LATENT 

TUBERCULOSIS 

INFECTION: A GUIDE 

FOR PRIMARY HEALTH 

CARE PROVIDERS
U.S. Department of Health and Human Services

Centers for Disease Control and Prevention

National Center for HIV/AIDS, Viral Hepatitis,

STD, and TB Prevention

Division of Tuberculosis Elimination

Atlanta, Georgia

2020

2
TABLE OF

CONTENTS

4 List of Abbreviations 

5 Introduction 

6 Targeted Testing for Tuberculosis 

8 Diagnosis of Latent TB Infection (LTBI) 

Appendix A 36 Sample TB Risk Assessment Tool

Appendix B

Identifying Persons from High Burden Countries 

Appendix C

Administration and Measurement of the TST

Appendix D

Situations Where Results from Both a TB Blood 

Test and TST May be Useful

Appendix E

Sample Documentation Forms

Appendix F

Latent TB Infection Treatment Regimens

Appendix G 

LTBI Testing and Treatment: Summary of 

U.S. Recommendations

Resources 

References 

37

38

40

42

44

46

54

57

20 Treatment of Latent TB Infection (LTBI) 

3
LIST OF 

ABBREVIATIONS

AFB

acid-fast bacilli

AIDS

acquired immunodeficiency 

syndrome

ALT

alanine aminotransferase

ART

antiretroviral therapy

AST

aspartate aminotransferase

ATS

American Thoracic Society

BCG

bacille Calmette-Guérin

CDC

Centers for Disease Control 

and Prevention

DOT

directly observed therapy

FDA

Food and Drug Administration

HIV

human immunodeficiency 

virus

IFN-γ

interferon-gamma

IGRA

interferon-gamma release 

assay

INH

isoniazid

LTBI

latent tuberculosis infection

MDR TB

multidrug-resistant 

tuberculosis

MMWR

Morbidity and Mortality 

Weekly Report

NTCA

National Tuberculosis 

Controllers Association 

PPD

purified protein derivative

QFT-Plus

QuantiFERON

®

-TB Gold Plus

RIF

rifampin

RPT

rifapentine

SAT

self-administered therapy 

TB

tuberculosis

TNF-alpha

tumor necrosis 

factor-alpha

T-Spot

T-SPOT

®

.TB test 

TST

tuberculin skin test

USPSTF

U.S. Preventive Services Task 

Force

WHO

World Health Organization

4
INTRODUCTION

Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis 

(M. tuberculosis). Not everyone infected with TB bacteria becomes sick. As 

a result, two TB-related conditions exist: latent TB infection (LTBI) and TB 

disease. It is estimated that up to 13 million people in the United States (U.S.) 

have LTBI. People with LTBI are infected with M. tuberculosis, but they do not 

have TB disease. People with LTBI do not have signs and symptoms of TB 

disease, and they cannot spread M. tuberculosis to others. While not everyone 

with LTBI will develop TB disease, about 5–10% of infected people will develop 

TB disease over their lifetimes if not treated for LTBI. 

Progression from untreated LTBI to TB disease accounts for approximately 

80% of U.S. TB cases. Identifying and treating people with LTBI is essential for 

controlling and eliminating TB disease in the U.S. LTBI treatment is effective for 

preventing TB disease. Primary care providers play a key role in achieving the 

goal of TB elimination because of their access to populations at high risk for TB.

This guide is intended for primary care providers who care for individuals 

and populations who may be at risk for infection with M. tuberculosis. This 

document is not meant to be used as a substitute for CDC guidelines, but 

rather as a ready and useful reference. For detailed information regarding the 

diagnosis and treatment of LTBI, please refer to the following CDC guidelines:

• Guidelines for the Treatment of Latent Tuberculosis Infection: 

Recommendations from the National Tuberculosis Controllers 

Association and CDC, 2020

• American Thoracic Society/Infectious Diseases Society of America/

Centers for Disease Control and Prevention Clinical Practice Guidelines: 

Diagnosis of Tuberculosis in Adults and Children

Further guidance can be found in the References section, Appendix F, and 

Appendix G. Clinicians should contact their state and local TB control offices for 

additional information on diagnosing and treating LTBI. Contact information can 

be located on the State TB Control Offices website.

5
TARGETED TESTING 

FOR TUBERCULOSIS

Targeted testing is an essential TB prevention and control strategy that is used 

to identify and treat individuals with LTBI who are at high risk for developing 

TB disease. Identifying individuals with LTBI is essential to the goal of TB 

elimination because treatment of LTBI can prevent infected individuals from 

developing TB disease and thereby stop the further spread of TB to others.

The CDC and the U.S. Preventive Services Task Force (USPSTF) recommend 

testing people who are at increased risk for TB infection. During routine patient 

evaluations, health care providers should identify individuals who are at high 

risk for TB and test them for LTBI. A few simple questions will help health care 

providers assess a patient’s risk (see Appendix A for a sample risk assessment 

tool). TB testing activities should be done only when there is a plan for followup care to evaluate and treat all individuals diagnosed with LTBI or TB disease. 

People who are at low risk for LTBI generally should not be tested. Testing in 

low-risk populations can take resources away from other important activities. 

Also, positive test results in low-risk populations are sometimes inaccurate.

Identifying People at 

High Risk for TB

Generally, groups at high risk fall into two broad categories (Table 1):

1.People who are at high risk for exposure to 

or infection with M. tuberculosis

2.People who are at high risk 

for developing TB disease 

once infected with 

M. tuberculosis

6
TABLE 1.

Groups at High Risk for TB Infection and TB Disease

People at High Risk for 

Exposure to or Infection 

with M. tuberculosis

People at High Risk for 

Developing TB Disease after 

Infection with M. tuberculosis

• Contacts of people known or 

presumed to have infectious TB 

disease

• People who were born in or who 

frequently travel to countries 

where TB disease is common, 

including Mexico, the Philippines,

Vietnam, India, China, Haiti, and 

Guatemala (see Appendix B)

• People who currently live or used

to live in large group settings 

where TB is more common, such 

as homeless shelters, prisons, 

jails, or nursing homes 

• Employees of high-risk 

congregate settings

• Health care workers who serve 

patients with TB disease

• Populations defined locally as 

having an increased incidence 

of LTBI or TB disease, including 

medically underserved 

populations, low-income 

populations, or people who abuse 

drugs or alcohol 

• Infants, children, and 

adolescents exposed to adults 

who are at increased risk for

LTBI or TB disease

• People living with HIV

• Children younger than 5 years 

of age

• People recently infected with 

M. tuberculosis (within the last 2 years)

• People with a history of untreated 

or inadequately treated TB disease

• People who are receiving 

immunosuppressive therapy such 

as tumor necrosis factor 

(TNF)-alpha antagonists, systemic 

corticosteroids equivalent 

to/greater than 15 mg of 

prednisone per day, or 

immunosuppressive drug therapy 

following organ transplantation 

• People with silicosis; chronic renal 

failure; leukemia; or cancer of the 

head, neck, or lung

• People with diabetes mellitus

• People who have had a 

gastrectomy or jejunoileal bypass

• People who have low body weight

• People who use substances (such 

as injection drug use)

• Populations defined locally as 

having an increased incidence 

of disease due to M. tuberculosis, 

including medically underserved 

and low-income populations

7
DIAGNOSIS OF LATENT 

TB INFECTION (LTBI)

The diagnosis of LTBI is based on information gathered from the medical history, 

a TB test (i.e., a TB blood test [interferon-gamma release assay {IGRA}] or a 

tuberculin skin test [TST]), a chest radiograph, a physical examination, and 

sputum examinations in certain circumstances. TB disease must be excluded 

before initiating treatment for LTBI, because failure to do so may result in 

inadequate treatment and development of drug resistance. Key differences 

between LTBI and TB disease are listed in Table 2.

TABLE 2. 

Differentiating Between LTBI and TB Disease

Latent TB Infection (LTBI) TB Disease

• No symptoms or physical findings

suggestive of TB disease

• TB blood test or TST result

usually positive

• Chest radiograph is typically

normal 

• If done, respiratory specimens are

smear and culture negative

• Cannot spread TB bacteria

to others

• Should consider treatment for LTBI

to prevent TB disease

• Symptoms may include one or 

more of the following: fever, 

cough, chest pain, weight loss, 

night sweats, hemoptysis, fatigue,

and decreased appetite

• TB blood test or TST result

usually positive

• Chest radiograph is usually 

abnormal, but may be normal 

in people with advanced 

immunosuppression or 

extrapulmonary TB disease

• Respiratory specimens are usually

smear and/or culture positive, but 

may be negative in people with 

extrapulmonary TB disease or 

minimal/early pulmonary 

TB disease

• Can spread TB bacteria to others

• Needs treatment for TB disease

8
Tests for TB Infection 

Currently, the available methods of testing for M. tuberculosis infection are the TB 

blood tests (interferon-gamma release assays [IGRAs]) and the Mantoux tuberculin 

skin test (TST). 

