Background
Tuberculosis (TB), a multisystemic disease with myriad presentations and manifestations, is the most common cause of infectious disease–related mortality worldwide. The World Health Organization (WHO) has estimated that 2 billion people have latent TB and that globally, in 2009, the disease killed 1.7 million people.[1] New TB treatments are being developed,[2] and new TB vaccines are under investigation. (See Epidemiology and Treatment and Management, below.)[3]
Although TB rates are decreasing in the United States, the disease is becoming more common in many parts of the world. In addition, the prevalence of drug-resistant TB is also increasing worldwide. Co-infection with the human immunodeficiency virus (HIV) has been an important factor in the emergence and spread of resistance. (See Treatment of Multidrug-Resistant TB, below.)[4]
TB is an ancient disease. Signs of skeletal TB (Pott disease) were evident in Europe from Neolithic times (8000 BCE), in ancient Egypt (1000 BCE), and in the pre-Columbian New World. TB was recognized as a contagious disease by the time of Hippocrates (400 BCE), when it was termed "phthisis" (Greek from phthinein, to waste away).
Mycobacterium tuberculosis, a tubercle bacillus, is the causative agent of TB. It belongs to a group of closely related organisms—including M africanum, M bovis, and M microti —in the M tuberculosis complex. Robert Koch discovered and isolated M tuberculosis in 1882. (See Etiology, below.) An image of the bacterium is seen below.
Acid-fast bacillus smear showing characteristic cording in Mycobacterium tuberculosis. World incidence of TB increased with population density and urban development, so that by the Industrial Revolution in Europe (1750), it was responsible for more than 25% of adult deaths. Indeed, in the early 20th century, TB was the leading cause of death in the United States. (See Etiology and Epidemiology, below.)
The US Centers for Disease Control and Prevention (CDC) has been recording detailed epidemiologic information on tuberculosis (TB) since 1953. The incidence of TB has been declining since the early 20th century because of various factors, including basic infection-control practices (isolation). Beginning in 1985, a resurgence of TB was noted. The increase was observed primarily in ethnic minorities and especially in persons infected with HIV. TB control programs were revamped and strengthened across the United States. (See Epidemiology.)
As an AIDS (acquired immunodeficiency syndrome)-related opportunistic infection, TB is associated with HIV infections, with dual infections being frequently noted. Globally, coinfection with HIV is highest in South Africa, India, and Nigeria.
Persons with AIDS are 20-40 times more likely than immunocompetent persons to develop active TB.[5] Correspondingly, TB is the leading cause of mortality among persons infected with HIV.[6]
Worldwide, TB is most common in Africa, the West Pacific, and Eastern Europe. These regions are plagued with factors that contribute to the spread of TB, including the presence of limited resources, HIV infection, and multidrug-resistant (MDR) TB. Consequently, although international public health efforts have put a huge curb on the rate of increase in TB, these regions account for the continued increase in global TB. (See Epidemiology.)
Drug-resistant TB
MDR-TB is defined as resistance to the 2 most effective first-line drugs, isoniazid and rifampin.[6] Another type of resistant TB, called extensively drug-resistant TB (XDR-TB), is resistant to isoniazid, rifampin, and second-line drugs used to treat MDR-TB. Mortality rates for patients with XDR-TB are similar to those of patients from the preantibiotic era. (Approximately 1 in 13 M tuberculosis isolates currently shows a form of drug resistance.)[6]
Multiple factors contribute to the drug resistance of M tuberculosis, including incomplete and inadequate treatment or adherence to treatment, logistical issues, virulence of the organism, multidrug transporters, host genetic factors, and HIV infection.
According to WHO, the prevalence of MDR-TB has been 1.1% in newly diagnosed patients; it is reportedly even higher in patients who have previously received anti-TB treatment (7%).
MDR-TB and XDR-TB are becoming increasingly significant.[7] Genotype studies have shown that between 63% and 75% of XDR-TB cases progress through acquisition of resistance.[8]
According to the US National TB Surveillance System (NTSS), between 1993 and 2006 a total of 49 cases (3% of evaluable MDR-TB cases) met the revised case definition for XDR-TB. The largest number of XDR-TB cases was found in New York City and California.
The success rate of treatment with standard short-course chemotherapy (SCC) is less than 60% in patients with MDR-TB, compared with a success rate of more than 85% in patients with drug-susceptible TB.
