education forhealth care students and providers.
Professional societies and specialty boards are means for reachingprivate medical providers. Including TB as a subject in statemedical society programs, hospital grand rounds, and medicalspecialty board examinations would be a valuable resource forproviders serving populations at low risk. New linkages shouldbe established to reach providers serving populations at highrisk (e.g., foreign-born, homeless, and HIV-infected persons).For example, the AIDS Education and Training Centers fundedby the Health Resources and Services Administration are a resourcefor reaching HIV/AIDS providers, and foreign physicians' associationsand community-based organizations are potential partners forreaching international medical graduates and health care providersof foreign-born persons.
Laboratory Services for Optimal TB Control
The diagnosis of TB, management of patients with the disease,and public health control services rely on accurate laboratorytests. Laboratory services are an essential component of effectiveTB control, providing key information to clinicians (for patientcare) and public health agencies (for control services).
Up to 80% of all initial TB-related laboratory work (e.g., smearand culture inoculation) is performed in hospitals, clinics,and independent laboratories outside the public health system,whereas more than 50% of species identification and drug susceptibilitytesting is performed in public health laboratories (205). Thus,effective TB control requires a network of public and privatelaboratories to optimize laboratory testing and the flow ofinformation. Public health laboratorians, as a component ofthe public health sector with a mandate for TB control, shouldtake a leadership role in developing laboratory networks andin facilitating communication among laboratorians, clinicians,and TB controllers.
Role of Public Health Laboratories.
Public health laboratories should ensure that clinicians andpublic health agencies within their jurisdictions have readyaccess to reliable laboratory tests for diagnosis and treatmentof TB (206). Specific tasks to ensure the availability, accessibility,and quality of essential laboratory services are (1) assessmentof the cost and availability of TB laboratory services and (2)development of strategic plans to implement and maintain a systemsapproach to TB testing (207). In this process, public healthlaboratories should assess and monitor the competence of laboratoriesthat perform any testing related to the diagnosis, management,and control of TB within their jurisdictions; develop guidelinesfor reporting and tracking of laboratory results; and educatelaboratory staff members, health care providers, and publichealth officials about available laboratory tests, new technologies,and indications for their use. For example, public health laboratoriesshould lead the discussion on the costs, logistics requirements(e.g., collection and transport of clinical specimens withinthe required time), and quality assurance issues associatedwith the use of QFT-G, the new test for latent M. tuberculosisinfection (103). The process of coordinating TB laboratory servicesis usually best organized at the state level (208), and theAssociation of Public Health Laboratories has compiled descriptionsof successful organizational models for integrated laboratoryservices (207).
Role of Clinical Laboratories.
Because the majority of initial TB laboratory work related todiagnosis of TB is conducted in hospitals, clinics, and independentlaboratories (205), clinicians and public health agencies areincreasingly dependent on the laboratory sector for the confirmationof reported cases, and public health laboratories are similarlydependent for referral of specimens for confirmatory testingand archiving. However, as a result of laboratory consolidationat the regional or national level (206), private laboratoriesare experiencing more difficulties in fulfilling this function.In certain instances, consolidation has resulted in poor communicationamong laboratory personnel, clinicians, and public health agencies(206, 209). Problems also have been identified in specimen transport,test result reporting, and quality control (206, 209, 210).In response, certain states (e.g., Wisconsin Department of Healthand Family Services. HFS145. Control of Communicable Diseases.Available online at http://www.legis.state.wi.us/rsb/code/hfs/hfs145.pdf)have adopted laws and regulations that mandate essential clinicallaboratory services for TB control (e.g., drug susceptibilitytesting and reporting of the first M. tuberculosis isolate fromeach patient and submission of isolates to the state publichealth laboratory).
The clinical laboratory sector should accept the responsibilitiesthat accompany its emergence as a provider of essential TB testing(209). This statement provides recommendations to guide turnaroundtimes for essential tests, reporting to clinicians and jurisdictionalpublic health agencies, and referral of specimens to publichealth laboratories or their designees.
Essential Laboratory Tests.
Six tests performed in clinical microbiological laboratoriesare recommended for optimal TB control services (Table 3). Theselaboratory tests should be available to every clinician involvedin TB diagnosis and management and to jurisdictional publichealth agencies charged with TB control. In addition, othertests that are useful in the diagnosis and management of selectedpatients and for specific TB control activities include M. tuberculosisgenotyping, serum drug levels, tests used for monitoring fordrug toxicity, and QFT-G for diagnosis of latent M. tuberculosisinfection (5, 103, 162). Access to these specialized tests shouldbe provided as needed.
TABLE 3. Essential laboratory tests for tuberculosis control
For suspected cases of pulmonary TB, sputum smears for AFB providea reliable indication of potential infectiousness; and for AFBsmear–positive pulmonary cases, a nucleic acid amplificationassay (NAA) provides rapid confirmation that the infecting mycobacteriaare from the M. tuberculosis complex. These two tests, whichshould be available with rapid turnaround times from specimencollection, facilitate decisions about initiating treatmentfor TB or a non-TB pulmonary infection, and, if TB is diagnosed,for reporting the case and establishing priority to the contactinvestigation.
Growth detection and identification of M. tuberculosis by cultureof sputum and other affected tissue is essential for confirmationof the identity of the organism and for subsequent drug susceptibilitytesting, which is recommended on all initial isolates for eachpatient. Cultures also remain the cornerstone for the diagnosisof TB in smear-negative pulmonary and extrapulmonary cases and,along with sputum smears for AFB, provide the basis for monitoringa patient's response to treatment, for release from isolation,and for diagnosing treatment failure and relapse (5). The useof liquid media systems, which can provide information in lesstime than solid media (in certain cases, 7 days), should beavailable in all laboratories that perform culture for mycobacteria.Detailed descriptions of these recommended laboratory tests;recommendations for their correct use; and methods for collecting,handling, and transporting specimens have been published (3,211).
RECOMMENDED ROLES AND RESPONSIBILITIES FOR TB CONTROL
This section delineates organizational and operational responsibilitiesof the public health sector that are essential to achieve thegoals of TB control in the United States. However, a centralpremise of this statement is that continuing progress towardelimination of TB in the United States will require the collaborativeefforts of a broad range of persons, organizations, and institutionsin addition to the public health sector, which has responsibilityfor the enterprise. For example, clinicians who provide primaryhealth care and other specialized health services to patientsat high risk for TB, academic medical centers that educate andtrain them, hospitals in which they practice, and professionalorganizations that serve their interests can all make meaningfulcontributions to improve the detection of TB cases, one of themost important obstacles to continuing progress (Box 1). Similarly,important roles exist for such entities as community-based organizationsrepresenting populations at risk for TB and the pharmaceuticalindustry, which takes academic advances and develops the toolsfor diagnosis, treatment, and prevention of TB. This sectiondiscusses the importance to the TB elimination effort of participantsoutside the public health sector and proposes specific rolesand responsibilities that each could fulfill toward that goal.The sponsoring organizations intend for these proposals to serveas the basis for discussion and consensus building on the importantroles and responsibilities of the non–public health sectorin continuing progress toward the elimination of TB in the UnitedStates.
Public Health Sector
The infrastructure for TB control has been discussed extensivelyin recent years. An analysis of contributing factors to therise in the number of TB cases during 1985–1992 concludedthat the resurgence never would have occurred had the publichealth infrastructure been left in place and supported appropriately(212). The need to maintain the TB-control infrastructure hasbeen expressed repeatedly (1, 2, 13, 213, 214).
Public health activities have been described as consisting offour interrelated components: mission/purpose, structural capacity,processes, and outcomes (215). Among these four components,structural capacity (i.e., persons who do the work of publichealth, their skills and capacities, the places where they work,the way they are organized, the equipment and systems availableto them, and the fiscal resources they command) represents thepublic health infrastructure for TB control.
The responsibility for TB control and prevention in the UnitedStates rests with the public health system through federal,state, county, and local public health agencies. Programs conductedby these agencies were critical to the progress that has beenmade in TB control, and the deterioration of those programsafter the loss of categoric federal funding contributed to theresurgence of TB in the United States during 1985–1992(1, 2, 13, 212–214). Since 1992, as a result of increasedfunding for TB-control programs, national incidence of TB diseasehas declined. In 2004, $147 million in federal funds were dedicatedto domestic TB control, compared with $6.6 million in 1989,during the resurgence. These funds have been used to rebuildpublic health–based TB-control systems, and the successachieved highlights the critical role of the public health systemin TB control.
TB control in the United States has traditionally been conductedthrough categoric programs established to address the medicalaspects of the disease and the specific interventions requiredfor its successful prevention and management (17, 216). CDC'sDivision of TB Elimination, in partnership with other CDC entitiesthat conduct TB-related work, provides guidance and oversightto state and local jurisdictions by conducting nationwide surveillance;developing national policies, priorities, and guidelines; andproviding funding, direct assistance, education, and programevaluation. Setting the national agenda for support of basicand clinical research is also a critical function of federalhealth agencies, including NIH and CDC, with support from nongovernmentorganizations such as ATS and IDSA.
To meet the priorities of basic TB control (Box 4), state andlocal public health agencies with responsibility for TB controlshould provide or ensure the provision of a core group of functions(Box 5). Jurisdictional public health agencies should ensurethat competent services providing these core elements functionadequately within their jurisdictions and are available withminimal barriers to all residents.
BOX 5. CORE RESPONSIBILITIES FOR CONTROL OF TB BY A JURISDICTIONALPUBLIC HEALTH AGENCY
Assessment of the extent and characteristicsof TB in the jurisdiction through collection and analysis ofepidemiologic and other data
Development of policies and proceduresand of a plan for controlling TB, on the basis of the assessmentof the problem
Assurance of diagnostic, clinical, and preventiveservices needed to implement the plan for controlling TB
Monitoringand evaluating the effectiveness of the plan for controllingTB
Providing information and education to policy makers, healthcare professionals, and the public regarding control of TB inthe jurisdiction
How the core components of TB control are organized differsamong jurisdictions, depending on the local burden of disease,the overall approach to public health services within the jurisdiction,budgetary considerations, the availability of services withinand outside the public health sector, and the relationshipsamong potential participants. Certain jurisdictions providecore program components themselves, whereas other jurisdictionscontract with others to provide them. In the majority of cases,the organization includes a mix in which the public health agencyprovides certain services, contracts for others, and works collaborativelywith partners and stakeholders to accomplish the remainder (48).Sharing of direct services, including patient management, increasesthe importance of the public health sector, which retains responsibilityfor success of the process. This evolving role of the publichealth sector in TB control is consistent with the widely acceptedconcept of the three core functions of public health that IOMproposed in 1988: assessment, policy development, and assurance(43).
Health Insurance Portability and Accountability Act.
The Health Insurance Portability and Accountability Act (HIPAA)of 1996 included provisions to protect the privacy of individuallyidentifiable health information. To implement these privacyprotections, the U.S. Department of Health and Human Serviceshas issued a ruling on how health care providers may use anddisclose personally identifiable health information about theirpatients; these regulations provide the first national standardsfor requirements regarding the privacy of health information(217).
HIPAA also recognizes the legitimate need for public healthauthorities and others responsible for ensuring the public'shealth and safety to have access to personal health informationto conduct their missions and the importance of public healthdisease reporting by health care providers. HIPAA permits disclosureof personal health information to public health authoritieslegally authorized to collect and receive the information forspecified public health purposes. Such information may be disclosedwithout written authorization from the patient. Disclosuresrequired by state and local public health or other laws arealso permitted. Thus, HIPAA should not be a barrier to the reportingof suspected and verified TB cases by health care providers,including health care institutions. Additional information aboutHIPAA is available at http://www.hhs.gov/ocr/hipaa.
Roles and Responsibilities of Federal Public Health Agencies.
Establishment of standards and guidelines. Federal agenciesshould take a leadership role in developing and promulgatingstandards of public health and clinical practice for TB, incollaboration with professional medical societies, state andlocal TB-control programs, and other organizations. These partnershipshave served the medical and public health communities and shouldbe continued and strengthened.
Financial and technical supportfor TB control and elimination.Federal agencies should continueto provide financial and technicalsupport for TB control andelimination within their own institutionsand jurisdictionsand to provide direct support to state andlocal TB-controlprograms through CDC cooperative agreements.In addition, CDCshould continue to provide technical assistancethrough theassignment of medical and administrative staff tostate andlocal TB-control programs and by responding to requestsforassistance with TB outbreaks. In relation to these responsibilities,CDC should determine the level of necessary financial supportfrom the federal government needed to control and prevent TBin the United States.
National reporting, surveillance, andanalysis. Federal agenciesshould continue to support the collection,aggregation, anddistribution of national surveillance datathrough cooperativeagreements with state and local TB programs.Consultation andtechnical support from federal resources arealso essentialto maintain the state and local network of surveillancethroughoutthe United States.
Program oversight and monitoring.Federal agencies should facilitatedevelopment of quality improvementprograms and establishmentof quality indicators for state andlocal TB-control programs.
Education and training. Althoughmultiple participants in TBcontrol are responsible for educationand training of patientsand health care providers, federalagencies should take thelead in developing training and educationmaterials to facilitateTB control at the state and local levels.
Public health research. Federal agencies should plan, conduct,and support basic, clinical, and public health research leadingto improvements in TB diagnosis, treatment, and prevention.
Evaluation of immigrants and refugees outside the United States.Federal agencies are responsible for ensuring that legal immigrantsand refugees are evaluated appropriately for TB before theirarrival in the United States and for notifying state and localTB-control programs of the arrival in their jurisdictions ofimmigrants and refugees with suspected TB. Agencies involvedin evaluating and reporting arriving immigrants and refugeesshould ensure the quality and timeliness of those processes.
Coordination of interstate TB-control efforts. Federal agenciesshould take the lead in resolving interstate TB-control issues,including movement of TB patients across state lines and multistateTB outbreaks.
Roles and Responsibilities of Jurisdictional Public Health Agencies. PLANNING AND POLICY DEVELOPMENT.
The blueprint for TB control for a given area is a responsibilityof the jurisdictional public health agency. Policies and plansshould be based on a thorough understanding of local epidemiologicdata and on the capabilities and capacities of clinical andsupport services for clients, the fiscal resources availablefor TB control, and ongoing indicators of program performance.Open collaboration is essential among public health officialsand community stakeholders, experts in medical and nonmedicalTB management, laboratory directors, and professional organizations,all of whom provide practical perspectives to the content ofstate and local TB-control policy. Policies and procedures shouldreflect national and local standards of care and should offerguidance in the management of TB disease and LTBI.
A written TB-control plan that is updated regularly should bedistributed widely to all interested and involved parties. Theplan should assign specific roles and responsibilities; defineessential pathways of communication between providers, laboratories,and the public health system; and assign sufficient resources,both human and financial, to ensure its implementation, includinga responsible case manager for each suspected and verified caseof TB. The plan should include the provision of expert consultationand oversight for TB-related matters to clinicians, institutions,and communities. It should provide special guidance to locallaboratories that process TB-related samples, assist local authoritiesin conducting contact or outbreak investigations and DOT, andprovide culturally appropriate information to the community.Systems to minimize or eliminate financial and cultural barriersto TB control should be integral to the plan, and persons withTB and persons at high risk with TB infection should receiveculturally appropriate education about TB and clinical services,including treatment, with no consideration for their abilityto pay. Finally, the plan should be consistent with currentlegal statutes related to TB control. Relevant laws and regulationsshould be reviewed periodically and updated as necessary toensure consistency with currently recommended clinical and publichealth practice (e.g., mandatory reporting laws, institutionalinfection-control procedures, hospital and correctional systemdischarge planning, and involuntary confinement laws) (218).
COLLECTION AND ANALYSIS OF EPIDEMIOLOGIC AND OTHER DATA.
The development of policies and plans for the control of TBwithin a jurisdiction requires a detailed understanding of theepidemiology of TB within the jurisdiction. Mandatory and timelycase reporting from community sources (e.g., providers, laboratories,hospitals, and pharmacies) should be enforced and evaluatedregularly. To facilitate the reporting process and data analyses,jurisdictions should modify systems as necessary to accommodatelocal needs and evolving technologies. State and local TB-controlprograms should have the capability to monitor trends in TBdisease and LTBI in populations at high risk and to detect newpatterns of disease and possible outbreaks. Populations at highrisk should be identified and targeted for active surveillanceand prevention, including targeted testing and treatment ofLTBI (4).
Timely and accurate reporting of suspected and confirmed TBcases is essential for public health planning and assessmentat all levels. Analyses of these data should be performed atleast annually to determine morbidity, demographic characteristics,and trends so that opportunities for targeted screening fordisease or infection can be identified. Regular reviews of clinicaldata (e.g., collaborative formal case presentations and cohortanalyses of treatment outcomes; completeness, timeliness andeffectiveness of contact investigations; and treatment of LTBI)may be used as indicators of program performance.
Data should be collected and maintained in a secure, computerizeddata system that contains up-to-date clinical information onpersons with suspected and confirmed cases and on other personsat high risk. Each case should be reviewed at least once monthlyby the case manager and by field or outreach staff to identifyproblems that require attention. The TB-case registry shouldensure that laboratory data, including data on sputum cultureconversion and drug susceptibility testing of clinical isolates,are promptly reported, if applicable, to the health care providerso any needed modifications in management can be made. Thisrequires a communications protocol for case managers, providers,and the public health and private laboratory systems that willtransmit information in a timely fashion. Aggregate programdata should be available to the health care community and tocommunity groups and organizations with specific interests inpublic health to support education and advocacy and to facilitatetheir collaboration in the planning process.
CLINICAL AND DIAGNOSTIC SERVICES FOR PATIENTS WITH TB AND THEIR CONTACTS.
TB-control programs should ensure that patients with suspectedor confirmed TB have ready access to diagnostic and treatmentservices that meet national standards (3, 5). These servicesare often provided by state- or city-supported TB specialtyclinics and staffed by health department personnel or by contractedservice providers; however, persons may seek medical care forTB infection or disease in the private medical sector. Regardlessof where a person receives medical care, the primary responsibilityfor ensuring the quality and completeness of all TB-relatedservices rests with the jurisdictional health agency, and healthdepartments should develop and maintain close working relationswith local laboratories, pharmacies, and health care providersto ensure that standards of care, including those for reporting,are met.
Clinical services provided by the health department, contractedvendors, or private clinicians should be competent, accessible,and acceptable to members of the community served by the jurisdiction.Hours of clinic operation should be convenient, and waitingintervals between referral and appointments should be kept toa minimum. Persons with symptoms of TB should be accommodatedimmediately (i.e., on a walk-in basis). Staff, including providers,should reflect the cultural and ethnic composition of the communityto the extent that this is possible, and competent clinicalinterpreter services should be available to those patients whodo not speak English. All clinical services, including diagnosticevaluation, medications, clinical monitoring, and transportation,should be available without consideration of the patient's abilityto pay and without placing undue stress on the patient thatmight impair completion of treatment.
Clinical facilities should provide diagnostic, monitoring, andscreening tests, including radiology services. Health care providers,including nurses, clinicians, pharmacists, laboratory staffmembers, and public health officials, should be educated aboutthe use and interpretation of diagnostic tests for TB infectionand disease. Clinics and providers should monitor patients receivingTB medications at least monthly for drug toxicity and for treatmentresponse, according to prevailing standards of care (5). Counselingand voluntary testing for HIV infection should be offered toall persons with suspected and proven TB and to certain personswith LTBI, with referral for HIV treatment services when necessary.A case manager, usually a health department employee, shouldbe assigned to each patient suspected or proven to have TB toensure that adequate education is provided about TB and itsmanagement, standard therapy is administered continuously, andidentified contacts are evaluated for infection and disease.
A treatment plan for persons with TB should be developed immediatelyon report of the case. This plan should be reviewed periodicallyby the case manager and the treating clinician and modifiedas necessary as new data become available (219). The treatmentplan should include details about the medical regimen used,how and where treatment is to be administered, monitoring ofadherence, drug toxicity, and clinical and bacteriologic responses.Social and behavioral factors that might interfere with successfulcompletion of treatment also should be addressed.
Patient-specific strategies for promoting adherence to treatmentshould take into account each patient's clinical and socialcircumstances and needs (5). Such strategies might include theprovision of incentives or enablers (e.g., monetary payment,public transportation passes, food, housing, child care, ortransportation to the clinic for visits). Whether the patient'scare is managed by a public health clinic or in the privatesector, the initial strategy used should emphasize direct observationof medication ingestion by an HCW. Patient input into this process(e.g., regarding medications to be taken or the location ofDOT) is often useful as it can minimize the burden of treatmentand provide the patient a degree of control over an anticipatedlengthy course of therapy.
Expert medical consultation in TB should be available to thehealth care community, especially for patients who have drug-resistantdisease or medical diagnoses that might affect the course orthe outcome of treatment. Consultants may be employees of thehealth department or clinicians with expertise who are undercontract with the health department.
Inpatient care should be available to all persons with suspectedor proven TB, regardless of the person's ability to pay. Hospitalizedpatients with suspected proven TB should have access to expertmedical and nursing care, essential diagnostic services, medications,and clinical monitoring to ensure that diagnostic and treatmentstandards are met. Inpatient facilities that manage personswho are at risk for TB should have infection-control policiesand procedures in place to minimize the risk for nosocomialspread of infection. Facilities should report persons with suspectedor confirmed TB to the health department and arrange for dischargeplanning as required by statute.
Public health agencies should have legal authority and adequatefacilities to ensure that patients with infectious TB are isolatedfrom the community until they are no longer infectious. Thisauthority should include the ability to enforce legal confinementof patients who are unwilling or unable to adhere to medicaladvice (218, 220). This authority also should apply to nonadherentpatients who no longer are infectious but who are at risk forbecoming infectious again or becoming drug resistant.
TB-control programs should serve as sources of information andexpert consultation to the health care community regarding airborneinfection and appropriate infection-control practice. A TB program'spresence raises overall provider awareness of TB and facilitatestimely diagnosis, reporting, and treatment. Collaboration withlocal health care facilities to design and assist in periodicstaff education and screening is often a health department function.Expertise in airborne infections by TB-control personnel maybe shared with biologic terrorism programs to assist in thedesign and implementation of local protocols.
Contact investigation, including education and evaluation ofcontacts of persons with infectious TB, is a key component ofthe public health mandate for TB control. Often the primaryresponsibility of the case manager, contact investigation shouldproceed as quickly and as thoroughly as indicated by the characteristicsof the specific case and by those of the exposed contact (e.g.,young children or immunocompromised persons). This statementincludes recommendations on organizing and conducting contactinvestigations. TB-control programs that are prepared to implementenhanced TB-control strategies should initiate or facilitateimplementation by other medical providers of programs for targetedtesting and treatment of persons with LTBI on the basis of localepidemiologic data that identify populations at high risk. Apublic health approach to this activity is presented in thisstatement (see ESSENTIAL COMPONENTS OF TB CONTROL IN THE UNITEDSTATES).
Liaison with communities at high risk is critical to the successof TB control in any jurisdiction. TB-control programs shoulddevelop strong lines of communication with local community groupsand organizations and their health care providers to understandlocal priorities and beliefs about TB. Trusted community memberscan facilitate the design and implementation of strategies toimprove TB diagnosis and prevention. Community-based clinicalservices that use local providers who are educated in TB treatmentand prevention and who have a connection with the TB-controlprogram can improve community acceptance of prevention and treatmentof TB (221).
TRAINING AND EDUCATION.
TB-control programs should provide education and training inthe clinical and public health aspects of TB to all programstaff. Staff members should receive appropriate education atregular intervals on the basis of their particular responsibilitiesin the program and should demonstrate proficiency in those areaswhen tested. Public health TB programs also should educate healthcare providers (both public and private), community members,public health officials, and policy makers on the basis of localepidemiology and needs. To ensure the availability of a competentworkforce for TB that understands and meets the needs of itscommunity, state TB programs should use resources from CDC-fundednational TB centers, NIH-supported TB curriculum centers, NTCA,and other national and local agencies to create and implementeducation activities in coordination with schools of medicine,nursing, pharmacy, dentistry, and public health; community-basedorganizations and their constituents; local health care providers;and health care institutions (222). A Strategic Plan for PublicHealth Work Force Development (223) and a Strategic Plan forTuberculosis Training and Education have been developed.
