Alessandra Regatieri, MD; Yehia Abdelwahed, MD; Maria T. Perez, MD, FCAP; Larry M. Bush, MD, FACP 01/17/2011; Laboratory Investigation. 2011;42(1):11-16. © 2011 Nature Publishing Group
Abstract
The identification of latent tuberculosis infection (LTBI) in any individual or population has proven to carry significant importance not only for that person's health, but also for the control and eventual elimination of tuberculosis (TB) in the United States. Traditionally, the tuberculin skin test (TST) has served as the standard of care for the identification of prior exposure to Mycobacterium tuberculosis (MTB).
However, the specificity of a positive test is less than optimal. It is either due to previous vaccination intended to prevent TB or infection with nontuberculous mycobacterium (NTM). Newer tests classified as interferon-gamma release assays (IGRA) possess potential advantages over the TST when used for identifying those with MTB infection. We recently diagnosed a case of pleuropulmonary infection involving an unusual NTM, Mycobacterium interjectum (M. interjectum), in an immunocompromised man diagnosed 1 year after he had been treated for LTBI based on a reactive TST. A propos this experience, we discuss the beneficial role of IGRAs and review the literature on infection with M. interjectum.
Introduction
Historically, the tuberculin skin test (TST) has been relied upon for diagnosing persons who have been sensitized by Mycobacterium tuberculosis (MTB), a condition referred to as latent tuberculosis infection (LTBI).[1] In a TST survey conducted in 2000, an estimated 4.2% of the civilian, non-institutionalized U.S. population aged >1 year had LTBI. Although this represented a 60% decline from 1972,[2] the decrease in prevalence was not uniform across all of the segments of the population. Furthermore, approximately 9.4% of the 153,555 persons diagnosed with active tuberculosis (TB) during the 10-year period between 1998 and 2007 died either before treatment began or during therapy prior to completing the anti-tuberculous regimen. Because the rates of MTB infection and active TB vary considerably, targeted testing and the selection of those persons likely to benefit from treatment for latent infection (ie, persons who are at increased risk for a poor clinical outcome if active infection ensues), have been assigned a high priority.
Utilizing an intradermal injection of a polyvalent antigenic mixture labeled purified protein derivative (PPD), TST is designed to assess in vivo delayed-type hypersensitivity (DTH) (Type IV), thereby helping to identify those individuals who have been infected with MTB. The reliability of the TST may be influenced by its technical application and the need for a second encounter 48–72 hours after test administration in order to record any observed reaction. Currently the standard method for detecting LTBI, TST has limitations in regards to sensitivity and specificity. Conditions such as advanced age, immunocompromised states, prior vaccination with Bacillus Calmette-Guerin (BCG), and previous or current infection with nontuberculous Mycobacterium species (NTM), may hinder the interpretation of TST results.[3]
Accordingly, improved diagnostic tests to aid in the management of MTB disease have been approved by the U.S. Food and Drug Administration (FDA). Collectively known as interferon-gamma (IFN-γ) release assays (IGRAs), these novel laboratory tools have the potential advantage of heightened sensitivity and specificity, less interpreter bias, and test result availability in less than 24 hours. Additionally, the more recent of the IGRAs, QuantiFERON-TB Gold and QuantiFERON-TB GOLD In-Tube (QFT-G and QFT-GIT, Cellestis Limited, Carnegie, Victoria, Australia) and T-SPOT.TB (T-SPOT, Oxford Immunotec Limited, Abingdon, United Kingdom), are indicated for use in the diagnosis of latent as well as active infection with MTB.[4,5]
Recently, we encountered a man diagnosed with a pleural space infection involving Mycobacterium interjectum (M. interjectum) who previously had been treated with 9 months of isoniazid (INH) for LTBI following the discovery of a positive TST (12 mm of induration), performed in anticipation of treatment of an underlying rheumatologic condition with a tumor necrosis factor alpha (TNF-α) inhibitor. At the time of his positive TST, he was asymptomatic and was found to have a clear chest radiograph (CXR). A repeat CXR obtained 1 year later revealed new asymptomatic unilateral pleural thickening with an associated pleural effusion, subsequently confirmed by computerized tomographic (CT) scan imaging. His history of previous asbestos exposure prompted a thoracentesis in order to rule out the possibility of an occult mesothelioma. Upon cytologic examination, the exudative fluid was void of any cells suspicious for malignancy. However, microbiologic laboratory stains revealed the presence of acid-fast bacilli (AFB) subsequently identified as M. interjectum. Based on in vitro susceptibility test results, clarithromycin and rifabutin were administered for 6 months, during which time treatment with infliximab was discontinued. At clinical follow-up, he remained asymptomatic. However, no test of cure microbiologic data was made available. A propos this case, we discuss the potential role that an IGRA may have played in his earlier management, assuming the possibility of a false-positive TST elicited by infection with this uncommon NTM. In addition, we review the medical literature pertaining to infection with M. interjectum.
http://www.medscape.com/viewarticle/734337
Abstract
The identification of latent tuberculosis infection (LTBI) in any individual or population has proven to carry significant importance not only for that person's health, but also for the control and eventual elimination of tuberculosis (TB) in the United States. Traditionally, the tuberculin skin test (TST) has served as the standard of care for the identification of prior exposure to Mycobacterium tuberculosis (MTB).
