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DTBE | PDF | American Thoracic Society American Thoracic Society Diagnostic Standards and Classification of Tuberculosis in Adults and Children THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY AND THE CENTERS FOR DISEASE CONTROL AND PREVENTION WAS ADOPTED BY THE ATS BOARD OF DIRECTORS, JULY 1999. THIS STATEMENT WAS ENDORSED BY THE COUNCIL OF THE INFECTIOUS DISEASE SOCIETY OF AMERICA, SEPTEMBER 1999 CONTENTS culosis infection/disease and to present a classification scheme that facilitates management of all persons to whom diagnostic Introduction tests have been applied. I. Epidemiology The specific objectives of this revision of the Diagnostic II. Transmission of Mycobacterium tuberculosis Standards are as follows. III. Pathogenesis of Tuberculosis IV. Clinical Manifestations of Tuberculosis 1. To define diagnostic strategies for high- and low-risk pa- A. Systemic Effects of Tuberculosis tient populations based on current knowledge of tuberculo- B. Pulmonary Tuberculosis sis epidemiology and information on newer technologies. C. Extrapulmonary Tuberculosis 2. To provide a classification scheme for tuberculosis that is V. Diagnostic Microbiology based on pathogenesis. Definitions of tuberculosis disease A. Laboratory Services for Mycobacterial Diseases and latent infection have been selected that (a) aid in an B. Collection of Specimens for Demonstration of accurate diagnosis; (b) coincide with the appropriate re- Tubercle Bacilli sponse of the health care team, whether it be no response, C. Transport of Specimens to the Laboratory treatment of latent infection, or treatment of disease; (c) D. Digestion and Decontamination of Specimens provide the most useful information that correlates with E. Staining and Microscopic Examination the prognosis; (d) provide the necessary information for F. Identification of Mycobacteria Directly from appropriate public health action; and (e) provide a uni- Clinical Specimens form, functional, and practical means of reporting. Because G. Cultivation of Mycobacteria tuberculosis, even after it has been treated adequately, re- H. Identification of Mycobacteria from Culture mains a pertinent and lifelong part of a person’s medical I. Drug Susceptibility Testing history, previous as well as current disease is included in J. Genotyping of Mycobacterium tuberculosis the classification. K. Assessment of Laboratory Performance This edition of the Diagnostic Standards has been prepared VI. Tuberculin Skin Test as a practical guide and statement of principles for all persons A. Tuberculin involved in the care of patients with tuberculosis. References B. Immunologic Basis for the Tuberculin Reaction have been included to guide the reader to texts and journal ar- C. Administration and Reading of Tests ticles for more detailed information on each topic. D. Interpretation of Skin Test Reactions E. Boosted Reactions and Serial Tuberculin Testing I. EPIDEMIOLOGY F. Previous Vaccination with BCG G. Definition of Skin Test Conversions Tuberculosis remains one of the deadliest diseases in the world. H. Anergy Testing in Individuals Infected with HIV The World Health Organization (WHO) estimates that each VII. Classification of Persons Exposed to and/or Infected with year more than 8 million new cases of tuberculosis occur and Mycobacterium tuberculosis approximately 3 million persons die from the disease (1). Ninety- VIII. Reporting of Tuberculosis five percent of tuberculosis cases occur in developing coun- References tries, where few resources are available to ensure proper treatment and where human immunodeficiency virus (HIV) infection may be common. It is estimated that between 19 and 43% of the world’s population is infected with Mycobacterium INTRODUCTION tuberculosis, the bacterium that causes tuberculosis infection The “Diagnostic Standards and Classification of Tuberculosis and disease (2). in Adults and Children” is a joint statement prepared by the In the United States, an estimated 15 million people are in- American Thoracic Society and the Centers for Disease Con- fected with M. tuberculosis (3). Although the tuberculosis case trol and endorsed by the Infectious Disease Society of America. rate in the United States has declined during the past few The Diagnostic Standards are intended to provide a framework years, there remains a huge reservoir of individuals who are for and understanding of the diagnostic approaches to tuber- infected with M. tuberculosis. Without application of effective treatment for latent infection, new cases of tuberculosis can be expected to develop from within this group. Tuberculosis is a social disease with medical implications. It Am J Respir Crit Care Med Vol 161. pp 1376–1395, 2000 has always occurred disproportionately among disadvantaged Internet address: www.atsjournals.org