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Minnesota Department of Health

Tuberculosis Prevention and Control Program

Recommendations for Targeted Tuberculin Testing


and Treatment of Latent Tuberculosis Infection
(based on national guidelines of the Centers for Disease Control and Prevention (CDC) and
the American Thoracic Society (ATS); revised based on updated CDC/ATS guidelines issued August 8, 2003.)

Rationale: Targeted tuberculin testing for latent tuberculosis (TB) infection (LTBI) is a strategic
component of TB control that identifies persons at high risk for developing TB disease who would
benefit by treatment of LTBI, if detected. Persons with increased risk for developing TB disease
include those recently infected with Mycobacterium tuberculosis and those with LTBI who have
clinical conditions that are associated with an increased risk for progression of LTBI to active TB.
Infected persons who are at high risk for developing active TB should be considered for treatment
of LTBI regardless of age.

Targeted tuberculin testing programs should be conducted only among high-risk persons.
Screening persons at low risk for TB is discouraged because it diverts resources away from higher
priority TB control activities and because the likelihood of false-positive tuberculin skin test
(TST) results increases among low-risk populations. The decision to administer a TST should be
a decision to assess the patient and consider treatment of LTBI if the person has a positive TST
result. Testing is discouraged unless a plan has been developed to complete a course of treatment
for persons found to have LTBI.

Targeted Screening Recommendations: Persons in the following high-risk groups should


receive tuberculin skin testing using the intradermal (Mantoux) method. If the TST result is
positive based on the criteria listed below, the patient should be considered as a candidate for
treatment of LTBI. Treatment of LTBI should not begin until active TB disease is excluded.
Careful evaluation including a chest x-ray and assessment for pulmonary and extrapulmonary
symptoms is necessary to rule out the possibility of active TB disease. Persons suspected of
having TB disease should receive the recommended multi-drug regimen for treatment of TB
disease until the diagnosis is confirmed or ruled out. Voluntary HIV counseling and testing
should be offered to persons diagnosed with LTBI.

1. A TST reaction of > 5 mm of induration is considered positive for the following persons.
These persons should be given treatment for LTBI if their TST result is positive:

• HIV-infected persons,
• Recent contacts of a person with infectious TB disease,
• Persons with fibrotic changes on a chest x-ray consistent with inactive or past TB*,
• Persons with organ transplants and other immunosuppressed persons (e.g., those
receiving the equivalent of > 15 mg/day of prednisone for > 1 month).

* For persons with a chest x-ray result consistent with inactive or prior TB, the clinician should carefully
consider the need for further evaluation (i.e., mycobacterial cultures) to definitively rule out the possibility of
active TB disease before initiating treatment of LTBI.
2. A TST reaction of > 10 mm of induration is considered positive for the following persons.
These persons should be considered for treatment of LTBI if their TST result is positive:

• Foreign-born persons from high-prevalence areas (e.g., Africa, Asia, Eastern Europe,
South/Central America)H
• Injection drug users;
• Residents and employees of high-risk congregate settings (e.g., correctional facilities,
nursing homes, homeless shelters, other health care facilities);
• Mycobacteriology laboratory personnel;
• Persons recently infected with M. tuberculosis, as evidenced by an increase of > 10
mm in TST result documented within the past 2 years;
• Persons with clinical conditions that increase the risk of progression to TB disease
[e.g., substance abuse, diabetes mellitus, silicosis, cancer of the head or neck,
hematologic and reticuloendothelial disease such as Hodgkin’s disease or leukemia,
end-stage renal disease, intestinal bypass or gastrectomy, chronic malabsorption
syndromes, low body weight (i.e., 10% or more below ideal for the given
population)];
• Children < 4 years of age, or children and adolescents exposed to adults in high-risk
categories.
H
National guidelines recommend treatment of LTBI for persons recently (i.e., within the past 5 years)
arrived in the U.S. from high-prevalence countries. These persons should be given high priority for targeted
TB screening and treatment of LTBI. Because local epidemiologic data demonstrate the uniquely high
percentage of TB that occurs among foreign-born persons in Minnesota, the Minnesota Department of
Health recommends that TB screening and treatment of LTBI be considered for foreign-born persons from
(or persons who have traveled extensively to) high-prevalence areas, regardless of the length of time since
their arrival in the U.S. Clinical data suggest that the risk of hepatotoxicity associated with isoniazid therapy
increases directly with the patient’s age. Therefore, when prescribing treatment of LTBI, the clinician should
consider the patient’s age, among other risk factors, in relation to the risk of developing TB disease. Bacille
Calmette-Guerin (BCG) vaccination is NOT a contraindication for tuberculin skin testing; a history of
BCG vaccination should be disregarded when interpreting the TST result.

3. A TST reaction of > 15 mm of induration is considered positive for persons with no


known risk factors for TB. These persons may be considered for treatment of LTBI if
their TST result is positive.

