Hospital Infection Control

Tuberculosis infection control

What are the key principles of preventing nosocomial transmission of tuberculosis?

Effective tuberculosis (TB) infection control measures for healthcare and other institutional settings are based on a hierarchy of control measures (administrative, environmental, and respiratory protection). Administrative controls are the most important and consist of measures to reduce the risk of exposure to persons with infectious TB (i.e., those with pulmonary and/or laryngeal TB).

Administrative controls include the careful screening of patients for symptoms and signs of TB, isolation or separation of those with suspected or confirmed TB from others (e.g., in airborne infection isolation rooms for inpatients), rapid diagnosis and implementation of effective anti-TB therapy as well as healthcare worker (HCW) directed measures (surveillance for TB infection and disease among HCWs and education of all HCWs on TB infection control measures).

As a package, the hierarchy of control measures has been demonstrated to terminate outbreaks and prevent healthcare-associated transmission of TB. Most experiences regarding the efficacy of TB infection control measures have been reported from high-income countries while the overwhelming burden of TB disease is found in low- and middle-income countries (LMICs).

What are the key conclusions for available clinical trials and meta-analyses that inform control of tuberculosis in healthcare and other institutional settings?

There are no randomized controlled trials that have assessed the efficacy of TB infection control measures. Data from observational studies including interventions implemented following outbreaks of nosocomial transmission of TB have demonstrated that a hierarchy of control measures is effective in terminating outbreaks of institutional transmission of TB and preventing subsequent transmission of Mycobacterium tuberculosis.

The observational studies strongly suggest that administrative controls are the most important measures in preventing nosocomial transmission of TB in institutional settings.

What are the consequences of ignoring key concepts related to tuberculosis Infection Control?

Failure to implement effective TB infection control measures has resulted in explosive and devastating outbreaks of nosocomial transmission of TB.

Transmission of multi-drug-resistant (MDR, resistance to at least both isoniazid and rifampin) or extensively drug-resistant (XDR, resistance to isoniazid, rifampin, a fluoroquinolone, and one second line injectable agent, such as amikacin, capreomycin, or kanamycin) strains of M. tuberculosisto patients and HCWs has been associated with significant morbidity and mortality, especially among HIV-infected and other immunocompromised persons.

Outbreaks have been reported from both developed countries and LMICs but transmission often goes undetected in LMICs due lack of effective surveillance and diagnostic capacity in many locations where little attention is paid to TB infection control measures. In one outbreak reported from South Africa, 52 of 53 patients with XDR-TB died within the median time from diagnosis to death of only 16 days.

The reports of the emergence of XDR-TB, nosocomial transmission, and high mortality due to XDR-TB among HIV-infected persons has emphasized the need for healthcare institutions throughout the world to implement effective TB infection control measures.

What other information supports the key conclusions of studies focused on tuberculosis infection control, e.g., case-control studies and case series?

Observational studies have demonstrated the efficacy of the hierarchy of TB infection control measures, which include administrative controls, environmental controls, and personal respiratory protection (PRP). Implementation of these measures have terminated outbreaks and prevented nosocomial transmission of TB.

Factors facilitating nosocomial transmission of TB included inefficient infection control procedures (delayed recognition and diagnosis of TB, clustering of patients with undiagnosed or diagnosed infectious TB with highly susceptible patients such as those with HIV infection), laboratory delays in identification and susceptibility testing of M. tuberculosis, inadequate environmental controls, and delayed initiation of effective anti-TB therapy.

Most reports of the implementation of effective TB infection control measures have come from high-income and low burden countries. There are very limited data on the implementation of effective TB infection control measures from LMICs.

Summary of current controversies.

Because there are no controlled trials on single interventions for infection control, there is controversy about the relative contribution of each component in the hierarchy of TB infection control measures although observational studies clearly suggest that administrative controls are the most important.

The greatest controversy in the United States (U.S.) has focused on PRP because of federal mandates from the Occupational Safety and Health Administration (OSHA) requiring annual fit testing of HCWs (for N-95 respirators) and due to lack of data on the precise level of effectiveness of respiratory protection in protecting HCWs from M. tuberculosis infections in institutional settings.

Observational studies have demonstrated that TB outbreaks in the U.S. were terminated prior to the availability or use of N-95 or HEPA respirators or use of fit testing. Fit testing is time consuming, logistically difficult, and can be expensive at large institutions that may have thousands of HCWs. There is no definitive data of the benefit of fit testing in the healthcare setting and recent publications by NIOSH have demonstrated a variety of problems with it.

A NIOSH study demonstrated that there was little or no additional benefit of fit testing for those models of N-95 respirators with good fitting characteristics. Poor fitting respirators with fit testing continued to be inferior to good fitting respirators without fit testing. Thus, those respirators with good fitting characteristics provided better protection out of the box without fit testing than did respirators with poor fitting respirators after fit testing. Currently, there is no provision requiring good fit characteristics as part of the certification process for N95 respirators.

Other controversies include how best to implement TB infection control measures in resource-limited settings. TB infection control has largely been ignored in most low- and middle-income country (LMIC) healthcare settings. How best to implement these measures in resource-limited areas requires further investigation and demonstration projects as well as political will.

Whether use of environmental controls (e.g., enhanced natural ventilation and use of ultra-violet [UV] germicidal irradiation) can obviate the need for full implementation of administrative controls in resource-limited areas also requires further investigation.

Overview of important clinical trials, meta-analyses, case control studies, case series, and individual case reports related to tuberculosis infection control.

See Table I, Table II, Table III, Table IV, Table V, Table VI, and Table VII.

Table I

Table II

Table III

Table IV

Table V

Table VI

Table VII

Controversies in detail.

