Tuberculosis

Editor's Note: This issue of In the Clinic has been updated. One third of the world population has Mycobacterium tuberculosis infection (1). Despite recent progress in the United States, tuberculosis infection remains prevalent in immigrants, immunosuppressed persons, and other high-risk groups (3). Latent tuberculosis infection (LTBI) is the most prevalent form of tuberculosis in the United States (2). LTBI can progress to active tuberculosis disease, especially in individuals with a suppressed cell-mediated immunity. Active tuberculosis disease in immuno-suppressed patients can be difficult to diagnose and can progress to disseminated forms of tuberculosis disease associated with high mortality (4). New methods of diagnosing tuberculosis disease have entered practice in recent years (5), but the diagnosis of LTBI can be challenging in some high-risk populations (6, 7). The introduction of directly observed therapy with first-line antituberculous regimens (8) was an important advance in therapy, but multidrug-resistant tuberculosis (MDR-TB) and the extensively resistant form of MDR-TB remain significant threats to international and local tuberculosis control efforts (9, 10). Screening and Prevention Who should be screened for tuberculosis? Clinicians should screen all individuals at risk for tuberculosis infection, including close contacts of persons who have active pulmonary tuberculosis. Table 1 identifies asymptomatic individuals who should be screened because they are at high risk for exposure to active tuberculosis or at high risk for disease once infected. Table 1. Risk Factors for Tuberculosis Infection or Progression to Disease After Infection What tests are used to screen for tuberculosis? The tuberculin skin test (TST) with purified protein derivative (PPD) and the Mantoux method have been in use for more than 100 years to screen for tuberculosis. The TST result may not become positive for 8 to 10 weeks after exposure to active tuberculosis. The TST can give false-positive results in patient with previous bacille Calmette-Gurin (BCG) vaccination or other mycobacterial infections and false-negative results in anergic or immunosuppressed patients; however, previous BCG vaccination should not change the interpretation of the TST in most adults. The newer interferon- release assays (IGRAs), including the 2 U.S. Food and Drug Administration-approved commercial tests (T-SPOT.TB [Oxford Immunotec, Oxford, United Kingdom], and QuantiFERON-TB Gold and its In-tube version [Cellestis, Valencia, California]) can also be used in circumstances in which the TST is currently used (11). IGRAs assess the T-cell lymphocyte response to specific M. tuberculosis antigens (for example, ESAT-6 and CFP-10) and are more specific, and possibly more sensitive, than TST (12, 13). However, information about IGRA performance is limited in immunocompromised patients and patients receiving immunosuppressive therapy (6, 14). The commercially available IGRAs also have limitations; indeterminate results can occur in immunosuppressed patients, more so with QuantiFERON TB Gold than T-SPOT.TB (6). Discordant results between TST and IGRA testing also occur in about 20% of individuals (13), which could be related, at least in part, to differences in performance characteristics of these tests (5) and to characteristics of the studied populations, such as the prevalence of persons previously vaccinated with BCG and the proportion of persons born outside the United States (15, 16). In addition to their improved specificity compared with TST, IGRAs have several practical advantages. They do not require a second visit for reading and they do not trigger amnestic responses. Longitudinal data supporting the predictive value of IGRA testing is limited, however, in contrast to the many studies of TST for predicting active tuberculosis (17). A recent study from a high-incidence area of tuberculosis in Africa found that initial test results were positive in only 56% of TST testing and 52% of IGRA testing in close household contacts who developed active tuberculosis during 2 years of follow up. Of these close household contacts who developed active tuberculosis, 71% had a positive result with either TST or IGRA during their initial evaluations (18). Another prospective study (19) from a country with a low incidence of tuberculosis suggests that IGRA testing could be more accurate than TST for diagnosing LTBI and for detecting individuals who will progress to active tuberculosis, but more longitudinal data are needed, especially in immunosuppressed individuals. What can patients do to reduce their likelihood of becoming infected with tuberculosis? Tuberculosis is mainly transmitted by the airborne route from a patient with respiratory symptoms, and its ability to infect others decreases significantly after 2 weeks of effective therapy (20, 22). Therefore, prevention of tuberculosis transmission involves promptly identifying and treating patients