Guidelines for the Investigation of Contacts of Persons with Infectious Tuberculosis

The linkage between cases should be confirmed by genotyping results if isolates have been obtained (122). Any secondary case that is unexpectedly linked to a known index patient represents a potential failure of certain contact investigation, and therefore the strategy for the original investigation should be reassessed to determine whether the strategy for finding contacts was optimal and whether the priorities were valid or if additional contacts must be sought. If a secondary case occurred because treatment for a known contact with LTBI was not started or completed, then the strategies for treatment and completion should be reviewed.

An outbreak increases the urgency of investigations and places greater demands on the health department. Therefore, whenever possible, a suspected linkage between cases should be corroborated by genotyping results before intensifying an investigation. Even if genotypes match, an epidemiologic investigation is required for determining probable transmission linkages (122--125).

In an outbreak, contacts can be exposed to more than one case, and cases and contacts can be interrelated through multiple social connections which complicate efforts to set priorities. Social network analysis offers an alternative framework (see Other Topics) (126). The risk factors contributing to a specific outbreak should be determined, because these findings will affect the investigation and inform the strategy.

Contagious TB undiagnosed or untreated for an extended period, or an extremely contagious case. The challenges created by the extended infectious period include the patient's inability to remember persons and places and a greater number of contacts in a greater number of places. Social network techniques (see other topics) and setting-based investigations are proxy methods for finding contacts. A highly contagious case, sometimes with several pulmonary cavities or laryngeal disease, suggests a greater number of high-priority contacts. If an outbreak has been discovered, and if the patient has one of these forms of TB, any contacts who have indeterminate exposure data should be classified as high priority.

Sometimes a delay in treating TB is caused by failure to suspect TB or to report it. Opportunities for educating the providers should be pursued immediately, especially if contacts are likely to seek health care from the same providers.

Multidrug resistance can cause prolonged contagiousness if a standard treatment regimen for drug susceptible TB is being administered. This problem can be prevented by obtaining initial susceptibility results, by monitoring the patient's condition and response to therapy, and by suspecting MDR TB when the patient has treatment failure, relapse, or slow recovery from illness (127).

Source patient visiting multiple sites. A TB patient who has an active, complex social life and who frequents multiple sites where transmission of M. tuberculosis could occur is also less likely to be able to name all contacts. Proxy interviews (see Investigating the Index Patient and Sites of Transmission) and setting-based investigations are methods that supplement the patient's recall.

Patient and contacts in close or prolonged company. When an outbreak has been discovered, high priority is recommended for contacts having close or prolonged exposure.

Environment promoting transmission. A small interior space with poor ventilation can act as the focus of intense transmission of M. tuberculosis. High priority is recommended for all contacts who spent time with an outbreak source patient in such spaces, even if the periods of exposure were brief or unknown.

Certain larger environments (e.g., a warehouse worksite or a school bus [128,129]) have been reported as sites of intensive transmission when patients were highly contagious or when patients and contacts were in prolonged company. If the evidence from the investigation indicates a link between the site and transmission in an outbreak, the contacts in such a site should be designated as high priority, regardless of the site's characteristics.

Contacts very susceptible to disease after M. tuberculosis infection. Urgency is required when outbreak cases are diagnosed in contacts who are relatively more susceptible to progression from M. tuberculosis infection to TB disease. Other contacts with similar susceptibility should be sought. If such an outbreak includes children aged <5 years, a source-case investigation should be undertaken if the contagious source is unknown initially (see Source-Case Investigations). Intensified methods for active case finding among contacts are recommended.

Gaps in contact investigations and follow-up. Omissions, errors, and system failures can resurface later in the form of secondary TB cases (i.e., an outbreak). Tracing back cases in an outbreak indicates whether prevention opportunities were missed in previous contact investigations or other prevention activities (e.g., targeted testing).

Extra-virulent strain of M. tuberculosis. The existence of such strains has not been demonstrated. Determining which strains are more infective or pathogenic for humans is not yet possible, and the relevance of greater/faster pathogenicity of certain strains in laboratory animals is not fully understood yet (58,128,130).

Congregate Settings

Overall concerns associated with congregate settings include 1) the substantial numbers of contacts, 2) incomplete information regarding contact names and locations, 3) incomplete data for determining priorities, 4) difficulty in maintaining confidentiality, 5) collaboration with officials and administrators who are unfamiliar with TB, 6) legal implications, and 7) media coverage. Certain settings require intensified onsite approaches for ensuring that contacts are completely evaluated and for meeting objectives for treating LTBI. Requests for supplemental resources are recommended when the scope or duration of an investigation is expected to disrupt other essential TB control functions.