(MDR-TB and XDR-TB not only produce fulminant and fatal disease among patients infected with HIV [time from TB exposure to death averages 2-7 mo] but are also highly infectious, with conversion rates of as much as 50% in exposed health care workers.)
Global surveillance and treatment of TB
As previously stated, multidrug resistance has arisen from poor compliance with TB therapies , resulting in difficulties in controlling the disease. Consequently, a threat of global pandemic occurred in the late 1980s and early 1990s. Reacting to these signals, the World Health Organization developed a plan to try to identify 70% of the world's cases of TB and to completely treat at least 85% of these cases by the year 2000.
Out of these goals were born major TB surveillance programs and the concept of directly observed therapy (DOT), which requires a third party to witness compliance with pharmacotherapy. With worldwide efforts, global detection of smear-positive cases rose from 11% (1991) to 45% (2003), with 71-89% of those cases undergoing complete treatment.
Approach to TB in the emergency department
Despite the importance of early isolation of patients with active TB, a standardized triage protocol with acceptable sensitivities has yet to be developed.[9] Moran et al demonstrated that among patients with active TB in the emergency department (ED), TB was often unsuspected, and isolation measures were not used.[10] The difficulty in establishing such a protocol only highlights the importance of the emergency physician’s role in the prompt identification and isolation of active TB.
A large percentage of ED patients are at increased risk for having active TB, including homeless/shelter-dwelling patients, travelers from endemic areas, immunocompromised patients, health care workers, and incarcerated patients. Therefore, emergency physicians must consider the management and treatment of TB as a critical public health measure in the prevention of a new epidemic.[11]
For high-risk cases, prehospital workers can assist in identifying household contacts who may also be infected or who may be at high risk of becoming infected.
Prehospital workers should be aware that any case of active TB in a young child indicates disease in 1 or more adults with close contact, usually within the same household. TB in a child is a sentinel event indicating recent transmission.
Extrapulmonary involvement in TB
Extrapulmonary involvement occurs in one fifth of all TB cases; 60% of patients with extrapulmonary manifestations of TB have no evidence of pulmonary infection on chest radiographs or sputum culture.
Cutaneous TB
The incidence of cutaneous TB appears low. In areas such as India or China, where TB prevalence is high, cutaneous manifestations of TB (overt infection or the presence of tuberculids) have been found in less than 0.1% of individuals seen in dermatology clinics.
Ocular TB
TB can affect any structure in the eye and typically presents as a granulomatous process. Keratitis, iridocyclitis, intermediate uveitis, retinitis, scleritis, and orbital abscess are within the spectrum of ocular disease. Choroidal tubercles and choroiditis are the most common ocular presentations of TB. Adnexal or orbital disease may be seen with preauricular lymphadenopathy. Because of the wide variability in the disease process, presenting complaints will vary.
Most often, patients will complain of blurry vision that may or may not be associated with pain and red eye. In the rare case of orbital disease, proptosis, double vision, or extraocular muscle motility restriction may be the presenting complaint. Preseptal cellulitis in children with spontaneous draining fistula may also occur. In cases of both pulmonary and extrapulmonary TB, there may be ocular findings without ocular complaints.
In patients with confirmed active pulmonary or active nonocular extrapulmonary TB, ocular incidence ranges from 1.4-5.74%. In HIV patients, the incidence of ocular TB may be higher, with a reported prevalence of from 2.8-11.4%.
TB and the legal system
Laws vary from state to state, but communicable-disease laws typically empower public health officials to investigate suspected cases of TB, including potential contacts of persons with TB. In addition, patients may be incarcerated for noncompliance with therapy.
Pathophysiology
Infection with M tuberculosis results most commonly from infected aerosol exposure through the lungs or mucous membranes. In immunocompetent individuals, this usually produces a latent/dormant infection; only about 5% of these individuals later show evidence of clinical disease. (See Etiology.)
Alterations in the host immune system that lead to decreased immune effectiveness can allow M tuberculosis organisms to reactivate, with tubercular disease resulting from a combination of direct effects from the replicating infectious organism and from subsequent inappropriate host immune responses to tubercular antigens.
Molecular typing of M tuberculosis isolates in the United States by restriction fragment-length polymorphism analysis suggests more than one third of new patient occurrences of TB result from person-to-person transmission, with the remainder resulting from reactivation of latent infection.
