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Tuberculin Testing and Treatment of Latent Tuberculosis Infection

Andrew Catanzaro, MD

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Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection

Identifying Latent Cases of TB decreases morbidity, mortality, and spread of TB through our community

“Unity has become the Health Department”

Louis Padilla, MD 2007

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Outline

• Latent TB: Screening and Treatment

• Active TB: Screening

• Cases

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Latent TB: Screening and Treatment

• Define LTBI

• TB pathogenesis

• TB epidemiology

• TST Testing

• INH: Risk, Benefit, Alternatives

5What is Latent TB Infection (LTBI)? Subclinical Disease

LTBI is the presence of

• M. tuberculosis organisms (tubercle bacilli)

• without symptoms or radiographic evidence of TB disease.

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TB Pathogenesis

• Transmission via inhalation of “Red Snappers”

– Cough, sneeze, talking release AFB droplets

– 1 cough = 3,000 AFB

– Talking for 5 minutes = 3,000 AFB

– 1 AFB is infectious in the middle and upper respiratory tract

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TB Pathogenesis (2)

• Infection results in the respiratory tract

• Identified by macrophages in the lung

• Incomplete control at the lymph nodes

• Development of immunity (3-8 weeks)

• Caseation, cavitation, fibrosis OR

• Latent TB infection

• Lifetime Reactivation: 10% of non-immunosuppressed

LTBI vs. Pulmonary TB DiseaseLatent TB Infection

• TST* positive

• Negative chest radiograph

• No symptoms or physical findings suggestive of TB disease

Pulmonary TB Disease

• TST usually positive

• Chest radiograph may be abnormal

• Symptoms may include one or more of the following: fever, cough, night sweats, weight loss, fatigue, hemoptysis, decreased appetite

• Respiratory specimens may be smear or culture positive

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TB Epidemiology

• US 5.2 cases/100,000

• DC 10/100,000 cases per year

• About 50 cases per year

• Unity takes care of 20% of DC residents

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Tuberculosis Epidemiology (2)

• 50% cases foreign born

• Worldwide 12 countries give 70% infection

– India

– China

– Indonesia

– Bangladesh

– Pakistan

– Nigeria

– Philippines

– South Africa

– Russian Federation

– Ethiopia

– Viet Nam

– Democratic Republic of Congo

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TB Epidemiology (3)TB Cases in Immigrants, 2006

Total Cases 7,700

• Mexico 25%

• Philippines 10%

• Viet Nam 8%

• India 7%

• China 5%

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Latent TB: Screening and Treatment

• Define LTBI

• TB pathogenesis

• TB epidemiology

• TST Testing

• INH: Risk, Benefit, Alternatives

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TST Testing Goals

• Detects persons with LTBI who would benefit from treatment

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TST New FeaturesTuberculin skin testing

• Emphasis on targeting persons at high risk

• 5-mm induration cutoff level for immunosuppressed (e.g. HIV positive) patients

• Skin-test conversion defined as increase of 10 mm of induration within a 2-year period, regardless of age

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4 MMWR August 61, 2004; 53(33): 683-686

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Before you test:Identify Risk Factors

That Lead to Development of TB Disease

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Persons at Risk for DevelopingTB Disease

• Those who have been recently infected

• Those with clinical conditions that increase their risk of progressing from LTBI to TB disease

Persons at high risk for developing TB disease fall into 2 categories

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Recent Infection as a Risk Factor (1)

• Close contacts to person with infectious TB

• Skin test converters (within past 2 years)

• Recent immigrants from TB-endemic regions of the world (within 5 years of arrival to the U.S.)

Persons more likely to have been recently infected include

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Recent Infection as a Risk Factor (2)

• Residents and employees of high-risk congregate settings (e.g., correctional facilities, homeless shelters, health care facilities)

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Increased Risk for Progression toTB Disease (1)

• HIV-infected persons

• Those with a history of prior, untreated TB or fibrotic lesions on chest radiograph

Persons more likely to progress from LTBI to TB disease include

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Increased Risk for Progression toTB Disease (2)

• Underweight or malnourished persons

• Injection drug users

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Increased Risk for Progression toTB Disease (3)

• Persons with certain medical conditions such as– Silicosis

– Diabetes mellitus

– Chronic renal failure or on hemodialysis

– Gastrectomy or jejunoilial bypass

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Tuberculin Testing

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Mantoux Tuberculin Skin Test

• Preferred method of skin testing for M. tuberculosis infection

• TST is useful for

– Determining how many people in a group are infected (e.g., contact investigation)

– Examining persons who have symptoms of TB

Reading the TST (1)• Measure reaction in 48 to 72

hours

• Measure induration, not erythema

• Record reaction in millimeters, not “negative” or “positive”

• Ensure trained health care professional measures and interprets the TST

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Pretesting (2)

• Educate regarding significance of a positive TST result

• Positive TST reactions can be measured accurately for up to 7 days

• Negative reactions can be read accurately for only 72 hours

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TST Interpretation (1)

5-mm induration is interpreted as positive in

• HIV-infected persons

• Close contacts to an infectious TB case

• Persons with chest radiographs consistent with prior untreated TB (e.g. fibrosis)

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TST Interpretation (3)

10-mm induration is interpreted as positive in

• Recent immigrants

• Injection drug users

• Residents or employees of congregate settings

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TST Interpretation (4)

10-mm induration is interpreted as positive in (cont.)