TB Blood Tests 

(Interferon-Gamma Release Assays [IGRAs])

An IGRA is a type of blood test that is used to determine if a person is infected with

M. tuberculosis by measuring the immune response to TB proteins in whole blood.

Specimens are mixed with peptides that simulate antigens derived from

M. tuberculosis and controls. In most people infected with M. tuberculosis, the white 

blood cells recognize the simulated antigens and release interferon-gamma (IFN-γ).

There are two U.S. Food and Drug Administration (FDA) approved TB blood tests

commercially available in the U.S.:

• QuantiFERON®-TB Gold Plus (QFT-Plus)

• T-SPOT®.TB test (T-Spot)

A TB blood test should not be performed on a person who has written documentation of 

either a previous positive TB test result (TB blood test or TST) or treatment for TB disease. 

See Table 3 for advantages and limitations of TB blood tests.

TABLE 3.

Advantages and Limitations of TB Blood Tests

Advantages of TB Blood Tests Limitations of TB Blood Tests

• Requires only one patient visit to

conduct the test

• Does not cause booster phenomenon

(see Special Considerations in Testing 

for TB Infection)

• Not subject to the biases and errors

associated with TST placement and 

reading

• Results can be available within

24 hours

• Unaffected by the bacille CalmetteGuérin (BCG) vaccine and most 

nontuberculous mycobacteria (NTM)

• Blood samples must be 

processed within 8 to 32 hours

after collection

• Errors in collecting or 

transporting blood specimens 

or in running and interpreting 

the test can decrease the 

accuracy of TB blood tests

• Tests may be expensive

9
Interpretation of TB Blood Test Results

Interpretation of TB blood test results depends on the test being used. QFT-Plus 

results are based on the amount of IFN-γ that is released in response to the

M. tuberculosis antigens and control substances. T-Spot results are based on the

number of IFN-γ producing cells (spots) produced. Laboratories should provide 

both the qualitative and quantitative results.

• Qualitative results are reported as positive, negative, indeterminate, 

invalid, or borderline (Table 4).

• Quantitative results are reported as numerical values that include 

responses to the TB antigen and two controls, nil and mitogen. 

Quantitative results may be useful for clinical decision-making in 

individual cases, in combination with risk factors.

TABLE 4.

Interpretation of TB Blood Test Results

TB Blood Test Result Interpretation

Positive M. tuberculosis infection likely.

Negative M. tuberculosis infection unlikely, but cannot be 

excluded, especially if

1. Patient has signs and symptoms consistent

with TB disease.

2. Patient has a high risk for developing TB 

disease once infected with M. tuberculosis

(e.g., the patient is immunosuppressed).

Indeterminate (QFTPlus only) or Invalid 

(T-Spot only)

The test did not provide useful information 

about the likelihood of M. tuberculosis

infection. Repeating a TB blood test or 

performing a TST may be useful.

Borderline 

(T-Spot only) 

Repeating a TB blood test or performing a TST 

may be useful.

10
Tuberculin Skin Test (TST)

The Mantoux tuberculin skin test (TST) is also called the TB skin test. The TST is 

used to determine if a person has been infected with M. tuberculosis. If a person 

is infected, a delayed-type hypersensitivity reaction is detectable 2–8 weeks 

after infection. The skin test is administered intradermally using the Mantoux 

technique by injecting 0.1 ml of 5 tuberculin units of purified protein derivative 

(PPD) solution. The reading and interpretation of TST reactions should be 

conducted within 48–72 hours after administration. For more information about 

tuberculin skin testing, visit the CDC website for additional resources 

(see Resources) and refer to Appendix C.

The TST should not be performed on a person who has written documentation 

of a previous positive TB test result (TB blood test or TST) or treatment for 

TB disease.

Interpretation of Tuberculin Skin Test Reactions 

Interpretation of TST results is based on the measurement of the reaction in 

millimeters (mm), the person’s risk of acquiring TB infection, and the risk of 

progression to disease if infected (Table 5). A TST that was not measured and 

recorded in mm of induration must be repeated. Interpretation of the TST 

result is the same for people who have had BCG 

vaccination as it is for those who have not, 

because a majority of BCG crossreactivity wanes with time.

TST results should only be 

read by a trained health 

care professional. 

Training is essential 

for health care 

professionals to gain 

proficiency in the 

administration and 

interpretation of 

the TST.

11
TABLE 5. 

Interpretation of Tuberculin Skin Test (TST) Reactions

5 or more millimeters

A TST reaction of ≥5 mm of induration is considered positive for:

• People living with HIV

• Recent contacts of people with infectious TB 

• People with chest x-ray findings suggestive of previous TB disease 

• People with organ transplants 

• Other immunosuppressed patients (e.g., patients on prolonged therapy 

with corticosteroids equivalent to/greater than 15 mg per day of 

prednisone or those taking TNF-alpha antagonists)

10 or more millimeters

A TST reaction of ≥10 mm of induration is considered positive for:

• People born in countries where TB disease is common, including Mexico, 

the Philippines, Vietnam, India, China, Haiti, and Guatemala 

• People who abuse drugs 

• Mycobacteriology laboratory workers 

• People who live or work in high-risk congregate settings (e.g., nursing 

homes, homeless shelters, or correctional facilities) 

• People with certain medical conditions that place them at risk for TB (e.g., 

silicosis, diabetes mellitus, severe kidney disease, certain types of cancer, 

or certain intestinal conditions)

• People with a low body weight (<90% of ideal body weight)

• Children younger than 5 years of age 

• Infants, children, and adolescents exposed to adults in high-risk categories

15 or more millimeters

A TST reaction of ≥15 mm of induration is considered positive for:

• People with no known risk factors for TB

12
Although TB testing activities should generally be targeted towards groups 

or people at risk, certain individuals may be required to have testing 

for employment or school attendance independent of risk. CDC and the 

American Thoracic Society (ATS) do not recommend a testing approach that is 

independent of a risk assessment.

Selecting a Test to Detect TB Infection

Health care providers are encouraged to use TB blood tests to screen for LTBI. 

There are a few preferences and special considerations when determining 

which test to use.

• TB blood tests are the preferred method of testing for the following:

• Groups of people who might be less likely to return for TST reading 

and interpretation (e.g., homeless people or drug users)

• People who have received the BCG vaccine 

• People who are likely to be infected with M. tuberculosis and are at a 

low to intermediate risk of progression to TB disease

• People who are unlikely to be infected with M. tuberculosis (note: 

those who are unlikely to be infected generally should not be tested 

for TB; a confirmatory test is recommended if the initial test is 

positive in people unlikely to be infected) 

• Current U.S. guidelines suggest the TST as the recommended method of 

testing for children younger than 5 years of age while noting that some 

experts use TB blood tests in younger children. Clinicians may also choose 

to consult the American Academy of Pediatrics (AAP) guidance on the use 

of the TB blood test in children.

In general, using either a TB blood test or a TST is acceptable medical and 

public health practice. Routine testing with both TST and TB blood tests is NOT

recommended; however, there are certain situations where results from both 

tests may be useful (See Appendix D).

13
Special Considerations in 

Testing for TB Infection

Bacille Calmette-Guérin (BCG) TB Vaccine

In many parts of the world where TB is common, the BCG vaccine is used 

to protect infants and young children from serious, life-threatening disease 

(specifically miliary TB and TB meningitis). The World Health Organization 

(WHO) recommends that the BCG vaccine be administered during infancy 

in TB endemic countries. However, BCG is not generally recommended for 

use in the U.S. because of the low risk of infection with M. tuberculosis, the 

variable effectiveness of the vaccine against adult pulmonary TB, and the 

vaccine’s potential interference with TST reactivity. The BCG vaccine should be 

considered in consultation with a TB expert only for select individuals who meet 

specific criteria.

The BCG vaccine may cause a false-positive TST reaction. There is no reliable 

way to distinguish a positive TST reaction caused by BCG vaccination from a 

reaction caused by true TB infection. When using the TST, people who have 

been vaccinated with BCG should always be further evaluated for LTBI or TB 

disease as if they were not vaccinated with BCG. TST reactivity caused by BCG 

vaccine generally wanes with the passage of time, but periodic skin testing 

may prolong (boost) reactivity in vaccinated people. TST reactions should be 

interpreted based on risk stratification regardless of BCG vaccination history.

TB blood tests use M. tuberculosis specific antigens that do not cross react with 

BCG and, therefore, do not cause false positive reactions in BCG recipients. TB 

blood tests are the preferred test for people who have received the BCG vaccine.

HIV Infection

Worldwide, TB is a leading cause of death among people living with HIV. The 

risk of progression from LTBI to TB disease is 7% to 10% each year for those with 

both LTBI and untreated HIV infection. Those with LTBI who are not HIV infected 

have a 10% risk over their lifetime. Thus, the risk of progression to TB disease 

is 10 times greater for those who are HIV infected. This risk is substantially 

reduced with effective antiretroviral therapy (ART) for HIV, but the risk is still 

higher than it is for HIV-negative people with LTBI.

14
All people with HIV should be tested for LTBI at the time of HIV diagnosis, 

regardless of their epidemiological risk of TB exposure. A negative TB 

blood test or TST result does not exclude LTBI, particularly among people 

with advanced HIV infection or AIDS, as they may have a compromised 

ability to react to tests for TB infection. Annual testing for LTBI using TST is 

recommended for people with HIV who are at high risk for repeated or ongoing 

exposure to people with active TB disease.