Verhagen et al demonstrated that large clusters of TB are associated with an increased number of tuberculin skin test-positive contacts, even after adjusting for other risk factors for transmission.[12] The number of positive contacts was significantly lower for index cases with isoniazid-resistant TB compared with index cases with fully-susceptible TB. This suggests that some TB strains may be more transmissible than other strains and that isoniazid resistance is associated with lower transmissibility.
Uveitis caused by TB is the local inflammatory manifestation of a previously acquired primary systemic tubercular infection. There is some debate regarding molecular mimicry, as well as a nonspecific response to noninfectious tubercular antigens, which may produce active ocular inflammation in the absence of bacterial replication.
Etiology
M tuberculosis is a slow-growing, obligate aerobe and a facultative, intracellular parasite. The organism grows in parallel groups called cords (as seen in the image below). It retains many stains after decoloration with acid-alcohol, which is the basis of acid-fast stains.
Acid-fast bacillus smear showing characteristic cording in Mycobacterium tuberculosis. Mycobacteria, such as M tuberculosis, are aerobic, non-spore-forming, nonmotile, facultative, intracellular, curved rods measuring 0.2-0.5 μm by 2-4 μm. Their cell walls contain mycolic, acid-rich, long-chain glycolipids and phospholipoglycans (mycocides) that protect mycobacteria from cell lysosomal attack and also retain red basic fuchsin dye after acid rinsing (acid-fast stain).
Humans are the only known reservoir for M tuberculosis. The organism is spread primarily as an airborne aerosol from infected to noninfected individuals (although transdermal and GI transmission have been reported). These droplets are 1-5 μm in diameter; a single cough can generate 3000 infective droplets, with as few as 10 bacilli needed to initiate infection.
When inhaled, droplet nuclei are deposited within the terminal airspaces of the lung. The organisms grow for 2-12 weeks, until they reach 1000-10,000 in number, which is sufficient to elicit a cellular immune response that can be detected by a reaction to the tuberculin skin test.
Exposure to M tuberculosis can occur when common airspace is shared with an individual who is in the infectious stage of TB.
Mycobacteria are highly antigenic, and they promote a vigorous, nonspecific immune response. Their antigenicity is due to multiple cell wall constituents, including glycoproteins, phospholipids, and wax D, which activate Langerhans cells, lymphocytes, and polymorphonuclear leukocytes.
Because of the ability of M tuberculosis to survive and proliferate within mononuclear phagocytes, which ingest the bacterium, M tuberculosis is able to invade local lymph nodes and spread to extrapulmonary sites, such as the bone marrow, liver, spleen, kidneys, bones, and brain, usually via hematogenous routes.
When a person is infected with M tuberculosis, the infection can take 1 of a variety of paths, most of which do not lead to actual TB. The infection may be cleared by the host immune system or suppressed into an inactive form called latent tuberculosis infection (LTBI), with resistant hosts controlling mycobacterial growth at distant foci before the development of active disease. Patients with LTBI cannot spread disease.
Although mycobacteria are spread by blood throughout the body during initial infection, primary extrapulmonary disease is rare except in immunocompromised hosts. Infants, older persons, or otherwise immunosuppressed hosts are unable to control mycobacterial growth and develop disseminated (primary miliary) TB. Patients who become immunocompromised months to years after primary infection also can develop late, generalized disease.
The lungs are the most common site for the development of TB; 85% of patients with TB present with pulmonary complaints. Extrapulmonary TB can occur as part of a primary or late generalized infection. An extrapulmonary location may also serve as a reactivation site; extrapulmonary reactivation may coexist with pulmonary reactivation.
The most common sites of extrapulmonary disease are mediastinal, retroperitoneal, and cervical (scrofula) lymph nodes; vertebral bodies, adrenals, meninges, and the GI tract. That pathology of these lesions is similar to that in the lungs. (The most common site of tuberculous lymphadenitis (scrofula) is in the neck, along the sternocleidomastoid muscle. It is usually unilateral and causes little or no pain. Advanced cases of tuberculous lymphadenitis may suppurate and form a draining sinus.)
Infected end organs typically have high, regional oxygen tension (as in the kidneys, bones, meninges, eyes, and choroids, and in the apices of the lungs). The principal cause of tissue destruction from M tuberculosis infection is related to the organism's ability to incite intense host immune reactions to antigenic cell wall proteins.