INFORMATION MANAGEMENT.
Information-management systems are key factors in medical safetyand quality improvement (224, 225) and should be prioritizedby all TB-control programs. Information technology can improvecare of patients with TB through standardized collection ofdata; tracking of test results and details of treatment, includingadministration of DOT; and prediction of interactions amongmedications. Information technology can also facilitate analysisand rapid distribution of epidemiologic data and the managementof individualized treatment plans (5) and support ongoing programperformance analyses. Barriers to successful implementationof information technology include costs and resistance to change.
MONITORING AND EVALUATION.
The systematic monitoring and analysis of program activitiesis a critical factor in enhancing program performance. Evaluationtechniques provide TB programs with an evidence-based approachto assess and improve their TB-control strategies by understandingwhat causes good or bad program performance. Evaluation canalso be used for program advocacy, assessing staffing needs,training and capacity building, directing limited resourcesto the most productive activities, accounting for availableresources, generating additional resources, and recognizingachievement (226).
Each public health agency should develop its own prioritiesfor program evaluation on the basis of the nature and dimensionsof the TB problem in its jurisdiction and the way that servicesare organized. In general, the first priority for evaluationefforts should be to focus on those activities and outcomesthat relate most directly to the key strategies of TB control:detecting patients with infectious TB and administering a completecourse of treatment, finding contacts and other persons at highrisk with LTBI and treating them, and interrupting transmissionof M. tuberculosis in high-risk settings (Box 4).
Targets for program performance have been established by CDC(227) to assist public health agencies in treating TB patients,protecting their contacts, and improving the quality of casereporting for national surveillance (Table 4). These nationalobjectives for program performance provide a starting pointfor state and local TB-control programs to use for program evaluation,but each TB-control program should establish methods to evaluateits performance.
TABLE 4. National performance measures and objectives for tuberculosis control
TB case management has typically been evaluated by reviewingindividual charts and case conferences. However, cohort analysis,a systematic evaluation of the treatment outcomes of all TBcases during a stipulated period of time, is the preferred meansof determining the number and percentage of cases that completea course of treatment in 12 months or less. Cohort analysesshould be a cornerstone of evaluation by all TB-control programs.A guide to cohort analysis and other evaluation tools has beenpublished (228). National objectives have been set for completingtreatment for LTBI among contacts of infectious cases of TB(Table 4). Other program areas that should be monitored throughformal evaluation methods include timeliness and completenessof reporting of TB cases and suspected cases, frequency of useof a recommended treatment regimen for patients with TB andLTBI, and quality of the program's databases for surveillanceand case management.
To respond to the need for improved and standardized programevaluation activities, CDC and six state TB-control programshave established an Evaluation Working Group whose goal is toimprove the capacity of TB-control programs to routinely conductself-evaluations and use the findings to improve and enhancetheir programs. The group is developing indicators for programperformance and an inventory of evaluation tools, includingdata collection instruments, data analysis methods, and evaluationtraining materials. During the next 2 years, a draft set ofthese materials will be tested in three TB-control programsfor utility, feasibility, and accuracy. Ultimately, this packageof evaluation materials and resources will be made availableto all TB-control programs.
Public Health Workforce.
No single model exists for staffing public health TB-controlprograms. Approaches to TB control should be flexible and adaptableto local needs and circumstances. Two components of the publichealth workforce, public health nurses and community outreachworkers, merit specific attention.
PUBLIC HEALTH NURSES.
Public health nurses are registered nurses with a Bachelor ofScience degree who are employed or whose services are contractedfor by health departments. Certain states require certificationfor additional competencies before being hired as a public healthnurse. Public health nurses traditionally have played a prominentrole in TB control in the United States. Their training, includingthat in nonmedical aspects of disease, has provided nurses withthe special skills needed to manage or coordinate the medicaland the sociobehavioral concerns associated with the preventionand treatment of TB (229). Their training includes (1) designingcontact and source-case investigations; (2) educating patients,contacts, and families; (3) identifying ineffective drug therapyregimens and drug toxicities; (4) recognizing patient behaviorsthat might lead to poor adherence; and (5) developing strategiesto encourage completion of therapy. As health departments adaptto changing health care environments, the role of public healthnurses working to control TB also is evolving to accommodatethe varied mechanisms by which services are delivered. Standardsof practice for TB nursing are being updated by the NationalTuberculosis Nurse Consultant Coalition, a section of NTCA,to guide jurisdictions in creating and maintaining a specializednursing resource for TB control and prevention.
COMMUNITY OUTREACH WORKERS.
Community outreach workers are staff members who provide services,such as DOT, to patients outside of the clinic. They may alsobe classified as disease investigation specialists or communityhealth educators. Because TB has become concentrated in specificpopulations (e.g., foreign-born and homeless persons) in theUnited States, outreach workers have assumed a key role in TBcontrol. Often members of the communities they serve, outreachworkers connect the health care system with populations at highrisk, ensuring that the principles and processes of TB controlare communicated to and understood by those populations. Outreachworkers' functions include facilitating treatment for patientsand contacts; providing DOT; educating patients, their families,workplace personnel, and communities; and participating in contactinvestigations. In each case, outreach workers form a bridgebetween patients and health care providers to achieve commonunderstandings and acceptance of plans for diagnoses and treatment.Clinicians with specialized expertise, including nurse–casemanagers, should supervise outreach workers.
Clinicians
Clinicians in medical practice in the non–public healthsector play a vital role in TB control throughout the UnitedStates. Hospital- or clinic-based medical practitioners, includingthose working in emergency departments (EDs), are usually thefirst source of medical care for persons with TB (230–232);they also may provide ongoing management for patients with TB(48). The role of medical practitioners in TB control will increaseas TB morbidity in the United States decreases and jurisdictionsreduce or even eliminate public health clinical services forTB.
Medical practitioners are often not sufficiently knowledgeableabout TB (233), and clinicians in private practice frequentlydo not follow recommended guidelines and make errors in prescribinganti-TB therapy (231, 234, 235). The failure of public healthand private practitioners to interact effectively is a weaklink in global TB control (236). Successful models exist foracknowledging and facilitating the work of private medical practitionersin the complex process of diagnosing and treating persons withTB. For example, for each reported TB case in New Mexico, acollaborative case-management strategy is used that includestreating clinicians and pharmacists from the private sectorin addition to public health case managers (48). Another modelof effective private–public partnerships was employedin NYC during the 1985–1992 TB resurgence, with healthdepartment case management and DOT for patients under privatecare (13).
As TB elimination efforts continue, the role of medical practitionerswill further expand because they provide access to populationsthat have been targeted for testing and treatment of LTBI. Greaterparticipation by the non–public health sector in preventiveintervention has been advocated (2, 51), and clinical standardshave been published to guide medical practitioners in managingpatients with TB disease and LTBI (8).
Roles and Responsibilities of Clinicians.
Private medical practitioners should
— understand prevalentmedical conditions, including thosewith public health implications,of populations within theirpractice;
— understand applicablestate laws and regulations forreporting diseases and the needto report cases;
— understand the range of responsibilities,statutoryand otherwise, that arise when TB is suspected ina patientunder medical evaluation, including (1) the need forpromptestablishment of diagnosis; (2) use of consultants andhospitalizationif indicated; (3) reporting the suspected caseto the jurisdictionalpublic health agency and cooperating withsubsequent publichealth activities; and (4) developing, inpartnership with thepublic health agency, a treatment planthat optimizes the likelihoodthat the patient will completethe recommended course of therapy;
— incorporate currentrecommendations for diagnosis (3),standard treatment of TB(5), and targeted testing and treatmentof LTBI (4); and
—be able to place and read tuberculin skin tests, ruleout suspectedTB disease (by clinical examination, history,and chest radiograph),and treat and monitor treatment for LTBI.
Providers of medicalcare for children and adolescents shouldalso
— usea questionnaire to screen all new patients for riskfactorsfor LTBI and give those with risk factors a tuberculinskintest to be interpreted by a trained health care provider(237),and
— place and interpret tuberculin skin tests of familymembers of children with LTBI when this service is not otherwiseaccessible.
Clinicians who administer treatment that can suppressthe immunesystem should administer a questionnaire about riskfactorsfor TB. If risk factors are present, a tuberculin skintestshould be administered and the result obtained before orcommensuratewith starting immunosuppressive therapy.
Civil Surgeons
Civil surgeons are licensed physicians who are certified bythe U.S. Citizenship and Immigration Service to conduct a requiredhealth screening examination, including testing for LTBI andactive TB disease, on foreign-born persons living in the UnitedStates who apply for permanent residency. In 2002, approximately679,000 foreign-born persons applied for permanent residencyand were screened by civil surgeons, compared with 245,000 suchpersons in 1995 (238). CDC has responsibility for providingguidance on screening and treatment but has no regulatory rolein monitoring the quality or outcomes of these examinations.
Because of their access to foreign-born persons at high risk,civil surgeons are a critical component of TB control. U.S.-basedimmigration screening can identify foreign-born persons withLTBI for whom treatment is indicated (239). Although civil surgeonsreceive immigration-focused training, little information isavailable on the knowledge, attitudes, and practices of civilsurgeons. A recent survey indicated that among 491 physiciansserving as civil surgeons in California, Massachusetts, andNew York, the majority were graduates of U.S. medical schools,75% were primary care practitioners, and 47% were board-certifiedin their specialty. Among 5,739 foreign-born applicants examinedby these civil surgeons, 1,449 (25%) received nonstandard screening(240). As a result of these findings, efforts are under wayto develop guidance documents and training materials for physicianswho screen immigrants for TB infection and disease.
Roles and Responsibilities of Civil Surgeons.
Civil surgeons should
— understand current guidelinesfor the diagnosis (3)and treatment of TB (5) and LTBI (4),
— establish a working relationship with the jurisdictionalhealth agency and report suspected and confirmed cases of TB,and
— develop a referral mechanism for evaluation forTB diseaseand LTBI of persons seeking adjustment of immigrationstatus.
Community Health Centers
Community health centers typically provide primary health careservices to populations that encounter barriers to receivingthose services at other sites in the health care system, suchas low-income working persons and their families, immigrantsand refugees, uninsured persons, homeless persons, the frailelderly, and poor women and children. Patients at high riskfor TB often receive primary and emergency health care in communityhealth centers (51). For example, community health centers incertain inner-city areas might serve primarily a clientele ofhomeless persons, whereas centers in neighborhoods in whichcertain racial and ethnic populations are concentrated mightbecome predominant health care providers for immigrants andrefugees. Newly arriving refugee families are frequently directedto community health centers to receive federally supported healthscreening services, which might include targeted testing andtreatment for LTBI. Persons with symptoms of TB might go firstfor evaluation and care to a community health center. For thesereasons, community health centers are a critical part of effortsto control and prevent TB.
Roles and Responsibilities of Community Health Centers.
Community health centers should
— provide their medicalstaff with the skills and knowledgeneeded to conduct a TB riskassessment of their clients, diagnoseand initiate treatmentfor TB disease, and diagnose and treatLTBI (241);
—develop close working relationships with consultantphysicians,hospitals, and clinical laboratories and with thepublic healthagency that serves their jurisdiction;
— arrange forreporting patients with suspected TB, ensuringavailabilityof diagnostic services (e.g., sputum smears forAFB, culturesfor M. tuberculosis, and chest radiographs), andproviding consultationand referral of patients for diagnosis,treatment, and hospitalization,as indicated);
— understand federal and state programsthat support screening,diagnostic, and treatment services forpatients at high riskand make prevention, diagnosis, and treatmentof TB a high priority;
— work with public health agenciesto educate patientsabout the personal and public health implicationsof TB andLTBI and motivate them to accept prevention services;and
— establish recommended infection-control practices(10)to protect patients and staff.
Hospitals
Hospitals provide multiple services that are instrumental tothe diagnosis, treatment, and control of TB. Hospitals withactive outpatient and EDs often serve as sites of acute andprimary medical care for homeless persons, inner-city residents,immigrants and refugees, and other persons at high risk forTB. Also, hospital staff members often provide medical consultationservices for the diagnosis and management of TB by public healthand community clinicians. Laboratory services provided by hospitalsfor community-based medical care providers might include keydiagnostic tests for TB.
TB cases often are detected during hospitalization at acute-carehospitals (230, 242). In a prospective cohort study at 10 sitesin the United States, 678 (45%) of 1,493 patients reported withTB received their diagnosis during hospitalization (230). Hospital-basedhealth professionals evaluate patients for TB, establish thediagnosis, and initiate treatment regimens and reporting ofcases to public health departments. Instances of delayed recognition,diagnosis, and treatment for TB among hospitalized patientssubsequently found to have TB have been reported (24, 178),indicating a need for more effective training and educationof hospital medical staff members.
Because 25 to 45% of patients with TB receive their diagnosticevaluation while in a hospital (230, 242), hospitals have anopportunity to provide patient-based teaching on TB for theirown staff members and for health professionals from the communityserved by the hospital. Venues such as staff conferences andmedical grand rounds, conducted regularly by hospitals, canbe sources of training and education on clinical, laboratory,and public health concerns that arise during evaluation andinitial medical management of hospitalized patients with TB.
Hospitals should protect their patients, staff, and visitorsfrom exposure to M. tuberculosis. The importance of effectiveTB infection control was emphasized during the 1985–1992TB resurgence in the United States, when hospitals were identifiedas sites of transmission of multidrug-resistant TB (243). Implementationof effective infection-control guidelines has been effectivein reducing transmission of TB in hospitals (56, 244, 245).
Roles and Responsibilities of Hospitals.
Hospitals that deliver inpatient care for TB should developpolicies that ensure that patients suspected to have contagiousforms of the disease are isolated and that effective infection-controlmeasures are implemented. Such hospitals should provide recommendedTB-related diagnostic testing and should ensure that patientsreceive a standard treatment regimen (245).
Hospitals shouldpromptly report any patient with a suspectedor confirmed diagnosisof TB to the jurisdictional public healthagency. A writtenpolicy for discharging patients with TB, developedin collaborationwith the public health agency, should be prepared.Certain stateshave regulations stipulating that the jurisdictionalpublichealth agency should approve discharge from hospitalof patientswith TB. Patients with TB should be discharged ona standardanti-TB regimen, and advance arrangements shouldbe made toensure follow-up after discharge. Close coordinationbetweenthe hospital and the jurisdictional public health agencycanenhance patient follow-up after discharge (5, 56).
Hospitalsshould develop a written policy and plan for preventionof thenosocomial transmission of TB. Recommendations have beenpublishedto guide the development of an infection-control plan(10) andare reviewed in this statement. New guidelines forpreventionof transmission of M. tuberculosis in health caresettings willbe published by CDC in 2005.
Hospitals should take responsibilityfor the training and ongoingmedical education of their medicaland house staff in the prevailingdiseases of the populationsto which they provide care. Whenappropriate, education shouldinclude the local epidemiologicprofile of TB, the best currentdiagnostic tests and recommendedtreatment regimens, appropriateinfection-control measures,and case management responsibilities(i.e., reporting, protectionof contacts, importance of treatmentuntil cure, and the conceptof public health case management).
Academic Institutions
Academic institutions (including schools of medicine, publichealth, and nursing) have an opportunity to contribute to TBcontrol in the United States and worldwide. Students from diversedisciplines, including the clinical and laboratory sciences,nursing, epidemiology, and health services, should be introducedto applicable concepts of public health in general and, becauseTB is a major cause of preventable illness and death in developingcountries (44), to TB in particular. During the resurgence ofTB in the United States during 1985–1992, expertise inTB was limited. Federal funding for programs (e.g., the NIHNational Heart, Lung, and Blood Institute's Tuberculosis AcademicAward program) helped provide funding to incorporate teachingof TB more fully into medical school curricula. Researchersat academic institutions are critical to efforts to improvethe prevention, management, and control of TB because of theirefforts to develop new tools, including new diagnostic tests,new drugs, better means of identifying and treating LTBI, andbasic research to create a vaccine for TB (180, 246, 247).
As with hospitals, academic institutions can provide benefitsto other participants in TB control. Conferences, grand rounds,and other presentations are a source of continuing educationfor private medical practitioners and other community-basedHCWs. As well-trained specialists, researchers at academic institutionscan provide clinical, radiographic, and epidemiologic consultationto medical practitioners and public health agencies. A majorityof academic institutions manage university-based hospitals,which often serve populations at high risk. University hospitalscan become models for TB risk assessment of patients, inpatientcare, and infection-control practice, and they can serve astertiary care sites for an entire community or region.
Partnerships between academic institutions and public healthagencies are mutually beneficial (248). In certain cases, healthdepartments and public health TB clinics are staffed or managedby faculty physicians from academic institutions. This partnershipfacilitates use of these clinics for graduate medical trainingfor physicians in subspecialty areas (e.g., pulmonary and infectiousdiseases), enhances training for clinic staff, and providesopportunities for clinical and operational research.
Roles and Responsibilities of Academic Institutions.
Academic institutions (including schools of medicine, publichealth, and nursing) should incorporate TB education into theircurricula. Training and teaching programs should include theroutine applications of TB risk assessment. Students and traineesin all medical disciplines should understand and appreciatethe importance and roles of the primary and specialty medicalcare providers and public health, including the necessary collaborationbetween academic institutions and local, state, and federalpublic health agencies.
Academic institutions should serveas repositories of expertisein the treatment and managementof TB and as a resource forpublic health and community-basedclinicians and other HCWs.
Academic institutions should partnerwith public health agenciesto improve TB control. Partnershipsare mutually beneficial.For academic institutions, partnershipsprovide additional sitesfor education and training, opportunitiesfor clinical research,and, for patients with TB, a systematictransition from hospitalto outpatient care, including DOT.Public health agencies gainexposure to students and trainees,a ready source of referralfor consultation and management ofcomplex medical problems,and research opportunities.
Academicinstitutions should provide leadership in conductingresearchin diagnostics, drugs, and vaccines for TB.
Medical Professional Organizations
Because they are involved with medical practice, research, education,advocacy, and public health, medical professional organizationsare critical partners in TB-control efforts. Greater participationof the non–public health medical sector is needed to maintainclinical expertise in the diagnosis and management of TB inan era of declining incidence. Organizations whose membershipsinclude primary care medical practitioners can make significantcontributions to the control, prevention, and elimination ofTB by including TB in their training and education agendas.
ATS and IDSA both support TB-control efforts in the United States.With a membership of approximately 14,000 health professionals,including clinicians trained in pulmonary diseases, ATS conductsresearch, education, patient care, and advocacy to prevent respiratorydiseases worldwide. IDSA promotes and recognizes excellencein patient care, education, research, public health, and theprevention of infectious diseases. In recent years, IDSA hasjoined ATS in focusing education and advocacy activities onTB through its annual meetings, publications, and sponsorshipof this series of statements.
Other medical professional organizations also can support TB-controlefforts. Medical professional organizations can (1) provideTB education to their members through meetings, symposia, statements,and web sites; (2) serve as venues for better communicationbetween the private medical and public health sectors; (3) promotethe TB research agenda locally and nationally; and (4) advocatefor resources for strong TB control globally and in the UnitedStates.
Roles and Responsibilities of Medical Professional Organizations.
Medical professional organizations should train and educatetheir members and other health professionals (e.g., privatemedical practitioners, nurses, epidemiologists, laboratory specialists,or program administrators) regarding the clinical and publichealth aspects of the risk assessment, diagnosis, treatment,control, and prevention of TB. Training and education can beprovided in traditional venues, such as scientific meetingsand symposiums, and electronically through web sites. As continuingmedical and nursing education is now a prerequisite to licensure,medical professional organizations are a convenient educationresource for the private medical community.
Medical professionalorganizations should provide professionalleadership on clinicalpractice and control of TB by participatingin the developmentor endorsement of guidelines, influencingprofessional schoolcurricula, and establishing and supportingfellowship trainingprograms as applicable.
Medical professional organizationsshould provide advocacy foradequate funding for TB controland research through publiceducation campaigns.
Medical professionalorganizations should advocate the importanceof greater U.S.involvement in global control of TB by linkingU.S. health professionalswith those from other parts of theworld at meetings and symposia,including information on globalTB in statements and educationmaterials, providing their memberswith opportunities to serveas technical consultants, and participatingin special projectsto support or improve TB control in otherregions of the world.
Community-based Organizations
Involvement of community groups in TB control has long beenencouraged (17). The critical importance of such involvementis underscored by the trend in the United States for TB to belimited to certain populations at high risk (e.g., contactsof persons with active cases, persons born outside the UnitedStates, homeless persons, incarcerated persons, and personswith HIV infection). Programs for education and targeted testingand treatment of LTBI should be organized for these populations.
The public health sector frequently experiences difficulty ingaining access to persons in populations of high risk (51).Such persons might be socially marginalized, as in the caseof new refugees, or they might be suspicious of persons representinggovernment agencies, as in the case of undocumented aliens.Furthermore, the target population's own view of its health-carepriorities, often best articulated by community-based organizationsthat represent them, should be considered in the design of publichealth interventions (249). Social, political, religious, andhealth-related organizations that have arisen from grassrootsefforts to meet community needs often can facilitate accessto public health programs (221).
Community-based organizations can be particularly effectivein providing information and education on TB to their constituencies.As part of the communities they serve, such organizations areoften highly regarded in their communities, and their messagesmight be accepted more positively than those delivered by thejurisdictional health department.
Roles and Responsibilities of Community-based Organizations.
Community-based organizations should be aware of their constituents'health risks. Organizations providing services to populationsat risk for TB should partner with the jurisdictional publichealth TB program and medical care providers from the communityto facilitate access to diagnostic, treatment, and preventionservices for the target population. As resources allow, organizationsshould provide assistance for treatment services to their constituency(e.g., DOT, incentives and enablers, and other outreach services).
When serving a population at risk for TB, community-basedorganizationsshould become involved in advocacy initiatives,such as stateand local TB advisory committees and coalitions.
Community organizations serving populations at high risk shouldwork with public health agencies and educational institutionsto develop education materials that are tailored culturallyand linguistically to their populations.
Correctional Facilities
Correctional facilities are common sites of TB transmissionand propagation (250, 251). Incidence of TB and of LTBI is substantiallyhigher in prisons and jails than in the general population (252,253). TB is believed to be the leading cause of death for prisonersworldwide (254).
Targeted testing for and treatment of LTBI in correctional facilitieshave been demonstrated to have a substantial public health impact(124). Testing and treatment for LTBI is performed more easilyin prisons (255) because the length of stay is generally sufficientto permit completion of a course of treatment. Jails have provedconvenient sites for targeted testing, but subsequent treatmentof LTBI has proved challenging (256). Innovative methods forassuring completion of treatment for LTBI in jail detaineeshave been proposed (257).
Because of their communal living arrangements, correctionalfacilities, like health care facilities, have the responsibilityto limit the transmission of TB within the institution and toprotect their inhabitants and staff from exposure. This is aparticular challenge in jails because of the short lengths ofstay for the majority of detainees. Even in prison systems,abrupt and unexpected transfers of detainees among institutionsmight occur, with little consideration for health issues. Prisonsand jails frequently house HIV-infected persons in separatefacilities to ensure adequate health care. However, recent publicationsdescribing outbreaks of TB in such settings have emphasizedthe hazard of this strategy (35, 126).
Roles and Responsibilities of Correctional Facilities.
Correctional facilities should work with the jurisdictionalpublic health agency to develop and maintain an accurate epidemiologicprofile of the risk for TB in the inmate population.
On thebasis of the local epidemiology of TB, correctional facilitiesshould develop written policies to establish effective programsto screen for active TB, respond promptly when cases occur withinthe facility, provide targeted testing and treatment programsfor inhabitants and detainees with LTBI, and provide ongoing,competency-based education of all staff members.
Correctionalfacilities should establish ongoing working relationswith publichealth agencies, hospitals, and other communitypartners forpolicy development, consultation and referral.
Correctionalfacilities should develop firm linkages for referralof personsunder treatment for TB disease and LTBI.