Outbreaks of nosocomial transmission of TB were terminated with multiple interventions implemented at a single time (Table VIII). Because there are no controlled trials on single interventions for TB infection control, there has been some controversy about the relative contribution of each component in the three-tiered hierarchy of TB infection controls.

Table VIII

Table IX

It is clear however from observational studies carried out at the time of the outbreaks (which led to termination of the outbreaks and prevention of further nosocomial transmission) that administrative controls are the most important component of TB infection control measures.

The CDC defines "Administrative Controls" as "managerial measures" that reduce the risk for exposure to persons who might have active TB disease.

Examples include coordinating efforts with the local or state health department; conducting a TB risk assessment for the healthcare setting; developing and instituting a written TB infection-control plan to ensure prompt detection, airborne infection isolation (AII) (e.g., putting the patient in a negative pressure respiratory isolation room), and prompt initiation of treatment of persons with suspected or confirmed TB disease; and screening and evaluating HCWs who are at risk for TB disease or who might be exposed to M. tuberculosis.

In the U.S., a major controversy has focused on PRP because of federal mandates from the Occupational Safety and Health Administration (OSHA) requiring fit testing of HCWs (for N-95 respirators). While the use of respiratory protection has been widely accepted by healthcare providers in the U.S., there is a lack of data on the effectiveness or contribution of respiratory protection in protecting HCWs from M. tuberculosis infections in institutional settings.

TB outbreaks in the U.S. were terminated prior to the availability or use of N-95 or HEPA respirators or the use of fit testing (Table VIII). The most contentious issues regarding respiratory protection has to do with the mandate from OSHA that fit testing of healthcare providers in the U.S. are carried out on an annual basis.

OSHA maintains regulatory control over TB in healthcare settings under the Code of Federal Regulations (CFR) Title 29, Part 1910.134 (related to respiratory protection) and enforcement for TB is based on the OSHA General Duty Clause Section 5(a)(1) which provides: "Each employer shall furnish to each of his employees employment and a place of employment which are free from recognized hazards that are causing or are likely to cause death or serious physical harm to his employees."

According to the CDC TB infection control guidelines, a fit test is used to determine which respirator fits the user adequately and to ensure that the user knows when the respirator fits properly and fit testing provides a means to determine which respirator model and size fits the wearer best and to confirm that the wearer can don the respirator properly to achieve a good fit.

Furthermore, the CDC guidelines state that periodic fit testing for respirators used in TB environments can serve as an effective training tool in conjunction with the content included in employee training and retraining. Improved fitting respirators should provide better protection but there are no data from real world settings regarding prevention of transmission of M. tuberculosis.

A number of reports and an Institute of Medicine panel have indicated that there are major limitations of currently used fit-testing methods. Fit testing is time consuming, logistically difficult, and can be expensive at large institutions that may have thousands of HCWs.

Objections to the annual requirement of fit testing for HCWs have been raised because of the lack of definitive data of the benefit of fit testing in the healthcare setting.

A NIOSH study demonstrated that there was little or no additional benefit of fit testing for those models of N-95 respirators with good fitting characteristics (Figure 3). Poor fitting respirators could have their fit improved with fit testing but continued to be inferior to good fitting respirators without fit testing. Thus, those respirators with good fitting characteristics provided better protection out of the box without fit testing than did respirators with poor fitting respirators after fit testing. Currently, there is no provision requiring good fit characteristics as part of the N-95 certification process used by NIOSH.

Another current controversy is the frequency of testing of HCWs for latent TB infection (LTBI) and the best test to use for testing healthcare providers for latent TB infection.

The positive predictive value of the diagnostic test for LTBI is the probability that a person with a positive test result is actually infected with M. tuberculosis. The positive predictive value is dependent on the prevalence of infection with M. tuberculosis in the population being tested and the sensitivity and specificity of the test.

Testing of very low risk populations can result in more false positive tests than true positive tests. Because of the decreasing incidence of TB in the U.S. over the past two decades, updated CDC guidelines recommended frequency of testing of healthcare provides be based on a risk assessment at the institution which is based on the number of patients with active TB provided care at the institution.

The risk assessment is based on the size of the institution and the number of patients with active TB who receive care at the institution. The guidelines provide a stratification that includes "low risk", "medium risk", and ongoing transmission. These CDC recommendations on the frequency of testing of U.S. HCWs for LTBI are shown in Table X.

Table X

Institutions that provide care to very few or no patients with active TB are classified as "low risk" and recommended to perform only baseline testing for LTBI among healthcare providers and following an exposure. Hospitals and health care institutions (with ≥200 which provide care to 6 or more patients with active TB) are classified as "medium risk" and are recommended to perform testing at baseline and on an annual basis.

While reducing the frequency of testing, especially among low risk HCWs is reasonable, these recommendations are based on expert opinion rather than clinical studies. Large numbers of HCWs at "medium risk" institutions are also at minimal risk for acquiring LTBI at many U.S. institutions and better measures are needed to indicate which HCWs should be targeted. In one study done at a hospital in a high incidence area in the U.S. (which is a fraction of what would be seen in a middle or low income country), the risk of LTBI was based on income and area of residence and not on occupational exposure.

Another controversy involves which diagnostic test for LTBI should be used for screening and serial testing of healthcare providers. For over 100 years, the tuberculin skin test (TST) had been the only diagnostic test available for LTBI. Given the limitations of the TST, the development of newer and more effective diagnostic tests has been emphasized and is urgently needed.

A new generation of diagnostics tests for LTBI, the T-cell based interferon-γ release assays (IGRAs) that measure T-cell release of interferon-γ in response to stimulation with relatively TB-specific antigens, have become available.