Lesions in TB development
The typical TB lesion is epithelioid granuloma with central caseation necrosis. The most common site of the primary lesion is within alveolar macrophages in subpleural regions of the lung. Bacilli proliferate locally and spread through the lymphatics to a hilar node, forming the Ghon complex.
Early tubercles are spherical, 0.5- to 3-mm nodules with 3 or 4 cellular zones demonstrating (1) a central caseation necrosis, (2) an inner cellular zone of epithelioid macrophages and Langhans giant cells admixed with lymphocytes, (3) an outer cellular zone of lymphocytes, plasma cells, and immature macrophages, and (4) a rim of fibrosis (in healing lesions).
Initial lesions may heal and the infection become latent before symptomatic disease occurs. Smaller tubercles may resolve completely. Fibrosis occurs when hydrolytic enzymes dissolve tubercles, and larger lesions are surrounded by a fibrous capsule. Such fibrocaseous nodules usually contain viable mycobacteria and are potential lifelong foci for reactivation or cavitation. Some nodules calcify or ossify and are seen easily on chest radiographs.
Tissues within areas of caseation necrosis have high levels of fatty acids, low pH, and low oxygen tension, all of which inhibit growth of the tubercle bacillus.
If the host is unable to arrest the initial infection, the patient develops progressive, primary TB with tuberculous pneumonia in the lower and middle lobes of the lung. Purulent exudates with large numbers of acid-fast bacilli can be found in sputum and tissue. Subserosal granulomas may rupture into the pleural or pericardial spaces and create serous inflammation and effusions.
With the onset of host-immune response, lesions that develop around mycobacterial foci can be either proliferative or exudative. Both types of lesions develop in the same host, since infective dose and local immunity vary from site to site.
Proliferative lesions develop where the bacillary load is small and host cellular-immune responses dominate. These tubercles are compact, with activated macrophages admixed, and are surrounded by proliferating lymphocytes, plasma cells, and an outer rim of fibrosis. Intracellular killing of mycobacteria is effective, and the bacillary load remains low.
Exudative lesions predominate when large numbers of bacilli are present and host defenses are weak. These loose aggregates of immature macrophages, neutrophils, fibrin, and caseation necrosis are sites of mycobacterial growth. Without treatment, these lesions progress and infection spreads.
Risk factors
Four factors contribute to the likelihood of transmission, as follows:
- Number of organisms expelled
- Concentration of organisms
- Length of exposure time to contaminated air
- Immune status of the exposed individual
Infected patients living in crowded or closed environments pose a particular risk to noninfected persons. Approximately 20% of people in household contact develop infection (positive tuberculin skin test). Microepidemics have occurred in closed environments such as submarines and on transcontinental flights.
Populations at high risk for acquiring the infection also include hospital employees, inner-city residents, nursing home residents, and prisoners.
Increased risk of acquiring active disease occurs with HIV infection, intravenous (IV) drug abuse, alcoholism, diabetes mellitus (3-fold risk), silicosis, immunosuppressive therapy, cancer of the head and neck, hematologic malignancies, end-stage renal disease, intestinal bypass surgery or gastrectomy, chronic malabsorption syndromes, and low body weight. The risk is also higher in infants younger than 5 years.
Tumor necrosis factor-alpha (TNF-a) antagonists, used in the treatment of rheumatoid arthritis, psoriasis, and several other autoimmune disorders, have been associated with a significantly increased risk for TB.[13] Reports have included atypical presentations, extrapulmonary and disseminated disease, and deaths. Patients scheduled to begin therapy with a TNF-α antagonist should be screened for latent TB and counseled regarding the risk of TB.
Immunosuppressive therapy also includes chronic administration of systemic steroids (prednisone or its equivalent, given >15 mg/d for ≥4 wk or more) and/or inhaled steroids. Inhaled steroids, in the absence of systemic steroids, were associated with a relative risk of 1.5.[14]
Smoking has been shown to be a risk factor for TB; smokers who develop TB should be encouraged to stop smoking to decrease the risk of relapse.[15]
Obesity in elderly patients has been associated with a lower risk for pulmonary TB.[16]
TB in children
In children younger than 5 years, the potential for development of fatal miliary TB or meningeal TB is a significant concern.
Osteoporosis, sclerosis, and bone involvement are more common in children with TB. The epiphyseal bones can be involved due to their high vascularity.
Children do not commonly infect other children, because they rarely develop cough and sputum production is scant. However, cases of child-child and child-adult TB transmission are well-documented. Go to Pediatric Tuberculosis for complete information on this topic.
