1. 1
Tuberculin Testing
and Treatment of Latent
Tuberculosis Infection
Andrew Catanzaro, MD

2. 2
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

3. 3
Outline
• Latent TB: Screening and Treatment
• Active TB: Screening
• Cases

4. 4
Latent TB: Screening and
Treatment
• Define LTBI
• TB pathogenesis
• TB epidemiology
• TST Testing
• INH: Risk, Benefit, Alternatives

5. 5
What 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.

6. 6
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

7. 7
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

8. LTBI vs. Pulmonary TB Disease
Latent 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

9. 9
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

10. 10
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

11. 11
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

13. 13
TST Testing Goals
• Detects persons with LTBI who would
benefit from treatment

14. 14
TST New Features
Tuberculin 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
____________________________________________________
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 Developing
TB 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

17. 17
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

18. 18
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 to
TB 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 to
TB Disease (2)
• Underweight or malnourished persons
• Injection drug users

21. 21
Increased Risk for Progression to
TB Disease (3)
• Persons with certain medical conditions
such as
– Silicosis
– Diabetes mellitus
– Chronic renal failure or on hemodialysis
– Gastrectomy or jejunoilial bypass

22. 22
Tuberculin Testing

23. 23
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

24. 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

25. 25
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)

27. 27
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

33. 33
Treatment Guidelines
Treatment 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
_____________________________________
6
MMWR 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

46. 46
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
7
MMWR June 9, 2000; 49(No. RR-6): 39

48. 48
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

49. 49
Guidelines Available Online
• CDC’s Morbidity and Mortality Weekly
Report
http://www.cdc.gov/mmwr
• American Thoracic Society
http://www.thoracic.org/statements/