• Persons with clinical conditions that place them at high risk

• Children < 4 years; infants, children, and adolescents exposed to adults at high-risk

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TST Interpretation (5)

• Persons with no known risk factors for TB.*

*Although skin testing programs should be conducted only among high-risk groups, certain individuals may require TST for employment or school attendance. Diagnosis and treatment of LTBI should always be tied to risk assessment.

15-mm induration is interpreted as positive in

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BCG Vaccination

• BCG vaccination

– Reactivity in BCG vaccine recipients generally wanes over time; positive TST result is likely due to TB infection if risk factors are present

– Thus a history of BCG vaccination is irrelevant to testing

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Factors That May Cause False-Negative TST Reactions (2)

• Recent TB infection

– Defined as 2 to 10 weeks after exposure

• Very young age

– Newborns

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LTBI Treatment Regimens

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Treatment GuidelinesTreatment of LTBI

• HIV-negative persons – INH for 9 months preferred regimen

• Rifampin for 4 months is an alternative

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Treatment of LTBI

Motivators:

5% TB Infection Rate at 1 year

15% Lifetime risk of TB

1 case of reactivation can result in 200-300 cases of TB

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Initiating Treatment

Before initiating treatment for LTBI

• Rule out TB disease (i.e., wait for culture result if specimen obtained)

• Determine prior history of treatment for LTBI or TB disease

• Assess risks and benefits of treatment

• Determine current and previous drug therapy

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Rifampin Regimens (1)

• Rifampin (RIF) given daily for 4 months is an acceptable alternative when treatment with INH is not feasible.

• In situations where RIF cannot be used (e.g., HIV-infected persons receiving protease inhibitors), rifabutin may be substituted.

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Regimens (2)

• RIF daily for 4 months (120 doses within 6 months)

• RIF and PZA for 2 months should generally not be offered due to risk of severe adverse events6

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6MMWR August 8, 2003; 52 (31): 735-739

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Completion of Therapy

Completion of therapy is based on the total number of doses administered, not on duration alone.

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Management of Patient Who Missed Doses

• Extend or re-start treatment if interruptions were frequent or prolonged enough to preclude completion

• When treatment has been interrupted for more than 2 months, patient should be examined to rule out TB disease

• Recommend and arrange for DOT as needed

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Monitoring During Treatment - Risk

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Clinical Monitoring (1)

• Rash

• Anorexia, nausea, vomiting, or abdominal pain in right upper quadrant***

• Fatigue or weakness

• Dark urine***

• Persistent numbness in hands or feet***

Instruct patient to report signs or symptoms of adverse drug reactions

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Clinical Monitoring (2)

• Review why on treatment

• Discuss adherence to treatment

• Adverse symptoms – rash, hepatitis

• Plans to continue treatment

Monthly visits should include a brief physical exam and a review of

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Clinical Monitoring (3)

• Incidence of hepatitis* in persons taking INH is lower than previously thought (0.1 to 0.15%)

• Hepatitis risk increases with age– Uncommon in persons < 20 years old– Nearly 2% in persons 50 to 64 years old

• Risk increased with underlying liver disease or heavy alcohol consumption

*subclinical

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Laboratory Monitoring (1)

Baseline liver function tests (e.g., AST, ALT, and bilirubin) are not necessary except for patients with the following risk factors:

• HIV infection

• History of liver disease

• Alcoholism

• Pregnancy or in early postpartum period

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Laboratory Monitoring (2)

Repeat laboratory monitoring if patient has

• Abnormal baseline results

• Current or recent pregnancy

• High risk for adverse reactions

• Symptoms of adverse reaction

• Liver enlargement or tenderness during examination

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Clinical/Laboratory Monitoring• Routine baseline and follow-up monitoring

not required except for– HIV-infected persons

– Pregnant women or those in early postpartum period

– Persons with chronic liver disease or who use alcohol regularly

• Monthly monitoring for signs or symptoms of possible adverse effects

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Laboratory Monitoring (3)

• Asymptomatic elevation of hepatic enzymes seen in 10%-20% of people taking INH

– Levels usually return to normal after completion of treatment

• Some experts recommend withholding INH if transaminase level exceeds 3 times the upper limit of normal if patient has symptoms of hepatotoxicity, and 5 times the upper limit of normal if patient is asymptomatic7

7MMWR June 9, 2000; 49(No. RR-6): 39

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Summary: TB Prevention

For every patient

• Assess TB risk factors – immigrant status, immunosuppressed

• If risk is present, perform TST

• If TST or QFT is positive,

1. Rule out active TB disease

2. Discuss R/B/A

3. Consider baseline LFTs

4. Initiate treatment for LTBI

5. Monitor and reinforce need for treatment

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Guidelines Available Online

• CDC’s Morbidity and Mortality Weekly Reporthttp://www.cdc.gov/mmwr

• American Thoracic Societyhttp://www.thoracic.org/statements/