Core Curriculum on Tuberculosis:

What the Clinician Should Know

Sixth Edition 2013

CS234269
To View or Order the Core Curriculum on Tuberculosis

To view or download the Core Curriculum, please visit: www.cdc.gov/tb. 

If you would like to request a print copy of the Core Curriculum, 

please use the CDC publication online ordering system at www.cdc.gov/tb.

All copies are free of charge.
Introduction to the Core Curriculum on Tuberculosis

i

Sixth Edition 2013

Centers for Disease Control and Prevention

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

Division of Tuberculosis Elimination

Introduction to the

Core Curriculum on Tuberculosis:

What the Clinician Should Know

Introduction to the Core Curriculum on Tuberculosis

iii

Introduction to the

Core Curriculum on Tuberculosis:

What the Clinician Should Know

Table of Contents

Introduction to the Core Curriculum on Tuberculosis . . . . . . . . . . . . . . . . . . . . . i

About the Curriculum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

Continuing Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x

Key Tuberculosis Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xii

Chapter 1– Overview of Tuberculosis Epidemiology in the United States . . . 1

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Progress Toward TB Elimination in the United States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

TB Disease Trends in the United States, 1982– 2011 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Chapter 2– Transmission and Pathogenesis of Tuberculosis . . . . . . . . . . . . . 19

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Transmission of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Pathogenesis of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Drug-Resistant TB (MDR and XDR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

TB Classification System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Introduction to the Core Curriculum on Tuberculosis

iv

Chapter 3– Testing for Tuberculosis Infection and Disease . . . . . . . . . . . . . . 45

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Identifying High-Risk Groups for M. tuberculosis Testing . . . . . . . . . . . . . . . . . . . . . . . . 47

Testing Methods for TB Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

BCG Vaccination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

Chapter 4– Diagnosis of Tuberculosis Disease . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

Medical Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

Chapter 5– Treatment for Latent Tuberculosis Infection . . . . . . . . . . . . . . . . 109

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111

Candidates for the Treatment of Latent TB Infection (LTBI) . . . . . . . . . . . . . . . . . . . . . 112

LTBI Treatment Regimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

LTBI Treatment Regimens for Specific Situations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

Patient Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

Chapter 6– Treatment of Tuberculosis Disease . . . . . . . . . . . . . . . . . . . . . . . . 139

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141

Treatment and Monitoring Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Introduction to the Core Curriculum on Tuberculosis

v

Adherence Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

TB Disease Treatment Regimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

TB Disease Treatment Regimens for Specific Situations . . . . . . . . . . . . . . . . . . . . . . . . . . 165

Patient Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176

Evaluating Response to Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187

Chapter 7– Tuberculosis Infection Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191

Infectiousness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192

TB Infection Control Measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196

TB Infection Control Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199

TB Infection Control in Nontraditional Facility-Based Settings . . . . . . . . . . . . . . . . . . . . 218

TB Infection Control in the Home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226

Chapter 8– Community Tuberculosis Control . . . . . . . . . . . . . . . . . . . . . . . . . . 227

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229

Roles and Responsibilities of the Public Health Sector Providers . . . . . . . . . . . . . . . . . . . 229

Roles and Responsibilities of Specific Private Health Sector Providers . . . . . . . . . . . . . . . 236

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248

Appendix A– Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

Appendix B– Answers to the Study Questions . . . . . . . . . . . . . . . . . . . . . . . . 259

Appendix C– PowerPoint Slide Set . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267

Introduction to the Core Curriculum on Tuberculosis

vii

About the Core Curriculum on Tuberculosis: 

What the Clinician Should Know

Purpose

The Core Curriculum on Tuberculosis: What the Clinician Should Know (Core Curriculum) presents 

information about tuberculosis (TB) for health-care professionals. This document, produced by the 

Centers for Disease Control and Prevention (CDC) Division of Tuberculosis Elimination (DTBE), 

updates the 2000 Core Curriculum. It is intended for use as a reference manual for clinicians caring 

for persons with or at high risk for TB disease or infection. In addition, it was designed to be 

useful in developing educational programs. It is not meant to provide detailed answers to all public 

health or clinical questions about TB, nor is it meant as a substitute for any specific guidelines. It is 

anticipated that new guidelines will be published at future dates that will supersede information in 

the Core Curriculum, and these new guidelines will be posted on the CDC DTBE website: 

www.cdc.gov/tb.

An update on TB for clinicians is critical today. Research to find new treatment regimens and more 

effective use of current ones continues as multidrug-resistant and extensively drug-resistant TB cases 

challenge the public health community. The increased complexity of TB and HIV co-infection 

has required updated guidelines for prevention and treatment. Testing, diagnosis, and patient 

management and public health practice have also been revised.

Target Audience

The audience for this course includes clinicians who are caring for persons with or at high risk for TB 

disease or infection.
Introduction to the Core Curriculum on Tuberculosis

viii

Goal

The goal of the Core Curriculum is to provide the reader with information about TB. Upon 

completion of this educational activity, the reader should possess a clear working knowledge 

of the diagnosis, treatment, and prevention of TB infection and disease.

Materials

The Curriculum

The Core Curriculum includes the following materials: 

• Print-based self-study manual with the following 8 chapters: 

» Chapter 1. Overview of Tuberculosis Epidemiology in the United States 

» Chapter 2. Transmission and Pathogenesis of Tuberculosis

» Chapter 3. Testing for Tuberculosis Infection and Disease

» Chapter 4. Diagnosis of Tuberculosis

» Chapter 5. Treatment of Latent Tuberculosis Infection

» Chapter 6. Treatment of Tuberculosis Disease

» Chapter 7. Tuberculosis Infection Control

» Chapter 8. Community Tuberculosis Control

• Each chapter includes

» Chapter objectives

» Content topics with study questions

» Chapter summary

» References

• Appendix A–Glossary

• Appendix B–Answers to the study questions

• Appendix C–PowerPoint slides
Introduction to the Core Curriculum on Tuberculosis

ix

Estimated Time for Completion

The curriculum is designed in a self-study format so that each person can work at his or her 

own pace. The actual time it takes to complete the Core Curriculum may differ from person to 

person. Listed below are estimates of the time needed to complete each chapter and the entire 

8-chapter course.

Core Curriculum on Tuberculosis: What the Clinician Should Know

Estimated Time for Completion 

Chapter Title Estimated Time

for Completion

1 Overview of Tuberculosis Epidemiology in the 

United States

15 minutes

2 Transmission and Pathogenesis of Tuberculosis 25 minutes

3 Testing for Tuberculosis Infection and Disease 45 minutes

4 Diagnosis of Tuberculosis 50 minutes

5 Treatment of Latent Tuberculosis Infection 55 minutes

6 Treatment of Tuberculosis Disease 100 minutes

7 Tuberculosis Infection Control 65 minutes

8 Community Tuberculosis Control 35 minutes

TOTAL 6 hours and 30 minutes

Study Questions 

Study questions are included throughout each chapter to provide a review of the content and help 

the reader apply the content to real-life situations. The format of the questions includes either 

multiple choice or matching. For each question, select the ONE BEST ANSWER. Answers to the 

study questions are available in Appendix B.

PowerPoint Slide Set 

The Core Curriculum is accompanied by a PowerPoint slide set for use in presentations and training 

programs. Images of the slides are included in Appendix C. The slide set may be downloaded from 

the CDC DTBE website at . 

To View or Order the Core Curriculum on Tuberculosis

To view or download the Core Curriculum, please visit: www.cdc.gov/tb. 

If you would like to request a print copy of the Core Curriculum, please use the CDC publication 

online ordering system at www.cdc.gov/tb.

All copies are free of charge.
Introduction to the Core Curriculum on Tuberculosis

x

Course Objectives

The overall objectives for the entire Core Curriculum are listed below. 

• Identify TB disease trends in the United States.

• Describe the transmission and pathogenesis of TB.

• Identify appropriate TB testing methods.

• Describe the five components of a TB medical evaluation.

• Describe LTBI treatment regimens.

• Describe treatment regimens for TB disease.

• List common adverse drug reactions to TB medications.

• Discuss the three levels of an effective TB infection control program. 

• Describe the roles and responsibilities for TB control and prevention in the public and private 

health care sectors.

Continuing Education

Continuing education (CE) is offered free of charge for various professions based on approximately 

6.5 hours of instruction. In order to receive CE credit/contact hours, you must complete an exam 

and course evaluation. No minimum score is necessary to receive credit/contact hours. Upon 

successful completion of the course, exam, and evaluation, your CE certificate will be issued by 

CDC Training and Continuing Education Online.

Continuing Education Registration and Test

You can register and take the test for CE credits/contact hours online for the Core Curriculum. 

• Origination Date: February 15, 2011

• Renewal Date: February 15, 2013

• Expiration Date: Check the online registration website to determine the expiration date of the 

CE credits/contact hours. 

Continuing Education Credits/Contact Hours

The following CE credits/contact hours are available free of charge for the Core Curriculum: 

• Continuing education units (CEUs)

The CDC has been approved as an Authorized Provider by the International Association 

for Continuing Education and Training (IACET), 1760 Old Meadow Road, Suite 500, 

McLean, VA 22102. The CDC is authorized by IACET to offer 0.6 ANSI/IACET CEUs 

for this program.

• Continuing medical education (CMEs)

The CDC is accredited by the Accreditation Council for Continuing Medical Education 

(ACCME®) to provide continuing medical education for physicians.
Introduction to the Core Curriculum on Tuberculosis

xi

The CDC designates this enduring material for a maximum of 6.5 AMA PRA Category 

1 CreditsTM. Physicians should only claim credit commensurate with the extent of their 

participation in the activity.

• Continuing nursing education (CNEs)

The CDC is accredited as a provider of Continuing Nursing Education by the American 

Nurses Credentialing Center’s Commission on Accreditation. 

This activity provides 6.5 contact hours.

• Continuing education contact hours in health education (CECH)

Sponsored by the CDC, a designated provider of continuing education contact hours (CECH) 

in health education by the National Commission for Health Education Credentialing, Inc. 

This program is designed for Certified Health Education Specialists (CHES) and/or Master 

Certified Health Education Specialists (MCHES) to receive up to 6.5 Category I continuing 

education contact hours. Maximum advanced level continuing education contact hours 

available are 0. CDC provider number GA0082.

Online Registration and Test

To receive continuing education, you must register for this specific course and submit an evaluation 

at the CDC Training and Continuing Education Online website.

• Go to www2a.cdc.gov/TCEonline

• Log in as a participant. (Note: If you are a first-time user of this online system, you will need to 

log in as a new participant and create a participant profile.) 

» When you receive your reset password by e-mail, log in as a participant and 

change the password. 

• At Participant Services, click on Search and Register, type a keyword from the course title into 

the keyword search, such as “Core,” and click View. You can also find the course by typing in 

the course number. The course number for this activity is SS1604.

• Click on the title, Core Curriculum on Tuberculosis, select the type of credit/contact hours you 

wish to receive at the bottom, and click Submit.

• Verify the demographic information and click Submit at the bottom.

• Complete the course evaluation. 

• Complete the course posttest (if applicable).

• At Participant Services, click on Certificates and Transcripts and print your continuing 

education certificate. 

For assistance with the online system, call 1(800)-41-TRAIN Monday through Friday from 

8:00 AM to 4:00 PM Eastern Standard Time, or e-mail ce@cdc.gov.

Disclosure Statement

CDC, our planners, and our reviewers wish to disclose they have no financial interests or other 

relationships with the manufacturers of commercial products, suppliers of commercial services, or 

commercial supporters. Planners have reviewed content to ensure there is no bias.
Introduction to the Core Curriculum on Tuberculosis

xii

Content does not include any discussion of the unlabeled use of a product or a product under 

investigation with the exception of Levofloxacin, Moxifloxacin, Gatifloxacin, and Rifabutin.

The CDC does not accept commercial support.

Key Tuberculosis Resources

Tuberculosis Reporting, Guidelines, and Recommendations

Clinicians should immediately contact their state health department if they have a patient with 

suspected or confirmed TB disease. The health department can assist in providing guidance and 

overall public health management of the patient. Contact information for each state TB control 

office can be found at www.cdc.gov/tb/links/tboffices.htm.

For additional information about TB guidelines and recommendations, contact 

the following sources:

• CDC DTBE website: www.cdc.gov/tb

• TB Regional Training and Medical Consultation Centers (RTMCCs): 

http://www.cdc.gov/tb/education/rtmc/default.htm

• American Lung Association: www.lungusa.org/

• American Thoracic Society: www.thoracic.org

Additional Education and Training Resources

• Find TB Resources website: www.findtbresources.org

• TB Regional Training and Medical Consultation Centers product list: 

https://sntc.medicine.ufl.edu/rtmccproducts.aspx

Content Experts

Content experts included staff from the Centers for Disease Control and Prevention, Division of 

Tuberculosis Elimination. 

For Additional Information 

For additional information on TB, visit the CDC DTBE website at www.cdc.gov/tb. If you have 

questions on state-specific TB guidelines, please contact your state TB control office. A list of state 

TB control offices can be found on the CDC DTBE website at www.cdc.gov/tb/links/tboffices.htm
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

1

Chapter 1 

Overview of Tuberculosis Epidemiology 

in the United States

Table of Contents

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Progress Toward TB Elimination in the United States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 

TB Disease Trends in the United States, 1982– 2011 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Chapter Objectives

After working through this chapter, you should be able to 

• Discuss progress toward tuberculosis (TB) elimination in the United States; 

• Identify TB disease trends in the United States; and

• List the racial and ethnic groups that are disproportionately affected by TB disease in the 

United States.

Chapter 1: Overview of Tuberculosis Epidemiology in the United States

3

Progress Toward TB Elimination in the United States

In 1989, the Centers for Disease Control and Prevention (CDC) announced the goal of eliminating 

TB from the United States by the year 2010. A Strategic Plan for the Elimination of Tuberculosis in 

the United States was published in 1989 and reassessed in 1999 to identify the actions necessary to 

achieve elimination. The achievement of this goal was thwarted by the TB resurgence that occurred 

in the late 1980s and early 1990s. This resurgence was fueled by the following factors:

• The onset of the human immunodeficiency virus (HIV) epidemic;

• Increases in immigration of persons from countries where TB disease was common;

• TB transmission in congregate settings; and

• The development of multidrug-resistant (MDR) TB.

These factors occurred at a time when decades of cuts in funding had resulted in inadequate support 

for TB control and other public health efforts, and in the deterioration of TB control programs. As 

a result, federal, state, and local TB control officials had very few resources for TB control activities. 

Subsequently, the United States renewed its commitment to TB control in the 1990s and mobilized 

new resources. In 1993, the upward trend of new TB cases reversed, and the number of new cases 

has continued its decline up to and through 2011. This can be attributed to the increase in funds 

and resources which enabled TB programs to improve their control efforts to

• Promptly identify persons with TB disease;

• Start appropriate treatment for persons with TB disease; and

• Ensure patients complete treatment.

Despite unprecedented low rates of TB disease, elimination of TB faces some major barriers 

including 

• TB disease in high-risk populations where it is difficult to detect, diagnose, and treat;

• Persistence and growth of the global TB epidemic; and

• Limitations of current control measures and the need for new tests and treatments, including 

an effective vaccine.
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

4

TB Disease Trends in the United States, 1982–2011

The resurgence of TB disease, which began in the mid-1980s, was marked by several years of 

increasing case counts until its peak in 1992. Case counts began decreasing in 1993, and 2011 

marked the 19th year of decline in the total number of TB cases reported in the United States 

since the peak of the resurgence (Figure 1.1). From 1993 until 2002, the total number of TB cases 

decreased 5%–7% annually. Although rates continued to decline from 2003 through 2008, it was at 

a much slower rate. However, an unprecedented decline occurred in 2009, when the total number of 

TB cases decreased by more than 10% from 2008 to 2009. In 2011, a total of 10,528 TB cases were 

reported. This represents a decline of 5.8% from 2010 (Table 1.1).

Fig 1.1

Reported TB Cases*

United States, 1982– 2011

*Updated as of June 25, 2012.

Year

Number of Cases

1985-1992

Resurgence 

0

5,000

10,000

15,000

20,000

25,000

30,000

1982

1984

1986198819901992

1994

1996199820002002

2004

2006200820102011
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

5

Table 1.1

TB Morbidity

United States, 2006– 2011

Year No. Rate*

2006 13,727 4.6

2007 13,278 4.4

2008 12,895 4.2

2009 11,528 3.8

2010 11,171 3.6

2011 10,528 3.4

*Cases per 100,000, updated as of June 25, 2012

While national trends indicate that there has been a decline in the overall number of cases since 1993, 

cases continue to be reported. It is important to focus on local epidemiology to identify trends in 

individual states or regions.

While national trends indicate that there has been a decline in the 

overall number of cases since 1993, cases continue to be reported.

In 2011, a total of 38 states reported a rate less than or equal to 3.4 TB cases per 100,000, the 2011 

national average. Twelve states and D.C. reported a rate above 3.4 TB cases per 100,000; these 

areas accounted for 67% of the national total in 2011 and have also experienced substantial overall 

decreases in cases and rates from 1992 through 2011 (Figure 1.2).
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

6

Figure 1.2

TB Case Rates* 

United States, 2011

*Cases per 100,000.

>3.4 (2011 national average)

< 3.4

D.C.

TB Case Rates by Origin

During 1993 to 2003, rates declined in both the U.S.-born and the foreign-born populations; 

however, the decline was substantially less among foreign-born populations. In 2002, for the first 

time, TB cases among foreign-born persons accounted for the majority (51.2%) of TB cases in the 

United States. Overall, the number of cases in foreign-born persons has remained virtually level with 

approximately 7,000–8,000 cases each year, until 2009 when the number dropped to 6,854. That 

decreasing trend continued in 2011 with the number of cases in foreign-born persons dropping to 

6,510. The number of cases in U.S.-born persons decreased from more than 17,000 in 1993 to 3,981 

in 2011.

In 2002, for the first time, TB cases among foreign-born persons 

accounted for the majority (51.2%) of TB cases in the United States. 
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

7

Percentage of TB Cases among Foreign-Born Persons 

in the United States, 2001–2011

The percentage range of the total number of TB cases that occurred in foreign-born persons in each 

state is high¬lighted for 2001 and 2011 in side-by-side maps (Figure 1.3). The number of states with 

less than 25% of their TB cases among foreign-born persons decreased from 13 states in 2001 to 6 

states in 2011. The number of states with 25%-49% of cases among foreign-born persons decreased 

from 14 states in 2001 to 11 states in 2011. However, the number of states that had 50% or more of 

their cases among foreign-born persons increased from 23 states in 2001 to 34 states in 2011. 

Figure 1.3

Percentage of TB Cases Among Foreign-Born Persons

United States, 2001– 2011*

*Updated as of June 25, 2012.

2001

DC

2011

DC

>50%

25%–49%

<25%

The countries of birth of foreign-born persons reported with TB disease in the United States have 

remained relatively constant since 1986. Seven countries accounted for 61% of the total cases in 

foreign-born persons in 2011 (Table 1.2 and Figure 1.4). 
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

8

Table 1.2

Countries of Birth of Foreign-Born Persons 

Reported with TB in the United States, 2011

Country

Percent of Total 

Foreign-Born Cases 

in the United States

Mexico 22%

Philippines 11%

Vietnam 8%

India 8%

China 6%

Guatemala 3%

Haiti 3%

Other Countries (135) 39%

Figure 1.4

Countries of Birth of Foreign-Born Persons Reported with TB

United States, 2011

Mexico

(22%)

Philippines

(11%)

India

(8%)

Vietnam

(8%)

China

(6%)

Guatemala

(3%)

Haiti

(3%)

Other

Countries

(39%) 
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

9

Race and Ethnicity

Figure 1.5 shows the declining trend in TB rates by race/ethnicity during the years 2003– 2011. 

Asians had the highest TB rates, which declined from 29.9 per 100,000 in 2003 to 20.9 in 2011, 

and had a percent decline over the time period of 30%. Rates also declined in the following racial/

ethnic groups: among non-Hispanic blacks or African-Americans, from 11.7 in 2003 to 6.3 in 2011 

(-46%); among Hispanics, from 10.3 to 5.8 (-44%); among American Indians and Alaska Natives, 

from 8.2 to 5.6 (-32%); and among non-Hispanic whites, from 1.4 to 0.8 (-43%). Rates decreased 

among Native Hawaiian or Other Pacific Islanders after two years of increase since 2008, from 16.2 

in 2003 to 15.9 in 2011(-2%). 

Figure 1.5

TB Case Rates by Race/Ethnicity*

United States, 2003– 2011**

*All races are non-Hispanic

**Updated as of June 25, 2012. Cases per 100,000

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

2003 2004 2005 2006 2007 2008 2009 2010 2011

Years

Asian Hispanic or Latino

Native Hawaiian or Other Pacific Islander American Indian or Alaska Native

Black or African-American White

Several important factors likely contribute to the disproportionate burden of TB in minorities, 

including the following:

• Infection acquired in the country of origin in foreign-born minorities;

• Unequal distribution of TB risk factors contributing to

» An increased exposure to TB 

» An increased risk of developing TB disease once infected with M. tuberculosis

(e.g., HIV infection); 

• Lower socioeconomic status and the effects of crowding
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

10

HIV-Infected Persons

HIV-infected persons are at high risk for developing TB disease after infection with M. tuberculosis. In 

the age group of 25–44 among persons reported with TB disease, the percentage of HIV coinfection 

declined from a high of 29% in 1993 to 10% in 2011. In all ages, the percentage of HIV coinfection 

decreased from 15% in 1993 to 6% in 2011. 

Figure 1.6 provides minimum estimates of HIV coinfection among persons reported with TB from 

1993 through 2011. Since the addition of the request for HIV status to the individual TB case report 

in 1993, incomplete reporting has provided a challenge to calculating reliable estimates. Results from 

the cross-matching of TB and AIDS registries have been used to supplement reported HIV test results. 

Figure 1.6

Estimated HIV Coinfection in Persons Reported with TB

United States, 1993– 2011*

*Updated as of June 25, 2012

Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group. 

% Coinfection

0

5

10

15

20

25

30

1993

19941995

19961997199819992000

2001

20022003

20042005

20062007200820092010

2011

Aged 25–44 All Ages

Year

HIV-infected persons are at high risk for developing TB 

disease after infection with M. tuberculosis.
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

11

Multidrug-Resistant TB

Multidrug-resistant TB (MDR TB) is caused by an organism that is resistant to at least isoniazid and 

rifampin, the two most potent TB drugs; it is a serious public health concern. Both U.S.-born and 

foreign-born persons had decreases in the number and percentage of cases of MDR TB, although the 

decline in U.S.-born persons has been greater (Figure 1.7). As a result, the percentage of all primary 

MDR TB cases reported and associated with being foreign born increased from approximately 25% 

of all MDR TB cases in 1993 to 83% in 2011.

Figure 1.7

Primary MDR TB in U.S.-Born vs. Foreign-Born Persons

United States, 1993– 2011*

*Updated as of June 25, 2012.

Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid 

and rifampin. 

U.S.-born Foreign-born

% Resistant

0

1

2

3

1993199419951996199719981999200020012002200320042005200620072008200920102011

Year of Diagnosis

Primary MDR TB cases reported in foreign-born persons increased 

from approximately 25% of all MDR cases in 1993 to 83% in 2011.
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

12

Extensively Drug-Resistant TB 

Extensively drug-resistant TB (XDR TB) is a rare type of MDR TB that is resistant to isoniazid 

and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., 

amikacin, kanamycin, or capreomycin). For 1993– 2011, the annual numbers of reported XDR 

TB cases, as determined by the initial drug-susceptibility test (DST), are shown below (Figure 1.8). 

There is no apparent trend in the number of XDR TB cases over time in the United States. The 

greatest number of cases reported in a single year that met the XDR TB case definition was 10 in 

1993. There were no cases reported in 2003 or 2009. One case of XDR TB was reported in 2010 

and six cases in 2011. 

There is no apparent trend in the number of XDR TB 

cases over time in the United States. 

Figure 1.8

XDR TB Case Count Defined on Initial DST* by Year 

1993– 2011**

* Drug susceptibility test

** Updated as of June 25, 2012.

Note: Extensively drug-resistant TB (XDR TB) is defined as resistance to isoniazid and rifampin, plus resistance to any 

fluoroquinolone and at least one of three injectable second-line anti-TB drugs. 

Case Count

Year of Diagnosis

0

2

4

6

8

10

12

1993

19941995

19961997199819992000

2001

20022003

20042005

20062007200820092010

2011

Identifying Groups at High Risk for TB

The decrease in TB cases and MDR TB is encouraging; however, the earlier resurgence of TB 

provides a valuable lesson. Every TB case is a potential outbreak. Health departments must be 

prepared to identify promptly and treat persons who have active TB disease, as well as identify 

and treat close contacts who may have become infected from persons with active TB disease. By 

understanding which groups are at higher risk for becoming infected with M. tuberculosis, health 

departments can better focus TB prevention and control efforts (Table 1.3).
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

13

Table 1.3

Persons at Higher Risk for Exposure to 

and/or Infection with M. tuberculosis

Description

• Close contacts of persons known or suspected to have TB disease

• Foreign-born persons from areas that have a high incidence of TB disease 

(e.g., Africa, Asia, Eastern Europe, Latin America, and Russia)

• Persons who visit areas with a high prevalence of TB disease, especially if 

visits are frequent or prolonged

• Residents and employees of high-risk congregate settings 

(e.g., correctional facilities, long-term care facilities, and homeless shelters)

• Health-care workers who serve clients who are at increased risk for TB disease

• Populations defined locally as having an increased incidence of latent M. tuberculosis

infection or TB disease, possibly including medically underserved, low-income 

populations, or persons who abuse drugs or alcohol

• Infants, children, and adolescents exposed to adults who are at increased risk for 

latent tuberculosis infection or TB disease

Study Questions

1.1 In 2011, how many TB cases were reported from the 50 states and D.C.? 

(circle the one best answer)

A. 5,466

B. 10,528

C. 21,553

1.2 Which of the following statements is true about TB case rates between 1993 and 2011?

(circle the one best answer)

A. Rates increased in both foreign-born populations and U.S.-born populations.

B. Rates decreased in both foreign-born populations and U.S.-born populations.

C. Rates remained level in both foreign-born populations and U.S.-born populations.
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

14

The following countries of birth of foreign-born persons accounted for 61% of the total number 

of TB cases in the United States in 2011. Match the country of birth with its percentage of total 

TB cases among foreign-born persons. (Choose the one best answer and write the letter for the 

correct answer on the line next to the question number.) 

Country of Birth

Percent of Total TB Cases in 

Foreign-Born Persons in the 

United States, 2011 

(Answers may be used more than once)

____ 1.3 China

____ 1.4 Guatemala

____ 1.5 Haiti

____ 1.6 India

____ 1.7 Mexico

____ 1.8 Philippines

____ 1.9 Vietnam

A. 3%

B. 6%

C. 8%

D. 11%

E. 22%

1.10 Which of the following statements about trends in TB rates by race/ethnicity in the 

United States, from 2003 to 2011, are true? (circle the one best answer)

A. Rates declined among Asians and Pacific Islanders from 29.9 per 100,000 in 2003 to 

20.9 in 2011.

B. Rates declined by at least 22% among non-Hispanic blacks or African Americans, 

Hispanics, American Indians and Alaska Natives, and non-Hispanic whites from 

2003 to 2011.

C. Rates increased among Hispanics, from 8.1 per 100,000 in 2003 to 19.9 in 2011.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

15

1.11 Which of the following factors contribute to the disproportionate burden of TB disease in 

minorities? (circle the one best answer)

A. Infection acquired in the country of origin in foreign-born minorities.

B. Unequal distribution of TB risk factors (e.g., HIV), contributing to increased 

exposure to TB disease or to an increased risk of developing TB disease once 

infected with M. tuberculosis.

C. Lower socioeconomic status and the effects of crowding.

D. A, B, and C are all correct.

E. Only A and B are correct.

1.12 Which of the following statements about MDR TB and XDR TB in the United States are 

true? (circle the one best answer)

A. Primary MDR TB cases reported in foreign-born persons increased from approximately 

25% among all MDR TB cases in 1993 to 83% in 2011.

B. There is no apparent trend in the number of XDR TB cases over time in the United States. 

C. The annual number of cases of counted XDR TB cases during 1993– 2011 was 160. 

D. A, B, and C are correct.

E. Only A and B are correct.

1.13 Of the following persons, who is LEAST likely to be exposed to TB disease?

(circle the one best answer)

A. Trang was born in Vietnam and recently immigrated to the United States.

B. Frank lives in a homeless shelter.

C. Joshua attends high school in Canton, Ohio.

D. Ellen is a nurse at the Texas State Penitentiary at Huntsville.
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

16

Chapter Summary

The resurgence of TB disease, which began in the mid-1980s, was marked by several years of 

increasing case counts until its peak in 1992. Case counts began decreasing in 1993, and 2011 

marked the 19th year of decline in the total number of TB cases reported in the United States since 

the peak of the resurgence. From 1993 until 2002, the total number of TB cases decreased 5%– 7% 

annually. Although rates continued to decline from 2003 through 2008, it was at a much slower rate. 

However, an unprecedented decline occurred in 2009, when the total number of TB cases decreased 

by more than 10% from 2008 to 2009. In 2011, a total of 10,528 TB cases were reported. This 

represents a decline of 5.8% from 2010.

HIV-infected persons are at high risk for developing TB disease after infection with M. tuberculosis. 

In the age group of 25–44 among persons reported with TB disease, the percentage of HIV 

coinfection declined from a high of 29% in 1993 to 10% in 2011. In all ages, the percentage of HIV 

coinfection decreased from 15% in 1993 to 6% in 2011. 

MDR TB is caused by an organism that is resistant to at least isoniazid and rifampin, the two most 

potent TB drugs; it is a serious public health concern. Both U.S.-born and foreign-born persons had 

decreases in the number and percentage of cases of MDR TB, although the decline in U.S.-born 

persons has been greater. As a result, the percentage of all primary MDR TB cases reported and 

associated with being foreign-born increased from approximately 25% of all MDR TB cases in 1993 

to 83% in 2011. 

There is no apparent trend in the number of XDR TB cases over time in the United States. The 

greatest number of cases reported in a single year that met XDR TB case definition was 10 in 1993. 

There were no cases reported in 2003 or 2009. One case of XDR TB was reported in 2010 and six 

cases in 2011.

References

CDC. A strategic plan for the elimination of tuberculosis in the United States. MMWR 1989; 38 

(Suppl No. S-3). www.cdc.gov/mmwr/preview/mmwrhtml/00001375.htm 

CDC. CDC’s Response to Ending Neglect: The Elimination of Tuberculosis in the United States. 

Atlanta, Ga: U.S. Department of Health and Human Services, CDC; 2002. 

CDC. Controlling tuberculosis in the United States: Recommendations from the American Thoracic 

Society, CDC, and the Infectious Diseases Society of America. MMWR 2005; 54 (No. RR-12).

www.cdc.gov/mmwr/PDF/rr/rr5412.pdf

CDC. Essential components of a tuberculosis prevention and control program: Recommendations of 

the Advisory Council for the Elimination of Tuberculosis. MMWR 1995; 44 (No. RR-11).

www.cdc.gov/mmwr/preview/mmwrhtml/00038823.htm 

CDC. Extensively drug-resistant tuberculosis—United States, 1993–2006. MMWR 2007; 56 (11): 

250–3. www.cdc.gov/mmwr/preview/mmwrhtml/mm5611a3.htm
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17

CDC. Guidelines for preventing opportunistic infections among HIV-infected persons—2002. 

MMWR 2002; 51 (No. RR-08). www.cdc.gov/mmwr/preview/mmwrhtml/rr5108a1.htm

CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 

2005. MMWR 2005; 54 (No. RR-17). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e

CDC. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and 

adolescents. MMWR 2009; 58 (No. RR-4). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr58e324a1.htm?s_cid=rr58e324a1_e

CDC. Guidelines for the investigation of contacts of persons with infectious tuberculosis. MMWR

2005; 54 (No. RR-15). www.cdc.gov/mmwr/pdf/rr/rr5415.pdf

CDC. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed 

and HIV-infected children. MMWR 2009; 58 (No. RR-11). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr58e0826a1.htm

CDC. Notice to Readers: Updated guidelines on managing drug interactions in the treatment of 

HIV-related tuberculosis. MMWR 2008; 57 (04): 98. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5704a4.htm?s_cid=mm5704a4_e

CDC. Plan to combat extensively drug-resistant tuberculosis. MMWR 2009; 58 (RR-03).

www.cdc.gov/mmwr/preview/mmwrhtml/rr5803a1.htm?s_cid=rr5803a1_e

CDC. Prevention and control of tuberculosis in correctional and detention facilities. MMWR 2006; 

55 (No. RR-09). www.cdc.gov/mmwr/PDF/rr/rr5509.pdf

CDC. Reported HIV status of tuberculosis patients—United States, 1993– 2005. MMWR 2007; 56 

(42): 1103–6. www.cdc.gov/mmwr/preview/mmwrhtml/mm5642a2.htm?s_cid=mm5642a2_e

CDC. Reported tuberculosis in the United States, 2011. Atlanta, Ga: U.S. Department of Health and 

Human Services, CDC; October 2012. www.cdc.gov/tb/statistics/reports/2011/default.htm

CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR 2000; 49 

(No. RR-6). www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm

Updates:

Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis 

infection—United States, 2004– 2008. MMWR 2010; 59 (08):224– 9.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5908a3.htm?s_cid=mm5908a3_e

Adverse event data and revised American Thoracic Society/CDC recommendations against the use 

of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 2003. 