After the initiation of ART, repeat testing for LTBI is recommended for HIVinfected people previously known to have negative TB blood test or TST 

results, because the immune response may be restored by ART.

Booster Phenomenon

One factor that can affect the accuracy of the baseline TST is the booster 

phenomenon. Some people infected with M. tuberculosis may have a negative 

reaction to the TST if many years have passed since they became infected. 

However, if they are tested again within a year of the first test, they may have 

a positive reaction indicating likely TB infection. This is because the first 

test stimulates, or boosts, their ability to react to the test. This is commonly 

referred to as the “booster phenomenon” and may incorrectly be interpreted 

as a skin test conversion (going from negative to positive). It may appear that 

these people were infected between the first and second skin tests; however, 

the second reaction is actually a boosted reaction (due to TB infection that 

occurred a long time ago). These people should still be considered for LTBI 

treatment after ruling out TB disease, particularly if they have risk factors for 

progression to disease.

To avoid misinterpretation, a strategy called two-step testing has been 

developed for telling the difference between boosted reactions and reactions 

caused by recent infection. For people who will be retested periodically, twostep testing should be used for the initial skin test. If the first TST result in the 

two-step baseline testing is positive, consider the person infected and evaluate 

and treat the person accordingly. If the first test result is negative, the TST 

should be repeated in 1–3 weeks. If the second test result is positive, consider 

the person infected and evaluate and treat the person accordingly. If both tests 

are negative, consider the person uninfected and classify the TST as negative at 

baseline testing (see Figure 1). 

15
When TB blood tests are used, there is no need for a second test because boosting 

does not occur. TB blood tests do not boost subsequent test results because, 

unlike the TST, the patient is not exposed to the M. tuberculosis antigens. However, 

the TST can boost a subsequent TB blood test. Therefore, if a person will be tested 

with both the TST and a TB blood test, it is recommended to conduct the TB blood 

test either before or at the same time as the TST.

Figure 1. 

Two-Step TST Testing

16
TB Screening and Testing of Health Care Personnel

In 2019, the Centers for Disease Control and Prevention (CDC) and the 

National Tuberculosis Controllers Association (NTCA) released updated 

recommendations for TB screening, testing, and treatment of health care 

personnel. These recommendations state that all U.S. health care personnel 

should be screened for TB upon hire (i.e., pre-placement). Annual TB testing of 

health care personnel is not recommended unless there is a known exposure 

or ongoing transmission. The screening process includes a baseline individual 

TB risk assessment, TB symptom evaluation, TB test (TB blood test or TST), and 

additional evaluation for TB disease as needed. 

If the TST is used to test health care personnel upon hire (pre-placement), the 

“two-step method” is recommended.

If a TB blood test is used for baseline testing, two-step testing is not required. 

The local health department should be notified immediately if TB disease

is suspected. 

Contacts

Contacts are people who have been exposed to a person with known or 

presumptive infectious TB (e.g., pulmonary or laryngeal TB with a positive 

sputum smear). For contacts of a person with infectious TB disease, retesting 

8–10 weeks after the end of exposure is indicated when the initial TB blood test 

or TST result is negative. In contact investigations, retesting is not called twostep testing. The second test is needed to determine if infection occurred but 

was too recent to be detected at the time of the first test. This is because it can 

take 2–8 weeks after being infected with M. tuberculosis for the body’s immune 

system to mount a response detectable by the tests.

Children younger than 5 years of age and immunosuppressed contacts (e.g., 

persons living with HIV) who have negative TB blood test or TST results should 

have a chest radiograph. If the chest radiograph is normal, treatment should be 

started for LTBI and the contact should be retested 8 to 10 weeks after their last 

exposure to the person with TB. 

If testing is repeated, the same type of test (TB blood test or TST) should be 

used. If the repeat test result is positive, treatment should be continued. If the 

repeat test result is negative, treatment can usually be discontinued.

17
Pregnancy

Pregnant women should be targeted for TB testing only if they have a specific 

risk factor for M. tuberculosis infection or for progression from LTBI to TB disease. 

The TST is both safe and reliable throughout the course of pregnancy. TB 

blood tests are also safe to use during pregnancy, but they have not been fully 

evaluated for diagnosing TB infection in pregnant women. Therefore, the test 

results should be interpreted with caution and with the help of a TB expert.

If a TB blood test or TST reaction is positive in a pregnant woman, obtain a chest 

radiograph using proper shielding.

Other Diagnostic Considerations

Chest Radiograph

Chest radiographs (x-rays) help differentiate between LTBI and pulmonary 

TB disease in individuals with positive tests for TB infection. The following 

guidelines are recommended:

• A chest radiograph should be ordered as part of a medical evaluation for a 

person who has a positive TB blood test or TST result.

• A chest radiograph is indicated in the absence of a positive test result for TB 

infection when a person is a close contact of an infectious TB patient and 

treatment for LTBI will be started (e.g., “window prophylaxis” in a young 

child or immunocompromised person).

• Children younger than 5 years of age should have both posterioranterior and lateral views; all others should have at least posterioranterior views.

• Other views or additional studies should be done based on the health care 

provider’s judgment.

• People with nodular or fibrotic lesions consistent with old TB are highpriority candidates for treatment of LTBI after TB disease is excluded.

• People with fully calcified, discrete granulomas on chest radiograph do not 

have an increased risk for progression to TB disease.

18
Sputum Examination for Acid-Fast 

Bacilli (AFB) Smear 

and Culture

Sputum examination is indicated 

for people with positive test 

results for TB infection 

and either an abnormal 

chest radiograph or the 

presence of respiratory 

symptoms (even when 

the chest radiograph 

is normal).

For people with HIV 

infection, sputum 

examination should 

be considered even 

with a normal chest 

radiograph. In the 

context of advanced HIV, 

chest radiographs can 

appear normal.

Physical Examination 

and Medical History

Physical examination and medical history 

(which includes obtaining information about previous 

positive tests for TB infection, previous treatment for LTBI or TB disease, and 

a risk assessment for liver disease) are indicated for individuals with positive 

TB test results. Written documentation of a previous positive TB blood test or 

TST result is required; a patient’s verbal history is not sufficient. Appendix E

provides an example of a documentation form.

19
TREATMENT OF LATENT 

TB INFECTION (LTBI)

Overview

There are several treatment regimens available for the treatment of LTBI (see 

Table 6 and Appendix F). Providers should work with patients to choose the 

appropriate regimen based on the following:

• Drug-susceptibility results of the presumed source case (if known)

• Coexisting medical conditions

• Potential for drug-drug interactions

In 2020, CDC and NTCA released updated guidelines on the treatment of LTBI. 

While all the regimens are effective, short-course rifamycin-based 3- or 4-month 

regimens are the preferred treatment options for LTBI. Short-course LTBI 

treatment regimens are effective, are safe, and have higher completion rates than 

longer 6- to 9-month regimens of isoniazid (INH) monotherapy. If short-course 

treatment is not an option (e.g., due to drug interactions with rifamycins), CDC 

and NTCA recommend 6 or 9 months of daily INH as effective alternative LTBI 

treatment regimens. It is important for clinicians and pharmacists to know the 

difference between rifampin (RIF) and rifapentine (RPT). RIF and RPT are not 

interchangeable, and clinicians and pharmacists should ensure that patients 

receive the correct medication for the prescribed treatment regimen.

Clinicians should contact their state and local TB control offices for additional 

information on diagnosing and treating LTBI. Contact information can be located 

on the State TB Control Offices website.

Treatment Regimens

Three Months of Once-weekly Isoniazid (INH) 

plus Rifapentine (RPT) Regimen (3HP)

The 3-month regimen of 12 once-a-week doses of INH and RPT is also known 

as the 3HP regimen. The regimen can be given under directly observed therapy 

(DOT) or self-administered therapy (SAT). Health care providers should choose 

the mode of administration (DOT or SAT) based on local practice, individual 

patient attributes and preferences, and other considerations (including risk of 

progression to severe forms of TB disease).

20
The 3HP regimen is recommended for people older than 2 years of age, 

including people with HIV/AIDS who are taking antiretroviral medications 

that have acceptable drug-drug interactions with RPT, such as efavirenz and 

raltegravir.*

The 3HP regimen of INH and RPT is NOT recommended for the following 

individuals:

• Children younger than 2 years of age

• People with HIV/AIDS who are taking antiretroviral medications with 

clinically significant or unknown drug interactions with once-weekly RPT*

• People presumed to be infected with INH- or RIF-resistant M. tuberculosis

• Pregnant women or women expecting to become pregnant during the 

3-month regimen

Four Months of Daily Rifampin (RIF) 

Regimen (4R)

A 4-month regimen of RIF, also known as 4R, is recommended for HIV-negative 

adults and children of all ages. The 4R regimen is especially recommended for 

people who cannot tolerate INH or who have been exposed to INH-resistant TB. 

LTBI treatment with RIF should be given daily for 4 months. 

RIF should not be used to treat HIV-infected people taking some combinations 

of ART.* In situations where RIF cannot be used, sometimes another drug, 

rifabutin (RBT), may be substituted.