Maintaining confidentiality for an index patient is difficult if the patient was conspicuously ill or was absent from the setting while ill (see Data Management and Evaluation of Contact Investigations). Permission should be sought from the index patient before sharing information with any officials (e.g., supervisors, managers, or administrators) at the setting. Collaboration with officials at the setting is essential for obtaining access to employee and occupancy rosters, ascertaining contacts, performing onsite diagnostic evaluations or treatment, and offering education to associates (e.g., classmates, friends, or coworkers) of the index patient.

For congregate settings, the types of information for designating priorities are site specific, and therefore a customized algorithm is required for each situation. The general concepts of source-case characteristics, duration and proximity of exposure, environmental factors that modify transmission, and susceptibility of contacts to TB should be included in the algorithm (see Decisions to Initiate a Contact Investigation, Index Patient and Sites of Transmission, and Assigning Priorities to Contacts).

The optimum approach for a setting-based investigation is to interview and test contacts on site. If this is not possible, then the contacts should be invited for evaluation at the health department, which should consider having additional personnel or extended hours. As a last resort, contacts can be notified in writing to seek diagnostic evaluation with their own health-care providers. In this case, the letter should inform health-care providers regarding the TB exposure (including drug susceptibility results), diagnostic methods (including a 5 mm skin test cut point), treatment recommendations for LTBI, and a reference telephone number at the health department for obtaining consultation. Health-care providers also should receive a form for each contact that can be used to return diagnostic results and treatment decisions to the health department.

Certain congregate settings create opportunities for efficient onsite supervision of treatment for numerous contacts. Treatment can be delivered by having health department personnel visit the setting twice weekly for intermittent therapy, or by collaborating with a health professional hired by the setting. Arrangements are needed to maintain confidentiality with this approach. Officials and administrators at the setting are likely to be concerned regarding liability, which can be addressed in advance with legal counsel.

For constructive media coverage, the health department should collaborate with the setting in focusing on clear, consistent information. News reports that are factually accurate and that correctly describe the role of the health department can facilitate the investigation (see Communicating Through the News Media).

Correctional Facilities

The Advisory Council for the Elimination of Tuberculosis (ACET) has issued guidance on preventing and controlling TB in correctional facilities (131). Jails and prisons have been implicated in TB outbreaks (132--135). Multiple factors can hinder contact investigations. The best preparation for conducting contact investigations in jails and prisons is preexisting formal collaboration between correctional and public health officials. If collaboration has not been established before a contact investigation is needed, creating it as part of the investigation is necessary.

Certain correctional populations have a high prevalence of HIV infection, and reviewing the HIV testing policies, procedures, and aggregate statistics is recommended. If inmates have not been offered voluntary counseling, testing, and referral for HIV infection, and TB exposure is suspected, offering voluntary HIV counseling, testing, and referral is strongly recommended.

Inmates move about within correctional facilities on both daily and weekly schedules that can affect TB exposures. In addition, inmates are transferred within and between jails or prisons. Certain correctional settings have convenient, comprehensive longitudinal records for the locations of inmates that are essential for drawing up contact lists, estimating exposure periods, and assigning priorities to contacts. A tour of exposure sites within each setting helps in estimating exposure intensity.

Prisons typically have onsite health services, but jails might not. Certain prisons and jails test new inmate admissions and employees for M. tuberculosis infection, and certain prisons have periodic surveillance testing of employees, inmates, or both. Health-care providers in an onsite system can provide invaluable assistance in reviewing health records and evaluating and treating contacts. If medical record data (e.g., previous exposure and skin test results) cannot be retrieved rapidly, health department officials should consider requesting additional resources.

Investigations in jails can be especially challenging because of rapid turnover of inmates and crowding. The number of contacts who had close proximity to an index patient/inmate can be great, and yet exposure might be brief. This complicates the process of assigning priorities. Unless tracking records for inmates who were in a confined space with an infectious TB patient allow a determination that aggregate exposure was brief (e.g., <8 hours), these contacts should be assigned high priority. High-priority contacts who are transferred, released, or paroled from a correctional facility before medical evaluation for TB should be traced.

Unless they have been released or paroled, prison inmates with LTBI can complete a treatment regimen while incarcerated. In contrast, inmates in jails who are contacts are unlikely to be able to complete treatment while incarcerated. A low completion rate is anticipated when inmates are released or paroled unless follow-through supervision can be arranged.