Recommended Treatment of LTBI: Several acceptable regimens are available for treatment of
LTBI. Providers should select an appropriate regimen with consideration for each patient’s
specific circumstances. The following regimens are listed in order of preference based on clinical
studies and programmatic considerations. The recommended regimens are those that have been
studied in clinical trials and for which the most efficacy data are available. For children,
adolescents or persons with chest x-ray results consistent with inactive or past TB, isoniazid
given daily or by directly observed therapy (DOT) twice weekly for 9 months are the only
recommended regimens (unless exposed to isoniazid-resistant TB.) All regimens consisting of
isoniazid are considered acceptable for use in pregnant women. For special circumstances,
such as persons exposed to drug-resistant TB disease, contact the Minnesota Department of Health
TB Prevention and Control Program or consult CDC guidelines.
Acceptable regimens:
a. recommended regimen:

isoniazid daily x 9 months a

b. other acceptable regimens b:


• isoniazid twice weekly by DOT x 9 months a,c,d
• isoniazid daily x 6 months a,d,e,f
• isoniazid twice weekly by DOT x 6 months a,c,d,e,f
• rifampin daily x 4 months d,g

c. generally should not be offered b:



rifampin/pyrazinamide daily x 2 months or twice weekly by DOT x 2-3 months c,d,e,h
a
Routine use of pyridoxine (vitamin B6) in conjunction with isoniazid is not indicated. Persons with conditions that
increase the risk of neuropathy (i.e., diabetes, pregnancy, uremia, alcoholism, seizure disorder, malnutrition, HIV
infection) may be given pyridoxine (vitamin B6) 25-50 mg/day with isonaizid.
b
All regimens other than the recommended regimen should be used only when 9 months of daily isoniazid is not
feasible (e.g., correctional facility inmates who will be incarcerated for less than 9 months, college students or other
persons in residential settings for less than 9 months, and persons who cannot tolerate isoniazid).
c
Directly observed therapy (DOT) must be used for all persons receiving intermittent (e.g., twice weekly) dosing.
d
Not recommended for those with fibrotic lesions on chest radiograph.
e
Not recommended for HIV-infected persons.
f
Not recommended for children aged < 18 years.
g
In HIV-infected persons, most protease inhibitors or delavirdine should not be administered concurrently with
rifampin. Web-based information about interactions between RIF and HIV-related drugs is updated frequently. The
latest specific recommendations should be consulted.
h
Consult a medical expert in the treatment of TB and LTBI before offering this regimen. Based on investigations of
patients who developed severe or fatal liver injury associated with this regimen, CDC and ATS revised their
guidelines in August 2003 to recommend against the use of rifampin/pyrazinamide (RIF/PZA) in most situations. The
use of RIF/PZA may be considered in carefully selected situations and only when frequent and close monitoring of the
patient for adverse effects is provided. The regimen should never be offered to patients who: 1) are concurrently
taking other medications associated with liver injury; 2) drink excessive amounts of alcohol, even if alcohol use is
discontinued during treatment; 3) have underlying liver disease, or 4) have a history of INH-associated liver injury.
See the revised recommendations presented in Reference #3 [MMWR 2003;52(735-739)] below.

Adherence to Therapy: The patient’s adherence to the prescribed regimen is critical to


successful prevention of TB disease. Completion of therapy is based on the total number of doses
administered rather than duration of therapy alone. For example, a 9-month regimen of daily
isoniazid should consist of at least 270 doses administered within 12 months, allowing for minor
interruptions in therapy.

Pre-Treatment Evaluation and Monitoring During Treatment of LTBI:


Baseline laboratory testing is not routinely recommended. Instead, a careful medical history
should be conducted before initiating treatment to determine whether the patient has any
preexisting medical conditions or risk factors associated with an increased likelihood of adverse
effects of treatment. Baseline hepatic measurements including serum bilirubin and either AST
(SGOT) or ALT (SGPT) are indicated for HIV-infected persons, foreign-born persons from
countries where viral hepatitis is endemic and for whom complete hepatitis serology results are
unknown, pregnant or post-partum (3 months) women, regular users of alcohol, and patients with
a history or initial evaluation indicative of hepatitis or cirrhosis. Baseline laboratory testing
should be considered on an individual basis for older persons and patients taking medications for
chronic medical conditions. Because the risk for progression from LTBI to active TB disease is
increased substantially in persons with HIV infection, voluntary HIV counseling and testing
should be offered to persons with LTBI.

All patients receiving treatment of LTBI should have a face-to-face follow-up evaluation by
a clinician or nurse at least monthly for side effects, signs or symptoms of hepatitis or active
TB disease, and adherence to the prescribed regimen. To facilitate this, MDH recommends
that clinicians dispense no more than a 30-day supply of medication at a time. Hepatic
testing should be repeated monthly throughout the course of treatment for persons with abnormal
baseline results and those with hepatitis, cirrhosis, regular alcohol use, or risk factors for chronic
liver disease. Also, laboratory testing is indicated to evaluate adverse side effects that occur
during treatment. If the patient’s transaminase levels exceed the upper limit of normal by three-
fold (in conjunction with symptoms of hepatitis) to five-fold (in an asymptomatic patient) or if the
patient reports symptoms of other adverse reactions (e.g., peripheral neuropathy), discontinuation
of isoniazid should be strongly considered and the patient should be reevaluated promptly.

References:
1. Am J Respir Crit Care Med 2000;161:1376-1395.
2. MMWR 2001;50(15)
3. MMWR 2003;52(735-739).

Revised December 2003

Tuberculosis (TB) Prevention and Control Program


625 Robert Street North
P.O. Box 64975
Minneapolis, MN 55164-0975
651-201-5414
www.health.state.mn.us/tb