MMWR 2003; 52 (31):735– 9. www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm
Chapter 1: Overview of Tuberculosis Epidemiology in the United States

18

Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis 

infection, and revisions in American Thoracic Society/CDC recommendations—United States, 

2001. MMWR 2001; 50 (34):733–5 www.cdc.gov/mmwr/preview/mmwrhtml/mm5034a1.htm

Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent 

tuberculosis infection—New York and Georgia, 2000. MMWR 2001; 50 (15): 289– 91. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5015a3.htm

CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to 

treat latent Mycobacterium tuberculosis infection recommendations—United States, 2011. MMWR

2011; 60 (48): 1650–1653. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6048a3.htm?s_

cid=mm6048a3_w

Errata (February 3, 2012)

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a7.htm

CDC. Treatment of tuberculosis. MMWR 2003; 52 (No. RR-11). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm

Errata (January 7, 2005)

www.cdc.gov/mmwr/preview/mmwrhtml/mm5351a5.htm

CDC. Trends in tuberculosis morbidity—United States, 1992– 2002. MMWR 2003; 52 (11):

217–22. www.cdc.gov/mmwr/preview/mmwrhtml/mm5211a2.htm 

CDC. Trends in tuberculosis—United States, 2007. MMWR 2008; 57 (11): 281– 285. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5711a2.htm

CDC. Tuberculosis elimination revisited: Obstacles, opportunities, and a renewed commitment. 

MMWR 1999; 48 (No. RR-9). www.cdc.gov/mmwr/preview/mmwrhtml/rr4809a1.htm

CDC. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of 

tuberculosis. MMWR 2009; 58 (01): 7– 10. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5801a3.htm?s_cid=mm5801a3_e

CDC. Updated guidelines for using interferon gamma release assays to detect Mycobacterium 

tuberculosis infection—United States, 2010 MMWR 2010; 59 (RR-5); 1– 25. 

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm?s_cid=rr5905a1_e

Institute of Medicine, Committee on Elimination of Tuberculosis in the United States. Geiter L J, 

editor. Ending Neglect: The Elimination of Tuberculosis in the United States. Washington, D.C., 

National Academy Press; 2000. www.nap.edu/catalog/9837.html

World Health Organization. A WHO/The Union Monograph on TB and Tobacco Control. Geneva, 

Switzerland; 2007.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

19

Table of Contents

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Transmission of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Pathogenesis of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Drug-Resistant TB (MDR and XDR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

TB Classification System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Chapter Objectives

After working through this chapter, you should be able to 

• Identify ways in which tuberculosis (TB) is spread;

• Describe the pathogenesis of TB;

• Identify conditions that increase the risk of TB infection progressing to TB disease;

• Define drug resistance; and

• Describe the TB classification system.

Chapter 2 

Transmission and Pathogenesis 

of Tuberculosis

Chapter 2: Transmission and Pathogenesis of Tuberculosis

21

Introduction

TB is an airborne disease caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis) 

(Figure 2.1). M. tuberculosis and seven very closely related mycobacterial species (M. bovis, 

M. africanum, M. microti, M. caprae, M. pinnipedii, M. canetti and M. mungi) together comprise 

what is known as the M. tuberculosis complex. Most, but not all, of these species have been found to 

cause disease in humans. In the United States, the majority of TB cases are caused by M. tuberculosis. 

M. tuberculosis organisms are also called tubercle bacilli. 

Figure 2.1

Mycobacterium tuberculosis

Transmission of TB

M. tuberculosis is carried in airborne particles, called droplet nuclei, of 1– 5 microns in diameter. 

Infectious droplet nuclei are generated when persons who have pulmonary or laryngeal TB disease 

cough, sneeze, shout, or sing. Depending on the environment, these tiny particles can remain 

suspended in the air for several hours. M. tuberculosis is transmitted through the air, not by surface 

contact. Transmission occurs when a person inhales droplet nuclei containing M. tuberculosis, and 

the droplet nuclei traverse the mouth or nasal passages, upper respiratory tract, and bronchi to reach 

the alveoli of the lungs (Figure 2.2). 

M. tuberculosis is carried in airborne particles, called droplet nuclei, of 1– 5

microns in diameter. Infectious droplet nuclei are generated when persons 

who have pulmonary or laryngeal TB disease cough, sneeze, shout, or sing.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

22

Figure 2.2 

Transmission of TB

TB is spread from person to person through the air. The dots in the air 

represent droplet nuclei containing tubercle bacilli.

Factors that Determine the Probability of M. tuberculosis Transmission 

There are four factors that determine the probability of transmission of M. tuberculosis (Table 2.1). 

Table 2.1

Factors that Determine the

Probability of Transmission of M. tuberculosis 

Factor Description

Susceptibility Susceptibility (immune status) of the exposed individual

Infectiousness Infectiousness of the person with TB disease is directly related to the 

number of tubercle bacilli that he or she expels into the air. Persons who 

expel many tubercle bacilli are more infectious than patients who expel few 

or no bacilli (Table 2.2) (see Chapter 7, TB Infection Control)

Environment Environmental factors that affect the concentration of M. tuberculosis

organisms (Table 2.3)

Exposure Proximity, frequency, and duration of exposure (Table 2.4)
Chapter 2: Transmission and Pathogenesis of Tuberculosis

23

Table 2.2

Characteristics of a Patient with TB Disease that

Are Associated with Infectiousness

Factor Description

Clinical • Presence of cough, especially lasting 3 weeks or longer

• Respiratory tract disease, especially with involvement of the 

larynx (highly infectious)

• Failure to cover the mouth and nose when coughing

• Inappropriate or inadequate treatment (drugs, duration)

Procedure • Undergoing cough-inducing or aerosol-generating 

procedures (e.g., bronchoscopy, sputum induction, 

administration of aerosolized medications)

Radiographic and laboratory • Cavitation on chest radiograph

• Positive culture for M. tuberculosis

• Positive AFB sputum smear result

The infectiousness of a person with TB disease is directly related to the number 

of tubercle bacilli that he or she expels into the air. Persons who expel many 

tubercle bacilli are more infectious than patients who expel few or no bacilli.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

24

Table 2.3

Environmental Factors that Enhance the Probability that

M. tuberculosis Will Be Transmitted

Factor Description

Concentration of infectious 

droplet nuclei

The more droplet nuclei in the air, the more probable that 

M. tuberculosis will be transmitted

Space Exposure in small, enclosed spaces

Ventilation Inadequate local or general ventilation that results in insufficient 

dilution or removal of infectious droplet nuclei

Air circulation Recirculation of air containing infectious droplet nuclei

Specimen handling Improper specimen handling procedures that generate 

infectious droplet nuclei

Air Pressure Positive air pressure in infectious patient’s room that causes 

M. tuberculosis organisms to flow to other areas

Table 2.4

Proximity and Length of Exposure Factors that Can Affect

Transmission of M. tuberculosis

Factor Description

Duration of exposure to a person with 

infectious TB

The longer the duration of exposure, the higher 

the risk for transmission

Frequency of exposure to infectious person The more frequent the exposure, the higher the 

risk for transmission

Physical proximity to infectious person The closer the proximity, the higher the risk for 

transmission

Young children with pulmonary and laryngeal TB disease are less likely than adults to be infectious. 

This is because children generally do not produce sputum when they cough. However, transmission 

from children can occur. Therefore, children and adolescents with TB disease should be evaluated 

for infectiousness using the same criteria as adults. These criteria include presence of cough lasting 

3 weeks or longer; cavitation on chest radiograph; or respiratory tract disease with involvement of 

lungs, airways, or larynx (see Chapter 3, Testing for Tuberculosis Infection and Disease).

Young children with pulmonary and laryngeal TB disease 

are less likely than adults to be infectious.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

25

Study Questions

2.1 How is TB spread? (circle the one best answer)

A. From sharing eating utensils with an infected person.

B. From person to person through the air.

C. From insect bites. 

D. From touching surfaces that are contaminated with M. tuberculosis.

2.2 The probability that M. tuberculosis will be transmitted depends on...

(circle the one best answer)

A. Susceptibility (immune status) of the exposed individual.

B. Infectiousness of the person with TB.

C. Proximity, frequency, and duration of exposure.

D. Environmental factors that affect the concentration of M. tuberculosis organisms.

E. A, B, C, and D are correct.

Are the following statements about infectiousness true or false? (Choose the one best answer and 

write the letter for the correct answer on the line next to the question number.)

Statement about Infectiousness True or False

____ 2.3 The infectiousness of a person with TB disease is 

directly related to the number of tubercle bacilli 

that he or she expels into the air.

____ 2.4 Persons who expel few or no tubercle bacilli are 

just as infectious as those who expel many bacilli.

A. True

B. False

2.5 Which of the following environmental factors do NOT increase the probability that 

M. tuberculosis will be transmitted? (circle the one best answer)

A. Exposure in small enclosed spaces.

B. Inadequate local or general ventilation that results in insufficient dilution or removal of 

infectious droplet nuclei.

C. Recirculation of air containing infectious droplet nuclei.

D. Improper specimen handling procedures that generate infectious droplet nuclei.

E. Negative pressure in an infectious TB patient’s room.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

26

Pathogenesis of TB

Infection occurs when a person inhales droplet nuclei containing tubercle bacilli that reach the 

alveoli of the lungs. These tubercle bacilli are ingested by alveolar macrophages; the majority of these 

bacilli are destroyed or inhibited. A small number may multiply intracellularly and are released when 

the macrophages die. If alive, these bacilli may spread by way of lymphatic channels or through the 

bloodstream to more distant tissues and organs (including areas of the body in which TB disease 

is most likely to develop: regional lymph nodes, apex of the lung, kidneys, brain, and bone). This 

process of dissemination primes the immune system for a systemic response. Further details about 

pathogenesis of latent tuberculosis infection (LTBI) and TB disease are described in Figure 2.3.

Figure 2.3

Pathogenesis of LTBI and TB Disease

1.

Area of 

detail for 

boxes 2, 4, 

and 5 

Droplet nuclei containing 

tubercle bacilli are 

inhaled, enter the lungs, 

and travel to the alveoli.

2.

Bronchiole

Tubercle bacilli

Alveoli

Tubercle bacilli multiply in 

the alveoli.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

27

3.

Brain

Bone Larynx

Lymph node

Lung

Spine

Kidney

A small number of 

tubercle bacilli enter the 

bloodstream and spread 

throughout the body. 

The tubercle bacilli may 

reach any part of the 

body, including areas 

where TB disease is more 

likely to develop (such as 

the brain, larynx, lymph 

node, lung, spine, bone, 

or kidney).

4.

Special 

immune cells 

form a barrier 

shell (in this 

example, 

bacilli are in 

the lungs)

Within 2 to 8 weeks, 

special immune cells 

called macrophages 

ingest and surround the 

tubercle bacilli. The cells 

form a barrier shell, called 

a granuloma, that keeps 

the bacilli contained and 

under control (LTBI).

5.

Shell breaks 

down and 

tubercle 

bacilli escape 

and multiply

If the immune system 

cannot keep the tubercle 

bacilli under control, the 

bacilli begin to multiply 

rapidly (TB disease). 

This process can occur 

in different areas in the 

body, such as the lungs, 

kidneys, brain, or bone 

(see diagram in box 3).

Infection occurs when a person inhales droplet nuclei containing 

tubercle bacilli that reach the alveoli of the lungs.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

28

Latent Tuberculosis Infection (LTBI)

Persons with LTBI have M. tuberculosis in their bodies, but do not have TB disease and cannot

spread the infection to other people. A person with LTBI is not regarded as having a case of TB. The 

process of LTBI begins when extracellular bacilli are ingested by macrophages and presented to other 

white blood cells. This triggers the immune response in which white blood cells kill or encapsulate 

most of the bacilli, leading to the formation of a granuloma. At this point, LTBI has been 

established. LTBI may be detected by using the tuberculin skin test (TST) or an interferon-gamma 

release assay (IGRA) (see Chapter 3, Testing for Tuberculosis Disease and Infection). It can take 2 to 

8 weeks after the initial TB infection for the body’s immune system to be able to react to tuberculin 

and for the infection to be detected by the TST or IGRA. Within weeks after infection, the immune 

system is usually able to halt the multiplication of the tubercle bacilli, preventing further progression. 

Persons with LTBI have M. tuberculosis in their bodies, but do not 

have TB disease and cannot spread the infection to other people.

TB Disease

In some people, the tubercle bacilli overcome the immune system and multiply, resulting in 

progression from LTBI to TB disease (Figure 2.4). Persons who have TB disease are usually infectious 

and may spread the bacteria to other people. The progression from LTBI to TB disease may occur at 

any time, from soon to many years later. Body fluid or tissue from the disease site should be collected 

for AFB smear and culture (see Chapter 5, Treatment for Latent Tuberculosis Infection). Positive 

culture for M. tuberculosis confirms the diagnosis of TB disease. Table 2.5 indicates the differences 

between LTBI and TB disease. 

Persons who have TB disease may spread the bacteria to other people.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

29

Figure 2.4

Progression of TB

People who are exposed to M. tuberculosis may or may not develop LTBI.

People with LTBI may or may not develop TB disease.

People Exposed to M. tuberculosis

Infected 

with 

M. tuberculosis?

Negative 

TST or IGRA result

Positive

TST or IGRA result

Does not develop 

LTBI or 

TB disease

Not Infectious

No Yes

Abnormal 

chest radiograph

Symptoms

May have

positive culture

Normal 

chest radiograph

May develop 

symptoms

later in life

No Symptoms

Has LBTI

Not Infectious

Has TB Disease

May be infectious
Chapter 2: Transmission and Pathogenesis of Tuberculosis

30

Table 2.5

LTBI vs. TB Disease

Person with 

LTBI (Infected)

Person with

TB Disease (Infectious)

Has a small amount of TB bacteria in his/her 

body that are alive, but inactive

Has a large amount of active TB bacteria in 

his/her body

Cannot spread TB bacteria to others May spread TB bacteria to others

Does not feel sick, but may become sick if the 

bacteria become active in his/her body

May feel sick and may have symptoms 

such as a cough, fever, and/or weight loss

Usually has a TB skin test or TB blood test 

reaction indicating TB infection

Usually has a TB skin test or TB blood test 

reaction indicating TB infection

Radiograph is typically normal Radiograph may be abnormal

Sputum smears and cultures are negative Sputum smears and cultures may be positive

Should consider treatment for LTBI to prevent 

TB disease

Needs treatment for TB disease

Does not require respiratory isolation May require respiratory isolation

Not a TB case A TB case

Risk of Developing TB Disease over a Lifetime 

Without treatment, approximately 5% of persons who have been infected with M. tuberculosis will 

develop disease in the first year or 2 after infection, and another 5% will develop disease sometime 

later in life. Thus, without treatment, approximately 10% of persons with normal immune systems 

who are infected with M. tuberculosis will develop TB disease at some point in their lives.

Sites of TB Disease

TB disease can occur in pulmonary and extrapulmonary sites.

Pulmonary

TB disease most commonly affects the lungs; this is referred to as pulmonary TB. In 2011, 67% of 

TB cases in the United States were exclusively pulmonary. Patients with pulmonary TB usually have 

a cough and an abnormal chest radiograph, and may be infectious. Although the majority of TB 

cases are pulmonary, TB can occur in almost any anatomical site or as disseminated disease. 

Extrapulmonary

Extrapulmonary TB disease occurs in places other than the lungs, including the larynx, the lymph 

nodes, the pleura, the brain, the kidneys, or the bones and joints. In HIV-infected persons, 

extrapulmonary TB disease is often accompanied by pulmonary TB. Persons with extrapulmonary 

TB disease usually are not infectious unless they have 1) pulmonary disease in addition to 
Chapter 2: Transmission and Pathogenesis of Tuberculosis

31

extrapulmonary disease; 2) extrapulmonary disease located in the oral cavity or the larynx; or 

3) extrapulmonary disease that includes an open abscess or lesion in which the concentration of 

organisms is high, especially if drainage from the abscess or lesion is extensive, or if drainage fluid is 

aerosolized. Persons with TB pleural effusions may have underlying pulmonary TB that is masked on 

chest radiograph because the effusion fluid compresses the lung. These patients should be considered 

infectious until pulmonary TB disease is excluded. 

Miliary TB

Miliary TB occurs when tubercle bacilli enter the bloodstream and disseminate to all parts of 

the body, where they grow and cause disease in multiple sites. This condition is rare but serious. 

“Miliary” refers to the radiograph appearance of millet seeds scattered throughout the lung. It is most 

common in infants and children younger than 5 years of age, and in severely immunocompromised 

persons. Miliary TB may be detected in an individual organ, including the brain; in several organs; 

or throughout the whole body. The condition is characterized by a large amount of TB bacilli, 

although it may easily be missed, and is fatal if untreated. Up to 25% of patients with miliary TB 

may have meningeal involvement. 

Central Nervous System 

When TB occurs in the tissue surrounding the brain or spinal cord, it is called tuberculous 

meningitis. Tuberculous meningitis is often seen at the base of the brain on imaging studies. 

Symptoms include headache, decreased level of consciousness, and neck stiffness. The duration 

of illness before diagnosis is variable and relates in part to the presence or absence of other sites of 

involvement. In many cases, patients with meningitis have abnormalities on a chest radiograph 

consistent with old or current TB, and often have miliary TB.

Risk of LTBI Progressing to TB Disease

Anyone who has LTBI can develop TB disease, but some people are at higher risk than others (Table 

2.6). HIV infection is the greatest risk factor for the development of TB disease in persons with 

LTBI, due to a weakened immune system. The risk of developing TB disease is 7% to 10% each year

for persons who are infected with both M. tuberculosis and HIV and who are not receiving highly 

active treatment for HIV; it is 10% over a lifetime for persons infected only with M. tuberculosis

(Figure 2.5). Children younger than 5 years of age are also at increased risk for progression of LTBI 

to TB disease.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

32

Table 2.6

Persons at Increased Risk for Progression of LTBI to TB Disease

Persons at Increased Risk

• Persons infected with HIV;

• Children younger than 5 years of age;

• Persons who were recently infected with M. tuberculosis (within the past 2 years);

• Persons with a history of untreated or inadequately treated TB disease, including persons with 

fibrotic changes on chest radiograph consistent with prior TB disease;

• Persons who are receiving immunosuppressive therapy such as tumor necrosis factor-alpha 

(TNF) antagonists, systemic corticosteroids equivalent to/greater than 15 mg of prednisone per 

day, or immunosuppressive drug therapy following organ transplantation;

• Persons with silicosis, diabetes mellitus, chronic renal failure, leukemia, or cancer of the head, 

neck, or lung;

• Persons who have had a gastrectomy or jejunoileal bypass;

• Persons who weigh less than 90% of their ideal body weight;

• Cigarette smokers and persons who abuse drugs and/or alcohol; and

• Populations defined locally as having an increased incidence of disease due to 

M. tuberculosis, including medically underserved, low-income populations.

Figure 2.5

Risk of Developing TB Disease 

Risk Factor Risk of Developing TB Description

TB infection and 

no risk factors

About 10% over a lifetime

For people with TB infection, no risk 

factors, and no treatment, the risk is about 

5% in the first 2 years after infection and 

about 10% over a lifetime.

TB infection and 

diabetes

About 30% over a lifetime

For people with TB infection and diabetes, 

and with no treatment, the risk is three 

times as high, or about 30% over a lifetime.

TB infection and 

HIV infection

About 7% to 10% PER YEAR

For people with TB infection and 

untreated HIV infection and with no LTBI 

treatment, the risk is about 7% to 10% PER 

YEAR, a very high risk over a lifetime.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

33

Anyone who has LTBI can develop TB disease, but some people are at higher 

risk than others. HIV infection is the highest risk factor for development of 

TB disease in persons with LTBI owing to weakening of the immune system.

Study Questions

2.6 Which statement about the difference between LTBI and TB disease is true?

(circle the one best answer)

A. Tubercle bacilli are in the body only with TB disease.

B. Persons with LTBI cannot spread TB bacteria to others.

C. Sputum smears and cultures are positive with LTBI but NOT with TB disease.

Which of the following patient characteristics indicate LTBI, TB disease, or both?

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Patient Characteristics

Type of TB

(Answers May Be Used 

More Than Once)

____ 2.7 Has a positive TB skin test or TB 

blood test reaction.

____ 2.8 May spread TB bacteria to others.

____ 2.9 Has TB bacteria in his/her body.

____ 2.10 May require respiratory isolation.

____ 2.11 Is NOT a case of TB.

A. LTBI

B. TB disease

C. Both LTBI and 

TB disease
Chapter 2: Transmission and Pathogenesis of Tuberculosis

34

2.12 TB disease most commonly affects which part of the body?

(choose the one best answer)

A. Bone

B. Lungs

C. Kidneys

D. Brain

E. None of the above

The following persons have LTBI. Which persons have factors that put them either at an 

increased risk or NOT at an increased risk of progressing to TB disease? 

(Choose the one best answer, and write the letter for the correct answer on the line next to the 

question number.) 

Persons with LTBI Risk of Progressing 

to TB Disease

____ 2.13 Susan has osteopenia.

____ 2.14 Andy has diabetes.

____ 2.15 Cindy is 3 years old.

A. Increased risk

B. Not an increased risk

Case Study–Daniel

Daniel, a 30-year-old male, visits the Jackson County Health Department for a 

tuberculosis test because he is required to have one before he starts his new job at the 

Brice Nursing Home. He has a positive reaction to the test. He has no symptoms of TB 

and his chest x-ray findings are normal.

2.16 Should Daniel be considered a case of TB?

(circle the one best answer)

A. Yes, because he had a positive reaction to the tuberculosis test.

B. No, because he has TB infection, but no evidence of TB disease.

2.17 Should Daniel be considered infectious?

 (circle the one best answer)

A. Yes, the test indicates that he has TB infection. Therefore he is infectious.

B. No, because he has TB infection, but not TB disease. Therefore he is not infectious.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

35

Case Study–Lorena

Lorena, a 45-year-old female, is referred to the Galion County Health Department by 

her private physician because she was diagnosed with LTBI. She is obese, has high blood 

pressure, and has heart problems. She reports that she has injected illegal drugs in the 

past and also tested positive for HIV infection. 

What conditions does Lorena have that increase the risk that she will develop TB disease?

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Conditions of Persons with LTBI Risk of Progressing to

TB Disease

____ 2.18 Obesity

____ 2.19 High blood pressure

____ 2.20 Heart problems

____ 2.21 Injection of illegal drugs

____ 2.22 HIV

A. Increased risk

B. Not an increased risk

Drug-Resistant TB (MDR and XDR)

Drug-resistant TB is caused by M. tuberculosis organisms that are resistant to the drugs normally used 

to treat the disease (Figure 2.6). Drug-resistant TB is transmitted in the same way as drug-susceptible 

TB, and is no more infectious than drug-susceptible TB. However, delay in the recognition of drug 

resistance or prolonged periods of infectiousness may facilitate increased transmission and further 

development of drug resistance.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

36

Figure 2.6

Drug-Resistant Tuberculosis

TB

with any 

drug

resistance

MDR TB* 

with drug 

resistance to at least 

the first-line drugs 

isoniazid and 

rifampin

XDR TB**

with drug resistance

to the first-line drugs 

isoniazid and rifampin 

and to specific 

second-line drugs

All 

TB 

 * Often resistant to additional drugs

** Resistant to any fluoroquinolone and at least one of three injectable second-line drugs 

(i.e., amikacin, kanamycin, or capreomycin)

Drug-resistant TB is caused by M. tuberculosis organisms that 

are resistant to the drugs normally used to treat the disease. 

Drug-resistant TB is transmitted in the same way as drug-susceptible 

TB, and is no more infectious than drug-susceptible TB.

Multidrug-Resistant TB

Multidrug-resistant TB (MDR TB) is caused by organisms resistant to the most effective anti-TB 

drugs, isoniazid and rifampin. These drugs are considered first-line drugs and are used to treat most 

persons with TB disease (see Chapter 6, Treatment of Tuberculosis Disease).

Multidrug-resistant TB (MDR TB) is caused by organisms resistant 

to the most effective anti-TB drugs, isoniazid and rifampin.

Extensively Drug-Resistant TB 

Extensively drug-resistant TB (XDR TB) is a relatively rare type of drug-resistant TB. XDR TB is 

resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable 

second-line drugs (i.e., amikacin, kanamycin, or capreomycin). Because XDR TB is resistant to 

first-line and second-line drugs, patients are left with treatment options that are more toxic, more 

expensive, and much less effective. 
Chapter 2: Transmission and Pathogenesis of Tuberculosis

37

Types of Drug-Resistant TB Disease

Drug-resistant TB disease can develop in two different ways, called primary and secondary

resistance (Table 2.7). Primary resistance occurs in persons who are initially infected with resistant 

organisms. Secondary resistance, or acquired resistance, develops during TB therapy, either 

because the patient was treated with an inadequate regimen, did not take the prescribed regimen 

appropriately, or because of other conditions such as drug malabsorption or drug-drug interactions 

that led to low serum levels.

Circumstances in which an exposed person is at an increased risk of infection with drug-resistant TB 

include the following:

• Exposure to a person who has known drug-resistant TB disease;

• Exposure to a person with TB disease who has had prior treatment for TB (treatment failure or 

relapse) and whose susceptibility test results are not known;

• Exposure to a person with TB disease from an area in which there is a high prevalence of drug 

resistance, or travel to one of these areas (see the World Health Organization’s “Tuberculosis: 

MDR-TB & XDR-TB: The 2008 Report” for a list countries with highest prevalence of drug 

resistance at www.who.int/tb/features_archive/drs_factsheet.pdf); or

• Exposure to a person who continue to have positive smear and cultures after 2 months of 

combination chemotherapy.

Table 2.7

Primary and Secondary MDR TB

Primary MDR TB

(Infected with Drug-Resistant Organisms)

Secondary MDR TB

(Acquired or Developed Drug Resistance)

Caused by person-to-person transmission of 

drug-resistant organisms

Develops during TB treatment

• Exposure to a person who 

» Has known drug-resistant TB

» Had prior treatment for TB (treatment 

failure or relapse and whose 

susceptibility test results are not known)

» Is from an area in which there is a high 

prevalence of drug resistance

» Continues to have positive smears and 

cultures after 2 months of combination 

chemotherapy

• Travel in areas with a high prevalence of 

drug-resistant TB disease

Develops because the patient

• Was not treated with the appropriate 

treatment regimen

Or

• Did not follow the treatment regimen as 

prescribed 

» Took the drugs incorrectly

» Took the drugs irregularly

• Malabsorption 

• Drug-drug interactions causing low serum 

levels
Chapter 2: Transmission and Pathogenesis of Tuberculosis

38

Study Questions

2.23 Which of the following statements is true about drug-resistant TB disease?

(choose the one best answer)

A. Drug-resistant TB disease is transmitted in the same way as drug-susceptible TB disease.

B. Drug-resistant TB disease is NO more infectious than drug-susceptible TB disease.

C. Drug-resistant TB disease is easily treated with standard drug regimens.

D. A, B, and C are all correct.

E. Only A and B are correct.

2.24 Which of the following types of TB disease is caused by the organism M. tuberculosis?

(choose the one best answer.) 

A. Drug-susceptible TB

B. MDR TB

C. XDR TB

D. A, B, and C are all correct.

E. Only A and B are correct.

What are the characteristics for each type of TB disease? 

(Choose the one best answer, and write the letter for the correct answer on the line next to the 

question number.) 

Characteristic Type of TB

____ 2.25 Resistant to isoniazid and rifampin, plus 

any fluoroquinolone, and at least one of 

three injectable second-line drugs.

____ 2.26 Resistant to at least the two first-line drugs, 

isoniazid and rifampin.

A. MDR TB 

B. XDR TB
Chapter 2: Transmission and Pathogenesis of Tuberculosis

39

What type of drug-resistant TB does each patient have? 

(Choose the one best answer, and write the letter for the correct answer on the line next to the 

question number.) 

Patient Type of Drug-Resistant TB

____ 2.27 Sally is diagnosed with and treated for 

TB by her family physician. She is not 

placed on directly observed therapy DOT; 

thus she often forgets to take her antiTB medicine and takes only part of her 

prescribed regimen. Because of inadequate 

treatment, she now has MDR TB.

____ 2.28 Li, a 13-year-old boy, immigrates from 

China with his family. He gets MDR TB 

from his older brother.

A. Primary resistance 

B. Secondary 

“acquired” resistance

TB Classification System

The current clinical classification system for TB used in the United States is based on the 

pathogenesis of the disease (Table 2.8). It is intended mainly as an operational framework for 

public health programs. This classification system provides clinicians the opportunity to track the 

development of TB in their patients. Health-care providers should comply with state and local laws 

and regulations requiring the reporting of TB disease. All persons with Class 3 (clinically active) or 

Class 5 (TB suspected) TB should be reported promptly to the local or state health department. A 

patient should not have a Class 5 classification for more than 3 months.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

40

Table 2.8

TB Classification System

Class Type Description

0 No TB exposure

Not infected

• No history of TB exposure and no evidence of 

M. tuberculosis infection or disease

• Negative reaction to TST or IGRA

1 TB exposure

No evidence of infection

• History of exposure to M. tuberculosis

• Negative reaction to TST or IGRA 

(given at least 8 to 10 weeks after exposure)

2 TB infection

No TB disease

• Positive reaction to TST or IGRA 

• Negative bacteriological studies 

(smear and cultures) 

• No bacteriological or radiographic evidence of 

active TB disease

3 TB clinically active • Positive culture for M. tuberculosis OR

• Positive reaction to TST or IGRA, plus clinical, bacteriological, 

or radiographic evidence of current active TB

4 Previous TB disease

(not clinically active)

• May have past medical history of TB disease

• Abnormal but stable radiographic findings

• Positive reaction to the TST or IGRA 

• Negative bacteriologic studies 

(smear and cultures) 

• No clinical or radiographic evidence of current 

active TB disease

5 TB suspected • Signs and symptoms of active TB disease, but medical 

evaluation not complete
Chapter 2: Transmission and Pathogenesis of Tuberculosis

41

Study Questions

What is the TB classification for each of the following patients?

(Choose the one best answer, and write the letter for the correct answer on the line next to the 

question number.) 

Patient TB Classification

____ 2.29 Sonya has a positive reaction to a TST. There is 

no bacteriological or radiographic evidence of 

TB disease.

____ 2.30 Luke has signs and symptoms of TB disease, 

but his medical evaluation is not complete.

____ 2.31 Sergei has a past medical history of TB disease. 

His radiographic findings are abnormal, but 

stable. He has a positive reaction to an IGRA. 

Both smear and culture results are negative and 

there is no clinical or radiographic evidence of 

current TB disease.

____ 2.32 Joseph has a history of exposure to 

M. tuberculosis and a negative TST result. 

____ 2.33 Louisa has no history of TB exposure and no 

evidence of M. tuberculosis infection or disease. 

She had a negative IGRA result.

____ 2.34 Rosella has a positive culture for 

M. tuberculosis.

A. 0 No exposure

Not infected

B. 1 TB exposure

No evidence of infection

C. 2 TB infection

No TB disease

D. 3 TB, clinically active

E. 4 Previous TB disease

(not clinically active)

F. 5 TB disease suspected

Chapter Summary

TB is an airborne disease caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis). 

M. tuberculosis and seven very closely related mycobacterial species (M. bovis, M. africanum, 

M. microti, M. caprae, M. pinnipedii, M. canetti and M. mungi) together comprise what is known as 

the M. tuberculosis complex. Most, but not all, of these species have been found to cause disease in 

humans. In the United States, the majority of TB cases are caused by M. tuberculosis. M. tuberculosis

organisms are also called tubercle bacilli.

M. tuberculosis is carried in airborne particles, called droplet nuclei, of 1– 5 microns in diameter. 

Infectious droplet nuclei are generated when persons who have pulmonary or laryngeal TB disease 

cough, sneeze, shout, or sing. Depending on the environment, these tiny particles can remain 

suspended in the air for several hours. M. tuberculosis is transmitted through the air, not by surface 

contact. Transmission occurs when a person inhales droplet nuclei containing M. tuberculosis, and 
Chapter 2: Transmission and Pathogenesis of Tuberculosis

42

the droplet nuclei traverse the mouth or nasal passages, upper respiratory tract, and bronchi to reach 

the alveoli of the lungs.

TB disease most commonly affects the lungs; this is referred to as pulmonary TB disease. In 2009, 

71% of TB cases in the United States were exclusively pulmonary. Patients with pulmonary TB disease 

usually have a cough and an abnormal chest radiograph, and may be infectious. Although the majority 

of TB cases are pulmonary, TB can occur in almost any anatomical site or as disseminated disease. 

