Tuberculosis transmission and control in health care settings

INTRODUCTION — The transmission of tuberculosis (TB) in health care facilities is an important public health concern; careful infection control measures are required to prevent health care-associated transmission [1-3].

Issues related to control of TB transmission will be reviewed here. Issues related to TB screening in health care workers are discussed separately. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)", section on 'Health care workers in some settings'.)

TB TRANSMISSION — Person-to-person transmission of TB occurs via inhalation of droplet nuclei (airborne particles 1 to 5 microns in diameter). Coughing and singing facilitate formation of droplet nuclei [4-8], though these particles are generated in the absence of either activity. (See "Tuberculosis: Natural history, microbiology, and pathogenesis".)

Factors associated with elevated risk for TB transmission via droplet nuclei include [9,10]:

●Presence of active untreated pulmonary or laryngeal TB

●Presence of cavitary disease

●Presence of sputum with positive nucleic acid amplification (NAA) test result for Mycobacterium tuberculosis (MTb) complex

●Presence of sputum with positive smear for acid-fast bacilli (AFB)

●Presence of sputum with positive MTb culture (even if sputum is AFB smear negative)

●Short time (<9 days) to positive Mycobacterium tuberculosis culture

While negative sputum AFB smears suggest a lower organism burden, cases identified only by sputum culture or nucleic acid amplification (NAA) still confer a substantial transmission risk. In one study including more than 1500 patients with culture positive TB, those with negative smears were responsible for about 17 percent of TB transmission [11]. The transmission risk of NAA-negative patients on antituberculous therapy for less than one week appears to be lower than that of smear-negative patients (5 versus 11 percent in one retrospective study from the United States, a low-incidence country), but is not negligible [12].

Procedures that can result in the dispersal of droplet nuclei–associated risk for TB transmission include [1]:

●Endotracheal intubation

●Bronchoscopy

●Sputum induction

●Chest physical therapy

●Administration of aerosolized drugs

●Irrigation of a tuberculous abscess

●Autopsy on a cadaver with untreated TB disease

Patients with isolated extrapulmonary TB are not contagious; however, such patients require careful evaluation for presence of concurrent pulmonary or laryngeal TB. Concurrent pulmonary TB is common in patients with pleural or pericardial TB.

Immunocompromised patients with extrapulmonary TB should be presumed to have pulmonary TB until proven otherwise with negative sputum samples for AFB smear and culture or NAA testing, even if chest radiography is normal.

Rarely, TB can be spread by transplanted organs or bone allografts [13,14].

COMPONENTS OF TUBERCULOSIS INFECTION CONTROL — Hospital-based infection control programs are critical for limiting nosocomial transmission of TB. Important measures for a successful program include designating responsibility for TB infection control and having a written TB infection control plan [1]. Components of infection control include use of airborne infection isolation and respiratory protection as discussed in the following sections.

Health care workers (HCWs) should be educated regarding TB symptoms, transmission, and prevention. Those who care for patients with respiratory illness in facilities that care for patients who have or who are at risk for TB also should be trained in effective use of respiratory protection.

Airborne infection isolation — Hospitalized patients with known, untreated pulmonary or laryngeal/airway TB, patients with pulmonary TB who are not responding to multiple-drug treatment, or patients with suspected, active pulmonary TB should be placed in an airborne infection isolation (AII; previously called negative pressure isolation [NPI]) room, if possible.

An AII room is a single-occupancy patient care room with a ventilation system that generates negative pressure relative to outside the room, allowing air to flow into the room but not out of the room into the corridor or to other occupied areas (since air will naturally flow from areas with higher pressure to areas with lower pressure), thereby preventing infectious droplets from escaping the room. The doors and windows of AII rooms must be kept closed to maintain negative pressure, and the pressure should be verified at least daily.

At least 6 air exchanges per hour are recommended (for construction prior to 2001); for renovations or newer construction, 12 or more exchanges per hour are considered standard [1,15,16].

Air should be exhausted to the outdoors (where the droplet nuclei are diluted in the outdoor air), far removed from any intake vents, people, or animals and in accordance with applicable federal, state, and local regulations on environmental discharges. If recirculation to general ventilation is unavoidable, air must be passed through an appropriately maintained high-efficiency particulate air (HEPA) filter system installed in the exhaust ducts to remove infectious droplets from the air before it is returned to the general circulation [1].

Anterooms are useful for maintaining negative pressure. If an anteroom is present, an individual entering the patient's room should open the anteroom door, enter the anteroom, and close the anteroom door. Then the individual should open the AII room door, enter the AII room, and close the AII room door. The anteroom door and the AII room door should not be open simultaneously. All individuals entering the room must wear appropriate respiratory protection [1]. (See 'Use of masks' below.)