Two IGRA tests are now commercially available and have been approved by the U.S. FDA. These include the QuantiFERON-TB Gold® In-Tube (QFT) assay (Cellestis Ltd., Carnegie, Australia), and the T-SPOT.TB® assay (Oxford Immunotec, Oxford, UK).

These IGRAs do not cross react with BCG and are more specific than the TST when testing BCG-vaccinated persons. The CDC has published guidelines for use of these IGRAs and generally recommends that they can be used in place of TST including serial testing of HCWs.

However, there have been little or no published data on the use of the IGRAs for serial testing of healthcare providers. A recent report suggests that the use of IGRAs for serial testing can result in high rates of false positive tests among healthcare providers working in low TB incidence areas such as the U.S.

The specificity of the IGRAs is much greater than the TST among foreign-born persons who have had a BCG vaccination, a group frequently encountered among HCWs. However, as noted above there are very limited data on the use of IGRAs for serial testing of HCWs and no definition of what constitutes a conversion using the IGRAs (only a static cut off for positive and negative). This has the potential to lead to conversions or reversions for those who have a result near the cut off for a positive IGRA test.

While the U.S. CDC has endorsed the use of IGRAs for serial testing of HCWs, the Canadian Tuberculosis Committee (CTC) has concluded that there is insufficient published evidence to recommend serial IGRA testing in populations exposed to TB, such as HCWs or prison staff and inmates. The CTC recommends against the use of IGRAs for serial testing of HCWs and that serial screening for LTBI should continue to be done using the TST.

They do suggest that IGRAs may be used as a confirmatory test if a false-positive TST is suspected in a low-risk HCW. Clearly more data are needed on the utility of IGRAs when used for serial testing as well as definitions for what constitutes an IGRA conversion.

Other controversies include how best to implement TB infection control measures in resource-limited settings. TB infection control has been largely ignored in most low- and middle-income healthcare settings.

How best to implement TB infection control measures in resource-limited areas requires further investigation, demonstration projects, and political will.

In addition to the risk of TB transmission to other patients, for many who may have HIV or other immunocompromising conditions, nosocomial TB transmission to HCWs further deepens the already severe human resources crisis in global health and in HIV and TB services.

In a review of M. tuberculosis infection and TB disease in HCWs, the median annual incidence was 5.8% (range, 0%–11%) in low-income countries and there was consistently a higher TB incidence among healthcare providers compared to the general population.

The risk was linked to degree of TB exposure and the presence or absence of airborne infection control. Whether the use of environmental controls (e.g., enhanced natural ventilation and use of ultra-violet [UV] germicidal irradiation) can obviate the need for full implementation of administrative controls (in which patients who are infectious are rapidly detected and geographically isolated from susceptible patients) in resource-limited areas also requires further investigation.

What national and international guidelines exist related to tuberculosis infection control policies?

The U.S. CDC has published TB infection-control guidelines for the U.S.; these guidelines may also be applicable for other resource-rich countries. The World Health Organization published TB infection control guidelines in 2009 that are applicable to all member states but are particularly focused on LMICs.

The guidelines from both CDC and WHO are based on a 3-tiered hierarchy of control measures (outlined in Table V) which include: (1) administrative or work practice controls, (2) environmental controls, and (3) PRP. These guidelines are intended to work synergistically at both the public health policy and local facility implementation levels.

Efficacy of tuberculosis infection control measures

During outbreaks of nosocomial transmission of TB (summarized in Table I and Table II), which frequently affected HIV-infected patients, multiple TB infection control measures were implemented simultaneously and thus the impact of individual measures could not be established.

However, it is clear from observational data that administrative controls are the most important component of a TB infection control program. Outbreaks at multiple institutions in the U.S. were terminated primarily through the implementation of administrative controls, before extensive engineering controls were fully implemented, and without the use of respirator fit-testing programs and before the availability of N-95 respirators (Table VIII).

In addition, at an institution that had an extensive respiratory protection program but insufficient administrative and engineering controls, a healthcare-associated outbreak of MDR-TB occurred which affected a number of patients and HCWs.

A hierarchy of TB infection control measures (administrative, engineering, and respiratory protection) are recommended by the CDC and WHO and have been demonstrated to terminate outbreaks and prevent healthcare-associated transmission of TB (Table V).

Administrative controls are the most important TB infection control measure and encompass the screening of patients and early isolation, diagnosis, and treatment. Engineering controls are the second level of the hierarchy and reduce the concentration of infectious droplet nuclei in ambient air. The third level of the hierarchy is the use of respiratory protective equipment (respirators) in situations that pose a high risk for exposure.

Administrative Controls

Administrative controls are the most important component of TB infection control measures and consist of measures to reduce the risk of exposure to persons with infectious TB (Table VI). Administrative controls focus on early detection of TB, isolation, diagnosis and prompt initiation of anti-TB therapy.

CDC guidelines recommend that the first step in implementing administrative controls is risk assessment. Risk assessment should take into account community incidence of disease; number of patients with TB seen at the facility each year; number of MDR cases; timeliness of the recognition, isolation, and evaluation of patients with suspected or confirmed TB; the number of HIV-seropositive patients with TB seen per year, and evidence for institutional transmission.

A risk classification scheme has been published by the CDC for use in the U.S. (Table X). The main goal is to develop and implement procedures that result in the early identification of patients with TB, placement of patients with suspected or confirmed TB in airborne infection isolation, and rapid initiation of appropriate chemotherapy for the treatment of TB.

Patients with negative sputum or respiratory specimen AFB smears with low clinical suspicion for TB can be considered to have been “ruled out” for TB and discharged from AII rooms unless there remains high clinical suspicion.