Workplaces

A substantial number of persons spend the majority of their waking hours in their workplaces, which can be crowded. Duration and proximity of exposure can be greater than for other settings. Details regarding employment, hours, working conditions, and workplace contacts should be obtained during the initial interview with the index patient (see Investigating the Index Patient and Sites of Transmission), and the workplace should be toured after accounting for confidentiality and permission from workplace administrators or managers. Employee lists are helpful for selecting contacts, but certain employees might have left the workplace and thus been omitted from current employee lists.

Occasional customers of a business workplace (e.g., intermittent visitors to a fast-food restaurant) should be designated as low-priority contacts. Customers who visit a business workplace repeatedly should be assigned priorities as in other investigations (see Assigning Priorities to Contacts), especially susceptible or vulnerable contacts.

Workplace administrators or managers are likely to express concern regarding liability, lost productivity, and media coverage. In addition, they might have limited obligations to protect patient confidentiality. All these issues can be addressed during planning. For example, the assistance of the health department's media relations specialist can be offered to the workplace. For questions of liability and requirements under law, discussions between the health department's and the workplace's legal counsels are recommended.

Hospitals and Other Health-Care Settings

Nearly every type of health-care setting has been implicated in transmission of M. tuberculosis, and guidance on preventing transmission has been provided by CDC, the Healthcare Infection Control Practices Advisory Committee, and other organizations (42,136). State governments have different degrees of regulatory authority over health-care settings. Personnel collaborating with hospitals and other health-care entities should have knowledge of applicable legal requirements.

Infection control practitioners, although vital partners in these settings, might not be familiar with TB contact investigations. Multiple settings have engineers who can describe and test the environmental systems. Such an investigation should be planned jointly as a collaboration between the setting and the health department. Initial discussions should include data sharing and divisions of responsibilities. Liability, regulations, confidentiality, media coverage, and occupational safety are complex for health-care settings. Occupational Safety and Health Administration rules, which are interpreted differently by different jurisdictions, might require hospital administrators to report when employees are reported to be infected from occupational exposure. Public health officials should consider inviting legal counsel to the initial planning sessions with health-care administrators.

The majority of health-care settings have policies for testing employees for M. tuberculosis infection at the time of employment and, in settings where exposure is anticipated, periodically thereafter. Test results are helpful as baseline data. The availability of baseline results for contacts who were patients or clients of the setting is variable; long-term care facilities might have these data.

Schools

This category includes child care centers, preschools, primary through secondary schools, vocational schools that replace or immediately follow secondary school, and colleges or universities. Contact investigations at juvenile detention centers and adult education systems should be managed along the same lines as investigations conducted in correctional settings and in workplaces, respectively.

Early collaboration with school officials and community members is recommended when considering an investigation related to a school, even if preliminary information suggests that an investigation is unnecessary. The typical features of contact investigations in schools are the potentially substantial numbers of contacts and difficulties in assigning priorities to contacts who have undetermined durations and proximities of exposure. The potential is great for controversies among public health officials, school officials, and the guardians of the children.

The presence of TB in schools often generates publicity. Ideally, the health department should communicate with the school and parents (and guardians) before any media report a story. TB control officials should anticipate media coverage and plan a collaborative strategy (see Communicating Through the News Media).

Consent, assent, and disclosure of information are more complex for nonemancipated minors than for adults. Each interaction with a minor is also a potential interaction with the family. The health department typically has limited alternatives for evaluating a minor if permission is not granted. Anticipatory legal consultation is recommended.

Public health officials should visit the school to check indoor spaces, observe general conditions, and interview maintenance personnel regarding ventilation. Class assignment records help in listing contacts, estimating durations of exposure, and setting priorities. However, certain schools purge these files at the end of each school year, in which case interviews with students and personnel are necessary to list contacts.

Extramural activities add other exposure sites and contacts. Clubs, sports, and certain classes require additional information gained from interviewing the patient, the patient's guardians, and school personnel. For patients who ride school buses, a bus company might keep a roster of riders with addresses.

The strategy for contact investigations in child care centers, preschools, and primary schools depends on whether the index patient is a child (i.e., preadolescent) or an adult (e.g., a teacher or caregiver). The potential infectiousness of an adult in the school should be determined (see Decisions to Initiate a Contact Investigation and Investigating the Index Patient and Sites of Transmission).

