INTRODUCTION

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Background

Tuberculosis (TB) is the number one infectious disease killer worldwide. The World Health Organization estimates that 2 billion people have latent TB, while another 3 million people worldwide die each year due to TB.

In the United States, the isoniazid (INH) resistance rate was 7.8% in 2005, with the individual state rates varying from 0-14.9%. The overall rate of multidrug resistant TB (MDR-TB; with resistance to at least isoniazid and rifampin) was 1.2%, with the individual state rates varying from 0-3.7%. Worldwide, the number of new MDR-TB cases in 2005 was estimated at 460,000.

Pathophysiology

Humans are the only known reservoir for Mycobacterium tuberculosis. TB is transmitted by airborne droplet nuclei, which may contain fewer than 10 bacilli. Exposure to TB occurs by sharing common airspace with a patient who is infectious. When inhaled, droplet nuclei are deposited within the terminal airspaces of the lung. Upon encountering the bacilli, macrophages ingest and transport the bacteria to regional lymph nodes.

The bacilli have 4 potential fates: (1) they may be killed by the immune system, (2) they may multiply and cause primary TB, (3) they may become dormant and remain asymptomatic, or (4) they may proliferate after a latency period (reactivation disease). Reactivation disease may occur following either (2) or (3) above.

Frequency

United States

Beginning in 1985, a resurgence of TB was noted. The increase was primarily observed in ethnic minorities and especially in persons infected with HIV. TB control programs were revamped and strengthened across the United States. After peaking at 25,287 cases in 1993, the number of reported cases began to fall again. In 2005, 14,903 cases of TB were reported to the US Centers for Disease Control and Prevention (CDC). This corresponds to a rate of 4.8 cases per 100,000 population. In 2005, 7,656 cases (54.3% of all cases in the United States) were reported among foreign-born persons. More than half (56%) of cases involving foreign-born individuals in 2005 were reported in persons from Mexico (25%), the Philippines (11%), Vietnam (8%), India (7%), and China (5%). Foreign-born persons account for a steadily increasing proportion of all reported TB cases. An estimated 10-15 million people in the United States have latent infection.

International

An estimated 20-33% of the world's population is infected with M tuberculosis. 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 (eg, Balkan countries). Countries in Eastern Europe have an intermediate prevalence. Costa Rica, western and northern Europe, the United States, Canada, Israel, and most countries in the Caribbean have the lowest prevalence.

Mortality/Morbidity

The case-fatality rate for TB was 50% for untreated patients before the advent of antibiotic therapy. Deaths worldwide are estimated at 3 million per year. In the United States, the mortality rate dropped from 12.4 deaths per 100,000 population in 1953 to 0.6 deaths per 100,000 population in 1993; this is approximately 7% per newly identified case.

• MDR-TB cases have a higher reported mortality rate. Patients with underlying diseases predisposing to active TB also have higher mortality rates.
• The mortality rate of untreated congenital TB is 50%.
• TB can mimic congenital syphilis or cytomegalovirus (CMV) infection.

Race

Based on 2005 CDC data, Hispanics, blacks, and Asians had TB rates that were 7.3%, 8.3%, and 19.6% times those in whites, respectively. However, race is not clearly an independent risk factor. Risk is best defined on the basis of social, economic, and medical factors.

Sex

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. Men are more likely to have a positive tuberculin skin test result. The reason for these differences may be social rather than biological in nature.

Age

In the 1997 CDC data for the United States, more than 60% of cases occurred in persons aged 25-64 years. The age-specific risk was highest in persons older than 65 years. Infection in infants and young children (up to 5 y) always indicates recent transmission. If left untreated, it may result in life-threatening meningitis or disseminated disease. Elderly patients may not have typical signs and symptoms of infection because they may not mount a good immune response. In elderly patients, an active tuberculous infection may manifest as a nonresolving pneumonitis.