Patients should be educated about the purpose of the isolation room and be instructed to cover their nose and mouth when coughing or sneezing, even while in the isolation room. Procedures should be performed in the AII room whenever possible to minimize exposure of others in the hospital to the patient. Patients should wear a surgical mask if they must leave the room [17]. (See 'Use of masks' below.)

Entry of visitors and HCWs should be restricted to minimize TB transmission.

Use of masks — N95 masks should be available outside AII rooms in several sizes to optimize fit and ensure usage.

Health care workers — HCWs should wear respiratory protection in the following circumstances:

●While in the room of a patient with known or suspected active infectious TB

●While accompanying a patient with known or suspected active infectious TB, such as during transit

●While present during a procedure for a patient with known or suspected active infectious TB that induce coughing or aerosolization, such as:

•Endotracheal intubation

•Bronchoscopy

•Sputum induction

•Chest physical therapy

•Administration of aerosolized drugs

•Irrigation of a tuberculous abscess

•Autopsy on a cadaver with untreated TB disease

Appropriate respiratory protection consists of an N95 mask or a powered air-purifying respirator (PAPR). These are designed to protect the user from exposure to aerosolized droplets within the environment.

N95 masks filter particles ≥1 micrometer in diameter with at least 95 percent efficiency given flow rates up to 50 liters per minute. N95 masks must fit to a person's face with less than 10 percent seal leakage. HCWs should be fit tested in order to determine the most appropriate N95 mask size [1]. HCWs who are unable to use an N95 mask due to poor fit (for example, individuals with beards or those whose facial structure precludes a tight seal) should use a PAPR.

The optimal interval for repeat N95 mask fit testing is uncertain. The Occupational Safety and Health Administration (OSHA) requires annual fit testing [18], although this standard was designed to protect workers against industrial aerosols. Evidence for annual N95 mask fit testing in health care settings is limited, and good TB control outcomes have been reported by a program that did not perform annual fit testing [19].

Patients — Patients with known or suspected TB should be instructed to cover the mouth and nose with tissues when coughing or sneezing. Patients should wear a surgical mask when outside AII rooms; surgical masks are designed to prevent the release of respiratory secretions of the person wearing the mask from entering the environment. Patients need not wear a mask while inside AII rooms [1,17].

Patients with known or suspected TB do not require an N95 mask, since these are designed to protect the user from inhalation of infected aerosolized droplets within the patient's closed environment.

Visitors — Visitors should wear N95 masks while visiting patients with known or suspected active TB; HCWs should provide instructions on how to use the mask. (See 'Health care workers' above.)

Contact investigation — Contact investigation for known or suspected infectious cases should be initiated as soon as possible to identify secondary cases of active and latent TB or, in some situations, a source case; such investigations of patient family members and other close contacts in the community identified by the patient or others are generally performed in collaboration with public health officials [20,21].

Within a health care facility, contact investigation may be warranted if a patient with infectious TB received care prior to institution of infection control measures. Contact investigation is also warranted if a HCW is newly diagnosed with active, potentially infectious TB and may have exposed others while working prior to diagnosis. Identification of nosocomial TB transmission should prompt review of institutional TB control policy and practices.

An individual with acid-fast bacilli (AFB) smear-positive TB is generally considered to have been infectious beginning three months prior to the first smear-positive sputum or three months prior to the onset of symptoms, whichever is earlier. For individuals with AFB smear-negative TB, the contagious period is considered to have begun one month prior to onset of symptoms [1].

Patients and HCWs with potential exposure should be screened by symptoms and tuberculin skin test (TST) or interferon-gamma release assay (IGRA), unless baseline positive TST or IGRA has been documented previously. If initial screening is negative, testing should be repeated 8 to 10 weeks following the end of the exposure.

In one study including than 4400 contacts of patients with culture-confirmed pulmonary TB in the United States and Canada, the risk of TB disease over the course of five years was 4 percent; 75 percent of cases were identified within three months of the index patient's diagnosis [22].

Assessing compliance — Several studies have been performed to assess compliance with infection control programs for TB in health care facilities. One prospective study from two institutions which had experienced outbreaks of multidrug-resistant (MDR) TB found that, over a two-year period, 19 percent of patients with pulmonary TB were not isolated on their first hospital day and, of patients placed into TB isolation, only 8 percent proved to have TB [23]. Individuals entering airborne isolation rooms did not wear masks in up to 4 percent of cases, and approximately half of individuals wore surgical masks rather than N95 masks even though N95 masks were available.