In a source-case investigation of a child aged <5 years who has TB and who attends preschool or child care, all adults in these settings should be included if the source case has not been located in the family or household (see Source-Case Investigations). Certain home-based child care centers include adults who do not provide child care but who still share airspace with the children. Source-case investigations should not be pursued in primary and higher-level schools unless other evidence points to the school as the focus.

In secondary and higher levels of education, students usually have adult-form TB, and infectiousness can be estimated by the standard criteria (see Decisions to Initiate a Contact Investigation and Investigating the Index Patient and Sites of Transmission). With advancing education, academic schedules and extramural social schedules become more complex, and the information reported by the index patient is more important for a thorough investigation than it is for younger children.

Multiple jurisdictions have pre-employment requirements for TB clearance screening (e.g., a test for M. tuberculosis infection) at schools or daycare settings, and certain jurisdictions require TB clearance for entering students. Certain colleges and universities also have these requirements. These baseline data are helpful for interpreting results from the investigation.

Schools that have onsite health services can administer DOT to students with LTBI, or the health department can send workers twice weekly to provide intermittent therapy. This approach should be coordinated with the annual school cycle.

School breaks, vacations, graduations, and transfers disrupt the contact investigation. In collaboration with school officials, the health department can notify, by mail, students and other contacts who will be unavailable at the school. These contacts should be referred for evaluation at the health department. Contacts seeking care from their own health-care providers should receive written instructions to give their providers.

Shelters and Other Settings Providing Services for Homeless Persons

ACET and CDC have provided guidance for providing TB control services to homeless persons and for preventing TB transmission at settings providing services to them (137). The challenges that can be anticipated for a contact investigation involving a homeless TB patient include difficulty locating the patient and contacts if they are mobile, episodic incarceration, migration from one jurisdiction to another, psychiatric illnesses (including chemical dependency disorders) that hinder communication or participation, and preexisting medical conditions (in particular, HIV infection). When names or locations of specific contacts are unknown, interviews with the patient and potential contacts should focus on social networks and settings, including correctional facilities.

One surrogate for degree of exposure at an overnight shelter is the bed/cot assignment. The proximity and duration of overlap should be estimated as closely as possible for selecting high-priority contacts. Certain daytime-use settings keep sign-in lists, but these might lack information regarding overlap of visits.

Homeless persons frequently seek health care from multiple volunteer providers, halfway houses, chemical dependency treatment programs, community clinics, urgent care centers, and hospital emergency departments. Consultation and assistance from health-care providers in these systems can be helpful. This also creates an opportunity for collaboration, contact ascertainment, and mutual education.

Site visits and interviews are crucial, because the social communities of homeless persons are likely to vary by situation. A contact investigation presents an opportunity to review the screening and testing services and to offer assistance with these and other means of decreasing transmission of M. tuberculosis (e.g., environmental controls). However, transmission also could occur at sites besides shelters (e.g., jails, taverns, abandoned buildings, and cars).

Settings providing services to homeless persons are affected by policies, laws, and regulations according to their service population, location, and funding sources, and certain of these issues are relevant for the contact investigation. Access to visitation and occupancy rosters (or logs) and to other information regarding persons, vital for listing contacts and determining priorities, might be restricted by law (e.g., at settings that provide treatment for substance-abuse disorders), and the terms of access should be negotiated.

Low treatment-completion rates have been reported for treatment of LTBI diagnosed at homeless shelters (137--140). TB control officials should work with setting administrators to offer onsite supervised intermittent treatment. Sites with more stable populations are likely to benefit most from this approach.

Transportation Modes

Transmission of M. tuberculosis has been confirmed on military vessels at sea, commercial aircraft, passenger trains, and school buses (85,129,141--144). However, transmission is unlikely unless ventilation is restricted or exposure is long or repetitive. Investigations for these settings should be assigned low priority unless ventilation is restricted or single-trip exposure time is >8 hours (cumulative if the trip has multiple segments) as currently recommended for commercial airline travel, or at least two separate trips were taken with the index patient (145).

Drug or Alcohol Usage Sites

Shared sites of drug or alcohol usage (e.g., taverns and crack houses), have been implicated as sites of M. tuberculosis transmission (146,147). Potential factors are close person-to-person proximity, repetitive exposure, and poor ventilation. Routine interviews might not generate a complete contact list for these settings, and the patient's social network should be explored for other information sources. Connections to correctional settings should be sought. HIV infection is associated with multiple forms of substance abuse, and HIV counseling, testing, and referral services are recommended.