Three Months of Daily Isoniazid (INH) and 

Rifampin (RIF) Regimen (3HR)

The 3-month regimen of INH and RIF, also known as 3HR, is given daily. 3HR 

is one of the three preferentially recommended short-course rifamycin-based 

regimens for adults and children of all ages, including HIV-negative and HIVpositive patients as drug interactions* allow. 

* Information about drug-drug interactions between specific anti-mycobacterial agents, 

including rifamycins (rifampin, rifabutin, and rifapentine) and antiretroviral agents, is available 

from Department of Health and Human Services, Guidelines for the Use of Antiretroviral Agents in 

Adults and Adolescents with HIV.

21
Six or Nine Months of Daily Isoniazid (INH) 

Regimens (6H or 9H)

If short-course treatment is not an option (e.g., due to drug interactions with 

rifamycins), regimens of 6 or 9 months of daily INH are considered alternative 

treatment regimens. Six months of daily INH, also known as 6H, is strongly 

recommended for HIV-negative adults and children of all ages and is a 

treatment option for HIV-positive adults and children of all ages. Nine months of 

daily INH, also known as 9H, is another treatment option for both HIV-negative 

and HIV-positive adults and children of all ages. Patients can be treated daily or 

twice weekly with INH. Patients being treated twice weekly should receive DOT.

It is important to note that although efficacious, treatment regimens of 6 

or 9 months of daily INH have higher liver toxicity risk and lower treatment 

completion rates than shorter rifamycin-based regimens.

22
TABLE 6. 

LTBI Treatment Regimens

Drug(s) Duration Dose and 

Age Group Frequency Total 

Doses

Isoniazid 

(INH)*

 and 

Rifapentine 

(RPT)†

3 months Adults and children aged >12 years 

INH:

15 mg/kg rounded up to the nearest 

50 or 100 mg; 900 mg maximum 

RPT:

10.0–14.0 kg, 300 mg 

14.1–25.0 kg, 450 mg 

25.1–32.0 kg, 600 mg 

32.1–49.9 kg, 750 mg ≥50.0 kg, 

900 mg maximum 

Children aged 2–11 years: 

INH*: 25 mg/kg; 900 mg maximum 

RPT†

: as above 

Once weekly 12

Rifampin 

(RIF)¶

4 months Adults: 10 mg/kg 

Children: 15-20 mg/kg**

Maximum dose: 600 mg 

Daily 120

Isoniazid 

(INH)*

 and 

Rifampin 

(RIF)¶

3 months Adults

INH*

: 5 mg/kg; 300 mg maximum

RIF¶

: 10 mg/kg; 600 mg maximum

Children

INH*: 10-20 mg/kg††; 300 mg maximum

RIF¶

: 15-20 mg/kg; 600 mg maximum

Daily 90

Isoniazid 

(INH)*

6 months Adults: 5 mg/kg 

Children: 10-20 mg/kg††

Maximum dose: 300 mg 

Daily 180

Adults: 15 mg/kg 

Children: 20-40 mg/kg††

Maximum dose: 900 mg 

Twice 

weekly§

52

Isoniazid 

(INH)*

9 months Adults: 5 mg/kg 

Children: 10-20 mg/kg††

Maximum dose: 300 mg 

Daily 270

Adults: 15 mg/kg 

Children: 20-40 mg††

Maximum dose: 900 mg 

Twice 

weekly§

76

* Isoniazid is formulated as 100-mg and 300-mg tablets.

†

 Rifapentine is formulated as 150-mg tablets in blister packs that should be kept sealed until use.

§

 Intermittent regimens must be provided via directly observed therapy (i.e., a health care worker observes the ingestion of medication).

DOT or self-administered therapy (SAT) may be used for the 3-month regimen of INH and RPT.

¶

 Rifampin (rifampicin) is formulated as 150-mg and 300-mg capsules.

** The American Academy of Pediatrics acknowledges that some experts use rifampin at 20–30 mg/kg for the daily regimen when 

prescribing for infants and toddlers (Source: American Academy of Pediatrics. Tuberculosis. In: Kimberlin DW, Brady MT, Jackson MA, Long 

SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:829–53).

†† The American Academy of Pediatrics recommends an isoniazid dosage of 10–15 mg/kg for the daily regimen and 20–30 mg/kg for the 

twice-weekly regimen.”

23
Special Considerations for 

LTBI Treatment

Directly Observed Therapy (DOT)

DOT for LTBI treatment should be considered for people who are at especially 

high risk for TB disease (e.g., young children) and are either taking an 

intermittent regimen or who may have difficulty with treatment adherence. 

Because of the importance of each dose, DOT must be used for patients on INH 

regimens given twice weekly. 

Contacts

Contacts should be evaluated immediately for LTBI and TB disease. If a contact’s 

TB blood test (interferon-gamma release assay [IGRA]) or TST result is positive 

and TB disease is excluded, the contact should be considered high priority 

for LTBI treatment (see the guidance below). Contacts who have negative test 

results should be retested 8–10 weeks after their last exposure to infectious TB. 

This is because it can take 2–8 weeks after being infected with M. tuberculosis for 

the body’s immune system to mount a response detectable by the tests.

LTBI treatment is sometimes given to people who are at high risk for rapidly 

developing TB disease, even if they have a negative TB blood test or TST result 

and less than 8–10 weeks have passed since they were last exposed to TB. These 

contacts include:

• Immunosuppressed people, including those who are HIV infected 

• Children younger than 5 years of age 

Treatment should be continued until the results of the second test and other 

medical evaluation are known. For contacts at high risk of TB disease, such as 

people with HIV/AIDS, a full course of LTBI treatment may be recommended 

even in the absence of a positive TB blood test or TST result. Consult with your 

local TB control program about the management of such contacts.

Providers should choose the appropriate LTBI regimen based on drugsusceptibility results of the presumed source case (if known).

24
• If a person is exposed to known drug-susceptible TB or drug 

susceptibility is unknown: 

• Positive TB blood test or TST result → Treat with a short-course 

rifamycin-based regimen (note: if short-course treatment is not an 

option, 6 or 9 months of daily INH is an alternative option)

• If a person is exposed to known INH-resistant TB: 

• Positive TB blood test or TST result → Treat with RIF for 4 months 

(note: before starting treatment, it is important to confirm that the 

source case’s M. tuberculosis isolate is susceptible to RIF)

• If a person is exposed to known RIF-resistant TB: 

• Positive TB blood test or TST result → Treat with INH (note: 

before starting treatment, consult an expert in the treatment of 

drug-resistant TB) 

• If a person is exposed to known multidrug-resistant (MDR) TB: 

• Positive TB blood test or TST result → Treat with later-generation

fluoroquinolone (note: before starting treatment, consult an expert 

in the treatment of MDR TB)

In general, contacts with a positive TB blood test or TST who can provide 

written documentation of prior adequate treatment for LTBI do not need 

to be retreated. Retreatment may be indicated for people at high risk of 

becoming re-infected and progressing to TB disease (e.g., young children and 

immunosuppressed people). In complicated situations, a TB expert should

be consulted. 

People with HIV/AIDS

• For information about drug-drug interactions between specific antimycobacterial and antiretroviral agents, see Guidelines for the Use of 

Antiretroviral Agents in Adults and Adolescents Living with HIV. 

• LTBI treatment for people with HIV/AIDS should be provided in consultation 

with an expert in the management of HIV and TB coinfection. 

• If the test for TB infection is negative, consider LTBI treatment if the person 

has had recent exposure to infectious TB, as discussed above.

25
Pregnancy

• For most pregnant women, LTBI treatment can be delayed until 2–3 

months post-partum to avoid administering unnecessary medication 

during pregnancy. 

• There is potential for an increased risk of hepatotoxicity during 

pregnancy and the first 2–3 months of the post-partum period.

• For women who are at high risk for progression from LTBI to TB disease, 

especially those who are a recent contact of someone with infectious TB 

disease, LTBI treatment should not be delayed on the basis of pregnancy 

alone, even during the first trimester.

• Before starting LTBI treatment, TB disease must be excluded through a 

symptom review and chest radiograph. For pregnant women at high risk 

for progression to TB disease, careful clinical monitoring or laboratory 

monitoring should be conducted. 

• Pregnant women can take any of the following regimens for the treatment 

of LTBI:

• 4-month daily regimen of RIF (4R)

• 3-month daily regimen of INH and RIF (3HR)

• 6- or 9-month daily regimen of INH (6H or 9H) 

• Supplementation with 25–50 mg/day of pyridoxine (vitamin B6) is 

recommended for pregnant women taking INH to ameliorate possible 

adverse effects of the drug. 

• For women in the post-partum period (within 3 months of delivery), 

baseline liver function tests should be conducted. 

• The 3HP regimen is not recommended for pregnant 

women or women expecting to become 

pregnant during the treatment period 

because its safety during pregnancy has 

not been studied.

 Breastfeeding Women

• Breastfeeding is not contraindicated 

in women taking INH or RIF 

separately.

26
• Breastfeeding women who are taking INH must be given a vitamin 

B6 supplement.

• However, there currently is not enough data to indicate whether the 

3HP regimen is safe for women to take while breastfeeding.

