Mycobacterium Tuberculosis
Melanie Gerrior
Cassandra D. Salgado
Preston L.W. Church
INTRODUCTION
Almost one-third of the world’s population is infected with tuberculosis (TB). In 2010, nearly nine million people developed TB associated illness and 1.4 million succumbed to TB-related death.
TB continues to be a leading cause of mortality among patients with human immunodeficiency virus (HIV). Others at increased risk are inmates in correctional facilities, the elderly, the homeless, and foreign-born persons.
In the United States, 10,521 cases of TB (3.4 cases per 100,000 persons) were reported in 2011, which was a 6.4% decline compared to 2010. Incident TB among foreignborn persons in the United States was 12 times greater than US-born persons, and Asians surpassed Hispanics as the largest racial/ethnic group represented. Most foreignborn persons with TB have latent TB infection (LTBI) acquired abroad.
Despite continued decline in US TB cases, this still falls short of the 2010 goal of TB elimination set in 1989.
PATHOGENESIS
TB spreads from person to person through the air by droplet nuclei (1 mm to 5 mm) containing Mycobacterium tuberculosis. Infectious droplets are produced when persons with pulmonary or laryngeal TB cough, sneeze, or speak. Additionally, procedures that generate aerosols such as sputum induction, bronchoscopy, and processing infectious specimens may spread TB.
After inhalation, infectious droplet nuclei may reach respiratory bronchioles or alveoli. Depending on bacterial virulence and the inherent host defense mechanisms of the alveolar macrophages, infection may be established and replication may ensue.
The tubercle bacillus grows slowly, dividing every 25 to 32 hours within the macrophage. Initially, there is no host response until a sufficient number of organisms are produced (2 to 12 weeks). Then there is a cellular immune response that can be detected by reaction to the tuberculin skin test (TST).
Before cellular immunity develops, bacilli spread via lymphatics to hilar lymph nodes and through the bloodstream to distant sites. Sites with favorable microenvironments for replication of the organism include the upper lungs, kidneys, bones, and brain.
For most individuals with normal cell-mediated immune function, proliferation of M. tuberculosis is halted through collections of activated T cells and macrophages that form granulomas. Small numbers of viable organisms exist in the center of the granulomas, which may become necrotic.
Sometimes a primary complex is seen on chest imaging; however, the majority of pulmonary TB infections are clinically and radiographically inapparent. Most often, a positive TST is the only sign that infection with M. tuberculosis has occurred.
Individuals who successfully halt replication of TB and thus do not have active disease are classified as having LTBI. These individuals cannot transmit the organism to other persons; however, it is estimated that approximately 10% of individuals with LTBI will develop active disease. Thus, for adequate control and possible elimination of TB, preventive treatment for this group is needed.
LATENT TUBERCULOSIS INFECTION
Persons with increased risk for developing TB include those who have had recent infection with M. tuberculosis and those who have clinical conditions that are associated with an increased risk for progression of LTBI to active TB such as HIV, intravenous drug use, diabetes, chronic renal failure, or immunosuppression.
Persons with LTBI who are considered to be at high risk for developing active TB should be offered treatment irrespective of age and irrespective of bacille Calmette-Guérin (BCG) immunization.
Diagnosis of Latent Tuberculosis
For more than a century, the diagnosis of LTBI has depended on the intradermal injection of purified protein derivative, the TST. Guidelines for interpretation are regularly updated by the Centers for Disease Control (CDC) (Table 63-1).
Table 63-1 Criteria for a Positive Tuberculin Skin Test
Induration ≥5 mm
Induration ≥10mm
Induration ≥15 mm
HIV-positive persons
Residents and employees of high-risk settings: healthcare facilities, prisons and jails, longterm care facilities, homeless shelters, mycobacteriology labs
Persons with no risk factors for TB
Recent contacts of TB case patients
Recent immigrants (within 5 years) from high prevalence countries
Fibrotic changes on chest radiograph consistent with prior TB
Injection-drug users
Immunosuppression, including organ transplantation, ≥15 mg/day prednisone ≥30 days
Other conditions associated with increased risk of disease, including silicosis, diabetes mellitus, chronic renal failure, leukemias and lymphomas, lung cancer, head and neck cancer, weight loss ≥10% of ideal body weight, gastrectomy, jejunoileal bypass
Adapted from CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Morb Mortal Wkly Rep 2000; 49 (RR-6):1-51.
Table 63-2 Ability of TST and IGRAs to Predict Risk of Progression to Active TB
Sensitivity
Specificity
Positive Predictive Value
Negative Predictive Value
TST
90%-100%
29%-39%
2.7%-3.1%
99%-100%
IGRA
80%-90%
56%-83%
4%-8%
99%-100%
Pooled results from four published studies examining household contacts of an active TB case. Positive TST defined as a reaction >5 mm induration.
TST sensitivity is reduced in immunosuppressed individuals, those with active infection, and in the first 8 to 12 weeks after primary infection; in the latter two situations, a negative TST is never sufficient to exclude infection.
False positive TST results may occur from cross-reactions due to exposure to environmental mycobacteria including M. avium-intracellulare complex and M. marinum.
BCG in infancy (established benefit) should not contribute to a positive TST after 4 to 5 years postvaccination. The effect of BCG vaccine later in life or due to boosting is more difficult to assess but may result in a positive TST up to 10 years later in 25% of recipients.
Whole-blood interferon gamma release assays (IGRAs) based on quantification of IFN-γ released by sensitized lymphocytes in response to early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) are an alternative to TST. These antigens are common to all mycobacterium tuberculosis (MTB) isolates and pathogenic M. bovis strains but not BCG strains of M. bovis.
Even though some mycobacteria (M. szulgai, M. kansasii, M. marinum) may produce false positive results, the specificity of IGRAs is superior to that of the TST. The sensitivity may be slightly less than the TST; however, the ability to identify individuals at risk for progression to active TB is similar (Table 63-2).Related posts:
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