Special Sites Not Under Jurisdiction

Examples of sites that are not under the jurisdiction of the local or state health department are those under the jurisdiction of the U.S. government (e.g., military bases), diplomatic missions, or reservations for American Indian/Alaska Native tribes. If these sites have their own health-care systems, the health department can offer technical consultation and can request data from contact investigations. At sites that do not have health-care systems, agreements can be made between local TB control officials and the onsite authorities to delegate the public health response to the health department.

Index Patient Unable to Participate

Approximately 8% of pulmonary TB patients with AFB detected on sputum microscopy have no contacts listed (17,50). TB patients who have few or no contacts listed are more likely to be homeless or to have died (i.e., before an interview could be conducted). This implies that the patients might have had contacts, but learning who the contacts were is difficult. Social-network information, setting-based investigations, and proxy methods are recommended to supplement the contact list. In addition, any person in whom a case of pulmonary TB was diagnosed at death indicates that a possible delay in diagnosis has occurred, which could infer increased and prolonged infectiousness and a need to increase the scope of the investigation.

MDR TB

The occurrence of MDR TB does not change recommendations for assigning contact priorities. Special consideration should be given to instances when resistance is acquired during treatment or when drug resistance was detected late during the treatment course, because these patients might have had prolonged periods of infectiousness. Treatment regimens for infected contacts require expert consultation (see Treatment for Contacts with LTBI) (6).

Interjurisdictional Contact Investigations

Contact investigations that overlap multiple jurisdictional areas require joint strategies for finding contacts, having them evaluated, treating the infected contacts, and gathering data. A different solution usually is required for each situation.

Multiple jurisdictions within the United States. The index patient and associated contacts might have stable residences, but travel among sites in different jurisdictions. The health department that counts the index patient is responsible for leading the investigation and notifying the health departments in other jurisdictions regarding contacts residing in those jurisdictions. Notifications should include requests for follow-through results of contact evaluation and treatment. A team of representatives from the multiple health departments can increase the efficiency of such an investigation by planning the overall strategy together and monitoring the progress.

Migratory workers. ACET has issued specific TB prevention and control recommendations for migratory agricultural workers (148). An investigation for any migratory workers requires a strategy that is adjusted to their migration and work schedule. The workers' itinerary should be ascertained during initial planning, and health departments in successive destinations should be notified. A selection from among three general types of contact record management is recommended: 1) the transfer of patient records from one health department to the next on the itinerary; 2) the continual referral of information to a single coordinating health department throughout the investigation; or 3) patient ownership of records, with each patient responsible for keeping information while moving. Because of the duration of treatment, treating LTBI is the most difficult phase. Certain seasonal workers remain in one place as long as several months during off-season, and this period should be used to deliver as much treatment as possible.

Contagious TB patient traveling within the United States. Officials from the health department that initially encountered the patient should interview the patient to gather as much identifying and locating information as possible for contacts who were visited during the patient's travels. These data should be referred to the jurisdictions in which the contacts are located. The jurisdiction that counts the index patient is assigned responsibility for managing the contact investigation overall.

International contact investigations. The United States and Mexico participate in the Referral System for Binational TB Patients Pilot Project, which coordinates follow-up care when a TB patient moves between these two countries, mainly between participating jurisdictions. Cure TB also contributes to continuity of care in other regions of the two countries. Neither of these systems includes contact investigations at present. TBNet is a health-care system for migratory agricultural workers who are receiving treatment for LTBI and thus includes contacts. For cases or contacts in Canada, U.S. health departments should notify TB control coordinators in provincial health departments.

Unusual Events Causing Exposure to M. tuberculosis Complex

The normal mode of transmission is person to person by the airborne route. Unusual events (e.g., laboratory accidents) also can cause M. tuberculosis transmission. In contrast, M. bovis transmission usually occurs via infected dairy products, which is preventable by pasteurization.

Animals with human-type or bovine TB. Multiple mammalian and certain nonmammalian species are susceptible to human-type TB, presumably through exposure to persons with TB who are contagious. Multiple animal hosts also can contract bovine TB (i.e., infection with M. bovis), probably from exposure to other infected animals or from consuming infected dairy products or contaminated feed.

Standard methods for diagnosing M. tuberculosis infection and disease have not been described for the majority of species. Evaluation and management of an animal exposed to M. tuberculosis should be referred to a veterinarian, who can consult with the state veterinarian. Animal-to-human transmission of human TB in a household has not been confirmed, and the human contacts should be designated as low priority. However, determining the source of M. tuberculosis infection for an animal with TB is recommended.