• Supplementation of pyridoxine (vitamin B6) is recommended for nursing 

women and for breastfed infants.

• The amount of INH or RIF in breast milk is inadequate for treatment of 

infants with LTBI.

• RIF can cause orange discoloration of body fluids, including breast milk. 

Orange discoloration of body fluids is expected and harmless.

Infants and Children

• Because of their young age, infants and young children with LTBI are known 

to have been recently infected and are at high risk for progressing to TB 

disease. 

• Infants and young children are also more likely than older children and 

adults to develop life-threatening forms of TB disease.

• Testing adults who have been in close social contact with the child may be 

warranted to determine whether a person with infectious TB disease can be 

found. Consult with your local TB control program.

• Children under 5 years of age who are contacts of an adult with infectious 

TB disease should receive treatment for LTBI even if the initial TST or blood 

test result is negative and less than 8–10 weeks have passed since their last 

exposure to infectious TB; this is called window prophylaxis. Before starting 

window prophylaxis, TB disease should be excluded by chest radiograph 

and symptom review.

• A second TST or blood test should be administered 8–10 weeks after 

the last exposure to someone with infectious TB disease. If testing is 

repeated, the same type of test (TB blood test or TST) should be used. If 

the repeat test result is positive, treatment should be continued. If the 

repeat test result is negative, treatment can usually be discontinued. 

Window prophylaxis can be discontinued if all of the following 

conditions are met:

i. The infant is 6 months of age or older.

ii. Second TST or blood test result is also negative.

iii. Second TST or blood test was performed 8 or more weeks after 

 the child was last exposed to an adult with infectious TB disease.

27
• In certain instances, medical providers might decide to prescribe a 

complete course of LTBI treatment even if the second TST or blood test 

is negative, particularly if the exposure to someone with TB disease 

is substantial.

• Although all of the LTBI regimens are effective, health care providers should 

prescribe the more convenient shorter treatment regimens, when possible. 

• The following regimens are recommended for the treatment of LTBI

in children:

• 3-month once weekly regimen of INH and RPT (3HP)

• 4-month daily regimen of RIF (4R)

• 3-month daily regimen of INH and RIF (3HR)

• 6- or 9-month daily regimen of INH (6H or 9H) 

• 3HP is recommended for children older than 2 years of age and may be 

given via DOT or SAT. 

• 4R and 3HR treatment regimens are recommended for children of any age. 

6H or 9H regimens are recommended alternative treatment regimens for 

children of any age.

• DOT for LTBI treatment should be considered for people who are at 

especially high risk for TB disease (e.g., young children) and are either 

taking an intermittent regimen or who may have difficulty with treatment 

adherence. Because of the importance of each dose, DOT must be used for 

patients on INH regimens given twice weekly.

• Risk of INH-related hepatitis in infants, children, and adolescents

is minimal.

• Routine monitoring of serum liver enzymes is not necessary unless the 

child has risk factors for hepatotoxicity.

Additional Notes of Importance

• Old fibrotic lesions can represent previous TB disease. Persons with old 

fibrotic lesions with TST results of ≥5 mm of induration or a positive TB 

blood test result and negative culture should be treated for LTBI.

• Calcified solitary pulmonary nodules, calcified hilar lymph nodes, and 

apical pleural capping represent healed primary M. tuberculosis infection 

and do not increase the risk of TB disease. The decision to treat for LTBI 

would be the same as for a person with a normal chest radiograph.

28
• Treatment must be modified if the patient is a contact of an individual with 

drug-resistant TB disease. Consult a TB expert if the known source of TB 

infection has drug-resistant TB.

Adverse Effects of Drugs Used 

to Treat LTBI

Some health care providers have concerns about treating patients for LTBI. 

These concerns have traditionally been related to the length of treatment and 

the potential side effects of medications. For patients without drug intolerability 

or drug-drug interactions, short-course (3–4 months) rifamycin-based treatment 

regimens are preferred over the longer-course (6–9 months) INH monotherapy 

for treatment of LTBI. Short-course LTBI treatment regimens are effective, are 

safe, and have higher completion rates than longer 6- or 9-month regimens 

of INH monotherapy. Shorter, rifamycin-based treatment regimens generally 

have a lower risk of hepatotoxicity than longer 6- or 9-month regimens of INH 

monotherapy.

As with any treatment, the health care provider must weigh the risks and 

benefits for each individual. Obtaining a detailed and accurate medical history 

and updating information at frequent intervals will identify persons who require 

close monitoring; this will aid in determining the most appropriate course of 

action. CDC guidelines, drug package inserts, and other authoritative medical 

sources should be consulted whenever there is a question about side effects or 

drug-drug interactions.

To ensure safe and efficacious treatment for LTBI, the health care provider 

should periodically assess the patient’s progress. The sections that follow 

discuss some of the adverse effects of INH and rifamycins, as well as 

recommendations for monitoring during treatment and for assessing and 

ensuring adherence.

Possible Adverse Effects of INH

• Elevated serum liver enzyme concentrations: Asymptomatic elevation 

of serum liver enzyme concentrations occurs in 10%–20% of people taking 

INH; liver enzyme concentrations usually return to normal even when 

treatment is continued. 

• It is generally recommended that INH be withheld if a patient’s 

transaminase level exceeds 3 times the upper limit of normal if 

associated with symptoms, or 5 times the upper limit of normal if the 

patient is asymptomatic.

29
• Clinical hepatitis: Clinical hepatitis occurs in less than 1% of people taking 

INH and is more common when INH is combined with other hepatotoxic 

agents. Factors that may increase either of these rates or the severity of 

hepatitis include daily alcohol consumption, underlying liver disease or 

risks for liver disease, and the concurrent use of other medications that are 

metabolized in the liver. Symptomatic hepatitis is rare in patients younger 

than 20 years of age, but severe and fatal cases have been reported. 

• Patients of all ages with underlying risk factors for liver disease should 

be monitored clinically.

• Peripheral neuropathy: Peripheral neuropathy occurs in less than 1% of 

people taking INH at conventional doses. It is more likely in the presence of 

other conditions associated with neuropathy. Persons with risk factors for 

neuropathy (e.g., pregnant women; breastfeeding infants; persons infected 

with HIV; those with diabetes, alcoholism, malnutrition, or chronic renal 

failure; or those who are of advanced age) are given pyridoxine (vitamin 

B6). Vitamin B6 can be administered at 25–50 mg/day with 6H, 9H, or 3HR, 

and at 50 mg/week with 3HP to prevent neuropathy. 

Possible Adverse Effects of Rifampin (RIF) and 

Rifapentine (RPT)

• Hepatotoxicity: Shorter, rifamycin-based treatment regimens 

generally have a lower risk of hepatotoxicity than longer 6- or 9-month 

regimens of INH monotherapy. Evidenced by transient asymptomatic 

hyperbilirubinemia, hepatotoxicity may occur in 0.6% of persons 

taking RIF.

• Cutaneous reactions: Pruritus/itching (with or without a rash) or other 

cutaneous reactions may occur in some persons taking RIF. The reactions 

are generally self-limited and may not be a true hypersensitivity; continued 

treatment may be possible.

• Hypersensitivity reactions: Rarely, rifamycins can be associated with 

hypersensitivity reactions, including hypotension, anaphylaxis, nephritis or 

thrombocytopenia, and manifested by symptoms such as fever, headache, 

dizziness/lightheadedness, musculoskeletal pain, petechiae, and pruritus.

• Gastrointestinal symptoms: Symptoms such as nausea, anorexia, and 

abdominal pain are rarely severe enough to discontinue treatment.

• Discoloration of body fluids: Orange-red discoloration of body fluids, 

such as urine and breast milk, is expected and harmless, but patients 

should be advised beforehand. Soft contact lenses and dentures may be 

permanently stained.

30
• Drug-drug interactions: RIF and RPT have drug-drug interactions with 

numerous medications. They are known to reduce concentrations of 

methadone, warfarin, hormonal contraceptives, tricyclic antidepressants, 

haloperidol, diazepam, and phenytoin. Dose adjustment of the companion 

medication may be necessary. Women using hormonal contraceptives 

should be advised to consider an alternative method of contraception (e.g., 

a barrier method).

• Contraindication with certain antiretroviral therapy (ART) 

medications: Rifampin (RIF) should not be used in HIV-infected individuals 

being treated with certain antiretroviral medications, such as protease 

inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs), 

integrase strand transfer inhibitors, and the CCR5 antagonist maraviroc. 

Substitution of rifabutin (RBT) for RIF in the 4-month regimen may be 

considered for such patients. Rifapentine (RPT) should not be used in 

HIV-infected persons taking antiretroviral medications that have clinically 

significant or unknown drug interactions with RPT. Clinicians are referred 

to the AIDSinfo guidelines, Guidelines for the Prevention and Treatment of 

Opportunistic Infections in Adults and Adolescents with HIV, that present 

the most current recommendations for TB treatment for persons with HIV 

infection and LTBI.

Patient Monitoring and Education 

During Treatment

To ensure safe and efficacious treatment for LTBI, the health care provider 

should periodically assess the patient’s progress. This evaluation involves 

clinical monitoring, laboratory testing, and patient education.