High sensitivity is needed for the detection of previously undiagnosed patients with TB in order to prevent healthcare-associated transmission of TB. Therefore, only a relatively small proportion of patients placed in airborne isolation precautions may turn out to have TB. At Grady Memorial Hospital in Atlanta, the “rule out” ratio of patients isolated to patients found to have TB is 10:1.

Given the limitation of the number of airborne infection isolation rooms at healthcare facilities, these rooms need to be utilized efficiently. This has been accomplished at some institutions by clustering airborne infection isolation rooms on a respiratory isolation ward.

In addition, guidelines allow collection of sputum samples as often as every 8 hours with the provision that one specimen is early morning sputum. Recent data also suggests that the sensitivity of two sputum specimens for AFB smear and culture is similar to that of three specimens.

There is limited experience but clearly great need to implement TB infection controls measures in LMIC institutional settings where the highest burden of TB is seen given the devastating consequences of healthcare-associated transmission of TB, especially among HIV-infected persons. (Table IX)

In resource-limited areas, the WHO have recommended developing an infection control plan, educating HCWs and patients, improving sputum collection practices, performing triage and evaluation of suspected TB patients in inpatient and outpatient settings and reducing exposure in the laboratory. A framework suggested by WHO is shown in Table XI.

Table XI

Political will and support is crucial in LMIC given the lack of attention to TB infection control measures in most areas in the past. Implementation of administrative controls in LMIC will require devising mechanisms to separate or isolate those with TB or suspected TB from other patients, improvement in diagnostic capacity to ensure high quality smear microscopy to “rule out” (or “rule in”) TB, avoiding unnecessary hospital admissions, and discharging patients with TB as soon as possible from institutions, ensuring adequate TB services in the community to provide directly observed therapy, and continue TB treatment in the community.

Given that in many LMIC, patients are housed in large multi-bed rooms, fundamental changes will need to be made in how care is provided to patients in LMIC in order to implement effective infection control measures, especially in areas of high HIV prevalence.

Super-infection of patients undergoing treatment for drug-susceptible TB with MDR or XDR-TB has been reported; therefore, cohorting of known TB patients with different susceptibility results is not without risk. Ideally mechanisms should be established to allow potentially infectious patients to be placed in private rooms. However, such facilities are rarely found in LMIC hospitals. Demonstration projects that investigate how best to implement administrative controls and the hierarchy of control measures in LMIC are urgently needed.

As part of administrative controls, surveillance programs should be established to assess rates of recent infection and/or active TB disease among HCWs. In high-income countries that do not routinely use BCG vaccination, such as the U.S., recommendations exist for the routine testing of HCWs for LTBI.

The frequency of testing for LTBI is based on the risk assessment as described above. For low risk settings, only baseline testing at the time of employment is recommended by the CDC and testing following an unprotected exposure is recommended. For medium risk settings, annual routine mandatory testing of HCWs for LTBI is recommended by the CDC. Those found to have a positive test for LTBI should have a chest radiograph performed and evaluated for treatment of LTBI. Analysis of testing results for LTBI should be carried out periodically and clusters of positive tests should be investigated.

Surveillance for active TB disease among patients and HCWs should also be carried out at healthcare facilities, both in high-income countries as well as LMIC (Table XI). In all countries but especially in LMIC with a high burden of TB and HIV and where effective TB infection control measures have not been fully implemented, voluntary HIV serologic testing should be offered to all HCWs.

Those HCW found to be HIV-infected should be offered opportunities to be re-assigned to low risk areas, where they are unlikely to come in contact with TB patients. In MDR-TB outbreaks throughout the world, HIV-infected HCWs have been infected, developed active disease, and died from drug resistant TB.

HCWs should receive education regarding effective TB infection control measures and the need to appreciate the risk of occupational exposure to patients with TB as well as the measures adopted to prevent nosocomial transmission. TB infection and disease among HCWs due to occupational exposure should not be viewed as an inevitable and unpreventable part of being a HCW, especially in LMIC where this has often been the case. Patients and their families should be taught about TB transmission and good cough hygiene.

All states in the U.S. require that TB cases be reported to local public health officials. Healthcare facilities and public health officials need to work closely with regards to discharge planning in order to ensure a seamless transition of care from an inpatient setting to an outpatient clinic and to help ensure patients are not lost to follow up after discharge. In addition, those providing care to patients with TB must ensure that patients are discharged on an appropriate anti-TB regimen and that directly observed therapy and close follow up as an outpatient are arranged.

Environmental controls

Environmental controls are the second tier of defense in the hierarchy of TB infection control measures, after administrative controls.

Environmental controls include technologies for the removal or inactivation of airborne M. tuberculosis. These technologies include natural ventilation, local exhaust ventilation, general ventilation, HEPA filtration, and ultraviolet germicidal irradiation (UVGI).

Local exhaust ventilation using a booth hood or tent can be an efficient engineering control technique because it captures a contaminant at its source. Local exhaust ventilation should be used for cough generating and aerosol generating procedures.

General ventilation systems dilute and remove contaminated air and control airflow patterns in a room. The CDC recommends that rooms in existing healthcare settings should have an airflow of greater than or equal to 6 air changes per hour (ACH) and new construction or renovation of healthcare settings should be designed so that rooms achieve an airflow of greater than or equal to 12 ACH.

Based on the risk assessment for the setting, the required number of AII rooms, other negative-pressure rooms, and local exhaust devices should be determined. Grouping AII rooms in one area might facilitate the care of patients with TB disease and the installation and maintenance of optimal environmental controls.

Healthcare settings serving populations with a high prevalence of TB disease may need to improve the existing general ventilation system or use air-cleaning technologies in general-use areas (e.g., waiting rooms, EMS areas, and radiology suites).