In another report including three institutions, patients determined to be at risk for active TB were placed in rooms that were not designed for negative pressure in 19 percent of cases. In addition, some patients were placed in rooms designed for negative pressure although the negative pressure was not activated or functional (11 percent of cases) [24].

These studies highlight the need for regular review of compliance with established infection control policies for the control of TB.

Surveillance — Surveillance should include analyses of TB incidence and affected groups in the community, with tabulation of cases over at least the previous five years in order to develop risk profiles for specific patient populations. Collaboration with local or state public health can facilitate this. Lapses in infection control should be identified and corrected. Drug susceptibility data for TB cases should be reviewed. HCWs with risk for exposure to TB should undergo annual serial testing for TB infection.

Clues suggestive of potential patient-to-patient transmission include a high proportion of cases with prior hospitalizations in the previous year, a sudden increase in cases (especially MDR-TB), or multiple TB patients with identical drug-susceptibility patterns or DNA genotype. Surveillance data in relevant regions should be reviewed for an increase in TST or IGRA conversion.

In regions with low TB incidence rate (including the United States), HCWs in facilities with low TST conversion rates need not undergo routine serial TB screening, in the absence of a known exposure or ongoing transmission. Routine serial TB testing may be reasonable for those HCWs at increased risk for occupational exposure to TB (such as pulmonologists or respiratory therapists) or for HCWs in certain settings (such as emergency departments). This is discussed further separately. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)", section on 'Health care workers in some settings'.)

CLINICAL APPROACH

Assessing risk for tuberculosis — Care for patients with known or suspected active pulmonary TB begins with clinical assessment for the likelihood of active pulmonary TB, which should be suspected in the following circumstances in a person with risk for TB infection:

●Cough of ≥2 weeks' duration, particularly when accompanied by one or more of the following: fever, night sweats, weight loss, and hemoptysis

●Unexplained cough and fever (of any duration) in the context of HIV infection

●Community-acquired pneumonia that has not improved after five days of treatment in the setting of increased risk for TB (as summarized below)

●Incidental findings on chest radiography suggestive of TB in the setting of increased risk for TB (as summarized below), even in absence of symptoms

Factors associated with increased risk for TB infection include:

●Recent exposure to a person with a case of infectious TB

●History of a positive test result for M. tuberculosis infection

●Substance use disorder

●Birth in or travel to a region where TB incidence is high

●Residents and employees of high TB-risk congregate settings such as homeless shelters and prisons, based on local epidemiology

●Membership in a medically underserved and/or low-income population with high rates of TB

Medical risk factors for progression to active TB include:

●HIV infection

●Diabetes mellitus

●Immunosuppression (including biologic agents such as tumor necrosis factor-alpha inhibitors)

●Chronic renal failure

●Hematologic malignancy

●Head/neck cancer

●Weight >10 percent below ideal body weight

●Silicosis

●Gastrectomy or jejunoileal bypass

Risk factors for TB are discussed further separately. (See "Epidemiology of tuberculosis", section on 'Risk factors' and "Pulmonary tuberculosis: Clinical manifestations and complications" and "Diagnosis of pulmonary tuberculosis in adults".)

Diagnostic evaluation — Diagnostic evaluation for pulmonary TB includes history and physical examination (with attention to TB risk factors, if any), chest radiography, and sputum acid-fast bacilli (AFB) smear and culture with at least one specimen sent for nucleic acid amplification (NAA) testing [25-27]. A series of at least three high-quality sputum specimens should be collected in 8- to 24-hour intervals (with at least one specimen obtained in the early morning). (See "Diagnosis of pulmonary tuberculosis in adults".)

If the patient with suspected active pulmonary TB is unable to produce an adequate sputum sample, sputum induction or bronchoscopy should be pursued. Such procedures should be performed with proper respiratory protection for health care workers (HCWs), and bronchoscopes must be disinfected properly. (See 'Health care workers' above and "Flexible bronchoscopy in adults: Overview", section on 'Infection control'.)

Clinical triaging — Diagnostic evaluation for TB may be performed in the outpatient or inpatient setting [2,28]. Hospitalization with airborne infectious (ie, respiratory) isolation is appropriate if social or clinical circumstances preclude outpatient management or if there is public health risk for transmission [1,2,28]. Assessments of the patient's social circumstances (eg, living, employment, school, access to health care resources) by public health personnel can be used to determine whether hospitalization is warranted. There is no need to hospitalize on the basis of suspected infectiousness if the patient poses no danger to public health. Consultation and expert assistance is available from state health departments and from United States Centers for Disease Control and Prevention-supported Regional Centers of Excellence [29].

