Sections

Treatment

Approach Considerations

Isolate patients with possible tuberculosis (TB) infection in a private room with negative pressure (air exhausted to outside or through a high-efficiency particulate air filter). Medical staff must wear high-efficiency disposable masks sufficient to filter the tubercle bacillus. Continue isolation until sputum smears are negative for 3 consecutive determinations (usually after approximately 2-4 wk of treatment). Unfortunately, these measures are neither possible nor practical in countries where TB is a public health problem.

Drug therapy

For initial empiric treatment of TB, start patients on a 4-drug regimen: isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. Once the TB isolate is known to be fully susceptible, ethambutol (or streptomycin, if it is used as a fourth drug) can be discontinued.^[1]

Patients with TB who are receiving pyrazinamide should undergo baseline and periodic serum uric acid assessments, and patients with TB who are receiving long-term ethambutol therapy should undergo baseline and periodic visual acuity and red-green color perception testing. The latter can be performed with a standard test, such as the Ishihara test for color blindness.

After 2 months of therapy (for a fully susceptible isolate), pyrazinamide can be stopped. Isoniazid plus rifampin are continued as daily or intermittent therapy for 4 more months. If isolated isoniazid resistance is documented, discontinue isoniazid and continue treatment with rifampin, pyrazinamide, and ethambutol for the entire 6 months. Therapy must be extended if the patient has cavitary disease and remains culture-positive after 2 months of treatment.

Directly observed therapy (DOT) is recommended for all patients. With DOT, patients on the above regimens can be switched to 2- to 3-times per week dosing after an initial 2 weeks of daily dosing. Patients on twice-weekly dosing must not miss any doses. Prescribe daily therapy for patients on self-administered medication.

Monitoring

Patients diagnosed with active TB should undergo sputum analysis for Mycobacterium tuberculosis weekly until sputum conversion is documented. Monitoring for toxicity includes baseline and periodic liver enzymes, complete blood cell (CBC) count, and serum creatinine.

Seizures from isoniazid overdose

A special regimen exists for patients with TB who are actively seizing or who have overdosed on antimycobacterial medication. In these patients, overdose with isoniazid should be suspected. The administration of diazepam can be attempted to control seizure activity, but IV pyridoxine is the drug of choice, in a gram-for-isoniazid-ingested-gram dose. If the ingested dose is unknown, 5 g of pyridoxine can be used empirically. For patients who are awake and alert, an oral dose of activated charcoal (1 g/kg) with sorbitol can be administered.

Treatment During Pregnancy

Pregnant women with active TB should be treated, even in the first stage of pregnancy. Isoniazid, rifampin, and ethambutol may be used. In the United States, pyrazinamide is reserved for women with suspected multidrug-resistant TB (MDR-TB). Elsewhere in the world, pyrazinamide is commonly used in pregnant women with TB. Streptomycin should not be used, because it has been shown to have harmful effects on the fetus.

Preventive treatment is recommended during pregnancy, especially in the following types of patients:

Pregnant women with a positive tuberculin skin test result who are HIV seropositive or who have behavioral risk factors for HIV infection but who decline HIV testing
Pregnant women with a positive tuberculin skin test result who have been in close contact with a patient who is smear-positive for pulmonary TB
Pregnant women who had a documented tuberculin skin test conversion during the previous 2 years

Pregnant women are at an increased risk for isoniazid-induced hepatotoxicity and should undergo monthly alanine aminotransferase (ALT) monitoring while on treatment. This risk continues 2-3 months into the postpartum period. Pyridoxine should also be administered to pregnant women receiving isoniazid.

Breastfeeding can be continued during preventive therapy. Many experts recommend supplemental pyridoxine for the breastfed infant.

Lin et al reported that women diagnosed with TB during pregnancy are at an increased risk of having babies who are of low birthweight and are small for their gestational age. However, preterm birth was not more common in women with TB.^[74]

Treatment in Children

Most children with TB can be treated with isoniazid and rifampin for 6 months, along with pyrazinamide for the first 2 months if the culture from the source case is fully susceptible.

For postnatal TB, many experts increase the treatment duration to 9 or 12 months because of the possible impaired immune system in children younger than 12 months. Bacillus Calmette-Guérin (BCG) vaccine is not recommended in infants in the United States but is commonly used around the world.

Isoniazid tablets may be crushed and added to food. Isoniazid liquid without sorbitol should be used to avoid osmotic diarrhea, which can cause decreased absorption.

Rifampin capsules may be opened and the powder added to food. If rifampin is not tolerated, it may be taken in divided doses 20 minutes after light meals.

Ethambutol is often avoided in young children because of difficulties monitoring visual acuity and color perception. However, studies show that ethambutol (15 mg/kg) is well tolerated and can prevent further resistance if the child is infected with a resistant strain. Go to Pediatric Tuberculosis for complete information on treatment of children.

Bedaquiline is also a consideration as part of a 4-drug regimen for multidrug-resistant pulmonary tuberculosis in children aged 5 years or older when an effective treatment regimen cannot otherwise be provided.

Treatment in HIV-Infected Patients

Treatment regimens for active or latent TB in patients with HIV infection are similar to those used in HIV-negative patients, but dose adjustments may be necessary.^{[2, 3]}The most significant differences involve the avoidance of rifampin in patients who are on protease inhibitors. Rifabutin may be used in place of rifampin in such patients.