Epidemiology
TB prevalence in the United States
With the improvement of living conditions and the introduction of effective treatment (streptomycin) in the late 1940s, the number of patients in the United States reported to have tuberculosis (TB) underwent a steady decline (126,000 TB patients in 1944; 84,000 in 1953; 22,000 in 1984; 14,000 in 2004), despite explosive growth in the total population (140 million people in 1946, 185 million in 1960, 226 million in 1980).
On a national level, the incidence of tuberculosis is at an all-time low. In 2011, a total of 10,521 incident TB cases were reported in the United States, reflecting a 6.4% decline from 2010 to 3.4 cases per 100,000 population.[17]
Demographics of TB in the United States
Nearly half of all TB cases reported (50.4%) have been found to come from 4 states: California, Florida, New York, and Texas.
In 2011, more than 60% of cases of TB reportedly occurred among foreign-born persons. Approximately 54% of TB cases involving foreign-born individuals in 2011 were reported in persons from 5 countries: Mexico (21.3%), the Philippines (11.5%), Vietnam (8.2%), India (7.6%), and China (5.6%). An estimated 10-15 million people in the United States have latent TB infection.
International prevalence of TB and M tuberculosis infection
Globally, more than 1 in 3 individuals is infected with tubercle bacillus.
An estimated 9.27 million incident TB cases were reported internationally in 2007, an increase from 9.24 million in 2006. However, although the total number of cases increased, the number of cases per capita decreased from a global peak of 142 cases per 100,000 in 2004 to 139 cases per 100,000 in 2007.[1, 18]
Countries with the highest prevalence include Russia, India, Bangladesh, Pakistan, Indonesia, Philippines, Vietnam, Korea, China, Tibet, Hong Kong, Egypt, most sub-Saharan African countries, Brazil, Mexico, Bolivia, Peru, Colombia, Dominican Republic, Ecuador, Puerto Rico, El Salvador, Nicaragua, Haiti, Honduras, and areas undergoing civil war.
The prevalence of TB in countries in Eastern Europe is intermediate. The prevalence of TB is lowest in Costa Rica, western and northern Europe, the United States, Canada, Israel, and most countries in the Caribbean.
Africa, which is home to 13% of the world's population and 13 of the 15 countries with the highest TB incidence, shoulders over 25% of the annual global TB burden in terms of cases and deaths.
Mortality in TB
Internationally, TB a primary infectious cause of morbidity and mortality.
As previously noted, WHO estimated that 1.7 million people worldwide died of TB in 2009.[1]
In the United States, 2800 TB deaths are reported annually.
Race prevalence
As previously mentioned, in 2007 almost 60% of cases of TB reportedly occurred among foreign-born persons.
This skewed distribution is most likely due to socioeconomic factors. Elevated rates of TB infection are seen in individuals immigrating from Mexico, the Philippines, India, Southeast Asia, Africa, the Caribbean, and Latin America.
Based on 2007 CDC data, the frequency of TB in Hispanics, blacks, and Asians were 7.6, 8.5, and 23.5 times higher than in whites, respectively.[1] However, race is not clearly an independent risk factor, as foreign-born persons account for 77% of TB cases among Hispanics and 96% of TB cases among Asians, but only 29% of TB cases among blacks. Risk is best defined based on social, economic, and medical factors.
Sex prevalence
Despite the fact that TB rates have declined in both sexes in the United States, certain differences exist. TB rates in women decline with age, but in men, rates increase with age. In addition, men are more likely than women to have a positive tuberculin skin test result. The reason for these differences may be social, rather than biologic, in nature.
The estimated sex prevalence for TB varies by source, from no sex prevalence to a male-to-female ratio in the United States of 2:1.
Age predilection
Higher rates of TB infection are seen in young, nonwhite adults (peak incidence, 25-40 y) than in white adults. In addition, white adults manifest the disease later (peak incidence, age 70 y) than do nonwhite persons.
In the United States, more than 60% of TB cases occur in persons aged 25-64 years; however, the age-specific risk is highest in persons older than age 65 years.[1]
TB is uncommon in children aged 5-15 years.
Prognosis
Among published studies involving DOT treatment of tuberculosis (TB), the rate of recurrence ranges from 0-14%.[19] In countries with low TB rates, recurrences usually occur within 12 months of treatment completion and are due to relapse.[20] In countries with higher TB rates, most recurrences after appropriate treatment are probably due to reinfection rather than relapse.[21]
Full resolution is generally expected with few complications in cases of non-MDR-TB and non-XDR-TB, when the drug regimen is completed.