Applicable approaches include:

  • single-pass, non-recirculating systems that exhaust air to the outside.

  • recirculation systems that pass air through HEPA filters before recirculating it to the general ventilation system.

  • room-air recirculation units with HEPA filters and UVGI systems.

HEPA filters can be used to filter infectious droplet nuclei from the air and must be used when discharging air from local exhaust ventilation booths directly into the surrounding room and when discharging air from an AII room (or other negative-pressure room) into the general ventilation system.

UVGI is an air-cleaning technology that can be used in a room or corridor to irradiate the air in the upper portion of the room (upper-air irradiation) and is installed in a duct to irradiate air passing through the duct (duct irradiation) or incorporated into room air-recirculation units. UVGI can be used in ducts that recirculate air back into the same room or in ducts that exhaust air directly to the outside.

Environmental controls that involve mechanical ventilation such as HVAC (heating, ventilation, and air conditioning) systems and creation of negative pressure AII rooms are very costly and may be prohibitively expensive for many institutions in LMIC.

High ACH can be created with natural ventilation in certain situations (e.g., older buildings with a "sanatorium design" that have high ceilings and large windows that can be opened) (Figure 1). This approach is not feasible in cold climates.

Figure 1

An additional study examined the impact of UV lights on air from a TB-HIV ward, which was exposed to guinea pigs. Control guinea pigs exposed to untreated air from the TB-HIV ward had significantly higher rates of TB infection and active TB disease compared to guinea pigs exposed to UV treated air from the TB-HIV ward (Figure 2).

Figure 2

Figure 3

Further data is needed from human studies on whether such strategies as enhanced natural ventilation and UV lights will prevent nosocomial transmission of TB to other patients and HCWs in settings where administrative controls have not been fully implemented.

Personal respiratory protection

The first two levels of the infection control hierarchy minimize the number of areas in which exposure to M. tuberculosis might occur. PRP refers to the use of respirators and other devices intended to prevent the wearer from inhaling airborne hazards, in this case M. tuberculosis.

Respiratory protection is recommended for use by HCWs and visitors entering rooms in which patients with active TB disease are being isolated and persons present during cough-inducing or aerosol-generating procedures performed on patients with suspected or confirmed TB. Laboratory workers conducting aerosol-producing procedures also require respiratory protection.

Recommendations for PRP and mandates issued by OSHA for U.S. institutions are discussed further in CDC guidelines. Limitations of the required fit-testing mandates are discussed above. In the U.S., the minimum level of protection required is that provided by a N95 respirator.

What other consensus group statements exist and what do key leaders advise?

Other reports (in addition to the WHO guidelines) emphasizing the need for TB infection control efforts in the era of HIV and antiretroviral therapy roll out that are particularly focused on LMIC have been published. The need for operational research focused on TB infection control practices and scale-up in LMIC have been emphasized in these reports.

Operational research issues

Further research is needed in order to assess different TB infection control measures and the impact they have on TB healthcare-associated transmission. Operational research around how best to implement and scale up TB infection control strategies in LMIC are urgently needed. Studies are needed to determine how best to implement a hierarchy of control measures (especially administrative controls) in LMIC and operational research regarding infection control efficiency and cost-effectiveness.

A major limitation at many institutions is lack of laboratory capacity to facilitate rapid and accurate diagnosis of TB. Studies are needed to explore how rapid molecular diagnostics, which include commercially available real-time PCR methodologies (Gene Xpert TB/RIF) for detection of M. tuberculosis and drug resistant TB can enhance TB infection control strategies. Table XII outlines public policy issues that need to be addressed, and Table XIII lists areas where additional research is urgently needed.

Table XII

Table XIII

References

Beck-Sague, C, Dooley, SW, Hutton, MD, Otten, J, Breeden, A, Crawford, JT. "Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients". JAMA. vol. 268. 1992. pp. 1280-1286.

Fischl, MA, Uttamchandani, RB, Daikos, GL, Poblete, RB, Moreno, JN, Reyes, RR. "An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection". Ann Intern Med. vol. 117. 1992. pp. 177-183.

Edlin, BR, Tokars, JI, Grieco, MH, Crawford, JT, Williams, J, Sordillo, EM. "An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome". N Engl J Med. vol. 326. 1992. pp. 1514-1521.

Jereb, JA, Klevens, RM, Privett, TD, Smith, PJ, Crawford, JT, Sharp, VL. "Tuberculosis in health care workers at a hospital with an outbreak of multidrug-resistant Mycobacterium tuberculosis". Arch Intern Med. vol. 155. 1995. pp. 854-859.

Pearson, ML, Jereb, JA, Frieden, TR, Crawford, JT, Davis, BJ, Dooley, SW, Jarvis, WR. "Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis. A risk to patients and health care workers". Ann Intern Med. vol. 117. 1992. pp. 191-196.

Ikeda, RM, Birkhead, GS, DiFerdinando, GT, Bornstein, DL, Dooley, SW, Kubica, GP, Morse, DL. "Nosocomial tuberculosis: an outbreak of a strain resistant to seven drugs". Infect Control Hosp Epidemiol. vol. 16. 1995. pp. 152-159.

Coronado, VG, Beck-Sague, CM, Hutton, MD, Davis, BJ, Nicholas, P, Villareal, C. "Transmission of multidrug-resistant Mycobacterium tuberculosis among persons with human immunodeficiency virus infection in an urban hospital: epidemiologic and restriction fragment length polymorphism analysis". J Infect Dis. vol. 168. 1993. pp. 1052-1055.