with active tuberculosis. For hospitalized patients, prevention includes isolating patients with tuberculosis from other patients and strictly applying other hospital infection control practices (23, 24). Patients usually can be removed from airborne infection isolation when they are no longer considered infectious. Patients are no longer infectious when they are on adequate tuberculosis drug therapy, have had a significant clinical response to therapy, and have had negative results on 3 consecutive sputum smears for acid-fast bacilli (AFB). Some patients can be isolated from outsiders at home after appropriate evaluation and the initiation of outpatient treatment. Isolation of patients at home assumes that household contacts already have been exposed and that further exposure will not affect their outcomes. Two studies, one in India and one in Arkansas, showed similar rates of disease or infection in exposed household contacts whether the patient was admitted to the hospital or allowed to remain at home for initial treatment (25, 26). However, if household contacts of the patients with infectious tuberculosis are at high risk (for example, infants or immuno-compromised persons), housing the patient elsewhere until he or she meets noninfectious criteria should be strongly considered. Hospitalization may be required until housing can be obtained (27). Educating health care workers to evaluate exposed persons for active tuberculosis by obtaining sputum for AFB testing when they have respiratory symptoms has been shown to improve the case detection rates in primary care settings (28). What should clinicians tell patients with active tuberculosis to protect household members and other contacts from infection? Clinicians should teach patients to cough into disposable tissues and to cover their nose and mouth when coughing or sneezing to contain droplet nuclei before they are expelled into the air. Patients who are placed in airborne infection isolation rooms should be educated about the transmission of tuberculosis, the reasons for isolation, and the importance of staying in their rooms. Every effort should be made to help the patient follow the isolation policy (29). Hospital employees and physicians who come in contact with an infectious or suspected infectious patient should wear previously fitted particulate respirators certified by the National Institute for Occupational Safety and Health for protection against tuberculosis, which does not include surgical masks. What are the physician's public health responsibilities after making a diagnosis of active tuberculosis? All 50 U.S. states require physicians to notify public health authorities about all patients suspected of having active tuberculosis (22, 23), which can enable identification of other cases and potentially prevent further transmission of tuberculosis in the community. Genetic fingerprinting of tuberculosis isolates during an outbreak can help public health authorities detect tuberculosis infection in the community (30). Clinical Bottom Line: Screening and Prevention Clinicians should screen persons who have close contact with a person who has active pulmonary tuberculosis, and screen other persons who are at high risk for infection or for progression to disease once infected. Clinicians should screen with TST or IGRAs and should prevent infection by identifying and treating persons with active pulmonary tuberculosis. Patient airborn infection isolation is an important part of early treatment and prevention of transmission. Persons who provide care to patients with active pulmonary tuberculosis should wear particulate respirators. Clinicians should notify public health authorities about patients with suspected active tuberculosis. Diagnosis What signs and symptoms suggest active tuberculosis? Although tuberculosis can cause disease in many parts of the body, this article focuses on pulmonary tuberculosis because it is the most common form of the disease. Clinicians should consider a diagnosis of pulmonary tuberculosis and evaluate patients for tuberculosis if the patient has constitutional or pulmonary signs and symptoms, such as cough longer than 2 to 3 weeks (may not be productive until later in course of disease), hemoptysis (more likely with cavitation and rarely a presenting symptom), chest pain, fever, chills, night sweats, weight loss, easy fatigability, or anorexia. Some patients have classic signs and symptoms, but it is rare for someone to have most of the classic signs and symptoms except in advanced disease, and many patients will have few of them. Some patients with active pulmonary tuberculosis infection can be fairly asymptomatic. Table 2 shows some of the main findings from the history and the physical examination that are associated with active tuberculosis disease. Table 2. Findings from the History and Physical Examination in Patients with Active Tuberculosis One study reviewed 101 patients admitted to respiratory isolation to rul