The degree of risk for aerosol-inducing procedures (e.g., intubation, bronchoscopy, or necroscopy) performed on an animal having TB is unknown. However, these procedures are likely to create infectious aerosols. If infection control precautions for preventing M. tuberculosis transmission were not implemented during the procedures, then in-room contacts are assigned high priority.

The evaluation and management of animals exposed to M. bovis should be referred to a veterinarian. Cases of M. bovis in animals should be reported to the state veterinarian. Animal-to-human transmission of M. bovis from necropsy procedures has been confirmed (149).

Patients who acquire M. bovis infection from ingestion are more likely to have extrapulmonary TB (e.g., scrofula or peritonitis), but pulmonary disease is possible. Contact investigations regarding persons who have pulmonary TB caused by M. bovis should be planned according to the guidelines provided in this report. However, the potential for transmission is less clear. Current and proposed tests for infection (e.g., the TST and QuantiFERON^®-TB Gold [QFT-G, manufactured by Cellestis Limited, Carnegie, Victoria, Australia]) detect M. bovis infection, but the tests are not approved specifically for this indication. After active M. bovis disease has been excluded by symptom review, examination, and tests as indicated by findings, suspected latent M. bovis infection should be treated as ordinary M. tuberculosis infection.

Multiple laboratory mammals, especially nonhuman primates, are highly susceptible to human-type TB. Federal animal welfare regulations administered by the U.S. Department of Agriculture (http://www.nal.usda.gov/awic/legislat/awicregs.htm) apply to laboratory animals and certain animals used in exhibitions. If such animals are exposed to infectious TB, consultation with the state veterinarian is recommended.

Microbiology laboratory accidents. Routine laboratory procedures for manipulating either patient specimens or cultured isolates of M. tuberculosis generate infectious aerosols. Unintentional events (e.g., spills outside containment areas) and system failures can cause exposure. A contact investigation for such scenarios should be based on the location of persons in the room at the time of the event and the airflow in the room. Consultation with a microbiologist is recommended. In general, baseline skin test results are available for workers in laboratories in which M. tuberculosis is cultured or kept.

Surgical wounds, abscesses, embalming, and autopsies. Diseased tissues are not typical sources of infection unless procedures create aerosols: water-jet irrigation, dripping fluids, electrical cauterization, and cutting with power tools. If procedures were performed on infected tissues before infection control precautions were instituted, then persons in the room at the time should be designated as high-priority contacts.

Percutaneous inoculations. M. tuberculosis can cause infection and local disease in skin or deeper tissue after direct inoculation by a contaminated object. Percutaneous exposure would be highly unusual in anyone except a health-care worker, who should have a previous result from baseline testing for infection. A 9-month INH treatment regimen should be started if the M. tuberculosis is likely to be susceptible to it. Treatment should be stopped if a repeat test for M. tuberculosis is negative >8 weeks after exposure, and treatment should be extended to the full course if the test result is positive. If the baseline test result was positive, the full 9 months of treatment is recommended. During treatment, the person should be examined monthly for signs of local infection or spread to regional lymph nodes.

Source-Case Investigations

A source-case investigation seeks the source of recent M. tuberculosis infection, perhaps newly diagnosed TB disease (43). TB disease in children aged <5 years typically indicates that the infection must be recent. For this reason, it is a sentinel public health event. Young children usually do not transmit TB to others, and their contacts are unlikely to be infected because of exposure to them (150). A source-case investigation moves in the opposite direction of contact investigation, but the principles used in contact investigation apply. Source-case investigations concerning adults with TB disease are not discussed in this report (42,131,151).

Source-case investigations typically have low yield for the effort required. They are not recommended unless a TB control program is achieving its objectives (in particular, treatment of infected contacts) when investigating infectious cases.

Source-Case Investigation for a Child with TB Disease

The yield of source-case investigations for children who have TB disease varies, typically <50% on average (152--156). Source-case investigations can be considered for children aged <5 years. A younger age cut-off might be advisable because the focus would be on more recent transmission. An investigation may be started before the diagnosis of TB is confirmed because waiting for confirmation can decrease the chances of finding associates.

Source-Case Investigation for a Child with Latent M. tuberculosis Infection

A search for the source of infection for a child who has LTBI is unlikely to be productive (157--159). These kinds of investigations are recommended only regarding infected children aged <2 years and only if data are monitored to determine the value of the investigation.