Outpatient management — During diagnostic evaluation, outpatients should be instructed to remain at home without visitors and away from other family members. Individuals particularly susceptible to TB (such as small children and immunocompromised individuals) should not visit or live with patients who may be infectious. These types of decisions are usually made in conjunction with the local public health authority, which should be notified at the time TB is suspected. (See "Diagnosis of pulmonary tuberculosis in adults", section on 'Reporting and public health'.)

Inpatient management

Initiating airborne precautions — Components of airborne precautions include implementation of airborne isolation and use of masks. Inpatients with known or suspected active pulmonary TB should be placed in an airborne infection isolation (AII) room, if possible [30]. The approach to assessing TB risk is described in the preceding section. (See 'Assessing risk for tuberculosis' above.)

If an AII room is not available, patients should wear a surgical mask and be placed in an enclosed area; contact with others (especially with young children or immunocompromised patients) should be avoided. Such patients then should be referred to a facility with an AII room [1,17]. If an area other than an AII room is used, it should be ventilated and should not be used again for at least one hour after the patient has departed. (See 'Airborne infection isolation' above.)

HCWs and visitors should wear an N95 mask while in contact with a patient with known or suspected active TB, as described above. (See 'Health care workers' above and 'Visitors' above.)

Patients with known or suspected TB should wear a surgical mask when outside AII rooms. (See 'Patients' above.)

Discontinuing airborne precautions — Airborne precautions (including use of AII room and masks) may be discontinued when infectious TB is deemed clinically unlikely and one or more of the following criteria applies [31-33]:

●An alternative diagnosis explaining the clinical syndrome has been established.

●Demonstration of three consecutive negative AFB sputum smear results.

●Using NAA testing, demonstration of two negative-sputum Xpert MTB/RIF results (algorithm 1) [31]. Multiple sputum specimens for AFB smear and culture are still warranted in such cases, for the following reasons:

•To maximize diagnostic sensitivity (culture is more sensitive than Xpert MTB/RIF testing)

•To perform drug susceptibility testing

•To diagnose non-tuberculous mycobacterial infection

For circumstances in which a diagnosis of TB is established, airborne precautions (including use of AII room and masks) may be discontinued after antituberculous therapy has been administered for at least two weeks (with evidence of clinical improvement) and three subsequent negative sputum AFB smears [1]. In general, cough frequency is reduced after two weeks of appropriate antituberculosis therapy, which considerably diminishes the potential for airborne transmission [34]. Serial Xpert MTB/RIF results from patients who are receiving therapy should not be used to determine when a patient with laboratory-confirmed pulmonary TB may be released from AII, since polymerase chain reaction detects only nucleic acid and provides no indication of viability of the organism in the specimen or of their infectiousness.

The Xpert MTB/RIF assay has been approved by the US Food and Drug Administration (FDA) for use in place of serial acid-fast sputum smears to aid in decisions regarding whether continued airborne infection isolation is warranted for patients with suspected TB [35]. Sputum quality is critical to the performance of this test. Further guidance regarding this indication, including protocols and algorithms that may be replicated, has been issued by the National Tuberculosis Controllers Association and the Association of Public Health Laboratories [31]. Other issues related to use of the Xpert MTB/RIF are discussed further separately. (See "Diagnosis of pulmonary tuberculosis in adults".)

Use of Xpert MTB/RIF for guiding decisions regarding airborne infection isolation is based on results of studies demonstrating that negative Xpert MTB/RIF results from one or two sputum specimens are highly predictive of the results of two or three negative acid-fast sputum smears [32,36,37]. When compared with the results of two or three serial fluorescence-stained acid-fast sputum smears, a single Xpert MTB/RIF assay result detected approximately 97 percent of patients who were AFB smear positive and culture confirmed as infected with M. tuberculosis complex (MTBC); two serial Xpert MTB/RIF assay results detected 100 percent of AFB smear–positive, MTBC culture–positive patients [36]. These findings confirm results of other reports [25,26,38,39].

"Ruling out" infectious TB must include appropriate clinical judgment. Sputum AFB smears are relatively insensitive, especially in regions with low TB prevalence where individuals tend to present for care earlier in the course of illness. The Xpert MTB/RIF assay detects 95 to 100 percent of AFB smear-positive cases but only 50 to 70 percent of smear-negative, culture-positive cases of pulmonary TB [40,41]. Therefore, clinical judgment remains paramount, even with negative Xpert MTB/RIF results.