Poor prognostic markers include extrapulmonary involvement, an immunocompromised state, older age, and a history of previous treatment.
In a prospective study of 199 patients with TB in Malawi, 12 (6%) died. Risk factors for dying were reduced baseline TNF alpha response to stimulation (with heat-killed M tuberculosis), low body mass index, and elevated respiratory rate at TB diagnosis.[22]
Patient Education
For patient education information, see the Bacterial and Viral Infections Center, as well as Tuberculosis.
Additional information can be found through the following sources:
- World Health Organization Tuberculosis
World Health Organization. Global tuberculosis control 2010. World Health Organization. Available at http://www.who.int/tb/publications/global_report/en/index.html. Accessed Jan 21, 2011.
[Best Evidence] Burman WJ, Goldberg S, Johnson JL, Muzanye G, Engle M, Mosher AW, et al. Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis. Am J Respir Crit Care Med. Aug 1 2006;174(3):331-8. [Medline].
Asensio JA, Arbués A, Pérez E, Gicquel B, Martin C. Live tuberculosis vaccines based on phoP mutants: a step towards clinical trials. Expert Opin Biol Ther. Feb 2008;8(2):201-11. [Medline].
Wells CD, Cegielski JP, Nelson LJ, Laserson KF, Holtz TH, Finlay A, et al. HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis. Aug 15 2007;196 Suppl 1:S86-107. [Medline].
WHO. Fact Sheet 104. World Health Organization. Available at http://www.who.int/mediacentre/factsheets/fs104/en/index.html. Accessed October 13, 2010.
CDC. Plan to combat extensively drug-resistant tuberculosis: recommendations of the Federal Tuberculosis Task Force. MMWR Recomm Rep. Feb 13 2009;58:1-43. [Medline].
World Health Organization. Antituberculosis drug resistance in the world. The WHO/IUATLD global project on anti-tuberculosis drug resistance surveillance WHO. Geneva. 2008;1-120. [Full Text].
Mlambo CK, Warren RM, Poswa X, Victor TC, Duse AG, Marais E. Genotypic diversity of extensively drug-resistant tuberculosis (XDR-TB) in South Africa. Int J Tuberc Lung Dis. Jan 2008;12(1):99-104. [Medline].
Sokolove PE, Lee BS, Krawczyk JA, Banos PT, Gregson AL, Boyce DM, et al. Implementation of an emergency department triage procedure for the detection and isolation of patients with active pulmonary tuberculosis. Ann Emerg Med. Apr 2000;35(4):327-36. [Medline].
Moran GJ, McCabe F, Morgan MT, Talan DA. Delayed recognition and infection control for tuberculosis patients in the emergency department. Ann Emerg Med. Sep 1995;26(3):290-5. [Medline].
Menzies D, Joshi R, Pai M. Risk of tuberculosis infection and disease associated with work in health care settings. Int J Tuberc Lung Dis. Jun 2007;11(6):593-605. [Medline].
Verhagen LM, van den Hof S, van Deutekom H, Hermans PW, Kremer K, Borgdorff MW, et al. Mycobacterial factors relevant for transmission of tuberculosis. J Infect Dis. May 2011;203(9):1249-55. [Medline].
Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. Oct 11 2001;345(15):1098-104. [Medline].
Brassard P, Suissa S, Kezouh A, Ernst P. Inhaled Corticosteroids and Risk of Tuberculosis in Patients with Respiratory Diseases. Am J Respir Crit Care Med. Oct 1 2010;[Medline].
Slama K, Chiang CY, Enarson DA, Hassmiller K, Fanning A, Gupta P, et al. Tobacco and tuberculosis: a qualitative systematic review and meta-analysis. Int J Tuberc Lung Dis. Oct 2007;11(10):1049-61. [Medline].
Leung CC, Lam TH, Chan WM, Yew WW, Ho KS, Leung G, et al. Lower risk of tuberculosis in obesity. Arch Intern Med. Jun 25 2007;167(12):1297-304. [Medline].
CDC. Trends in Tuberculosis – United States, 2011. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6111a2.htm?s_cid=mm6111a2_w.