Antiretroviral therapy

Patients with HIV and TB may develop a paradoxical response (immune reconstitution inflammatory syndrome [IRIS]) when starting antiretroviral therapy. This response has been attributed to a stronger immune response to M tuberculosis. Clinical findings include fever, worsening pulmonary infiltrates, and lymphadenopathy.

However, in an open-label, randomized trial, Abdool Karim et al concluded that the initiation of antiretroviral therapy during TB therapy significantly improved patient survival. In this study, the mortality rate with simultaneous initiation of antiretroviral therapy and TB therapy was 5.4 deaths per 100 person-years (25 deaths in 429 patients), compared with 12.1 deaths per 100 person-years (27 deaths in 213 patients) with antiretroviral therapy started after the completion of TB therapy, a relative reduction of 56%.^[4]

Subsequent studies by these and other researchers found that starting antiretroviral therapy early (eg, within 4 weeks after the start of TB treatment) reduced progression to AIDS and death. In patients with higher CD4+ T-cell counts, however, deferring initiation of antiretroviral therapy until the continuation phase of TB treatment may be a reasonable strategy, because the risks of IRIS and of adverse events that necessitate switching of antiretroviral drugs are lower with later initiation of antiretroviral therapy.^[5]

Treatment length and recurrence rate

Swaminathan et al reported a significantly lower bacteriologic recurrence rate with 9 months, instead of 6 months, of an intermittent (3 times/wk) 4-drug regimen in patients with HIV infection and newly diagnosed TB. Mortality was similar in both groups. The rate of acquired rifampin resistance was high in both groups and was not altered by the longer TB treatment.^[2]

Tuberculous meningitis

In patients with tuberculous meningitis, dexamethasone added to routine 4-drug therapy reduces complications.

Treatment of Tuberculosis Resistant to a Single Drug

The CDC reported that 9.4% of TB cases were resistant to isoniazid in 2018 (16% of these were MDR-TB).^[75]TB that is resistant to isoniazid (with or without resistance to streptomycin) can be treated with rifampin, pyrazinamide, and ethambutol for 6 months. Therapy should be extended to 9 months if the patient remains culture-positive after 2 months of treatment.

TB that is resistant to only rifampin (an unusual occurrence) can be treated with isoniazid, a fluoroquinolone (levofloxacin or moxifloxacin), and ethambutol for 12-18 months, depending on clinical response. Therapy should include pyrazinamide for at least the first 2 months of treatment.

A CDC analysis of resistance to pyrazinamide in US cases showed that such resistance increased from 2% in 1999 to 3.3% in 2009. Pyrazinamide monoresistance was associated with younger age, Hispanic ethnicity, HIV infection, and extrapulmonary disease.^{[76, 77]}TB resistant to pyrazinamide can be treated with isoniazid and rifampin for 9 months. Ethambutol should be included for the first 2 months of treatment.

Treatment of Multidrug-Resistant Tuberculosis

Multidrug-resistant TB (MDR-TB) refers to isolates that are resistant to both isoniazid and rifampin (and possibly other drugs). When MDR-TB is suspected, because of a relevant history or epidemiologic information, start treatment empirically before culture results become available; obtain molecular drug susceptibility testing, if possible. Once results are known, the regimen is modified according to susceptibilities. (Costs are many times higher for the treatment of MDR-TB.) Never add a single new drug to a failing regimen.

Administer at least 5 drugs for the intensive phase of treatment and at least 4 drugs for the continuation phase (listed in order of preference), as follows:^{[6, 7]}

A fluoroquinolone: levofloxacin or moxifloxacin preferred
Bedaquiline
Linezolid
Clofazimine (available only through Investigational New Drug application through FDA)
Cycloserine
An aminoglycoside: streptomycin or amikacin preferred
Ethambutol
Pyrazinamide
Delamanid
Ethionamide
Para-aminosalicylic acid

Successful MDR-TB treatment is more likely in association with such factors as lower prior patient exposure to anti-TB drugs, a higher number of anti-TB drugs to which the infection is still susceptible, and a shorter time since the first TB diagnosis (indicating less advanced disease).

The intensive-phase treatment for MDR-TB should be 5-7 months, followed by the continuation phase, so that the total duration of treatment is 15-24 months after culture conversion. The drugs should be prescribed daily (no intermittent therapy), and the patient should always be on DOT. Weekend DOT may not be possible; therefore, giving self-administered oral drugs on Saturdays and Sundays may be reasonable. All patients should be closely observed for 2 years after completion of treatment, with a low threshold for referral to TB centers.

The diarylquinoline antimycobacterial, bedaquiline (Sirturo), was approved by the FDA in December 2012 as part of a 22-week multidrug regimen for pulmonary MDR-TB. Approval was based on phase 2 data that showed bedaquiline significantly improved time to sputum culture conversion and included 2 consecutive negative sputum cultures collected at least 25 days apart during treatment. At week 24, sputum culture conversion was observed in 77.6% of patients in the bedaquiline treatment group compared with 57.6% of patients in the placebo treatment group (p = 0.014).^{[78, 79]}

In another phase II study by Diacon et al, bedaquiline (TMC207) added to standard therapy for MDR-TB reduced the time to conversion to a negative sputum culture compared with placebo and increased the proportion of patients with conversion of sputum culture (48% vs 9%).^[80]

Bedaquiline gained FDA approval in August 2019 for adolescents aged 12 years or older and for children as young as 5 years in May 2020. This approval was based on evidence from a single-arm, open-label, phase 2 study that enrolled 15 pediatric patients with confirmed or probable MDR-TB infection. The patients were treated with the recommended dosage of bedaquiline for 24 weeks in combination with a background regimen.^[81]

Provisional guidelines from the CDC include the use of bedaquiline on a case-by-case basis in children, HIV-infected persons, pregnant women, persons with extrapulmonary MDR-TB, and patients with comorbid conditions on concomitant medications when an effective treatment regimen cannot otherwise be provided.^{[82, 83]}

The diagnosis of extensively drug-resistant TB (XDR-TB) is established with an isolate that is resistant to isoniazid, rifampin, at least 1 of the quinolones, and at least 1 injectable drug. Treatment options for XDR-TB are very limited, and XDR-TB carries a very high mortality rate.