CLINICAL

Section 3 of 11  

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History

• Pulmonary tuberculosis (TB): Typical symptoms of pulmonary TB include a productive cough, fever, and weight loss. Occasionally, patients may present with hemoptysis or chest pain. Other systemic symptoms include anorexia, fatigue, or night sweats.
• Tuberculous meningitis: Patients may present with a headache that is either intermittent or persistent for 2-3 weeks. Subtle mental status changes may progress to coma over a period of days to weeks. Fever may be low-grade or absent.
• Skeletal TB: The most common site of involvement is the spine (Pott disease). Symptoms include back pain or stiffness. Lower extremity paralysis occurs in as many as half the patients with undiagnosed Pott disease. Tuberculous arthritis usually involves only 1 joint. Although any joint may be involved, the hip or the knee is affected most commonly, followed by the ankle, elbow, wrist, and shoulder. Pain may precede radiographic changes by weeks to months.
• Genitourinary TB: Reported symptoms include flank pain, dysuria, or frequency. In men, genital TB may manifest as epididymitis or a scrotal mass. In women, genital TB may mimic pelvic inflammatory disease. TB causes approximately 10% of sterility in women worldwide and approximately 1% in industrialized countries.
• Gastrointestinal TB: Any site along the gastrointestinal tract may become infected. Symptoms are referable to the site infected, including the following: nonhealing ulcers of the mouth or anus; difficulty swallowing with esophageal disease; abdominal pain mimicking peptic ulcer disease with stomach or duodenal infection; malabsorption with infection of the small intestine; and pain, diarrhea, or hematochezia with infection of the colon.
• Tuberculous lymphadenitis (scrofula): The most common site is in the neck along the sternocleidomastoid muscle. It usually is unilateral, with little or no pain. Advanced disease may suppurate and form a draining sinus.
• Cutaneous TB: Direct inoculation may result in an ulcer or wartlike lesion. Contiguous spread from an infected lymph node typically results in a draining sinus. Hematogenous spread may result in a reddish brown plaque on the face or extremities (lupus vulgaris) or tender nodules or abscesses.

Physical

Findings upon physical examination depend on the organs involved.

• Patients with pulmonary TB have abnormal breath sounds, especially over the upper lobes or areas involved.
• Signs of extrapulmonary TB differ depending on the tissues involved. Signs may include confusion, coma, neurologic deficit, chorioretinitis, lymphadenopathy, and cutaneous lesions (as described above).
• Postnatal TB is contracted via the airborne route. The most common findings are adenopathy and a lung infiltrate. However, the chest radiography findings can be normal in infants with disseminated disease. Many experts increase treatment time to 9 or 12 months because of the possible impaired immune system in children younger than 12 months. Bacille Calmette-Guérin vaccine is not recommended for infants in the United States but is commonly used around the world.

Causes

M tuberculosis is a slow-growing organism, requiring 4-8 weeks for visible growth on solid medium. The organism grows in parallel groups called cords (see Image 1). It retains many stains after decoloration with acid-alcohol, which is the basis of acid-fast stains.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Blastomycosis
Catscratch disease

WORKUP

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Lab Studies

• Patients suspected of having tuberculosis (TB) should submit sputum for smear and culture. Sputum should be collected in the early morning on 3 consecutive days. For hospitalized patients, sputum may be collected every 8 hours. For patients unable to produce any sputum (eg, children), early morning gastric aspirate may produce a good specimen. Another option is fiberoptic bronchoscopy with transbronchial biopsy and bronchial washings. Biopsy of bone marrow, liver, or blood cultures occasionally may be necessary and helpful.
• Traditional mycobacterial cultures require weeks for growth and identification. Newer technologies, including ribosomal RNA probes or DNA polymerase chain reaction, allow identification within 24 hours. The DNA probes are approved for direct testing on smear-positive or smear-negative sputa. However, sensitivity is higher on smear-positive specimens.
• Obtain the following laboratory tests:
• • CBC count
  • Chemistries, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
  • Alkaline phosphatase
  • Total bilirubin
  • Uric acid
  • Creatinine
• Obtain HIV serology in all patients with TB.
• For congenital TB, the best diagnostic test is the examination of the placenta for pathology, histology, and culture. Mycobacterial blood cultures of the newborn also may be helpful. Treatment may be necessary until placental cultures are negative.

Imaging Studies

• Chest radiographs may show a patchy or nodular infiltrate (see Images 2-3). TB may be found in any part of the lung, but upper-lobe involvement is most common. The lordotic view may better demonstrate apical abnormalities.
• Primary TB is more likely to mimic the appearance of routine community-acquired pneumonia on chest radiography, in contrast to reactivation TB. More recent studies show that either may be associated with pleural effusion or cavitation.
• Various patterns may be seen, as follows:
• • Cavity formation is indicative of advanced infection and is associated with a high bacterial load.
  • Noncalcified round infiltrates may be confused with lung carcinoma.
  • Homogeneously calcified nodules (usually 5-20 mm) are tuberculomas and represent old infection rather than active disease.
  • Miliary TB is characterized by the appearance of numerous small nodular lesions, resembling millet seeds, on chest radiography.
• Computed tomography scanning of the chest may help to better define abnormalities in patients with vague findings on chest radiography.
  