WHO. Global tuberulosis control 2008: surveillance, planning, financing. World Health Organization. Available at http://www.who.int/topics/tuberculosis/en/. Accessed October 13, 2010.
Cox HS, Morrow M, Deutschmann PW. Long term efficacy of DOTS regimens for tuberculosis: systematic review. BMJ. Mar 1 2008;336(7642):484-7. [Medline]. [Full Text].
Jasmer RM, Bozeman L, Schwartzman K, Cave MD, Saukkonen JJ, Metchock B, et al. Recurrent tuberculosis in the United States and Canada: relapse or reinfection?. Am J Respir Crit Care Med. Dec 15 2004;170(12):1360-6. [Medline].
van Rie A, Warren R, Richardson M, Victor TC, Gie RP, Enarson DA, et al. Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N Engl J Med. Oct 14 1999;341(16):1174-9. [Medline].
Waitt CJ, Peter K Banda N, White SA, Kampmann B, Kumwenda J, Heyderman RS, et al. Early deaths during tuberculosis treatment are associated with depressed innate responses, bacterial infection, and tuberculosis progression. J Infect Dis. Aug 2011;204(3):358-62. [Medline]. [Full Text].
Badak FZ, Kiska DL, Setterquist S, Hartley C, O'Connell MA, Hopfer RL. Comparison of mycobacteria growth indicator tube with BACTEC 460 for detection and recovery of mycobacteria from clinical specimens. J Clin Microbiol. Sep 1996;34(9):2236-9. [Medline]. [Full Text].
Tan SH, Tan BH, Goh CL, Tan KC, Tan MF, Ng WC, et al. Detection of Mycobacterium tuberculosis DNA using polymerase chain reaction in cutaneous tuberculosis and tuberculids. Int J Dermatol. Feb 1999;38(2):122-7. [Medline].
Vieites B, Suárez-Peñaranda JM, Pérez Del Molino ML, Vázquez-Veiga H, Pardo F, Del Rio E, et al. Recovery of Mycobacterium tuberculosis DNA in biopsies of erythema induratum--results in a series of patients using an improved polymerase chain reaction technique. Br J Dermatol. Jun 2005;152(6):1394-6. [Medline].
Sonnenberg P, Glynn JR, Fielding K, Murray J, Godfrey-Faussett P, Shearer S. How soon after infection with HIV does the risk of tuberculosis start to increase? A retrospective cohort study in South African gold miners. J Infect Dis. Jan 15 2005;191(2):150-8. [Medline].
Muga R, Ferreros I, Langohr K, de Olalla PG, Del Romero J, Quintana M, et al. Changes in the incidence of tuberculosis in a cohort of HIV-seroconverters before and after the introduction of HAART. AIDS. Nov 30 2007;21(18):2521-7. [Medline].
Sterling TR, Lau B, Zhang J, Freeman A, Bosch RJ, Brooks JT, et al. Risk Factors for Tuberculosis After Highly Active Antiretroviral Therapy Initiation in the United States and Canada: Implications for Tuberculosis Screening. J Infect Dis. Sep 2011;204(6):893-901. [Medline]. [Full Text].
Bassett IV, Wang B, Chetty S, Giddy J, Losina E, Mazibuko M, et al. Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. Clin Infect Dis. Oct 1 2010;51(7):823-9. [Medline].
Brown M, Varia H, Bassett P, Davidson RN, Wall R, Pasvol G. Prospective study of sputum induction, gastric washing, and bronchoalveolar lavage for the diagnosis of pulmonary tuberculosis in patients who are unable to expectorate. Clin Infect Dis. Jun 1 2007;44(11):1415-20. [Medline].
[Best Evidence] Choi JH, Lee KW, Kang HR, Hwang YI, Jang S, Kim DG, et al. Clinical efficacy of direct DNA sequencing analysis on sputum specimens for early detection of drug-resistant Mycobacterium tuberculosis in a clinical setting. Chest. Feb 2010;137(2):393-400. [Medline].
Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. Sep 9 2010;363(11):1005-15. [Medline]. [Full Text].
Boehme CC, Nicol MP, Nabeta P, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. Apr 30 2011;377(9776):1495-505. [Medline].
Minion J, Leung E, Menzies D, Pai M. Microscopic-observation drug susceptibility and thin layer agar assays for the detection of drug resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. Oct 2010;10(10):688-98. [Medline].