Coronado, V, Valway, S, Finelli, L. "Nosocomial Transmission of multidrug- resistant M. Tuberculosis among intravenous drug users with human immunodeficiency virus infection". Abstracts of the Third Annual Meeting of the Society for Hospital Epidemiology of America, Chicago, April 18-20. 1993.

"Centers for Disease Control and Prevention. Outbreak of multidrug-resistant tuberculosis at a hospital--New York City, 1991". MMWR Morb Mortal Wkly Rep. vol. 42. 1993. pp. 433-424.

Zaza, S, Blumberg, HM, Beck-Sague, C, Haas, WH, Woodley, CL, Pineda, M. "Nosocomial transmission of Mycobacterium tuberculosis: role of health care workers in outbreak propagation". J Infect Dis. vol. 172. 1995. pp. 1542-1549.

Kenyon, TA, Ridzon, R, Luskin-Hawk, R, Schultz, C, Paul, WS, Valway, SE. "A nosocomial outbreak of multidrug-resistant tuberculosis". Ann Intern Med. vol. 127. 1997. pp. 32-36.

"Centers for Disease Control and Prevention. Tuberculosis outbreak in a community hospital--District of Columbia, 2002". MMWR Morb Mortal Wkly Rep. vol. 53. 2004. pp. 214-216.

Rullan, JV, Herrera, D, Cano, R, Moreno, V, Godoy, P, Peiro, EF. "Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis in Spain". Emerg Infect Dis. vol. 2. 1996. pp. 125-129.

Moro, ML, Gori, A, Errante, I, Infuso, A, Franzetti, F, Sodano, L, Iemoli, E. "An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients of two hospitals in Milan, Italy. Italian Multidrug-Resistant Tuberculosis Outbreak Study Group". AIDS. vol. 12. 1998. pp. 1095-1102.

Haas, DW, Milton, S, Kreiswirth, BN, Brinsko, VL, Bifani, PJ, Schaffner, W. "Nosocomial transmission of a drug-sensitive W-variant Mycobacterium tuberculosis strain among patients with acquired immunodeficiency syndrome in Tennessee". Infect Control Hosp Epidemiol. vol. 19. 1998. pp. 635-9.

Huang, HY, Jou, R, Chiang, CY, Liu, WC, Chiu, HJ, Lee, JJ. "Nosocomial transmission of tuberculosis in two hospitals for mentally handicapped patients". J Formos Med Assoc. vol. 106. 2007. pp. 999-1006.

Huang, WL, Jou, R, Yeh, PF, Huang, A. "Outbreak Investigation Team. Laboratory investiation of a nosocomial transmission of tuberculosis at a district general hospital". J Formos Med Assoc. vol. 106. 2007; Jul. pp. 520-7.

"Centers for Disease Control and Prevention. Nosocomial transmission of Mycobacterium tuberculosis found through screening for severe acute respiratory syndrome --- Taipei, Taiwan, 2003". MMWR Morb Mortal Wkly Rep. vol. 53. 2004. pp. 321-322.

Chen, TC, Lu, PL, Yang, CJ, Lin, WR, Lin, CY, Jou, R, Feng, MC, Wang, TH, Ho, CK, Hwang, JJ, Chen, YH, Chiang, HC, Huang, MS, Chen, TP. "Management of a nosocomial outbreak of Mycobacterium tuberculosis Beijing/W genotype in Taiwain: an emphasis on case tracing with high-resolution computed tomography". Jpn J Infect Dis. vol. 63. 2010. pp. 199-203.

Jarvis, WR. "Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis". Am J Infect Control. vol. 23. 1995. pp. 146-151.

Ritacco, V, Di Lonardo, M, Reniero, A, Ambroggi, M, Barrera, L, Dambrosi, A. "Nosocomial spread of human immunodeficiency virus-related multidrug-resistant tuberculosis in Buenos Aires". J Infect Dis. vol. 176. 1997. pp. 637-642.

Sacks, LV, Pendle, S, Orlovic, D, Blumberg, L, Constantinou, C. "A comparison of outbreak- and non-outbreak-related multidrug-resistant tuberculosis among human immunodeficiency virus-infected patients in a South African hospital". Clin Infect Dis. vol. 29. 1999. pp. 96-101.

Narvskaya, O, Otten, T, Limeschenko, E, Sapozhnikova, N, Graschenkova, O, Steklova, L. "Nosocomial outbreak of multidrug-resistant tuberculosis caused by a strain of Mycobacterium tuberculosis W-Beijing family in St. Petersburg, Russia". Eur J Clin Microbiol Infect Dis. vol. 21. 2002. pp. 596-602.

Gandhi, NR, Moll, A, Sturm, AW, Pawinski, R, Govender, T, Lalloo, U. "Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa". Lancet. vol. 368. 2006. pp. 1575-1580.

Blumberg, HM, Lautenbach, E, Woeltje, K, Malani, PN. "Tuberculosis infection control in healthcare settings". Practical handbook for healthcare epidemiologists.. University of Chicago Press. 2010. pp. 331-348.

Pai, M, Kalantri, S, Aggarwal, AN, Menzies, D, Blumberg, HM. "Nosocomial tuberculosis in India". Emerg Infect Dis. vol. 12. 2006. pp. 1311-1318.

"WHO policy on TB infection control in health-care facilities, congregate settings, and households". WHO/HTM/TB/2009. vol. 419.

Interim policy on collaborative TB/HIV activities. WHO/HTM/TB/2004.330;WHO/HTM/HIV/2004.1. WHO. 2004.

Getahun, H, Kittikraisak, W, Heilig, CM, Corbett, EL, Ayles, H, Cain, KP, Grant, AD, Churchyard, GJ, Kimerling, M, Shah, S, Lawn, SD, Wood, R, Maartens, G, Granich, R, Date, AA, Varma, JK. "Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies". PLoS Med. vol. 8. 2011. pp. e1000391.