Persons with LTBI have M. tuberculosis in their bodies, but do not have TB disease and cannot spread 

the infection to other people. A person with LTBI is not regarded as a case of TB disease. The process 

of LTBI begins when extracellular bacilli are ingested by macrophages and presented to other white 

blood cells. This triggers the immune response in which white blood cells kill or encapsulate most of 

the bacilli, leading to the formation of a granuloma. At this point, LTBI has been established. LTBI 

may be detected by using the TST or IGRA. It can take 2 to 8 weeks after the initial TB infection 

for the body’s immune system to be able to react to tuberculin and for the infection to be detected 

by the TST or IGRA. Within weeks after infection, the immune system is usually able to halt the 

multiplication of the tubercle bacilli, preventing further progression. 

In some people, the tubercle bacilli overcome the immune system and multiply, resulting in 

progression from LTBI to TB disease. Persons who have TB disease are usually infectious and may 

spread the bacteria to other people. The progression from LTBI to TB disease may occur soon or 

many years after infection. Body fluid or tissue from the disease site should be collected for AFB 

smear and culture. Positive culture for M. tuberculosis confirms the diagnosis of TB disease. 

Drug-resistant TB disease can develop in two different ways, called primary and secondary resistance. 

Primary resistance occurs in persons who are initially exposed to and infected with resistant organisms. 

Secondary resistance, or acquired resistance, develops during TB therapy, either because the patient 

was treated with an inadequate regimen or did not take the prescribed regimen appropriately, or 

because of other conditions such as drug malabsorption or drug-drug interactions that led to low 

serum levels.

MDR TB is caused by organisms resistant to both isoniazid and rifampin, which are the two most 

effective anti-TB drugs. These drugs are considered first-line drugs and are used to treat most persons 

with TB disease.

XDR TB is a relatively rare type of drug-resistant TB. XDR TB is resistant to both isoniazid 

and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs 

(i.e., amikacin, kanamycin, or capreomycin). Because XDR TB disease is resistant to first-line and 

second-line drugs, patients are left with treatment options that are more toxic, more expensive, 

and much less effective.

The current clinical classification system for TB used in the United States is based on the pathogenesis 

of the disease. It is intended mainly as an operational framework for public health programs. This 

classification system provides clinicians the opportunity to track the development of TB in their 

patients. Health-care providers should comply with state and local laws and regulations requiring 

the reporting of TB disease. All persons with Class 3 (clinically active) or Class 5 (TB suspected) TB 

should be reported promptly to the local or state health department. A patient should not have a 

Class 5 classification for more than 3 months.
Chapter 2: Transmission and Pathogenesis of Tuberculosis

43

References

American Thoracic Society and CDC. Diagnostic standards and classification of tuberculosis in 

adults and children. Am J Respir Crit Care Med 2000; 161 (4): 1376– 1395. 

http://ajrccm.atsjournals.org/cgi/reprint/161/4/1376

American Thoracic Society and Infectious Diseases Society of America. Diagnosis, treatment, 

and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175: 

367–416. www.thoracic.org/statements/resources/mtpi/nontuberculous-mycobacterial-diseases.pdf

CDC. A strategic plan for the elimination of tuberculosis from the United States. MMWR 1989; 38 

(Suppl No. S-3). www.cdc.gov/mmwr/preview/mmwrhtml/00001375.htm

CDC. Controlling tuberculosis in the United States: Recommendations from the American Thoracic 

Society, CDC, and the Infectious Diseases Society of America. MMWR 2005; 54 (No. RR-12).

www.cdc.gov/mmwr/PDF/rr/rr5412.pdf

CDC. Essential components of a tuberculosis prevention and control program: Recommendations of 

the Advisory Council for the Elimination of Tuberculosis. MMWR 1995; 44 (No. RR-11).

www.cdc.gov/mmwr/preview/mmwrhtml/00038823.htm

CDC. Extensively drug-resistant tuberculosis—United States, 1993– 2006. MMWR 2007; 56 (11): 

250–3. www.cdc.gov/mmwr/preview/mmwrhtml/mm5611a3.htm

CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care 

settings, 2005. MMWR 2005; 54 (No. RR-17). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e

CDC. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults 

and adolescents. MMWR 2009; 58 (No. RR-4). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr58e324a1.htm?s_cid=rr58e324a1_e

CDC. Management of persons exposed to multidrug-resistant tuberculosis. MMWR 1992; 41 

(No. RR-11): 59– 71. www.cdc.gov/mmwr/preview/mmwrhtml/00031296.htm 

CDC. National action plan to combat multidrug-resistant tuberculosis. MMWR 1992; 41 

(No. RR-11): 1– 48. www.cdc.gov/mmwr/preview/mmwrhtml/00031159.htm 

CDC. Recommendations for prevention and control of tuberculosis among foreign-born persons: 

Report of the Working Group on Tuberculosis among Foreign-born Persons. MMWR 1998; 47 

(No. RR-16). www.cdc.gov/mmwr/preview/mmwrhtml/00054855.htm

CDC. Reported Tuberculosis in the United States, 2011. Atlanta, Ga: U.S. Department of Health 

and Human Services, CDC; September 2012. www.cdc.gov/tb/statistics/reports/2011/default.htm

CDC. Screening for tuberculosis and tuberculosis infection in high-risk populations: 

Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR 1995; 44 

(No. RR-11): 18– 34. www.cdc.gov/mmwr/preview/mmwrhtml/00038873.htm 
Chapter 2: Transmission and Pathogenesis of Tuberculosis

44

CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR 2000; 49 

(No. RR-6). www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm

Updates:

Adverse event data and revised American Thoracic Society/CDC recommendations against the 

use of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 

2003. MMWR 2003; 52 (31):735– 9.

www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm

Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis 

infection, and revisions in American Thoracic Society/CDC recommendations—United States, 

2001. MMWR 2001; 50 (34):733– 5

www.cdc.gov/mmwr/preview/mmwrhtml/mm5034a1.htm

Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent 

tuberculosis infection—New York and Georgia, 2000. MMWR 2001; 50 (15): 289– 91. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5015a3.htm

CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat 

latent Mycobacterium tuberculosis infection recommendations—United States, 2011. MMWR 2011; 

60 (48): 1650– 1653.

 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6048a3.htm?s_cid=mm6048a3_w

Errata (February 3, 2012)

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a7.htm

CDC. Treatment of tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society 

of America. MMWR 2003; 52 (No. RR-11). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm

Errata (January 7, 2005)

www.cdc.gov/mmwr/preview/mmwrhtml/mm5351a5.htm

CDC. Tuberculosis elimination revisited: Obstacles, opportunities, and a renewed commitment. 

MMWR 1999; 48 (No. RR-9). www.cdc.gov/mmwr/preview/mmwrhtml/rr4809a1.htm

CDC. Updated guidelines for using interferon gamma release assays to detect Mycobacterium 

tuberculosis infection— United States, 2010. MMWR 2010; 59 (No. RR-05). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm?s_cid=rr5905a1_e
Chapter 3: Testing for Tuberculosis Infection and Disease

45

Chapter 3 

Testing for Tuberculosis Infection 

and Disease

Table of Contents

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Identifying High-Risk Groups for M. tuberculosis Testing . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Testing Methods for TB Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

BCG Vaccination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

Chapter Objectives

After working through this chapter, you should be able to 

• Describe why high-risk groups should be tested for M. tuberculosis infection;

• Identify appropriate testing methods for M. tuberculosis infection; 

• Identify special considerations when using tuberculin skin tests (TSTs); and

• Discuss general recommendations for the use of interferon-gamma release assays (IGRAs).

Chapter 3: Testing for Tuberculosis Infection and Disease

47

Introduction

Targeted testing is a TB control strategy that is used to identify, evaluate, and treat persons who are 

at high risk for latent tuberculosis infection (LTBI) or at high risk for developing TB disease once 

infected with M. tuberculosis. Identifying persons with LTBI is important to the goal of TB control 

and elimination because treatment of LTBI can prevent infected persons from developing TB 

disease and stop the further spread of TB. All testing activities should be accompanied by a plan for 

appropriate follow-up medical evaluation and treatment. Necessary medical evaluation and treatment 

resources need to be identified before testing activities begin. 

Targeted testing is a TB control strategy that is used to identify, evaluate, and 

treat persons who are at high risk for latent tuberculosis infection (LTBI) or 

at high risk for developing TB disease once infected with M. tuberculosis.

Study Question

3.1 Why is targeted testing conducted? (circle the one best answer)

G. To identify, evaluate, and treat persons who are at high risk for latent tuberculosis 

infection.

H. To identify, evaluate, and treat persons who are at high risk for developing TB disease 

once infected with M. tuberculosis.

I. To identify the strain of TB bacteria that a patient may have so the correct treatment 

regimen can be provided.

J. A, B, and C are all correct.

K. Only A and B are correct.

Identifying High-Risk Groups for M. tuberculosis Testing

As part of their routine evaluation, health-care providers should identify and test persons who are 

at high risk for acquiring TB infection or at high risk of progressing to TB disease if infected. In 

some select settings, active case finding may be more appropriate than testing for M. tuberculosis

infection. Flexibility is needed in defining high-risk groups for testing. The changing epidemiology 

of TB indicates that the risk for TB disease or LTBI among groups currently considered high risk 

may decrease over time, and groups currently not identified as being at risk may subsequently be 

considered high risk (see Chapter 1, Overview of Tuberculosis Epidemiology in the United States).

Evaluation of Persons with Positive TB Test Results

Health-care or other (e.g., correctional) facilities should consult with their local health department 

before starting a testing program, to ensure resources are available for the evaluation and treatment of 
Chapter 3: Testing for Tuberculosis Infection and Disease

48

persons whose test results for LTBI or TB disease are positive. Persons with a positive test result for 

TB infection should be evaluated for TB disease and, if disease is ruled out, considered for treatment 

of LTBI (see Chapter 5, Treatment of Latent Tuberculosis Infection).

Health-care or other (e.g., correctional) facilities should consult with 

their local health department before starting a testing program to 

ensure there are resources available for the evaluation and treatment 

of persons whose test results for LTBI or TB disease are positive.

Follow-up TSTs or IGRAs and serial chest radiographs are unnecessary for persons who have a 

positive test result for TB infection and who have had TB disease ruled out or for persons who refuse 

or are unable to receive treatment for LTBI. These persons should be educated about the signs and 

symptoms of TB disease (Figure 3.1). 

Figure 3.1

Evaluation of Persons with Positive TB Test Results

Person has a positive test 

for TB infection

TB disease ruled out 

Consider for LTBI treatment

Person accepts and is able to 

receive treatment for LTBI 

If person refuses or is unable 

to receive treatment for LTBI, 

follow-up TST or IGRA and serial 

chest radiographs are unnecessary 

Develop a plan of 

treatment with patient to 

ensure adherence Educate patient about signs and 

symptoms of TB disease
Chapter 3: Testing for Tuberculosis Infection and Disease

49

Study Question

3.2 Which of the following statements about evaluating persons with a positive TB test is 

true? (circle the one best answer)

A. Persons with a positive test for TB infection should be evaluated for TB disease and, if 

disease is ruled out, considered for treatment of LTBI.

B. If a person refuses or is unable to receive treatment for LTBI, follow-up TST or IGRA 

tests and serial chest radiographs are unnecessary. 

C. All persons who have a positive test result for TB infection should receive LTBI treatment.

D. A, B, and C are all correct.

E. Only A and B are correct.

Testing Methods for TB Infection

Selection of the most suitable test(s) for detection of M. tuberculosis infection should be based on 

the reasons and the context for testing, test availability, and overall cost effectiveness of testing. 

Currently, there are two methods available for the detection of M. tuberculosis infection in the United 

States. The tests are:

• Mantoux tuberculin skin test (TST)

• Interferon-gamma release assays (IGRAs)

» QuantiFERON-TB Gold In-Tube test (QFT-GIT)

» T-SPOT.TB test

Currently, there are two methods available for the detection of 

M. tuberculosis infection in the United States. The tests are:

• Mantoux tuberculin skin test (TST)

• Interferon-gamma release assays (IGRAs)

These tests help clinicians differentiate infected from uninfected people. However, a negative reaction 

to any of the tests does not exclude the diagnosis of LTBI or TB disease. The decisions about 

medical or public health management should include epidemiological, historical, and other clinical 

information when using IGRA or TST results. Decisions should not be based on TST or IGRA 

results alone. Additional tests are needed to diagnose TB disease. A comparison of the TST and the 

IGRA is included in Table 3.1.

A negative reaction to a TST or IGRA does not exclude 

the diagnosis of LTBI or TB disease.
Chapter 3: Testing for Tuberculosis Infection and Disease

50

The decisions about medical or public health management should include 

epidemiological, historical, and other clinical information when using IGRA 

or TST results. Decisions should not be based on TST or IGRA results alone.

Table 3.1

TST vs IGRAs

TST IGRA

Tuberculin is injected under the 

skin and produces a delayed-type 

hypersensitivity reaction if the person 

has been infected with M. tuberculosis 

Blood is drawn for testing; test measures 

the immune response to the TB bacteria in 

whole blood 

Requires two or more patient visits to 

conduct the test 

Requires one patient visit to conduct the test

Results are available 48 to 72 hours later Results can be available in 24 hours 

(depending on the batching of specimens 

by the laboratory and transport)

Can cause booster phenomenon Does not cause booster phenomenon

Reading by HCW may be subjective Laboratory test not affected by HCW 

perception or bias

BCG vaccination can cause falsepositive resultBCG vaccination does not cause falsepositive result and infection with most 

nontuberculous mycobacteria does not

cause false-positive result

A negative reaction to the test 

does not exclude the diagnosis of 

LTBI or TB disease

A negative reaction to the test does not

exclude the diagnosis of LTBI or TB disease

Mantoux Tuberculin Skin Test (TST)

The TST is used to determine if a person is infected with M. tuberculosis. In this test, a substance 

called purified protein derivative (PPD), which is derived from tuberculin, is injected under the skin. 

Typically PPD produces a T-cell mediated delayed-type hypersensitivity reaction if the person has 

been infected with M. tuberculosis. In most people who have TB infection, the immune system will 

recognize the PPD because it is extracted from the tubercle bacilli that caused the infection. It takes 

2 to 8 weeks after initial infection with M. tuberculosis for the immune system to be able to react to 

PPD and for the infection to be detected by the TST.

The TST is used to determine if a person is infected with M. tuberculosis. 

In this test, a substance called PPD is injected under the skin.
Chapter 3: Testing for Tuberculosis Infection and Disease

51

It takes 2 to 8 weeks after initial infection with M. tuberculosis

for the body’s immune system to be able to react to PPD 

and for the infection to be detected by the TST.

In some people who are infected with M. tuberculosis, the ability to react to PPD may wane over the 

years. When these people receive a TST many years after infection, they may have an initial negative 

reaction. Subsequent TSTs may produce a positive reaction (see Boosted Reaction in this chapter).

Administering the TST

The TST is performed by intradermal injection of 0.1 ml of PPD containing 5 tuberculin units into 

the volar surface of the forearm. The injection should be made with a disposable 27-gauge tuberculin 

syringe, intradermally (just beneath the surface of the skin), with the needle bevel facing upward. 

This should produce a discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter 

(Figure 3.2). Institutional guidelines regarding universal precautions for infection control (e.g., the 

use of gloves) should be followed (see Chapter 7, TB Infection Control).

The TST is performed by intradermal injection of 0.1 ml of PPD 

containing 5 tuberculin units into the volar surface of the forearm.

Reading the TST 

The reaction to the TST should be assessed 48 to 72 hours after the injection by a health-care worker 

trained to read TST results. Reactions to PPD usually begin 5 to 6 hours after injection, reach a 

maximum at 48 to 72 hours, and subside over a period of a few days. However, positive reactions 

often persist for up to 1 week or longer. Health-care workers should not ask patients to read their 

own skin test.

The reaction to the TST should be assessed 48 to 72 hours after the 

injection by a health-care worker trained to read TST results.

The TST is read by palpating the site of injection to find an area of induration (firm swelling). 

The diameter of the indurated area should be measured across the forearm (Figure 3.3). Erythema 

(redness) should not be measured (Figure 3.4). Induration should be recorded in millimeters, even 

those classified as negative. If no induration is found, “0 mm” should be recorded.

The TST is read by palpating the site of injection to find an area of induration 

(firm swelling). The diameter of the indurated area should be measured across 

the forearm (Figure 3.3). Erythema (redness) should not be measured.
Chapter 3: Testing for Tuberculosis Infection and Disease

52

Figure 3.2

Administering the Mantoux TST

Figure 3.3

Reading the TST Correctly

Only the induration is being measured. 

This is CORRECT. 

The correct example below measures 10 mm.

Figure 3.4

Reading the TST Incorrectly

The erythema is being measured. 

This is INCORRECT.

The incorrect example below measures 30 mm. 
Chapter 3: Testing for Tuberculosis Infection and Disease

53

Interpreting TST Reactions

Interpretation of TST reactions depends on the measurement (in millimeters) of induration and the 

person’s risk of acquiring TB infection or the risk of progression to TB disease if infected (Table 3.2). 

Induration of 5 or more millimeters is interpreted as a positive result in the following groups: 

• HIV-infected persons;

• Recent contacts of persons with infectious TB disease;

• Persons with fibrotic changes on a chest radiograph consistent with prior TB; and

• Patients with organ transplants and other immunosuppressed patients (including patients 

receiving the equivalent of ≥ 15 mg/day of prednisone for ≥ 1 month).

Induration of 10 millimeters or more is interpreted as a positive result in persons who do not meet 

the preceding criteria, but who have other risk factors for TB. These include the following: 

• Recent arrivals to the United States (< 5 years) from high-prevalence areas (e.g., Africa, Asia, 

Eastern Europe, Latin America, and Russia);

• Injection drug users; 

• Residents and employees of high-risk congregate settings (e.g., correctional facilities, long-term 

care facilities, homeless shelters, and hospitals);

• Mycobacteriology laboratory personnel;

• Persons with medical conditions that increase the risk for progression to TB disease, including 

silicosis, diabetes mellitus, chronic renal failure, certain types of cancer (e.g., leukemia and 

lymphomas, or cancer of the head, neck, or lung), gastrectomy or jejunoileal bypass, and 

weight loss of at least 10% below ideal body weight;

• Children younger than 5 years of age; and 

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

An induration of 15 millimeters or greater is interpreted as a positive result in persons with 

no known risk factors for TB who, except for certain testing programs required by local law or 

regulation, would otherwise not be tested. Targeted testing programs should only be conducted 

among higher risk groups.

Interpretation of TST reactions depends on the measurement (in 

millimeters) of the induration and the person’s risk of acquiring TB 

infection or the risk of progression to TB disease if infected.
Chapter 3: Testing for Tuberculosis Infection and Disease

54

Table 3.2

Interpreting the TST Reaction

5 or more millimeters 10 or more millimeters 15 or more millimeters

An induration of 5 or more 

millimeters is considered 

positive for

• HIV-infected persons

• Recent contacts of persons 

with infectious TB

• People who have fibrotic 

changes on a chest 

radiograph

• Patients with organ 

transplants and other 

immunosuppressed 

patients (including patients 

taking a prolonged course 

of oral or intravenous 

corticosteroids or TNF-α

antagonists)

An induration of 10 or more 

millimeters is considered 

positive for

• People who have come to 

the United States within 

the last 5 years from areas 

of the world where TB is 

common (for example, 

Asia, Africa, Eastern Europe, 

Russia, or Latin America)

• Injection drug users 

• Mycobacteriology lab 

workers

• People who live or work 

in high-risk congregate 

settings

• People with certain 

medical conditions that 

place them at high risk 

for TB (silicosis, diabetes 

mellitus, severe kidney 

disease, certain types 

of cancer, and certain 

intestinal conditions)

• Children younger than 

5 years of age

• Infants, children, and 

adolescents exposed 

to adults in high-risk 

categories

An induration of 15 or more 

millimeters is considered 

positive for

• People with no known risk 

factors for TB

TST False-Positive Reactions 

The TST is a valuable tool, but it is not perfect. Several factors can lead to false-positive or falsenegative skin test reactions (Table 3.3). Infection with nontuberculous mycobacteria can sometimes 
Chapter 3: Testing for Tuberculosis Infection and Disease

55

cause a false-positive reaction to the TST. Another cause of a false-positive reaction is BCG (bacille 

Calmette-Guérin), a vaccine for TB disease that is rarely used in the United States. People who have 

been vaccinated with BCG may have a positive reaction to the TST even if they do not have TB 

infection (see BCG Vaccination in this chapter).

A false-positive reaction may also occur if an incorrect antigen is used or when the results are not

measured or interpreted properly.

People who have been vaccinated with BCG may have a positive 

reaction to the TST even if they do not have TB infection.

TST False-Negative Reactions 

Some people have a negative reaction to the TST even though they have been infected with 

M. tuberculosis. A false-negative reaction can be caused by many things (Table 3.3).

Some people have a negative reaction to the TST even 

though they have been infected with M. tuberculosis. 

Anergy

A common cause of false-negative reactions is anergy. Anergy is the inability to react to a TST 

because of a weakened immune system. The absence of a reaction to a TST does not exclude a 

diagnosis of TB disease or infection with M. tuberculosis. Anergy may be caused by many factors, 

including advanced HIV infection, other acute or chronic bacterial, viral or fungal infections, 

sarcoidosis, poor nutrition, certain medications (e.g., TNF-alpha blockers or oral steroids), 

live virus vaccinations, TB disease itself, and other factors. HIV-infected persons may have a 

compromised ability to react to TST because of cutaneous anergy associated with progressive HIV 

immunosuppression; however, the usefulness of anergy testing in tuberculin-negative, HIV-infected 

persons who might benefit from treatment of LTBI has not been demonstrated.

Factors causing false-negative reactions may include, but are not limited to, the following:

• Concurrent viral infection (e.g., measles, mumps, chicken pox, HIV);

• Concurrent bacterial infection (e.g., typhoid fever, brucellosis, typhus, leprosy, pertussis);

• Concurrent fungal infection;

• Chronic renal failure;

• Low protein states (e.g., severe protein depletion, afibrinogenemia);

• Diseases affecting lymphoid organs (e.g., Hodgkin’s disease, lymphoma, chronic leukemia, 

sarcoidosis);

• Immunosuppressive drugs (e.g., medical steroids);

• Children aged 6 months or less or elderly patients (i.e., immature or waning immunity);

• Stress (e.g., surgery, burns, mental illness, graft-versus-host reactions);
Chapter 3: Testing for Tuberculosis Infection and Disease

56

• Incorrect storage or handling of antigen or results that are not measured or interpreted 

properly;

• Vaccinations using live virus; or

• Recent TB infection.

Vaccinations

Vaccination with live viruses may interfere with TST reactivity and cause false-negative reactions; 

this includes measles, mumps, rubella, oral polio, varicella, yellow fever, BCG, and oral typhoid. For 

persons scheduled to receive TST and live virus vaccines, the testing should be done either on the 

same day as vaccination or at least 1 month after vaccination to minimize the potential for a falsenegative TST reaction.

Infection occurs within 8 weeks of skin testing 

False-negative TST reactions may occur if the TB infection occurred within 8 weeks of skin testing. 

For this reason, it is recommended that contacts of a person with infectious TB disease who have a 

negative reaction to the initial TST be retested at least 8 weeks after the last time they were in contact 

with the person who has infectious TB disease.

False-negative TST reactions may occur if the TB infection 

occurred within 8 weeks of skin testing.
Chapter 3: Testing for Tuberculosis Infection and Disease

57

Table 3.3

False-Positive and False-Negative Reactions to the TST

Type of Reaction Possible Cause People at Risk

False-positive Nontuberculous mycobacteria 

(NTM)

People infected with NTM

BCG vaccination People vaccinated with BCG

Administering of incorrect antigen Any person being tested

Incorrect interpretation of TST result Any person being tested

False-negative Anergy HIV-infected people, other people 

with weakened immune systems, 

severe TB disease, and some viral 

illness (e.g., measles, mumps, and 

chicken pox) or bacterial infection 

(e.g., typhoid, etc.)

Recent TB infection People infected with M. tuberculosis

within the past 8 weeks

Concurrent viral infection People injected with a live-virus 

vaccination

Concurrent bacterial infection People with typhoid fever, 

brucellosis, typhus, leprosy, 

pertussis

Concurrent fungal infection People with fungal infection

Chronic renal failure People with renal failure

Low protein states People with severe protein 

depletion or afibrinogenemia

Diseases affecting lymphoid organs People with Hodgkin’s disease, 

lymphoma, chronic leukemia, 

sarcoidosis

Immunosuppressive drugs People taking medical steroids, TNFalpha blockers or comparable drugs

Very young or elderly persons Newborns or elderly patients with 

immature or waning immunity

Stress People who have had surgery, 

burns, mental illness, graft-versushost reactions

Incorrect storage or handling of 

antigen, administering the TST, or 

results that are not measured or 

interpreted properly

Any person being tested
Chapter 3: Testing for Tuberculosis Infection and Disease

58

Special Considerations When Using TST

Boosted Reaction

The booster phenomenon occurs mainly in previously infected, older adults whose ability to react 

to tuberculin has waned over time (Figure 3.5). When these people are skin tested many years after 

they were infected with M. tuberculosis, they may have an initial negative reaction. However, if they 

are tested again within a year of the first test, they may have a positive reaction. This is because the 

first TST “triggered the memory” of the immune system, boosting its ability to react to the second 

TST. It may appear that these people were infected between the first and second tests (recent TB 

infection). The second, positive test reaction is actually a boosted reaction due to TB infection that 

occurred a long time ago. These people may still be considered for LTBI treatment if they fit into a 

high-risk category for progression to TB disease.

The booster phenomenon occurs mainly in previously infected, 

older adults whose ability to react to tuberculin has waned over time.

Figure 3.5

The TST Booster Phenomenon

The person is skin tested.

The person has a negative reaction. This is 

because over time, the person’s ability to react to 

tuberculin lessens. However, this skin test 

“triggers the memory” of the immune system to 

recognize and react to tuberculin.

The person is skin tested again, up to 1 year 

later. For this example, we assume that the 

person was NOT exposed to TB during this time.

A person is infected

with M. tuberculosis.

The person has 

a positive reaction. This is a boosted 

reaction due to TB infection that occurred a long 

time ago, not during the time between the 

two skin tests.

As the years pass, the 

person’s ability to react to 

tuberculin lessens.

Occurs mainly in previously 

infected, older adults 

whose ability to react to 

tuberculin has decreased 

over time.
Chapter 3: Testing for Tuberculosis Infection and Disease

59

Two-step TST Testing

Two-step testing is a strategy used to reduce the likelihood that a boosted reaction will be 

misinterpreted as a recent infection (Figure 3.6). Two-step testing should be used for the initial skin 

testing of persons who will be retested periodically, such as health-care workers. 

Two-step testing is a strategy used to reduce the likelihood that a 

boosted reaction will be misinterpreted as a recent infection.

If the reaction to the first test is classified as negative, a second test should be repeated 1 to 3 weeks 

later. A positive reaction to the second test probably represents a boosted reaction. On the basis 

of this second test result, the person should be classified as previously infected. This would not be 

considered a skin test conversion or a new TB infection; however, the patient may still be a candidate 

for LTBI treatment. If the second test result is also negative, the person should be classified as having 

a negative baseline TST result. 

Figure 3.6

Two-Step TST Testing

What is 

the 

Reaction?

Retest 

1-3 weeks later

Person probably 

has TB infection

The reaction is considered a boosted reaction 

(due to TB infection that occurred a long time ago). 

Note: The person does have LTBI; a decision must be 

made whether to treat or not.

Person probably 

does NOT have

 TB infection

Repeat TST at 

regular intervals; 

a positive reaction 

could be due to a 

recent TB infection.

Negative Positive

Baseline skin test

Follow-up for 

positive TST and evaluate 

for LTBI treatment

What is 

the 

Reaction?

Negative Positive

Follow-up for 

positive TST and evaluate 

for LTBI treatment
Chapter 3: Testing for Tuberculosis Infection and Disease

60

Pregnant Women

TST is both safe and reliable throughout the course of pregnancy. Pregnant women should receive a 

TST if they have a specific risk factor for acquiring LTBI or for progression of LTBI to TB disease. 

No documented episodes of TST-related fetal harm have been reported since the test was developed, 

and no evidence exists that the TST has adverse effects on the pregnant mother.

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

Occupational Exposure 

Guidelines for interpreting TST reactions should also be applied to persons who may have 

occupational exposure to TB (e.g., health-care workers; staff of nursing homes, drug treatment 

centers, or correctional facilities). Thus, the appropriate cutoff for defining a positive reaction 

depends on the employee’s individual risk factors for TB, including recent TB exposure and the 

prevalence of TB in the facility (based on facility risk assessment). In facilities where the risk of 

exposure is very low, 15 mm or greater induration may be an appropriate cut-off for employees with 

no other known risk factors. 

Residents and employees of high-risk congregate facilities should be tested for TB with the two-step 

method upon employment or entry into the facility, and thereafter at intervals determined by the 

annual risk assessment in that facility (see Chapter 7, TB Infection Control).

Residents and employees of high-risk congregate facilities should be tested for 

TB with the two-step method upon employment or entry into the facility and 

thereafter at intervals determined by the annual risk assessment in that facility.
Chapter 3: Testing for Tuberculosis Infection and Disease

61

Study Questions

3.3 A negative reaction to a TST or IGRA does not exclude the diagnosis of LTBI or TB 

disease. (circle the one best answer)

A. True

B. False

3.4 After TB has been transmitted, how long does it take for the body’s immune system to be 

able to react to tuberculin?

(circle the one best answer)

A. 48 to 72 hours

B. 7 to 10 days

C. 2 to 8 weeks

D. 6 months or more

What induration size is considered a positive TST reaction for the following people? 

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Persons Who Received a TST Size of Induration

____ 3.5 Prieta lives in a homeless shelter in El Paso 

and has poor access to health care.

____ 3.6 Gloria has no known risk factors for TB.

____ 3.7 Elwood has HIV infection.

A. 5 or more millimeters

B. 10 or more millimeters

C. 15 or more millimeters
Chapter 3: Testing for Tuberculosis Infection and Disease

62

Match the factors associated with TST with the appropriate term. 

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Factors Associated with TST Terms

____ 3.8 Mainly occurs in previously infected, older 

adults whose ability to react to tuberculin 

has lessened over time.

____ 3.9 May occur in people who have been 

vaccinated with BCG.

____ 3.10 Should be used for initial skin testing of 

persons who will be retested periodically.

____ 3.11 May occur in people who were recently 

infected with M. tuberculosis.

____ 3.12 Is the inability to react to a TST because of 

a weakened immune system.

A. False-positive skin test 

reaction

B. False-negative skin test 

reaction

C. Anergy

D. Boosted reaction

E. Two-step testing

3.13 Is it safe for a pregnant woman to have a TST?

(choose the one best answer)

A. Yes

B. No

Case Study–Bret

Bret comes to the county health department for a TST. He believes that he has been 

exposed to TB, and he knows he is at high risk for TB disease because he is HIV infected. 

He is given a TST, and his reaction is read 48 hours later as 0 millimeters of induration.

3.14 Which of the following reasons is a possible interpretation for this result? 

(circle the one best answer)

A. He may not have TB infection.

B. It may be less than 8 weeks since he was exposed to TB. 

C. He may be anergic.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 3: Testing for Tuberculosis Infection and Disease

63

Interferon-Gamma Release Assays (IGRAs)

IGRAs detect the presence of M. tuberculosis infection by measuring the immune response to TB 

proteins in whole blood. IGRAs cannot differentiate between LTBI and active TB disease. As with 

the TST, additional tests are needed to diagnose or rule out TB disease. IGRAs may be used for 

surveillance purposes or to identify people who are likely to benefit from treatment, including people 

who are or will be at increased risk of progression to TB disease if infected with M. tuberculosis.

Two IGRAs are commercially available and approved by the U.S. Food and Drug Administration 

(FDA) as aids in diagnosing M. tuberculosis infection:

• QuantiFERON®-TB Gold In-Tube test (QFT-GIT); and

• T-Spot®.TB test. 

IGRAs identify the presence of M. tuberculosis infection by measuring 

the immune response to the TB proteins in whole blood. IGRAs cannot 

differentiate between LTBI and active TB disease. As with the TST, 

additional tests are needed to diagnose or rule out TB disease.

IGRAs may be used for surveillance purposes or to identify people who 

are likely to benefit from treatment, including people who are or will be at 

increased risk of progression to TB disease if infected with M. tuberculosis.

General Recommendations for the Use of IGRAs

An IGRA may be used in place of (but not in addition to) a TST in all situations in which 

CDC recommends a TST as an aid in diagnosing M. tuberculosis infection, with the preferences 

and specific considerations noted below (Table 3.4).

• Preferred for testing persons from groups that historically have poor rates of return for 

TST reading.

• Preferred for testing persons who have received BCG (as a vaccine or for cancer therapy) 

(see BCG Vaccination in this chapter).

• Generally should not be used for testing children younger than 5 years of age unless used 

in conjunction with TST.