Correctional facilities,following requirements of the OccupationalSafety and HealthAdministration and other regulatory agencies,should developinfection-control programs to protect inhabitants,detainees,staff, and visitors from exposure to TB (258). Correctionalfacilities should continually evaluate the effectiveness ofthe institutional TB-control program to eliminate transmissionwithin the facility.
Pharmaceutical and Biotechnology Industries
Because of their essential role in developing new diagnostics,drugs, and vaccines, the pharmaceutical and biotechnology industriesare partners in TB control. Although development of new toolsfor diagnosis, treatment, and prevention of TB has been deemedessential to the effort to combat the disease globally and tocontinue to make progress toward its elimination in the UnitedStates and other developed countries (1, 2, 45, 259), progressin these fields has been slow. Slow progress in this field hasbeen attributed to private industry's perception that such productsare not needed in developed countries and do not offer profitopportunities in resource-poor countries (246, 260). However,new public–private partnerships are emerging to facilitatethe development of essential new tools (261), including threepartnerships established with support from the Bill and MelindaGates Foundation: the Global Alliance for Tuberculosis DrugDevelopment (http://www.tballiance.org), the Aeras Global TuberculosisVaccine Foundation (http://www.aeras.org), and the Foundationfor Innovative New Diagnostics (http://www.finddiagnostics.org).These organizations have provided venues to identify and addressobstacles 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 globalTB control effort by assisting in making drugs for TB, includingsecond-line drugs for patients with multidrug-resistant TB,more affordable (262, 263). Such actions can enable pharmaceuticalcompanies to become leaders in efforts to improve TB controland prevention.
Roles and Responsibilities of the Pharmaceutical and Biotechnology Industries.
The pharmaceutical and biotechnology industries should
—understand the dimensions of the global TB epidemicand realizetheir key role in developing the necessary toolsfor diagnosis,treatment, and prevention of TB;
— respond to the currentsurge of interest in TB globallyby reexamining the costs ofnew product development and by consideringpotential new publicand private funding and the markets forsuch products in developingcountries;
— contribute their perspectives and becomeinvolved incoalitions such as NCET, the Global Partnershipto Stop Tuberculosis,the Global Alliance for Tuberculosis DrugDevelopment, and theFoundation for Innovative New Diagnostics;and
— work with other stakeholders to ensure accessof essentialproducts 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 activitiesthat begin when a diagnosis of TB is first suspected and endwith the completion of a course of treatment for the illness.TB case management describes the activities undertaken by thejurisdictional public health agency and its partners to ensuresuccessful completion of TB treatment and cure of the patient.The rationale and methodology of TB case management have beendescribed previously (5). Organizational aspects of case managementfrom the viewpoint of the jurisdictional public health agencyare also discussed in this statement.
Case detection includes the processes that lead to the presentation,evaluation, receipt of diagnosis, and reporting of persons withactive TB. Case detection involves patients with active TB whoseek medical care for symptoms associated with TB, their accessto health care, their health care providers, the consultantsand clinical laboratories used by those health care providers,and the responsible public health agency. Although steadilyincreasing treatment completion rates (14) indicate that progresshas been made in the management of patients with TB, TB casedetection is still problematic. Delays in diagnosis and reportof TB cases continue to be common. Also, despite the 44% reductionin TB incidence in the United States since 1992, the proportionof pulmonary cases that are sputum smear–positive at diagnosishas changed little, accounting for more than 60% of all reportedcases (14). The majority of pulmonary TB cases continue to bediagnosed at an advanced stage. Earlier diagnosis would resultin less individual morbidity and death, greater success in treatment,less transmission to contacts, and fewer outbreaks of TB. Improvementin the detection of TB cases is essential to progress towardelimination of TB in the United States (Box 1).
The first step in improving TB case detection is to remove barriersin access to medical services that are often encountered bypersons 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 authoritiesif medical care is accessed (19). Foreign-born persons, particularlyrecently arrived immigrants, refugees, and other persons oflow SES might not have access to primary health services becausethey do not have health insurance or they are not familiar withthe U.S. medical care system (20, 118, 266).
Removing patient-related barriers to health care is particularlydifficult. Improved patient education about TB is needed (18).Continuing immigration from countries at high risk, often includingpersons with strong cultural views about TB, underscores theneed for patient education. As with other interventions to enhanceTB control and prevention, local public health action shouldbe based on the local pattern of disease. In developing educationmessages and outreach strategies, public health authoritiesshould work with organizations that serve communities at highrisk to gain community input (203). This statement providesrecommendations on working with community-based organizations,key informants, and academic institutions to gain ethnographicinformation, learn about the health beliefs and values of populationsat high risk within the community, and develop targeted interventionsthat will be most effective.
The majority of TB cases are detected during the medical evaluationof symptomatic illnesses (19, 267). Persons experiencing symptomsultimately attributable to TB usually seek care not at a publichealth TB clinic but rather from other medical practitionersand health care settings. In 18 California counties with thehighest TB morbidity of persons during 1996–1997, initialpoints of entry into the health care system for persons whoreceived a diagnosis of TB were hospital inpatient evaluations(45%), private outpatient offices or clinic evaluations (32%),TB clinic evaluations (12%), and other sites (11%), includinga non-TB clinic in a health department and correctional facilities(California Tuberculosis Controllers Association, unpublisheddata, 2003). A similar pattern was observed in Washington State.In Seattle and its suburban areas in 1997, primary care practitionersor clinics reported 48% of TB cases during evaluations of outpatientswith symptoms and 32% during hospital evaluations; only 2% ofcases were diagnosed during a public health TB clinic evaluationfor a symptomatic illness (Seattle–King County Departmentof Public Health, unpublished data, 1998).
These data indicate that the professionals in the primary healthcare sector, including hospital and ED clinicians, should betrained to recognize patients with symptoms consistent withTB. Dramatic reductions in TB were recorded in New York City(13) and Baltimore (195) in association with extensive educationcampaigns for health care providers in the community. Thesestudies indicate the need to maintain clinical expertise forthe diagnosis and treatment of TB (24, 41).
Because pulmonary disease among adults is most frequently associatedwith the spread of TB, the following discussion and recommendationsregarding TB case detection are limited to considerations ofpulmonary TB among adults. A classic set of historic features,signs, symptoms, and radiographic findings occurring among adultsshould raise a suspicion of pulmonary TB and prompt a diagnosticinvestigation (3, 189, 267–271). Historic features includeexposure to TB, a positive test result for M. tuberculosis infection,and the presence of risk factors such as immigration from ahigh-prevalence area, HIV infection, homelessness, or previousincarceration. Signs and symptoms typical of TB include prolongedcoughing with production of sputum that might be bloody, fever,night sweats, and weight loss. On a chest radiograph, the classicalfindings 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 estimated10 to 100 persons are suspected on the basis of clinical criteriaand must be evaluated (272, 273).
The clinical presentation of TB varies considerably as a resultof the extent of disease and the host response. In addition,variation in clinical symptoms and signs of TB is associatedwith underlying illnesses (e.g., HIV infection, chronic renalfailure, alcoholism, drug abuse, and diabetes mellitus). Thesigns of TB are also associated with race and ethnicity andare attributed to unknown factors (3, 267, 270). The chest radiographamong persons with advanced HIV infection and pulmonary TB,for example, might have lower lobe and lobar infiltrates, hilaradenopathy, or interstitial infiltrates (274). TB should besuspected in any patient who has persistent cough for more than2 to 3 weeks or other compatible signs and symptoms as notedpreviously (10, 267, 275).
In the drive toward TB elimination in the United States, effectiveTB case detection is essential, and medical practitioners shouldrecognize patients in their practice who are at increased riskfor TB and be aware of the possibility of diagnosing TB if theyobserve compatible symptoms. Guidelines have been provided forthe initial steps of TB case detection in five clinical scenariosencountered by providers of primary health care, including thoseserving in medical EDs (Table 5). In these settings, evidenceexists to support proceeding with a diagnostic evaluation forpulmonary TB. The subsequent management of suspected cases inthese scenarios depends on the judgment of the medical practitioner,in consultation with specialists in internal medicine, pulmonarydiseases, or infectious diseases if necessary (5). These recommendationsdo not cover the spectrum of clinical presentations of pulmonaryTB in adults and are not meant to substitute for sound clinicaljudgment.
TABLE 5. Guidelines for the evaluation of pulmonary tuberculosis in adults in five clinical scenarios
Cases of pulmonary TB also are detected through directed publichealth activities designed to detect TB disease among certainpersons who have not sought medical care. Compared with personswhose cases were detected passively by medical practitionersamong patients who have sought medical care, persons whose casesare detected actively are usually in a less advanced stage ofpulmonary disease, as manifested by the absence of symptomsand by negative sputum AFB smear results. Although no supportingliterature exists, cases detected in that stage of disease mightbe less advanced and easier to cure.
Active efforts to detect cases of TB among persons who havenot sought medical care are routinely made during evaluationof contacts of patients with pulmonary TB (30, 31, 276) andof other persons with newly diagnosed infection with M. tuberculosis(4). Screening for TB also is performed during evaluation ofimmigrants and refugees with class B1 or class B2 TB notificationstatus (277–279), during evaluations of persons involvedin TB outbreaks (34, 35, 136, 172, 280, 281), and occasionallyin working with populations with a known high incidence of TB(167, 185). Screening for TB disease is indicated when the riskfor TB in the population is high and when the consequences ofan undiagnosed case of TB are severe (282), such as in jailsand prisons (253, 283).
Screening for TB disease (i.e., active case finding) might contributesubstantially to overall TB case detection. A population-basedstudy from Los Angeles indicated that 30% of reported TB casesduring the period of study were detected through screening activities(267). During 1998–2001, of 356 TB cases reported by theSeattle–King County TB Program, 40 (11%) were detectedthrough active case detection in contact investigation and evaluationsof immigrants and refugees with class B1 and B2 TB notificationstatus.
The clinical settings in which TB has been effectively detectedamong 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 withclass B1 and B2 TB notification status should be given highestpriority by all TB-control programs. The yield of detectingTB cases during screening at homeless shelters increased sharplyin an outbreak setting (Table 6). Although prevalence data fromindividual studies are not available, investigations undertakento control TB outbreaks that involved diverse settings and groupsof immunocompetent and immunocompromised persons have consistentlybeen productive in detecting TB cases and high rates of LTBIamong exposed persons (34, 35, 136, 173, 280, 281). Outbreakinvestigations should be counted among the settings in whichscreening for active TB is recommended.
TABLE 6. Settings, methodologies, and outcomes for detecting tuberculosis in persons without symptoms
Contact Investigation and Outbreak Control
Contact investigation is an essential function of TB controlin the United States (Box 4) (1, 17). The investigation of acase of TB results in identifying approximately 10 contacts(284). Among close contacts, approximately 30% have LTBI, and1 to 3% have progressed to TB disease (30, 284). Without intervention,approximately 5% of contacts with newly acquired LTBI progressto TB disease within 2 years of the exposure (285). The prevalenceof TB among close contacts is approximately 1,000/100,000 population(> 100-fold higher than in the general population) (285). Examinationof contacts is therefore one of the most important activitiesfor identifying persons with disease and those with LTBI whohave a high risk for acquiring TB disease.
Transmission of M. tuberculosis has occurred in health carefacilities (286, 287), bars (134, 288), doctors' offices (289),airplanes (290), crack houses (291), respite facilities thatprovide care for HIV-infected persons (136), drug rehabilitationmethadone centers (36), navy ships (292), homeless shelters(120), schools (173), church choirs (140), and renal transplantunits (141). The utility and importance of contact investigationsin those settings and also for populations at high risk (e.g.,foreign-born persons [293], children [294–297], and personsexposed to multidrug-resistant TB cases [91, 298]) has alsobeen documented.
In the United States, state and local public health agenciesperform 90% of contact investigations as part of the publichealth mandate for TB control (Box 5) (2). Public health TB-controlprograms are responsible for ensuring that contact investigationsare conducted effectively and that all exposed contacts areidentified, provided with access to adequate care, and followedto completion of therapy. For health agencies to fully dischargethis responsibility, adequate funding and political commitmentare required.
Health agencies use a general epidemiologic framework for contactinvestigations (299). However, this approach alone might havelimited effectiveness because of factors such as initial diagnosticdelays and failure to ensure completion of therapy for LTBI.Consequently, programs have recognized the necessity of wideningtraditional contact investigation sites to include nonhouseholdlocations (e.g., homeless shelters, correctional facilities,nursing homes, and hospices that serve HIV-infected persons)and households. Genotyping studies have documented that traditionalcontact investigation methods have failed to identify contactsor detect transmission of M. tuberculosis (28, 33, 34, 151,172). As a result, IOM (2) and ACET (1) have called for thedevelopment and implementation of enhanced techniques for contactinvestigation.
The primary goal of a contact investigation is to identify personswho were exposed to infectious M. tuberculosis and ensure thatthey are tested for M. tuberculosis infection, screened forTB disease, are followed up, and complete a standard courseof treatment, if indicated. Secondary goals are to stop transmissionof M. tuberculosis by identifying undetected patients with infectiousTB and to determine whether a TB outbreak has occurred. In thatcase, an expanded outbreak investigation should ensue.
Steps of a Contact Investigation.
State and local public health agencies, often represented byTB-control programs, are responsible for initiating and conductingcontact investigations and evaluating their outcomes to ensuretheir effectiveness. A contact investigation has 14 steps, asfollows:
Setting priorities. A contact investigation is consideredoncea suspected or confirmed case of TB comes to the attentionofthe jurisdictional TB-control program. At that time, a decisionshould be made about the priority of that investigation amongother TB-control activities. Not all cases of TB require a contactinvestigation, and certain investigations will have greaterpriority than others. Priorities should be decided on the basisof the characteristics of the source-case, of the environmentof the place(s) of exposure, and of the contacts. The threemost important categories of information used to establish prioritiesfor 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 withpulmonary TB, positive sputum AFB smear results, and cavitationnoted on a chest radiograph are more infectious and thereforehave a higher priority for contact investigation. The use ofan NAA test is helpful in rapidly differentiating between pulmonarydisease caused by M. tuberculosis and nontuberculous mycobacteria,thus avoiding unnecessary contact investigations. Persons withpulmonary TB who have negative sputum AFB smear results tendto be less infectious, and their contacts should be investigated,but with lower priority. Contacts of patients with extrapulmonaryTB should be evaluated if the patient has concurrent pulmonaryor laryngeal disease, the contacts are at increased risk foracquiring TB disease (e.g., children aged < 5 years and HIV-infectedpersons), or the patient has pleural TB (300). Pleural TB isa manifestation of primary TB and often occurs among personswho have been recently infected. In addition, persons with pleuralTB can have positive sputum AFB smear results. Children youngerthan 5 years with TB, regardless of the site of disease, shouldhave a contact investigation to identify the source-case.
Definingthe beginning and end of the period of infectiousness.Beforea contact investigation can be started, the period ofinfectiousnessof the index case should be determined. Thisperiod sets thelimits for the investigation, allows for settingprioritiesfor contacts within the designated timeframe, anddeterminesthe scheduling for follow-up tests. Exactly whena patient becomesinfectious is unknown; the usual assumptionis that the patientbecomes infectious approximately 3 monthsbefore diagnosis;however, it might be longer, depending onthe history of signsand symptoms, particularly cough and theextent of disease.The end of the period is defined as the timewhen contact withthe index case is broken or when all of thecriteria for determiningwhen during therapy a patient withpulmonary TB has become noninfectious(Box 3) are met. Patientswith multidrug-resistant TB who areon inadequate therapy orwho have persistently positive sputumAFB smear or culture resultsmight remain infectious for a prolongedperiod of time. Thosepatients, if not in effective isolation,should be reassessedfor new contacts as long as they remaininfectious.
Medical record review. For potential transmissionrisk and infectiousnessof a case to be assessed, all currentlyavailable informationabout the reported case or suspect isobtained through casemedical record reviews, conversationswith the health care provideror other reporting source, andlaboratory report reviews. Thisinformation can be disclosedby covered entities for publichealth activities as providedby the Privacy Rule of HIPAA (217).
Case interview and reinterview.The patient interview may beconducted in the hospital, at thepatient's home, or whereverconvenient and conducive to establishingtrust and rapport.The ability to conduct an effective interviewmight determinethe success or failure of the contact investigation.All personswith whom the patient has been in close contactand the locationsthat the patient commonly frequents shouldbe identified. Goodinterviewing skills can elicit vital informationthat otherwisemight not be forthcoming. For different reasons(e.g., stigmatization,embarrassment, or involvement in illegalactivities), patientsmight be reluctant to identify contactsor places they frequent.Developing an ability to interviewpatients effectively so asto elicit contacts requires trainingand periodic review bysupervisors, and only trained personnelshould interview patients.A patient should be interviewed assoon as possible after notificationand reinterviewed 1 to 2weeks later to clarify data or obtainmissing data. When possible,the second interview should beconducted at the patient's primaryresidence. Also, all interviewsshould be conducted in the patient'sprimary language and withsensitivity to the patient's culture.
Field investigation. Field investigations enable investigatorsto (1) interview or reinterview identified contacts and obtainan adequate medical history to evaluate previous exposure toTB, existence of prior M. tuberculosis infection, existenceof disease and treatment, risk factors for acquiring TB, andsymptoms; (2) obtain locator information; (3) apply a tuberculinskin test to identified contacts (the role of QFT-G in the assessmentof contacts has not been determined); (4) observe contacts forany signs or symptoms suggestive of TB; (5) schedule subsequentmedical evaluations and collect sputum samples from any contactwho is symptomatic; (6) identify sources of health care andmake referrals; (7) identify additional contacts who might alsoneed follow-up; (8) educate contacts about the purpose of theinvestigation and the basics of TB pathogenesis and transmission;(9) observe the contact's environment for possible transmissionfactors (e.g., crowding and poor ventilation); (10) assess contacts'psychosocial needs and other factors that might influence compliancewith medical recommendations; and (11) reinforce confidentiality.Visits to the exposure site(s) should be conducted as soon aspossible. Contacts at higher risk for disease progression andmore severe disease (e.g., young children and HIV-infected persons)require the most rapid follow-up. Transmission sites might involvesocial networks not customarily considered in traditional contactinvestigations. For example, in certain TB cases reported separatelyin different communities, participation in a church choir wasidentified as a common factor (140). The contact investigationfailed to identify the source-patient's choir contacts, resultingin secondary cases of TB. In an outbreak associated with a floatingcard game, the outbreak was propagated because a network ofpersons engaged in illegal activities was not identified (172).These examples demonstrate the importance of congregate activitiesbeyond work and socially defined high-risk contacts.
Clinicalevaluation of contacts. All close contacts of patientswithpulmonary or laryngeal TB and a positive culture resultforM. tuberculosis or a positive sputum AFB smear result shouldreceive a tuberculin skin test unless they have documentationof a previously positive test. Highest priority for tuberculinskin testing and follow-up evaluation should be given to (1)contacts identified as being at highest risk for recent infectionon the basis of their history of exposure to the case-patientand risk for transmission and (2) those at high risk for progressionfrom M. tuberculosis infection to TB disease (e.g., infants,young children, HIV-infected persons, and other persons whosemedical conditions predispose them to progress from infectionto disease). Among children and infants, children younger than3 years are at greatest risk for rapid progression and shouldreceive the highest priority for all preventive interventionsfor contacts. For the greatest level of protection of childrenexposed to TB to be ensured, all children younger than 5 yearsshould be considered to be high-risk contacts. Regardless ofwhere the tuberculin skin test is performed (e.g., field visit,TB clinic, or referral site), arrangements should be made toensure that the skin test is read within 48 to 72 hours. Contactswho have tuberculin skin test reactions 5 mm or larger and whohave no history of a prior positive result are considered atrisk for newly acquired M. tuberculosis infection. Those personsshould receive a chest radiograph and medical evaluation forTB disease. Adults and children aged 5 years and older shouldreceive a single posterior-anterior radiograph (4); childrenyounger than 5 years should receive both posterior-anteriorand lateral TB radiographs (4). The following contacts shouldhave a chest radiograph regardless of skin test result: (1)persons with symptoms of TB, (2) persons who are immunosuppressedor who have other risk factors for progression from M. tuberculosisinfection to TB disease, and (3) children younger than 5 years.The presence of HIV coinfection might affect decisions aboutsubsequent management of contacts (e.g., prescribing prophylactictreatment and completing treatment for LTBI regardless of resultsof a tuberculin skin test). An HIV-infected contact also shouldbe effectively counseled about the substantial risk for diseaseprogression and the need to accept and adhere to a course oftreatment for LTBI. Although contacts of HIV-infected personswith TB have substantial risk for HIV infection themselves,contacts of TB cases without HIV infection have low rates ofHIV infection (301), suggesting that offering HIV testing toall contacts might not be cost-effective. The decision shouldbe based on local data demonstrating that contacts of TB casesare at high risk for HIV infection (i.e., the contacts havea prevalence of HIV infection of 1% [302]). The local epidemiologyof TB, HIV infection, and TB/HIV coinfection also may be usedas a basis for the decision. If resources are limited, and iflocal data indicate that HIV infection contributes only minimallyto the TB problem (i.e., the HIV seroprevalence of contactsis likely to approach 0.1% of the general U.S. population),then the highest priority for voluntary HIV counseling and testingshould be assigned to contacts of HIV-infected persons withTB and those who have identified risk factors for HIV (303).Contacts who have a documented prior positive tuberculin skintest and who are not known or likely to be immunocompromisedgenerally do not require further evaluation unless they havesymptoms suggestive of TB disease. However, candidates for treatmentof LTBI on the basis of other criteria (4) should first receivea medical evaluation, including a chest radiograph, to excludeTB. Contacts with a negative tuberculin skin test should beretested approximately 8 to 12 weeks after the first test unlessthe initial skin test was performed more than 8 weeks afterthe contact's last exposure to the index patient. Every 3 months,all contacts with negative skin test results who remain in closecontact with an infectious patient should receive a repeat tuberculinskin test and, if symptoms of TB disease are present, a chestradiograph. A contact whose repeated test is positive ( 5 mm)should receive a chest radiograph if one has not been takenrecently. If the radiograph is normal, the contact should beevaluated for treatment of LTBI; if it is abnormal, the patientshould be evaluated for TB disease or other cause of the abnormality.TB-control programs should find and evaluate all persons whohave had sufficient contact with a patient with infectious TBto become infected. Contacts at high risk (e.g., infants, youngchildren, and HIV-infected persons) should be identified andevaluated rapidly to prevent the onset of serious, potentiallylife-threatening complications (e.g., TB meningitis). In certainjurisdictions, legal measures have been put in place to ensurethat contact evaluation and follow-up occurs (304). The useof existing communicable disease laws should be considered forcontacts that fail to comply with the examination requirements.All contacts should be assessed routinely for obstacles to theirparticipation in the evaluation process. Any structural barrierthat 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.
Treatmentof contacts with LTBI. Contacts with LTBI should betreatedunless compelling contraindications exist. For completionoftherapy to be ensured, contacts should be placed on DOT wheneverpossible. If resources do not allow that all infected contactsreceive DOT, priority should be assigned to (1) children youngerthan 5 years, (2) contacts with HIV infection, (3) other contactswith risk factors for progression to TB disease (4), (4) contactswith documented skin test conversion, and (5) contacts of patientswith positive sputum AFB smear results and cavities on chestradiography. Contacts on self-administered therapy should bemonitored monthly by personal interview for adverse effectsand adherence until treatment is completed.
Primary prophylaxisof high-risk contacts. Because tuberculinskin test resultsmight take 8 to 10 weeks to become positiveafter infectionwith M. tuberculosis, a contact's initial skintest result mightbe negative even if the person is infected.A second test shouldbe placed 8 to 12 weeks after the contact'slast exposure tothe infectious patient, so the possibilityof LTBI for thosepersons can be better evaluated. During the8- to 12-week windowperiod between a first and second skintest, the following contactswith initially negative tuberculinskin test results shouldreceive treatment for LTBI after TBdisease has been ruled outby clinical examination and chestradiograph: (1) contacts youngerthan 5 years (with highestpriority given to those younger than3 years) and (2) contactswith HIV infection or who are otherwiseimmunocompromised (4).If the second skin test result is negative(< 5 mm), thecontact is immunocompetent (including immunocompetentyoungchildren) and no longer exposed to infectious TB, treatmentfor 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 shouldbe completed. If the second skin test result is negative butthe person remains in close contact with an infectious patient,treatment for LTBI should be continued if the contact is (1)younger than 5 years; (2) aged 5 to 15 years, at the clinician'sdiscretion; or (3) HIV-seropositive or otherwise immunocompromised.