Procedures for Source-Case Investigation

Seeking a source case follows the same overall procedures as a standard contact investigation. Parents or guardians usually are the best informants. Such persons are termed associates. Attention focuses on ill associates who have symptoms of TB disease. A source-case investigation should begin with the closest associates (e.g., household members).

Limited data are needed for assessing the productivity of source-case investigations. These data include the number of index patients investigated for their sources, the number of associates screened for TB disease, and the number of times that a source is found.

Other Topics

Cultural Competence

Culture refers to the integrated pattern of knowledge, beliefs, and behavior that is passed from one generation to another (160), including how persons act and interact. If contact investigations are to be productive, cultural differences must be respected and understood. Cultural competence is the knowledge and interpersonal skills that allow health-care providers to appreciate and work with persons from cultures other than their own. It involves awareness of cultural differences, self-awareness, and sensitivity to a patient's culture and adaptation skills.

Language and culture are important factors in TB contact investigations. The ability to understand cultural norms and to bridge the gaps that exist between cultures requires training and experience. Influencing patients to participate in a contact investigation increasingly depends on the cultural competency of the health-care worker. Training that is derived from the National Standards for Culturally and Linguistically Appropriate Services in Health Care is recommended (161).

Language interpreters need basic knowledge regarding TB, transmission, contact investigations, and the medical care of contacts. Patient confidentiality is a critical element of training. The use of family-member interpreters is discouraged. The majority of family members do not have a medical orientation. Patients might feel reluctant to reveal contacts of a family member.

Social Network Analysis

Social network analysis might offer an effective way to list TB contacts and assign priorities to them (162--166). Social network analyses have been tested retrospectively on TB outbreak investigations (126,167--170) and contact investigations (171,172). However, the use of social network analysis to improve contact investigations has not been tested prospectively, the methods might require additional labor, and further operational research is needed.

Use of Blood Tests for the Detection of Latent M. tuberculosis Infection

The majority of experience with diagnosing M. tuberculosis infection, especially LTBI, in contacts has been with the TST. Newly released blood tests now have potential use for this purpose. The initial QuantiFERON^®-TB test (QFT) is a whole blood assay that measures IFN-g release in response to purified protein derivative (PPD). Good agreement was reported with the skin test in healthy adults being tested for LTBI, and QFT was approved by the U.S. Food and Drug Administration (FDA) (173,174). Data are insufficient to demonstrate the accuracy of QFT test for testing contacts, and it was not recommended for this situation (175).

Recently, QFT-G was approved by FDA for use as an in vitro diagnostic to aid in diagnosing M. tuberculosis infection, including both LTBI and TB disease. This test detects the release of IFN-g from lymphocytes of sensitized persons when their blood is incubated with peptide mixtures simulating two M. tuberculosis proteins called ESAT-6 and CFP-10. These proteins are secreted by all M. tuberculosis and pathogenic M. bovis strains, but are absent from all BCG vaccine strains and commonly encountered non-tuberculous mycobacteria. Therefore, QFT-G offers the possibility of detecting M. tuberculosis infection with greater specificity than has been possible previously with tests that used tuberculin PPD as the TB antigen (175,176).

CDC recommends that QFT-G can be used in all circumstances in which the TST is currently used, including contact investigations (177). QFT-G can be used in place of and not in addition to the TST. A positive QFT-G result should prompt the same evaluation and management as a positive TST. No reason typically exists to follow a positive QFT-G with a TST. For persons with recent contact to infectious TB, negative QFT-G results typically should be confirmed with a repeat test performed 8--10 weeks after the end of exposure. Studies to identify the most appropriate times to re-test contacts with QFT-G have not been reported. Until more specific data are available, the timing of QFT-G testing should be similar to that used for the TST.

Concern has been expressed that the QFT-G test might be somewhat less sensitive than the TST in detecting LTBI (177). As with a negative TST, a negative QFT-G result alone should not be used to exclude M. tuberculosis infection in severely immunosuppressed adults, children aged <5 years, or patients about to undergo treatment with TNF-a inhibitors, in whom the consequences of accepting a false-negative result could be especially severe.

Another blood test for detection of infection, the ELISPOT test (marketed as T-SPOT-TB), is similar in principle to QFT ELISPOT results correlate with TB exposure risk better than skin test results for contacts of pulmonary TB patients), and like QFT-G, it appears able to differentiate between BCG vaccination and M. tuberculosis infection (178,179). ELISPOT has not yet been approved for use in the United States.