Other Tests

• Tuberculin skin testing (Mantoux test) is the most widely available test for diagnosing tuberculous infection in the absence of active disease (latent infection). The tuberculin skin test involves an intradermal injection of 5 tuberculin units of purified protein derivative. The response is measured as the amount of induration at 48-72 hours. The size of induration, rather than erythema, is diagnostic. Interpretation of skin testing depends on the size of induration, age, and patient risk factors. The tuberculin skin test is not a sensitive test for active TB. Three cutoff points of clinical significance exist; the criteria for each cutoff point are listed below.
• • Larger than or equal to 5 mm
  • • Close contacts to newly diagnosed TB
    • HIV positive
    • Patients with organ transplant or patients who are taking the equivalent of more than 15 mg/d of prednisone for 1 month or more
    • Patients with fibrotic lesions on chest radiography (not granulomas)
  • Larger than or equal to 10 mm
  • • Patients with medical conditions that increase the risk of TB (eg, diabetes mellitus, hematologic malignancies, carcinoma of the head and neck, IV drug use [known to be HIV negative], end-stage renal disease, silicosis, malnutrition, jejunoileal bypass, gastrectomy)
    • Recent converter - At least 10-mm increase in skin test in past 2 years (regardless of age)
    • Recent immigrants (within 5 y) from a high-prevalence country
    • Children younger than 4 years exposed to adults at high risk for TB
    • Residents and employees of facilities for long-term care, including correctional institutions, nursing homes, homeless shelters, and mental institutions
  • Larger than or equal to 15 mm - Persons with none of the above
• Whole blood assay based on interferon-gamma release (IGRA) with ESAT-6 and CFP-10 antigens (QuantiFERON-TB Gold) can also be used to screen for latent TB infection and offers certain advantages over tuberculin skin testing. Overall, sensitivity and specificity are comparable to those of tuberculin skin testing; however, a second encounter for reading is unnecessary, unlike with tuberculin skin testing. Results are reported as positive, negative, or indeterminate. Patients with indeterminate result are likely to have evidence of immunosuppression.

TREATMENT

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Medical Care

• For the initial empiric treatment of tuberculosis (TB), start patients on a 4-drug regimen: isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. Once the isolate is known to be fully susceptible, ethambutol (or streptomycin if used as a fourth drug) can be discontinued.
• • 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 or remains culture positive after 2 months of treatment.
• Directly observed therapy (DOT) is recommended for all patients. Patients on the above regimens as DOT 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.
• The diagnosis of MDR-TB is established with an isolate that is resistant to both isoniazid and rifampin. Resistance may be initial (no known history of prior treatment) or secondary (acquired during therapy or because of previous inadequate therapy).
• Risk factors for initial resistance include exposure to a patient who has MDR-TB or being from a country or region with a high prevalence of resistance. Symptoms and radiographic findings do not differentiate MDR-TB from fully susceptible TB. Suspect MDR-TB if the patient is on DOT with the 4 first-line drugs (no diarrhea) and symptoms do not improve within 1-2 weeks.
• Continue treatment for MDR-TB for 18-24 months after sputum 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. Consult an expert on MDR-TB. Costs may be as high as $100,000-1,000,000 for complete treatment. Treatment should include an injectable drug together with at least 3 more drugs to which the isolate is susceptible.
• The diagnosis of extended drug-resistant TB (XDR-TB) is established with an isolate that is resistant to isoniazid, rifampin, at least one of the quinolones, and at least one injectable drug. Treatment options for XDR-TB are very limited, and patients with XDR-TB have very high mortality rates.

Surgical Care

• Surgical resection of an infected lung may be considered to reduce the bacillary burden in MDR-TB. Procedures include segmentectomy (rarely used), lobectomy, and pneumonectomy. Pleurectomies for thick pleural peel are rarely indicated. However, intraoperative infection of uninvolved lung tissue has been observed.
• Complications include the usual perioperative complications, recurrent disease, and bronchopleural fistulas.

Consultations

• Infectious disease specialist
• Pulmonologist
• General or thoracic surgeon

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antimycobacterials

The goals are to shorten the clinical course, prevent complications, prevent the development of latency and/or subsequent recurrences, and decrease transmission. For patients with latent infection, the goal of therapy is to prevent progression of disease.