Expanding the contact investigation. Defining the extent ofthe contact investigation is the responsibility of the investigatingTB-control program. Once testing of high-priority contacts iscompleted, the extent of transmission of M. tuberculosis shouldbe evaluated. Consideration can then be given to expanding theinvestigation to include contacts at lower risk for infection.In general, the contact investigation need be expanded onlyif excessive transmission is detected, on the basis of the followingcriteria: (1) secondary cases of TB are identified in contacts,(2) documented skin test conversions exist, and (3) comparisonof skin test positivity among contacts with available data onthe baseline prevalence of skin test positivity in the populationindicates the probability of transmission. When a contact investigationis expanded, resources should continue to be directed to personsidentified as being at greatest risk. In any case, the totalcontact-tracing process should be completed 3 months or lessafter initiation of the investigation, unless evidence of transmissionrequires further expansion of testing.
Data management anduse in decision making. Maintenance of datais crucial to allaspects of the contact investigation. Protocolsshould be developedto maximize the efficiency of the process,given available resources.Data should be collected for casesand contacts by using standardizedforms (paper or electronic)with standard definitions and formats,according to nationalguidelines (305). Data elements shouldmirror those collectedby the states and CDC, but individualjurisdictions may electto expand the data elements.
Evaluation.Contact investigation steps should be adequatelydocumented,so the process can be monitored and evaluated. Nationalperformancemeasures for TB control stipulate that programsshould completetreatment of LTBI among 61% of contacts of infectiousTB cases(Table 4). Additional parameters should also be trackedandevaluated. Programs should determine whether the indicationsgiven previously for conducting a contact investigation areapplied to all reported cases. In addition, for each TB casethat is investigated, the number of contacts identified shouldbe recorded. For each contact identified, outcomes to monitorinclude (1) whether the contact evaluation took place (includingplacing and reading the first and second tuberculin skin tests,if applicable) and was completed and (2) whether the recommendedprotective interventions (including screening for TB disease,treatment for LTBI, and prophylaxis within the window period)were offered, accepted, started, and completed. Results of theevaluation should be aggregated and recorded for stipulatedintervals 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 completedevaluation; (3) among those evaluated, the number and percentageeligible 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 routinelyin the United States. However, CDC collects aggregate data onthe outcomes of contact investigations from state and localTB control programs through the Aggregate Report for ProgramEvaluation. Routine collection and review of these data canprovide the basis for evaluation of contact investigations forTB control programs.
Education and training for contact investigations.The educationneeds for all aspects of the investigation process(includingmedical abstraction, patient interviewing, culturalcompetency,maintaining patient confidentiality, and how toperform tuberculinskin testing) should be continuously assessed.All involvedstaff should receive ongoing training. CDC-fundedregional trainingcenters offer training courses in contactinvestigation andinterviewing skills.
Confidentiality. Maintainingconfidentiality is a critical componentof the contact investigationprocess. Guidelines for releaseof confidential informationrelated to conducting contact investigationsshould be developed.An example of appropriate release of confidentialmedical informationis the release of an index case patient'sdrug susceptibilitytest results to a clinician caring for acontact with LTBI orone who has progressed to active TB.
Contact investigationsamong special populations. Contact investigationsoften areconducted among special populations or locations (e.g.,homelessshelters, correctional facilities, HIV residentialfacilities,schools, worksites, health care facilities, activedrug users,and those living along the U.S.–Mexico border).Guidelinesoffering specific recommendations for contact investigationsunder 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 resultin continued transmission of TB. Missed epidemiologic linksamong patients with TB can have severe consequences as evidencedin an outbreak associated with a floating card game in the ruralSouth (172) and an outbreak in Kansas among exotic dancers andtheir close contacts that occurred during a 7-year period (38).
When TB occurs with high incidence, clusters of cases that haveepidemiologic links likely occur constantly but tend to blendinto the generally high morbidity (306). In a low-incidencesetting, however, clusters of linked TB cases can be identifiedmore readily. Three criteria have been established to determinethat a TB outbreak is occurring (162): (1) an increase has occurredabove the expected number of TB cases, (2) transmission is continuingdespite adequate control efforts by the TB-control program,and (3) contact investigations associated with the increasedcases require additional outside help.
TB outbreaks have occurred in low-incidence areas in which expertiseand experience in dealing with such outbreaks might be lacking.Such outbreaks have occurred among different populations andsettings, including a young foreign-born child in North Dakota(25); exotic dancers and their contacts in Kansas (38); homelesspersons in Syracuse, New York (120); factory workers in Maine(188); and limited, seemingly unrelated clusters of cases thatwere the cause over time of perpetuating transmission in Alabama(307).
For an increase in the expected number of TB cases (the firstcriterion of an outbreak) to be identified, the local epidemiologyof TB should be understood. Detection of a TB outbreak in anarea in which prevalence is low might depend on a combinationof factors, including recognition of sentinel events, routinegenotype cluster analysis of surveillance data, and analysisof M. tuberculosis drug-resistance and genotyping patterns.
When an outbreak is identified, short-term investigation activitiesshould follow the same principles as those for the epidemiologicpart of the contact investigation (i.e., defining the infectiousperiod, settings, risk groups, mode of transmission, contactidentification, and follow-up). However, long-term activitiesrequire continued active surveillance, M. tuberculosis genotyping,additional contact investigations and related follow-up foradditional cases, and continuing education of providers, staff,and patients. Consequently, a plan for long-term support shouldexist from the outset of the investigation.
A written protocol should be developed. At a minimum, the protocolshould outline the outbreak response plan, including indicationsfor initiating the plan, notification procedures, compositionof the response team, sources of staffing, plan for follow-upand treatment of contacts, indications for requesting CDC assistance,and a process for evaluation of the outbreak response. The outbreakresponse plan should also include information on how to workstrategically with the media during the public health emergency.CDC offers training packages to assist public HCWs in mediacommunications, including emergency and crisis communication.This training emphasizes preventive planning, event responseactivities, and postevent follow-up. Information on public healthcommunication programs is available at http://www.cdc.gov/communication/cdcynergy.htm.
Targeted Testing and Treatment of LTBI
An estimated 9.5 to 14.7 million persons in the United Stateshave LTBI (39). Continued progress toward eliminating TB inthe United States and reducing TB among foreign-born personswill be impossible without devising effective strategies tomeet this challenge. Guidelines on targeted testing and treatmentof LTBI have been published (4) and revised (308). Those guidelinesinclude recommendations for diagnosing LTBI and treating infectedpersons, 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 bythe Food and Drug Administration, and guidelines for its usewill be published by CDC. This section outlines a recommendedapproach to planning and implementing programs for targetedtesting and treatment of LTBI to create an effective publichealth tool for communitywide prevention of TB.
Targeted testing and treatment of persons with LTBI is not anew concept for the prevention of TB in the United States (309).The effectiveness of treating LTBI among populations at highrisk has been established in clinical trials (285), but thisintervention has not been proven to have an impact on the incidenceof TB in the United States. Theoretically, the epidemiologicimpact would be considerable if cases of TB in a populationwere largely the result of progression of LTBI and if all personsat high risk with latent infection could be identified and treatedsuccessfully. Practically, those circumstances rarely exist.In the United States, the effectiveness of targeted testingand treatment of LTBI as a public health measure has been limitedby 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 courseof treatment (45, 312).
Two approaches exist to increasing targeted testing and treatmentof LTBI. One is to promote clinic-based testing of persons whoare under a clinician's care for a medical condition (e.g.,HIV infection or diabetes mellitus), which also confers a riskfor acquiring TB. This approach, which depends on a person'srisk profile for TB and not on the local epidemiology of thedisease, requires education of health care providers and dependsultimately on their initiative. Although difficulties existin quantifying and evaluating its effectiveness, this approachcould conceivably become a useful tool to reduce the incidenceof TB among foreign-born and other persons at high risk becausethey can be accessed conveniently where they receive primaryhealth care services. The other approach is to establish specificprograms that target a subpopulation of persons who have a highprevalence of LTBI or who are at high risk for acquiring TBdisease if they have LTBI, or both. This approach presumes thatthe jurisdictional TB-control agency has identified the pocketsof high TB risk within its jurisdiction through epidemiologicanalysis and profiling (313–316). Those high-risk pocketsmight consist of foreign-born, homeless, or HIV-infected persons,or they might be geographic regions (e.g., a neighborhood withina city or town) or specific sites (e.g., a homeless shelteror an HIV-housing facility).
The epidemiologic profile should include an assessment of therisk for TB in the population or at the site, the ease of accessto the population or site, and the likelihood of acceptanceof and adherence to targeted testing and treatment. For thisassessment to be facilitated, populations at high risk may beseparated into three tiers (Box 6). Assignment of groups tothese three tiers is based on six criteria: (1) incidence ofTB; (2) prevalence of LTBI; (3) risk for acquiring TB diseaseif the person is infected with M. tuberculosis; (4) likelihoodof accepting treatment for LTBI and adhering to it; (5) easeof access to the population; and (6) in a congregate setting,the consequence of transmission of M. tuberculosis.
BOX 6. PRIORITY POPULATION SUBPOPULATIONS AND SITES FOR TARGETEDTESTING AND TREATMENT OF LATENT TB INFECTION
Tier 1
Personsworking in or served by clinics or community health organizationsproviding care to HIV-infected persons
Prisoners
Legal immigrantsand refugees with class B1 and B2 TB notification status
Recentlyarrived refugees
Other well-defined groups in congregate livingfacilities
Persons enrolled in substance abuse treatment programs*
Tier2
Jail detainees
Persons working or living in homeless shelters
Immigrantsreporting for adjustment of status
Tier 3
Other foreign-bornpersons at high risk (i.e., those that immigrated 5 years fromcountries with a high incidence of TB)
* Persons enrolledin substance abuse treatment programs should be considered atransition group between Tier 1 and Tier 2, depending on thelocal epidemiology of TB.
Tier 1 is made up of well-defined populations at high risk thatcan also be conveniently accessed and followed, either in locationssuch as clinics or community health centers, prisons, or othercongregate living sites or through mandatory registration. Personsin this tier often have a high prevalence of TB and LTBI (immigrantsand refugees with class B TB notification status), an increasedrisk for TB disease if infected with M. tuberculosis (personswith HIV infection), or both (certain homeless and detainedpopulations). The consequences of the spread of TB in congregatesettings increase the necessity of preventive action. Location-based,high-risk communities in Tier 1 are, for the most part, readilyidentifiable and easily accessible, often have their own resources,and generally include the probability of access for a long enoughperiod to permit completion of treatment for LTBI. These populationsshould be the first priority for targeted testing programs.
Persons enrolled in substance-abuse treatment centers may beconsidered transitional between Tier 1 and Tier 2, dependingon local epidemiologic and demographic factors. Substance abusersmight have a high prevalence of LTBI. Injection drug users alsomight have an increased risk for acquiring TB if they are infectedwith M. tuberculosis and at increased risk for HIV infection(317). Access and factors related to acceptance and completionof therapy also might vary by location. Typically, substanceabuse treatment centers that include long-term inpatient treatmentor regularly scheduled appointments (e.g., methadone treatmentcenters) are the best choices for intervention because easeof ongoing access allows sufficient time for completion of therapy.Voluntary HIV counseling and testing should be offered routinelyas part of any targeted testing program among this population.
Populations in Tier 2 also include identifiable and accessiblepopulations made up of persons at high risk, but the distinguishingcharacteristic is that obtaining satisfactory rates of completionof treatment for LTBI might be difficult because of dispersalof the population throughout a larger community or a brief durationof residency in congregate settings. For example, in Atlanta,Georgia, after local epidemiology of TB was analyzed, communitysites for targeted testing and treatment of LTBI of residentsof high-risk inner-city areas were identified (184). Sites ofaccess included outpatient areas of the public hospital, thecity jail, clinics serving homeless persons, and neighborhoodsfrequented by substance abusers. Although 65% of the targetedpopulation that had a tuberculin skin test placed returned tohave the skin test read, only 20% of those with an indicationfor treatment of LTBI completed a course of therapy; this represented1% of persons who underwent targeted testing.
Tier 3 consists of persons born in countries with a high incidenceof TB or U.S.-born persons in racial/ethnic minority populationswith high prevalence of LTBI who do not necessarily have anincreased risk for progressing to TB disease. Eventually, thecontrol of TB among foreign-born persons and progress towardelimination of TB in the United States depends on achievinggreater success in preventing TB among populations at high riskby widespread targeted testing and treatment of LTBI in thepublic and private medical sectors. However, establishing successfultargeted testing and treatment programs for foreign-born personswho are not found in Tier 1 or Tier 2 settings is challenging.Obstacles include the limitations of the tuberculin skin testto differentiate between reactions attributable to BCG or infectionwith M. tuberculosis, the prevalent belief among a substantialnumber of foreign-born persons that BCG vaccination is the causeof a positive test for M. tuberculosis infection and is alsoprotective against TB disease, language and cultural barriers,barriers in access to medical care, and difficulties in providingoutreach and education.
Typical Tier 3 populations are new refugee and immigrant groupsthat are not yet assimilated into U.S. society. Such populationsmight be ignorant of their TB risk, usually lack ready accessto health care services, and might have strong cultural understandingsabout TB that are at variance with those that guide TB-controlactivities in the United States. TB-prevention activities inthis kind of community are highly cost-intensive (221). Engagingsuch communities is a challenging task.
Community-based TB prevention for Tier 3 populations requiresa partnership between the jurisdictional health department andthe affected community. The community should gain an understandingof the TB problem as it relates to them and should participatein the design of the intervention. Community education is essentialfor this approach to succeed. The target population should beinvolved in the design and implementation phases of the intervention,interventions should be developed within the cultural contextof the targeted population, and intermediate goals or benchmarksshould show the population that program activities are achievingsuccess. For example, in Los Angeles, California, the publichealth TB program contracted with community-based organizationsto screen and provide treatment for LTBI to persons at riskin Latino and Asian neighborhoods and at schools teaching Englishas a second language (249). In Cambridge, Massachusetts, a coalitionof Haitian community groups identified TB education as an issuefor their community; strategies to achieve this goal includeddevelopment of a videotape written and produced for viewingin Haitian barbershops and beauty salons in the community, alottery, and measures for evaluation in terms of knowledge andfuture access to care (S. Etkind, Massachusetts Department ofHealth, personal communication, 2002).
For communities in Tier 3, TB is only one (and often not themost important) of multiple medical and public health needs.A broad approach should be adopted that includes TB preventionwith other activities to improve health status. Certain Tier3 populations have achieved sufficient self-identity and developmentto establish access to health care through a community healthcenter, individual medical providers, or clinics. Those communitiesthat have an already established route of access to health carehave an infrastructure in place to establish programs for targetedtesting and treatment of LTBI. Obstacles to overcome often includelack of medications and chest radiographs, the need for a systemto track patients who do not return for monthly appointments,and the capacity to evaluate the program.
Programs for population-based targeted testing and treatmentfor LTBI often have been conducted by public health agenciesthrough TB-control programs. However, recent studies have alsodescribed the establishment of such programs in non–publichealth venues. Promising results, in terms of access to personsat high risk and completion of treatment of LTBI, have beenachieved from nontraditional sites, including syringe exchanges(318), jails (256), neighborhood health clinics (319), homelessshelters (320), and schools (321, 322). This trend indicatesa widening interest in this means of preventing TB and is possiblyinfluenced by the emergence of community-oriented primary care(241, 323), which places primacy on interventions for specificpatients that help prevent disease and preserve the health ofthe 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 willincrease. Also, because persons in Tier 3 populations generallyhave a lower risk for progression from LTBI to TB disease, theeffectiveness and impact of a program will be less than effortsdirected to Tier 1 and Tier 2 populations. Whatever populationis selected or strategy is employed for the targeted testingproject, programs should systematically evaluate the activityto ensure the efficient use of resources. Process, outcome,and impact indicators should be selected and routinely monitoredby the program.
For purposes of monitoring and evaluation, activities associatedwith targeted testing and treatment for M. tuberculosis infectioncan be divided into three phases: the testing itself, the medicalevaluation of persons with positive test results, and the treatmentof those persons with LTBI. Performance indicators should beselected for each phase. For the testing phase, indicators includethe number of persons at high risk identified and the numberand proportion of those that were actually tested. Among thosetested, the number and proportion that had a positive resultfor M. tuberculosis infection should be tracked. Useful indicatorsfor the medical evaluation phase include the proportion of personswith a positive test result who completed a medical evaluationand the number and proportion that were determined to have TBdisease. Indicators for the treatment phase include the proportionof eligible persons starting treatment for LTBI and the numberand proportion that completed treatment. Reasons for failureto complete treatment (e.g., adverse drug effects, loss of interest,and loss to follow-up) should be monitored. Costs should bemeasured for each phase of the project. The cost per personwith LTBI completing treatment provides a measure of the relativeefficiency of the program. Finally, the impact of the programcan be estimated by estimating the number of cases of TB prevented,which is dependent on the number of persons completing treatmentand the estimated risk for progressing to TB disease.
Surveillance of persons with LTBI does not routinely occur inthe United States. However, CDC has recently developed a nationalsurveillance 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 thesafety of treatment regimens recommended in current guidelines(4, 324).
This section contains recommendations for measures to controland prevent TB in five populations (children, foreign-born persons,HIV-infected persons, homeless persons, and detainees and prisonersin correctional facilities). Each of these populations occupiesan 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 athigher risk for exposure to M. tuberculosis or for progressionfrom exposure to disease, or both. Furthermore, nationwide surveillanceand surveys (27, 118–120, 127, 136, 139, 150, 198, 295,315, 325, 326) indicate that the epidemiology of TB in thesepopulations is similar from community to community, which suggeststhat the recommended control measures are subject to generalizationand can be applied more or less uniformly throughout the UnitedStates.
Children, foreign-born persons, HIV-infected persons, homelesspersons, and detainees and prisoners should not be assumed tobe the only populations at high risk for TB, nor are homelessshelters and detention facilities the only settings in needof enhanced TB-control strategies. Local surveillance and surveysfrequently have identified populations and settings of highTB risk and transmission that required the formulation of specificcontrol measures (122, 137, 152, 313, 315, 316, 327, 328). Thisis the primary reason why state and local surveillance shouldbe conducted to develop a clear understanding of the epidemiologyof TB at the jurisdictional level.
Most important, the concept of identifying and targeting populationsand settings at high risk should be viewed as a dynamic ratherthan as a static process. Such populations emerge and recedein importance at the local, state, and national levels. Forexample, foreign-born persons received little attention in the1992 edition of this statement (6). A population whose riskfor TB is now being recognized and delineated is U.S.-born non-Hispanicblacks, who account for approximately 25% of TB morbidity inthe United States and who have TB rates approximately eighttimes those of whites (Table 2) (329, 330). CDC and collaboratingpublic health agencies in Chicago, Illinois, and the statesof Georgia and South Carolina are exploring new strategies toaddress this problem (331).
Control of TB among Children and Adolescents
The occurrence of TB among infants and young children indicatesrecent transmission of M. tuberculosis and often the presencein the community of an unidentified adult with infectious TB.Thus, a case of TB in a child is a sentinel health event thatsignals a public health breakdown (197). Also, certain featuresof TB among children mandate special considerations in casedetection and case management, contact investigations, and targetedtesting and treatment of LTBI. For example, if LTBI resultsfrom exposure to TB in infancy and early childhood, a substantialrisk exists for rapid progression to TB disease, including thedevelopment of potentially lethal forms of TB (198, 294, 325).The recommendations in this statement for control of TB amongchildren and adolescents should receive high priority in allstate 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 diseasedo so within 3 to 12 months of contracting M. tuberculosis infection.Infants and toddlers younger than 3 years are especially proneto the rapid progression from infection to disease, and theyoften acquire severe forms of TB, including meningitis and disseminateddisease. The most important step to detect and prevent TB amongchildren is the timely identification and effective treatmentof adults with active TB. The cornerstone of TB prevention amongchildren is high-quality contact investigations of suspectedcases of pulmonary TB in adults, because 20 to 40% of pediatriccases of TB could have been prevented if contact investigationhad been more timely and thorough (198, 293, 325).
Contact investigation of adult pulmonary TB cases is crucialto the detection, control, and prevention of pediatric TB andits complications (332, 333). The yield of detection of TB andLTBI is high, with an average of 50% of childhood householdcontacts having LTBI or TB disease (31, 60). Because 50% orless of cases of TB among children are asymptomatic despiteabnormal radiographic findings, contact investigation leadsto earlier discovery of TB among children, better treatmentoutcomes, and fewer complications (326). Also, children withLTBI or TB disease identified through contact investigationare 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 toidentify and treat infants and young children who have beenexposed to a person with a contagious case of TB and who mightbe infected but nevertheless have a negative tuberculin skintest (the role of QFT-G for diagnosis of LTBI in children youngerthan 17 years has not been determined). A tuberculin skin testmight take 2 to 3 months after infection to become positivein an infant or toddler. However, the incubation period forsevere TB, including meningitis and disseminated disease, mightbe only 4 to 6 weeks. Failure to give empiric treatment forLTBI to exposed infants and young children with negative tuberculinskin test results, particularly those younger than 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 forchildren than it is for adults (333). Children with TB mightlive in socially disorganized or disadvantaged homes and receivecare from multiple adults. A chaotic environment can lead toa 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 gapsin treatment that require extensions of therapy (326). Intensivecase management, including use of incentives and enablers, isa 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 generallyconducted to identify the adult source-case. Identifying a source-caseserves to establish the diagnosis of TB in the majority of childrenand, if the source-case is culture-positive for M. tuberculosis,to determine the likely drug susceptibility pattern of the infectingstrain of M. tuberculosis in the child.
Even with optimal medical evaluation, M. tuberculosis can beisolated from less than 50% of children with clinically suspectedTB. While microbiologic testing determines the diagnosis ofTB for the majority of adults, positive culture results oftenare lacking for children. In the majority of cases, the diagnosisof pediatric TB is established by the triad of (1) a positivetuberculin skin test result, (2) either an abnormal chest radiographor physical examination or both, and (3) discovery of a linkto a known or suspected case of contagious pulmonary TB. Becauseculture yields from children with TB are low, determining thedrug susceptibility pattern from the source-case isolate oftenis the only way to determine optimal treatment for childrenwith either LTBI or TB disease (334, 335).
Because TB among infants and young children usually occurs withinweeks to months of contracting infection with M. tuberculosis,having a child with disease is a marker of recent transmissionfrom someone in the child's environment. The source-case, oftena parent or other caregiver (336–338), might not havebeen identified as having TB by the time the child becomes ill.Consequently, parents and other adults who are close contactsof children hospitalized with TB should be evaluated themselvesfor TB disease as soon as possible to serve as a case-detectiontool and to prevent nosocomial transmission of M. tuberculosis(339). A chest radiograph should be performed on these familymembers to exclude pulmonary TB; certain centers have implementedthis recommendation by requiring that adults who accompany achild have a chest radiograph performed and interpreted immediatelywhile at the health care facility (339). Other adult familymembers or friends also should be required to show evidenceof a normal chest radiograph, performed by the health departmentor other provider, before being allowed to visit the child.Because TB in the child, not LTBI, is the reliable marker ofrecent infection, chest radiograph screening of accompanyingadults is not necessary if the child has LTBI without TB disease.
Associate investigations (i.e., efforts to identify and evaluatehousehold contacts of a child with LTBI to identify the infectiousperson responsible for the child's infection) are often performedas part of the evaluation of a child with LTBI (5, 17, 340–343).The usefulness of this approach depends on the criteria forplacing skin tests on children. If testing of children at lowrisk is undertaken, associate investigations will be costly,have a low yield, and divert TB-control resources from moreimportant activities. Associate investigations of children athigh risk, however, usually detect a limited number of personswith TB but do identify substantial numbers of other personswith LTBI who are candidates for treatment (341–343).
