New ATS/CDC Guidelines for Testing and Treatment of Latent Tuberculosis [MMWR 2000; 49: RR-6]: This is the Official Statement of the ATS/CDC Joint Statement entitled "Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection." The major change concerns the endorsement of shorter, rifampin-based regimens as alternatives to INH. INH for 6-12 months has been the standard treatment for latent tuberculosis for over 30 years, but this regimen is flawed due to poor adherence attributed to the long duration of treatment and toxicity. Changes from prior recommendations for testing and treatment are presented below:

Tuberculin testing:

• Testing is recommended for patients at high risk; testing for patients at low risk is discouraged.
• The criteria for a positive test for patients with organ transplants, persons receiving the equivalent of 15 mg/day prednisone for one month or more, and other immunosuppressed patients should be 5 mm induration instead of 10 mm induration.
• Skin test conversion is defined as an increase of at least 10 mm induration during a two-year period regardless of age.

Treatment of latent tuberculosis:

• The standard duration of INH treatment should be nine months for those with and without HIV infection.
• The short course rifampin plus pyrazinamide regimen should be two months for patients with and without HIV infection.
• The rifampin regimen should be four months for patients with and without HIV infection.

Clinical and laboratory monitoring:

• Baseline and follow-up laboratory monitoring is not necessary except for patients with HIV infection, pregnant women, patients who regularly use alcohol and those with chronic liver disease.
• Clinical monitoring for signs and symptoms of adverse reactions is still recommended.

Special considerations:

• Pregnancy: Women at risk for progression including those with HIV and those who have recently been infected should receive INH for nine months. Pregnant women at lower risk for progression should delay treatment until after delivery.
• Contact with INH-resistant strains: Rifampin plus pyrazinamide regimen is recommended for two months or rifampin for four months.
• Suspected infection with INH and rifampin resistant strains plus high-risk: Pyrazinamide plus ethambutol or pyrazinamide plus a quinolone (levofloxacin or ofloxacin) for six months (immunocompetent) or 12 months (immunosuppressed).

Change in nomenclature: In an effort to promote widespread implementation, the new guidelines use the term "treatment of latent tuberculosis infection" instead of "preventive therapy" or "Chemoprophylaxis."
Groups at risk for tuberculosis: Targeted testing programs should be directed to persons identified as having increased risk of latent tuberculosis infection including the following:

• Close contacts of persons with pulmonary tuberculosis.
• Immigrants of areas of the world with high TB rates.
• Epidemiologically-defined groups: homeless, HIV-infected, injection drug users, and persons who work or reside in the following settings: hospitals, homeless shelters, corrections facilities, nursing homes and residential homes for AIDS.
• Conditions associated with increased rates of progression to active tuberculosis: The highest risk is persons with pulmonary fibrotic lesions on chest x-ray that suggest untreated prior TB, silicosis, jejunoileal bypass, solid organ transplantation. Categories associated with a modest increase in risk (2 - 5 fold) include diabetes, gastrectomy and those at least 15% underweight. Corticosteroid treatment is believed to be a risk, but dose and duration are arbitrary; available data suggest that the equivalent of prednisone at 15 mg/day or more for 2 - 4 weeks is the lower limit of increased risk.

The risks for tuberculosis in some of these populations is shown in the following table:

Sensitivity and specificity of the tuberculin test: The sensitivity approaches 100% in persons who are immunocompetent. False positive tests are due to infections with MOTT and persons who have received BCG vaccine. The tuberculin test with over 20 mm induration is usually not caused by BCG.
Treatment of latent tuberculosis: Recommendations are summarized in the following table using standard nomenclature for the strength of the recommendation (A - C) and the quality of supporting evidence (I - III).

Interpretation of tuberculin: Three thresholds recommended for defining a positive tuberculin reaction are 5 mm, 10 mm and 15 mm.

• 5 mm threshold: HIV infection, recent contacts of tuberculosis, persons with fibrotic changes on X-ray consistent with TB, organ transplant recipients and other immunosuppressed patients including those receiving the equivalent of at least 15 mg/day of prednisone for at least one month.
• 10 mm threshold: Recent immigrants from high-prevalence countries, injection drug users, residents and employees of high-risk settings, microbiology laboratory personnel, persons with clinical conditions that place them at risk including: silicosis, diabetes, chronic renal failure, leukemia, lymphoma, cancer of the head, neck or lung, weight loss exceeding 10% of ideal body weight, gastrectomy, and jejunoileal bypass.
• 15 mm threshold: Persons with other risk factors (although these patients should probably not have been tested in the first place).

Monitoring: Clinical monitoring is indicated for all patients and laboratory monitoring is advocated for selected patients based on risk, primarily of hepatoxicity.

• Clinical monitoring includes patient education regarding signs and symptoms of adverse effects of drugs (unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, paresthesias, persistent fatigue, weakness, fever lasting over three days, abdominal tenderness, and easy bruising, bleeding or arthralgia), and they should be warned to suspend treatment with any of these symptoms. Clinical monitoring should be done at least monthly during INH or rifampin alone and should be done at two, four, and eight weeks for those receiving rifampin plus pyrazinamide.
• Laboratory monitoring: Baseline tests should be done in patients with HIV infection, a history of liver disease, alcoholism, and pregnancy. Liver function tests should include AST or ALT and bilirubin. Patients receiving rifampin or rifabutin should also have a CBC at baseline if they are in the high-risk category. The test should be repeated in those with abnormal baseline measurements and those with symptoms of adverse reactions.