Schuurmans MM, Ellmann A, Bouma H, Diacon AH, Dyckmans K, Bolliger CT. Solitary pulmonary nodule evaluation with 99mTc-methoxy isobutyl isonitrile in a tuberculosis-endemic area. Eur Respir J. Dec 2007;30(6):1090-5. [Medline].
Mazurek GH, Jereb J, Lobue P, Iademarco MF, Metchock B, Vernon A. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR Recomm Rep. Dec 16 2005;54:49-55. [Medline].
Ang M, Htoon HM, Chee SP. Diagnosis of tuberculous uveitis: clinical application of an interferon-gamma release assay. Ophthalmology. Jul 2009;116(7):1391-6. [Medline].
[Guideline] Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep. Jun 25 2010;59:1-25. [Medline].
Manuel O, Humar A, Preiksaitis J, Doucette K, Shokoples S, Peleg AY, et al. Comparison of quantiferon-TB gold with tuberculin skin test for detecting latent tuberculosis infection prior to liver transplantation. Am J Transplant. Dec 2007;7(12):2797-801. [Medline].
Mazurek GH, Weis SE, Moonan PK, Daley CL, Bernardo J, Lardizabal AA, et al. Prospective comparison of the tuberculin skin test and 2 whole-blood interferon-gamma release assays in persons with suspected tuberculosis. Clin Infect Dis. Oct 1 2007;45(7):837-45. [Medline].
[Best Evidence] Chang KC, Leung CC. Systematic review of interferon-gamma release assays in tuberculosis: focus on likelihood ratios. Thorax. Mar 2010;65(3):271-6. [Medline].
Leung CC, Yam WC, Yew WW, Ho PL, Tam CM, Law WS, et al. T-Spot.TB outperforms tuberculin skin test in predicting tuberculosis disease. Am J Respir Crit Care Med. Sep 15 2010;182(6):834-40. [Medline].
Diel R, Loddenkemper R, Niemann S, Meywald-Walter K, Nienhaus A. Negative and Positive Predictive Value of a Whole-Blood Interferon-{gamma} Release Assay for Developing Active Tuberculosis: An Update. Am J Respir Crit Care Med. Jan 1 2011;183(1):88-95. [Medline].
Kim SH, Lee SO, Park JB, Park IA, Park SJ, Yun SC, et al. A prospective longitudinal study evaluating the usefulness of a T-cell-based assay for latent tuberculosis infection in kidney transplant recipients. Am J Transplant. Sep 2011;11(9):1927-35. [Medline].
[Best Evidence] Jafari C, Thijsen S, Sotgiu G, Goletti D, Domínguez Benítez JA, Losi M, et al. Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study. Am J Respir Crit Care Med. Oct 1 2009;180(7):666-73. [Medline]. [Full Text].
[Best Evidence] Lin HC, Lin HC, Chen SF. Increased risk of low birthweight and small for gestational age infants among women with tuberculosis. BJOG. Apr 2010;117(5):585-90. [Medline].
[Best Evidence] Swaminathan S, Narendran G, Venkatesan P, Iliayas S, Santhanakrishnan R, Menon PA, et al. Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial. Am J Respir Crit Care Med. Apr 1 2010;181(7):743-51. [Medline].
Centers for Disease Control and Prevention. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis. CDC. Available at http://www.cdc.gov/tb/TB_HIV_Drugs/default.htm. Accessed 08/20/2008.
[Best Evidence] Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. Feb 25 2010;362(8):697-706. [Medline].
[Best Evidence] Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. Jun 4 2009;360(23):2397-405. [Medline].
CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep. Jun 9 2000;49:1-51. [Medline]. [Full Text].
CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR. 2011;60:1650-1653. [Full Text].
Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365:2155-2166.
Becerra MC, Appleton SC, Franke MF, Chalco K, Arteaga F, Bayona J, et al. Tuberculosis burden in households of patients with multidrug-resistant and extensively drug-resistant tuberculosis: a retrospective cohort study. Lancet. Jan 8 2011;377(9760):147-52. [Medline].
Weir RE, Gorak-Stolinska P, Floyd S, Lalor MK, Stenson S, Branson K, et al. Persistence of the immune response induced by BCG vaccination. BMC Infect Dis. Jan 25 2008;8:9. [Medline]. [Full Text].
[Guideline] American Thoracic Society, CDC, and Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. Jun 20 2003;52:1-77. [Medline].
[Guideline] CDC. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep. Jan 16 2009;58(1):7-10. [Medline].
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