TARGETED TESTING AND TREATMENT OF LTBI.
In the 1950s and 1960s, child-centered TB-control activitieswere based on periodic testing of all children for LTBI (344).However, as the number of TB cases dropped, the disease becameconcentrated among persons at high risk in particular subpopulations.Consequently, the majority of U.S. children have negligiblerisk for acquiring LTBI. Among children at low risk, the majorityof positive tuberculin skin test results are false positivescaused by nonspecific reactivity or exposure to nontuberculousmycobacteria in the environment (344). False-positive resultslead to unnecessary health care expenditures and anxiety forthe child, family, school, and HCWs (345). Thus, while the testingof children with an expected high prevalence of LTBI is desirable,mass testing of children with a low prevalence of LTBI is counterproductiveand should not be undertaken.
The optimal approach is to perform tuberculin skin testing onlyon those children with specific risk factors for LTBI. A questionnairethat assesses risk factors for TB can be used successfully inclinics and private offices to identify children at risk forLTBI (237, 346–348); this approach can also be used toidentify at-risk college students (349). The screening toolis the questionnaire; only those children whose answers indicatethat they are at risk for LTBI should receive a tuberculin skintest. Use of a questionnaire can also address issues relatedto discrimination; all children in a setting such as a schoolor child care center can be screened easily, but only thosewith identified risk factors for LTBI should receive a tuberculinskin test, thereby diminishing the number of false-positiveresults.
No single questionnaire has been validated for use in all settingsand for all ages of children. Factors that have correlated highlywith risk for LTBI among children in more than one study include(1) previous positive tuberculin skin test result, (2) birthin a foreign country with high prevalence, (3) nontourist travelto a high-prevalence country for more than 1 week, (4) contactwith person with TB, and (5) presence in the household of anotherperson with LTBI. Questions pertaining to a locally identifiedpopulation 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 theUnited States, the completion rate associated with 6 to 9 monthsof self-supervised isoniazid therapy is only 30 to 50%. As LTBIamong young children might progress rapidly to TB disease, DOTis recommended. Children with LTBI, who are most likely to benefitfrom DOT because of their high risk for rapid progression ofinfection to disease, include contacts of persons with recentlydiagnosed 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. During1992–2003, the number of TB cases decreased 64% amongU.S.-born persons but increased 8% among persons born outsidethe United States (14, 15). During 1992–2003, the percentageof TB cases in the United States that occurred among foreign-bornpersons increased from 27% in 1992 to 53.3% in 2003 (15), andthe number of states in which more than 50% of reported casesof 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, NewYork, Texas, and Virginia) accounted for 71% of cases amongforeign-born persons. Foreign-born persons with TB have beenmore likely than U.S.-born persons to harbor drug-resistantstrains of M. tuberculosis; in 2003, 10.6% of foreign-born personswith TB had TB with primary isoniazid resistance, compared with4.6% of U.S.-born persons with TB (14).
The increase in cases of TB among foreign-born persons has beenattributed to at least three factors (350). First, the numberof persons entering the United States from other countries inwhich TB occurs with high incidence (44) now accounts for morethan 75% of the immigrant flow (116, 278); during 1994–2003,an estimated 80 to 86% of immigrants admitted to the UnitedStates came from high-incidence countries (351). Second, foreign-bornpersons are subject to cultural and linguistic barriers thatmight affect health-seeking behavior and access to medical care,resulting in delays in diagnosis and difficulty in understandingand completing treatment (18, 19, 194, 325). Third, these barriers,which have implications for the treatment, control, and preventionof TB among foreign-born persons, have not been sufficientlyappreciated and addressed in TB-control program planning inthe United States.
Precise information is lacking to assist in the identificationof foreign-born persons who have an elevated risk for acquiringTB during residence in the United States. Immigrants enteringeither Canada or the United States have a risk for TB duringtheir early years of residence that approximates that of residentsof the country of birth (115, 352, 353). Over time, the riskdeclines and approaches that of residents of the host country.Consequently, recent guidelines have designated immigrants fromcountries with a high prevalence of TB who have resided in theUnited States fewer than 5 years as foreign-born persons athigh risk (4).
Criteria for characterizing countries as having a high prevalenceof TB have not been developed, and no consensus exists on whichcountries should be designated as having a high prevalence ofTB. In rank order, the 14 countries listed most frequently ascountry of origin of foreign-born persons with reported TB inthe 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 accountedfor 76% of cases among foreign-born persons during 1999–2002(14). Estimated incidence rates of TB in these countries in2002 ranged from 33/100,000 population (Mexico) to 406/100,000population (Somalia) (354). However, the country of origin offoreign-born persons with TB can vary substantially among localitieswithin a state and between states and regions across the UnitedStates.
State and local TB control programs should develop their ownprofiles of risk for TB among foreign-born persons as part ofthe jurisdiction's overall epidemiologic analysis of TB andthen define which immigrant and foreign-born populations intheir areas should be considered as being at high risk for TB.Data sources for TB programs to use in making this determinationinclude (1) World Health Organization data on the estimatedincidence of TB in countries of origin (354); (2) local epidemiologicand surveillance data (151, 152, 313–316, 355); (3) publishedguidelines (4, 279), and other sources of data (115, 116); (4)qualitative information on refugee and immigrant movement intothe jurisdiction; and (5) availability of resources to establishcontrol and prevention measures targeted toward the foreign-bornpopulation. The principles and priorities of TB control amongforeign-born persons at high risk are not different from thosefor control of TB among U.S.-born persons (Box 4). However,for the reasons given previously, TB control among foreign-bornpersons at high risk might present challenges requiring targetedstrategies specific to that population (152, 356).
How Foreign-born Persons Enter the United States.
Foreign-born persons enter the United States legally throughdifferent official channels (Table 7). As a condition of entry,persons migrating as immigrants, refugees, and asylees are requiredto be screened for diseases of public health significance, includingTB. Persons entering in the nonimmigrant category do not requirepreentry screening. Persons who enter the country without legaldocumentation are referred to as unauthorized aliens.
TABLE 7. U.s. citizenship and immigration services immigration categories, by tuberculosis screening mandate
During 1992–2002, an estimated 380,000 to 536,000 personsentered the United States annually as immigrants, refugees,or asylees (Table 8). In 2002, among the estimated 516,000 personsin those categories, 86.6% were from countries with high incidenceof TB. Immigrants, refugees, and asylees constitute only a fractionof foreign-born persons who enter the United States each year;the majority (20–35 million persons) enter in one of thenonimmigrant subcategories (Table 8). The majority of enteringnonimmigrants are tourists or business travelers who spend onlya short time in the United States. However, an estimated 850,000to 1.9 million workers, students, and other visitors and theirfamilies might reside in the United States for multiple years(Table 8).
TABLE 8. Numbers of foreign-born persons who entered the united states, by immigration category—united states, 2002
A nonimmigrant, refugee, or asylee residing in the United Stateswho meets the eligibility requirements and applies for a changein visa status to that of a lawful permanent resident shouldundergo required health screening assessment by a civil surgeon.During 2002, of the 679,305 persons who adjusted their immigrationstatus under this program, 536,995 (79%) were from countrieswith high incidence of TB (238). In addition, an estimated 7million unauthorized aliens resided in the United States inJanuary 2000, and during 1990–1999, the unauthorized alienpopulation increased annually by approximately 350,000 persons(357).
Current Requirements for TB Screening of Immigrants.
U.S. immigration law mandates screening outside the United Statesfor applicants designated as immigrants who are applying forpermanent residence status and for applicants designated asrefugees or asylees (Table 7). The purpose of mandated screeningis to deny entry to persons who have either communicable diseasesof public health import or physical or mental disorders associatedwith harmful behavior, abuse drugs or are addicted to drugs,or are likely to become wards of the state. The current listof infectious diseases of public health significance that aregrounds for exclusion include infectious TB, HIV infection,leprosy, and certain sexually transmitted diseases (358). Worldwide,approximately 400 licensed local physicians, designated as "panelphysicians," perform these medical examinations. Panel physiciansare appointed by U.S. embassies and consulates that issue visas.CDC is responsible for monitoring the quality of these examinationsand for providing technical guidance and consultation for TBdiagnosis and treatment.
The TB screening process is a program for active TB case detectiondesigned to deny entry to persons with infectious pulmonaryTB (identified by positive sputum AFB smear results). For persons15 years and older, a brief medical history and a chest radiographare obtained (Figure 4). If the chest radiograph is consideredcompatible with pulmonary TB, three sputum specimens are obtainedand examined for AFB. Although procedures vary from site tosite, smears are usually performed by Ziehl-Neelsen stainingand examined with light microscopy. Cultures for M. tuberculosisare not required and are not routinely performed. Persons youngerthan 15 years are evaluated only if they have symptoms thatare consistent with TB or are a contact of person with infectiousTB. A test for M. tuberculosis infection is performed, and achest radiograph is obtained if the test is positive or if thechild is suspected to have TB.
Figure 4. Tuberculosis (TB) screening process for immigrants and refugees conducted outside the United States. *AFB = acid-fast bacilli.
Persons with abnormal chest radiographs suggestive of TB andwith AFB-positive sputum smear results are classified as havingclass A TB, which is an excludable condition for entry intothe United States (358). Persons so designated have two options:(1) to complete a course of treatment for TB, including documentednegative sputum AFB smears at the end of treatment, at whichpoint they are classified according to their chest radiographresults and may enter the United States; or (2) to receive TBtreatment until sputum smear results for AFB convert from positiveto negative and then apply for an immigration waiver. A U.S.health care provider who agrees to assume responsibility forthe completion of TB treatment after a person's arrival in theUnited States should sign the waiver. The waiver is countersignedby a representative of the jurisdictional public health agencyof the person's intended U.S. destination. An applicant whosechest radiograph is compatible with active TB but whose sputumAFB smear results are negative is classified as having classB1 status and may enter the United States. If the chest radiographis 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 statusare identified at ports of entry to the United States by CISon entry to the United States and reported to CDC's Divisionof Global Migration and Quarantine (DGMQ). DGMQ notifies stateand local health departments of refugees and immigrants withTB classifications who are moving to their jurisdiction andneed follow-up evaluations. Persons with a class A waiver arerequired to report to the jurisdictional public health agencyfor evaluation or risk deportation. For persons with class B1and B2 status, however, the stipulated evaluation visits tothe health agency are voluntary.
Persons Seeking Adjustment of Status after Arrival.
Persons seeking to adjust their immigration status after residingin the United States with nonimmigrant visa status should undergoa 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 applicantseeking adjustment of status has a tuberculin skin test readingof 5 mm or larger, a chest radiograph is required. If the radiographis compatible with active TB, the person is referred to thejurisdictional public health agency for further evaluation (358).Civil surgeons are also advised that persons with a positivetuberculin test result and no signs or symptoms of TB diseaseshould be referred to public health agencies for evaluationfor treatment of LTBI, following ATS/CDC/IDSA guidelines (4,324).
Because data on the outcomes of TB screening of persons seekingto adjust their immigration status are not aggregated or analyzed,only limited information is available. In an evaluation of thescreening practices in five U.S. Immigration and NaturalizationService jurisdictions, among 5,739 applicants eligible for screeningthrough tuberculin skin testing, 4,290 (75%) were consideredto 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 duringMay 1987–December 1988 (239). Applicants were screenedwith tuberculin skin testing, chest radiographs, or both. Among4,840 applicants who had a tuberculin skin test placed, 2,039(42%) had a reaction of 10 mm or larger. Sixteen persons (0.7%)were sputum culture–positive for M. tuberculosis. Therapywith isoniazid was recommended for 1,029 applicants, of whom716 (70%) completed 6 months of treatment.
Immigration Status of Foreign-born Persons with TB.
Studies have sought to identify the initial immigration statusof foreign-born persons with reported TB. During 1992–1993in Hawaii, 78% of TB cases occurred among immigrants, 4% amongstudent 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 casesamong foreign-born persons who had resided in the United Statesfor less than 1 year occurred among immigrants or refugees (293);immigration status was not determined among the remaining foreign-bornpersons. During 1998–2000, a total of 59% of foreign-bornpersons with TB in Tarrant County, Texas, were immigrants orrefugees, 24% were unauthorized immigrants, and 17% were nonimmigrantstudents and workers (316).
Assessment of TB Screening Requirements for Immigrants.
The priority for immigration screening efforts is to detectcases of pulmonary TB among persons applying for permanent residencein the United States and to prevent the most infectious personsfrom entering the United States. However, requirements for screeningoutside the United States do not apply to the majority of foreign-bornpersons entering the United States because those classifiedas nonimmigrants and unauthorized immigrants do not undergoscreening (Table 7) (277).
Furthermore, a significant proportion of immigrants with classB1 (4–14%) and B2 (0.4%–4%) status allowed to enterthe United States with abnormal chest radiographs because ofhaving AFB-negative sputum smears on screening outside the UnitedStates are later discovered (on the basis of follow-up evaluationsby U.S. public health agencies) to have active TB at the timeof entry (350). This finding has great importance for TB-controlactivities in certain U.S. jurisdictions.
IOM, NTCA, and CDC have suggested changes in the screening proceduresfor immigrants, as follows:
IOM has recommended that testingfor M. tuberculosis infectionbe added as a requirement to themedical evaluation for immigrantvisa applicants from countrieswith high incidence of TB (2).
IOM has recommended that (1)a class B4 TB designation be createdfor persons with normalchest radiographs and positive tuberculinskin tests and that(2) immigrants with B4 status be requiredto undergo an evaluationfor TB and, when indicated, completean approved course of treatmentfor LTBI before receiving apermanent residency card.
CDChas proposed enhancing training and oversight of panel physiciansoutside the United States and of civil surgeons in the UnitedStates to improve the quality of immigration screening (359).CDC is also working to develop an electronic system for notifyingjurisdictional public health agencies about the arrival of classB immigrants.
NTCA has called for (1) clarification of legaland fiscal issuesassociated with domestic evaluation and treatmentof immigrants,(2) efforts to educate immigrants with classB1 and B2 statusabout their responsibilities for follow-up,and (3) operationalresearch to address the cost effectivenessof screening additionalcategories of immigrants.
Considerationalso should be given to broadening the scope ofmedical evaluationsfor immigrants. The costs and benefits ofextending the requirementfor screening to all visa applicantsplanning to reside in theUnited States for more than 6 monthsshould be examined. Considerationis being given to adding sputumcultures to the sputum AFB smearevaluation of visa applicantswho, on the basis of an abnormalchest radiograph, are suspectedto have pulmonary TB or who,at least for persons with smear-positiveTB cases, are fromcountries with known high rates of drug resistance.
TB Control at the U.S.–Mexican Border.
The U.S.–Mexican border presents specific challenges toTB 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) comprisethe U.S.–Mexican border, and an estimated 1 million personscross the border daily. In the six Mexican border states, estimatedannual TB incidence is 27.1 cases/100,000 population, comparedwith 5.1 cases/100,000 population in the United States (359).In 1999, Mexico was the country of origin for 23% of foreign-bornpersons in the United States with reported TB, and 75% of thosecases were reported from the four U.S. border states. In 1996,those same states reported 83% of TB cases among foreign-bornHispanics (360). The high rate of TB at the border, the substantialnumber of border crossings, the substantial geographic areainvolved, and the prevalent cultural and linguistic barriersmake TB control a challenge in this region.
Recommendations to improve TB control at the U.S.-Mexican borderhave been published (361). These recommendations include useof a binational case definition and development of a binationalregistry of TB cases, improvements in clinical care of binationalTB patients and close contacts by cross-border case-managementstrategies, development of performance indicators for theseactivities, 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 timeof entry of foreign-born persons into the United States fromdomestically occurring disease obscures the progress that certainstates and cities have made in TB control. Standardized reportingof new TB cases does not allow separating TB among foreign-bornpersons that is present at the time of entry from cases thatarise during residence in the United States. This is more thana semantic distinction because cases of TB that occur amongshort-term visitors and workers, students, and unauthorizedaliens are counted as U.S. incident cases even though a substantialnumber are imported (115). Surveys using sputum cultures indicatethat 4 to 13% of immigrants and refugees with class B1 statushave TB disease at the time of entry (279). TB present at thetime of entry is likely to contribute to the higher incidencerates of TB noted among foreign-born persons in the first 2years after arrival (115). The importance of imported casesand the need to distinguish them from domestic cases has alsobeen demonstrated in the smallpox, polio, and measles eradicationefforts in North America.
CASE DETECTION.
Multiple factors common to the experience of foreign-born personsin the United States might lead to delays in the detection ofTB. Preexisting culturally derived beliefs about TB might serveas a disincentive to seek health care when symptoms of TB areexperienced (18, 279). Also, foreign-born persons wishing toreceive a medical evaluation might encounter financial, linguistic,or other barriers to access (19). Once medical services aresought, foreign-born persons are likely to receive their evaluationfrom certain kinds of health care providers (e.g., foreign-bornphysicians or those working in community health centers or hospitalEDs) rather than from TB clinics conducted by public healthagencies. These challenges to optimal case detection among foreign-bornpersons will require (1) targeted public education for foreign-bornpopulations at high risk to explain that TB is a treatable,curable disease; (2) better access to medical services, especiallyfor recently arrived immigrants and refugees; and (3) maintenanceof clinical expertise in the diagnosis and management of TBamong medical practitioners (Box 1).
The TB screening process for visa applicants (i.e., identificationof persons with abnormal chest radiographs) has provided opportunitiesfor active case detection in follow-up evaluations in the UnitedStates. Data derived from programs that have sought to identifyactive TB cases on the basis of positive sputum cultures forM. tuberculosis among immigrants with class B notification statusindicate that 3 to 14% of the approximately 6,000 immigrantswith class B1 status who enter the United States each year and0.4 to 4.5% of the 12,000 immigrants with class B2 status haveTB at the time of entry (279). In San Francisco, California,during July 1992–December 1993, of 182 immigrants withclass B1 status who received follow-up evaluations, 27 (14.8%)had active TB and 134 (73.3%) had inactive TB (362). Among 547immigrants with class B2 status, 24 (4.3%) had active TB and301 (54.5%) had inactive TB. In California, 3.5% of all personswith a class B notification status who arrived during January1992–September 1995 were reported to have active TB within1 year or less of arrival (277). Recent arrivals with classB notification status accounted for 38% of all foreign-bornpersons with TB reported within 1 year of arrival. Among 124immigrants and refugees in Hawaii who were reported during 1992–1993to have TB with 1 year or less of arrival, 78 (63%) had beenclassified as having class B1 status and 17 (14%) as havingclass B2 status (350). However, a study from Los Angeles suggestedthat the visa application process was more effective in identifyingcases among persons recently arrived from Southeast Asia thanamong those from Mexico and Central America (363).
An active class B1/B2 follow-up program can be relatively costeffective. During October 1995–June 1996, in Santa ClaraCounty, California, 87% of immigrants with class B status respondedto letters inviting them to receive a follow-up evaluation,resulting in a cost of $9.90 to locate one immigrant with classB1/B2 status and $175.88 to locate one person with TB (364).
CASE MANAGEMENT.
As with case detection, cultural and linguistic differencesmight impede successful treatment outcomes among foreign-bornpersons. Case management of persons whose primary language isnot English depends on reliable and competent medical translation.Providers and agencies that work with foreign-born patientsat high risk should ensure that adequate translation and interpretationservices are available. In jurisdictions in which the majorityof the cases occur among foreign-born person, providing theseservices can be costly. For example, in 2000, the Tarrant CountyHealth Department TB Program (Fort Worth, TX), spent approximately$24,000 on professional translation services (365). Ideally,professional services should be used for translation ratherthan relatives or family friends (365).
Culturally derived attitudes and beliefs about TB and its treatmentcan also be impediments to the management of TB among foreign-bornpersons. Each culture has its own knowledge, attitudes, andbeliefs about TB and how it should be treated. For example,in a study that used focus groups to evaluate attitudes regardingTB among Filipino immigrants, participants expressed a beliefthat TB was extremely contagious (264) and mentioned the associatedsocial stigma and isolation. Although all participants agreedthat medical therapy was necessary, participants also trustedthe effectiveness of traditional treatments. As more of theburden of TB in the United States is borne by foreign-born persons,the need for health care providers to understand cultural attitudestoward TB will increase.
Case management is particularly difficult at the U.S.–Mexicoborder where, until recently, tracking systems for persons whomigrated between the two countries were not in place. A newbinational system has been established to ensure continuityof care and completion of TB treatment for patients who migratebetween the United States and Mexico and to coordinate the referralof patients between the health systems of both countries. Theproject is now being tested in four U.S.–Mexican jurisdictions(San Diego, CA, and Tijuana, Baja California; El Paso, TX–LasCruces, NM, and Ciudad Juarez, Chihuahua; Webb and Cameron Counties,TX, and Matamoros, Tamaulipas; and Arizona and Sonora). If thepilot project proves successful, this binational TB patientreferral and information system will likely be expanded to otherparts of the United States and Mexico.
CONTACT INVESTIGATION.
Contact investigations have a particularly high yield when conductedon foreign-born patients. In Seattle, for example, contactsof foreign-born persons with TB were more numerous (6.0 vs.3.4 per case) and substantially more likely to be have positivetuberculin skin test results (50 vs. 18%) and to be startedon treatment for LTBI (40 vs. 23%) than were contacts of U.S.-bornpersons with TB (293). A multicenter survey from around theUnited States demonstrated that the tuberculin skin test waspositive among 71% of foreign-born contacts compared with 32%of all close contacts (31). Although not all foreign-born contactsidentified during a contact investigation are recently infected,the majority would nevertheless be considered candidates fortreatment of LTBI under current guidelines (4). In addition,a Canadian study indicated that contact investigations weremore cost effective than preimmigration screening and postarrivalsurveillance (276).
TARGETED TESTING AND TREATMENT OF LTBI.
Surveys using molecular epidemiologic methods have consistentlydemonstrated that less clustering of M. tuberculosis isolatesoccurs from foreign-born patients than from U.S.-born patients;this has been interpreted as evidence that less person-to-personspread of TB occurs among foreign-born persons in the UnitedStates and that the majority of cases of TB among foreign-bornpersons occur as a result of activation of a latent infection(150–152, 356). In fact, one reason for the lack of progressin reducing TB among foreign-born persons might be that insufficientattention has been given to targeted testing and treatment (152),which should be the most applicable prevention strategy forthis population, in which TB disease occurs mainly by progressionfrom LTBI.
The success of programs for targeted testing and treatment ofLTBI among populations at high risk in the United States hasbeen thwarted by poor interest in the intervention on the partof medical practitioners and poor adherence by patients (51).Among foreign-born persons, these problems are magnified bythe lack of access to care and by cultural and linguistic obstacles.Successful models for administering targeted testing and treatmentof LTBI among refugees have been published; these models areresource-intensive and require a commitment to working withinthe population's cultural contexts (202, 221). In addition,the use of DOT increases treatment completion rates (366).
Other opportunities to conveniently access foreign-born personsfor targeted testing programs include school-based testing offoreign-born students. The majority of persons residing as studentsin the United States remain long enough to receive targetedtesting for LTBI and, if TB is diagnosed, to complete a courseof treatment. Screening for TB is required by 61% of collegesand universities: for all students in 26%, for all internationalstudents in 8%, and for students in specific academic programsin 47% (367). School-based screening also has been evaluatedamong younger students (150, 322, 345). In California, widespreadTB screening of kindergarten and high school students yieldeda low prevalence of skin test reactors and a limited numberof cases of TB, but foreign-born students were more than 30times more likely than U.S.-born students to have the infection(345). In a cost–benefit analysis, screening all studentswould be expected to prevent 14.9 cases/10,000 children screened,whereas targeted testing would prevent 84.9 cases/10,000 screenedand would be less costly (345).
