Tuberculosis: Epidemiology, Diagnosis, and Treatment of Latent Infection

Philip A. LoBue

Tuberculosis is a pulmonary and systemic infectious disease caused by Mycobacterium tuberculosis. It is spread from person to person by airborne transmission of droplet nuclei 1 to 5 μm in diameter. Several factors determine the probability of transmission: (1) infectiousness of the source patient—a positive sputum smear for acid-fast bacilli or a cavity on chest radiograph being strongly associated with infectiousness; (2) host susceptibility of the contact; (3) duration of exposure of the contact to the source patient; and (4) the environment in which the exposure takes place: a small, poorly ventilated space providing the highest risk. Even among household contacts of active tuberculosis patients, the risk of infection is surprisingly low; the United States Public Health Service (USPHS) reported an approximate 28% incidence of infection in household contacts. In addition, animal and human studies have demonstrated that tuberculosis transmission may dramatically decrease within days to weeks of instituting effective treatment.

Despite this relatively low transmission rate, tuberculosis remains a major global public health problem. There are almost 9 million new tuberculosis cases per year throughout the world and about 1.4 million people die of the disease annually. The human immunodeficiency virus (HIV) epidemic has dramatically altered tuberculosis epidemiology and is driving much of the global epidemic, especially in Africa. Nearly one quarter of worldwide HIV deaths are tuberculosis-related. The current epidemic has been accompanied by a rise in drug-resistant tuberculosis. Currently, it is estimated that each year there are almost 500,000 new cases of multidrug-resistant (MDR) tuberculosis (resistant to isoniazid and rifampin) globally, of which approximately 10% are extensively drug-resistant (MDR plus resistance to a fluorquinolone and any second-line injectable drug [amikacin, kanamycin, and capreomycin]).

In the United States, there had been a steady 4% to 7% annual decline in the case rate until 1984. Between 1985 and 1992, however, the annual incidence of tuberculosis increased by 20%. This increase was concentrated in young (predominantly aged 25–44), urban (especially New York, New Jersey, and California), racial, and ethnic minority populations. Tuberculosis also was found to be prevalent among the homeless, injection and noninjection drug users, and inmates of correctional facilities. In many of these groups, the rise in tuberculosis was linked to high rates of HIV infection. A second epidemiologic trend emerged with increased immigration to the United States of persons from countries where tuberculosis is prevalent (especially Latin America, South and Southeast Asia, Africa, and Eastern Europe). Before 1986, foreign-born persons accounted for 22% of tuberculosis cases. By 1997, this number had increased to 39% and in 2009 it reached 59%. In some locations, this phenomenon is even more pronounced. In California, for example, more than 75% of tuberculosis cases occur in persons born outside the United States. Because of extensive national, state, and local control efforts, the annual incidence of tuberculosis has been on the decline again since 1992, falling 57% between 1992 and 2011 (from 26,673 cases to 10,528 cases). Despite this welcome decline, the associations of tuberculosis with conditions such as HIV infection, homelessness, injection drug use, and foreign birth remain. Approximately 1% of US tuberculosis cases are MDR.

The tuberculin skin test (TST) is a major tool for investigating tuberculosis infection. It can be used diagnostically in the individual patient and epidemiologically in the general population. The TST (Mantoux method) is performed by the intracutaneous injection of a standardized, stabilized dose of 5 TU of purified protein derivative (PPD). The extent of induration is measured 48 to 72 hours later. Multiple puncture techniques (e.g., tine test) are not recommended. The interpretation of the TST is based on an individual’s epidemiologic risk factors for tuberculosis infection. The 2000 American Thoracic Society (ATS) guidelines for interpretation of TST results are as follows: (a) 5-mm induration is considered positive for (i) individuals with HIV infection or other comparable immunosuppression (equivalent to receiving 15 mg or greater of prednisone for 1 month or more), (ii) close contacts to an active tuberculosis case, or (iii) patients with a chest radiograph suggestive of prior tuberculosis (e.g., fibronodular) disease (also termed inactive disease); (b) 10-mm induration is considered positive for (i) recent immigrants (within the last 5 years) from high-incidence countries; (ii) injection drug users; (iii) residents and employees of high-risk congregate facilities, such as nursing homes, homeless shelters, or prisons; (iv) mycobacterial laboratory personnel; (v) persons with underlying medical conditions, such as diabetes, silicosis, end-stage renal disease, certain malignancies, and low body weight (loss of at least 10% of ideal body weight); or (vi) children younger than age 4 and infants, children, or adolescents exposed to adults at high risk; and (c) 15-mm induration is considered positive for all others.

A positive TST result is considered to indicate the presence of infection with M. tuberculosis. In the United States, it is recommended that persons who test positive receive treatment for latent tuberculosis to prevent progression to disease. Thus, an intent to test for latent tuberculosis should indicate an intent to treat for latent tuberculosis if it is found. Consequently, testing should be reserved for persons at high risk for latent infection or at high risk to progress to disease based on their epidemiologic profile.

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