• May be used in place of TST to test recent contacts of persons with infectious TB disease 

with special considerations for follow-up testing:

» IGRAs offer the possibility of detecting M. tuberculosis infection with greater specificity 

than with a TST;

» Data on the ability of IGRAs to predict subsequent TB are limited;

» If IGRAs are to be used in contact investigations, negative results obtained prior to 8 weeks 

typically should be confirmed by repeating the test 8 to 10 weeks after the end of exposure;

» Use of the same test for repeat testing will minimize misclassification errors that occur due 

to test discordance.
Chapter 3: Testing for Tuberculosis Infection and Disease

64

• May be used in place of a TST for periodic screening that addresses occupational exposure to 

TB disease (e.g., surveillance programs for health-care workers).

• IGRAs do not boost subsequent test results and can be completed following a single patient 

visit.

• Routine testing with both a TST and an IGRA is not recommended; however, results from 

both tests may be useful in the following situations when the initial test is negative:

» When the risk of infection, the risk of progression from infection to disease, and the risk 

of a poor outcome are high (e.g., HIV infection, children under 5 years of age who are 

exposed to persons with infectious TB); or

» When there is clinical suspicion for TB disease (e.g., signs, symptoms, and/or radiographic 

evidence suggestive of TB disease) and confirmation of M. tuberculosis infection is desired.

• Routine testing with both a TST and an IGRA is not recommended; however, results from 

both tests may be useful in the following situations when the initial test is positive:

» Additional evidence of infection is required to encourage compliance (e.g., foreign-born 

health-care workers who believe their positive TST is due to BCG); and

» In healthy persons who have a low risk of both infection and progression from infection to 

TB disease.

• Repeating an IGRA or performing a TST may be useful when the initial IGRA result is 

indeterminate, borderline, or invalid, and a reason for testing persists.

• Each institution and TB control program should evaluate the availability, overall cost 

effectiveness, and benefits of the use of IGRAs.

An IGRA may be used in place of (but not in addition to) TST in all situations in 

which CDC recommends TST as an aid in diagnosing M. tuberculosis infection.

As with the TST, IGRAs generally should not be used for testing persons who have a low risk for 

both infection and disease attributable to M. tuberculosis (with exception of those who are likely to 

be at increased risk in the future) because screening such persons diverts resources from TB control 

activities of higher priority and increases the number of false-positive results.
Chapter 3: Testing for Tuberculosis Infection and Disease

65

Table 3.4

Recommendations for the Use of IGRAs

Category Recommended Not Recommended

Groups 

for use

• Preferred for groups that historically have poor 

rates of return for TST reading

• Preferred for persons who have received BCG (as 

a vaccine or for cancer therapy)

• Children younger than 5 

years of age unless it is used 

in conjunction with TST

• Persons at low risk of 

infection

• Persons at low risk of disease 

due to M. tuberculosis (except 

those who are likely to be at 

increased risk in the future)

In place 

of TST

• Recent contacts of persons with TB disease with 

special considerations for follow-up testing

» If IGRAs are used in contact investigations, 

negative results obtained prior to 8 weeks 

typically should be confirmed by repeating 

the test 8 to 10 weeks after the end of 

exposure

» Use of the same test for repeat testing will 

minimize misclassification errors that occur 

due to test discordance

• Periodic screening that addresses occupational 

exposure to TB disease (e.g., surveillance 

programs for health workers)

Testing 

with 

both 

TST and 

IGRA 

Results from both tests may be useful when the 

initial test is negative

• When the following risks are high

» Risk of infection

» Risk of progression from infection to disease

» Risk of a poor outcome

• When there is clinical suspicion for active TB 

and confirmation of M. tuberculosis infection is 

desired 

Routine testing with both TST 

and IGRA
Chapter 3: Testing for Tuberculosis Infection and Disease

66

Category Recommended Not Recommended

Testing 

with 

both 

TST and 

IGRA

Results from both tests may be useful in the 

following situations when the initial test is 

positive:

• Additional evidence of infection is required to 

encourage compliance (e.g., foreign-born healthcare workers who believe their positive TST is due 

to BCG); and

• In healthy persons who have a low risk of both 

infection and progression from infection to TB 

disease.

Routine testing with both TST 

and IGRA

Study Questions

Match the characteristic with the type of TB test. 

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Characteristic Type of TB Test

____ 3.15 Used to detect TB infection.

____ 3.16 Blood is drawn for the test.

____ 3.17 PPD is injected for the test.

____ 3.18 Requires two or more patient visits to 

conduct test.

____ 3.19 Requires one patient visit to conduct test.

____ 3.20 Results need to be read in 48– 72 hours.

____ 3.21 Results can be available in 24 hours.

____ 3.22 BCG vaccination can cause false-positive 

result.

____ 3.23 BCG vaccination does not cause falsepositive result.

A. TST

B. IGRA

C. Both TST and IGRA
Chapter 3: Testing for Tuberculosis Infection and Disease

67

BCG Vaccination

The bacille Calmette-Guérin (BCG) vaccine is a live, attenuated (weakened) vaccine derived from a 

strain of Mycobacterium bovis that was developed over several years by Calmette and Guérin at the 

Pasteur Institute in Lille, France. An early version of BCG was first administered to humans in 1921. 

Since that time, many different strains have been derived and used throughout the world. BCG 

vaccination is not generally recommended in the United States because of the low risk of infection 

with M. tuberculosis, the variable efficacy of the BCG vaccine against pulmonary TB, the low risk of 

severe disseminated TB disease in young children in the United States, and the vaccine’s interference 

with the ability to determine TST reactivity. Many highly TB-prevalent countries vaccinate infants 

with BCG as part of their TB control effort to prevent children from contracting severe disseminated 

TB or TB meningitis.

BCG vaccination is not generally recommended in the United States 

because of the low risk of infection with M. tuberculosis, the variable 

efficacy of the BCG vaccine against pulmonary TB, the low risk of severe 

disseminated TB disease in young children in the United States and the 

vaccine’s interference with the ability to determine TST reactivity.

Recommendations for the Use of BCG Vaccination in the United States 

The BCG vaccine may be considered in limited circumstances for selected persons who meet specific 

criteria. The use of the BCG vaccine should be undertaken only after consultation with local health 

departments and experts in the management of TB. 

Recent BCG vaccination may cause a subsequent false positive reaction to the TST. Thus, it may 

complicate decisions to prescribe treatment for LTBI for BCG-vaccinated persons who have a 

positive TST result. In such cases, an IGRA would be the test of choice for LTBI diagnosis.

Recent BCG vaccination may cause a subsequent false positive reaction 

to the TST. Thus, it may complicate decisions to prescribe treatment 

for LTBI for BCG-vaccinated persons who have a positive TST result.
Chapter 3: Testing for Tuberculosis Infection and Disease

68

Infants and Children

In the United States, BCG vaccination should only be considered for those children who have a 

negative TST or IGRA result and who are continually exposed to, and cannot be separated from, 

adults who:

• Are untreated or ineffectively treated for TB disease (if the child cannot be given long-term 

treatment for infection); or

• Have TB disease caused by strains resistant to isoniazid and rifampin.

The BCG vaccination is contraindicated in children infected with HIV.

BCG vaccination is contraindicated in children infected with HIV.

Health-Care Workers

BCG vaccination of health-care workers should be considered on an individual basis in 

settings in which:

• A high percentage of TB patients are infected with M. tuberculosis strains resistant to 

both isoniazid and rifampin;

• Transmission of such drug-resistant M. tuberculosis strains to health-care workers and 

subsequent infection are likely; and

• Comprehensive TB infection control precautions have been implemented and have 

not been successful.

BCG vaccination should not be required for employment or for assignment of health-care workers 

in specific work areas. Health-care workers considered for BCG vaccination should be counseled 

regarding the risks and benefits associated with both BCG vaccination and treatment of LTBI. BCG 

vaccination is contraindicated in health-care workers who are infected with HIV.

Contraindications to BCG Vaccination

BCG is contraindicated in persons who have an impaired immune system from the following:

• HIV infection;

• Congenital immunodeficiency;

• Leukemia;

• Lymphoma;

• Generalized malignancy;

• High-dose steroid therapy;

• Alkylation agents;

• Antimetabolites; or

• Radiation therapy.

It is also prudent to avoid giving BCG vaccination to pregnant women, although no harmful effects 

of BCG on the fetus have been observed.
Chapter 3: Testing for Tuberculosis Infection and Disease

69

BCG vaccination should not be given to pregnant women. 

Interpretation of TB Testing Results in BCG-Vaccinated Persons

The TST or IGRA is not contraindicated for persons who have been vaccinated with BCG. 

The TST or IGRA results are used to support decisions about the diagnosis of infection with 

M. tuberculosis. TST in persons vaccinated with BCG should be interpreted using the same criteria 

for those not BCG vaccinated. The booster phenomenon may occur among persons who have had 

a prior BCG vaccination. 

The TST or IGRA is not contraindicated for persons who have been 

vaccinated with BCG. The TST or IGRA results are used to support 

decisions about the diagnosis of infection with M. tuberculosis.

TST in persons vaccinated with BCG should be interpreted using the 

same criteria for those not BCG vaccinated. The booster phenomenon 

may occur among persons who have had a prior BCG vaccination.

Study Questions

3.24 Which of the following statements about recommendations for using BCG in the United 

States is true? 

(choose the one best answer)

A. Should NOT be given to pregnant women.

B. Should be used for children infected with HIV.

C. Should be required for employment of all health-care workers.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 3: Testing for Tuberculosis Infection and Disease

70

Case Study–Anshuman

Anshuman recently immigrated from India. He is given a TST that results in an 

induration of 14 millimeters. He reports that he was vaccinated with BCG as a child. He 

also says that his wife was treated for pulmonary TB disease last year. 

Are the following statements about how to interpret Anshuman’s results true or false? 

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Statement True or False

____ 3.25 He has a positive reaction to the TST.

____ 3.26 He is a contact of a person with pulmonary TB. 

____ 3.27 There is no reliable way to distinguish a positive TST 

reaction caused by BCG or from a true TB infection. 

____ 3.28 Because he was vaccinated with BCG there is no need 

to evaluate him further. 

____ 3.29 He should be further evaluated for LTBI or TB 

disease.

A. True

B. False

Which of the following factors make it more likely that Anshuman’s positive reaction is due to 

TB infection? (Choose the one best answer and write the letter for the correct answer on the line 

next to the question number.) 

Factor Yes or No

____ 3.30 He is from an area of the world where TB is common, 

so he was probably exposed to TB in 

his native country.

____ 3.31 His wife has had pulmonary TB, which further 

increases the probability that he has been exposed 

to TB. 

____ 3.32 He had BCG as a child, not as an adult. 

A. Yes, a factor

B. No, not a 

factor
Chapter 3: Testing for Tuberculosis Infection and Disease

71

Chapter Summary

Targeted testing is a TB control strategy that is used to identify, evaluate, and treat persons who are 

at high risk for LTBI or at high risk for developing TB disease once infected with M. tuberculosis. 

Identifying persons with LTBI is important to the goal of TB control and elimination because 

treatment of LTBI can prevent infected persons from developing TB disease and stop the further 

spread of TB. All testing activities should be accompanied by a plan for appropriate follow-up 

medical evaluation and treatment. Necessary medical evaluation and treatment resources need to be 

identified before testing activities begin. 

As part of their routine evaluation, health-care providers should identify and test persons who are 

at high risk for acquiring TB infection or at high risk for progressing to TB disease if infected. In 

some select settings, active case finding may be more appropriate than testing for M. tuberculosis

infection. Flexibility is needed in defining high-risk groups for testing. The changing epidemiology 

of TB indicates that the risk for TB disease or LTBI among groups currently considered high risk 

may decrease over time, and groups currently not identified as being at risk may subsequently be 

considered high risk. 

Selection of the most suitable test(s) for detection of M. tuberculosis infection should be based on 

the reasons and the context for testing, test availability, and overall cost effectiveness of testing. 

Currently, there are two methods available for the detection of M. tuberculosis infection in the United 

States. The tests are:

• Mantoux tuberculin skin test (TST)

• Interferon-gamma release assays (IGRAs)

» QuantiFERON-TB Gold In-Tube test (QFT-GIT)

» T-Spot®.TB test

The TST is used to determine if a person is infected with M. tuberculosis. In this test, a substance 

called purified protein derivative (PPD), which is derived from tuberculin, is injected under the skin. 

Typically PPD produces a T-cell mediated delayed-type hypersensitivity reaction if the person has 

been infected with M. tuberculosis. In most people who have TB infection, the immune system will 

recognize the PPD because it is extracted from the tubercle bacilli that caused the infection. It takes 

2 to 8 weeks after initial infection with M. tuberculosis for the body’s immune system to be able to 

react to PPD and for the infection to be detected by the TST.

The booster phenomenon occurs mainly in previously infected, older adults whose ability to react 

to tuberculin has waned over time. When these people are skin tested many years after they were 

infected with M. tuberculosis, they may have an initial negative reaction. However, if they are tested 

again within a year of the first test, they may have a positive reaction. This is because the first TST 

“triggered the memory” of the immune system, boosting its ability to react to the second TST. It may 

appear that these people were infected between the first and second tests (recent TB infection). The 

second, positive test reaction is actually a boosted reaction due to TB infection that occurred a long 

time ago. These people may still be considered for LTBI treatment if they fit into a high-risk category 

for progression to TB disease.
Chapter 3: Testing for Tuberculosis Infection and Disease

72

IGRAs identify the presence of M. tuberculosis infection by measuring the immune response to the 

TB proteins in whole blood. These tests cannot differentiate between LTBI and active TB disease. As 

with the TST, additional tests are needed to diagnose or rule out TB disease. IGRAs may be used for 

surveillance purposes or to identify people who are likely to benefit from treatment, including people 

who are or will be at increased risk of progression to TB disease if infected with M. tuberculosis.

The bacille Calmette-Guérin (BCG) vaccine is a live, attenuated (weakened) vaccine derived from a 

strain of Mycobacterium bovis that was developed by Calmette and Guérin at the Pasteur Institute in 

Lille, France. An early version of BCG was first administered to humans in 1921. Since that time, 

many different strains have been derived and used throughout the world. BCG vaccination is not

generally recommended in the United States because of the low risk of infection with M. tuberculosis, 

the variable efficacy of the BCG vaccine against pulmonary TB, the low risk of severe disseminated 

TB disease in young children in the United States, and the vaccine’s interference with the ability 

to determine TST reactivity. Many highly TB-prevalent countries vaccinate infants with BCG as 

part of their TB control effort to prevent children from contracting severe disseminated TB or TB 

meningitis.

References

American Thoracic Society and CDC. Diagnostic standards and classification of tuberculosis in 

adults and children. Am J Respir Crit Care Med 2000; 161(4): 1376– 1395.

http://ajrccm.atsjournals.org/cgi/reprint/161/4/1376

CDC. A strategic plan for the elimination of tuberculosis in the United States. MMWR 1989; 38 

(Suppl No. S-3). www.cdc.gov/mmwr/preview/mmwrhtml/00001375.htm 

CDC. Controlling tuberculosis in the United States: Recommendations from the American Thoracic 

Society, CDC, and the Infectious Diseases Society of America. MMWR 2005; 54 (No. RR-12).

www.cdc.gov/mmwr/PDF/rr/rr5412.pdf

CDC. Essential components of a tuberculosis prevention and control program: Recommendations of 

the Advisory Council for the Elimination of Tuberculosis. MMWR 1995; 44 (No. RR-11).

www.cdc.gov/mmwr/preview/mmwrhtml/00038823.htm 

CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care 

settings, 2005. MMWR 2005; 54 (No. RR-17). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e

CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR 2000; 49 

(No. RR-6). www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm

Updates:

Adverse event data and revised American Thoracic Society/CDC recommendations against the 

use of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 

2003. MMWR 2003; 52 (31):735–9. www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm
Chapter 3: Testing for Tuberculosis Infection and Disease

73

Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis 

infection, and revisions in American Thoracic Society/CDC recommendations—United States, 

2001. MMWR 2001; 50 (34):733– 5 www.cdc.gov/mmwr/preview/mmwrhtml/mm5034a1.htm

Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent 

tuberculosis infection—New York and Georgia, 2000. MMWR 2001; 50 (15): 289– 91. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5015a3.htm

CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat 

latent Mycobacterium tuberculosis infection recommendations— United States, 2011. MMWR 2011; 

60 (48): 1650– 1653.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6048a3.htm?s_cid=mm6048a3_w

Errata (February 3, 2012) http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a7.htm

CDC. The role of BCG vaccine in the prevention and control of tuberculosis in the United States: 

A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory 

Committee on Immunization Practices. MMWR 1996; 45 (No. RR-4). 

www.cdc.gov/mmwr/preview/mmwrhtml/00041047.htm 

CDC. Tuberculosis elimination revisited: Obstacles, opportunities, and a renewed commitment. 

MMWR 1999; 48 (No. RR-9). www.cdc.gov/mmwr/preview/mmwrhtml/rr4809a1.htm 

CDC. Updated guidelines for using interferon gamma release assays to detect Mycobacterium 

tuberculosis infection—United States, 2010. MMWR 2010; 59 (No. RR-5).

 www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm?s_cid=rr5905a1_e

Chapter 4: Diagnosis of TB Disease

75

Chapter 4 

Diagnosis of Tuberculosis Disease

Table of Contents

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

Medical Evaluation.......................................................... 78

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

Chapter Objectives

After working through this chapter, you should be able to 

• Describe the five components of a TB medical evaluation;

• Identify the major components of TB diagnostic microbiology;

• List at least five symptoms of pulmonary TB disease;

• Explain the purpose and significance of acid-fast bacilli (AFB);

• Explain the purpose and significance of the culture; and 

• Explain the purpose and significance of genotyping.
Chapter 4: Diagnosis of TB Disease

76
Chapter 4: Diagnosis of TB Disease

77

Introduction

Tuberculosis (TB) is not as common as it was many years ago in the United States; consequently, 

clinicians do not always consider the possibility of TB disease when evaluating patients who have 

symptoms. As a result, the diagnosis of TB disease may be delayed or even overlooked, and the 

patient may remain ill and possibly infectious for a prolonged period. 

Not all persons with TB disease have symptoms; however, most persons with TB disease have one or 

more symptoms that lead them to seek medical care. All persons with symptoms of TB disease, or 

either a positive tuberculin skin test (TST) or an interferon-gamma release assay (IGRA) indicative 

of M. tuberculosis infection, should be medically evaluated to exclude TB disease.

Not all persons with TB disease have symptoms; however, most persons with 

TB disease have one or more symptoms that lead them to seek medical care.

All persons with symptoms of TB disease, or either a positive 

TST or IGRA indicative of M. tuberculosis infection, should 

be medically evaluated to exclude TB disease.

Study Question

4.1 All persons with symptoms of TB disease, or a positive TST or IGRA result indicating 

M. tuberculosis infection, should be medically evaluated to exclude TB disease.

(choose the one best answer)

C. True

D. False
Chapter 4: Diagnosis of TB Disease

78

Medical Evaluation

A complete medical evaluation for TB disease includes the following five components:

1. Medical history

2. Physical examination

3. Test for M. tuberculosis infection

4. Chest radiograph

5. Bacteriologic examination of clinical specimens.

1. Medical History

When conducting a medical history, the clinician should ask if any symptoms of TB disease are 

present; if so, for how long, and if there has been known exposure to a person with infectious 

TB disease. Equally important is obtaining information on whether or not the person has been 

diagnosed in the past with latent tuberculosis infection (LTBI) or TB disease. Clinicians may also 

contact the local health department for information on whether a patient has a past history of TB 

infection or disease. If the previous treatment regimen for TB disease was inadequate or if the patient 

did not adhere to therapy, TB disease may recur and possibly be drug-resistant. It is important to 

consider demographic factors (e.g., country of origin, age, ethnicity, occupation, or racial group) 

that may increase the patient’s risk for being exposed to TB infection (see Chapter 2, Transmission 

and Pathogenesis of Tuberculosis). Clinicians should determine if the patient has underlying medical 

conditions, especially human immunodeficiency virus (HIV) infection or diabetes, that increase the 

risk for progression to TB disease in those latently infected with M. tuberculosis. 

Clinicians should determine if the patient has underlying medical 

conditions, especially HIV infection and diabetes, that increase the risk for 

progression to TB disease in those latently infected with M. tuberculosis.

As discussed in Chapter 2, Transmission and Pathogenesis of Tuberculosis, TB disease most 

commonly affects the lungs and is referred to as pulmonary TB disease. Pulmonary TB disease 

usually causes one or more of the symptoms indicated in Table 4.1.

TB disease most commonly affects the lungs and 

is referred to as pulmonary TB disease.
Chapter 4: Diagnosis of TB Disease

79

Extrapulmonary TB disease may cause symptoms related to the part of the body that is affected 

(Table 4.1). For example, TB of the spine may cause back pain; TB of the kidney may cause blood 

in the urine; TB meningitis may cause headache or confusion. Extrapulmonary TB disease should 

be considered in the differential diagnosis of ill persons who have systemic symptoms and who are at 

high risk for TB disease.

Both pulmonary and extrapulmonary TB disease symptoms can be caused by other diseases; 

however, they should prompt the clinician to consider TB disease.

Both pulmonary and extrapulmonary TB disease symptoms 

can be caused by other diseases; however, they should 

prompt the clinician to consider TB disease.

Table 4.1

Symptoms of Pulmonary and Extrapulmonary TB Disease

Symptoms of 

Pulmonary TB Disease

(TB disease usually causes 

one or more of the symptoms)

Symptoms of 

Possible Extrapulmonary TB Disease

(Depends on the part of the body 

that is affected by the disease) 

• Cough (especially if lasting for 3 weeks or 

longer) with or without sputum production

• Coughing up blood (hemoptysis)

• Chest pain 

• Loss of appetite

• Unexplained weight loss

• Night sweats

• Fever

• Fatigue

• TB of the kidney may cause blood in the urine

• TB meningitis may cause headache or 

confusion

• TB of the spine may cause back pain

• TB of the larynx can cause hoarseness

• Loss of appetite

• Unexplained weight loss

• Night sweats

• Fever

• Fatigue
Chapter 4: Diagnosis of TB Disease

80

Study Questions

Match the patient symptoms with the type of TB.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Patient Symptoms Type of TB

____ 4.2 Regina has back pain and blood in her 

urine, unexplained weight loss, fever, 

fatigue, loss of appetite.

____ 4.3 Maria has a cough, loss of appetite, and 

unexplained weight loss. She has also been 

coughing up blood.

A. Pulmonary TB

B. Extrapulmonary TB

2. Physical Examination

A physical examination is an essential part of the evaluation of any patient. It cannot be used to 

confirm or rule out TB disease, but it can provide valuable information about the patient’s overall 

condition, inform the method of diagnosis, and reveal other factors that may affect TB disease 

treatment, if diagnosed.

A physical examination is an essential part of the evaluation of 

any patient. It cannot be used to confirm or rule out TB disease, 

but it can provide valuable information about the patient’s overall 

condition, inform the method of diagnosis, and reveal other 

factors that may affect TB disease treatment, if diagnosed.

Study Question

4.4 A physical examination can be used to confirm and rule out TB disease.

(circle the one best answer)

A. True

B. False
Chapter 4: Diagnosis of TB Disease

81

3. Test for M. tuberculosis Infection

Selection of the most suitable tests for detection of M. tuberculosis infection should be based on 

the reasons and the context for testing, test availability, and overall cost effectiveness of testing. 

Currently, there are two methods available for the detection of M. tuberculosis infection in the United 

States. The tests are:

• Mantoux tuberculin skin test (TST) (Figure 4.1); and 

• Interferon-gamma release assays (IGRAs)*

» QuantiFERON-TB Gold In-Tube test (QFT-GIT) (Figure 4.2);

» T-SPOT®.TB test (Figure 4.3).

*See Chapter 3, Testing for Tuberculosis Infection and Control

Figure 4.1

Mantoux Tuberculin

Skin Test 

Figure 4.2

QuantiFERON-TB Gold 

In-Tube Test (QFT-GIT)

Figure 4.3

T-SPOT®.TB Test

These tests help clinicians differentiate people infected with M. tuberculosis from those uninfected. 

However, a negative reaction to any of the tests does not exclude the diagnosis of TB disease or LTBI 

(see Chapter 3, Testing for Tuberculosis Infection and Disease).

TST and QFT tests help clinicians differentiate people infected with 

M. tuberculosis from those uninfected. However, a negative reaction to 

any of the tests does NOT exclude the diagnosis of TB disease or LTBI.

Study Question

4.5 A negative reaction for a TST or IGRA test excludes a person from having TB disease.

(choose the one best answer)

A. True

B. False
Chapter 4: Diagnosis of TB Disease

82

4. Chest Radiograph

With pulmonary TB being the most common form of disease, the chest radiograph is useful for 

diagnosis of TB disease. Chest abnormalities can suggest pulmonary TB disease (Figure 4.4). A 

posterior-anterior radiograph of the chest is the standard view used for the detection of TB-related 

chest abnormalities. In some cases, especially in children, a lateral view may be helpful.

Figure 4.4 

Chest Radiograph with Lower Lobe Cavity

In some instances, a computerized tomography (CT) scan may provide additional information. A 

CT scan provides more detailed images of parts of the body that cannot easily be seen on a standard 

chest radiograph; however, CT scans can be substantially more expensive. 

In pulmonary TB disease, radiographic abnormalities are often seen in the apical and posterior 

segments of the upper lobe or in the superior segments of the lower lobe. However, lesions may 

appear anywhere in the lungs and may differ in size, shape, density, and cavitation, especially in HIVinfected and other immunosuppressed persons. Radiographic abnormalities in children tend to be 

minimal with a greater likelihood of lymphadenopathy, more easily diagnosed on the lateral film.

Mixed nodular and fibrotic lesions may contain slowly multiplying tubercle bacilli and have the 

potential for progression to TB disease. Persons who have lesions consistent with findings of “old” 

TB disease on a chest radiograph and have a positive TST reaction or positive IGRA result should 

be considered high-priority candidates for treatment of LTBI (see Chapter 5, Treatment for Latent 

Tuberculosis Infection), but only after TB disease is excluded by obtaining three specimens for 

AFB smear and culture because “old” TB cannot be differentiated from active TB disease based on 

radiographic appearance alone. Conversely, fully calcified, discrete, nodular lesions without fibrosis 

likely represent granulomas and pose a lower risk for future progression to TB disease. 
Chapter 4: Diagnosis of TB Disease

83

In HIV-infected persons, pulmonary TB disease may present with atypical findings or with no 

lesions seen on the chest radiograph. The radiographic appearance of pulmonary TB disease in 

persons infected with HIV might be typical; however, cavitary disease is less common among such 

patients. More common chest radiograph findings for HIV-infected persons include infiltrates in 

any lung zone, mediastinal or hilar adenopathy, or, occasionally, a normal chest radiograph. Typical 

cavitary lesions are usually observed in patients with higher CD4 counts, and more atypical patterns 

are observed in patients with lower CD4 counts because cavitation is thought to occur as a result of 

the immune response to TB organisms. In HIV-infected persons, almost any abnormality on a chest 

radiograph may be indicative of TB disease. In patients with symptoms and signs of TB disease, a 

negative chest radiograph result does not exclude TB disease. 

Abnormalities seen on chest radiographs may be suggestive of, but are never diagnostic of, TB 

disease. Chest radiographs may be used to exclude pulmonary TB disease in an HIV-negative person 

who has a positive TST reaction or IGRA and who has no symptoms or signs of TB disease.

Abnormalities seen on chest radiographs may be suggestive of, but are 

never diagnostic of, TB disease. Chest radiographs may be used to exclude 

pulmonary TB disease in a person with a normal immune system who has a 

positive TST reaction or IGRA and who has no symptoms or signs of TB disease.

Study Question

4.6 Chest radiographs may be used to exclude pulmonary TB disease in an HIV-negative 

person who has a positive TST reaction or IGRA and who has no symptoms or signs of 

TB disease. (choose the one best answer)

A. True

B. False

5. Bacteriologic Examination of Clinical Specimens

Examinations of clinical specimens (e.g., sputum, urine, or cerebrospinal fluid) are of critical 

diagnostic importance. The specimens should be examined and cultured in a laboratory that 

specializes in testing for M. tuberculosis. The bacteriologic examination has five parts:

• Specimen collection, processing, and review

• AFB smear classification and results

• Direct detection of M. tuberculosis in clinical specimen using nucleic acid amplification (NAA)

• Specimen culturing and identification

• Drug-susceptibility testing
Chapter 4: Diagnosis of TB Disease

84

Specimen Collection, Processing, and Review

For diagnostic purposes, all persons suspected of having TB disease at any site should have sputum 

specimens collected for an AFB smear and culture, even those without respiratory symptoms. At least 

three consecutive sputum specimens are needed, each collected in 8- to 24-hour intervals, with at 

least one being an early morning specimen. If possible, specimens should be obtained in an airborne 

infection isolation (AII) room or other isolated, well-ventilated area (e.g., outdoors) (Figure 4.5).

For diagnostic purposes, all persons suspected of having TB disease 

at any site should have sputum collected for TB culture. At least three 

consecutive sputum specimens are needed, each collected in 8- to 24-

hour intervals, with at least one being an early morning specimen.

Figure 4.5

TB Patient Coughing Up Sputum

A TB patient has coughed up sputum and is spitting it into a sterile 

container. The patient is sitting in a special sputum collection booth 

that, if properly ventilated, prevents the spread of tubercle bacilli.

For diagnostic purposes, all persons suspected of having TB disease 

should have sputum collected for AFB smear and culture.

During specimen collection, patients produce an aerosol that may be hazardous to health-care 

workers or other patients in close proximity. For this reason, precautionary measures for infection 

control must be followed during sputum induction, bronchoscopy, and other common diagnostic 

procedures (see Chapter 7, TB Infection Control).
Chapter 4: Diagnosis of TB Disease

85

During specimen collection, patients produce an aerosol that may be 

hazardous to health-care workers or other patients in close proximity.

Specimen Collection Methods for Pulmonary TB Disease

There are four specimen collection methods for pulmonary TB disease (Table 4.2):

• Coughing

• Induced sputum

• Bronchoscopy

• Gastric aspiration

Coughing–Coughing is the most commonly used method of sputum collection. Coughing 

should be supervised to ensure that sputum is collected correctly. A health-care worker wearing the 

recommended personal protective equipment should coach and directly supervise the patient when 

sputum is collected (Figure 4.6). Patients should be informed that sputum is the material brought 

up from the lungs, and that mucus from the nose or throat and saliva are not good specimens. 

Unsupervised patients are less likely to provide an adequate specimen, especially the first time.

Patients should be informed that sputum is the material 

brought up from the lungs, and that mucus from the nose 

or throat and saliva are not good specimens.

Figure 4.6

Patient Coughing Up Sputum

Sputum Induction–For patients unable to cough up sputum, deep sputum-producing coughing 

may be induced by inhalation of an aerosol of warm, sterile, hypertonic saline (3%– 5%). Because 

induced sputum is very watery and resembles saliva, it should be labeled “induced” to ensure that the 

laboratory staff workers do not discard it.
Chapter 4: Diagnosis of TB Disease

86

Bronchoscopy–A bronchoscopy is a medical procedure that allows visualization of the inside of 

a person’s airways. The airways are called the bronchial tubes or bronchi. Bronchoscopy might be 

needed for specimen collection, especially if previous results have been nondiagnostic and doubt 

exists as to the diagnosis. At other times, bronchoscopy is considered because TB is among several 

other diagnoses being considered. If possible, examine three spontaneous or induced sputum to 

exclude a diagnosis of TB disease before bronchoscopy. If possible, avoid bronchoscopy on patients 

with suspected or confirmed TB disease or postpone the procedure until the patient is determined 

to be noninfectious, by confirmation of the three negative AFB sputum smear results (Figure 

4.7). Bronchial washings, brushings, and biopsy specimens may be obtained, depending on the 

bronchoscopy findings. Sputum collected after a bronchoscopy may also be useful for a diagnosis. 

A bronchoscopy should never be substituted for sputum collection, but rather used as an additional 

diagnostic procedure. 

Figure 4.7

Performing a Bronchoscopy

Whenever feasible, bronchoscopy should be performed in a room that meets the ventilation 

requirements for an airborne infection isolation (AII) room. Health-care workers should wear N95 

respirators while present during a bronchoscopy procedure on a patient with suspected or confirmed 

infectious TB disease (see Chapter 7, TB Infection Control).
Chapter 4: Diagnosis of TB Disease

87

Gastric Aspiration–Gastric aspiration is a procedure sometimes used to obtain a specimen for 

culture when a patient cannot cough up adequate sputum. A tube is inserted through the mouth 

or nose and into the stomach to recover sputum that was coughed into the throat and then 

swallowed. This procedure is particularly useful for diagnosis in children, who are often unable 

to cough up sputum (Figure 4.8). Gastric aspiration often requires hospitalization and should be 

done in the morning before the patient gets out of bed or eats, as it is the optimal time to collect 

swallowed respiratory secretions from the stomach. Specimens obtained by gastric aspiration should 

be transported to the lab immediately for neutralization or neutralized immediately at the site of 

collection.