In August 2019, the FDA approved pretomanid, a nitroimidazooxazine, for adults with XDR-TB, treatment-intolerant TB, or nonresponsive MDR-TB. Pretomanid kills actively replicating M tuberculosis by inhibiting mycolic acid biosynthesis, thereby blocking cell wall production. Efficacy was primarily demonstrated in a study of 109 patients who were treated with pretomanid plus bedaquiline and linezolid. Of the 107 patients who were evaluated 6 months after the end of therapy, treatment was successful in 95 (89%), far exceeding success rates of previously available treatments.^{[84, 85]}

A CDC analysis of the prevalence, trends, and risk factors for pyrazinamide polyresistance was associated with Hispanic ethnicity, Asian race, previous TB diagnosis, and normal chest x-ray and inversely associated with age 45 years and older. Pyrazinamide resistance in multidrug-resistant cases was associated with female sex and previous TB diagnosis. Bacterial lineage, rather than host characteristics, was the primary predictor of pyrazinamide resistance in M tuberculosis cases.^{[76, 77]}

Surgical resection

Surgical resection of an infected lung may be considered to reduce the bacillary burden in patients with MDR-TB. Surgery is recommended for patients with MDR-TB whose prognosis with medical treatment is poor. Surgery can be performed with a low mortality rate (< 3%), with prolonged periods of a chemotherapeutic regimen used for more than 1 year after surgery.

Procedures include segmentectomy (rarely used), lobectomy, and pneumonectomy. Pleurectomies for thick pleural peel are rarely indicated.

Intraoperative infection of uninvolved lung tissue has been observed in resections. Complications include the usual perioperative complications, recurrent disease, and bronchopleural fistulas.

Treatment of Latent TB

The antimycobacterial rifapentine (Priftin), which was previously approved for use against active pulmonary TB caused by Mycobacterium tuberculosis, has now been approved by the US Food and Drug Administration (FDA) for use, in combination with isoniazid, in the treatment of latent TB infection. Therapy was approved for patients aged 2 years or older who are at high risk of progression to TB disease.^{[86, 11]}

FDA approval for the new indication was partially based on a randomized study of more than 6000 patients in which a 12-dose, once-weekly regimen of directly observed therapy (DOT) with rifapentine plus isoniazid was compared with a regimen consisting of 9 months of self-administered daily isoniazid. The cumulative rate of tuberculosis disease development was 0.16% in the rifapentine-isoniazid group (5 out of 3074 patients), compared with 0.32% in the isoniazid group (10 out of 3074 patients).^{[86, 11]}

Patients with a clinically significant result on tuberculin skin testing or a positive interferon-gamma release assay (IGRA) result should receive a course of therapy for latent TB, once active infection and disease are ruled out. Recommended regimens for latent TB published by the US Centers for Disease Control and Prevention (CDC) are as follows^{[8, 12]}:

Isoniazid 300 mg - Daily for 9 months
Isoniazid 900 mg - Twice weekly for 9 months (administered as DOT)
Isoniazid 300 mg - Daily for 6 months (should not be used in patients with fibrotic lesions on chest radiography, patients with HIV infection, or children)
Isoniazid 900 mg - Twice weekly for 6 months (administered as DOT; should not be used in patients with fibrotic lesions on chest radiography, patients with HIV infection, or children)
Rifampin 600 mg - Daily for 4 months
Rifapentine 750-900 mg (based on weight) plus isoniazid 900 mg - Once-weekly for 12 weeks (self-administered or as DOT)
No longer recommended - Rifampin plus pyrazinamide daily for 2 months (increased liver toxicity)

Self-administered therapy versus directly observed therapy

A 2017 study has reported that self-administered therapy for latent tuberculosis infection (LTBI) may be a viable option for patients when direct medical oversight is unavailable.^[87]

As part of an open-label, phase 4 randomized clinical trial, researchers enrolled 1002 patients from outpatient TB clinics in the United States, Spain, Hong Kong, and South Africa between September 2012 and April 2014. Patients with active TB, prior treatment for TB lasting more than 1 week, contact with someone with a resistant form of TB, or prior intolerance to anti-TB agents were excluded. Most enrolled patients (n = 774) were in the United States; however, participants were demographically similar between groups. The median age was 36 years, and 48.1% of the patients were women.

Patients were randomly assigned to receive isoniazid or rifapentine once weekly by directly observed therapy (DOT), self-administered therapy (SAT) with weekly text message reminders, or SAT without reminders. The primary objective of the study was to compare treatment adherence, defined as completion of 11 or more doses of medication within 16 weeks. All participants were counseled on correct pill-taking and symptoms of drug toxicity. All patients had monthly follow-up visits both during therapy and for 28 days after the last dose to assess adherence and monitor for adverse events.