Discharge planning — Suspected or confirmed cases of TB should be reported promptly to the local or state public health department (in accordance with public health regulations) to expedite contact investigation, to assure adequate medication is provided and case management is initiated, and to plan outpatient follow-up. (See 'Contact investigation' above.)

Careful follow-up for subsequent clinical evaluation is required; this usually requires engagement with local public health officials. Clinical care should be arranged with a provider who has expertise with management of TB, if possible. The patient should be provided with an adequate supply of medication (not just the prescriptions) to last until the outpatient appointment. Case management with directly observed therapy should be arranged through local public health. (See "Adherence to tuberculosis treatment" and 'Contact investigation' above.)

In some circumstances, infectious patients (eg, patients with AFB smear-positive sputum) may be discharged to home (at the discretion of the clinician and local public health authorities), provided there are no household members who are immunocompromised or younger than five years of age [1]. Infectious patients should remain at home as much as possible; when receiving visitors or leaving home, patients should wear a surgical mask. (See 'Patients' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Tuberculosis transmission and control".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Tuberculosis (Beyond the Basics)")

SUMMARY

●Transmission of tuberculosis (TB) in health care facilities is an important public health concern. Person-to-person transmission of TB occurs via inhalation of droplet nuclei. Individuals with active untreated pulmonary or laryngeal disease may be contagious, particularly when cavitary pulmonary disease is present or when the sputum is acid fast-bacilli (AFB) smear positive. Patients with sputum smear-negative, culture-positive pulmonary TB also can transmit infection. (See 'TB transmission' above.)

●Hospital-based infection control programs are critical for limiting nosocomial transmission of TB. Components of infection control include use of airborne infection isolation (AII) and use of masks. (See 'Components of Tuberculosis infection control' above.)

●Suspicion for TB is critical to the initiation of measures to limit possible transmission, which may include AII and/or empiric initiation of treatment. Care for patients with known or suspected active pulmonary TB begins with clinical assessment for the likelihood of active pulmonary TB, which should be suspected in the circumstances outlined above. (See 'Assessing risk for tuberculosis' above.)

●Diagnostic evaluation for TB may be performed in the outpatient or inpatient setting. Hospitalization with airborne precautions is appropriate if social or clinical circumstances preclude outpatient management or if there is public health risk for transmission. (See 'Clinical triaging' above.)

●Hospitalized patients with known or suspected active infectious pulmonary TB should be placed in an AII room if possible; if an AII room is not available, patients should wear a surgical mask and be placed in an enclosed area with no exposure to others, including immune compromised persons or young children. An AII room is a single-occupancy patient care room with a ventilation system that generates negative pressure, allowing air to flow into the room but not out of the room and into the building air shared by other patients and staff, thereby preventing infectious droplets from escaping the room. (See 'Airborne infection isolation' above and 'Initiating airborne precautions' above.)

●Health care workers and visitors should wear an N95 mask while in contact with a patient with known or suspected active TB. N95 masks are designed to protect the user from exposure to aerosolized droplets within the environment. (See 'Health care workers' above and 'Visitors' above.)

●Patients with known or suspected TB should wear a surgical mask when outside AII. Surgical masks are designed to prevent the release of respiratory secretions of the person wearing the mask from entering the environment. Such patients need not wear an N95 mask and need not wear a surgical mask while inside AII. (See 'Patients' above.)

●Diagnostic evaluation for pulmonary TB includes chest radiography, sputum AFB smear and culture, and nucleic acid amplification (NAA) testing. A series of at least three high-quality sputum specimens should be collected in 8- to 24-hour intervals for smear and culture (with at least one specimen obtained in the early morning and sent for NAA testing). (See 'Diagnostic evaluation' above.)

●Airborne precautions (including use of AII room and masks) for a patient with suspected infectious TB may be discontinued after the diagnosis of infectious TB has been ruled out (algorithm 1) or after a diagnosis of TB has been established with initiation of antituberculous therapy for at least two weeks, with clinical response to treatment, and three subsequent negative AFB smears. Discontinuation of airborne precautions should follow applicable public health regulations. (See 'Discontinuing airborne precautions' above.)

●Suspected or confirmed cases of TB should be reported promptly to the local public health department in order to assure case management, expedite contact investigation, and plan outpatient follow-up. Clinical care should be arranged with a provider who has expertise with management of TB, if possible. The patient should be provided with an adequate supply of medication (not just prescriptions) to last until the outpatient appointment. Case management with directly observed therapy should be arranged through local public health. (See 'Discharge planning' above.)