populations such as the homeless, malnourished, and over- American Thoracic Society 1377 crowded. Within the past decade it also has become clear that of the pasteurization of milk and effective tuberculosis control the spread of HIV infection and the immigration of persons programs for cattle (13). Airborne transmission of both M. bo- from areas of high incidence have resulted in increased num- vis and M. africanum can also occur (14–16). Mycobacterium bers of tuberculosis cases. bovis BCG is a live-attenuated strain of M. bovis and is widely used as a vaccine for tuberculosis. It may also be used as an agent to enhance immunity against transitional-cell carcinoma II. TRANSMISSION OF Mycobacterium tuberculosis of the bladder. When used in this manner, adverse reactions Tuberculosis is spread from person to person through the air such as dissemination may be encountered, and in such cases by droplet nuclei, particles 1 to 5 ␮m in diameter that contain M. bovis BCG may be cultured from nonurinary tract system M. tuberculosis complex (4). Droplet nuclei are produced specimens, i.e., blood, sputum, bone marrow, etc. (17). when persons with pulmonary or laryngeal tuberculosis cough, sneeze, speak, or sing. They also may be produced by aerosol III. PATHOGENESIS OF TUBERCULOSIS treatments, sputum induction, aerosolization during bron- choscopy, and through manipulation of lesions or processing After inhalation, the droplet nucleus is carried down the bron- of tissue or secretions in the hospital or laboratory. Droplet chial tree and implants in a respiratory bronchiole or alveolus. nuclei, containing two to three M. tuberculosis organisms (5), Whether or not an inhaled tubercle bacillus establishes an in- are so small that air currents normally present in any indoor fection in the lung depends on both the bacterial virulence and space can keep them airborne for long periods of time (6). the inherent microbicidal ability of the alveolar macrophage Droplet nuclei are small enough to reach the alveoli within the that ingests it (4, 18). If the bacillus is able to survive initial de- lungs, where the organisms replicate. Although patients with fenses, it can multiply within the alveolar macrophage. The tu- tuberculosis also generate larger particles containing numer- bercle bacillus grows slowly, dividing approximately every 25 ous bacilli, these particles do not serve as effective vehicles for to 32 h within the macrophage. Mycobacterium tuberculosis transmission of infection because they do not remain airborne, has no known endotoxins or exotoxins; therefore, there is no and if inhaled, do not reach alveoli. Organisms deposited on immediate host response to infection. The organisms grow for intact mucosa or skin do not invade tissue. When large parti- 2 to 12 wk, until they reach 103 to 104 in number, which is suffi- cles are inhaled, they impact on the wall of the upper airways, cient to elicit a cellular immune response (19, 20) that can be where they are trapped in the mucous blanket, carried to the detected by a reaction to the tuberculin skin test. oropharynx, and swallowed or expectorated (7). Before the development of cellular immunity, tubercle ba- Four factors determine the likelihood of transmission of M. cilli spread via the lymphatics to the hilar lymph nodes and tuberculosis: (1) the number of organisms being expelled into thence through the bloodstream to more distant sites. Certain the air, (2) the concentration of organisms in the air deter- organs and tissues are notably resistant to subsequent multi- mined by the volume of the space and its ventilation, (3) the plication of these bacilli. The bone marrow, liver, and spleen length of time an exposed person breathes the contaminated are almost always seeded with mycobacteria, but uncontrolled air, and (4) presumably the immune status of the exposed indi- multiplication of the bacteria in these sites is exceptional. Or- vidual. HIV-infected persons and others with impaired cell- ganisms deposited in the upper lung zones, kidneys, bones, mediated immunity are thought to be more likely to become and brain may find environments that favor their growth, and infected with M. tuberculosis after exposure than persons with numerous bacterial divisions may occur before specific cellu- normal immunity; also, HIV-infected persons and others with lar immunity develops and limits multiplication. impaired cell-mediated immunity are much more likely to de- In persons with intact cell-mediated immunity, collections velop disease if they are infected. However, they are no more of activated T cells and macrophages form granulomas that likely to transmit M. tuberculosis (8). limit multiplication and spread of the organism. Antibodies Techniques that reduce the number of droplet nuclei
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