Figure 4.8

Performing a Gastric Aspiration
Chapter 4: Diagnosis of TB Disease

88

Table 4.2

Methods of Obtaining a Sputum Specimen

Method Description Advantage Disadvantage

Spontaneous 

sputum sample

Patient coughs up 

sputum into a sterile 

container

• Inexpensive

• Easy to do

• Patient may not be able to 

cough up sputum without 

assistance or may spit up 

saliva instead of sputum

• Health-care worker has to 

coach and supervise the 

patient when collecting 

sputum

Sputum induction Patient inhales a 

saline mist which 

can cause a deep 

cough

• Easy to do

• Use to obtain 

sputum when 

coughing sputum 

is not productive

• Specimens may be watery 

and may be confused with 

saliva (should be labeled 

“induced specimen”)

• Requires special 

equipment

• May cause bronchospasm

Bronchoscopy Bronchoscope is 

passed through 

the mouth or nose 

directly into the 

diseased portion 

of the lung, and 

sputum or lung 

tissue is removed

Use to obtain 

sputum when 

coughing or 

inducing sputum is 

not productive or 

other diagnoses are 

being considered

• Most expensive and 

invasive procedure

• Requires special 

equipment

• Must be done by a 

specialist in a hospital or 

clinic

• Requires anesthesia

Gastric washing Tube is inserted 

through the 

patient’s mouth or 

nose and passed 

into the stomach 

to get a sample of 

gastric secretions 

that contain sputum 

that has been 

coughed into the 

throat and then 

swallowed

Use to obtain 

samples in children, 

who do not

produce sputum 

when they cough

• Must be done as soon as 

patient wakes up in the 

morning; patient may be 

required to stay in hospital

• Can be uncomfortable for 

the patient
Chapter 4: Diagnosis of TB Disease

89

Specimen Collection Methods for Extrapulmonary TB

TB disease can occur in almost any anatomical site; thus, a variety of clinical specimens other than 

sputum (e.g., urine, cerebrospinal fluid, pleural fluid, pus, or biopsy specimens) may be submitted 

for examination when extrapulmonary TB disease is suspected (Figures 4.9 and 4.10). Procedures 

for the expeditious and recommended handling of the specimen must be in place or assured before 

the specialist performs an invasive procedure to obtain the specimen. Especially important is rapid 

transportation to the laboratory according to the laboratory’s instructions. It is important to note 

that the portion of the specimen placed in formalin for histologic examination cannot be used for 

culture.

TB disease can occur in almost any anatomical site; thus, a variety 

of clinical specimens other than sputum (e.g., urine, cerebrospinal 

fluid, pleural fluid, pus, or biopsy specimens) may be submitted for 

examination when extrapulmonary TB disease is suspected.

Figure 4.9

Clinical Specimen Used for 

Examination When Extrapulmonary

TB Disease Is Suspected

Figure 4.10

Collection Bottles Used for Collecting 

Specimens When Extrapulmonary 

TB Disease Is Suspected

AFB Smear Classification and Results

Detection of acid-fast bacilli in stained and acid-washed smears examined microscopically may 

provide the initial bacteriologic evidence of the presence of mycobacteria in a clinical specimen 

(Figure 4.11). Smear microscopy is the quickest and easiest procedure that can be performed. 

Detection of acid-fast bacilli in stained and acid-washed smears 

examined microscopically may provide the first bacteriologic 

evidence of the presence of mycobacteria in a clinical specimen.
Chapter 4: Diagnosis of TB Disease

90

Figure 4.11

Acid-Fast Bacilli Stained in Smear 

Tubercle bacilli are shown in red

There are two procedures commonly used for acid-fast staining: 

• Carbolfuchsin methods which include the Ziehl-Neelsen and Kinyoun methods 

(direct microscopy)

• Fluorochrome procedure using auramine-O or auramine-rhodamine dyes 

(fluorescent microscopy).

Studies have shown that there must be 5,000 to 10,000 bacilli per milliliter of specimen to allow the 

detection of bacteria in stained smears. In contrast, 10 to 100 bacilli are needed for a positive culture. 

Smear examination is a quick procedure; results should be available within 24 hours of specimen 

collection when specimens are delivered to the laboratory promptly. However, smear examination 

permits only the presumptive diagnosis of TB disease because the acid-fast bacilli in a smear may be 

acid-fast organisms other than M. tuberculosis. Also, many TB patients have negative AFB smears 

with a subsequent positive culture. Negative smears do not exclude TB disease (Table 4.3).

Many TB patients have negative AFB smears with a subsequent 

positive culture. Negative smears do not exclude TB disease.

When acid-fast bacilli are seen in a smear, they are counted. There is a system for reporting the 

number of acid-fast bacilli that are seen at a certain magnification. According to the number of 

acid-fast bacilli seen, the smears are classified as 4+, 3+, 2+, or 1+. The greater the number, the more 

infectious the patient (Table 4.3). 
Chapter 4: Diagnosis of TB Disease

91

Table 4.3

Smear Classification Results

Smear Result

(Number of AFB observed 

at 1000X magnification)

Smear Interpretation Infectiousness of Patient

4+ (>9/field) Strongly positive Probably very infectious

3+ (1-9/field) Strongly positive Probably very infectious

2+ (1-9/10 fields) Moderately positive Probably infectious

1+ (1-9/100 fields) Moderately positive Probably infectious

+/- (1-2/300 fields)* Weakly positive† Probably infectious

No acid-fast bacilli seen Negative Probably not infectious**

* There are variations on labeling for this result, and include listing the number of AFB counted. 

† Laboratories may report these smear results as “doubtful” or “inconclusive” based on CDC guidelines.

** The criteria for determining whether a patient may be considered noninfectious are discussed in 

Chapter 7 on TB Infection Control.

Direct Detection of M. tuberculosis in Clinical Specimen Using Nucleic Acid 

Amplification (NAA)

NAA tests are used to amplify DNA and RNA segments to rapidly identify the microorganisms in a 

specimen. NAA testing can reliably detect M. tuberculosis bacteria in specimens in hours as compared 

to 1 week or more for culture (Figure 4.12). Possible benefits of using NAA tests include

• Earlier laboratory confirmation of TB disease;

• Earlier treatment initiation;

• Improved patient outcomes;

• Interruption of transmission by early diagnosis, respiratory isolation and appropriate treatment; 

• Earlier, more efficient use of respiratory isolation; 

• Earlier initiation of contact investigation; and

• More effective public health interventions. 
Chapter 4: Diagnosis of TB Disease

92

NAA tests are used to amplify DNA and RNA segments to 

rapidly identify the microorganisms in a specimen. 

CDC recommends that NAA testing be performed on at least one respiratory specimen from each 

patient with signs and symptoms of pulmonary TB for whom a diagnosis of TB is being considered 

but has not yet been established, and for whom the test result would alter case management or TB 

control activities, such as contact investigations.

Figure 4.12

Nucleic Acid Amplification (NAA) Test

Clinicians should interpret all laboratory results in the context of the clinical situation. A single 

negative NAA test result should not be used as a definitive result to exclude TB disease, especially 

when the clinical suspicion of TB disease is moderate to high. Rather, the negative NAA test result 

should be used as additional information in making clinical decisions, to expedite testing for an 

alternative diagnosis, or to prevent unnecessary TB disease treatment.

Culture remains the gold standard for laboratory confirmation of TB disease, and growing bacteria 

are required to perform drug-susceptibility testing and genotyping. In accordance with current 

recommendations, sufficient numbers and portions of specimens should always be reserved for 

culture. Nonetheless, NAA testing should become standard practice for patients suspected of having 

TB, and all clinicians and public health TB programs should have access to NAA testing for TB to 

shorten the time to diagnosis.

Culture remains the gold standard for laboratory confirmation 

of TB disease, and growing bacteria are required to perform 

drug-susceptibility testing and genotyping.
Chapter 4: Diagnosis of TB Disease

93

Specimen Culture and Identification

Positive cultures for M. tuberculosis confirm the diagnosis of TB disease; however, in the absence 

of a positive culture, TB disease may also be diagnosed on the basis of clinical signs and symptoms 

alone. Culture examinations should be done on all diagnostic specimens, regardless of AFB smear or 

NAA results. The commercially available broth culture systems (e.g., BACTEC, MGIT, VersaTREK, 

MBBACT) allow detection of most mycobacterial growth in 4 to 14 days compared to 3 to 6 weeks 

for solid media (Figure 4.13). Laboratories performing TB cultures should routinely use a brothbased system (Table 4.4). 

Positive cultures for M. tuberculosis confirm the diagnosis of TB disease; 

however, in the absence of a positive culture, TB disease may also be 

diagnosed on the basis of clinical signs and symptoms alone.

Culture examinations should be done on all diagnostic 

specimens, regardless of AFB smear or NAA results.

Figure 4.13

Colonies of M. tuberculosis Grown in Culture
Chapter 4: Diagnosis of TB Disease

94

Table 4.4

Differences Between Sputum Smears and Cultures

Feature Smears Cultures

Equipment needed • Microscope

• Glass slides

• Special dyes

• Incubators

• Safety cabinet

• Culture plates or tubes

• Culture media, biochemicals for tests

Time needed to 

make report

• 1 day • 4 days to 12 weeks (depending on 

method used and how quickly the 

organism grows)

Basis of procedure • Looking for acid-fast bacilli 

on slide under microscope

• Growth and identification of tubercle 

bacilli or other mycobacteria on culture 

media in incubator

Significance of a 

negative report

• Patient is probably not

infectious

• Does not rule out TB disease 

(culture may be positive)

• No live tubercle bacilli found in 

specimen

• Does not rule out TB disease (live 

tubercle bacilli may be in other 

specimens and/or body sites)

Significance of a 

positive report

• Patient is more likely to be 

infectious (if acid-fast bacilli 

are tubercle bacilli)

• Acid-fast bacilli could 

be nontuberculous 

mycobacteria

• Confirms diagnosis of TB disease

Follow-up Bacteriologic Examination

Follow-up bacteriologic examinations are important for assessing the patient’s infectiousness 

and response to therapy. Specimens should be obtained at monthly intervals until two consecutive 

specimens sent for culture are reported as negative. Culture conversion is the most important 

objective measure of response to treatment. Conversion is documented by the first negative 

culture in a series of previously positive cultures. In addition, all subsequent culture results must 

remain negative.

Specimens should be obtained at monthly intervals until

two consecutive specimens sent for culture are reported as negative.
Chapter 4: Diagnosis of TB Disease

95

Reporting Results

Laboratories should report initial positive smears, positive M. tuberculosis cultures, and positive 

NAA results within 24 hours by telephone or fax to the primary health-care provider and health 

department. Out-of-state laboratories who receive referral specimens must contact the health-care 

provider and health department in the patient’s state of origin. Follow-up results may be reported 

by mail. It is the responsibility of the primary health-care provider to report all suspected or 

confirmed cases of TB disease promptly to the state or local health department unless state laws 

indicate otherwise. Prompt reporting to health authorities ensures that the person with TB disease 

can be adequately treated, interrupting the potential for ongoing transmission. It also ensures that 

contact investigations can be initiated quickly to find contacts of the patient who may have LTBI 

or TB disease.

Laboratories should report initial positive smears, positive M. tuberculosis

cultures, and positive NAA results within 24 hours by telephone or 

fax to the primary health-care provider and health department.

Drug-Susceptibility Testing

For all patients, the initial M. tuberculosis isolate should be tested for resistance to the first-line 

anti-TB drugs: isoniazid, rifampin, ethambutol, and pyrazinamide (Figure 4.14). The results of 

drug-susceptibility tests should direct clinicians to choose the appropriate drugs for treating each 

patient. Patients with TB disease who are treated with drugs to which their strain of TB is resistant 

may not be successfully cured. In fact, their strain of TB may become resistant to additional drugs.

For all patients, the initial M. tuberculosis isolate should 

be tested for resistance to the first-line anti-TB drugs: 

isoniazid, rifampin, ethambutol, and pyrazinamide.
Chapter 4: Diagnosis of TB Disease

96

Figure 4.14

Drug-Susceptibility Testing

Rapid, broth-based systems should be used to identify drug resistance as early as possible in order to 

ensure appropriate treatment. Susceptibility results from laboratories should be promptly forwarded 

to the physician and health department. Drug-susceptibility tests should be repeated for patients 

who do not respond as expected or who have positive culture results despite 3 months of adequate 

treatment. 

Second-line drug susceptibility testing should be done only in reference laboratories and generally be 

limited to specimens from patients who have the following characteristics:

• Prior TB disease treatment;

• Contact with a patient with known anti-TB drug resistance; 

• Demonstrated resistance to first-line anti-TB drugs; or

• Positive cultures after more than 3 months of treatment. 

A patient is diagnosed with multidrug-resistant TB (MDR TB) disease if the organisms are 

resistant to at least isoniazid and rifampin, the two most potent first-line anti-TB drugs. A patient 

is diagnosed with extensively drug-resistant TB (XDR TB) disease if the TB isolate is resistant to 

isoniazid and rifampin, any fluoroquinolone, and at least one of three injectable second-line drugs 

(i.e., amikacin, kanamycin, or capreomycin).

A patient is diagnosed with multidrug-resistant TB (MDR TB) 

disease if the organisms are resistant to at least isoniazid and 

rifampin, the two most potent first-line anti-TB drugs.
Chapter 4: Diagnosis of TB Disease

97

A patient is diagnosed with extensively drug-resistant TB (XDR TB) 

disease if the isolate is resistant to isoniazid and rifampin, 

any fluoroquinolone, and at least one of three injectable 

second-line drugs (i.e., amikacin, kanamycin, or capreomycin).

Molecular Detection of Drug Resistance

The drug resistance of clinical isolates as determined by conventional methods (e.g, broth-based 

and agar proportion) is due to the presence of mutations in specific M. tuberculosis genes. These 

mutations often are single base pair changes in the DNA sequence of the bacteria. There are a variety 

of commercial assays and laboratory developed tests that can detect mutations associated with drug 

resistance. The assays are done on patient specimens or isolates from patient specimens. 

• Line-probe assays use polymerase chain reaction (PCR) to amplify the region of a gene known 

to be associated with resistance. The amplified product is labeled and specifically joins to 

probes on a nitrocellulose strip. Mutations are detected by the lack of binding to probes with 

the normal sequence or by binding to probes specific for commonly occurring mutations.

• PCR amplification of genes known to be associated with drug resistance can be followed by 

DNA sequencing that can detect mutations.

• Real-time PCR with fluorescing probes that specifically join to the target can do so in one step, 

a technique sometimes called “molecular beacons.” 

All of these assays allow rapid detection of drug resistance through the identification of genetic 

mutations associated with resistance and provide preliminary guidance on effective therapy. 

Molecular detection of drug resistance should be considered for patients with the following 

characteristics:

• High risk of rifampin resistance, including MDR TB (e.g., previously treated TB, contact with 

someone with MDR TB, or being foreign born from a high-risk country);

• First-line drug susceptibility results are available and show resistance to rifampin;

• Infectiousness poses a risk to vulnerable contacts (e.g., daycare workers, nurses, and infants); and

• Contraindications to essential first-line medications (e.g., rifampin allergy). 

A limitation of molecular testing for drug resistance is that the clinical relevance of some mutations 

remains unknown. Further, not all biological mechanisms of resistance are known. As a result, 

if no mutations are detected by the molecular assay, resistance cannot be ruled out. Therefore, 

it is essential that conventional growth-based drug-susceptibility tests are done and used in 

conjunction with molecular results.

It is essential that conventional growth-based drug-susceptibility 

tests are done and used in conjunction with molecular results.
Chapter 4: Diagnosis of TB Disease

98

Study Questions

Indicate which of the following activities is a component of a complete medical evaluation for 

TB. (Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Activity Yes or No

____ 4.7 Medical history 

____ 4.8 Physical examination 

____ 4.9 Test for M. tuberculosis infection

____ 4.10 Chest radiograph

____ 4.11 Bone density testing

____ 4.12 Bacteriological examination of 

clinical specimens

A. Yes, is a component 

of a complete medical 

evaluation for TB

B. No, is not a component 

of a complete medical 

evaluation for TB 

Match the specimen collection method with how to use it.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Use of Specimen Collection Method Method

____ 4.13 Use only if there is a suspicion of TB disease 

and there are three negative sputum smears 

or induced sputum AFB results. 

____ 4.14 Best way to obtain specimens from children 

who cannot produce sputum.

____ 4.15 Use for extrapulmonary TB disease.

____ 4.16 Use for patients unable to cough up sputum 

to encourage deep coughing.

____ 4.17 Most common method for collecting 

sputum. 

A. Coughing

B. Sputum induction

C. Bronchoscopy

D. Gastric aspiration

E. Biopsy
Chapter 4: Diagnosis of TB Disease

99

4.18 What do laboratory personnel look for in a sputum smear?

(choose the one best answer)

A. White-blood cells

B. Fast-moving bacilli

C. Drug-resistant bacilli

D. Acid-fast bacilli

Case Study–Chin

Chin has symptoms of TB disease and a cavity on his chest radiograph, but all of his 

sputum smears are negative for acid-fast bacilli.

4.19 Does this rule out the diagnosis of pulmonary TB disease for Chin? 

(circle the one best answer)

A. Yes, because his sputum smears are negative for acid-fast bacilli. Even though he has 

symptoms of TB disease and a cavity on his chest radiograph, his sputum smears have to 

be positive for acid-fast bacilli to indicate a diagnosis of pulmonary TB disease.

B. No, because he has symptoms of TB disease and his abnormal chest x-ray suggest that 

he does have pulmonary TB disease. Also, M. tuberculosis may grow in the cultures even 

though there are no acid-fast bacilli on the smear.
Chapter 4: Diagnosis of TB Disease

100

Which of the following statements about nucleic acid amplification (NAA) tests and cultures 

are true or false? (Choose the one best answer and write the letter for the correct answer on the line 

next to the question number.) 

Statements about NAA and Cultures True or False

____ 4.20 NAA tests are used to amplify DNA and RNA 

segments to rapidly identify the microorganisms in a 

specimen. 

____ 4.21 Culture is required for growing bacteria for drugsusceptibility testing and genotyping.

____ 4.22 Culture is the gold standard for laboratory 

confirmation of TB disease.

____ 4.23 A single negative NAA test result should be used as a 

definitive result to exclude TB disease.

____ 4.24 Cultures should be done on all diagnostic specimens, 

regardless of AFB smear or NAA results.

A. True

B. False

4.25 During patient follow-up, how often should specimens be obtained?

(circle the one best answer)

A. At monthly intervals until one specimen sent for culture is reported as negative.

B. At monthly intervals until three consecutive specimens sent for culture are 

reported as negative.

C. At monthly intervals until two consecutive specimens sent for culture are 

reported as negative.
Chapter 4: Diagnosis of TB Disease

101

Are the following statements about drug-susceptibility testing true or false?

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Statements about Drug-Susceptibility Testing True or False

____ 4.26 For all patients, the initial M. tuberculosis isolate 

should be tested for resistance to the first-line anti-TB 

drugs.

____ 4.27 For all patients, the initial M. tuberculosis isolate 

should be tested for resistance to the second-line antiTB drugs.

____ 4.28 Drug-susceptibility tests should be repeated for 

patients who do not respond as expected.

____ 4.29 Drug-susceptibility tests should be repeated for 

patients who have positive culture results despite 3 

months of adequate therapy.

A. True

B. False

Case Study–Lea

Lea gave three sputum specimens, which were sent to the laboratory for smear 

examination and culture. The smear results were reported as 4+, 3+, and 4+.

4.30 What do these results tell you about Lea’s diagnosis and her infectiousness? 

(circle the one best answer)

A. Because the smears are positive, clinicians should suspect that Lea has TB disease. 

B. She is probably very infectious.

C. It is possible that the acid-fast bacilli are mycobacteria other than tubercle bacilli. 

Therefore, diagnosis of TB disease cannot be proven until further results are available. 

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 4: Diagnosis of TB Disease

102

Case Study–Francis

In the health clinic you see Francis, a new patient. She complains of weight loss, fever, 

and a cough of 4 weeks’ duration. When questioned, she reports that she has been treated 

for TB disease in the past and that she occasionally injects heroin. 

4.31 What parts of Francis’ medical history lead you to suspect TB disease? 

(circle the one best answer)

A. Her symptoms of TB disease (weight loss, fever, and a persistent cough). 

B. The fact that she has been treated for TB disease in the past. 

C. Her history of injecting illegal drugs (heroin).

D. A, B, and C are all correct.

E. Only A and C are correct.

4.32 What diagnostic tests should be done on Francis? 

(circle the one best answer)

A. Sputum specimen collection for smear and culture.

B. Drug-susceptibility testing if culture is positive.

C. Chest radiograph because she has symptoms of pulmonary TB disease. 

D. A, B, and C are all correct.

E. Only A and B are correct.

Genotyping

TB genotyping is a laboratory-based approach used to analyze the genetic material (i.e., DNA) 

of M. tuberculosis. The total genetic content is referred to as the genome. Specific sections of 

the M. tuberculosis genome form distinct genetic patterns that help distinguish different strains of 

M. tuberculosis. M. tuberculosis genotyping is based on polymorphisms in the number and genomic 

location of mycobacterial repetitive elements. M. tuberculosis isolates with identical genotypes suggest 

that there may have been recent TB transmission among the persons from whom they were isolated. 

The main purpose of genotyping is to add to TB controllers’ understanding of TB transmission in 

their community.

TB genotyping is a laboratory-based approach used to analyze 

the genetic material (i.e., DNA) of M. tuberculosis.
Chapter 4: Diagnosis of TB Disease

103

M. tuberculosis isolates with identical genotypes are often indicative of 

recent TB transmission among the persons from whom they were isolated.

When coupled with traditional epidemiologic investigations, analyses of the genotype of 

M. tuberculosis strains have confirmed suspected transmission and detected unsuspected transmission 

of M. tuberculosis. These analyses have also identified risk factors for recent infection with rapid 

progression to disease, demonstrated re-infection with different strains, identified weaknesses in 

conventional contact investigations, documented the existence of laboratory cross-contamination, 

and identified outbreaks of TB that were not previously recognized (Table 4.5). Genotyping has 

become an increasingly useful tool for studying the pathogenesis, epidemiology, and transmission of 

TB infection and disease.

Table 4.5

Use of Genotyping Analyses

How Genotyping Has Been Used

• Confirmed suspected transmission and detected unsuspected transmission of 

M. tuberculosis, when coupled with traditional epidemiologic investigations 

• Identified risk factors for recent infection with rapid progression to disease

• Demonstrated re-infection with different strains

• Identified weaknesses in conventional contact investigations

• Documented the existence of laboratory cross-contamination

• Identified outbreaks of TB that were not previously recognized

Study Question

4.33 What is the main purpose of genotyping? 

(choose the one best answer)

A. To amplify DNA and RNA segments to rapidly identify the microorganisms 

in a specimen. 

B. To add to TB controllers’ understanding of TB transmission in their community.

C. To determine drug susceptibility of TB strains.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 4: Diagnosis of TB Disease

104

Chapter Summary

TB is not as common as it was many years ago in the United States; consequently, clinicians do not

always consider the possibility of TB disease when evaluating patients who have symptoms. As a 

result, the diagnosis of TB disease may be delayed or even overlooked, and the patient may remain ill 

and possibly infectious for a prolonged period. 

Not all persons with TB disease have symptoms; however, most persons with TB disease have one or 

more symptoms that lead them to seek medical care. All persons with symptoms of TB disease, and 

either a positive TST or IGRA indicative of M. tuberculosis infection, should be medically evaluated. 

A complete medical evaluation for TB disease includes the following five components:

1. Medical history

2. Physical examination

3. Test for M. tuberculosis infection

4. Chest radiograph

5. Bacteriologic examination of clinical specimens

1. Medical History

When conducting a medical history, the clinician should ask if any symptoms of TB disease are 

present; if so, for how long, and if there has been known exposure to a person with infectious 

TB disease. Equally important is obtaining information on whether or not the person has been 

diagnosed in the past with LTBI or TB disease. 

TB disease most commonly affects the lungs and is referred to as pulmonary TB disease. 

Symptoms include:

• Cough (especially if lasting for 3 weeks or longer) with or without sputum collection

• Coughing up blood (hemoptysis)

• Chest pain 

• Loss of appetite

• Unexplained weight loss

• Night sweats

• Fever

• Fatigue

Extrapulmonary TB disease may cause symptoms related to the part of the body that is affected. 

For example, TB of the spine may cause back pain; TB of the kidney may cause blood in the urine; 

TB meningitis may cause headache or confusion. Extrapulmonary TB disease should be considered 

in the differential diagnosis of ill persons who have systemic symptoms and who are at high risk for 

TB disease.

Both pulmonary and extrapulmonary TB disease symptoms can be caused by other diseases; 

however, they should prompt the clinician to consider TB disease.
Chapter 4: Diagnosis of TB Disease

105

2. Physical Examination 

A physical examination is an essential part of the evaluation of any patient. It cannot be used to 

confirm or rule out TB disease, but it can provide valuable information about the patient’s overall 

condition, inform the method of diagnosis, and reveal other factors that may affect TB disease 

treatment, if diagnosed. 

3. Test for M. tuberculosis Infection 

Selection of the most suitable tests for detection of M. tuberculosis infection should be based on 

the reasons and the context for testing, test availability, and overall cost effectiveness of testing. 

Currently, there are two methods available for the detection of M. tuberculosis infection in the United 

States. The tests are:

• Mantoux tuberculin skin test (TST); and 

• Interferon-gamma release assays (IGRAs)

» QuantiFERON-TB Gold In-Tube test (QFT-GIT)

» T-SPOT®.TB test.

These tests may help clinicians differentiate people infected with M. tuberculosis from those 

uninfected. However, a negative reaction to any of the tests does not exclude the diagnosis of TB 

disease or LTBI.

4. Chest Radiograph

With pulmonary TB being the most common form of disease, the chest radiograph is useful for 

diagnosis of TB disease. Chest abnormalities can suggest pulmonary TB disease. A posterior-anterior 

radiograph of the chest is the standard view used for the detection of chest abnormalities. In some 

cases, especially in children, a lateral view may be helpful.

Abnormalities seen on chest radiographs may be suggestive of, but are never diagnostic of, TB 

disease. Chest radiographs may be used to exclude TB disease in an HIV-negative person who has a 

positive TST reaction or IGRA and who has no symptoms or signs of TB disease.

5. Bacteriologic Examination of Clinical Specimens 

Examinations of clinical specimens (for example, sputum or urine) are of critical diagnostic 

importance. The specimens should be examined and cultured in a laboratory that specializes in 

testing for M. tuberculosis. The bacteriologic examination has five parts:

• Specimen collection, processing, and review;

• AFB smear classification and results;

• Direct detection of M. tuberculosis in clinical specimen (NAA);

• Specimen culturing and identification; and

• Drug-susceptibility testing.
Chapter 4: Diagnosis of TB Disease

106

References

American Thoracic Society and CDC. Diagnostic standards and classification of tuberculosis in 

adults and children. Am J Respir Crit Care Med 2000; 161(4): 1376– 1395. 

http://ajrccm.atsjournals.org/cgi/reprint/161/4/1376

CDC. Controlling tuberculosis in the United States: Recommendations from the American Thoracic 

Society, CDC, and the Infectious Diseases Society of America. MMWR 2005; 54 (No. RR-12).

www.cdc.gov/mmwr/PDF/rr/rr5412.pdf

CDC. Essential components of a tuberculosis prevention and control program: Recommendations of 

the Advisory Council for the Elimination of Tuberculosis. MMWR 1995; 44 (No. RR-11).

www.cdc.gov/mmwr/preview/mmwrhtml/00038823.htm 

CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care 

settings, 2005. MMWR 2005; 54 (No. RR-17).

www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e

CDC. Prevention and treatment of tuberculosis among patients infected with human 

immunodeficiency virus: Principles of therapy and revised recommendations. MMWR 1998; 47 

(No. RR-20). www.cdc.gov/mmwr/preview/mmwrhtml/00055357.htm 

CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR 2000; 49 

(No. RR-06). www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm

Updates:

Adverse event data and revised American Thoracic Society/CDC recommendations against the 

use of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 

2003. MMWR 2003; 52 (31):735– 9. www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm

Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis 

infection, and revisions in American Thoracic Society/CDC recommendations—United States, 

2001. MMWR 2001; 50 (34):733– 5 www.cdc.gov/mmwr/preview/mmwrhtml/mm5034a1.htm

Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent 

tuberculosis infection—New York and Georgia, 2000. MMWR 2001; 50 (15): 289– 91. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5015a3.htm

CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to 

treat latent Mycobacterium tuberculosis infection recommendations—United States, 2011. MMWR

2011; 60 (48): 1650– 1653. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6048a3.htm?s_

cid=mm6048a3_w

Errata (February 3, 2012) http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a7.htm
Chapter 4: Diagnosis of TB Disease

107

CDC. The role of BCG vaccine in the prevention and control of tuberculosis in the United States: 

A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory 

Committee on Immunization Practices. MMWR 1996; 45 (No. RR-4). 

www.cdc.gov/mmwr/preview/mmwrhtml/00041047.htm

CDC. Treatment of tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society 

of America. MMWR 2003; 52 (RR-11). www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm

Errata (January 7, 2005) www.cdc.gov/mmwr/preview/mmwrhtml/mm5351a5.htm

CDC. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of 

tuberculosis. MMWR 2009; 58 (01): 7– 10. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5801a3.htm?s_cid=mm5801a3_e

CDC. Updated guidelines for using interferon gamma release assays to detect Mycobacterium 

tuberculosis infection—United States, 2010. MMWR 2010; 59 (RR-5). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm?s_cid=rr5905a1_e

Chapter 5: Treatment for Latent Tuberculosis Infection

109

Chapter 5 

Treatment for 

Latent Tuberculosis Infection

Table of Contents

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111

Candidates for the Treatment of LTBI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

LTBI Treatment Regimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

LTBI Treatment Regimens for Specific Situations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

Patient Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

Chapter Objectives

After working through this chapter, you should be able to 

• List the high-risk groups who should be given priority for latent tuberculosis infection (LTBI) 

treatment;

• Describe LTBI treatment regimens;

• Describe LTBI treatment regimens for specific situations; and

• Identify components of patient monitoring at baseline and during the treatment of LTBI.

Chapter 5: Treatment for Latent Tuberculosis Infection

111

Introduction

It is currently estimated that more than 11 million people in the United States have latent 

tuberculosis (TB) infection, which is about 4 percent of the total population. While not everyone 

with latent TB infection (LTBI) will develop TB disease, about 5 to 10 percent of infected people 

will develop TB disease if not treated. This equates to approximately 550,000 to 1,100,000 people 

who will develop TB at some point in their life, unless they receive adequate treatment for LTBI.

Treatment of LTBI is essential to controlling and eliminating TB disease in the United States. It 

substantially reduces the risk that persons infected with M. tuberculosis will progress to TB disease. 

Certain groups are at high risk of developing TB disease once infected. Targeted testing programs 

should be designed to identify persons who are at high risk for TB disease and who would benefit 

from treatment of LTBI. Targeted testing should be undertaken only if resources are identified 

and available to ensure full evaluation and treatment. There are two methods available for the 

detection of M. tuberculosis infection in the United States, the Mantoux tuberculin skin test (TST) 

and interferon-gamma release assays (IGRAs) (see Chapter 3, Testing for Tuberculosis Infection 

and Disease).

Targeted testing programs should be designed to identify persons who are 

at high risk for TB disease and who would benefit from treatment of LTBI.

Study Question

5.1 Which statement about the purpose of LTBI treatment is true?

(choose the one best answer)

F. It is given to people who have LTBI to prevent them from testing positive on a 

subsequent TST.

G. It is given to people who have LTBI to prevent the progression to TB disease.

H. It is given to people who have TB disease to prevent the disease from getting worse.

I. It is given to people who have TB disease to prevent them from becoming infectious.
Chapter 5: Treatment for Latent Tuberculosis Infection

112

Candidates for the Treatment of LTBI

Persons with Positive IGRA Result, or TST Reaction ≥5 mm

Persons in the following high-risk groups should be given treatment for LTBI if they have either a 

positive IGRA result or if their reaction to the TST is ≥5 mm (Table 5.1):

• HIV-infected persons;

• Recent contacts of persons with infectious TB disease;

• Persons with fibrotic changes on chest radiograph consistent with prior TB disease 

(once TB disease is excluded); and

• Patients with organ transplants, and other immunosuppressed patients (including patients 

receiving the equivalent of 15 mg/day of prednisone for >1 month).