FOLLOW-UP

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Further Inpatient Care

• Hospitalized patients with suspected or documented tuberculosis (TB) must be placed in appropriate isolation. This includes a private room with negative pressure and adequate air exchanges. Persons entering the room must wear masks or respirators capable of filtering droplet nuclei.
• Patients should remain in isolation until sputum becomes smear-negative; however, patients should not ordinarily be kept in the hospital for the sole purpose of providing isolation. Special arrangements are necessary for patients who live with children, individuals infected with HIV, or patients returning to a closed-group setting (eg, nursing home, correctional facilities, residential facility, homeless shelter).

Further Outpatient Care

• Patients diagnosed with active TB should have sputum examined for M tuberculosis weekly until sputum conversion is documented. Monitoring for toxicity includes baseline and periodic liver enzymes, complete blood cell count, and serum creatinine.
• In addition, patients on pyrazinamide should have baseline or periodic serum uric acid determinations, and patients on long-term ethambutol therapy should have baseline or 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.

Deterrence/Prevention

• Patients with a clinically significant result on tuberculin skin testing or positive IGRA result (see Other Tests) should be administered a course of therapy once active infection and disease is ruled out. Guidelines published by the CDC in 2000 now refer to this as treatment of latent TB. The recommended regimens are listed below:
• • Isoniazid daily for 9 months
  • Isoniazid twice weekly for 9 months (administered as DOT)
  • Isoniazid daily for 6 months (should not be used in patients with fibrotic lesions on chest radiography, patients with HIV, or children)
  • Isoniazid twice weekly for 6 months (administered as DOT, should not be used in patients with fibrotic lesions on chest radiography, patients with HIV, or children)
  • Rifampin daily for 4 months
  • Rifampin plus pyrazinamide daily for 2 months (this regimen is no longer recommended owing to an increased risk for liver toxicity)
• Children should be administered isoniazid for 9 months. In addition, children younger than 5 years who have close contact with a person with an active case of TB should be started on isoniazid even if results on skin testing are negative; preventive therapy can be stopped if results on repeat skin testing are negative 2-3 months after last contact with a culture-positive source case.
• Patients exposed to MDR-TB may be administered ethambutol plus pyrazinamide for 6-12 months or pyrazinamide plus levofloxacin for 6-12 months; the index isolate should be susceptible to all drugs used.
• 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. The 2-month combination of pyrazinamide plus rifampin is no longer recommended.

Complications

• Late complications of pulmonary TB 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. Therefore, re-treatment usually is not necessary, especially after DOT.
  • 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 and often contain mixed bacteria, including anaerobes.
  • Hemoptysis is the most common late complication. Broncholithiasis is the result of spontaneous lymph node migration into the bronchial tree and may be associated with postobstructive pneumonia or esophageal perforation. Chronic bronchitis may develop from bronchiectasis; bleeding from submucosal bronchial veins usually is self-limited.
  • Fibrothorax is the development of trapped lung due to pleural fibrosis and scarring.
  • The risk for carcinoma is controversial but should be considered with newly developing clubbing.

Prognosis

• The relapse rate following appropriate therapy is only 0-4% and occurs within the first 2 years after completion. Following successful completion of DOT, most cases of recurrent TB are probably due to reinfection rather than endogenous reactivation.

Patient Education

• For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center. Also, see eMedicine's patient education article Tuberculosis.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Laws vary from state to state, but communicable disease laws typically empower public health officials to investigate suspected cases of tuberculosis (TB), including potential contacts. In addition, patients may be incarcerated for noncompliance with therapy. For example, in the Denver Metro Tuberculosis Clinic from 1984-1994, 5% of patients were incarcerated for noncompliance and an additional 5% who were lost to follow-up before completing therapy would have been candidates for incarceration.