Wenger, PN, Otten, J, Breeden, A, Orfas, D, Beck-Sague, CM, Jarvis, WR. "Control of nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis among healthcare workers and HIV-infected patients". Lancet. vol. 345. 1995. pp. 235-240.

Maloney, SA, Pearson, ML, Gordon, MT, Del Castillo, R, Boyle, JF, Jarvis, WR. "Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers". Ann Intern Med. vol. 122. 1995. pp. 90-95.

Stroud, LA, Tokars, JI, Grieco, MH, Crawford, JT, Culver, DH, Edlin, BR. "Evaluation of infection control measures in preventing the nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis in a New York City hospital". Infect Control Hosp Epidemiol. vol. 16. 1995. pp. 141-147.

Blumberg, HM, Watkins, DL, Berschling, JD, Antle, A, Moore, P, White, N. "Preventing the nosocomial transmission of tuberculosis". Ann Intern Med. vol. 122. 1995. pp. 658-663.

Moro, ML, Errante, I, Infuso, A, Sodano, L, Gori, A, Orcese, CA. "Effectiveness of infection control measures in controlling a nosocomial outbreak of multidrug-resistant tuberculosis among HIV patients in Italy". Int J Tuberc Lung Dis. vol. 4. 2000. pp. 61-68.

McGowan, JE Jr. "Nosocomial tuberculosis: new progress in control and prevention". Clin Infect Dis. vol. 21. 1995. pp. 489-505.

Harries, AD, Hargreaves, NJ, Gausi, F, Kwanjana, JH, Salaniponi, FM. "Preventing tuberculosis among health workers in Malawi". Bull World Health Organ. vol. 80. 2002. pp. 526-531.

Yanai, H, Limpakarnjanarat, K, Uthaivoravit, W, Mastro, TD, Mori, T, Tappero, JW. "Risk of Mycobacterium tuberculosis infection and disease among health care workers, Chiang Rai, Thailand". Int J Tuberc Lung Dis. vol. 7. 2003. pp. 36-45.

Roth, VR, Garrett, DO, Laserson, KF, Starling, CE, Kritski, AL, Medeiros, EA. "A multicenter evaluation of tuberculin skin test positivity and conversion among health care workers in Brazilian hospitals". Int J Tuberc Lung Dis. vol. 9. 2005. pp. 1335-1342.

Waisman, JL, Palmero, DJ, Guemes-Gurtubay, JL, Videla, JJ, Moretti, B, Cantero, M. "[Evaluation of the control measures adopted against an epidemic of AIDS-related multidrug-resistant tuberculosis in a Latin-American hospital]". Enferm Infecc Microbiol Clin. vol. 24. 2006. pp. 71-76.

Escombe, AR, Oeser, CC, Gilman, RH, Navincopa, M, Ticona, E, Pan, W, Martinez, C, Chacaltana, J, Rodriguez, R, Moore, DA, Friedland, JS, Evans, CA. "Natural ventilation for the prevention of airborne contagion". PLoS Med. vol. 4. 2007 Feb. pp. e68.

Escombe, AR, Moore, DA, Gilman, RH, Navincopa, M, Ticona, E, Mitchell, B, Noakes, C, Martínez, C, Sheen, P, Ramirez, R, Quino, W, Gonzalez, A, Friedland, JS. "Evans CA. Upper-room ultraviolet light and negative air ionization to prevent tuberculosis transmission". PLoS Med. vol. 6. 2009 Mar 17. pp. e43.

Coffey, CC, Lawrence, RB, Campbell, DL, Zhuang, Z, Calvert, CA, Jensen, PA. "Fitting characteristics of eighteen N95 filtering-facepiece respirators". J Occup Environ Hyg. vol. 1. 2004. pp. 262-71.

Jensen, PA, Lambert, LA, Iademarco, MF, Ridzon, R. "Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005". MMWR Recomm Rep. vol. 54. 2005. pp. 1-141.

"Tuberculosis in the Workplace". Institute of Medicine. Washington National Academy Press. 2001.

"Occupational Safety and Health Administration". Healthcare Wide Hazards: Tuberculosis.

Coffey, CC, Lawrence, RB, Zhuang, Z, Duling, MG, Campbell, DL. "Errors associated with three methods of assessing respiratory fit". J Occup Environ Hyg. vol. 3. 2006. pp. 44-52.

Zhuang, Z, Coffey, CC, Ann, RB. "The effect of subject characteristics and respirator features on respirator fit". J Occup Environ Hyg. vol. 2. 2005. pp. 641-9.

Campbell, DL, Coffey, CC, Jensen, PA, Zhuang, Z. "Reducing respiratory fit test errors: a multi-donning approach". J Occup Environ Hyg. vol. 2. 2005. pp. 391-99.

Zhuang, Z, Coffey, CC, Jensen, PA, Campbell, DL, Lawrence, RB, Myers, WR. "Correlation between quantitative fit factors and workplace protection factors measured in acutal workplace environments at a steel foundry". AIHA J (Fairfax, Va). vol. 64. 2003. pp. 730-8.

Coffey, CC, Lawrence, RB, Zhuang, Z, Campbell, DL, Jensen, PA, Myers, WR. "Comparison of five methods for fit-testing N95 filtering-facepiece respirators". Appl Occup Environ Hyg. vol. 17. 2002. pp. 723-30.

Campbell, DL, Coffey, CC, Lenhart, SW. "Respiraotry protection as a function of respiratory fitting characteristics and fit-test accuracy". AIHAJ. vol. 62. 2001. pp. 36-44.