Additional resources regarding tuberculosis (TB) contact investigations are available from the following organizations:

• CDC, National Center for HIV, STD, and TB Prevention, Division of Tuberculosis Elimination (available at http://www.cdc.gov/nchstp/tb)
  --- Self-Study Modules on Tuberculosis 6--9 [Module 6: Contact Investigations]
  --- Effective TB Interviewing for TB Contact Investigations
  --- Effective TB Interviewing for Contact Investigation: Facilitator-Led Training Guide
  --- Effective TB Interviewing for Contact Investigation: Facilitator-Self-Study Modules
  --- Patient Education Booklet, "Contact Investigations" (Languages: English, Tagalog, Vietnamese, and Spanish)
  --- TB Education and Training resources Web Site (available at http://www.findTBresources.org);
• Northeastern National Tuberculosis Center (available at http://www.umdnj.edu/ntbcweb)
  --- Performance Guidelines for Contact Investigation: The TB Interview---A Supervisor's Guide for the Development and Assessment of Interviewing Skills
  --- TB Interviewing for Contact Investigation: A Practical Resource for the Healthcare Worker
  --- TB Simulated Patients: A Training Resource for the Contact Investigation Interview
  --- Performance Guidelines: A Supervisor's Guide for the Development and Assessment of Field Investigation Skills
  --- TB Field Investigation: A Resource for the Investigator
  --- Conducting a TB-Education Session as Part of the Congregate Setting Investigation
  --- Evaluating Congregate Setting Investigations in Tuberculosis Control;
• Charles P. Felton Model TB Center (available at http://www.harlemtbcenter.org)
  --- Addressing HIV/AIDS Issues in TB Contact Investigations;
• Francis J. Curry National Tuberculosis Center (available at http://www.nationaltbcenter.edu)
  --- Contact Investigation in a Worksite Toolbox
  --- Quality Improvement for TB Case Management: An Online Course
  --- Making the Connection: An Introduction to Interpretation Skills for TB Control
  --- Facilitating TB Outreach: Community Workers and Hard-To-Reach TB Populations;
• Southeastern National Tuberculosis Center (available at http://http://SNTC.medicine.ufl.edu); and
• Heartland National Tuberculosis Center (available at http://www.heartlandtbcenter.edu).

Acknowledgments

The following persons provided vital assistance in the preparation of this report: John Jereb, MD, Philip Lobue, MD, Michael F. Iademarco, MD, Division of TB Elimination; Terrence L. Chorba, MD, Ronald O. Valdiserri, MD, National Center for HIV, STD, and TB Prevention, CDC.

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179. Ewer K, Deeks J, Alvarez L, et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet 2003;361:1168--73.

* The age-cohort effect was strong in this study, but this factor is beyond the scope of these guidelines.

National Tuberculosis Controllers Association/CDC Workgroup on Contact Investigations
Membership List, December, 2005

Co-Chairs: Jon Tilinghast, MD, Oklahoma State Department of Health, Oklahoma City, Oklahoma; Zachary Taylor, MD, Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, CDC.

Members: Suzanne Banda, MPH, Evelyn Lancaster, Oregon Department of Human Resources, Portland, Oregon; Rajita Bhavaraju, MPH, Mark Wolman, MPH, Global Tuberculosis Institute, New Jersey Medical School, Newark, New Jersey; Sue Etkind, MS, Massachusetts Department of Public Health, Boston, Massachusetts; Kimberly W. Field, MSN, Lorena Jeske, MN, Washington State Department of Health, Olympia, Washington; Teresa Garrett, MS, Utah Department of Health, Salt Lake City, Utah; James M. Holcombe, MPPA, Mississippi State Department of Health, Jackson, Mississippi; Jennifer Flood, MD, Lisa Pascopella, PhD, Joan Sprinson, MPH, California Department of Health Services, Richmond, California; Dennis Minnice, MA, Chicago Department of Health, Chicago, Illinois; Jeff Taylor, MPH, Charles Wallace, PhD, Texas Department of State Health Services, Austin, Texas; Frank Wilson, MD, Arkansas Department of Health, Little Rock, Arkansas; John Jereb, MD, Nickolas DeLuca, PhD, Mary Reichler, MD, Phil LoBue, MD, Suzanne Marks, MPH, Scott McCoy, Maureen Wilce, MS, Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, CDC.

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Date last reviewed: 12/9/2005