The researchers documented overall completion rates of 87.2% (95% confidence interval [CI], 83.1% - 90.5%) in the DOT group, 74.0% (CI, 68.9% - 78.6%) in the SAT group, and 76.4% (CI, 71.3% - 80.8%) in the SAT with reminders group.

Specifically, among US patients, the researchers noted treatment completion rates of 85.4% (CI, 80.4% - 89.4%), 77.9% (CI, 72.7% - 82.6%), and 76.7% (CI, 70.9% - 81.7%), respectively. Using a 15% difference to define noninferiority, the researchers found SAT without reminders to be noninferior to DOT in the United States.

The researchers also found that adverse events were similar among all 3 groups.^[87]

Isoniazid plus rifapentine

This combination, approved by the FDA in November 2014, is indicated for patients aged 2 years and older who are at high risk for developing active TB disease (including those in close contact with active TB patients, patients who have had a recent conversion to a positive tuberculin skin test, HIV-infected patients, and those with pulmonary fibrosis on radiograph).

Consider using this 12-dose regimen among populations that are unlikely to complete longer courses of therapy with isoniazid alone. This regimen is not recommended for children under 2 years, pregnant women or women planning to become pregnant, or patients whose TB infection is presumed to be the result of exposure to a person with TB disease that is resistant to 1 of the 2 drugs.

The PREVENT TB Study compared this regimen with 9 months of self-administered, daily isoniazid (300 mg) therapy for latent tuberculosis. The combination therapy was shown to be as effective as isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate.^[11]

Isoniazid therapy in children

Children younger than 12 years should receive isoniazid for 9 months. In addition, children younger than 5 years who have close contact with a person who has active TB should be started on isoniazid, even if the results on skin testing are negative; preventive therapy can be stopped if the results on repeat skin testing are negative 2-3 months after last contact with a culture-positive source case. Alternatively, children aged 2-11 years may receive DOT with weight-base dosing of once-weekly rifapentine plus isoniazid for 12 weeks.^{[88, 11]}

MDR-TB and patient contacts

Household contacts of patients with MDR-TB have a particularly high risk for tuberculosis, 7.8% within 4 years in a study from Lima, Peru.^[89]Limited data are available on regimens for the treatment of patients exposed to MDR-TB. However, if treatment is initiated, at least 2 drugs should be given, and the index isolate should be susceptible to all drugs used

Therapy in patients with HIV infection

Recommended regimens in patients with HIV infection include rifampin alone daily for 4 months or isoniazid, daily or twice weekly, for 9 months. Patients on antiretroviral therapy may need rifabutin instead of rifampin because of potential drug interactions.

Prevention and Consultations

The BCG vaccine continues to be used throughout much of the world and usually provides protection until early childhood. Immunity begins to wane, however, as early as 3 months after administration.^[90]As previously noted, use of the BCG vaccine is not recommended in infants in the United States.

In early 2020, Darrah et al reported on the promising efficacy of BCG vaccine administered intravenously rather than intradermally in macaque monkeys. Intravenous immunization resulted in a significantly more robust T-cell response in lung lymph nodes, blood spleen, and bronchoalveolar lavage than traditional intradermal immunization. These findings have not been confirmed in human studies.^[91]

In a meta-analysis of eight randomized controlled studies involving a total of 10,320 patients aged 15 years or younger, Ayieko et al found that isoniazid prophylaxis reduced the risk of developing TB, with a pooled risk ratio (RR) of 0.65 (P = 0.004). However, isoniazid had no effect in children who initiated treatment at 4 months of age or earlier. When those patients were excluded, isoniazid prophylaxis reduced the risk of developing TB by 59% (RR, 0.41; P< 0.001).^[92]

The public health sector should be notified and involved in cases of TB. Local county health departments are expert and funded in the care of TB infection. Consultation with a primary care, pulmonology, internal medicine, or infectious disease specialist prior to initiating therapy is helpful, and it may be appropriate for this consultant to manage the antituberculous chemotherapy. Consult an expert on MDR-TB in cases of multidrug resistance.

Long-Term Monitoring

After completion of treatment for pulmonary TB, patients remain at risk for late complications, which include relapse, aspergilloma, bronchiectasis, broncholithiasis, fibrothorax, and possibly carcinoma. A copy of the chest radiograph at the time of completion of therapy should be provided to the patient to facilitate the diagnosis of late complications.

The relapse rate following appropriate completed therapy is only 0-4% and occurs within the first 2 years after completion. Aspergilloma is a fungus ball that develops in a residual lung abnormality (eg, pneumatocele, bulla, bleb, cyst). It may appear as a crescent sign on chest radiographs. Other superinfections may manifest with an air-fluid level (seen in the image below) and often contain mixed bacteria, including anaerobes.

Pulmonary tuberculosis with air-fluid level.

View Media Gallery

Hemoptysis is the most common late complication. Bleeding from submucosal bronchial veins is usually self-limited.