Clinical Monitoring

• All patients receiving LTBI treatment should be evaluated at least monthly 

for the following: 

• Adherence to the prescribed regimen

• Signs and symptoms of TB disease

• Adverse reactions (such as signs and symptoms of hepatitis)

• Patients being treated for LTBI who experience possible adverse reactions 

should be advised to stop medication and consult their health care 

provider immediately.

31
Laboratory Testing

• Baseline laboratory testing (measurements of serum AST, ALT, and bilirubin) 

is not routinely indicated for all patients at the start of LTBI treatment.

• Baseline testing can be considered on an individual basis, especially 

for patients taking other medications for chronic medical conditions.

• Laboratory testing at the start of LTBI therapy is recommended for patients 

with any of the following factors: 

• Liver disorders

• History of liver disease (e.g., hepatitis B or C, alcoholic hepatitis, 

or cirrhosis)

• Regular use of alcohol or injection drugs

• Risks for chronic liver disease

• HIV infection

• Pregnancy or the immediate post-partum period (i.e., within 3 months 

of delivery)

• After baseline testing, routine periodic retesting (e.g., monthly) is 

recommended for persons who had abnormal initial results and other 

persons at risk for hepatic disease.

• At any time during treatment, whether or not baseline tests were done, 

laboratory testing is recommended for patients who have symptoms 

suggestive of hepatitis (e.g., fatigue, weakness, malaise, anorexia, nausea, 

vomiting, abdominal pain, pale stools, brown urine, chills) or who 

have jaundice. 

• It is generally recommended that medication be withheld if a patient’s 

transaminase level exceeds 3 times the upper limit of normal if associated 

with symptoms, or 5 times the upper limit of normal if the patient is 

asymptomatic.

Patient Education

• Explain the disease process and rationale for medication in the absence of 

symptoms or radiographic abnormalities. 

• Review the importance of completing treatment for LTBI.

• Inform patients that RIF and RPT may cause urine or other body fluids to 

turn orange. This side effect is harmless.

32
• Instruct patients at the start of treatment to stop taking their medication 

and seek medical attention immediately if they experience any of the 

following medication side effects: 

• Dizziness or lightheadedness

• Loss of appetite

• Flu-like symptoms

• Severe diarrhea or light-colored 

stools

• Shortness of breath

• Feelings of sadness or 

depression

• Fever

• Unexplained anorexia

• Brown urine (color of coffee 

or cola)

• Icterus (jaundice)

• Rash

• Persistent paresthesia (tingling or 

prickling sensation) of hands 

and feet

• Persistent fatigue or weakness lasting 3 

or more days

• Abdominal tenderness, especially in right 

upper quadrant

• Easy bruising or bleeding

• Arthralgia (joint pain)

• Nausea

• Vomiting

• Discuss management of common side effects and the need to report to 

health care provider.

Assessing Patient Adherence

Many variables affect a patient’s adherence to LTBI treatment. Using shorter 

treatment regimens can help patients complete treatment. Health care providers 

should prescribe the more convenient shorter regimens when possible.

33
Episodes of non-adherence should be recognized and addressed as soon as 

possible. See Table 7 for examples of barriers to adherence.

TABLE 7. 

Examples of Barriers to Patient Adherence to 

LTBI Treatment

Clinic-Related Variables

• Long waiting time for appointment and referrals

• Long waiting time in provider’s office

• Inconvenient office hours

• Complicated telephone system (not user friendly)

• Cost

Patient-Related Barriers

• Misinformation or confusion about certain issues, such as 

• The meaning of test results

• Differences between injections, vaccines, TST, and blood tests

• The words “positive” and “negative” as they relate to test results

• Modes of TB transmission and prevention

• Exposure vs. becoming infected

• Safety of family and friends around someone with LTBI

• Residential instability

• Lack of financial resources

• Poor access to health care

• Stigma associated with TB

• Co-existing medical conditions

• Culture and language

• Religious practices (e.g., fasting from food)

Treatment Barriers

• Complexity and duration of treatment

• Medication side effects

• Obtaining refills

• Frequency of office visits

• Cost, including insurance co-payment

34
Techniques to Improve Adherence • Collaborate with the local health department to provide treatment. 

• Provide DOT if the patient is high risk (e.g., HIV infected, young child, or

TB contact).

• Use case management principles to coordinate care and services.

• Consider free or low-cost medication.

• Offer rewards for adherence (incentives), such as grocery store or restaurant 

vouchers, nutritional supplements, cell phone credits, or movie tickets.

• Provide enablers to overcome barriers, e.g., free transportation or public 

transportation vouchers.

• Provide patient education and instructions in patient’s primary language at 

every visit.

• Ensure confidentiality.

• Suggest or provide patient reminders, such as pill box, calendar, or timer.

Post-Treatment Follow Up • Patients should receive documentation that includes TB blood test or 

TST results, chest radiograph results, names and dosages of medication, 

and duration of treatment. Patients should be instructed to present this 

document any time future TB testing is required.

• Providers should re-educate 

patients about the signs and 

symptoms of TB disease and 

advise them to contact their 

medical provider if they 

develop any of these signs or 

symptoms.

• Among patients who have 

documented completion 

of LTBI treatment, serial or 

repeat chest radiographs 

are not indicated unless the 

patient develops signs or 

symptoms suggestive of 

TB disease.

35
APPENDIX A

SAMPLE TB RISK 

ASSESSMENT TOOL

Persons should be considered at increased risk for TB if any of the following 

statements are marked “Yes.”

Risk Factor Yes No

Temporary or permanent residence of ≥1 month in a 

country with a high TB rate.

Any country other than the United States, Canada, 

Australia, New Zealand, and those in northern Europe or 

western Europe.

Current or planned immunosuppression, including 

human immunodeficiency virus (HIV) infection, organ 

transplant recipient, treatment with a TNF-alpha 

antagonist (e.g., infliximab, etanercept, or other), chronic 

steroids (equivalent of prednisone ≥15 mg/day for ≥1 

month), or other immunosuppressive medication (e.g., 

cancer chemotherapy).

Close contact during lifetime with someone who has 

had infectious TB disease.

Adapted from: Risk assessment form developed by the California Department of Health, 

Tuberculosis Control Branch

36
APPENDIX B

IDENTIFYING 

PERSONS FROM HIGH 

BURDEN COUNTRIES

• Local epidemiologic profiles are the most useful resource to identify 

countries of highest risk. Health care providers should base testing and 

treatment decisions on local immigration patterns and epidemiology.

• In 2019, approximately 70% of TB cases in the United States occurred in nonU.S.-born persons. 

• The top five countries of birth of non-U.S.-born persons with TB were 

Mexico, the Philippines, Vietnam, India, and China.

• For a list of high burden countries and profiles of these countries, see the 

Stop TB Partnership website.

37
APPENDIX C

ADMINISTRATION 

AND MEASUREMENT 

OF THE TST*

Administration

The Mantoux test is the recommended tuberculin skin test (TST). It is administered 

by injecting 0.1 ml of 5 tuberculin units of purified protein derivative (PPD) solution 

intradermally into the volar surface of the forearm using a 27-gauge needle with a 

tuberculin syringe.

• Obtain results of all previous TSTs or TB blood tests. Ask patient to describe 

what the test area looked like 2–3 days after administration. Written 

documentation must be obtained for history to be applicable.

• Avoid areas of skin with veins, rashes, or excess hair.

• Cleanse the area with alcohol swab, allow area to dry, and inject all antigen 

just below the surface of the skin on the volar surface of the forearm, forming 

a 6–10 mm wheal (a pale, raised area with distinct edges; has orange-peel 

appearance and does not disappear immediately).

• If no wheal forms, or if a wheal forms that is less than 6 mm of induration, the 

test should be repeated immediately, approximately 2 inches from original site 

or on the other arm.

• If minor bleeding occurs, dab the injection site with a cotton swab.

• Avoid covering the area with a bandage or applying pressure to the injection site.

• Record the date, time, and location of TST administration.

• Instruct patient not to scratch the site, but to use a cool compress to relieve 

any itching or swelling.

• Inform patient that they will need to return for a reading of their TST within 

48–72 hours (2–3 days).

• Give written appointment card for their TST reading.

• Provide written information about the TST (pamphlet or brochure).

38
Measurement • Measure the induration (hard bump) rather than erythema (area of redness).

• Palpate area with fingertips, measuring the diameter of induration 

perpendicular to the long axis of the arm.

• Use ballpoint pen to mark edges of induration.

• Use a TST ruler or ruler with millimeters to measure the distance between 

the 2 points.

Recording and Documentation • Record date TST was administered.

• Record the brand name of the PPD solution, lot number, manufacturer, and 

expiration date on the patient record.

• Record results in millimeters of induration (0 mm if there is no induration) 

rather than as positive or negative.

• Record date and time of reading and name of person reading TST.

• Provide written documentation to patient and ordering health care provider.

Storage and Handling • PPD solution must be kept refrigerated at 36°– 46° F.

• Avoid fluctuations in temperature; do not store on the refrigerator door.

• Syringes must be filled immediately prior to administration.

• Store and transport the tuberculin in the dark as much as possible; avoid 

exposure to light.