Control of TB among Persons with HIV Infection
HIV and M. tuberculosis interact in ways that tend to worsenboth diseases among coinfected persons (368). When a personwith HIV infection is exposed to a patient with infectious TB,the risk for acquiring TB disease soon after that exposure ismarkedly increased (369). In outbreaks in which the start ofexposure could be determined, HIV-infected persons acquiredactive TB in as little as a month after exposure to a personwith infectious TB (136). HIV coinfection is also a highly potentrisk factor for progression from LTBI to TB (44, 46, 370). Personswith LTBI and HIV coinfection have a risk for progressing toTB disease of approximately 10%/year (317, 371, 372), whichis 113 to 170 times greater than the risk for a person withLTBI who is HIV-seronegative and has no other risk factors (4,44).
On a global level, HIV infection has had a substantial effecton the epidemiology of TB. Areas of the world most heavily affectedby 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 themost common cause of death among persons with HIV/AIDS in placeswhere the incidence of both diseases is high (374). In the UnitedStates, HIV infection has been associated with TB outbreaksin 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 declinein immune competence and death. However, the use of HAART usingcombination therapy plus protease inhibitors has prolonged thesurvival among persons with HIV infection (375–377). Theintroduction of HAART has also decreased the incidence of TBamong HIV-infected persons: an 80% decrease in risk for TB hasbeen demonstrated among HIV-infected persons receiving HAART(378).
With the declining incidence of TB in the United States since1992, the incidence of HIV infection among persons with TB alsohas decreased. This is likely attributable to increased understandingof the biological interactions between the two pathogens, leadingto more targeted TB-control efforts and to the introductionof HAART. Another factor is improved TB infection control inhealth care facilities, because HIV-infected persons were particularlyaffected by health care–associated transmission of M.tuberculosis (53).
HIV infection was a prominent cause of the 1985–1992 TBresurgence in the United States, especially the incursion ofhealth care–associated TB (including multidrug-resistantdisease). That fact, along with the knowledge that the globalepidemics of HIV infection and TB are continuing unabated (44),dictates a high degree of respect and vigilance for the adverseconsequences that HIV infection could impose on the epidemiologyof 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 withTB is useful for surveillance purposes to ensure that an optimaldrug regimen is chosen for treatment (5), to refer persons forHIV primary care if the case is newly detected, and to guidedecisions about contact investigations. TB is frequently thefirst illness that brings a person who has not previously receiveda diagnosis of HIV infection into the health care system.
Voluntary counseling and testing for HIV is recommended forall patients with TB (5), but this recommendation has not beenfully implemented, and reporting of HIV among persons with TBis incomplete (14). In 2003, HIV testing was performed for lessthan 50% of patients reported with TB in the United States,and only 63% of persons in the age group at greatest risk (personsaged 25–44 years) were tested (14). HIV counseling andtesting has also been recommended for contacts of persons withTB (302). However, recent data indicate that contacts of HIV-infectedpersons with TB have a high rate of HIV infection but that contactsof persons with TB without HIV infection do not (301). HIV testingfor other persons with LTBI should be limited to those who haveclinical or behavioral risk factors for HIV infection.
CASE DETECTION.
HIV coinfection affects the clinical and radiographic manifestationsof TB. HIV-infected patients are more likely than persons withoutHIV 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 aremore likely to have lower lobe or instititial infiltrates andmediastinal or paratracheal lymphadenopathy). These atypicalfeatures are heavily dependent on the patient's CD4 cell count;those with CD4 cell counts of more than 300 cells/µl usuallyhave manifestations, such as upper lobe cavitary infiltrates(274). Persons with HIV infection might also have pulmonaryTB despite a normal chest radiograph (274, 379).
HIV-infected patients are also vulnerable to other pulmonaryand systemic infections such as Pneumocystis carinii and pneumococcalpneumonias and disseminated M. avium complex disease. Althoughthe symptoms and signs of TB are usually different to the trainedclinician from those caused by other prevalent invasive pathogens(273, 381), HIV coinfection often results in delay in the diagnosisof TB as a result of altered clinical and radiographic manifestations(23).
Undetected transmission of M. tuberculosis to HIV-infected personscan have serious sequelae (136). A substantial outbreak of TBin a prison in South Carolina in 1999 demonstrated the widespreadconsequences of an unrecognized TB case in a congregate settingwith a substantial number of HIV-infected persons (37). In thatoutbreak, 32 TB cases and 96 tuberculin skin test conversionsresulted from a single unrecognized case. Similar outbreakshave occurred in hospitals (53, 244), HIV-living facilitiesand day-treatment programs (136), and homeless shelters (33).Such outbreaks underscore the importance of aggressive TB screeningand treatment in settings in which HIV-infected persons congregate.Screening for TB in those settings has been successfully conductedby using symptom checklists, tuberculin skin testing, and chestradiographs (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 antiretroviraltherapy have overlapping toxicities and potentially dangerousdrug interactions (382). Paradoxical responses to TB therapyare more common among HIV-infected persons (383). Use of multiple,potentially toxic medications also provides further challengeto adherence with TB treatment. Therefore, integration of managementof both HIV infection and TB is critical to the success of managementof both. Comprehensive case management, including DOT, is particularlyimportant (5). Among HIV-infected TB patients, more favorableoutcomes and survival have been associated with DOT than withself-administered therapy (384). ATS/CDC/IDSA guidelines shouldbe consulted for recommendations on length and mode of treatmentand selection of drug regimens (5). Finally, patients with HIVand TB bear the brunt of two conditions that are associatedwith clinical and social complexities that can be personallyoverwhelming. Both HIV infection and TB are associated withstigmatization, and patients with these concomitant conditionsoften suffer from isolation and a lack of social support.
CONTACT INVESTIGATION.
Despite controversy as to whether HIV-coinfected patients withTB 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 comparablerates of LTBI (369, 387). The higher risk for progressing rapidlyfrom exposure to M. tuberculosis to TB disease means that allof the medical and public health interventions (case detectionand reporting, initiation of an effective drug regimen, andidentification and evaluation of contacts) are more urgent whenworking to control HIV-associated TB (388).
Although offering HIV counseling and testing to all contactsof persons with infectious TB has been recommended (302), thisundertaking would be resource-intensive. Whereas prevalenceof HIV infection among contacts of HIV-infected persons is high,prevalence among contacts of persons with TB without HIV infectionor with undetermined status is negligible (301).
TARGETED TESTING AND TREATMENT OF LTBI.
HIV coinfection is the most important known risk factor forpersons with LTBI acquiring active TB (317, 371, 372). Treatmentof LTBI is effective in reducing the risk for progression toTB disease among HIV-coinfected persons (372, 389). Thus, allpossible efforts should be made to ensure that HIV-infectedpersons are tested for M. tuberculosis infection and that thosefound to have latent infection receive and complete a courseof treatment. In addition, knowledge of the HIV status of personsbeing evaluated for LTBI is desirable (1) in interpreting thetuberculin skin test result (e.g., 5 mm of induration is considereda positive test among persons with HIV infection [4]) and (2)in counseling persons with positive skin test results aboutthe risks and benefits of treatment for LTBI (the role of QFT-Gfor testing persons with HIV infection for LTBI has not beendetermined). According to current guidelines (302), personsbeing evaluated for LTBI should also be screened for HIV infectionby using self-reported clinical and behavioral risk factors.
INSTITUTIONAL INFECTION CONTROL.
Infection-control measures recommended to prevent transmissionof M. tuberculosis have been effective in limiting exposureof HIV-infected persons, including patients, visitors, and staffmembers, to M. tuberculosis in hospitals, extended care facilities,and correctional facilities (9, 244). Nevertheless, the riskfor rapid progression from exposure to TB disease means thatHIV-infected persons should continue to be advised of any potentialsites of institutional exposure so an informed choice regardingemployment or volunteering can be made.
Control of TB among Homeless Persons
The persistence of TB among homeless persons in the United Statesis a major public health problem. The homeless population isnot 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., livingon public support in residential hotels) (390). TB incidenceis high among homeless persons, and evidence exists of considerabletransmission of M. tuberculosis. Among 2,774 homeless personsenrolled during 1990–1994 in San Francisco, California,25 incident cases were identified for 1992–1996, for anannual rate of 270 cases/100,000 population (118). Among 20M. tuberculosis isolates from incident cases that were subjectedto genotyping study, 15 (75%) were clustered, indicating chainsof transmission in the population. Other molecular epidemiologystudies also have identified homelessness as an important riskfactor for clustering of M. tuberculosis isolates (33, 119,391, 392).
Shelters are key sites of TB transmission among homeless personsthroughout 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, during1995–1996, clusters of cases among homeless persons occurredsimultaneously in four homeless shelters (27). In Alabama, genotypingof isolates from TB cases reported in 1994–1998 revealedan undetected statewide outbreak of TB that was traced to transmissionin 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 beforereceiving a diagnosis; ventilation in the shelter was poor,and the population included vulnerable persons with risk factorsthat included HIV infection, substance abuse, and malnutrition(120).
Multiple barriers to the control of TB among homeless personshave been identified. Delays in detection of infectious caseshave been reported (20); in a computer simulation study thatmodeled multiple strategies for TB control among homeless persons,a 10% improvement in access to treatment led to greater declinesin disease and death after 10 years than comparable improvementsin treatment programs (394). Traditional methods of conductingcontact investigations often fail to identify contacts of homelesspersons with TB (30, 119, 120). Difficulties also have beenencountered in completing treatment for homeless patients withactive 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 personsmight occur as a result of delays in seeking medical care (181)and to the failure of medical providers to detect TB among thoseseeking care (20). Homeless persons with TB are disproportionatelylikely to receive care in hospital EDs and other urgent careclinics (232). For example, during 1994–1996, homelesspersons in Atlanta, Georgia, were more likely than other patientsto receive a diagnosis in a hospital ED (184). On the basisof sputum AFB smear results and radiologic findings, homelesspersons had more advanced disease at the time of diagnosis,another indication that they received diagnoses later in thecourse of their disease (184).
Shelters have proved to be effective sites for case detectionby use of screening procedures among homeless persons. DuringMay 1996–February 1997, among 127 homeless persons inAlabama for whom shelter-based screening was conducted by usingsymptom evaluation, sputum culture, and chest radiographs asthe screening package, four (3.1%) persons had TB disease (281).Symptom evaluation alone was not proven to be useful. In a similarstudy from London, United Kingdom, that employed symptom evaluation,tuberculin skin testing, and chest radiography, 1.5% of homelesspersons were determined to have TB (396).
On the basis of findings of a high prevalence of TB in shelter-usinghomeless populations, certain communities have implemented compulsoryscreening of shelter residents based on symptom evaluation ortuberculin skin testing with radiographs for those with positivetests. One such program in Portland, Oregon, initiated in 1985,was associated with an 89% reduction in TB morbidity in thegeographic area served by participating shelters during 1980–1995(397). The implementation of a similar screening program inshelters in Denver, Colorado, in 1995 led to lower rates ofactive TB and reduced transmission of TB disease, as demonstratedby less genotype clustering by DNA fingerprinting (167). Bothscreening programs were based on symptom evaluation, tuberculinskin testing, and chest radiography. The decrease in TB morbidityin both these studies was attributed to shelter-based case detectionthrough screening activities.
CASE MANAGEMENT.
Completion of treatment for active TB is more difficult forhomeless persons, particularly those who report substance abuse,including alcohol abuse (395). Homeless persons with activeTB are at high risk for poor adherence even with enhanced DOTand are more likely to default and move from the area of initialdiagnosis. They are also more likely to have legal action takenin the form of court-ordered treatment or detention. Comprehensivecase management that includes a variety of incentives and enablers,including food, temporary housing, transportation vouchers,and treatment for substance abuse and mental illness has improvedrates of treatment completion in this population.
Costs for homeless persons who are hospitalized for initialtreatment of active TB have been $2,000 more than costs forpersons who were not homeless (398). Excess hospital utilizationcould be attributable to social considerations, clinical indications(especially the need to render a patient noninfectious beforedischarge to a congregate living setting), or concerns aboutadherence to the plan of treatment. In San Diego, California,a novel housing program that used hostels facilitated the completionof treatment of TB in homeless persons (399). Completion ratesof 84 to 100% were achieved for persons housed at a designatedhostel in 1995. Certain TB-control programs in cities with substantialhomeless populations routinely provide temporary or longer termhousing in attempts to improve completion of treatment. TheCalifornia Department of Health allots funds for temporary housingof persons with TB to each of its county and local jurisdictions.The U.S. Department of Housing and Urban Development also providesfunding for housing patients with TB.
The beneficial impact on treatment outcomes of an integratedapproach to managing homeless patients with TB has been emphasized(394). For example, a social care and health follow-up programamong homeless patients in Spain was associated with a decreasein TB rates from 32.4/100,000 in 1987 to 19.8 cases/100,000in 1992, and better completion rates and reduced costs for hospitalizationswere also documented (400). In Massachusetts, 58 (34.5%) of214 persons hospitalized in a dedicated inpatient unit for difficultpatients with TB during 1990–1995 were homeless (401).Regardless of the case-management plan that is chosen, all suchinterventions should take into consideration the importanceof addressing major gaps in knowledge, attitudes, and beliefsabout TB among homeless persons (181).
CONTACT INVESTIGATION.
Contact investigations for cases of TB among homeless personsare particularly challenging. Homeless patients with TB oftenfail to identify contacts during routine investigation (30).Completing a contact evaluation in identified contacts and completingtreatment for LTBI among contacts that are homeless are oftendifficult (320, 391, 402). Interpretation of the results oftuberculin skin testing of contacts of homeless cases is problematicbecause the background prevalence of positive tuberculin skintests in the population is usually higher than that of the generalpopulation. As with contact investigations among other populationsat high risk, discerning when a contact investigation has becomea targeted testing program is often difficult. A proposed alternativeapproach to conducting contact investigations of homeless personsis to focus on possible sites or locations of exposure, suchas shelters (391, 393).
TARGETED TESTING FOR AND TREATMENT OF LTBI.
When homeless persons are identified as a population at highrisk on the basis of the local epidemiology of TB, targetedtesting and treatment protocols tailored to local circumstancesshould be developed. However, low rates of completion of therapyfor 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 isoniazidtherapy and 84 (20%) completed treatment (184). In another studyconducted in San Francisco, California, during 1991–1994that was designed to improve adherence, two novel interventions(biweekly preventive DOT with either a $5 incentive or a peerhealth adviser) were compared with the usual method of self-supervisedtreatment (402). Even though completion of treatment was nothigh for any of the three groups, multivariate analysis indicatedthat independent predictors of completion were being offeredthe monetary incentive and residence in a hotel or other stablehousing at entry into the study. That report confirmed an earlierfinding that advocated offering monetary incentives (320).
INSTITUTIONAL AND ENVIRONMENTAL CONTROLS.
Efforts have been made to reduce transmission of TB in sheltersfor homeless persons by enhancing institutional control measures.These efforts have included reducing shelter size (13), improvingventilation systems, and using germicidal ultraviolet light(280).
Control of TB among Detainees and Prisoners
Correctional facilities in the United States include jails andprisons, which serve different but complementary functions.Jails serve as pretrial detention centers and house persons(detainees) awaiting trial and those sentenced to less than1 year of incarceration. Local and county governments operatethe majority of jails. Jails are characterized by rapid turnoverof detainees with short lengths of stay. Prisons serve as sitesof detention for persons (prisoners) who have been sentencedand will be incarcerated for a known length of time, generallymore than 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 detainedin jails. Approximately 6 million persons are incarcerated injails or prisons each year for variable lengths of time (124,125).
Detainees and prisoners represent the poorest and most medicallyunderserved segments of the U.S. population, the same populationsegments at risk for LTBI and TB disease (124, 252, 253). Personsentering prisons have usually spent time in jail, and detaineesand prisoners eventually reenter the community. Consequently,TB outbreaks among detainees, prisoners, and the general populationof a geographic area are interrelated (127, 403), and closecoordination of TB-control activities is needed between healthprograms in correctional facilities and jurisdictional publichealth agencies.
Prisons have long been identified as sites of transmission ofM. 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 acquisitionof TB (127, 250, 256), an indication that jails often are alsosites of transmission. Correctional facilities are among themost important sites of transmission of M. tuberculosis in theUnited States.
Failure to detect TB in correctional facilities results in TBoutbreaks, 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 ofthe 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. tuberculosistransmission, 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 andamplifying the reservoir of TB in the United States (127, 405,407), little is known about the optimal means of case detectionof TB among detainees and prisoners. The majority of prisonshave adopted a case-detection strategy that is based on a surveyof TB symptoms obtained on admission, in which all entrantsare tested for M. tuberculosis infection 14 days or less afteradmission; universal chest radiographs of all entrants are rarelyoffered (410). No data have been published supporting the effectivenessof symptom surveys and testing for M. tuberculosis infectionfor detecting cases of TB and preventing transmission withinjail systems, although screening by tuberculin skin testingwas effective in controlling TB in one prison system (411).Certain substantial urban jails perform chest radiographs onall persons entering the institution in an attempt to minimizetransmission of TB (283, 412), and data indicate that this approachis cost-effective (412). Because nearly all prison entrantshave first been detained in a jail system, effective TB case-detectionprograms in jails will substantially decrease the probabilitythat persons with undetected active TB will be admitted to prison.
Once cases are detected, strategies similar to those used inthe community have led to high rates of successful treatmentcompletion (413). A particular problem for case management ina jail setting is the unanticipated release of detainees, whichoften precludes the development of an effective discharge plan.Strategies to better coordinate discharges with public healthauthorities should be promoted.
CONTACT INVESTIGATION.
Continuing outbreaks of TB in correctional facilities (37, 139)underscore the importance of prompt and thorough contact investigationsin jails and prisons. Contact investigations in correctionalfacilities involve two steps: (1) identifying and evaluatingpersons exposed before the source-case was incarcerated and(2) identifying and evaluating persons exposed during incarcerationof the source-case. Effective case detection is important tolimit the size of the latter group. Contact investigations oftenneed to be conducted broadly, among more than one facility,because of the movement of detainees within the correctionalsystem (414).
Conducting contact investigations based on the concentric circlemethod is difficult in correctional institutions. Frequently,a single infected person can expose up to several hundred personsboth before and after incarceration. Cases involving personswho were exposed before incarceration should be managed by thejurisdictional public health agency for the community in whichthe person lived before arrest. For the jurisdictional publichealth agency to carry out those contact investigations effectively,prompt notification and case reporting by the detention facilityis necessary. Guidelines for conducting contact investigationsin jails have been published (258).
TARGETED TESTING AND TREATMENT OF LTBI.
Targeted testing and treatment of latent TB among detaineesand prisoners has been described in detail (415–417).Because of the high risk for transmission of M. tuberculosisin correctional facilities, inmates incarcerated for more than14 days usually receive a test for M. tuberculosis infectionas part of TB case detection. Detainees and prisoners with LTBIoften are considered to be candidates for treatment of latentTB (124, 252, 253). Prisons often are an ideal setting for effectivetreatment of LTBI because of known location of the patient,length of stay, prohibition of illicit drugs and alcohol, anda predictable diet. Nevertheless, achieving high rates of completionof treatment for LTBI in prisons or jails has been difficult(257, 416, 417).
The majority of jail detainees are released in 14 days or lessof entry. If treatment for LTBI is started in the jail setting,community follow-up after release from jail is essential. Withoutspecific interventions to assure such follow-up, the probabilityof completion of treatment might be less than 10% (256, 257,418). Recent developments in short-course treatment of latentTB with a combination of rifampin and pyrazinamide for 2 monthsoffered promise in improving treatment completion rates (419).However, the toxicity of this regimen precludes its routineuse (324), and this combination should generally not be usedfor the treatment of LTBI in correctional settings because therates of toxicity have been similar to those observed in thewider community. In addition, detainees and prisoners have highrates of hepatitis C infection, making them especially proneto serious hepatotoxicity.
INSTITUTIONAL INFECTION CONTROL.
Correctional institutions have been sites of virulent outbreaksof TB, including multidrug-resistant TB, that have involvedHIV-infected inmates and staff (37, 139, 405, 408). Common findingsin these outbreaks have included the failure to isolate personswith active TB quickly. Another common finding has been diseaseassociated with rapid transmission of M. tuberculosis when immunosuppresseddetainees and prisoners are housed together. An effective infection-controlprogram can decrease the likelihood of TB transmission in correctionalinstitutions (420). Guidelines to assist correctional institutionsin developing effective infection-control programs have beenpublished (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 settingswhere patients with infectious TB congregated closely with susceptiblepersons (52–54, 170, 421). This epidemiologic diseasepattern had not been recognized in the United States since thedevelopment 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), andHIV-infected persons were prominent among those who contractedM. tuberculosis infection and rapidly acquired TB disease (52–54,170, 406, 408). Although incidence of TB in health care facilitieshas been markedly reduced because of the development and deploymentof effective infection-control measures (56, 422–424)and decreasing incidence of TB in different communities, TBdisease attributable to recent transmission of M. tuberculosisin other settings has not only persisted but has been recognizedin a wide variety of sites and settings and become an establishedepidemiologic pattern.
As a consequence of the changed epidemiology of TB in the UnitedStates, the primary strategies now required to control the diseaseinclude measures for its prevention in settings in which a riskfor transmission of M. tuberculosis exists (Box 4). Recommendationsfor infection-control measures in high-risk settings are providedin this statement. The approach to control of TB and other airborneinfections that was developed for health care facilities (10)is the most successful model and is outlined in detail in thisstatement. Recommendations are also provided for control oftransmission of M. tuberculosis in extended care facilities,correctional facilities, homeless shelters, and other high-risksettings.
Strategies for control of TB in health care facilities, whichalso are applicable for other settings in which high-risk personscongregate, are based on comprehensive guidelines issued byCDC in 1994 (10). New CDC guidelines for preventing transmissionof M. tuberculosis in health care facilities will be publishedin 2005. A draft of these guidelines has been published in theFederal Register (Draft Guidelines for Preventing the Transmissionof Mycobacterium tuberculosis in Health-Care Settings. FederalRegister 2004; 69: 70457–70458). In the assessment ofinstitutional risk for TB, three levels of risk (low, medium,and potential ongoing transmission) are recommended, based onthe recent experience with TB in the institution and in thecommunity it serves. The recommended frequency of testing ofemployees for M. tuberculosis infection varies, depending onthe institution's level of risk. The tuberculin skin test isrecommended for testing HCWs and other employees with a riskfor exposure to M. tuberculosis. QFT-G is also approved fordetecting LTBI; guidelines for the use of QFT-G will be publishedin the Morbidity and Mortality Weekly Report.
The risk for TB associated with health care facilities is relatedto the incidence of TB in the community served by the facilityand to the efficacy of infection-control measures (422). Implementationof infection-control guidelines (10) has markedly reduced riskfor exposure to TB in health care facilities during the pastdecade (56, 422–424) and has also contributed to the decreasingnumbers of TB cases. Implementation of effective infection-controlmeasures in the medical workplace is thus an important elementof broader national and international strategies to preventtransmission of TB (244).
Epidemiologic investigations of the early outbreaks of TB inhealth care facilities, including those involving multidrug-resistantcases, indicated that transmission usually occurred becauseof failure to identify and isolate patients with infectiousforms of TB. In certain instances, diagnosis of TB was delayedas a result of the atypical presentation of TB among patientswith HIV infection, especially those with low CD4 counts. Transmissionwas also facilitated by (1) the intermingling of patients withundiagnosed TB with patients who were highly susceptible, (2)inadequate laboratory facilities or delayed laboratory reporting,and (3) delayed institution of effective therapy. Other factorsfacilitating transmission included a lack of negative pressurerespiratory isolation rooms, recirculation of air from respiratoryisolation rooms to other parts of the hospital, failure to isolatepatients until they were no longer infectious, allowing isolatedpatients to leave their rooms without wearing a mask, and leavingrespiratory isolation room doors open (52–54, 170, 421,425, 426).