Other complications include the following:

Broncholithiasis - The result of spontaneous lymph node migration into the bronchial tree; may be associated with postobstructive pneumonia or esophageal perforation
Chronic obstructive pulmonary disease (COPD) - Bronchiectasis may progress to COPD
Fibrothorax - The development of trapped lung due to pleural fibrosis and scarring
Cancer - The risk of carcinoma is controversial but should be considered with newly developing clubbing

Adverse effects of antibiotic therapy in TB can be severe. They include the following:

Hepatitis
Peripheral neuropathy
Retrobulbar optic neuropathy

Guidelines

[Guideline] Treatment of tuberculosis. MMWR Recomm Rep. 2003 Jun 20. 52:1-77. [QxMD MEDLINE Link].
Swaminathan S, Narendran G, Venkatesan P, 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. 2010 Apr 1. 181(7):743-51. [QxMD MEDLINE Link].
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.
Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010 Feb 25. 362(8):697-706. [QxMD MEDLINE Link]. [Full Text].
Torok ME, Farrar JJ. When to start antiretroviral therapy in HIV-associated tuberculosis. N Engl J Med. 2011 Oct 20. 365(16):1538-40. [QxMD MEDLINE Link].
Nahid P, Mase SR, Migliori GB, Sotgiu G, Bothamley GH, Brozek JL, et al. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir Crit Care Med. 2019 Nov 15. 200 (10):e93-e142. [QxMD MEDLINE Link].
World Health Organization. WHO consolidated guidelines on drug-resistant tuberculosis treatment. 2019. [Full Text].
Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep. 2000 Jun 9. 49:1-51. [QxMD MEDLINE Link].
Menzies D, Adjobimey M, Ruslami R, et al. Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults. N Engl J Med. 2018 Aug 2. 379 (5):440-453. [QxMD MEDLINE Link].
Diallo T, Adjobimey M, Ruslami R, et al. Safety and Side Effects of Rifampin versus Isoniazid in Children. N Engl J Med. 2018 Aug 2. 379 (5):454-463. [QxMD MEDLINE Link].
Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8. 365(23):2155-66. [QxMD MEDLINE Link].
Borisov AS, Bamrah Morris S, Njie GJ, Winston CA, Burton D, Goldberg S, et al. Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection. MMWR Morb Mortal Wkly Rep. 2018 Jun 29. 67 (25):723-726. [QxMD MEDLINE Link].
Extensively Drug-Resistant Tuberculosis (XDR TB). Centers for Disease Control and Prevention. Available at http://www.cdc.gov/tb/publications/factsheets/drtb/xdrtb.htm. Accessed: November 7, 2012.
Asensio JA, Arbues A, Perez E, Gicquel B, Martin C. Live tuberculosis vaccines based on phoP mutants: a step towards clinical trials. Expert Opin Biol Ther. 2008 Feb. 8(2):201-11. [QxMD MEDLINE Link].
Wells CD, Cegielski JP, Nelson LJ, et al. HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis. 2007 Aug 15. 196 Suppl 1:S86-107. [QxMD MEDLINE Link].
Burman WJ, Goldberg S, Johnson JL, et al. Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis. Am J Respir Crit Care Med. 2006 Aug 1. 174(3):331-8. [QxMD MEDLINE Link].
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. 2009 Feb 13. 58:1-43. [QxMD MEDLINE Link].
Drug-resistant tuberculosis. World Health Organization. Available at http://www.who.int/tb/challenges/mdr/tdrfaqs/en/index.html. Accessed: November 26, 2012.
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. 2008 Jan. 12(1):99-104. [QxMD MEDLINE Link].
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].
CDC. Trends in Tuberculosis – United States, 2011. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6111a2.htm?s_cid=mm6111a2_w.
Sokolove PE, Lee BS, Krawczyk JA, et al. Implementation of an emergency department triage procedure for the detection and isolation of patients with active pulmonary tuberculosis. Ann Emerg Med. 2000 Apr. 35(4):327-36. [QxMD MEDLINE Link].
Moran GJ, McCabe F, Morgan MT, Talan DA. Delayed recognition and infection control for tuberculosis patients in the emergency department. Ann Emerg Med. 1995 Sep. 26(3):290-5. [QxMD MEDLINE Link].
Menzies D, Joshi R, Pai M. Risk of tuberculosis infection and disease associated with work in health care settings. Int J Tuberc Lung Dis. 2007 Jun. 11(6):593-605. [QxMD MEDLINE Link].
Verhagen LM, van den Hof S, van Deutekom H, et al. Mycobacterial factors relevant for transmission of tuberculosis. J Infect Dis. 2011 May. 203(9):1249-55. [QxMD MEDLINE Link].
Leung CC, Lam TH, Chan WM, et al. Lower risk of tuberculosis in obesity. Arch Intern Med. 2007 Jun 25. 167(12):1297-304. [QxMD MEDLINE Link].
Slama K, Chiang CY, Enarson DA, et al. Tobacco and tuberculosis: a qualitative systematic review and meta-analysis. Int J Tuberc Lung Dis. 2007 Oct. 11(10):1049-61. [QxMD MEDLINE Link].
Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001 Oct 11. 345(15):1098-104. [QxMD MEDLINE Link].
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. 2010 Oct 1. [QxMD MEDLINE Link].
Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV. Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. N Engl J Med. 1998 Mar 5. 338(10):640-4. [QxMD MEDLINE Link].
Cervino AC, Lakiss S, Sow O, Hill AV. Allelic association between the NRAMP1 gene and susceptibility to tuberculosis in Guinea-Conakry. Ann Hum Genet. 2000 Nov. 64:507-12. [QxMD MEDLINE Link].
Searle S, Blackwell JM. Evidence for a functional repeat polymorphism in the promoter of the human NRAMP1 gene that correlates with autoimmune versus infectious disease susceptibility. J Med Genet. 1999 Apr. 36(4):295-9. [QxMD MEDLINE Link]. [Full Text].
Tosh K, Campbell SJ, Fielding K, et al. Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa. Proc Natl Acad Sci U S A. 2006 Jul 5. 103(27):10364-8. [QxMD MEDLINE Link]. [Full Text].