Special Concerns

• Pregnancy
• • Pregnancy provides an opportunity to screen for TB; all pregnant mothers can have tuberculin skin testing performed. If skin-testing results are positive, chest radiograph can be performed with lead shielding (the amount of radiation exposure of a single chest radiograph has been compared to that incurred on a regular flight from New York to Los Angeles). The chest radiograph should not be delayed during the first 3 months of pregnancy if the patient has symptoms.
  • Active TB should be treated, even in women in the first stage of pregnancy. Isoniazid, rifampin, and ethambutol may be used. In the United States, pyrazinamide is reserved for only women who are suspected of having MDR-TB. Elsewhere in the world, pyrazinamide is commonly used in pregnant women with TB.
  • Preventive treatment is recommended during pregnancy, especially in the following situations:
  • • Pregnant women with a positive tuberculin skin test result who are HIV seropositive or who have behavioral risk factors for HIV infection but 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 have had a documented tuberculin skin test conversion in the past 2 years
  • Pregnant women are at an increased risk for isoniazid-induced hepatotoxicity and should undergo monthly 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 while on preventive therapy. Many experts recommend supplemental pyridoxine to the breastfed infant.
• Tuberculosis in children
• • TB in a child is a sentinel event indicating recent transmission, and contacts should be evaluated to find the source case as soon as possible. Children do not commonly infect other children because cough is rare and sputum production is scant. However, cases of child-child and child-adult transmission are well-documented.
  • Chest radiograph may show only hilar lymphadenopathy or a patchy infiltrate. Most children 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. Gastric aspirates or biopsies are not necessary if positive cultures have been obtained from the source case.
  • In children younger than 5 years, the potential for development of fatal miliary TB or meningeal TB is a significant concern. TB disease is uncommon in children aged 5-15 years (the golden age of childhood).
  • Isoniazid tablets may be crushed and added to food. Isoniazid liquid without sorbitol should be used to avoid osmotic diarrhea, causing 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.
• Human immunodeficiency virus
• • Patients with TB must be tested for HIV, and patients with HIV need periodic evaluation for TB with tuberculin skin testing and/or chest radiography. Patients with HIV and a positive tuberculin skin test result develop active TB at a rate of 3-16% per year.
  • Patients with TB and HIV are more likely to have disseminated disease and less likely to have upper-lobe infiltrates or classic cavitary pulmonary disease. Patients with a CD4 count of less than 200 may have mediastinal adenopathy with infiltrates.
  • Treatment regimens for active or latent TB in patients with HIV are similar to the treatment of individuals who are HIV negative. The most significant differences involve the avoidance of rifampin in patients who are on protease inhibitors or nonnucleoside reverse-transcriptase inhibitors. Rifabutin may be used in place of rifampin in patients who are on indinavir, nelfinavir, or efavirenz.
  • Patients with HIV and TB may develop a paradoxical response 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.

MULTIMEDIA

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Media file 1:  Tuberculosis. Acid-fast bacillus smear showing characteristic cording in Mycobacterium tuberculosis.
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Media type:  Photo

Media file 2:  Tuberculosis. This radiograph shows a patient with typical radiographic findings of tuberculosis.
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Media type:  X-RAY

Media file 3:  Tuberculosis. This is a chest radiograph taken after therapy of a patient with tuberculosis. For a chest radiograph showing typical radiographic findings of tuberculosis, see Image 2.
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Media type:  X-RAY

REFERENCES

Section 11 of 11

• Authors and Editors
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• Differentials
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• Advisory Council for the Elimination of Tuberculosis, Advisory Committee on Immunization Practices. The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. Apr 26 1996;45(RR-4):1-18. [Medline].
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• Khan K, Muennig P, Behta M. Global drug-resistance patterns and the management of latent tuberculosis infection in immigrants to the United States. N Engl J Med. Dec 5 2002;347(23):1850-9. [Medline].
• Kim HJ, Lee HJ, Kwon SY, et al. The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis. Chest 2006 May;129(5):1253-8.
• Larsen NM, Biddle CL, Sotir MJ. Risk of tuberculin skin test conversion among health care workers: occupational versus community exposure and infection. Clin Infect Dis. Oct 1 2002;35(7):796-801. [Medline].
• Mazurek GH, Jereb J, Lobue P, et al. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR-Recomm Rep. Dec 16 2005;54(15):49-55.
• Medical Section of the American Lung Association. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Am J Respir Crit Care Med. Aug 1997;156(2 Pt 2):S1-25. [Medline].
• Pomerantz M, Brown JM. Surgery in the treatment of multidrug-resistant tuberculosis. Clin Chest Med. Mar 1997;18(1):123-30. [Medline].
• Rao VK, Iademarco EP, Fraser VJ. Delays in the suspicion and treatment of tuberculosis among hospitalized patients. Ann Intern Med. Mar 2 1999;130(5):404-11. [Medline].
• World Health Organization. Antituberculosis drug resistance in the world. The WHO/IUATLD global project on anti-tuberculosis drug resistance surveillance. Geneva:. WHO;1997:1-227. [Full Text].
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Article Last Updated: Jan 8, 2007