Persons with Positive IGRA Result, or TST Reaction ≥10 mm 

Persons in the following high-risk groups should be considered for treatment of LTBI if they have 

either a positive IGRA result or if their reaction to the TST is ≥10 mm (Table 5.1):

• Recent arrivals to the United States (<5 years) from high-prevalence areas (e.g., Africa, Asia, 

Eastern Europe, Latin America, and Russia);

• Injection drug users;

• Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing 

homes, homeless shelters, and hospitals);

• Mycobacteriology laboratory personnel;

• Persons with medical conditions that increase the risk for progression to TB disease, i.e., 

silicosis, diabetes mellitus, chronic renal failure, certain types of cancer (e.g., leukemia and 

lymphomas, or cancer of the head, neck, or lung), gastrectomy or jejunoileal bypass, and 

weight loss of at least 10% from ideal body weight;

• Children younger than 5 years of age; and 

• Infants, children, and adolescents exposed to adults in high-risk categories (see Chapter 3, 

Testing for Tuberculosis Disease and Infection).
Chapter 5: Treatment for Latent Tuberculosis Infection

113

Table 5.1

High-Priority Candidates for LTBI Treatment Using IGRA or TST*

Groups Who Should Be Given 

High Priority for LTBI Treatment

People who have a positive 

IGRA result or a

TST reaction of

5 or more millimeters

People who have a positive 

IGRA result or a

TST reaction of

10 or more millimeters

• HIV-infected persons**

• Recent contacts of persons with infectious 

TB disease**

• Persons with fibrotic changes on chest 

radiograph consistent with prior TB disease

• Patients with organ transplants and other 

immunosuppressed patients (including 

patients receiving the equivalent of 

15 mg/day of prednisone for ≥1 month)

• Recent arrivals to the United States (<5 years) 

from high-prevalence areas (e.g., Asia, Africa, 

Eastern Europe, Russia, or Latin America)

• Injection drug users 

• Residents and employees of high-risk 

congregate settings (e.g., correctional 

facilities, nursing homes, homeless shelters, 

hospitals, or other health-care facilities)

• Mycobacteriology laboratory personnel

• Persons with medical conditions that 

increase the risk for progression to TB 

disease, including silicosis, diabetes mellitus, 

chronic renal failure, certain types of cancer 

(e.g., leukemia and lymphomas, or cancer 

of the head, neck or lung), gastrectomy or 

jejunoileal bypass, and weight loss of at least 

10% below body weight;

• Children younger than 5 years of age; or 

children and adolescents exposed to adults 

in high-risk categories

 * See Chapter 3, Testing for Tuberculosis Infection and Disease for information on interpreting a TST or IGRA 

result

** In certain circumstances, people in these categories may be given LTBI treatment even if they do not have a 

positive TST or IGRA result (see the Special Considerations for LTBI Treatment section in this Chapter).
Chapter 5: Treatment for Latent Tuberculosis Infection

114

Persons with No Known Risk Factors Who Have Positive IGRA Result, 

or TST Reaction ≥15 mm 

People without any risk factors generally should not be tested for TB infection. Testing should be 

targeted to groups at high risk for LTBI and TB disease (see Chapter 3, Testing for Tuberculosis 

Infection and Disease). However, if a person without any risk factors is tested and has a positive 

IGRA result or TST reaction that is ≥15 mm, he or she should be evaluated for LTBI treatment once 

TB disease is excluded. 

People without any risk factors generally should not be tested for TB infection.

Close Contacts Who Have a Negative IGRA or TST Result

Some contacts who have a negative IGRA or TST result should be evaluated for treatment of LTBI 

after TB disease has been ruled out. These contacts include: 

• Children less than 5 years of age

• Immunosuppressed persons

• Those at risk for rapid progression to TB disease once infected (see Chapter 3, Testing for 

Tuberculosis Infection and Disease)

Any contact who is to be treated for LTBI should have a chest radiograph to exclude pulmonary TB 

disease before starting treatment.

Any contact who is to be treated for LTBI should have a chest radiograph 

to exclude pulmonary TB disease before starting treatment.

Close contacts who have a negative IGRA or TST result should be retested 8 to 10 weeks after 

they were last exposed to infectious TB disease. This is due to the fact that it can take 2 to 8 weeks 

after TB infection for the body’s immune system to react to tuberculin and for the infection to 

be detected.

Close contacts who have a negative IGRA or TST result should be retested 

8 to 10 weeks after they were last exposed to infectious TB disease.
Chapter 5: Treatment for Latent Tuberculosis Infection

115

HIV-Infected Contacts

Contacts known or suspected to be HIV infected or who have other serious immunocompromising 

conditions should be started on treatment for LTBI regardless of their IGRA or TST result after 

TB disease has been excluded. Treatment of LTBI may be discontinued if the TST or IGRA result is 

negative on the second test given 8 to 10 weeks after the last exposure and if the person is no longer 

exposed to infectious TB disease. However, because HIV-infected and other immunocompromised 

persons may be anergic and not be able to manifest a positive TST or IGRA result if infected, in 

some cases medical providers may decide to prescribe a complete course of LTBI treatment even 

if the second TST or IGRA result is negative, particularly if the exposure to TB is substantial 

(e.g., prolonged, frequent exposure to very infectious TB patient). 

Contacts known or suspected to be HIV infected or who have other serious 

immunocompromising conditions should be started on treatment for LTBI 

regardless of their IGRA or TST result after TB disease has been excluded.

Infants and Young Children

Because of their age, infants and young children with LTBI are known to have been infected recently, 

and thus are at a high risk of their infection progressing to TB disease (Table 5.2). Infants and young 

children are also more likely than older children and adults to develop life-threatening forms of TB 

disease, especially meningeal and disseminated disease, because they do not have fully developed 

immune systems.

Because of their age, infants and young children with LTBI 

are known to have been infected recently, and thus are at a 

high risk of their infection progressing to TB disease.

Infants and young children are more likely than older children 

and adults to develop life-threatening forms of TB disease.
Chapter 5: Treatment for Latent Tuberculosis Infection

116

Window Prophylaxis

Children less than 5 years of age who are close contacts to an adult with infectious TB should receive 

treatment for LTBI even if the TST result is negative and once TB disease is excluded by chest 

radiograph and symptom review; this is called “window” prophylaxis. Also, infected infants may be 

anergic as late as 6 months of age. A second TST should be administered 8 to 10 weeks after the last 

exposure to infectious TB disease. Window prophylaxis can be discontinued if all of the following 

conditions are met:

• The infant is at least 6 months of age

• The second TST result is also negative

• The second TST was performed at least 8 weeks after the child was last exposed to an adult 

with infectious TB disease

Children less than 5 years of age who are close contacts to an adult with 

infectious TB should receive treatment for LTBI even if the TST result is negative 

once TB disease is excluded by chest radiograph and symptom review. 

Table 5.2

LTBI in Children

Infants and Young Children 

with LTBI

Treating Children Less than 5 Years of Age 

Who Are Close Contacts

• Are known to have been infected recently 

(because of their age)

• Are more likely than older children and 

adults to develop life-threatening forms of TB 

disease (e.g., disseminated TB, TB meningitis)

• Should provide LTBI treatment even if initial 

TST result is negative once TB disease is 

excluded (infected infants may be anergic as 

late as 6 months of age)

• Administer a second TST 8 to 10 weeks after 

the last exposure to infectious TB disease

• Discontinue window prophylaxis if all of the 

following conditions are met:

» Infant is at least 6 months of age

» Second TST result is also negative

» Second TST was performed at least 8 

weeks after the child was last exposed 

to infectious TB disease
Chapter 5: Treatment for Latent Tuberculosis Infection

117

Study Questions

Match the patient with the TST reaction size that makes them a candidate for LTBI.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Patients TST Reaction that Makes 

Them a Candidate for LTBI

____ 5.2 Peter is an injection drug user.

____ 5.3 Louis is HIV positive.

____ 5.4 Katrina, a 4-year-old, is a recent 

arrival from Mexico.

____ 5.5 Edith is a resident at the DeLand 

Nursing Home.

____ 5.6 Ann lives with her brother Joel, 

who has infectious TB disease.

____ 5.7 Richard is the recipient of a heart 

transplant.

____ 5.8 Sherry is a bank teller and has no 

known risk factors for TB.

____ 5.9 Ginny is a nurse in the Dade 

County Correctional Facility.

____ 5.10 Joe is diabetic.

A. ≥5 mm of induration

B. ≥10 mm of induration 

C. ≥15 mm of induration

5.11 The following close contacts to someone with infectious TB disease have a negative IGRA 

result. Which patient(s) should be evaluated for treatment of LTBI?

(choose the one best answer)

A. Bernard is being treated for leukemia.

B. Sophia is 6 years old.

C. Kathy works in a bakery.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 5: Treatment for Latent Tuberculosis Infection

118

5.12 When should close contacts who have a negative IGRA or TST result be retested? 

(choose the one best answer)

A. 4 to 6 weeks after they were last exposed to infectious TB disease.

B. 8 to 10 weeks after they were last exposed to infectious TB disease.

C. It is not necessary to retest them.

5.13 Which of the following statements is true about infants and young children with LTBI? 

(choose the one best answer)

A. Because of their age, they are known to have been infected recently.

B. They are at high risk of their infection progressing to TB disease.

C. They are less likely than older children and adults to develop life-threatening 

forms of TB disease.

D. A, B, and C are all correct.

E. Only A and B are correct.

LTBI Treatment Regimens

There are several treatment regimens available for the treatment of LTBI. Providers should choose the 

appropriate regimen based on 

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

• Coexisting medical illnesses; and 

• Potential for drug-drug interactions (Table 5.3). 

For persons who are at especially high risk for TB disease and are either suspected of nonadherence 

or are given an intermittent dosing regimen, directly observed therapy (DOT) for LTBI should 

be considered (for more information on DOT, see Chapter 6, Treatment of Tuberculosis Disease). 

This method of treatment is especially appropriate if the person in need of LTBI treatment lives 

with a household member who is on DOT for TB disease, or lives in an institution or facility where 

treatment for LTBI can be observed by a staff member. It is necessary to exclude TB disease before 

starting LTBI treatment.

For persons who are at especially high risk for TB disease and are either 

suspected of nonadherence or are given an intermittent dosing regimen, 

directly observed therapy (DOT) for LTBI should be considered.
Chapter 5: Treatment for Latent Tuberculosis Infection

119

Isoniazid (INH) Dosage

When INH alone is given to persons with TB disease, drug resistance may develop. For this reason, 

persons suspected of having TB disease should receive the recommended multidrug regimen for 

treatment of TB disease rather than INH monotherapy until the diagnosis is confirmed or excluded. 

There are two options for treatment with INH (Table 5.3):

• 9-month regimen

• 6-month regimen

INH is normally used alone for treatment of LTBI in a single daily dose of 300 mg in adults and 

10–20 mg/kg body weight in children, not to exceed 300 mg per dose. INH can be given two times 

a week at a dosage of 20–40 mg/kg by DOT for LTBI for children, or 900 mg for adults. 

The 9-month regimen is preferred because it is more efficacious. Treatment for LTBI for 6 months 

rather than 9 months may be more cost-effective and result in greater adherence by patients; 

therefore, local programs may prefer to implement the 6-month regimen rather than the 9-month 

regimen. Every effort should be made to ensure that patients adhere to LTBI treatment for at least 6 

months. 

When INH alone is given to persons with TB disease, drug resistance may 

develop. For this reason, persons suspected of having TB disease should 

receive the recommended multidrug regimen for treatment of disease 

rather than INH monotherapy until the diagnosis is confirmed or excluded.

9-Month INH Regimen

A 9-month INH regimen is considered optimal treatment. In order to be considered adequate 

treatment, the patient must receive a minimum of 270 doses administered within 12 months. The 

preferred regimen for children 2 to 11 years of age is 9 months of daily INH. Patients may be treated 

with a twice-weekly regimen as an alternative as long as they are undergoing DOT. In a twice-weekly 

regimen, 76 doses administered within 12 months is considered adequate therapy. 

6-Month INH Regimen

A 6-month INH regimen also provides substantial protection against developing TB disease, but 

it is less protective than the 9-month regimen. In order to be considered adequate treatment, the 

patient must receive a minimum of 180 doses administered within 9 months. Patients may be 

treated with a twice-weekly regimen given by DOT as an alternative regimen. In the twice-weekly 

regimen, 52 doses administered within 9 months is considered adequate therapy. This regimen is not 

recommended for children, or immunosuppressed persons, or those with evidence of previous TB on 

chest radiograph.
Chapter 5: Treatment for Latent Tuberculosis Infection

120

Isoniazid (INH) and Rifapentine (RPT) Regimen

3-Month INH-RPT Regimen (12-Dose Regimen)

The 12-dose regimen is a combination of INH and RPT given in 12 once-weekly doses under DOT. 

Because missed doses, altered dosing intervals or amounts, or incomplete treatment could jeopardize 

the 12-dose regimen efficacy or safety, DOT is strongly recommended for this regimen. Patients 

using the 12-dose regimen should undergo monthly clinical monitoring, including inquiries about 

side effects and a physical assessment for signs of adverse effects.

The 12-dose regimen 

• Is recommended as an equal option to 9 months of daily INH, but does not replace other 

recommended treatment options for LTBI (Table 5.3) 

• Is recommended for treating LTBI in 

» Otherwise healthy people, 12 years of age or older and who were recently in contact 

with infectious TB, or who had tuberculin skin test or positive blood test for TB 

infection conversions. 

• Can be considered for specific groups when it offers practical advantages, such as completion 

of treatment within a limited timeframe.

The 12-dose regimen is not recommended for children younger than 2 years, HIV-infected patients 

taking antiretroviral therapy (ART), patients with presumed INH or RIF-resistant M. tuberculosis, 

pregnant women, or women expecting to become pregnant within the treatment period.

The dosage for a combination 12-dose regimen of INH and RPT is: 

Isoniazid (INH)

• 15 mg/kg rounded up to the nearest 50 or 100 mg with a 900 mg maximum.

Rifapentine (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.

INH is formulated as 100 mg and 300 mg tablets. RPT is formulated as 150 mg tablets packed in 

blister packs that should be kept sealed until usage. New formulations with larger dosage per tablet 

and fixed-dose INH-RPT combinations are in development.

The 12-dose regimen is recommended as an equal option to 9 months of daily 

INH, but does not replace other recommended treatment options for LTBI.
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Table 5.3

Drug Regimens for the Treatment of LTBI*

Drug Duration Interval Minimum 

Doses Comments

INH 9 months Daily 270 • The preferred regimen is daily treatment for 

9 months

• Recommended regimen for people with HIV, for 

children, and for people with chest radiograph 

findings suggestive of previous TB disease

• DOT must be used with twice-weekly dosing

Twice 

weekly

 76

6 months Daily 180 • Not recommended for people with HIV, for 

children, or for people with chest radiograph 

findings suggestive of previous TB disease

• DOT must be used with twice-weekly dosing

Twice 

weekly

 52

INH 

and 

RPT

3 months Once 

weekly

12 • Recommended as an equal alternative to 9 

months of daily INH for otherwise healthy 

patients aged ≥12 years who were recently 

in contact with infectious TB, or who had 

tuberculin skin test or a positive blood test for 

TB infection conversions 

• The 12-dose regimen can be considered 

for other groups when it offers practical 

advantages, such as completion within a limited 

timeframe

• DOT is strongly recommended 

• Not recommended for children younger than 

2 years, HIV-infected patients taking ART, 

patients with presumed INH or RIF-resistant 

M. tuberculosis, pregnant women, or women 

expecting to become pregnant within the 

treatment period 

* For more detailed information on LTBI treatment, please refer to Targeted tuberculin testing and treatment of 

latent TB infection. MMWR 2000; 49 (No. RR-6).

http://www.cdc.gov/tb/publications/reportsarticles/mmwr/mmwr_updates.htm

* Adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin 

and pyrazinamide for treatment of latent tuberculosis infection. MMWR 2003; 52 (31).

http://www.cdc.gov/MMWR/preview/MMWRhtml/mm5231a4.htm

* Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent 

Mycobacterium tuberculosis infection. MMWR 2011; 60 (48). 

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6048a3.htm?s_cid=mm6048a3_w
Chapter 5: Treatment for Latent Tuberculosis Infection

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Table 5.4

Adverse Drug Reactions to INH

Adverse Reaction Comments

Peripheral 

neuropathy

• Uncommon at doses of 5 mg/kg

• Those at risk may also be given pyridoxine (vitamin B6) 

» Persons at high risk for neuropathy (e.g., diabetes, uremia, 

alcoholism, malnutrition, HIV infection)

» Pregnant women

» Persons with a seizure disorder

» Patients who develop signs and symptoms of peripheral 

neuropathy

Fatal hepatitis • Pregnant women are at increased risk

• Postpartum women are at increased risk, especially during the initial 

3-month postpartum period 

Elevated liver 

enzymes

• 10% to 20% of persons taking INH will have some mild elevation of 

liver enzymes. These tend to resolve even if INH is continued. 

• Discontinue INH if the following occurs:

» Measurements exceed 3 times the normal limit with 

symptoms present

» Measurements exceed 5 times the upper limit of normal 

in an asymptomatic individual

• Provide close clinical and laboratory monitoring if there are any 

signs or symptoms of hepatotoxicity or liver function test elevations 

less than the levels listed above

Rifampin (RIF) Regimen

For persons who cannot tolerate INH or have been exposed to INH-resistant TB, an alternative 

treatment regimen is 4 months of RIF. In order to be considered adequate treatment, the patient 

must receive a minimum of 120 doses administered within 6 months. RIF should not be used in 

HIV-infected persons being treated with some combinations of ART. In some situations where RIF 

cannot be used because of interactions with ART, another drug, rifabutin, may be used.

For persons who cannot tolerate INH or have been exposed to INHresistant TB, an alternative treatment regimen is 4 months of RIF.
Chapter 5: Treatment for Latent Tuberculosis Infection

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RIF should not be used in HIV-infected persons being 

treated with some combinations of ART.

Adverse Drug Reactions

Patients on treatment for LTBI should be instructed to report any signs and symptoms of adverse 

drug reactions to their health care provider, including

• Unexplained anorexia, nausea or vomiting, dark urine*, or icterus

• Persistent paresthesia of hands and feet

• Persistent weakness, fatigue, fever, or abdominal tenderness

• Easy bruising or bleeding

Peripheral neuropathy is associated with the use of INH, but is uncommon at doses of 5 mg/

kg (Table 5.4). Persons with risk factors for neuropathy (e.g., diabetes, uremia, alcoholism, 

malnutrition, HIV infection), pregnant women, and persons with seizure disorder may be given 

pyridoxine (vitamin B6) 10–50 mg/day with INH, as this may prevent neuropathy. Patients who 

develop signs and symptoms of peripheral neuropathy may also be started on vitamin B6.

About 10% to 20% of persons taking INH will have some mild, asymptomatic elevation of liver 

enzymes (ALT, AST). These abnormalities tend to resolve even if INH is continued. For this reason, 

routine monitoring of liver enzymes is not recommended for all patients receiving INH. In persons 

who experience symptoms consistent with liver injury, liver enzymes should be measured to evaluate 

for hepatotoxicity. If any of the liver enzymes exceed three times the normal limit with symptoms 

present, it is generally recommended that INH be withheld. For liver enzyme elevations less than 

three times the upper limit of normal in symptomatic patients, at minimum close clinical and 

laboratory monitoring should be instituted if treatment is to be continued. Additional information 

on monitoring patients on LTBI treatment is provided later in this chapter. 

About 10% to 20% of persons taking INH will have some 

mild, asymptomatic elevation of liver enzymes.

Some evidence suggests that pregnant women are at increased risk for fatal hepatitis associated with 

INH. This risk may also increase during the immediate postpartum period. These persons should be 

closely monitored for adverse reactions throughout the course of treatment.

Recommendation Against the Use of RIF/Pyrazinamide (PZA) Treatment Regimen

Recommendations for the use of a daily or a twice-weekly, 2-month regimen of RIF with PZA 

for LTBI treatment have changed due to associated severe liver injury. Based on the high rates of 

hospitalization and death from liver injury in patients treated with RIF and PZA for LTBI treatment, 

the American Thoracic Society (ATS) and CDC now recommend that this regimen not be offered to 

persons with LTBI. Alternative regimens are recommended for the treatment of LTBI (Table 5.1). 

RIF and PZA should continue to be administered in multidrug regimens for the treatment of 

persons with TB disease.
Chapter 5: Treatment for Latent Tuberculosis Infection

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RIF and PZA should not be offered to persons with LTBI. 

RIF and PZA should continue to be administered in multidrug 

regimens for the treatment of persons with TB disease.

Study Questions

5.14 What should an appropriate LTBI treatment regimen be based on?

(choose the one best answer)

A. Drug-susceptibility results of the source case (if known).

B. Coexisting medical illnesses.

C. Potential for drug-drug interactions.

D. A, B, and C are all correct.

E. Only A and B are correct.

5.15 Which of the following is a recommended LTBI treatment regimen?

(choose the one best answer)

A. INH given daily (270 doses) for 9 months.

B. INH and RPT given once weekly (12 doses) for 3 months.

C. INH and RIF given daily (270 doses of each drug) for 9 months.

D. A, B, and C are all correct.

E. Only A and B are correct.

5.16 Which of the following is an adverse reaction to INH?

(choose the one best answer)

A. Peripheral neuropathy

B. Fatal hepatitis

C. Elevated liver enzymes

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 5: Treatment for Latent Tuberculosis Infection

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5.17 Which of the following statements about the use of the RIF/PZA drug combination 

for treating LTBI is true? (circle the one best answer)

A. Can be used for both HIV-negative and HIV-infected patients who cannot tolerate INH.

B. Not recommended for LTBI treatment based on high rates of hospitalization and death 

from liver injury.

C. Is the recommended drug for treating pregnant women.

D. A, B, and C are all correct.

E. Only A and B are correct.

5.18 What LTBI treatment regimen may be recommended for people with a positive TST or 

IGRA result who have been exposed to INH-resistant TB disease?

(circle the one best answer)

A. RIF, at a minimum of 120 doses for 4 months.

B. RIF, at a minimum of 180 doses for 6 months.

C. RIF, at a minimum of 270 doses for 9 months.

LTBI Treatment Regimens for Specific Situations

HIV-Infected Persons

LTBI treatment of HIV-infected persons should be provided in consultation with an expert in the 

management of HIV and TB.

LTBI treatment of HIV-infected persons should be done in 

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

INH

A 9-month regimen of daily INH is considered the optimal treatment for HIV-infected adults with 

LTBI. To be considered adequate therapy, the patient must receive a minimum of 270 doses of INH 

administered within 12 months. HIV-infected children should receive 9 months of INH treatment 

for LTBI. To be considered adequate therapy for HIV-infected persons, twice-weekly regimens of 

INH must be administered by DOT and consist of at least 76 doses administered within 12 months.

In HIV-infected persons, INH may be administered together with nucleoside reverse transcriptase 

inhibitors (NRTIs), protease inhibitors, or non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

Children and adolescents who are HIV infected and/or have nutritional deficiencies should receive 

pyridoxine (vitamin B6) supplementation.
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INH-RPT (12-dose Regimen)

HIV-infected persons who are receiving ART should not take the 12-dose regimen of INH-RPT 

because the drug interactions have not been studied. However, HIV-infected persons who are 

otherwise healthy and are not receiving ART can be considered for the 12-dose regimen.

RIF

For HIV-infected patients who cannot tolerate INH or have been exposed to INH-resistant TB, an 

alternative treatment regimen is 4 months of RIF. To be considered adequate treatment, the patient 

must receive a minimum of 120 doses of RIF administered within 6 months. RIF should not be 

used in HIV-infected persons being treated with some combinations of ART. In some situations 

where RIF cannot be used because of interactions with ART, another drug, rifabutin, may be used. 

Most protease inhibitors and delavirdine should not be administered together with RIF. Rifabutin 

with appropriate dose adjustments can be used with protease inhibitors and NNRTIs (except 

delavirdine). For more information, please see Managing Drug Interactions in the Treatment of HIVRelated Tuberculosis www.cdc.gov/tb/publications/guidelines/TB_HIV_Drugs/default.htm.

Persons with Fibrotic Lesions

Persons who have a chest radiograph suggestive of old fibrotic lesions thought to represent previous 

TB disease should be treated for LTBI if they have the following:

• A positive IGRA result, or TST reaction (induration) of 5 mm or more;

• No symptoms of infectious TB disease; and

• No history of treatment for TB disease. 

These persons should be evaluated with three sputum specimens for AFB smear and culture and 

only treated for LTBI once these specimens are negative by culture. Acceptable regimen options are 

described in Table 5.5. 

Persons with evidence suggestive of healed, primary TB disease (i.e., calcified solitary pulmonary 

nodules, calcified hilar lymph nodes, and apical pleural capping) are not at increased risk for 

TB disease. Their risk for developing TB disease and the need for treatment of LTBI should be 

determined by consideration of other risk factors. 

Persons with evidence suggestive of healed, primary TB disease 

(i.e., calcified solitary pulmonary nodules, calcified hilar lymph nodes, 

and apical pleural capping) are not at increased risk for TB disease.
Chapter 5: Treatment for Latent Tuberculosis Infection

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Table 5.5

Drug Regimens for the Treatment of LTBI for Persons with Fibrotic Lesions

Drug Duration Interval Minimum 

Doses Comments

INH* 9 months Daily 270 Provide LTBI treatment for patients who have 

a chest radiograph suggestive of old fibrotic 

lesions thought to represent previous TB 

disease and

• A positive IGRA result or a TST reaction 

(induration of 5 mm or more)

• No symptoms of infectious TB disease

• No history of treatment for TB disease

• Three negative sputum smears and cultures

Twice 

weekly

 76

RIF 4 months Daily 120

* Preferred.

Contacts of Persons with Multidrug-Resistant TB

If a person is a contact of a patient with multidrug-resistant (MDR) TB, the risk of progressing to 

MDR TB disease should be considered before recommending treatment for LTBI. For persons likely 

to have been infected with a strain of M. tuberculosis resistant to both INH and RIF, alternative LTBI 

treatment regimens should be considered. The treatment of drug-resistant LTBI should be prescribed 

in consultation with an MDR TB expert.

If a person is a contact of a patient with multidrug-resistant 

(MDR) TB, the risk of progressing to MDR TB disease should be 

considered before recommending treatment for LTBI.

Pregnancy and Breast-feeding

INH administered either daily or twice weekly is the preferred regimen for the treatment of 

LTBI in pregnant women. Pregnant women taking INH should also take pyridoxine (vitamin 

B6) supplementation to ameliorate the side effects of the drug (Table 5.6). For pregnant women 

who are intolerant of INH or likely to be infected with an INH-resistant strain of M. tuberculosis, 

consultation with a TB expert is recommended.

The 12-dose regimen of INH-RPT is not recommended for pregnant women or women expecting 

to become pregnant during the treatment period because its safety in pregnancy has not yet been 

studied. 
Chapter 5: Treatment for Latent Tuberculosis Infection

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The 12-dose regimen of INH-RPT is not recommended for pregnant 

women or women expecting to become pregnant during the treatment 

period because its safety in pregnancy has not yet been studied.

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

HIV infected or diabetic, LTBI treatment should not be delayed on the basis of pregnancy alone, 

even during the first trimester. TB disease must be excluded through symptom review (to see an 

example, go to: http://health.state.ga.us/pdfs/tb/TB.Symp.Screen.09.Eng.pdf) and chest radiograph 

prior to initiation of LTBI treatment. For these women, careful clinical monitoring and/or lab 

monitoring should be conducted.

For women who are at high risk for the progression of LTBI to TB disease, 

especially those who are HIV infected or diabetic, LTBI treatment should not 

be delayed on the basis of pregnancy alone, even during the first trimester.

Breast-feeding is not contraindicated when a mother is being treated for LTBI. The amount of INH 

in the mother’s breast milk is inadequate to either harm or benefit an infant. Breast-fed infants of 

mothers who take INH should receive supplemental pyridoxine (vitamin B6). 

Table 5.6

Drug Regimens for the Treatment of LTBI

for Pregnancy and Breast-Feeding

Drug Duration Interval Minimum 

Doses Comments

INH 9 months Daily 270 • Do not delay initiation of therapy based 

on pregnancy alone, even during the first 

trimester for women who are at high risk 

for progression from LTBI to TB disease, 

especially those who are HIV infected or 

diabetic

• Breast-feeding is not contraindicated when 

a mother is being treated for LTBI

• The amount of INH provided in the mother’s 

breast milk is inadequate to either harm or 

benefit an infant. 

• Breast-feeding infants whose mothers are 

taking INH should receive supplemental 

pyridoxine (vitamin B6)

Twice 

weekly

 76
Chapter 5: Treatment for Latent Tuberculosis Infection

129

Study Questions

Case Study– Jesse

Jesse has fibrotic lesions representative of previous TB disease, a TST reaction of 5 mm, 

and no history of treatment for TB disease. 

5.19 How should Jesse be evaluated?

(choose the one best answer)

A. With a CT scan to determine the extent of lesions

B. With three sputum specimens for AFB smear and culture

C. With a bronchoscopy to obtain specimen samples

D. A, B, and C are all correct.

E. Only A and B are correct.

5.20 Once TB disease is ruled out, what should Jesse’s LTBI treatment regimen include?

(choose the one best answer)

A. 3 months of INH or 1 month of RIF 

B. 6 months of INH or 2 months of RIF 

C. 9 months of INH or 4 months of RIF 

5.21 Which of the following statements about pregnancy and breast-feeding is true?

(choose the one best answer)

A. The preferred regimen for the treatment of LTBI in pregnant women is INH taken daily 

or twice weekly, with pyridoxine supplement.

B. For pregnant women who are HIV infected, initiation of therapy should not

be delayed on the basis of pregnancy alone even during the trimester.

C. Breast-feeding is contraindicated when a mother is being treated for LTBI.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 5: Treatment for Latent Tuberculosis Infection

130

Patient Monitoring

Patient Medical Evaluation and Monitoring for LTBI Treatment

The components of patient monitoring for LTBI treatment include:

• Medical evaluation prior to LTBI treatment

• Baseline laboratory testing

• Monthly medical evaluation

• Routine laboratory monitoring 

• Treatment follow-up

Medical Evaluation Prior to LTBI Treatment

Before treatment for LTBI is started, clinicians should conduct a medical history to:

• Exclude the possibility of TB disease, including symptom review;

• Determine if there is a history of prior treatment for LTBI or TB disease; 

• Determine if there are any co-existing medical conditions that are a contraindication to LTBI 

treatment or are associated with an increased risk of adverse effects from treatment;

• Obtain information about current and previous drug therapy, including any previous or 

current adverse reactions to drugs considered for treatment of LTBI; and 

• Recommend HIV testing for all TB and LTBI patients after the patient is notified that testing 

will be performed, unless the patient declines (opt-out screening).

In addition, conducting a medical history provides an opportunity to establish rapport with the 

patient and to highlight important aspects of treatment, such as:

• Benefits of treatment;

• Importance of adherence to the treatment regimen;

• Possible adverse side effects of the regimen; and

• Establishment of an optimal follow-up plan.

A chest radiograph should be performed; LTBI treatment should only be prescribed if the radiograph 

is normal, without evidence of any findings consistent with TB disease. If there are any abnormalities 

consistent with TB disease or if the patient is symptomatic, the patient should have three sputum 

specimens collected for AFB smear and culture, and only be given treatment for LTBI once all three 

cultures are negative.

A chest radiograph should be performed; LTBI treatment 

should only be prescribed if the radiograph is normal, without 

evidence of any findings consistent with TB disease.
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Baseline Laboratory Testing

Baseline laboratory testing is not routinely indicated for all patients at the start of treatment for 

LTBI. Baseline hepatic measurements of serum AST (SGOT) or ALT (SGPT) and bilirubin are 

indicated for patients whose initial evaluation suggests a liver disorder. Baseline testing is also 

indicated for

• Patients with HIV infection;

• Women who are pregnant or in the immediate postpartum period (within 3 months after 

delivery); or

• Persons with a history of chronic liver disease (e.g., hepatitis B or C, alcoholic hepatitis or 

cirrhosis), persons who use alcohol regularly, and others who are at risk of chronic liver disease. 

Baseline laboratory testing is not routinely indicated in older persons. However, testing may be 

considered on an individual basis, particularly for patients who are taking other medications for 

chronic medical conditions. Active hepatitis and end-stage liver disease are relative contraindications 

to the use of INH or RIF for treatment of LTBI. Use of these drugs in such patients must be 

undertaken with caution. Patients with baseline abnormal liver function tests should be monitored at 

regular intervals with clinical and laboratory evaluation.

Patients with baseline abnormal liver function tests should be 

monitored at regular intervals with clinical and laboratory evaluation.

Baseline laboratory testing is not routinely indicated in older persons. 

However, testing may be considered on an individual basis, particularly for 

patients who are taking other medications for chronic medical conditions.

Monthly Evaluation

At least once a month, the patient should be evaluated for

• Adherence to the prescribed regimen;

• Signs and symptoms of TB disease; and

• Signs and symptoms of adverse effects, especially hepatitis (i.e., jaundice, loss of appetite, 

fatigue, and/or muscle and joint aches).

Routine Laboratory Monitoring

Routine laboratory monitoring during treatment of LTBI is recommended only for those whose 

baseline liver function tests are abnormal and for other persons with a risk of hepatic disease. 

Clinicians should order laboratory testing, such as liver function studies, for patients with symptoms 

compatible with hepatotoxicity, to evaluate possible adverse reactions that occur during the treatment 

regimen. If any of the liver enzymes exceed three times the normal limit with symptoms present or 

five times the upper limit of normal in an asymptomatic individual, it is generally recommended 

that INH be withheld. For liver enzyme elevations less than three times the upper limit of normal in 
Chapter 5: Treatment for Latent Tuberculosis Infection

132

symptomatic patients, at minimum close clinical and laboratory monitoring should be instituted if 

treatment is to be continued. 