Khor CC, Vannberg FO, Chapman SJ, et al. CISH and susceptibility to infectious diseases. N Engl J Med. 2010 Jun 3. 362(22):2092-101. [QxMD MEDLINE Link].
Intemann CD, Thye T, Niemann S, et al. Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains. PLoS Pathog. 2009 Sep. 5(9):e1000577. [QxMD MEDLINE Link]. [Full Text].
Rossouw M, Nel HJ, Cooke GS, van Helden PD, Hoal EG. Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene. Lancet. 2003 May 31. 361(9372):1871-2. [QxMD MEDLINE Link].
Levin M, Newport MJ, D'Souza S, et al. Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene?. Lancet. 1995 Jan 14. 345(8942):79-83. [QxMD MEDLINE Link].
Newport MJ, Huxley CM, Huston S, et al. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med. 1996 Dec 26. 335(26):1941-9. [QxMD MEDLINE Link].
Khor CC, Chapman SJ, Vannberg FO, et al. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat Genet. 2007 Apr. 39(4):523-8. [QxMD MEDLINE Link]. [Full Text].
Barreiro LB, Neyrolles O, Babb CL, et al. Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis. PLoS Med. 2006 Feb. 3(2):e20. [QxMD MEDLINE Link]. [Full Text].
Cox HS, Morrow M, Deutschmann PW. Long term efficacy of DOTS regimens for tuberculosis: systematic review. BMJ. 2008 Mar 1. 336(7642):484-7. [QxMD MEDLINE Link]. [Full Text].
Jasmer RM, Bozeman L, Schwartzman K, et al. Recurrent tuberculosis in the United States and Canada: relapse or reinfection?. Am J Respir Crit Care Med. 2004 Dec 15. 170(12):1360-6. [QxMD MEDLINE Link].
van Rie A, Warren R, Richardson M, et al. Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N Engl J Med. 1999 Oct 14. 341(16):1174-9. [QxMD MEDLINE Link].
Waitt CJ, Peter K Banda N, White SA, et al. Early deaths during tuberculosis treatment are associated with depressed innate responses, bacterial infection, and tuberculosis progression. J Infect Dis. 2011 Aug. 204(3):358-62. [QxMD MEDLINE Link]. [Full Text].
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. 2005 Dec 16. 54:49-55. [QxMD MEDLINE Link].
Ang M, Htoon HM, Chee SP. Diagnosis of tuberculous uveitis: clinical application of an interferon-gamma release assay. Ophthalmology. 2009 Jul. 116(7):1391-6. [QxMD MEDLINE Link].
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. 2007 Dec. 30(6):1090-5. [QxMD MEDLINE Link].
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. 2005 Jan 15. 191(2):150-8. [QxMD MEDLINE Link].
Muga R, Ferreros I, Langohr K, et al. Changes in the incidence of tuberculosis in a cohort of HIV-seroconverters before and after the introduction of HAART. AIDS. 2007 Nov 30. 21(18):2521-7. [QxMD MEDLINE Link].
Sterling TR, Lau B, Zhang J, 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. 2011 Sep. 204(6):893-901. [QxMD MEDLINE Link]. [Full Text].
Bassett IV, Wang B, Chetty S, et al. Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. Clin Infect Dis. 2010 Oct 1. 51(7):823-9. [QxMD MEDLINE Link].
[Guideline] Jensen PA, Lambert LA, Iademarco MF, Ridzon R. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005 Dec 30. 54:1-141. [QxMD MEDLINE Link].
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. 2007 Jun 1. 44(11):1415-20. [QxMD MEDLINE Link].
Jafari C, Thijsen S, Sotgiu G, 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. 2009 Oct 1. 180(7):666-73. [QxMD MEDLINE Link]. [Full Text].
Tan SH, Tan BH, Goh CL, et al. Detection of Mycobacterium tuberculosis DNA using polymerase chain reaction in cutaneous tuberculosis and tuberculids. Int J Dermatol. 1999 Feb. 38(2):122-7. [QxMD MEDLINE Link].
Vieites B, Suarez-Penaranda JM, Perez Del Molino ML, 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. 2005 Jun. 152(6):1394-6. [QxMD MEDLINE Link].
[Guideline] Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep. 2009 Jan 16. 58(1):7-10. [QxMD MEDLINE Link].
Reuters Health Information. Direct nucleic acid amplification testing improves TB diagnosis. Medscape Medical News. June 6, 2013. [Full Text].
Marks SM, Cronin W, Venkatappa T, et al. The Health-System Benefits and Cost-effectiveness of Using Mycobacterium Tuberculosis Direct Nucleic Acid Amplification Testing to Diagnose Tuberculosis Disease in the United States. Clin Infect Dis. 2013 May 22. [QxMD MEDLINE Link].
Badak FZ, Kiska DL, Setterquist S, et al. Comparison of mycobacteria growth indicator tube with BACTEC 460 for detection and recovery of mycobacteria from clinical specimens. J Clin Microbiol. 1996 Sep. 34(9):2236-9. [QxMD MEDLINE Link]. [Full Text].
Choi JH, Lee KW, Kang HR, 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. 2010 Feb. 137(2):393-400. [QxMD MEDLINE Link].
Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010 Sep 9. 363(11):1005-15. [QxMD MEDLINE Link]. [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. 2011 Apr 30. 377(9776):1495-505. [QxMD MEDLINE Link].
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. 2010 Oct. 10(10):688-98. [QxMD MEDLINE Link].
CDC. Classification of Tuberculin Skin Reactions. Available at http://www.cdc.gov/tb/publications/LTBI/diagnosis.htm#3. Accessed: June 11, 2012.
[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. 2010 Jun 25. 59:1-25. [QxMD MEDLINE Link].
Manuel O, Humar A, Preiksaitis J, et al. Comparison of quantiferon-TB gold with tuberculin skin test for detecting latent tuberculosis infection prior to liver transplantation. Am J Transplant. 2007 Dec. 7(12):2797-801. [QxMD MEDLINE Link].
Mazurek GH, Weis SE, Moonan PK, 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. 2007 Oct 1. 45(7):837-45. [QxMD MEDLINE Link].