However, the specificity of a positive test is less than optimal. It is either due to previous vaccination intended to prevent TB or infection with nontuberculous mycobacterium (NTM). Newer tests classified as interferon-gamma release assays (IGRA) possess potential advantages over the TST when used for identifying those with MTB infection. We recently diagnosed a case of pleuropulmonary infection involving an unusual NTM, Mycobacterium interjectum (M. interjectum), in an immunocompromised man diagnosed 1 year after he had been treated for LTBI based on a reactive TST. A propos this experience, we discuss the beneficial role of IGRAs and review the literature on infection with M. interjectum.
Introduction
Historically, the tuberculin skin test (TST) has been relied upon for diagnosing persons who have been sensitized by Mycobacterium tuberculosis (MTB), a condition referred to as latent tuberculosis infection (LTBI).[1] In a TST survey conducted in 2000, an estimated 4.2% of the civilian, non-institutionalized U.S. population aged >1 year had LTBI. Although this represented a 60% decline from 1972,[2] the decrease in prevalence was not uniform across all of the segments of the population. Furthermore, approximately 9.4% of the 153,555 persons diagnosed with active tuberculosis (TB) during the 10-year period between 1998 and 2007 died either before treatment began or during therapy prior to completing the anti-tuberculous regimen. Because the rates of MTB infection and active TB vary considerably, targeted testing and the selection of those persons likely to benefit from treatment for latent infection (ie, persons who are at increased risk for a poor clinical outcome if active infection ensues), have been assigned a high priority.
Utilizing an intradermal injection of a polyvalent antigenic mixture labeled purified protein derivative (PPD), TST is designed to assess in vivo delayed-type hypersensitivity (DTH) (Type IV), thereby helping to identify those individuals who have been infected with MTB. The reliability of the TST may be influenced by its technical application and the need for a second encounter 48–72 hours after test administration in order to record any observed reaction. Currently the standard method for detecting LTBI, TST has limitations in regards to sensitivity and specificity. Conditions such as advanced age, immunocompromised states, prior vaccination with Bacillus Calmette-Guerin (BCG), and previous or current infection with nontuberculous Mycobacterium species (NTM), may hinder the interpretation of TST results.[3]
Accordingly, improved diagnostic tests to aid in the management of MTB disease have been approved by the U.S. Food and Drug Administration (FDA). Collectively known as interferon-gamma (IFN-γ) release assays (IGRAs), these novel laboratory tools have the potential advantage of heightened sensitivity and specificity, less interpreter bias, and test result availability in less than 24 hours. Additionally, the more recent of the IGRAs, QuantiFERON-TB Gold and QuantiFERON-TB GOLD In-Tube (QFT-G and QFT-GIT, Cellestis Limited, Carnegie, Victoria, Australia) and T-SPOT.TB (T-SPOT, Oxford Immunotec Limited, Abingdon, United Kingdom), are indicated for use in the diagnosis of latent as well as active infection with MTB.[4,5]
Recently, we encountered a man diagnosed with a pleural space infection involving Mycobacterium interjectum (M. interjectum) who previously had been treated with 9 months of isoniazid (INH) for LTBI following the discovery of a positive TST (12 mm of induration), performed in anticipation of treatment of an underlying rheumatologic condition with a tumor necrosis factor alpha (TNF-α) inhibitor. At the time of his positive TST, he was asymptomatic and was found to have a clear chest radiograph (CXR). A repeat CXR obtained 1 year later revealed new asymptomatic unilateral pleural thickening with an associated pleural effusion, subsequently confirmed by computerized tomographic (CT) scan imaging. His history of previous asbestos exposure prompted a thoracentesis in order to rule out the possibility of an occult mesothelioma. Upon cytologic examination, the exudative fluid was void of any cells suspicious for malignancy. However, microbiologic laboratory stains revealed the presence of acid-fast bacilli (AFB) subsequently identified as M. interjectum. Based on in vitro susceptibility test results, clarithromycin and rifabutin were administered for 6 months, during which time treatment with infliximab was discontinued. At clinical follow-up, he remained asymptomatic. However, no test of cure microbiologic data was made available. A propos this case, we discuss the potential role that an IGRA may have played in his earlier management, assuming the possibility of a false-positive TST elicited by infection with this uncommon NTM. In addition, we review the medical literature pertaining to infection with M. interjectum.
http://www.medscape.com/viewarticle/734337
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