• Tuberculin testing solution should not be stored with other vials, such as 

Tdap, that could be mistaken for PPD.

* Contact the local health department TB program for training on the Mantoux tuberculin skin test. 

Contact information can be located at https://www.cdc.gov/tb/links/tboffices.htm.

39
APPENDIX D 

SITUATIONS WHERE 

RESULTS FROM BOTH 

A TB BLOOD TEST AND 

TST MAY BE USEFUL

Routine testing with both a TB blood test and a TST is not recommended. 

However, results from both tests might be useful in the following situations:

• When the initial test is negative and: 

• The risk for infection, progression to disease, and/or a poor outcome is 

high (e.g., HIV-infected persons or children younger than 5 years of age 

who are exposed to a person with infectious TB).

• There is clinical suspicion for TB disease (e.g., signs, symptoms, or 

radiographic evidence suggestive of TB disease) and confirmation of 

M. tuberculosis infection is desired.

• Taking a positive result from a second test as evidence of infection 

increases detection sensitivity.

• When the initial test is positive and: 

• Additional evidence of infection is desired to encourage acceptance 

and adherence to treatment. For example, when counseling a BCGimmunized person who has a positive TST, a subsequent positive TB 

blood test, the results of which are not affected by BCG immunization, 

might be meaningful to the patient in accepting LTBI diagnosis and 

treatment. Note: TB blood tests are the preferred method of testing for 

persons who have received the BCG vaccine.

• The person has a low risk of both infection and progression from 

infection to TB disease. Requiring a positive result from the second 

test as evidence of infection in a person at low risk increases the 

likelihood that the test reflects M. tuberculosis infection. 

40
In addition, repeating a TB blood test or 

performing a TST should occur when 

the initial TB blood test result is 

indeterminate, borderline, or invalid, 

and a reason for testing persists. 

Multiple negative results from 

any combination of these 

tests cannot exclude 

M. tuberculosis infection. 

Steps should be taken to 

minimize unnecessary 

and misleading testing of 

persons at low risk. Selection 

of the most suitable test or 

combination of tests for 

detection of M. tuberculosis

infection should be based on 

the reasons and the context 

for testing, test availability, 

and overall cost of testing.

41
APPENDIX E

SAMPLE 

DOCUMENTATION 

FORMS

Record of TB Blood Test

To Whom It May Concern:

The following is a record of TB blood test results:

Name: 

Date of birth: 

Type of test: Date blood collected: 

Laboratory: 

For QFT-Plus*:

Nil: IU/mL

TB1: IU/mL

TB1 minus Nil: IU/mL

TB2: IU/mL

TB2 minus Nil: IU/mL

Mitogen: IU/mL

Mitogen minus Nil: IU/mL

QFT-Plus Interpretation 

For T-SPOT®.TB:

Nil: spots

TB Panel A: spots

TB Panel A minus Nil: spots

TB Panel B: spots

TB Panel B minus Nil: spots

Mitogen: spots

T-Spot Interpretation

*also known as QuantiFERON®-TB Gold Plus

For more information consult manufacturers’ websites and package inserts.

42
Record of Tuberculin Skin Test

To Whom It May Concern:

The following is a record of Mantoux tuberculin skin test (TST) results:

Name: Date of birth: 

Date and time test administered: 

Administered by: 

Manufacturer of Purified Protein Derivative (PPD): 

Expiration date: Lot number: 

Time test read: Read by: 

Date: Induration: mm

TST interpretation: 

Record of Treatment Completion

To Whom It May Concern:

The following is a record of evaluation and treatment for M. tuberculosis infection:

Name: Date of birth: 

Tuberculin skin test (TST): Date: 

Results (in millimeters of induration): 

TB blood test: Date: Type of test: Result: 

Chest radiograph: Date: Result: 

Date medication started: Date completed: 

Medication(s): 

This person is not infectious. He/she may always have a positive TB test, so 

there is no reason to repeat the test. If you need any further information, please 

contact this office.

Provider Contact Information

Name: 

Phone Number: 

Address: 

Signature of Provider: Date: 

43
APPENDIX F

LATENT TB INFECTION 

TREATMENT REGIMENS

.

DRUG DURATION FREQUENCY 

Preferred

 ISONIAZID†

 AND

 RIFAPENTINE††

(3HP)

3 months Once weekly 

RIFAMPIN§

(4R) 4 months Daily 

ISONIAZID†

 AND

 RIFAMPIN§

 (3HR)

3 months Daily 

Alternative

ISONIAZID†

(6H/9H)

6 months

Daily 

Twice weekly 

¶ 

9 months

Daily 

Twice weekly 

¶ 

*For persons with HIV/AIDS, see Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with 

HIV available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/367/overview. †

Isoniazid is formulated as 100-mg and 300-mg tablets.

††Rifapentine is formulated as 150-mg tablets in blister packs that should be kept sealed until use.

¶

Intermittent regimens must be provided via directly observed therapy (i.e., a health care worker observes the 

ingestion of medication).

44
Treatment regimens for latent TB infection (LTBI) use isoniazid (INH), rifapentine (RPT), or 

rifampin (RIF). CDC and the National Tuberculosis Controllers Association preferentially 

recommend short-course, rifamycin-based, 3- or 4-month latent TB infection treatment 

regimens over 6- or 9-month isoniazid monotherapy. Clinicians should choose the 

appropriate treatment regimen based on drug susceptibility results of the presumed source case 

(if known), coexisting medical conditions (e.g., HIV*), and potential for drug–drug interactions. 

TOTAL DOSES DOSE AND AGE GROUP

12

Adults and children aged ≥12 yrs

INH: 

 15 mg/kg rounded up to the nearest 50 or 100 mg; 

 900 mg maximum

RPT:

 10–14.0 kg; 300 mg

 14.1–25.0 kg; 450 mg

 25.1–32.0 kg; 600 mg

 32.1–49.9 kg; 750 mg

 ≥50.0 kg; 900 mg maximum

Children aged 2–11 yrs

INH†

: 25 mg/kg; 900 mg maximum

RPT††: See above

120

Adults: 10 mg/kg; 600 mg maximum

Children: 15–20 mg/kg||; 600 mg maximum

90

Adults

INH†

: 5 mg/kg; 300 mg maximum

RIF§

: 10 mg/kg; 600 mg maximum

Children

INH†

: 10-20 mg/kg#; 300 mg maximum

RIF§

: 15-20 mg/kg; 600 mg maximum

180 Adults

Daily: 5 mg/kg; 300 mg maximum

Twice weekly: 15 mg/kg; 900 mg maximum 

52

270 Children 

Daily: 10–20 mg/kg#

; 300 mg maximum 

Twice weekly: 20–40 mg/kg# 

; 900 mg maximum 

76

§

Rifampin (rifampicin) is formulated as 150-mg and 300-mg capsules.

||The American Academy of Pediatrics acknowledges that some experts use rifampin at 20–30 mg/kg for the daily 

regimen when prescribing for infants and toddlers (Source: American Academy of Pediatrics. Tuberculosis. 

In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious 

Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:829–53).

#

The American Academy of Pediatrics recommends an INH dosage of 10–15 mg/kg for the daily regimen and 

20–30 mg/kg for the twice weekly regimen. 45
APPENDIX G LTBI 

TESTING AND TREATMENT: SUMMARY 

OF U.S. RECOMMENDATIONS

Eliminating tuberculosis (TB) in the United States 

requires expanding testing and treatment of 

latent TB infection.

The Centers for Disease Control and Prevention (CDC) and 

the U.S. Preventive Services Task Force (USPSTF) recommend 

testing people that are at increased risk for TB infection. 

Clinicians, health care agencies, and community organizations, 

especially those serving populations at risk, have a critical role 

in TB elimination.

46 JUNE 2020
WHO SHOULD 

BE TESTED FOR 

TB INFECTION?

CDC and the USPSTF recommend testing populations 

that are at increased risk for TB infection.

Anyone can get TB. However, some people have a higher 

risk of getting infected with TB bacteria. CDC supports 

the USPSTF recommendation to test certain groups at 

risk for TB infection. These groups include:

• People who were born in or who frequently travel 

to countries where TB disease is common, including 

Mexico, the Philippines, Vietnam, India, China, Haiti, 

Guatemala, or other countries with high rates of TB. 

(In general, people born in Canada, Australia, New 

Zealand, western European countries, or northern 

European countries are not considered at high risk for 

TB infection unless they spent time in a country with a 

high rate of TB.)

• People who currently live or used to live in large group 

settings where TB is more common, such as homeless 

shelters, prisons, or jails.

CDC also recommends testing for TB infection for other 

groups at risk. These groups include:

• Health care workers and others who work in places 

with high risk for TB transmission, such as hospitals, 

homeless shelters, correctional facilities, nursing 

homes, and residential homes for those with HIV.

• Anyone who has spent time with a person who has 

infectious TB disease.