Chang KC, Leung CC. Systematic review of interferon-gamma release assays in tuberculosis: focus on likelihood ratios. Thorax. 2010 Mar. 65(3):271-6. [QxMD MEDLINE Link].
Leung CC, Yam WC, Yew WW, et al. T-Spot.TB outperforms tuberculin skin test in predicting tuberculosis disease. Am J Respir Crit Care Med. 2010 Sep 15. 182(6):834-40. [QxMD MEDLINE Link].
Diel R, Loddenkemper R, Niemann S, Meywald-Walter K, Nienhaus A. Negative and positive predictive value of a whole-blood interferon-? release assay for developing active tuberculosis: an update. Am J Respir Crit Care Med. 2011 Jan 1. 183(1):88-95. [QxMD MEDLINE Link].
Kim SH, Lee SO, Park JB, 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. 2011 Sep. 11(9):1927-35. [QxMD MEDLINE Link].
Lin HC, Lin HC, Chen SF. Increased risk of low birthweight and small for gestational age infants among women with tuberculosis. BJOG. 2010 Apr. 117(5):585-90. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2018. 2019. [Full Text].
Kurbatova EV, Cavanaugh JS, Dalton T, Click E, Cegielski JP. Epidemiology of pyrazinamide-resistant tuberculosis in the United States, 1999-2009. Clin Infect Dis. 2013 Jul 9. [QxMD MEDLINE Link].
Boggs W. Increasing Prevalence of Pyrazinamide-Resistant Tuberculosis. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/808192. Accessed: July 29, 2013.
Sirturo (bedaquiline) prescribing information [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Johnson & Johnson. December, 2012. Available at [Full Text].
Tucker ME. FDA approves bedaquiline for resistant TB treatment. Medscape Medical News. Dec 31, 2012. Available at http://www.medscape.com/viewarticle/776901. Accessed: January 8, 2013.
Diacon AH, Pym A, Grobusch M, et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009 Jun 4. 360(23):2397-405. [QxMD MEDLINE Link].
Achar J, Hewison C, Cavalheiro AP, Skrahina A, Cajazeiro J, Nargiza P, et al. Off-Label Use of Bedaquiline in Children and Adolescents with Multidrug-Resistant Tuberculosis. Emerg Infect Dis. 2017 Oct. 23 (10):1711-1713. [QxMD MEDLINE Link]. [Full Text].
CDC. Provisional CDC guidelines for the use and safety monitoring of bedaquiline fumarate (Sirturo) for the treatment of multidrug-resistant tuberculosis. MMWR Recomm Rep. 2013 Oct 25. 62:1-12. [QxMD MEDLINE Link].
Barclay L. MDR TB: CDC Issues Guidelines for Use of New Drug. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/813151. Accessed: October 28, 2013.
Conradie F, Diacon AH, Everitt D, Mendel C, van Niekerk C, Howell P, et al. The NIX-TB trial of pretomanid, bedaquiline and linezolid to treat XDR TB. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2017. Seattle, Washington. February 15, 2017. [Full Text].
Pretomanid [package insert]. Hyderabad, India: Mylan (for TB Alliance). August, 2019. Available at [Full Text].
Sanofi Receives FDA Approval of Priftin® (Rifapentine) Tablets for the Treatment of Latent Tuberculosis Infection. Available at http://en.sanofi.com/Images/37707_20141202_priftin_en.pdf. Accessed: Dec 10 2014.
Belknap R, Holland D, Feng PJ, Millet JP, Caylà JA, Martinson NA, et al. Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial. Ann Intern Med. 2017 Nov 7. [QxMD MEDLINE Link].
CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR. 2011;60:1650-1653.
Becerra MC, Appleton SC, Franke MF, et al. Tuberculosis burden in households of patients with multidrug-resistant and extensively drug-resistant tuberculosis: a retrospective cohort study. Lancet. 2011 Jan 8. 377(9760):147-52. [QxMD MEDLINE Link].
Weir RE, Gorak-Stolinska P, Floyd S, et al. Persistence of the immune response induced by BCG vaccination. BMC Infect Dis. 2008 Jan 25. 8:9. [QxMD MEDLINE Link]. [Full Text].
Darrah PA, Zeppa JJ, Maiello P, et al. Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature. 2020 Jan. 577 (7788):95-102. [QxMD MEDLINE Link].
Ayieko J, Abuogi L, Simchowitz B, Bukusi EA, Smith AH, Reingold A. Efficacy of isoniazid prophylactic therapy in prevention of tuberculosis in children: a meta-analysis. BMC Infect Dis. 2014 Feb 20. 14:91. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Sterling TR, Njie G, Zenner D, Cohn DL, Reves R, Ahmed A, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020 Feb 14. 69 (1):1-11. [QxMD MEDLINE Link].
Hackethal V. Short TB Therapies Fail in Larger, Longer Trials. Medscape Medical News. Available at http://www.medscape.com/viewarticle/833799. Accessed: October 25, 2014.
Merle CS, Fielding K, Sow OB, et al. A four-month gatifloxacin-containing regimen for treating tuberculosis. N Engl J Med. 2014 Oct 23. 371(17):1588-98. [QxMD MEDLINE Link].
Jindani A, Harrison TS, Nunn AJ, et al. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med. 2014 Oct 23. 371(17):1599-608. [QxMD MEDLINE Link].
Gillespie SH, Crook AM, McHugh TD, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014 Oct 23. 371(17):1577-87. [QxMD MEDLINE Link].
Warner DF, Mizrahi V. Shortening treatment for tuberculosis--to basics. N Engl J Med. 2014 Oct 23. 371(17):1642-3. [QxMD MEDLINE Link].
CDC. Tuberculosis (TB). Data and Statistics. Available at http://www.cdc.gov/tb/statistics/default.htm. Accessed: June 7, 2012.
WHO. Global tuberulosis control 2008: surveillance, planning, financing. World Health Organization. Available at http://www.who.int/topics/tuberculosis/en/. Accessed: October 13, 2010.
Xu P, Chen H, Xu J, Wu M, Zhu X, Wang F, et al. Moxifloxacin is an effective and safe candidate agent for the tuberculosis treatment: a meta-analysis. Int J Infect Dis. 2015 Oct 16. [QxMD MEDLINE Link].