Treatment Follow-Up

Patients should receive documentation of TST or IGRA results, medication taken, treatment 

duration, and treatment completion dates. They should be told to present this documentation 

when they are required to be tested for TB. Patients should also be re-educated about the signs and 

symptoms of TB disease and advised to seek medical attention if these occur. They should be advised 

that treatment greatly reduces the risk of progression to disease, but does not entirely eliminate it.

Patients should be advised that treatment greatly reduces the risk 

of progression to disease but does not entirely eliminate it.

Study Questions

5.22 Why should patients receive a medical evaluation before starting treatment for LTBI?

(choose the one best answer)

A. To exclude the possibility of TB disease

B. To determine if there is a history of prior treatment for LTBI or TB disease

C. To determine existing medical conditions

D. A, B, and C are all correct.

E. Only A and B are correct.

Case Study–Edgar, Louise, and Samantha

Edgar was admitted to the hospital last week and diagnosed with infectious TB disease. 

He lives with his wife, Louise, and 1-year-old daughter Samantha. You visit their home 

to give both Louise and Samantha a TST. Neither one has symptoms of TB disease. You 

return 2 days later to read the results. You find that Louise has 14 mm of induration, but 

Samantha has no induration.

5.23 Why should Louise, Edgar’s wife, be evaluated for LTBI treatment? 

(choose the one best answer)

A. She is a close contact of someone with infectious TB disease.

B. She has a positive skin test reaction of greater than 5 mm.

C. She has an infant daughter.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 5: Treatment for Latent Tuberculosis Infection

133

5.24 After Louise is evaluated, when should she receive LTBI treatment?

(choose the one best answer)

A. After TB disease is ruled out.

B. After it has been determined that she has never been treated for TB infection or disease.

C. After any medical problems that may complicate therapy have been ruled out.

D. A, B, and C are all correct.

E. Only A and B are correct.

5.25 Should Samantha, Edgar’s daughter, receive LTBI treatment?

(choose the one best answer)

A. Yes, she should start LTBI treatment after TB disease has been excluded because she is a 

close contact of a person with infectious TB disease and she is less than 4 years old.

B. No, because she had a negative TST.

5.26 Baseline laboratory testing is routinely indicated for which of the following patients?

(choose the one best answer)

A. HIV-infected persons

B. Pregnant women 

C. Teenagers

D. A, B, and C are all correct.

E. Only A and B are correct.

5.27 Loretta is receiving LTBI treatment and is evaluated each month by her public health 

nurse. What should she be evaluated for?

(choose the one best answer)

A. Adherence to the prescribed regimen

B. Signs and symptoms of TB disease

C. Signs and symptoms of adverse effects, especially hepatitis

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 5: Treatment for Latent Tuberculosis Infection

134

5.28 Routine laboratory monitoring is recommended for which of the following patients with 

LTBI? (circle the one best answer)

A. Persons whose baseline liver function tests are abnormal

B. Persons with a risk of hepatic disease

C. All patients receiving LTBI 

D. A, B, and C are all correct.

E. Only A and B are correct.

Chapter Summary

Treatment of LTBI is essential to controlling and eliminating TB disease in the United States. It 

substantially reduces the risk that persons infected with M. tuberculosis will progress to TB disease. 

Certain groups are at high risk of developing TB disease once infected. Targeted testing programs 

should be designed to identify persons who are at high risk for TB disease and who would benefit 

from treatment of LTBI. Targeted testing should be undertaken only if resources are identified and 

available to ensure full evaluation and treatment. There are two methods available for the detection 

of M. tuberculosis infection in the United States, the TST and IGRAs.

Persons in the following high-risk groups should be given treatment for LTBI if they have either a 

positive IGRA result or if their reaction to the tuberculin skin test is ≥5 mm:

• HIV-infected persons;

• Recent contacts of persons with infectious TB disease;

• Persons with fibrotic changes on chest radiograph consistent with prior TB disease 

(once TB disease is excluded); and

• Patients with organ transplants, and other immunosuppressed patients (including patients 

receiving the equivalent of 15 mg/day of prednisone for ≥1 month).

Persons in the following high-risk groups should be considered for treatment of LTBI if they have 

either a positive IGRA result or if their reaction to the TST is ≥10 mm:

• Recent arrivals to the United States (<5 years) from high-prevalence areas (e.g. Africa, Asia, 

Eastern Europe, Latin America, and Russia);

• Injection drug users;

• Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing 

homes, homeless shelters, and hospitals);

• Mycobacteriology laboratory personnel;

• Persons with medical conditions that increase the risk for progression to TB disease, i.e., 

silicosis, diabetes mellitus, chronic renal failure, certain types of cancer (e.g., leukemia and 

lymphomas, or cancer of the head, neck, or lung), gastrectomy or jejunoileal bypass, and 

weight loss of at least 10% from ideal body weight;
Chapter 5: Treatment for Latent Tuberculosis Infection

135

• Children younger than 5 years of age; and 

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

People without any risk factors generally should not be tested for TB infection. Testing should 

be targeted to groups at high risk for LTBI and TB disease. However, if a person without any risk 

factors is tested and has a positive IGRA result or TST reaction that is ≥15 mm, he or she should be 

evaluated for LTBI treatment once TB disease is excluded.

There are several treatment regimens available for the treatment of LTBI. Providers should choose 

the appropriate regimen based on the susceptibility results of the presumed source case (if known), 

coexisting medical illnesses, and the potential for drug-drug interactions. 

INH Regimens

When INH alone is given to persons with TB disease, resistance may develop. For this reason, 

persons suspected of having TB disease should receive the recommended multidrug regimen for 

treatment of TB disease rather than INH monotherapy until the diagnosis is confirmed or excluded.

There are two options for treatment with INH:

• 9-month regimen

• 6-month regimen

INH is normally used alone for treatment of LTBI in a single daily dose of 300 mg in adults and 

10–20 mg/kg body weight in children, not to exceed 300 mg per dose. INH can be given two times 

a week at a dosage of 20–40 mg/kg by DOT for LTBI for children, or 900 mg for adults. 

The 9-month regimen is the preferred because it is more efficacious. Treatment for LTBI for 6 

months rather than 9 months may be more cost-effective and result in greater adherence by patients; 

therefore, local programs may prefer to implement the 6-month regimen rather than the 9-month 

regimen. Every effort should be made to ensure that patients adhere to treatment for LTBI infection 

for at least 6 months. 

9-Month INH Regimen

A 9-month INH regimen is considered optimal treatment. In order to be considered adequate 

treatment, the patient must receive a minimum of 270 doses administered within 12 months. The 

preferred regimen for children 2 to 11 years of age is 9 months of daily INH. Patients may be treated 

with a twice-weekly regimen as an alternative as long as they are undergoing DOT. In a twice-weekly 

regimen, 76 doses administered within 12 months is considered adequate therapy. 

6-Month INH Regimen

A 6-month INH regimen also provides substantial protection against developing TB disease, but it is 

less protective than the 9-month regimen. In order to be considered adequate treatment, the patient 

must receive a minimum of 180 doses administered within 9 months. Patients may be treated 

with a twice-weekly regimen given as DOT as an alternative. In a twice-weekly regimen, 52 doses 

administered within 9 months is considered adequate therapy. This regimen is not recommended for 

children, or immunosuppressed persons, or those with evidence of previous TB on chest radiograph.
Chapter 5: Treatment for Latent Tuberculosis Infection

136

3-Month INH-RPT Regimen (12-Dose Regimen)

The 12-dose regimen is a combination of INH and RPT given in 12 once-weekly doses under DOT. 

Because missed doses, altered dosing intervals or amounts, or incomplete treatment could jeopardize 

the 12-dose regimen efficacy or safety, DOT is strongly recommended for this regimen. Patients 

using the 12-dose regimen should undergo monthly clinical monitoring, including inquiries about 

side effects and a physical assessment for signs of adverse effects.

The 12-dose regimen does not replace other recommended treatment options for LTBI, but can 

be considered an equal option to the standard INH 9-month daily regimen for treating LTBI in 

otherwise healthy people, 12 years of age or older, who were recently in contact with infectious TB, 

or who had tuberculin skin test or blood test for TB infection conversions.

The dosage for a combination 12-dose regimen of INH and RPT is: 

Isoniazid (INH)

• 15 mg/kg rounded up to the nearest 50 or 100 mg, with a 900 mg maximum.

Rifapentine (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.

INH is formulated as 100 mg and 300 mg tablets. RPT is formulated as 150 mg tablets packaged in 

blister packs that should be kept sealed until usage. New formulations with larger dosage per tablet 

and fixed-dose INH-RPT combinations are in development.

For persons who are at especially high risk for TB disease and are either suspected of nonadherence 

or given an intermittent dosing regimen, DOT for LTBI should be considered. This method of 

treatment is especially appropriate if the person in need of LTBI treatment lives with a household 

member who is on DOT for TB disease, or lives in an institution or facility where treatment for TB 

infection can be observed by a staff member. It is necessary to exclude TB disease before starting 

LTBI treatment. 

Baseline laboratory testing is not routinely indicated for all patients at the start of treatment for 

LTBI. Baseline hepatic measurements of serum AST (SGOT) or ALT (SGPT) and bilirubin are 

indicated for patients whose initial evaluation suggests a liver disorder. Baseline testing is also 

indicated for:

• Patients with HIV infection;

• Women who are pregnant or in the immediate postpartum period (within 3 months of 

delivery); or

• Persons with a history of chronic liver disease (e.g., hepatitis B or C, alcoholic hepatitis or 

cirrhosis), persons who use alcohol regularly, and others who are at risk of chronic liver disease.
Chapter 5: Treatment for Latent Tuberculosis Infection

137

References

CDC. Controlling tuberculosis in the United States: Recommendations from the American Thoracic 

Society, CDC, and the Infectious Diseases Society of America. MMWR 2005; 54 (No. RR-12).

www.cdc.gov/mmwr/preview/mmwrhtml/rr5412a1.htm

CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care 

settings, 2005. MMWR 2005; 54 (No. RR-17). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e

CDC. Guidelines for the investigation of contacts of persons with infectious tuberculosis: 

Recommendations from the National Tuberculosis Controllers Association and CDC. MMWR

2005; 54 (No. RR-15). www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a1.htm

CDC. Management of persons exposed to multidrug-resistant tuberculosis. MMWR 1992; 

41 (RR-11): 59–71. www.cdc.gov/mmwr/preview/mmwrhtml/00031296.htm

CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR 2000; 

49 (No. RR-06). www.cdc.gov/MMWR/preview/MMWRhtml/rr4906a1.htm

Updates:

Adverse event data and revised American Thoracic Society/CDC recommendations against the 

use of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 

2003. MMWR 2003; 52 (31):735– 9. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm

Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis 

infection, and revisions in American Thoracic Society/CDC recommendations—United States, 

2001. MMWR 2001; 50 (34):733– 5 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5034a1.htm

Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent 

tuberculosis infection—New York and Georgia, 2000. MMWR 2001; 50 (15): 289– 91. 

www.cdc.gov/mmwr/preview/mmwrhtml/mm5015a3.htm

CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat 

latent Mycobacterium tuberculosis infection. MMWR 2011; 60 (48): 1650– 1653.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6048a3.htm?s_cid=mm6048a3_w

Errata (February 3, 2012)

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a7.htm

Chapter 6: Treatment of Tuberculosis Disease

139

Table of Contents

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141

Treatment and Monitoring Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

Adherence Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

TB Disease Treatment Regimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

TB Disease Treatment Regimens for Specific Situations . . . . . . . . . . . . . . . . . . . . . . . . . . . 165

Patient Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176

Evaluating Response to Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187

Chapter Objectives

After working through this chapter, you should be able to 

• Describe tuberculosis (TB) disease treatment adherence strategies;

• Identify anti-TB drugs;

• Describe treatment regimens for TB disease;

• Describe patient monitoring; and

• List common adverse drug reactions to TB medications.

Chapter 6 

Treatment of Tuberculosis Disease

Chapter 6: Treatment of Tuberculosis Disease

141

Introduction

The major goals of treatment for TB disease are to

• Cure the individual patient;

• Minimize risk of death and disability; and

• Reduce transmission of M. tuberculosis to other persons. 

To ensure that these goals are met, TB disease must be treated for at least 6 months and in some cases 

even longer. Most of the bacteria are killed during the first 8 weeks of treatment; however, there are 

persistent organisms that require longer treatment. If treatment is not continued for a long enough 

duration, the surviving bacteria may cause the patient to become ill and infectious again, potentially 

with drug-resistant disease.

There are several options for daily and intermittent therapy, but the goal of treatment for TB disease 

should be to provide the safest and most effective therapy in the shortest period of time. Given 

adequate treatment, almost all patients will recover and be cured. 

Regimens for the treatment of TB disease must contain multiple drugs to which the bacteria 

are susceptible. The standard of care for initiating treatment of TB disease is four-drug therapy. 

Treatment with a single drug can lead to the development of a bacterial population resistant to that 

drug. Likewise, the addition of a single drug to a failing anti-TB regimen can lead to additional 

resistance. When two or more drugs to which in vitro susceptibility has been demonstrated are given 

together, each helps prevent the emergence of tubercle bacilli resistant to the others.

The standard of care for initiating treatment of TB disease is 

four-drug therapy. Treatment with a single drug can lead to the 

development of a bacterial population resistant to that drug.

Study Questions

6.1 The major goals for treatment of TB disease include which of the following?

A. Curing the individual patient

B. Minimizing risk of death and disability

C. Reducing transmission of M. tuberculosis to other persons

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 6: Treatment of Tuberculosis Disease

142

Are the following statements about TB treatment true or false?

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.)

Statements True or False

____ 6.2 Most of the TB bacteria are killed during the first 8 weeks of 

treatment. However, some persistent organisms require longer 

treatment.

____ 6.3 Regimens for the treatment of TB disease need to only 

contain one drug to which the bacteria are susceptible.

____ 6.4 Treatment that is not continued for a long enough time allows 

the surviving bacteria to cause the patient to become ill and 

infectious again.

____ 6.5 Treatment with a single drug cannot lead to the development 

of a bacterial population resistant to that drug.

____ 6.6 When two or more drugs to which in vitro susceptibility has 

been demonstrated are given together, each helps prevent the 

emergence of tubercle bacilli resistant to the other drugs(s).

____ 6.7 Given adequate treatment, almost all patients will recover and 

be cured.

A. True

B. False
Chapter 6: Treatment of Tuberculosis Disease

143

Treatment and Monitoring Plan

For each patient with newly diagnosed TB disease, a specific treatment and monitoring plan should 

be developed in collaboration with the local TB control program within 1 week of the presumptive 

diagnosis. This plan should include:

• Description of the TB treatment regimen; 

• Methods of assessing and ensuring adherence to the TB treatment regimen; 

• Methods to monitor for adverse reactions; and

• Methods for evaluating treatment response.

Study Question

6.8 Which of the following should NOT be included in a treatment and monitoring plan?

(choose the one best answer)

A. Description of the TB treatment regimen

B. Methods of assessing and ensuring adherence to the TB treatment regimen

C. Methods to monitor for adverse reactions

D. Methods to prevent a patient returning to work when noninfectious

E. Methods for evaluating treatment response

Adherence Strategies

To treat TB disease and prevent acquired drug resistance, clinicians must ensure that their patients 

with TB disease follow the recommended course of treatment. However, ensuring that patients 

adhere to treatment can be difficult because patients are often unable or reluctant to take multiple 

medications for several months. Nonadherence to treatment is a major problem in TB control. 

Inadequate treatment can lead to 

• Treatment failure; 

• Relapse; 

• Ongoing transmission; and 

• Development of drug resistance. 

Responsibility for successful treatment is assigned to the health-care provider, not the patient. 

Health-care professionals should consult their health department’s TB control program to ensure 

their TB patients are able to adhere to a prescribed treatment regimen. The TB control program 

should assist the health-care professional in evaluating patient barriers to adherence and recommend 

directly observed therapy (DOT) and the use of incentives and enablers that may assist the patient in 

completing the recommended therapy. 
Chapter 6: Treatment of Tuberculosis Disease

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Inadequate treatment can lead to treatment failure, relapse, ongoing 

transmission, and the development of drug resistance.

Responsibility for successful treatment is assigned to 

the health-care provider, not the patient.

If these efforts are unsuccessful, the TB control program should take more restrictive action. The 

TB program should consider court-ordered DOT or, if all other measures fail, the involuntary 

isolation of a patient who is unwilling or unable to complete treatment. This is necessary to protect 

the general public from patients who are infectious, at risk of becoming infectious, or at risk for 

developing drug-resistant TB disease. A patient may be involuntarily isolated, but the patient cannot

be forced to swallow anti-TB drugs. Involuntary isolation should only be pursued as a last resort after 

all less-restrictive measures have failed.

Patient Education

Educating patients about TB disease helps ensure their successful completion of therapy. Health-care 

providers must take the time to explain clearly to patients what medication should be taken, how 

much, how often, and when. Patients should be clearly informed about possible adverse reactions 

to the medications they are taking and when to seek necessary medical attention. Providing patients 

with the knowledge they need regarding the consequences of not taking their medicine correctly 

is very important. In addition, patients should be educated about infection control measures and 

potential need for isolation (Table 6.1). HIV testing and counseling is recommended for all patients 

with TB disease in all health-care settings. The patient must first be notified that testing will be 

performed. The patient has the right to decline HIV testing and counseling (opt-out screening). 

Table 6.1

Patient Education

Topics to Include When Educating Patients

• What medication should be taken, how much, how often, and when

• Possible adverse reactions to the medications

• When to seek necessary medical attention

• Consequences of not taking their medicine correctly

• TB infection control measures and potential need for isolation

HIV testing and counseling is recommended for all patients 

with TB disease in all health-care settings.
Chapter 6: Treatment of Tuberculosis Disease

145

Case Management

Case management is a strategy used to ensure that patients complete treatment for TB disease. There 

are three elements of case management: 

1. Assigning responsibility;

2. Conducting a regular systematic review; and

3. Developing a plan to address barriers to adherence.

Case managers are health department employees, usually nurses or public health professionals, who 

are assigned primary responsibility for the management of specific patients. Case managers are 

held accountable for ensuring that each patient is educated about TB and treatment, ensuring that 

therapy is continuous and complete, and confirming that all contacts are evaluated according to 

CDC/National Tuberculosis Controllers Association guidelines. Some specific responsibilities may 

be assigned to other persons such as clinic supervisors, outreach workers, health educators, social 

workers, and human service workers. Case management is a patient-centered strategy. Whenever 

possible, a worker who has the same cultural and linguistic background as the patient should be 

assigned as case manager, to be able to help develop an individualized treatment adherence plan with 

the patient. 

Case managers are held accountable for ensuring that each patient is 

educated about TB and treatment, ensuring that therapy is continuous 

and complete, and confirming that all contacts are evaluated according 

to CDC/ National Tuberculosis Controllers Association guidelines.

Directly Observed Therapy (DOT)

DOT is a component of case management that helps ensure patients adhere to therapy. It is the 

method whereby a trained health-care worker or another trained designated person watches a 

patient swallow each dose of anti-TB drugs and documents it. DOT is the preferred core 

management strategy recommended by CDC for treatment of TB disease and, if resources allow, 

for latent tuberculosis infection (LTBI) treatment. DOT can reduce the development of drug 

resistance, treatment failure, or relapse after the end of treatment. Good case management, which 

includes establishing a relationship with the patient and addressing barriers to adherence, facilitates 

successful DOT.

DOT is the preferred core management strategy recommended 

by CDC for treatment of TB disease and, if resources allow, 

for latent tuberculosis infection (LTBI) treatment.

Nearly all the treatment regimens for drug-susceptible TB disease can be given intermittently if they 

are directly observed. Using intermittent regimens reduces the total number of doses a patient must 

take, as well as the total number of encounters with the health-care provider or outreach worker, 

making these regimens more cost-effective. Drug-resistant TB disease should always be treated with 
Chapter 6: Treatment of Tuberculosis Disease

146

a daily regimen and under direct observation. There are no intermittent regimens for treatment of 

multidrug-resistant (MDR) TB. If anti-TB drugs for the treatment of MDR TB need to be given 

twice daily, then DOT should be provided twice daily as well.

Nearly all the treatment regimens for drug-susceptible TB disease 

can be given intermittently if they are directly observed.

Drug-resistant TB disease should always be treated with a daily 

regimen and under direct observation. There are no intermittent 

regimens for treatment of multidrug-resistant (MDR) TB.

It is important that DOT be carried out at times and in locations that are as convenient as possible 

for the individual patient (Figures 6.1 and 6.2). Therapy may be directly observed in a medical office 

or clinic setting, but can also be observed by an outreach worker in the field (e.g., patient’s home, 

place of employment, school, or other mutually agreed-upon place). In some situations, staff of 

correctional facilities or drug treatment programs, home health-care workers, maternal and child 

health staff, or designated community members may provide DOT. In general, family members 

should not be the providers of DOT.

Figure 6.1

Conducting DOT in a

Clinic Setting

Figure 6.2

Conducting DOT in a Location 

Convenient for the Patient

DOT should be used for all children and adolescents with TB disease. Even when drugs are given by 

DOT, adherence to and tolerability of the regimen must be monitored closely. Parents should not be 

relied on to supervise DOT.
Chapter 6: Treatment of Tuberculosis Disease

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Incentives and Enablers

Incentives and enablers should be used to ensure adherence to therapy (Figure 6.3). Incentives are 

small rewards given to patients to encourage them to take their medicines and to keep DOT or clinic 

appointments. Enablers are things that help the patient receive treatment, such as bus fare to get to 

the clinic. Incentives and enablers should be chosen according to the patient’s needs, and they are 

frequently offered along with DOT.

Figure 6.3

Incentives and Enablers

Fixed-Dose Combination Drugs

Although there is no evidence indicating that fixed-dose combination medications are superior to 

individual drugs, expert opinion suggests that these formulations should be used when DOT is given 

daily or when DOT is not possible. The use of fixed-dose combination capsules or tablets facilitates 

DOT administration by minimizing the chance for error through the use of fewer tablets and may 

reduce the risk of acquired drug resistance since one medication cannot be selectively taken. In the 

United States, the Food and Drug Administration (FDA) has approved fixed-dose combinations 

of isoniazid and rifampin (Rifamate®) and of isoniazid, rifampin, and pyrazinamide (Rifater®). 

Clinicians should become familiar with the management of TB disease using these fixed-dose 

combination drugs.

The use of fixed-dose combination capsules or tablets facilitates 

DOT administration by minimizing the chance for error through 

the use of fewer tablets and may reduce the risk of acquired drug 

resistance since one medication cannot be selectively taken.
Chapter 6: Treatment of Tuberculosis Disease

148

Self-Administered Therapy

Patients on self-administered therapy should be asked routinely about adherence at follow-up visits. 

Pill counts should be performed consistently, and urine or blood tests can be used periodically to 

check for the presence of urine drug metabolites or appropriate blood serum level of the drugs. In 

addition, the response to treatment should be monitored closely for all patients. If culture results 

have not become negative after 2 months of treatment, the patient should be reevaluated and DOT 

should be considered for the remainder of treatment.

Study Questions

6.9 Inadequate treatment can lead to which of the following?

(choose the one best answer)

A. Treatment failure

B. Relapse

C. Ongoing transmission

D. Development of drug resistance

E. A, B, C, and D are all correct.

6.10 The responsibility for successful treatment is assigned to which of the following?

(choose the one best answer)

A. The patient

B. The health-care provider

C. The family of the patient

D. A, B, and C are all correct.

E. Only A and B are correct.

6.11 What should be included when educating a patient about TB treatment?

(choose the one best answer)

A. How to take the medication

B. Adverse reactions to the medications

C. Consequences of not taking the medication correctly

D. TB infection control measures

E. A, B, C, and D are all correct.
Chapter 6: Treatment of Tuberculosis Disease

149

6.12 What is case management? 

(choose the one best answer)

A. Includes assigning responsibilities, conducting a regular systematic review of the case, and 

developing a plan to address barriers to adherence.

B. Can be used to ensure that patients complete treatment for TB disease.

C. Can be used to identify all cases of TB from a source case.

D. A, B, and C are all correct.

E. Only A and B are correct.

6.13 What is DOT? 

(choose the one best answer)

A. A supervisor watches a health-care worker give a patient a bottle of prescribed pills.

B. A physician sees the patient once a month and counts the remaining pills in the 

medication bottles.

C. A health-care worker or another designated person watches the patient swallow each dose 

of the prescribed drugs.

D. The nurse uses special urine tests to detect the presence of medicine in the patient’s urine.

6.14 Which of the following statements about DOT is true?

(choose the one best answer)

A. Is the preferred core management strategy for treatment of TB disease.

B. Can reduce the development of drug resistance, treatment failure, or relapse after the 

end of treatment. 

C. Parents can always be relied upon to give DOT to their children. 

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 6: Treatment of Tuberculosis Disease

150

6.15 Which of the following statements about intermittent treatment regimens and DOT is 

true? (choose the one best answer)

A. Reduces the total number of doses the patient must take.

B. Reduces the total number of encounters with the health-care provider.

C. Are always used for drug-resistant TB disease.

D. A, B, and C are all correct.

E. Only A and B are correct.

6.16 DOT should always be used for all children and adolescents with TB disease. 

(circle the one best answer)

A. True

B. False
Chapter 6: Treatment of Tuberculosis Disease

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TB Disease Treatment Regimens

Current Anti-TB Drugs

Currently, there are 10 drugs approved by the U.S. Food and Drug Administration (FDA) for the 

treatment of TB disease (Table 6.2). In addition, the fluoroquinolones (levofloxacin, moxifloxacin, 

and gatifloxacin), although not approved by the FDA for TB disease, are commonly used to treat 

TB disease caused by drug-resistant organisms or for patients who are intolerant of some first-line 

drugs. Rifabutin, approved for use in preventing Mycobacterium avium complex disease in patients 

with HIV infection but not approved for TB disease, is useful for treating TB disease in patients 

concurrently taking drugs that interact with rifampin (e.g., certain antiretroviral drugs). Amikacin 

and kanamycin, nearly identical aminoglycoside drugs used in treating patients with TB disease 

caused by drug-resistant organisms, are not approved by the FDA for treatment of TB.

Of the approved drugs, isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide 

(PZA) are considered first-line anti-TB drugs and form the core of standard treatment regimens 

(Figure 6.4) (Table 6.2). Rifabutin (RBT) and rifapentine (RPT) may also be considered firstline drugs under certain circumstances. RBT is used as a substitute for RIF in the treatment of all 

forms of TB caused by organisms that are known or presumed to be susceptible to this agent. RBT 

is generally reserved for patients for whom drug-drug interactions preclude the use of rifampin. 

Streptomycin (SM) was formerly considered to be a first-line drug and, in some instances, is still 

used in the initial treatment regimen. However, an increasing prevalence of resistance to SM in many 

parts of the world has decreased its overall usefulness. The remaining drugs are reserved for special 

situations such as drug intolerance or resistance. 

INH, RIF, PZA, and EMB are considered first-line anti-TB drugs 

and form the core of standard treatment regimens.

Figure 6.4

First-line Anti-TB Agents

From left to right: INH, RIF, PZA, and EMB

form the core of initial treatment regimens.
Chapter 6: Treatment of Tuberculosis Disease

152

Table 6.2

Anti-TB Drugs Currently Used in the United States

Drug 

Classes Anti-TB Drugs Comments

First-line 

drugs

Isoniazid (INH) INH, RIF, PZA, and EMB form the core of initial treatment 

regimen. Rifampin (RIF)

Pyrazinamide (PZA)

Ethambutol (EMB)

Rifabutin* (RBT) May be used as a substitute for RIF in the treatment of 

all forms of TB caused by organisms that are known or 

presumed to be susceptible to this agent.

Rifapentine (RPT) May be used once weekly with INH in the continuation 

phase of treatment for HIV-negative patients with 

noncavitary, drug-susceptible pulmonary TB who have 

negative sputum smears at completion of the initial 

phase of treatment.

Secondline drugsStreptomycin (SM) • SM was formerly considered to be a first-line drug and 

in some instances, is still used in initial treatment.

• Increasing prevalence of resistance to SM in many 

parts of the world has decreased its overall usefulness.

Cycloserine These drugs are reserved for special situations such as 

drug intolerance or resistance. Capreomycin

ρ-Aminosalicylic acid

Levofloxacin*

Moxifloxacin*

Gatifloxacin*

Amikacin/Kanamycin*

Ethionamide

* Not approved by the U.S. Food and Drug Administration for use in the treatment of tuberculosis.

Rating System for TB Disease Treatment Recommendations

The recommended treatment regimens are based, in large part, on evidence from clinical trials and 

are rated on the basis of a system developed by the U.S. Public Health Service (USPHS) and the 

Infectious Diseases Society of America (IDSA) (Table 6.3).
Chapter 6: Treatment of Tuberculosis Disease

153

TB Disease Treatment Regimens 

There are four basic treatment regimens recommended for treating adults with TB disease caused 

by organisms that are known or presumed to be susceptible to INH, RIF, PZA, and EMB. Each 

treatment regimen consists of an initial 2-month treatment phase followed by a continuation phase 

of either 4 or 7 months (Table 6.5). The 4-month continuation phase is used for the majority of 

patients. Although these regimens are broadly applicable, there are modifications that should be 

made under specified circumstances (Tables 6.3 and 6.4).

There are four basic treatment regimens recommended for treating 

adults with TB disease caused by organisms that are known or 

presumed to be susceptible to INH, RIF, PZA, and EMB. Each 

treatment regimen consists of an initial 2-month treatment phase 

followed by a continuation phase of either 4 or 7 months.

Initial Phase

The initial phase of treatment is crucial for preventing the emergence of drug resistance 

and determining the ultimate outcome of the regimen. Four drugs—INH, RIF, PZA, and 

EMB—should be included in the initial treatment regimen until the results of drug-susceptibility 

tests are available. Each of the drugs in the initial regimen plays an important role. INH and RIF 

allow for short-course regimens with high cure rates. PZA has potent sterilizing activity, which allows 

further shortening of the regimen from 9 to 6 months. EMB helps to prevent the emergence of 

RIF resistance when primary INH resistance is present. If drug-susceptibility test results are known 

and the organisms are fully susceptible, EMB need not be included. For children whose clarity 

or sharpness of vision cannot be monitored, EMB is usually not recommended except when the 

risk of drug resistance is high or for children who have “adult-type” (upper lobe infiltration, cavity 

formation) TB disease.

Continuation Phase

The continuation phase of treatment is given for either 4 or 7 months. The 4-month continuation 

phase should be used in patients with uncomplicated, noncavitary, drug-susceptible TB, if there 

is documented sputum conversion within the first 2 months. The 7-month continuation phase is 

recommended only for

• Patients with cavitary or extensive pulmonary TB disease caused by drug-susceptible organisms 

and whose sputum culture obtained at the time of completion of 2 months of treatment is 

positive; 

• Patients whose initial phase of treatment did not include PZA; or

• Patients being treated with once-weekly INH and RPT and whose sputum culture at the time 

of completion of the initial phase (i.e., after 2 months) is positive.
Chapter 6: Treatment of Tuberculosis Disease

154

Table 6.3

Drug Regimens for Pulmonary TB in Adults Caused by

Drug-Susceptible Organisms*

Initial Phase Continuation Phase

Regimen Drugs Interval and Doses± § Regimen Drugs Interval and Doses± § Range of 

Total Doses

1 INH

RIF

PZA

EMB

7 days/week for 56 doses 

(8 weeks)

or

5 days /week for 40 doses 

(8 weeks)¶

1a INH

RIF

7 days/week for 126 

doses (18 weeks)

or

5 days/week for 90 

doses (18 weeks)

182– 130

(26 weeks)

1b# INH

RIF

2 days/week for 36 

doses (18 weeks)

92– 76

(26 weeks)

1c** INH

RPT

1 day/week for 18 doses 

(18 weeks)¶

74– 58

(26 weeks)

2 INH

RIF

PZA

EMB

7 days/week for 14 doses 

(2 weeks), then 2 days/

week for 12 doses (6 

weeks)

or

5 days/week for 10 doses 

(2 weeks),¶

then 2 days/week for 12 

doses (6 weeks)

2a# INH

RIF

2 days/week for 36 

doses (18 weeks)¶

62– 58

(26 weeks)

2b** INH

RPT

1 day/week for 18 doses 

(18 weeks)¶

44– 40

(26 weeks)

3 INH

RIF

PZA

EMB

3 times weekly for 

24 doses (8 weeks)

3a INH

RIF

3 times weekly for 54 

doses (18 weeks)¶

78

(26 weeks)

4 INH

RIF

EMB

7 days/week for 56 doses 

(8 weeks) 

or

5 days/week for 40 doses 

(8 weeks)¶

4a INH

RIF

7 days/week for 217 

doses (31 weeks)

or

5 days/week for 155 

doses (31 weeks)¶

273– 195

(39 weeks)

4b# INH

RIF

Twice weekly for 62 

doses (31 weeks)¶

118– 102

(39 weeks)

INH = isoniazid RIF = rifampin PZA = pyrazinamide EMB = ethambutol RPT = rifapentine

 * For more information on strength of recommendation and quality of supporting evidence, refer to treatment 

of tuberculosis guidelines. MMWR 2003; 52 (No.RR-11).