CDC guidelines recommend a hierarchy of TB infection-controlmeasures (10). In order of importance, these measures are administrativecontrols, engineering controls, and personal respiratory protection(Box 7). Administrative controls consist of measures to reducethe risk for exposure to persons with infectious TB, includingscreening of patients for symptoms and signs of TB at the timeof admission, isolating those with suspected disease, establishinga diagnosis, and promptly initiating standard therapy (5). Engineeringcontrol measures are designed to reduce dissemination of dropletnuclei containing M. tuberculosis from infectious patients andinclude the use of airborne-infection isolation rooms. The thirdlevel (and the lowest on the hierarchy of controls) is the useof personal respiratory protection devices such as N-95 respirators.Respirator usage for the prevention of TB is regulated by theOccupational and Health Safety Administration under the generalindustry standard for respiratory protection (29 C.F.R. 1910.134[2003]).
BOX 7. PRINCIPLES OF CONTROL AND PREVENTION OF TB IN HEALTHCARE FACILITIES, BY STRENGTH OF RECOMMENDATION AND QUALITY OFEVIDENCE*
A TB infection-control program should be establishedin all health care settings (sites that provide care to patientswith TB and sites that refer such patients to other facilities)to prevent transmission of M. tuberculosis. A hierarchy of controls(i.e., administrative, engineering, respiratory protection)should be implemented (AII).
A risk assessment should be implementedto determine the appropriate level of controls to implement.The risk assessment will also determine the frequency of testingof HCWs for latent TB infection (AIII).
BOX 7 CONTINUED
Administrativecontrols, designed to ensure the prompt recognition, isolation,diagnosis, and treatment of patients with infectious TB, arethe most important elements of an infection-control program(AII).
A high index of suspicion for TB should be maintainedby health care providers. Airborne-infection isolation shouldbe implemented for patients as soon as TB is suspected, whetherduring emergency care, during hospital evaluation, or in a clinicsetting (AIII).
When indicated, standard therapy for TB shouldbe promptly initiated, and the diagnosis confirmed or excludedas soon as possible (AII).
Surveillance should be conductedto ensure that rooms for airborne-infection isolation are functioningproperly. A risk assessment should determine the number of roomsfor airborne-infection isolation that are needed (AIII).
Institutionsthat do not provide care to persons with TB should have a planfor isolation and prompt transfer of suspected patients to otherfacilities (AIII).
Patients with infectious TB should be dischargedfrom hospital only when arrangements have been made to preventcontact with susceptible individuals (AIII).
Health care facilitiesshould cooperate closely with public health agencies to ensurethat patients with TB receive adequate planning for outpatientmanagement to ensure that treatment is continued until a completecourse of curative therapy has been administered (AIII).
AllHCWs should undergo baseline testing for latent TB infection.The frequency of subsequent testing should be based on resultsof the risk assessment. Employees with latent TB infection shouldbe encouraged to start and complete treatment, if indicated.Surveillance and analysis of results of serial testing of employeesfor M. tuberculosis infection should be conducted (AII).
Employeesshould regularly receive education on TB (AIII).
In implementing a comprehensive infection-control program forTB, institutions should first conduct a risk assessment to determinewhat measures are applicable. Risk for transmission of M. tuberculosisvaries widely, and procedures that are appropriate for an institutionin an area of high TB incidence (e.g., an inner-city hospitalor homeless shelter in a metropolitan high-incidence area) differfrom those applicable to an institution located in a low-incidencearea that is rarely used by patients with TB. The jurisdictionalpublic health TB-control program should assist in the developmentof the assessment, which should include data on the epidemiologyof TB in the community served by the institution and the numberof TB patients receiving evaluation and care.
The institutional risk for TB can be stratified according tothe size of the institution and the number of patients withTB as low risk, medium risk, or potential ongoing transmission.Hospitals with 200 beds or more that provided care for fewerthan six patients with TB during the previous year are categorizedas low risk, whereas those that cared for six or more patientsare categorized as medium risk. For hospitals with fewer than200 beds, those with fewer than three patients with TB in theprevious year are considered low risk, and those with threeor more cases are considered medium risk. Outpatient clinics,outreach programs, or home health settings that provide carefor fewer than three patients with TB per year are consideredlow risk, and those that care for three or more patients areconsidered medium risk. TB clinics, outreach programs, and othersettings in which HCWs are responsible for the care of personswith TB are classified as medium risk. Any institution, clinic,or setting with evidence of recent patient-to-patient or patient-to-employeetransmission of M. tuberculosis or of ongoing or unresolvedtransmission should be classified as having potential ongoingtransmission until effective control measures have been implementedand transmission is interrupted. Potential ongoing transmissionis a temporary classification.
When transmission of M. tuberculosis is suspected at a facility,an immediate investigation should be undertaken that includesconsultation with public health officials or experts in hospitalepidemiology and infection control. Evidence of potential transmissionof M. tuberculosis includes clusters of conversions of testsfor M. tuberculosis infection among employees from negativeto positive, increased rates of positive tests for M. tuberculosisinfection among employees, an employee with potentially infectiousTB, unrecognized TB among patients or employees, and recognitionof identical strains on genotyping of M. tuberculosis isolatesfrom patients or employees.
How often employees at health care facilities and other at-risksites for M. tuberculosis infection are tested depends on therisk assessment. The positive predictive value of the tuberculinskin test is low when populations with a low prevalence of infectionwith M. tuberculosis are tested (424, 427). Consequently, frequenttesting by using that method in low-incidence, low-risk settingsis discouraged. In addition, false-positive tests have beenreported when institutions changed brands of purified proteinderivative (PPD) reagent, for example from Tubersol to Aplisol(427).
At the time of employment, all HCWs should undergo baselinetesting (with two-step testing if the tuberculin skin test isused 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 settingsonly if exposure to a patient with infectious TB (i.e., a patientnot initially isolated but later found to have laryngeal orpulmonary TB) has occurred. Institutions in which ongoing transmissionof M. tuberculosis is documented should carry out testing forM. tuberculosis infection of HCWs at risk every 3 months untiltransmission has been terminated.
Employees testing positive for M. tuberculosis infection shouldreceive a chest radiograph to exclude TB disease and shouldbe evaluated for the treatment of LTBI based on current recommendations(4, 324). Compliance with therapy for LTBI among HCWs, includingclinicians, has historically been poor (428–430). Employeehealth clinics and infection-control departments should emphasizeto HCWs the importance of completion of therapy for LTBI. Ina comprehensive infection-control program that encourages HCWsto complete treatment for LTBI, higher completion rates havebeen 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 twiceas likely to acquire TB as those living in the community (252,433, 434). Certain considerations for control of TB in hospitalsapply also to extended care facilities, including (1) maintaininga high index of suspicion for the disease, (2) promptly detectingcases and diagnosing disease, (3) isolating infectious personsand initiating standard therapy, (4) identifying and evaluatingcontacts, and (5) conducting contact investigations when indicated.The value of treating LTBI in elderly residents of nursing homesso as to prevent future outbreaks has been documented (435).
In 1990, CDC published recommendations for TB control in extended-carefacilities (433). Those long-term care facilities that do nothave airborne-infection isolation rooms should transfer patientssuspected to have infectious TB to other facilities (includingacute-care hospitals) until the disease is ruled in or out andtreatment is started if indicated and continued until the patientis noninfectious (10). The risk assessment and frequency oftesting for LTBI for employees at long-term care facilitiesare similar to those described previously. Residents shouldbe tested on admission to the facility and should provide ahistory and undergo physical examination to identify symptomsand signs of TB. Residents with LTBI should be offered treatmentaccording to current recommendations (4, 324), with carefulmonitoring for drug toxicity.
Correctional facilities.
Common findings in outbreaks of TB in correctional facilitieswere the failure to recognize and isolate patients with TB andrapid progression of outbreaks when immunosuppressed detaineeswere housed together (405, 406, 408). Because of the substantialnumbers of cases of TB infection and disease that might resultfrom outbreaks at correctional facilities and the natural movementof inmates from incarceration to the general population, correctionalfacilities should be viewed as being among the most importantsites 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 principlesdeveloped for health care facilities (10) are also applicableto correctional facilities. In prisons and jails, the most importantactivity in TB infection control is efficient detection of infectiousTB cases, including those that are prevalent among persons enteringthe facility and those that arise during detention. A promptdiagnostic evaluation, respiratory isolation (including transferout of the facility if airborne-infection isolation rooms arenot available), and institution of a standard treatment regimenare urgent priorities when suspected cases are encountered.If this process is delayed, a substantial number of personsmight be exposed as a result of the congregate living arrangementsthat 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 immediatelyonce a case of TB has occurred at a facility. In a study conductedin the Maryland state correctional system, prisons that conductedprograms for targeted testing and treatment of LTBI among inmatesexperienced lower rates of tuberculin skin test conversions,an indication that this measure can contribute to successfulinfection control (420). A template is now available to assistjails in instituting an effective infection-control program(258).
Shelters for homeless persons.
As with correctional facilities, homeless shelters are importantsites of transmission of M. tuberculosis and an important causeof the continuing high incidence of TB among the homeless population(33, 118). Effective infection-control strategies in those venuesare use of M. tuberculosis genotyping for rapid identificationof clustered cases and sites of transmission (27, 33), screeningshelter users for TB disease, wide-ranging contact investigations,and engineering controls, including ultraviolet germicidal irradiation(437). A systematic shelter-based program for targeted testingand treatment of LTBI in Denver was also demonstrated to decreaseincidence of TB in the homeless population (167).
Because crowding and poor ventilation are often prevalent inshelters, infection-control efforts should also include engineeringmodifications to decrease exposure to M. tuberculosis. A guideto assist shelters in improving the safety of their environmentthrough modifications in ventilation, air filtration, and theintroduction of ultraviolet germicidal irradiation has beenpublished (438).
Other high-risk settings.
As the incidence of TB has receded in recent years, new patternsof transmission have become evident. Epidemiologic investigationsprompted by an increase in the incidence in TB in a communityor state or by the identification of clusters of cases withidentical M. tuberculosis genotype patterns have detected transmissionin such venues as crack houses (137) and bars (27). In addition,transmission has been identified in association with certainsocial activities that are not typically considered in routinecontact investigations: a church choir (140), a floating cardgame (172), exotic dancers and their contacts (38), a transgendersocial network (34), and persons who drink together in multipledrinking establishments (439).
Although special techniques have been developed for exploringchains of transmission of M. tuberculosis in complex socialnetworks (439), transmission of M. tuberculosis in such settingsis not amenable to prevention by available infection-controlstrategies. These newly identified patterns of transmissionof M. tuberculosis might be too complex to be detected and controlledby traditional approaches, and real-time M. tuberculosis genotypingcapable of identifying unsuspected linkages among incident casesmight be increasingly useful (131).
This new TB threat, transmission in previously unknown settings,has emerged at a time when local TB-control programs often arenot prepared to respond. As TB morbidity decreases in the UnitedStates and TB-control programs necessarily contract, new approacheswill emerge, particularly in low-incidence areas. One modelenvisions that local public HCWs who do not work exclusivelyon TB are served by regional TB supervisors, who in turn aresupported by statewide consultants and CDC specialists (172).
Implementation of the recommendations contained in this statementwill likely improve TB control and allow progress to be madetoward eliminating TB in the United States. However, achievingTB elimination as defined by ACET (i.e., one annual case ofTB per 1 million population [11]) will require substantial advancementsin the technology of diagnosis, treatment, and prevention ofthe disease. IOM has estimated that at the current rate of decline,approximately 6% annually, eliminating TB in the United Stateswould take more than 70 years (2). New tools are needed forthe diagnosis, treatment, and prevention of TB to acceleratethe decline in TB incidence and reach the elimination thresholdsooner (1, 2, 45). In addition, improved tests for the diagnosisof TB and LTBI and more effective drugs to treat them are neededto reduce the substantial worldwide burden of disease and deathresulting from TB (44).
AFB smear microscopy and the tuberculin skin test, the mostcommonly 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 early20th century; and rifampin, the most recent novel compound fortreatment of TB, was introduced in 1963. In the long term, thedevelopment of a new and effective vaccine would have the greatestimpact on the global epidemic of TB, and the United States shouldlead the research and advocacy efforts to develop such a vaccine(180, 440). However, other advances in TB diagnosis and treatmentmight substantially improve the control of TB in the UnitedStates. Better means to diagnose and treat LTBI are needed immediately.Breakthrough diagnostics and drugs that would facilitate themore effective usage of this therapeutic intervention to preventTB would have an immediate and lasting effect on the incidenceof the disease in the United States by affecting at least threeof the major challenges to TB control in the United States:the substantial pool of persons with LTBI, TB among foreign-bornpersons, and TB among contacts of persons with infectious TB(Box 1).
Public health interventions to control TB should be based onpractices that have been demonstrated to be effective. Becausean established scientific basis is lacking for certain fundamentalprinciples of TB control, including certain recommendationscontained in this statement, logic, experience, and expert opinionhave been used to guide clinical and public health practiceto control TB. In the preparation of these recommendations forTB control, deficiencies in evidence were frequently noted.Better understanding is needed of which persons among the millionsof foreign-born persons that enter the United States each year(Table 8) are at sufficient additional risk for TB to warrantpublic health intervention. The approaches recommended for thedevelopment of programs for targeted testing of LTBI need additionalverification. The new concepts of identifying contacts of infectiousTB cases (439) require refinement. The optimal method of reducingthe concentration of M. tuberculosis in ambient air in venuessuch as homeless shelters is not yet defined (438). Methodsto 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 theincrease in TB among foreign-born persons, the upsurge in reportsof TB outbreaks, and the persistent high incidence of the diseaseamong U.S.-born non-Hispanic blacks. Epidemiologic studies,including economic analyses, are needed to augment surveillancedata and facilitate decisions about allocation of effort andresources to address newly identified facets of the epidemiologyof TB.
As new diagnostics are introduced to TB control, operational,economic, and behavioral studies will be needed to determinetheir most effective use. For example, QFT, a new diagnostictest for LTBI, was licensed in 2001, and early research indicatedthat this new test might have advantages over the tuberculinskin test in distinguishing between latent M. tuberculosis infectionand infection with nontuberculous mycobacteria or vaccinationwith BCG (102). However, guidelines on testing for LTBI recommendedthat QFT should not be used in the evaluation of contacts ofinfectious cases of TB, for children younger than 17 years,for pregnant women, or for patients with immunocompromisingconditions, including HIV infection, because of a lack of datafrom studies in those populations (103). A newer version ofthe test, QFT-G, was licensed in 2004. The role of this newtest in these populations has not been determined Thus, considerableresearch remains to be done to delineate the advantages thisnew 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 infectionremains a major barrier to TB elimination. As evidence of theimportance of that intervention, completion of a course of treatmentis the first national performance standard for TB (Table 4).For the outcome of TB treatment to be improved, both patientand health care provider behaviors related to adherence to TBtreatment must be understood, and that understanding shouldbe 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 compilethe results and identify best practices. Gaps in knowledge remain,and the need exists to develop and implement a comprehensivebehavioral and social science research agenda to address thesedeficiencies.
GRADED RECOMMENDATIONS FOR THE CONTROL AND PREVENTION OF TB
Laboratorians, clinicians, and public health officials shouldwork together to develop an integrated system that ensures timelylaboratory testing and flow of information among laboratorians,clinicians, and TB controllers (AIII).
Public health laboratoriansshould take a leadership role todevelop the laboratory systemand assure that essential laboratorytests for TB control areavailable, accessible, standardized,reproducible, and withhigh sensitivity and specificity (AII).
Public health laboratoriesshould educate laboratory staffs,health care providers, andpublic health officials about themost effective uses of clinicalmicrobiologic laboratory services.Such activities might includeeducation programs, developmentof web-based or written materials,or direct consultation (standardpractice [SP]).
All microbiologylaboratories should subscribe to specifiedturnaround times(Box 2) from date of specimen collection todate when the followingresults 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).
Thefollowing laboratory results should be reported immediately(preferably by electronic or fax transmission) by the testinglaboratory to the responsible clinician and to the jurisdictionalTB control program:
— a positive smear for AFB and thesubsequent growth detection(culture) result of that specimen;
— identification of M. tuberculosis complex in any specimen;and
— drug susceptibility test results, especially whenisolatesare drug resistant (AII); and
Clinical microbiologicallaboratories should include, as partof quality improvement,a plan for identification and reviewof possible false-positiveresults. Any false-positive resultshould trigger an inquiryand a plan of correction (SP) (155).
Recommendations for TB Case Detection
Steps recommended by IOM (2) to improve public knowledge andawareness about the risk factors for TB, symptoms of TB, andthe implications of the diagnosis of latent infection shouldbe undertaken by TB-control programs, community-based organizationsrepresenting populations at high risk, and academic health sciencesinstitutions. Targeted education of populations at high riskmight be particularly effective in neutralizing the stigma associatedwith TB among foreign-born populations on the basis of culturalbeliefs in their country of origin. Programs for patient educationshould always be designed with input from the targeted community(AII).
Because nonpublic health medical practitioners mostoften conductthe initial evaluation on persons who have symptomsrelatedto TB, health departments, academic institutions, andmedicalprofessional organizations should provide continuingeducationabout TB to their constituent health care providers.These effortsshould be focused on clinicians serving populationsat highrisk for TB on the basis of local or regional trendsin TB epidemiology(AIII).
Jurisdictional public health agenciesshould ensure that clinicianswho evaluate persons with suspectedTB have access to current,accurate, and timely diagnostic services(SP).
Guidelines for detection of TB cases in clinical settingsshouldbe followed by primary care, ED, and hospital-based practitioners(Table 5).
Screening for TB cases during contact and outbreakinvestigationsand during the evaluation of immigrants and refugeeswith classA/B1/B2 TB notification status has a high yield offinding cases(Table 6) and should be given high priority asa method forTB case detection (AII).
Public health programsshould identify other opportunities forscreening for TB diseaseon the basis of the local epidemiologyof TB, such as in congregatesettings, homeless shelters, andcorrectional facilities inwhich the consequences of an undiagnosedcase are severe. Allcase detection activities should be evaluatedperiodically todetermine 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 comprehensivecontact investigation program to ensure that contacts of infectiousTB cases are identified, access to adequate care is provided,and therapy is completed (AIII).
TB-control programs shoulddevelop a protocol for conductingcontact investigations thatidentifies persons responsible foreach step of the investigationand outline processes to maximizethe efficiency of the processwithin the framework of availableresources (AIII).
TB-controlprograms should have procedures for voluntary HIVcounselingand testing of contacts. Those procedures shouldset prioritiesfor HIV counseling and testing of contacts onthe basis of locallyderived data on the risk for HIV infectionamong contacts or,alternatively, on the local epidemiologyof TB and HIV infection(BIII).
Tuberculin skin testing of contacts should establishas firstpriorities those contacts who are at highest risk forprogressingfrom LTBI to TB disease on the basis of transmissionrisk assessmentand the presence in contacts of risk factorsfor progression(e.g., age < 5 years, HIV infection, andother immunocompromisingconditions (AII) (4).
DOT for LTBIshould be considered for all contacts. High-riskcontacts shouldreceive highest priority for directly observedtreatment (AIII).
TB-control programs should apply existing communicable diseaselaws that protect the health of the community to contacts whofail to comply with the examination requirements (BIII).
TB-controlprograms should develop guidelines, in conjunctionwith theprogram legal office and in compliance with HIPAA rule,forrelease of confidential information related to conductingcontactinvestigations (BIII).
TB-control programs should evaluatethe effectiveness and impactof contact investigations and developinterventions to improveperformance when indicated (BIII).
TB-control programs should develop outbreak response plansfortheir jurisdictions. These plans should include indicationsfor initiating the plan, notification procedures, compositionof the response team, source of staffing, plan for follow-upand treatment of contacts, indications for requesting assistancefrom 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 strategiesfor targeted testing and treatment of LTBI (i.e., the programsatisfies national objectives for management of TB cases andcontacts; Table 4), it should begin by identifying populationsand communities at high risk for LTBI within its jurisdictionand establish priorities for intervention (AIII).
Populationsand communities should be categorized on the basisof the expectedimpact and efficacy of targeted testing in thesetting. Tier1 groups (Box 6) should receive the highest priority,followedby groups in Tier 2 and Tier 3 (AII).
Once the targeted populationor community has been identified,strategic and operationaldecisions should be made on how bestto establish the targetedtesting and treatment program. Questionsto decide include whereto locate the program, how to identifyand allocate resources,what training is needed for practitionersand patients, andwhat data management needs exist. Focus groups,influentialcommunity leaders, associations and community actionagencies,religious organizations, coalitions, block organizations,andinformal community groups all can contribute to these decisions(AII).
Public health agencies that establish targeted testingand treatmentprograms should maximize patient convenience andacceptancethrough strategies such as employing, when possible,staff membersfrom the populations being served, medical translation,culturalawareness and sensitivity, flexible clinic hours, outreachservicesfor patient transport, and the use of incentives andenablers.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, substanceabuse centers, and homeless shelters) should receive full supportfrom the jurisdictional public health agency. Such support mightbe decisive in the success of non–public health targetedtesting and treatment programs. Types of support should includetraining and education of providers, patient education materials,provisions of medication, radiographs and other laboratory services,clinical consultation, and design of tracking and data managementsystems (AII).
Targeted testing programs should be routinelyand systematicallyevaluated for their effectiveness, efficiency,and impact. Programsthat are not effective should be improvedor 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 crucialto the prevention of TB among children (AII).
Contact investigationof adults with infectious TB is the mostimportant activityfor early detection of TB among children,identification ofchildren with LTBI who are at high risk forprogressing to primaryTB and its sequellae, and determinationof the drug susceptibilitypattern of the M. tuberculosis isolatecausing TB disease orLTBI in a child. Contact investigationsshould be timely andthorough, and adequate resources for themshould be made available.This should be one of the highestpriority goals of any TB-controlprogram (AII).
Children younger than 5 years who have beenidentified as contactsof persons with infectious TB shouldreceive a clinical evaluation,including a tuberculin skin testand chest radiograph, to ruleout active TB. Once active TBhas been ruled out, children withpositive tuberculin skin testresults should receive a fullcourse of treatment for LTBI.Those who have negative skin testresults should also receivetreatment for presumed LTBI. Thisintervention is especiallycritical for infants and toddlersyounger than 3 years but isrecommended for all children youngerthan 5 years. A secondtuberculin test is then placed at least3 months after exposureto infectious TB has ended. If the secondtest result is positive,treatment should be continued for afull course of treatmentfor LTBI. If the second test resultis negative, treatment maybe stopped (AII).
Case management.
DOT should be the standard of care for treatment of TB diseaseamong children and adolescents (AII).
As adherence to treatmentis no better for children than foradults, all efforts shouldbe made to support children and familiesthrough treatment ofTB through comprehensive case management(AIII).
Contact investigation.
Infants and younger children with primary TB disease are rarelyif ever contagious. They do not need to be excluded from activitiesor isolated in health care settings (AII).
Children and adolescentsof any age with characteristics ofadult-type TB (i.e., productivecough and cavitary or extensiveupper lobe lesions on chestradiograph) should be consideredpotentially contagious at thetime of diagnosis (AII).
Infants with suspected or provencongenital pulmonary TB shouldbe considered contagious andeffective infection-control measuresshould be undertaken (AII).
Adults who accompany and visit children with TB in healthcaresettings should be evaluated for TB disease as soon aspossibleto exclude the possibility that they are the sourcecase forthe child. These adults should have a chest radiographto ruleout pulmonary TB and to prevent the possibility of transmissionwithin the health care setting (AII).
Testing of the contactsof children younger than 4 years withLTBI is recommended forpersons sharing a residence with thechild or those with equallyclose contact. Such investigationsmay be performed by publichealth agencies or primary healthcare providers (BII).
Targeted testing and treatment of LTBI.
Contact investigations of adults with TB and targeted tuberculinskin testing of foreign-born children from countries with ahigh incidence of TB are the best and most efficient methodsfor finding children with LTBI (AII).
Because foreign birthin a country with a high prevalence ofTB is the greatest attributablerisk factor for LTBI, childrenborn in or with extensive travelto such countries should betargeted for testing for LTBI. Thisincludes foreign-born adoptedchildren. Testing for LTBI amongchildren with low risk forinfection should be avoided (AII).
A risk assessment questionnaire can be used to identify childrenwith risk factors for LTBI who should undergo a tuberculin skintest (AI).
A decision to place a tuberculin skin test is acommitment toarrange evaluation and treatment for LTBI (SP).