Media Gallery

Acid-fast bacillus smear showing characteristic cording in Mycobacterium tuberculosis.
This radiograph shows a patient with typical radiographic findings of tuberculosis.
This is a chest radiograph taken after therapy was administered to a patient with tuberculosis.
Anteroposterior chest radiograph of a young patient who presented to the emergency department (ED) with cough and malaise. The radiograph shows a classic posterior segment right upper lobe density consistent with active tuberculosis. This woman was admitted to isolation and started empirically on a 4-drug regimen in the ED. Tuberculosis was confirmed on sputum testing. Image courtesy of Remote Medicine (remotemedicine.org).
Lateral chest radiograph of a patient with posterior segment right upper lobe density consistent with active tuberculosis. Image courtesy of Remote Medicine (remotemedicine.org).
Pulmonary tuberculosis with air-fluid level.
Under a high magnification of 15549x, this scanning electron micrograph depicts some of the ultrastructural details seen in the cell wall configuration of a number of Gram-positive Mycobacterium tuberculosis bacteria. As an obligate aerobic organism, M. tuberculosis can only survive in an environment containing oxygen. This bacterium ranges in length between 2-4 microns, with a width between 0.2-0.5 microns. Image courtesy of the Centers for Disease Control and Prevention/Dr. Ray Butler.
Numerous acid-fast bacilli (pink) from a bronchial wash are shown on a high-power oil immersion.
Necrotizing granuloma due to tuberculosis shown on low-power hematoxylin and eosin stain. There is central caseous necrosis and a multinucleated giant cell in the central left. Mixed inflammation is seen in the background.
This chest radiograph shows asymmetry in the first costochondral junctions of a 37-year-old man who presented with cough and fever. Further clarification with computed tomography is needed.
Axial noncontrast enhanced computed tomography with pulmonary window shows a cavity with an irregular wall in the right apex of a 37-year-old man who presented with cough and fever (same patient as above).
Coronal reconstructed computed tomography image shows the right apical cavity in a 37-year-old man who presented with cough and fever (same patient as above).
This posteroanterior chest radiograph shows right upper lobe consolidation with minimal volume loss (elevated horizontal fissure) and a cavity in a 43-year-old man who presented with cough and fever.
Axial chest computed tomography without intravenous contrast with pulmonary window setting shows a right apical thick-walled cavity and surrounding lung consolidation in a 43-year-old man who presented with cough and fever (same patient as above).
Coronal reconstructed computed tomography image shows the consolidated, partially collapsed right upper lobe with a cavity that is directly connected to a bronchus in a 43-year-old man who presented with cough and fever (same patient as above).
The posteroanterior chest radiograph shows a large cavity with surrounding consolidation in the lingular portion of the left upper lobe in a 43-year-old man who presented with cough and hemoptysis. There are also a few nodular opacities in the right mid-lung zone.
Axial chest computed tomography without intravenous contrast with pulmonary window setting through the mid-chest shows a large, irregular-walled cavity with nodules and air-fluid level and two smaller cavities in a 43-year-old man who presented with cough and hemoptysis (same patient as above). Small, patchy peripheral opacities are also present in the left lower lobe. In the right mid-lung, nodular opacities are in a tree-in-bud distribution, suggestive of endobronchial spread.
Coronal reconstructed computed tomography image shows the lingular cavity with irregular nodules and right mid-lung nodular opacities in a 43-year-old man who presented with cough and hemoptysis (same patient as above).

of 18

Author

Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic

Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, Infectious Diseases Society of Ohio

Disclosure: Received research grant from: Regeneron.

Coauthor(s)

Judith K Amorosa, MD, FACR Clinical Professor of Radiology and Vice Chair for Faculty Development and Medical Education, Rutgers Robert Wood Johnson Medical School

Judith K Amorosa, MD, FACR is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of University Radiologists, Radiological Society of North America, Society of Thoracic Radiology

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Acknowledgements

Erica Bang State University of New York Downstate Medical Center College of Medicine