Larsen, NM, Biddle, CL, Sotir, MJ, White, N, Parrott, P, Blumberg, HM. "Risk of tuberculin skin test conversion among health care workers: occupational versus community exposure and infection". Clin Infect Dis. vol. 35. 2002. pp. 796-801.

"American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection". Am J Resp Crit Care Med. vol. 161. 2000. pp. S221-247.

Pai, M, Zwerling, A, Menzies, D. "Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update". Ann Intern Med. vol. 149. 2008. pp. 177-84.

Herrera, V, Perry, S, Parsonnet, J, Banaei, N. "Clinical application and limitations of interferon-gamma release assays for the diagnosis of latent tuberculosis infection". Clin Infect Dis. vol. 52. 2011. pp. 1031-7.

Mazurek, M, Jereb, J, Vernon, A, LoBue, P, Goldberg, S, Castro, K. "Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, 2010". MMWR Recomm Rep. vol. 59. 2010. pp. 1-25.

Belknap, R, Wall, K, Teeter, L, Dorman, S, Weinfurter, P, Reves, R, Daley, CL. "Interferon-γ Release Assays (IGRAs) in Serial Testing for Latent Tuberculosis Infection in U.S. Health Care Workers". Am J Respir Crit Care Med. vol. 181. 2010. pp. A2263.

"Canadian Tuberculosis Committee. Recommendations on Interferon-gamma Release Assays for the Diagnosis of Latent Tuberculosis Infection—2010 Update. An Advisory Committee Statement (ACS)". Can Commun Dis Rep. vol. 36. 2010. pp. 1-22.

Shenoi, SV, Escombe, AR, Friedland, G. "Transmission of drug-susceptible and drug-resistant tuberculosis and the critical importance of airborne infection in the era of HIV infection and highly active antiretrovial therapy rollouts". Clin Infect Dis. vol. 50. 2010. pp. S231-7.

Joshi, R, Reingold, A, Menzies, D, Pai, M. "Tuberculosis among healthcare workers in low- and middle-income countries: a systematic review". PLoS Med. vol. 3. 2006. pp. e494.

Menzies, D, Joshi, R, Pai, M. "Risk of tuberculosis infection and disease associated with work in health care settings". Int J Tuberc Lung Dis. vol. 11. 2007. pp. 593-605.

Leonard, MK, Egan, KB, Kourbatova, E, White, N, Parrott, P, Del Rio, C, Blumberg, HM. "Increased efficiency in evaluating patients with suspected tuberculosis by use of a dedicated airborne infection isolation unit". Am J Infect Control. vol. 34. 2006. pp. 69-72.

Leonard, MK, Osterholt, D, Kourbataova, EV, Del Rio, C, Wang, W, Blumberg, H. "How many sputum specimens are necessary to diagnose pulmonary tuberculosis?". Am J Infection Control. vol. 33. 2005 Feb. pp. 58-61.

Mase, SR, Ramsay, A, Ng, V, Henry, M, Hopewell, PC, Cunningham, J, Urbanczik, R, Perkins, MD, Aziz, MA, Pai, M. "Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review". Int J Tuberc Lung Dis. vol. 11. 2007. pp. 485-95.

Gandhi, NR, Moll, A, Sturm, AW, Pawinski, R, Govender, T, Lalloo, U. "Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa". Lancet. vol. 368. 2006. pp. 1575-1580.

Narvskaya, O, Otten, T, Limeschenko, E, Sapozhnikova, N, Graschenkova, O, Steklova, L. "Nosocomial outbreak of multidrug-resistant tuberculosis caused by a strain of Mycobacterium tuberculosis W-Beijing family in St. Petersburg, Russia". Eur J Clin Microbiol Infect Dis. vol. 21. 2002. pp. 596-602.

"Centers for Disease Control and Prevention (CDC). Targeted tuberculin testing and treatment of latent tuberculosis infection". American Thoracic Society MMWR Recomm Rep. vol. 49. 2000. pp. 1-51.

"Centers for Disease Control and Prevention (CDC). Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations--United States, 2001". MMWR Morb Mortal Wkly Rep. vol. 50. 2001. pp. 733-5.

"Centers for Disease Control and Prevention (CDC). Recommendations for Use of an Isoniazid-Rifapentine REgiment with Direct Observation to Treat Latent Mycobacterium tuberculosis infection". MMWR Morb Mortal Wkly Rep. vol. 60. 2011. pp. 1650-3.

Bock, NN, Jensen, PA, Miller, B, Nardell, E. "Tuberculosis infection control in resource-limited settings in the era of expanding HIV care and treatment". J Infect Dis. vol. 196. 2007 Aug 15. pp. S108-13.

Boehme, CC, Nabeta, P, Hillemann, D, Nicol, MP, Shenai, S, Krapp, F, Allen, J, Tahirli, R, Blakemore, R, Rustomjee, R, Milovic, A, Jones, M, O'Brien, SM, Persing, DH, Ruesch-Gerdes, S, Gotuzzo, E, Rodrigues, C, Alland, D, Perkins, MD. "Rapid molecular detection of tuberculosis and rifampin resistance". N Engl J Med. vol. 363. 2010. pp. 1005-1015.

Boehme, CC, Nicol, MP, Nabeta, P, Michael, JS, Gotuzzo, E, Tahirli, R, Gler, MT, Blakemore, R, Worodria, W, Gray, C, Huang, L, Caceres, T, Mehdiyev, R, Raymond, L, Whitelaw, A, Sagadevan, K, Alexander, H, Albert, H, Cobelens, F, Cox, H, Alland, D, Perkins, MD. "Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study". Lancet. vol. 377. 2011. pp. 1495-1505.

You must be a registered member of Psychiatry Advisor to post a comment.

Sign Up for Free e-newsletters