A tuberculin skin test should always be placed, read, andinterpretedby specifically trained persons (SP).
In general,foreign-born children with LTBI should be treatedwith isoniazidunless information exists linking them to a specificcase ofisoniazid-resistant TB (AIII).
DOT should be considered stronglyas the means of treatmentfor newborns and infants, contactsof persons with recent cases,and immunocompromised childrenand adolescents with LTBI becausethey are at greatest riskfor progression to TB disease (AIII).
Recommendations for TB Control among Foreign-born Persons Surveillance.
Public health agencies in states and communities with a substantialnumber of TB cases among foreign-born persons should developenhanced surveillance methods to gain a detailed understandingof the local epidemiology of TB among foreign-born persons.This is important for program planning and to ensure that recentlyarrived immigrants, refugees, and other foreign-born personsat high risk have access to medical and public health services(AIII).
Imported cases of TB present at the time of entryshould bedistinguished from incident cases (i.e., those thatarise duringresidence in the United States; AIII).
Casesof TB among persons granted temporary entry to the UnitedStatesas visitors, students, and temporary workers and unauthorizedaliens (Table 7) should be distinguished from those among foreign-bornpermanent residents (AIII).
Cases identified as a result oftargeted testing activitiesshould be distinguished from thoseidentified by noting symptomsof active TB (AIII).
For TBcontrol along the U.S.–Mexico border to be facilitated,a binational TB case definition and TB registry system shouldbe adopted and evaluated (AIII).
Case detection.
Jurisdictional public health agencies responsible for TB controlshould undertake or engage community groups to undertake educationcampaigns for foreign-born persons at high risk. These campaignsshould communicate the importance of TB as a personal and publichealth threat, the symptoms to look for, how to access diagnosticand targeted testing services in the community, and the conceptof LTBI. The purpose of this education is to destigmatize theinfection, acquaint the population with available medical andpublic health services, and explain the approaches used to treat,prevent, and control TB (AIII).
Public health agencies conductingTB-control programs shouldestablish liaisons with primary carephysicians, community healthcenters, hospital EDs, and otherorganizations that providehealth care for foreign-born populationsat high risk to provideTB publications and guidelines and educationabout the localepidemiology of TB (AIII).
Public health agenciesconducting TB-control programs shouldestablish liaisons withcivil surgeons within their jurisdictions.They should alsoensure that civil surgeons have access to recentTB publicationsand guidelines and that they promptly reportall suspected casesof TB (AIII).
CDC should provide standardized education andtraining programswith a formal certification process for panelphysicians andcivil surgeons. As part of the certification,continuing educationprograms should be required (AIII).
Federal,state, and local public health agencies should assignhigh priorityto the follow-up of immigrants with a class ATB waiver andclass B1 and B2 TB notification status (AII).
Case management.
Culturally appropriate case management should be instituted,including readily available professional translation and interpretationservices, for all foreign-born persons. If possible, outreachworkers should be from the patient's own cultural background(AII).
Contact investigation.
Local and state jurisdictions should assign high priority tocontact investigations of foreign-born persons with TB becauseof the high likelihood of identifying persons with LTBI as wellas secondary TB cases (AII).
Culturally sensitive and appropriatecontact investigation protocolsshould be established (AIII).
Targeted testing and treatment of LTBI.
In jurisdictions where foreign-born persons constitute a majorproportion of the TB burden, targeted testing and treatmentof LTBI for foreign-born persons at high risk (4) should beimplemented as a primary means of preventing TB in the community.The tiered approach (Box 6), which is based on access to thetarget populations and likelihood of implementing a successfulprogram, should be employed (AII).
In developing the planfor targeted testing and treatment ofLTBI among foreign-bornpersons at high risk, TB-control programsshould collaboratewith health care providers, neighborhoodhealth centers, andcommunity advocacy groups that serve andwork with the targetpopulations (AII).
The testing of immigrants and refugeeswith a class A TB waiverand class B1 and B2 TB notificationstatus for LTBI as wellas for active TB should always be prioritized(AII).
Targeted testing and treatment of foreign-born childrenat highrisk younger than 15 years should be a priority (SP).
When resources permit, DOT for LTBI should be used to ensurehigh completion rates (BII).
Jurisdictional public healthagencies should work with localcolleges and universities todevelop targeted testing protocolsfor foreign-born studentsat high risk and assist with treatmentof LTBI (BIII).
Recommendations for TB Control among HIV-infected Persons HIV counseling and testing.
Voluntary HIV counseling and testing is recommended for allpatients with TB and should be considered the standard of care.In extreme circumstances, if establishing priorities is necessaryas a result of resource constraints, patients aged 25 to 44years should receive highest priority (SP).
Clinic staff membersat sites where patients with TB are followedshould receiveup-to-date education and training on the mostcurrent conceptsand methodology of voluntary HIV counseling,testing, and referral.If on-site HIV testing is not feasible,TB facilities shouldhave well-established arrangements forreferral to other testingsites (SP).
Voluntary HIV counseling and testing should beoffered routinelyto contacts of HIV-infected TB cases (AII).
Voluntary HIV counseling and testing should be offered toallcontacts that are members of populations with a prevalenceofHIV infection of 1% or greater (302). In other communitiesandsettings, the decision of whether to routinely offer voluntaryHIV counseling and testing to contacts of persons with infectiousTB should be based on the local epidemiology of HIV infectionand TB. In communities or settings where populations at riskfor TB are also known to have high rates of HIV infection (e.g.,injection drug users in inner cities [317]), all contacts shouldbe routinely offered voluntary HIV counseling and testing. Incommunities and settings in which the HIV seroprevalence likelyapproaches that of the general U.S. population (< 0.1%),a risk-factor assessment for HIV infection should be includedin the evaluation of contacts of infectious cases, and contactswith clinical or behavioral risk factors for HIV infection (302)should receive voluntary HIV counseling and testing (AII).
Personswith LTBI who are members of populations with a prevalenceofHIV infection of 1% or greater should be routinely offeredvoluntaryHIV counseling and testing (302). Otherwise, the decisionofwhether to routinely offer HIV counseling and testing topersonswith LTBI should based on the local epidemiology ofHIV infectionand TB. In communities or settings where populationsat riskfor TB are also known to have high rates of HIV infection(e.g.,injection drug users in inner cities [317]), routinecounselingand testing among patients with LTBI is indicated.In othercommunities and settings where the HIV seroprevalenceis likelyto approach that of the general U.S. population (<0.1%),a risk-factor assessment for HIV infection should beincludedas a standard part of the initial evaluation for allpersonsdiagnosed with LTBI. Persons with clinical or behavioralriskfactors (302) should receive HIV counseling and testing(AII).
Routine periodic cross-matches of jurisdictional HIV and TBcase registries should be conducted to ensure completeness ofreporting of both diseases (SP).
Case detection.
Physicians who provide primary care to persons with HIV infectionor populations at increased risk for HIV infection should maintaina high index of suspicion for TB. Every patient in whom HIVinfection has been newly diagnosed should be assessed for thepresence of TB or LTBI. This should include a history for symptomscompatible with TB (e.g., cough of 2–3 weeks' duration,fever, night sweats, weight loss, or hemoptysis, or unexplainedcough and fever; Table 5) and of exposure to persons with TB.Physical examination should include examination of extrapulmonarysites, such as lymph nodes, and a chest radiograph should betaken to check for findings of current or previous TB. Testingfor M. tuberculosis infection by using the tuberculin skin testshould be conducted, and patients with 5 mm or more of indurationbe considered to have a positive test and should receive, inaddition to chest radiography, a clinical evaluation to ruleout TB (4) (SP).
Public health agencies conducting TB-controlactivities shouldmaintain close contact with HIV control programs,medical practitionersand clinics, community-based organizations,homeless shelters,correctional facilities, and housing facilitiesthat serve personswith HIV infection to ensure that a highindex of awarenessof TB is maintained by persons who provideservices at thosesites and by their HIV-infected patients (AIII).
Health care facilities, social service agencies, and worksitesthat serve patients with HIV infection should establishfirmlines of referral for patients with respiratory symptoms(AIII).
Case management.
Public health agencies conducting TB-control activities shouldhave access to consultants with expertise in managing HIV relatedTB (SP).
Management of TB and HIV infection should be effectivelyintegratedand should include a multidisciplinary team of providersandsupportive care (AIII).
Comprehensive case management,including DOT, is strongly recommendedfor persons with HIVinfection who have TB (AII).
HIV-infected patients with TBand a CD4 count of less than 100cells/µl should receiveDOT daily or three times per week(A1).
Contact investigation.
Contact investigations of persons with TB and known or suspectedHIV infection and those conducted in any circumstance in whichHIV-infected persons could have been exposed to a person withinfectious TB should have the highest priority and be completedwithout delay (AII).
Persons with known or suspected HIV infectionwho have contactwith a patient with infectious pulmonary TBshould be offereda full course of treatment for LTBI regardlessof the initialresult of tuberculin skin testing once activeTB has been ruledout (AII).
Targeted testing and treatment of LTBI.
Targeted testing and treatment for LTBI are strongly recommendedat the time the diagnosis of HIV infection is established (AII).
For HIV-infected persons whose initial tuberculin skin testis negative, repetitive testing is recommended (at least yearly)if the local epidemiologic setting indicates an ongoing riskfor exposure to TB (AII).
An HIV-infected patient who is severelyimmunocompromised andwhose initial tuberculin skin test resultis negative shouldbe retested after the initiation of antiretroviraltherapy andimmune reconstitution, when CD4 cell counts aregreater than200 cells/µl (AII).
HIV-infected personswho receive a diagnosis of LTBI shouldreceive high priorityfor DOT (BIII).
Institutional infection control.
HIV-infected persons should be advised that certain occupationsand activities increase the likelihood of exposure to TB. Theseinclude employment and volunteer work in certain health carefacilities, correctional institutions, and shelters for thehomeless, as well as in other high-risk settings identifiedby jurisdictional health authorities. The decision about continuingemployment or volunteer activities in a high-risk setting shouldbe made in consultation with a health care professional andbe based on factors such as the person's specific duties inthe workplace, prevalence of TB in the community, and the degreeto which precautions are taken to prevent TB transmission inthe workplace (AIII).
Recommendations for TB Control among Homeless Persons Surveillance and case detection.
Information on whether the person is homeless should be includedfor each reported TB case to determine the importance of homelessnessin the TB morbidity in the state or community. This is particularlyimportant for communities that provide shelters or other congregateliving facilities that are conducive to the transmission ofTB (AII).
In designing programs for control and preventionof TB in homelesspersons, public health agencies should workclosely with providersof shelter, housing, primary health care,treatment for alcoholismor substance abuse, and social servicesto ensure a comprehensiveapproach to improving the health andwelfare of this population(AIII).
Public health agenciesshould closely monitor the location,mode (i.e., screening orsymptomatic presentation), and timelinessof diagnosis of TBin homeless persons in their community anduse such data todevelop more effective control strategies (AIII).
Public healthagencies should identify providers of medicalcare for homelesspersons and facilities that serve homelesspersons (e.g., hospitalEDs and correctional institutions) toensure that practicesand procedures are implemented to readilydetect and reportsuspected cases of TB (AIII).
Providers of primary healthcare for homeless persons shouldbe knowledgeable about howto diagnose (Table 5), isolate, andreport suspected cases ofTB (AIII).
Public health agencies should have ready accessto an inpatientfacility for the isolation and induction phaseof therapy ofhomeless patients with infectious TB (AII).
Publichealth agencies should be prepared to conduct activitiestodetect TB among persons without symptoms and enhance TB casedetection 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 TBin the homeless population, and (3) evidence of current transmissionof TB in the population. Shelters should always be suspectedas sites of transmission (AII).
Case management.
Case management for homeless persons with TB should be structuredto encourage adherence to treatment regimens by making TB treatmenta major priority for the patient. It should include provisionof housing, at least on a temporary basis; an increasing numberof models have demonstrated the importance of a housing incentivein successful treatment of TB in homeless persons. Case managementshould also include establishing linkages with providers ofalcohol and substance treatment services, mental health services,and social services (AII).
Contact Investigation.
Health departments should regularly evaluate their methods forcontact investigation for cases of TB among homeless personsto identify barriers and develop alternative strategies, suchas shelter- or other location-based contact investigations orientedto possible sites of transmission. Factors to evaluate shouldinclude timeliness of completing contact investigations, numberof contacts identified and evaluated per case, proportion ofevaluated contacts with LTBI and TB disease, and completionof treatment of LTBI among contacts (AII).
Targeted testing and treatment of LTBI.
Targeted testing and treatment of LTBI should be a priorityfor homeless populations because studies from throughout theUnited States have demonstrated high rates of transmission ofM. 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 infectionamong homeless persons (AII).
When high rates of transmissionof M. tuberculosis are documentedamong homeless persons, thosewith a positive test for M. tuberculosisinfection should bepresumed to be recently infected and treatedfor LTBI (AIII).
Institutional and environmental controls.
Organizations that provide shelter and other types of emergencyhousing for homeless persons should develop institutional TB-controlplans. Guidelines to facilitate this process are available fromCDC (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 programfor detainees and prisoners entering the facility as well asfor those who become ill during incarceration to ensure promptisolation of contagious cases of TB (AII).
Strategies forcase detection for incoming detainees and prisonersincludesymptom surveys (BIII), testing for M. tuberculosisinfectionfollowed by chest radiography (BIII) for those witha positivetest, and universal chest radiography in jails (BII).In eachsetting, the adopted strategy should receive ongoingevaluation.
Each correctional facility's health care program for inmatesand staff should ensure that training in the clinical and publichealth aspects of TB and other diseases of public health significanceis provided in an ongoing manner (SP).
Detainees and prisonerswith signs and symptoms of TB shouldbe placed in respiratoryisolation on-site or off-site untilinfectious TB is ruled out(SP).
Case-management strategies including DOT and incentivesshouldbe used to assure completion of therapy of detaineesand prisonerswith TB (BII).
When detainees and prisonersreceiving therapy for TB are transferredto another facilityor released from detention, responsibilityfor continuationof the treatment plan should be transferredto the appropriatefacility or agency, and the jurisdictionalTB-control programshould be notified (SP).
Contact investigation.
Contact investigations of infectious TB cases in correctionsfacilities should receive equal priority as effective case detectionas the primary means of aborting TB outbreaks. Facilities shouldhave written procedures for contact investigations and haveadequate staff to ensure prompt and thorough contact investigations.They should also consult with the jurisdictional public healthTB-control program (AII).
Targeted testing and treatment of LTBI.
Prisons should implement a treatment program for prisoners withLTBI as part of the effort to prevent the transmission of M.tuberculosis within their walls and to contribute to the overallgoal of TB elimination (AII).
Treatment programs for LTBIin jail detainees should be undertakenonly if it is possibleto develop a successful plan for communityfollow-up of releasedpersons on treatment (AII).
Reducing the length of treatmentfor LTBI is more likely tolead to completion of treatment incorrectional facilities;4 months of rifampin is recommendedas an alternative for thetreatment of LTBI (4, 324). Correctionalhealth providers needto consider the costs and benefits ofthis regimen comparedwith the standard 9-month course of isoniazidin each individualcase (BIII).
Institutional infection control.
Jails and prisons should implement effective infection-controlprograms including risk assessment, staff training, screeningand treatment of LTBI, isolation of inmates with infectiousforms of TB, treatment and discharge planning, and contact investigation(AII).
HIV-infected detainees and prisoners should not behoused togetherin a separate facility unless institutionalcontrol programsfollowing current guidelines have been establishedand provedto be effective in preventing the transmission ofM. 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 fortransmission of M. tuberculosis should have in place a TB infection–controlprogram; they should implement and enforce procedures to promptlyidentify, isolate, and either manage or refer persons with suspectedand confirmed infectious TB (AII).
All health care institutionsthat care for persons with TB andother sites that are at riskfor transmission should implementTB infection-control measuresbased on a hierarchy of administrativecontrols, engineeringcontrols, and respiratory protection.Administrative controlsand early recognition of persons withTB are the most importantparts of an airborne infection controlprogram for TB (AII).
Employees who have first contact with patients in settingsthatserve populations at high risk for TB should be trainedto detectpersons who could have infectious TB. Patients shouldbe routinelyasked about exposure to M. tuberculosis, previousTB infectionor disease, current symptoms suggestive of TB,and medical conditionsthat increase the risk for TB. The medicalevaluation shouldinclude an interview conducted in the patient'sprimary language,with the assistance of a medical interpreterif necessary (AIII).
The index of suspicion for TB shouldbe very high in healthcare settings located in geographic areaswhere TB is prevalentand those serving patients at high riskfor TB. Guidelines existfor conducting an evaluation for suspectedpulmonary TB in adultsat high risk (Table 5; AIII).
Amongpersons suspected of having TB, arrangements should beavailablefor the diagnosis to be promptly established and standardtherapyinitiated (AII).
HCWs and employees in other high-risk settingsshould be testedfor M. tuberculosis infection on employment.Subsequent testingshould be based on risk assessment (AIII).
Health care facilities and other high-risk institutions shouldconduct a risk assessment to determine the frequency of testingfor M. tuberculosis infection among employees, as a componentof the proper level of TB infection control measures (AIII).
For HCWs and employees in other high-risk settings with nootherrisk factors for TB, a cut-off of 15 mm induration (ratherthan10 mm) on the tuberculin skin test should be used to definea positive baseline test at the time of initial employment.An increase of 10 mm or more in reaction size is generally acceptedas a positive test result on subsequent testing unless the workeris a contact of a TB case or has HIV infection or is otherwiseimmunocompromised, in which case a result of 5 mm or more isconsidered positive (AIII).
Employees with M. tuberculosisinfection should have a chestradiograph performed to excludeTB disease and should be evaluatedfor treatment of LTBI, basedon current recommendations (AII).
HCWs and employees in otherhigh-risk settings with an indicationfor treatment of LTBIshould be encouraged to initiate and completetreatment (AII).
Residents admitted to long-term care facilities should betestedfor M. tuberculosis infection on admission (with a two-steptest if using tuberculin skin testing) and should receive ahistory and physical examination to detect symptoms and signsof TB. Residents with M. tuberculosis infection should be offeredtreatment if indicated (4, 324), with careful monitoring fordrug toxicity (BII).
Jails and prisons should develop andimplement effective infection-controlprograms, including riskassessment, staff training, screeningfor TB among incomingdetainees and prisoners, isolation ofinmates with infectiousforms of TB, treatment and dischargeplanning, and prompt andthorough contact investigations (AII).
In jails and prisons,HIV-infected inmates should not be housedtogether in a separatehousing unit unless institutional controlprograms followingcurrent guidelines have been establishedand proved to be effectivein preventing the transmission ofM. tuberculosis (AII).
Organizationsthat provide shelter and other types of emergencyhousing forhomeless persons should develop institutional TB-controlplans.Guidelines to facilitate this process are available fromtheFrancis J. Curry National TB Center (403) (AII).
TB-controlprograms should remain aware of the possibility ofTB diseaseas a result of current transmission when conductingepidemiologicsurveillance and contact investigations. M. tuberculosisgenotypingshould be immediately available to any program thatis investigatingpossible transmission of M. tuberculosis (AII).
In an eraof declining rates of TB in the United States, expertiseinthe recognition, diagnosis, and treatment of TB is likelytodecline, especially in areas in which incidence is low (48).Because the risk for spread of M. tuberculosis increases whenthe diagnosis is not promptly made, institutional educationprograms for HCWs, including physicians in training, shouldbe made a continuing priority (AIII).
Recommendations on Research for Progress toward Elimination of TB
A comprehensive TB research plan for the United States shouldbe developed that identifies the major areas of need and themost effective research approaches to meet those needs. CDCand NIH should convene a broadly based group of experts andstakeholders to develop this plan (AIII).
The availabilityof improved diagnostic tests and therapiesfor LTBI would havean immediate and lasting impact on the incidenceof TB in theUnited States, and research in those fields shouldbe a priority(AIII).
Research leading to a new and effective TB vaccineis one ofthe most important contributions that the United Statescanmake to the global TB epidemic and should be a priority(AIII).
The CDC-funded Tuberculosis Epidemiological StudiesConsortiumand Tuberculosis Trials Consortium represent excellentnew modelsfor bringing resources from the federal government,public healthagencies, and academia together to plan and implementresearchfor the assessment of new diagnostics and drugs andepidemiologicand operational research on TB. These initiativesshould bea priority (AIII).
Because a substantial numberof recommendations for TB controlare based on logic, anecdotalexperience, and expert opinion,additional research, includingclinical, operational, behavioral,and economic research shouldfocus on unanswered questions relatingto the basic elementsof TB control (AIII).
THIS DOCUMENT WAS DEVELOPED BY AN AD HOC COMMITTEE OF THE AMERICANTHORACIC SOCIETY, THE CENTERS FOR DISEASE CONTROL AND PREVENTION,AND THE INFECTIOUS DISEASE SOCIETY OF AMERICA. THE MEMBERS AREAS FOLLOWS:
CHARLES M. NOLAN, M.D., Chair (ATS)
HENRY M. BLUMBERG, M.D., Co-chair (IDSA)
ZACHARY TAYLOR, M.D., Co-chair (CDC)
JOHN BERNARDO, M.D.
PATRICK J. BRENNAN, M.D.
NANCY E. DUNLAP, M.D., PH.D.
CHARLES L. DALEY, M.D.
WAFAA M. EL-SADR, M.D.
SUE ETKIND, M.S.
MARK FITZGERALD, M.D.
JAMES B. MCAULEY, M.D.
MARISA MOORE, M.D.
NOREEN L. QUALLS, D.P.H.
RANDALL R. REVES, M.D.
SARAH E. ROYCE, M.D.
MAX SALFINGER, M.D.
JEFFREY R. STARKE, M.D.
WANDA WALTON, PH.D.
STEPHEN E. WEIS, D.O.
JAN YOUNG, M.S.
Acknowledgments
The authors thank the following persons who provided constructiveand helpful insights: W. J. Burman, M.D., Denver Public Health,Denver, Colorado; E. P. Desmond, M.D., California Departmentof Health Services, Richmond; P. C. Hopewell, M.D., San FranciscoGeneral Hospital, University of California, San Francisco; A.Green Rush, Francis J. Curry National Tuberculosis Center, SanFrancisco, California; R. J. O'Brien, M.D., Foundation for InnovativeNew Diagnostics, Geneva, Switzerland; T. Oemig, Wisconsin Divisionof Public Health, Madison, Wisconsin; P. M. Small, M.D., TheBill and Melinda Gates Foundation, Seattle; G. Wang, M.D., PugetSound Neighborhood Health Centers, Seattle, Washington; K. G.Castro, M.D., M. F. Iademarco, M.D., L. Nelson, M.D., T. R.Navin, M.D., T. Shinnick, M.D., Division of TB Elimination,National Center for HIV, STD, and TB Prevention, CoordinatingCenter for Infectious Diseases, CDC. The authors also thankA. Lipavsky and B. Nodell who also assisted in the preparationof this report.
FOOTNOTES
THIS OFFICIAL JOINT STATEMENT OF THE AMERICAN THORACIC SOCIETY,THE CENTERS FOR DISEASE CONTROL AND PREVENTION, AND THE INFECTIOUSDISEASES SOCIETY OF AMERICA WAS APPROVED BY THE ATS BOARD OFDIRECTORS, JUNE 2004, THE CENTERS FOR DISEASE CONTROL AND PREVENTION,NOVEMBER 2004, AND THE IDSA BOARD OF DIRECTORS, MARCH 2005.
Conflict of Interest Statement: None of the members of the adhoc committee has a financial relationship with a commercialentity that has an interest in the subject of this manuscript.
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CONTENTS
SUMMARY
release assay result (e.g., QuantiFERON-TB Gold test [QFT-G]; Cellestis Limited, Carnegie, Victoria, Australia). The tuberculin skin test measures delayed-type hypersensitivity; QFT-G, an ex vivo test for detecting latent M. tuberculosis infection, measures a component of cell-mediated immune response (
(TNF-
1% [
5 years from countries with a high incidence of TB)
1910.134 [2003]). 
(AIII).