47
Some people with weaker immune systems, such 

as those with certain health conditions or who take 

certain medications, have a higher risk of developing 

TB disease once infected. Testing for TB infection 

should be part of their regular medical care. Health 

conditions that increase a person’s risk of developing 

TB disease once infected include:

• HIV infection

• Recent infection with 

M. tuberculosis (within 

the last two years)

• History of untreated or 

inadequately treated 

TB disease

• Medical treatments that 

suppress the immune 

system (such as tumor 

necrosis factor-alpha 

[TNF] antagonists, 

corticosteroids, or drug 

therapy following organ 

transplants)

• Silicosis; chronic renal 

failure; leukemia; or 

cancer of the head, 

neck, or lung

• Diabetes mellitus

• A gastrectomy or 

jejunoileal bypass

• Low body weight (<90% 

of ideal body weight)

• Substance use (such as 

injection drug use)

Children, especially those under age 5, have a higher 

risk of developing TB disease once infected. Therefore, 

testing for TB infection in children is important if they 

are in one of the risk groups noted above.

48
RECOMMENDED TESTS FOR TB INFECTION:

Testing for TB infection should be a routine 

and integral part of health care for patients 

with increased risk for TB. Health care 

providers are encouraged to use newer 

TB blood tests to screen for TB infection.

There are two kinds of tests that are used to determine 

if a person has been infected with TB bacteria: the TB 

blood test and the TB skin test.

TB Blood Tests (Interferon Gamma 

Release Assays [IGRAs]) 

TB blood tests (sometimes called IGRAs) use a blood 

sample to find TB infection. The tests measure the 

response of TB proteins when they are mixed with a 

small amount of blood. Only one visit is required to 

draw blood for the test.

TB blood tests are the preferred method of TB testing for people 

5 years of age and older who have received the bacille CalmetteGuérin (BCG) vaccine.

49
TB Skin Test (TST) 

The TB skin test is also called the Mantoux tuberculin 

skin test (TST). With a TB skin test, a health care provider 

injects a small amount of testing fluid (called tuberculin 

or PPD) into the skin on the lower part of the arm.

After 2-3 days, the skin test reaction must be examined 

by a trained health care worker. The health care 

worker measures any swelling where the tuberculin 

was injected to determine if the reaction to the test is 

positive or negative.

TB skin tests are an acceptable alternative in situations 

where a TB blood test is not available, is too costly, or is 

too burdensome.

A positive reaction to a TB blood test (IGRA) or TB skin 

test (TST) usually means TB infection. More tests, such 

as a chest x-ray, are needed to rule out TB disease.

A diagnosis of latent TB infection is made if a person 

has a positive TB blood test (IGRA) or TST result and a 

medical exam does not indicate TB disease.

50
RECOMMENDED TREATMENT REGIMENS FOR LATENT TB INFECTION:

Treating latent TB infection is effective in preventing TB disease 

and less costly than treating TB disease.

There are several treatment regimens for the treatment of latent 

TB infection.

• These regimens use the drugs isoniazid, rifapentine, or rifampin.

CDC and the National Tuberculosis Controllers Association 

(NTCA) preferentially recommend short-course, rifamycin-based, 

3- or 4-month latent TB infection treatment regimens over 6- or 

9-month isoniazid monotherapy (6H or 9H, respectively).

• Short-course regimens include:

• Three months of once-weekly isoniazid plus 

rifapentine (3HP)

• Four months of daily rifampin (4R)

• Three months of daily isoniazid plus rifampin (3HR)

• Short-course latent TB infection treatments are effective, are 

safe, and have higher completion rates than longer treatments.

• If a short-course treatment regimen is not an option, 6H 

or 9H is an effective alternative latent TB infection 

treatment regimen.

51
Shorter regimens help patients 

finish treatment.

All treatment must be modified if the patient is a contact of an 

individual with drug-resistant TB disease. Consultation with a TB 

expert is advised if the known source of TB infection has drugresistant TB.

Clinicians should choose the appropriate treatment regimen 

based on drug susceptibility results of the presumed source case 

(if known), coexisting medical conditions (e.g., HIV infection), 

and potential for drug- drug interactions.

Clinicians may choose to administer latent TB infection 

treatment through directly observed therapy (DOT) or selfadministered therapy (SAT) based on local practice, individual 

patient attributes, and provider preferences.

52
CDC’s One-stop Shop for Information, 

Guidance, and Education

The Latent TB Infection Online Resource Hub is a 

collection of downloadable materials for informing 

and educating the public, health care providers, policy 

makers, and other partners about the importance of 

expanded latent TB infection testing and treatment. 

Available resources include:

• Guidance Documents

• Fact Sheets for 

Clinicians & Patients

• Communication 

Templates

• Key Messages & Social 

Media Content

• Slide Sets

• Images & Videos

• Infographics

• Helpful Links & More

 Follow @CDC_TB on Twitter

 Like @CDCTB on Facebook

LATENT TB 

INFECTION ONLINE 

RESOURCE HUB 

53
RESOURCES

Websites • Centers for Disease Control and Prevention (CDC)

Division of Tuberculosis Elimination

• State TB Control Offices

• Find TB Resources 

• World Health Organization

TB Centers of Excellence for Training, 

Education, and Medical Consultation

The CDC’s Division of Tuberculosis Elimination funds four TB Centers of 

Excellence for Training, Education, and Medical Consultation (TB COEs). The TB 

COEs are regionally assigned to cover all 50 states and the U.S. territories.

The TB COEs support domestic TB control and prevention efforts with a focus on 

two major activities:

• Increasing knowledge, skills, and abilities for TB prevention and control 

through communication, education, and training activities

• Improving sustainable, evidence-based TB clinical practices and patient 

care through the provision of expert medical consultation

To view all of the educational materials developed by the TB COEs, visit the 

TB COE’s Products website.

For the most current information about the TB COEs, visit the CDC website.

Educational Materials for Health Care Providers*

Online Resources

• Latent TB Infection Online Resource Hub (CDC)

• Mantoux Tuberculin Skin Test Training Resources (CDC)

• Latent TB Infection Treatment Regimens – Treatment Table (CDC)

• Latent TB Infection Treatment – FAQs for Clinicians (CDC)

• Latent TB Infection Testing and Treatment: Summary of U.S 

Recommendations (CDC) 54
Booklets and Pocket Cards

• Management for Latent Tuberculosis Infection in Children and Adolescents: 

A Guide for the Primary Care Provider (Global Tuberculosis Institute at 

Rutgers) 

• “Addendum 2014”

• Diagnosis and Treatment of Latent Tuberculosis Infection Pocket Drug Card

(Global Tuberculosis Institute at Rutgers) 

• TB Screening Tests in Children (Heartland National TB Center)

Fact Sheets

• Targeted Tuberculin Testing and Interpreting Tuberculin Skin Test 

Results (CDC)

• Treatment of Latent Tuberculosis Infection: Maximizing Adherence (CDC) 

• Interferon-Gamma Release Assay (IGRAs) (CDC) 

• BCG Vaccine (CDC) 

Slide Set 

• Targeted TB Testing and Treatment of Latent Tuberculosis Infection (CDC)

Videos

• Latent TB Videos for Healthcare Providers (Curry International TB Center 

and TB Free California) 

• TB Personal Stories (CDC) 

*View and download CDC education and training materials at the TB publications and products 

website. Select materials are available in print and can be ordered from the CDC-INFO On 

Demand publications system.

Educational Materials for Patients

Brochures 

• 12-Dose Regimen for Latent TB Infection (English, Chinese, Haitian Creole, 

Marshallese, Spanish, Tagalog, Vietnamese) (CDC) 

• Questions and Answers About Tuberculosis (English, Spanish) (CDC) 

• Patient Education Series (English, Spanish, Tagalog, Vietnamese) (CDC) 

55
Medication Trackers

• 12-Dose Regimen for Latent TB Infection-Medication Tracker (English, 

Chinese, Haitian Creole, Marshallese, Spanish, Tagalog, Vietnamese) (CDC)

• 4R Regimen for Latent TB Infection-Medication Tracker (CDC) 

• 3HR Regimen for Latent TB Infection-Medication Tracker (CDC)

Fact Sheets 

• What You Need to Know About Your Medicine for Latent Tuberculosis (TB) 

Infection – Fact Sheet Series (CDC) 

• You Can Prevent TB (CDC) 

Videos

• TB Personal Stories (CDC) 

*CDC education and training materials may be viewed and downloaded online at the patient & 

general public materials website. Select materials are available in print and can be ordered from 

the CDC-INFO On Demand publications system.

56
REFERENCES

1. American Academy of Pediatrics (AAP). Tuberculosis. In: Red Book 2018: Report 

of the Committee on Infectious Diseases. Itasca, IL: AAP; 2018. https://redbook.

solutions.aap.org/book.aspx?bookid=2205. 

2. Borisov AS, Bamrah Morris S, Njie GJ, et al. Update of Recommendations for Use 

of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium 

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volumes/67/wr/mm6725a5.htm?s_ cid=mm6725a5_w. 

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rccm.201909-1874ST.

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Tuberculosis Infection: Recommendations from the National Tuberculosis 

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RecommendationStatementFinal/latent-tuberculosis-infection-screening.

58
NOTES

59
Publication Number 22-0468

Centers for Disease Control and Prevention

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

Division of Tuberculosis Elimination

www.cdc.gov/tb

@cdc_TB @CDCTB

CDC-INFO: http://wwwn.cdc.gov/dcs/RequestForm.aspx