± When DOT is used, drugs may be given 5 days/week and the necessary doses adjusted accordingly.

§ Patients with cavitation on initial chest x-ray and positive cultures at completion of 2 months of therapy should 

receive a 7-month continuation phase.

¶ Patients on regimens given less than 7 days a week should receive DOT.

# Regimens given less than 3 times a week are not recommended for HIV-infected patients with CD4+ counts 

less than 100

** Used only for HIV-negative patients with negative sputum smears at completion of 2 months of therapy and 

who do not have cavitation on initial chest x-ray. For patients started on this regimen and found to have 

positive culture from the 2-month specimen, treatment should be extended an extra 3 months.
Chapter 6: Treatment of Tuberculosis Disease

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Table 6.4

Dosage Recommendations for the Treatment of TB in Adults and Children1

Dose in mg/kg (maximum dosage in parentheses)

Drug Adults/Children2 Daily 1 time/week3 2 times/week3 3 times/week3

INH

Adults 5 mg/kg

(300 mg)

15 mg/kg 

(900 mg)

15 mg/kg

(900 mg)

15 mg/kg

(900 mg)

Children 10– 15 mg/kg

(300 mg)

20– 30 mg/kg

(900 mg)

RIF

Adults 10 mg/kg

(600 mg)

10 mg/kg

(600 mg)

10 mg/kg

(600 mg)

Children 10– 20 mg/kg

(600 mg)

10– 20 mg/kg

(600 mg)

RBT

Adults 5 mg/kg

(300 mg)

5 mg/kg

(300 mg)

5 mg/kg

(300 mg)

Children Appropriate dosing for children unknown

RPT

Adults

10 mg/kg

(600 mg) 

(continuation phase)

Children This drug is not approved for use in children

PZA

Adults

weight

40– 55 kg 18.2– 25 mg/kg

(1000 mg)

36.4– 50 mg/kg

(2000 mg)

27.3– 37.5 mg/kg

(1500 mg)

56– 75 kg 20– 26.8 mg/kg

(1500 mg)

40– 53.6 mg/kg

(3000 mg)

33.3– 44.6 

(2500 mg)

76– 90 kg 22.2–26.3 mg/kg

(2000 mg)

44.4– 52.6 mg/kg

(4000 mg)

33.3– 39.5 mg/kg

(3000 mg)

Children 15– 30 mg/kg

(2000 mg)

50 mg/kg

(2000 kg)

EMB4

Adults

weight

40– 55 kg 14.5– 20 mg/kg

(800 mg)

36.4– 50 mg/kg

(2000 mg)

21.8– 30 mg/kg

(1200 mg)

56– 75 kg 16– 21.4 mg/kg 

(1200 mg)

37.3– 50 mg/kg

(2800 mg)

26.7– 35.7 mg/kg

(2000 mg)

76– 90 kg 17.8– 21.1 mg/kg

(1600 mg)

44.4– 52.6 mg/kg

(4000 mg)

26.7– 31.6 mg/kg

(2400 mg)

Children 15– 20 mg/kg

(1000 mg)

50 mg/kg

(2500 mg)

INH= isoniazid RIF= rifampin RBT= rifabutin RPT= rifapentine PZA= pyrazinamide EMB= ethambutol

 1 Although these regimens are broadly applicable, modifications may be needed for certain circumstances 

(patients on antiretroviral therapy [ART]). For more information, refer to treatment of tuberculosis guidelines. 

MMWR 2003; 52 (No.RR-11).

 2 For purposes of this document, adult dosing begins at age 15 years. Children weighing more than 40 kg 

should be dosed as adults. Adjust doses as the patient’s weight changes.

 3 All patients prescribed an intermittent regimen should be given DOT.

 4 Ethambutol should be used with caution in young children since it is difficult to monitor their vision. However, 

if they have TB that is resistant to INH or RIF, a dose of 15 mg/kg per day can be used.
Chapter 6: Treatment of Tuberculosis Disease

156

Treatment Completion

Treatment completion is defined primarily as the ingestion of the total number of doses prescribed 

within the specified time frame. The duration of therapy depends on the drugs used, the drugsusceptibility test results of the isolate, and the patient’s response to therapy (see Chapter 4, 

Drug-Susceptibility Testing). Most patients with previously untreated pulmonary TB disease can 

be treated with either a 6-month or a 9-month regimen, although the 6-month regimen is used 

for the majority of patients. All 6-month regimens must contain INH, RIF, and initially, PZA. 

The goal is to complete all doses within 1 year (Table 6.5).

The duration of therapy depends on the drugs used, the drug susceptibility 

test results of the isolate, and the patient’s response to therapy.

Most patients with previously untreated pulmonary TB disease can 

be treated with either a 6-month or a 9-month regimen, although 

the 6-month regimen is used for the majority of patients.
Chapter 6: Treatment of Tuberculosis Disease

157

Table 6.5

TB Treatment Phases

Phase Purpose Treatment

Initial phase • Kills most of the tubercle 

bacilli during the first 8 

weeks of treatment, but 

some bacilli can survive 

longer

• Prevents the emergence 

of drug resistance

• Determines the ultimate 

outcome of the regimen

Initial 2-month treatment regimen

• Includes four drugs in the treatment 

(usually INH, RIF, PZA, and EMB)

• Each of the drugs plays an important role 

for short-course regimens with high cure 

rates

• Multiple drugs are needed to prevent the 

development of drug-resistant TB disease

Continuation 

phase

• Kills remaining tubercle 

bacilli (after initial phase)

• If treatment is not

continued long enough, 

the surviving bacilli may 

cause TB disease in the 

patient at a later time

An addition of either 4 or 7 months of 

treatment 

• 4 months is used for majority of patients

• 7 months is recommended only for persons 

» Who have drug-susceptible cavitary or 

extensive pulmonary TB disease and 

whose sputum culture obtained at 

the time of completion of 2 months of 

treatment is positive

» Whose initial phase of treatment did 

not include PZA

» Who are treated with once-weekly INH 

and RPT and whose sputum culture at 

the time of completion of the initial 

phase is positive

Treatment 

completion

Defines the number of 

doses ingested within a 

specified time frame

Duration depends on 

• Drugs used

• Drug susceptibility test 

results of the isolate

• Patient’s response to 

therapy

Most patients with previously untreated 

pulmonary TB disease can be treated with 

either

• 6-month regimen (preferred) containing 

INH, RIF, and initially PZA

or 

• 9-month regimen containing INH and RIF
Chapter 6: Treatment of Tuberculosis Disease

158

Follow-Up After Treatment

Routine follow-up after treatment is not necessary for patients who have had a satisfactory response 

to a 6- or 9-month regimen with both INH and RIF (Table 6.6). Patients whose organisms were 

fully susceptible to the drugs being used should be instructed to promptly report the development of 

any symptoms, particularly prolonged cough, fever, or weight loss. Patients with resistance to both 

INH and RIF should be monitored for 2 years post-treatment. For patients with organisms resistant 

to INH or RIF, follow-up evaluation must be individualized.

Table 6.6 

Follow-Up After Treatment

Patients Type of Follow-Up

Have a satisfactory response to 6- or 9- month 

regimen with both INH and RIF

Routine follow-up after treatment is not

necessary

Have organisms that were fully susceptible to 

drugs being used

Patients should promptly report any of the 

following symptoms: 

• Prolonged cough

• Fever

• Weight loss

Have organisms resistant to INH and RIF Patients should be monitored for 2 years posttreatment 

Have organisms resistant to INH or RIF Follow-up must be individualized

Treatment Interruptions

Interruptions in the treatment of TB disease are common. Health-care providers are responsible 

for deciding whether to restart a complete course of treatment or to continue as intended. These 

decisions should be based on when the interruption occurred and the duration of the interruption. 
Chapter 6: Treatment of Tuberculosis Disease

159

Treatment Interruption During Initial Phase

If the interruption occurred during the initial phase, the following guidelines apply (Figure 6.5) 

(Table 6.7):

• Lapse is ≥14 days–restart treatment from the beginning 

• Lapse is <14 days–continue treatment to complete planned total number of doses (as long as 

all doses are completed within 3 months)

Figure 6.5

Algorithm for Management of

Initial Phase Treatment Interruptions

Is it 

for <14 

days?

Start over from 

the beginning

Start over from 

the beginning

No Yes

Treatment is 

interrupted

Continue treatment

to complete total

doses required

Can 

the initial 

phase treatment 

be completed 

within 3 

months?

No Yes

Treatment Interruption During Continuation Phase

If the interruption occurred during the continuation phase, the following guidelines apply 

(Figure 6.6) (Table 6.7). If the patient received:

• ≥80% of doses, and sputum was acid-fast bacilli (AFB) smear negative on initial 

testing–further therapy may not be necessary;

• ≥80% of doses, and sputum was AFB smear positive on initial testing– continue therapy; 

• <80% of doses, and lapse is less than 3 months in duration– continue therapy until all doses are 

completed (full course); or

• <80% of doses, and lapse is greater than 3 months in duration– restart therapy from the 

beginning of initial phase.
Chapter 6: Treatment of Tuberculosis Disease

160

Figure 6.6

Algorithm for Management of

Continuation Phase Treatment Interruptions

Is the 

percentage

of doses

<80%?

If sputum smear was 

AFB negative at 

baseline, additional 

treatment may not be 

necessary

If sputum smear was 

AFB positive at 

baseline, continue 

treatment to complete 

planned total number 

of doses warranted

No Yes

Determine the total 

percentage of 

doses completed

Is the 

duration of 

interruption 

<3 months?

No Yes

Continue 

treatment

Start initial phase

 4-drug regimen 

from the beginning

Can

treatment 

be completed 

within required time 

frame for 

regimen?

No

Complete 

treatment

Yes

Start initial phase

 4-drug regimen 

from the beginning
Chapter 6: Treatment of Tuberculosis Disease

161

Table 6.7

Treatment Interruptions

When 

Interruption 

Occurs

Situation Guidelines

During initial 

phase

Lapse is <14 days in duration Continue treatment to complete planned 

total number of doses (as long as all doses 

are completed within 3 months)

Lapse is ≥14 days in duration Restart treatment from the beginning

During 

continuation 

phase

Received ≥80% of doses 

and sputum was AFB smear 

negative on initial testing

Further therapy may not be necessary

Received ≥80% of doses 

and sputum was AFB smear 

positive on initial testing

Continue therapy until all doses are 

completed

Received <80% of doses and 

lapse is <3 months in duration

Continue therapy until all doses are 

completed (full course)

If treatment cannot be completed within 

recommended timeframe for regimen, 

restart therapy from the beginning

Received <80% of doses and 

lapse is ≥3 months in duration

Restart therapy from the beginning, new 

initial and continuation phase

Decision to Treat Culture-Negative TB Disease

Alternative diagnoses must be considered carefully with appropriate diagnostic studies undertaken in 

patients who have what appears to be culture-negative pulmonary TB disease. Patients who, based 

on careful clinical and radiographic evaluation, are thought to have pulmonary TB disease should 

have treatment initiated with INH, RIF, PZA, and EMB even when the initial sputum smears are 

negative. Figure 6.7 provides an algorithm for treatment of culture-negative TB.
Chapter 6: Treatment of Tuberculosis Disease

162

Figure 6.7

Algorithm to Guide Treatment of Culture-Negative TB

Is initial 

culture 

positive?

No Yes

Continue treatment 

for culture-positive TB Was there 

symptomatic 

or chest x-ray 

improvement after 

2 months of 

treatment?

No Yes

Continue treatment 

of INH/RIF daily or 

twice weekly for 

2-4 months

High clinical suspicion for active TB 

despite negative smears based on:

• Abnormal chest x-ray

• Clinical symptoms

• No other diagnosis

• Positive IGRA or tuberculin skin test

• High risk of acquiring TB infection

Patient placed on initial phase regimen: 

INH, RIF, EMB, and PZA for 2 months

• Discontinue treatment

• Patient presumed to 

have LTBI

• Treatment completed
Chapter 6: Treatment of Tuberculosis Disease

163

Study Questions

Indicate whether the following statements about the initial phase of treatment are true or false.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Statements about Initial Phase of Treatment True or False

____ 6.17 Consists of 2 months of treatment.

____ 6.18 Is crucial for preventing the emergence of 

drug resistance.

____ 6.19 Treatment regimen usually consists of 6 drugs.

A. True

B. False

Indicate whether the following statements about the continuation phase of treatment are true 

or false. (Choose the one best answer and write the letter for the correct answer on the line next to 

the question number.)

Statements about Continuation Phase of Treatment True or False

____ 6.20 Consists of either 4 or 7 months of treatment.

____ 6.21 The 4-month continuation phase is used in the 

majority of patients.

____ 6.22 The 7-month continuation phase is usually only used 

for patients with extrapulmonary TB.

A. True

B. False

6.23 Treatment completion is defined primarily as the ingestion of the total number of doses 

prescribed within the specified time frame. 

(choose the one best answer)

A. True

B. False

6.24 The duration of therapy depends on which of the following? 

(choose the one best answer)

A. Drugs used

B. Drug-susceptibility test results of the isolate

C. Patient’s response to therapy

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 6: Treatment of Tuberculosis Disease

164

6.25 Which of the following statements about follow-up after treatment is true?

(choose the one best answer)

A. Follow-up evaluation must be individualized for patients with organisms resistant to 

INH or RIF or both.

B. Routine follow-up after treatment is not necessary for patients who have had a 

satisfactory response to a 6- or 9-month regimen with both INH and RIF.

C. Follow-up evaluation is not needed for patients with continued positive cultures.

D. A, B, and C are all correct.

E. Only A and B are correct.

The following patients have had an interruption in treatment. Match the patient with the 

treatment decision.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Patient Treatment Decision

____ 6.26 During the initial phase of treatment, Perry has 

had a lapse in therapy that was less than 14 days.

____ 6.27 During the initial phase of treatment, Walter has 

had a lapse in therapy that was greater than 14 

days.

____ 6.28 During the continuation phase of treatment, 

Desiree has had a lapse in therapy after receiving 

more than 80% of doses. She had a negative smear 

on initial testing.

____ 6.29 During the continuation phase of treatment, 

Maurine has had a lapse in therapy for cavitary TB 

after receiving less than 80% of doses. Her lapse is 

more than 3 months in duration.

____ 6.30 During the continuation phase of treatment, 

Ratcliff had a lapse in therapy after receiving more 

than 80% of doses. His sputum was AFB smear 

positive on initial testing.

____ 6.31 During the continuation phase of treatment, Alex 

has had a lapse in therapy after receiving less than 

80% of doses. His lapse is less than 3 months in 

duration. 

A. Restart treatment from the 

beginning

B. Continue treatment to 

complete planned total 

number of doses (as long 

as all doses are completed 

within 3 months)

C. Further treatment may not 

be necessary

D. Continue therapy until all 

doses are completed
Chapter 6: Treatment of Tuberculosis Disease

165

TB Disease Treatment Regimens for Specific Situations

TB disease treatment regimens for specific situations require special management and should be 

administered in consultation with a TB expert. Specific situations include the following people:

• Pregnant women

• Breast-feeding women

• Infants and children 

• HIV-infected persons

TB disease treatment regimens for specific situations require special 

management and should be administered in consultation with a TB expert.

Pregnant Women

Untreated TB disease represents a greater hazard to a pregnant woman and her fetus than does its 

treatment. Because of the risk of TB to the fetus, treatment of TB in pregnant women should be 

initiated whenever the probability of maternal disease is moderate to high. The initial treatment 

regimen should consist of INH, RIF, and EMB. Although all of these drugs cross the placenta, they 

do not appear to have teratogenic effects. Streptomycin is the only anti-TB drug documented to 

have harmful effects on the human fetus (congenital deafness) and should not be used. Although 

detailed teratogenicity data are not available, PZA can probably be used safely during pregnancy and 

is recommended by the World Health Organization (WHO) and the International Union Against 

Tuberculosis and Lung Disease (IUATLD). If PZA is not included in the initial treatment regimen, 

the minimum duration of therapy is 9 months. 

Untreated TB disease represents a greater hazard to a pregnant 

woman and her fetus than does its treatment.

Streptomycin is the only anti-TB drug documented to have harmful effects 

on the human fetus (congenital deafness) and should not be used.

For pregnant women with MDR TB, treatment should only be done in consultation with an MDR 

TB expert. Many of the medications currently used for treatment of MDR TB may be harmful to 

the fetus.
Chapter 6: Treatment of Tuberculosis Disease

166

Breast-feeding

Breast-feeding should not be discouraged for women being treated with first-line anti-TB drugs, 

because the small concentrations of these drugs in breast milk do not produce toxicity in the nursing 

newborn. Conversely, drugs in breast milk should not be considered to serve as effective treatment 

for TB disease or for LTBI in a nursing infant. Pyridoxine (vitamin B6

) supplementation (25 mg/

day) is recommended for all women taking INH who are either pregnant or breast-feeding. The 

amount of pyridoxine in multivitamins is variable, but generally less than the needed amount. 

Infants and Children 

Infants and children with TB disease should be treated with the regimens recommended for 

adults, with the exception that EMB is not used routinely in children. For children whose clarity 

or sharpness of vision cannot be monitored, EMB is usually not recommended except when the 

risk of drug resistance is high or for children who have “adult-type” (upper lobe infiltration, cavity 

formation) TB disease. In infants, TB is much more likely to disseminate; therefore, treatment 

should be started as soon as the diagnosis is suspected. Children commonly develop primary TB 

disease which generally affects the middle and lower lung. Children should be treated with three 

(rather than four) drugs in the initial phase (INH, RIF, and PZA). In general, extrapulmonary TB in 

children can be treated with the same regimens as pulmonary disease. Exceptions are disseminated 

TB and tuberculous meningitis, for which there are inadequate data to support 6-month therapy; 

thus 9 to 12 months of treatment is recommended.

In infants, TB is much more likely to disseminate; therefore, treatment 

should be started as soon as the diagnosis is suspected.

HIV-Infected Persons

Management of HIV and TB coinfection is complex, and the clinical and public health 

consequences associated with the failure of treatment and other negative outcomes are serious. HIVinfected patients are on numerous medications, some of which interact with anti-TB drugs. It is 

therefore strongly recommended that experts in the treatment of HIV-related TB be consulted.

The treatment regimens listed in Table 6.3 are effective for people living with HIV, with two 

exceptions due to increased risk of developing acquired drug resistance:

• Once-weekly administration of INH and RPT in the continuation phase should not be used in 

any HIV-infected patient; and

• Patients with advanced HIV (CD4 counts less than 100) should be treated with daily or three 

times weekly therapy in both the initial and continuation phase.

Every effort should be made to use a rifamycin-based regimen for the entire course of therapy in 

coinfected patients. The key role of the rifamycins in the success of TB disease treatment mandates 

that the drug-drug interactions between the rifamycins and antiretroviral drugs be managed 

appropriately, rather than using TB treatment regimens that do not include a rifamycin or by 

withholding antiretroviral therapy until completion of anti-TB therapy.
Chapter 6: Treatment of Tuberculosis Disease

167

Of particular concern is the interaction of rifamycins with antiretroviral agents and other antiinfective drugs. Rifampin can be used for the treatment of TB with certain combinations of 

antiretroviral agents. Rifabutin, which has fewer drug-drug interactions due to its decreased 

induction of the cytochrome P450 system, may also be used in place of rifampin and appears 

to be equally effective, although the doses of the rifabutin and antiretroviral agents may require 

adjustments and should be administered with expert consultation.

Therefore, patients with HIV-related TB disease should be treated with a regimen including a 

rifamycin for the full course of TB disease treatment, unless the isolate is resistant to the rifamycins 

or the patient has a severe side effect that is clearly due to the rifamycins.

HIV-infected patients are on numerous medications, some of which 

interact with anti-TB drugs. It is therefore strongly recommended 

that experts in the treatment of HIV-related TB be consulted.

Treatment Duration

Six months should be considered the minimum duration of treatment for HIV-infected adults, 

even for patients with culture-negative TB disease. If there is evidence of a slow or suboptimal 

response (e.g., cultures are still positive after 2 months of therapy), the continuation phase should be 

prolonged to 7 months (a total of 9 months of treatment). DOT and other adherence- promoting 

strategies should be used in all patients with HIV-related TB disease. 

Predicting Drug Interactions Involving Rifampin

Much is known about the interactions of antiretroviral agents and RIF. In addition, knowledge of 

the mechanisms of drug interactions can help predict the likelihood of an interaction, even if that 

specific combination of drugs has not been formally evaluated. A major concern in treating TB 

disease in HIV-infected persons is the interaction of RIF with certain antiretroviral agents (some 

protease inhibitors [PIs] and nonnucleoside reverse transcriptase inhibitors [NRTIs]). Rifabutin, 

another rifamycin that has fewer drug-drug interactions, may be used as an alternative to RIF. 

As new antiretroviral agents and more pharmacokinetic data become available, these 

recommendations are likely to be modified. For more information, see Managing Drug Interactions 

in the Treatment of HIV-Related Tuberculosis at: www.cdc.gov/tb/publications/guidelines/TB_HIV_

Drugs/default.htm

Pregnancy in HIV-Infected Women

A number of issues complicate the treatment of the HIV-infected pregnant woman who has 

TB disease. Pregnancy alters the distribution and metabolism of a number of drugs, including 

antiretroviral drugs (there is very little information on whether the metabolism of anti-TB drugs is 

altered during pregnancy). Notably, the serum concentrations of protease inhibitors are decreased 

during the latter stages of pregnancy. There are no published data on drug-drug interactions between 

anti-TB and antiretroviral drugs among pregnant women. However, it is likely that the effects of RIF 

on protease inhibitors are exacerbated during pregnancy. 
Chapter 6: Treatment of Tuberculosis Disease

168

HIV-Infected Children

HIV-infected children with TB disease are at greater risk for severe, life-threatening manifestations 

(e.g., disseminated disease, meningitis). There are very limited data on the absorption, metabolism, 

and elimination of anti-TB drugs among children, particularly among very young children (< 2 years 

of age). For more information, please see Managing Drug Interactions in the Treatment of HIVRelated Tuberculosis at: www.cdc.gov/tb/publications/guidelines/TB_HIV_Drugs/specialpop.htm

HIV-infected children with TB disease are at greater risk for severe, lifethreatening manifestations (e.g., disseminated disease, meningitis).

Persons with Additional Treatment Considerations

A number of medical conditions or disease characteristics require additional treatment considerations 

and TB treatment decisions should be made in consultation with a TB expert. These include:

• Renal insufficiency/end-stage renal disease 

• Hepatic disease

• Extrapulmonary TB disease

• Drug-resistant TB disease

• Culture-negative TB disease

Renal Insufficiency and End-stage Renal Disease 

Renal insufficiency complicates the management of TB disease because some anti-TB drugs are 

cleared by the kidneys. Alteration in dosing of anti-TB drugs is commonly necessary in patients with 

renal insufficiency and end-stage renal disease (ESRD) requiring hemodialysis. The dosage of antiTB drugs should not be decreased because the peak serum concentrations may be low and smaller 

doses may decrease drug efficacy. Instead, the dosing interval of anti-TB drugs should be increased. 

Based on creatinine clearance, most anti-TB drugs can be given three times a week immediately after 

hemodialysis. Consultation with the patient’s nephrologist is advised.

Renal insufficiency complicates the management of TB disease 

because some anti-TB drugs are cleared by the kidneys.

Alteration in dosing of anti-TB drugs is commonly necessary in patients with 

renal insufficiency and end-stage renal disease (ESRD) requiring hemodialysis.
Chapter 6: Treatment of Tuberculosis Disease

169

Hepatic Disease

The treatment of TB disease in patients with unstable or advanced liver disease is problematic for 

several reasons: 

• The likelihood of drug-induced hepatitis is greater;

• The implications of drug-induced hepatitis for patients with marginal hepatic reserve are 

potentially serious, even life-threatening; and 

• Fluctuations in the indicators of liver function related to the pre-existing liver disease can 

confound monitoring for drug-induced hepatitis.

Thus, clinicians may consider regimens with fewer potentially hepatotoxic agents in patients with 

advanced or unstable liver disease. Expert consultation is advisable in treating such patients. It should 

be noted that TB disease itself may involve the liver, causing abnormal liver function; thus, not all 

abnormalities in liver function tests noted at baseline should be attributed to causes other than TB 

disease. The hepatic abnormalities caused by TB disease will improve with effective treatment.

Clinicians may consider regimens with fewer potentially hepatotoxic 

agents in patients with advanced or unstable liver disease. 

Expert consultation is advisable in treating such patients.

Extrapulmonary TB Disease

As a general rule, the principles used for the treatment of pulmonary TB disease also apply to 

extrapulmonary forms of the disease. A 6-month treatment regimen is recommended for patients 

with extrapulmonary TB disease, unless the organisms are known or strongly suspected to be 

resistant to the first-line drugs. If PZA cannot be used in the initial phase, the continuation phase 

must be increased to 7 months. The exception to these recommendations is central nervous system 

TB, for which the optimal length of therapy has not been established but some experts recommend 

9 to 12 months. Most experts do recommend corticosteroids to be used as additional therapy for 

patients with TB meningitis and pericarditis. Consultation with a TB expert is recommended.

As a general rule, the principles used for the treatment of pulmonary 

TB disease also apply to extrapulmonary forms of the disease. 

A 6-month treatment regimen is recommended for patients with 

extrapulmonary TB disease, unless the organisms are known or 

strongly suspected to be resistant to the first-line drugs.
Chapter 6: Treatment of Tuberculosis Disease

170

Drug-Resistant TB Disease

Drug-resistant TB disease can develop in two different ways, called primary and secondary 

resistance. Primary resistance occurs in persons who are initially exposed to and infected with 

resistant organisms. Secondary resistance, or acquired resistance, develops during TB therapy, 

either because the patient was treated with an inadequate regimen or because the patient did not

take the prescribed regimen appropriately or because of other conditions such as drug malabsorption 

or drug-drug interactions leading to low serum levels (see Chapter 2, Transmission and Pathogenesis 

of Tuberculosis).

Drug-resistant TB disease can develop in two different ways:

• Primary resistance 

» Occurs in persons who are initially exposed to and infected

 with resistant organisms

• Secondary resistance, or acquired resistance

» Develops during TB therapy because of

 − patient being treated with an inadequate regimen, 

 − patient not taking prescribed regimen appropriately,

 − drug malabsorption, or

 − drug-drug interactions leading to low serum levels

Drug resistance in a patient with newly diagnosed TB disease may be suspected on the basis of 

previous treatment, contact with a known drug-resistant case, or time spent in a region in which 

drug resistance is common. Drug resistance can be proven only by drug-susceptibility testing (see 

Chapter 4, Diagnosis of Tuberculosis Disease).

Patients with strains of M. tuberculosis resistant to both INH and RIF (multidrug-resistant) are at 

high risk for 

• Treatment failure;

• Relapse; 

• Further acquired resistance; or

• Death.

These patients must be referred immediately to an expert in the management of drug-resistant TB 

disease; or consultation should be obtained from specialized treatment centers. 

Patients with strains of M. tuberculosis resistant to both INH and RIF 

(multidrug-resistant) are at high risk for treatment failure, relapse, 

further acquired resistance, or death. These patients must be referred 

immediately to an expert in the management of drug-resistant TB disease; 

or consultation should be obtained from specialized treatment centers. 
Chapter 6: Treatment of Tuberculosis Disease

171

Management of patients with drug-resistant TB disease is based on the following guidelines:

• A single new drug should never be added to a failing regimen;

• In patients with MDR organisms resistant to first-line drugs in addition to INH and RIF, 

regimens employing four to six drugs that are new to the patient and to which the isolate 

shows in vitro susceptibility appear to be associated with better results; 

• Patients with multidrug-resistant organisms should receive the highest priority for DOT, which 

should be administered either in the hospital, home, or other facility;

• The use of drugs to which there is demonstrated in vitro resistance is not encouraged because 

there is little or no efficacy of these drugs and alternative medications may be available;

• Resistance to RIF is associated in nearly all instances with cross-resistance to rifabutin and 

rifapentine (RPT);

• There is no cross-resistance between SM and the other injectable agents, amikacin, kanamycin, 

and capreomycin (although resistance to all may occur as independent events); cross-resistance 

between amikacin and kanamycin is not universal but frequently seen; 

• Resistance to PZA is uncommon in the absence of resistance to other first-line drugs; if 

monoresistance to PZA is observed, consideration must be given to the possibility that the 

disease is caused by M. bovis, not M. tuberculosis; and

• Intermittent therapy should not be used in treating TB disease caused by drug-resistant 

organisms, except perhaps for injectable agents after the initiation phase (usually 2 to 3 

months) of daily therapy. 

Table 6.8 provides information on drug classes for TB, types of drug-resistant TB, and appropriate 

anti-TB drugs for treatment. 
Chapter 6: Treatment of Tuberculosis Disease

172

Table 6.8

Drug Classes for TB

Drug Classes Anti-TB Drugs

DrugSusceptible 

TB

MultidrugResistant TB 

(MDR TB)

Extensively 

Drug Resistant 

TB (XDR TB) 

First-line oral drugs

• Standard treatment 

for drugsusceptible TB

• Four drugs for 

6–9 months

• Safe, effective, 

inexpensive

• 95% cure 

• Based on solid 

scientific evidence 

from ~30 years of 

drug discovery and 

controlled clinical 

trials, 1943–72

INH Susceptible Resistance by 

definition

Resistance by 

definition

RIF Susceptible Resistance by 

definition

Resistance by 

definition

PZA Susceptible Resistance 

possible or likely

Resistance 

possible or likely

EMB Susceptible Resistance 

possible or likely

Resistance 

possible or likely

Second-line drugs

• Treatment based 

on laboratory 

drug-resistance 

testing and 

epidemiological 

information

• Four to six drugs 

for 2 years

Aminoglycosides 

and 

Capreomycin

N/A Resistance 

possible

Resistance by 

definition

Quinolones N/A Resistance 

possible

Resistance by 

definition

Thioamides N/A Resistance 

possible

Resistance 

possible or likely

Cycloserine N/A Resistance 

possible

Resistance 

possible or likely

ρ-Aminosalicylic 

Acid

N/A Resistance 

possible

Resistance 

possible or likely

Culture-Negative TB Disease

Failure to isolate M. tuberculosis from appropriately collected specimens in persons who, because of 

clinical or radiographic findings, are suspected of having pulmonary TB disease does not exclude 

a diagnosis of TB disease. Low bacillary populations, temporal variations in the number of bacilli 

being expelled, and errors in specimen processing all may result in failure to isolate organisms from 

patients who have TB disease. It should be emphasized that alternative diagnoses must be considered 

carefully and appropriate diagnostic studies undertaken in patients who have what appears to be 
Chapter 6: Treatment of Tuberculosis Disease

173

culture-negative TB disease. At a minimum, patients suspected of having pulmonary TB disease 

should have three sputum specimens (using sputum induction with hypertonic saline if necessary) 

for AFB smear and culture as part of the diagnostic evaluation prior to or coincident with treatment 

initiation. Depending on the clinical features and differential diagnosis, other diagnostic testing, 

such as bronchoscopy with bronchoalveolar lavage and biopsy, should be considered before making a 

presumptive diagnosis of culture-negative TB disease. 

Failure to isolate M. tuberculosis from appropriately collected specimens in 

persons who, because of clinical or radiographic findings, are suspected of 

having pulmonary TB disease does not exclude a diagnosis of TB disease.

Patients who, on the basis of careful clinical and radiographic evaluation, are thought to have a 

high likelihood of having pulmonary TB disease should have treatment initiated with INH, RIF, 

PZA, and EMB even when the initial sputum smears are negative. If M. tuberculosis is isolated in 

culture, treatment for TB disease should be continued. Patients who have negative cultures but who 

still are presumed to have pulmonary TB disease should have a thorough follow-up clinical and 

radiographic evaluation at the time 2 months of therapy has been completed to determine whether 

there has been a response that can be attributed to anti-TB treatment. If there is either clinical or 

radiographic improvement and no other etiology is identified, treatment should be continued for TB 

disease. A 4-month INH and RIF regimen for culture-negative TB disease has been demonstrated 

to be successful. However, because the results of cultures may not be known for 3 to 8 weeks and 

because of the possibility of drug resistance, use of two-drug therapy with INH and RIF alone is not

recommended in the initial phase of treatment (i.e., first 2 months) while culture results are pending. 

The continuation phase can be shortened to 2 months using INH and RIF for HIV-negative 

patients once it is known that cultures are negative. However, HIV-infected patients with culturenegative pulmonary TB should be treated for a minimum of 6 months (total). Figure 6.7 provides an 

algorithm for treatment of culture-negative TB.

Patients who, on the basis of careful clinical and radiographic 

evaluation, are thought to have a high likelihood of having pulmonary 

TB disease should have treatment initiated with INH, RIF, PZA, 

and EMB even when the initial sputum smears are negative.

On occasion, patients who are being evaluated for pulmonary TB disease will be found to have 

positive AFB smears, but negative cultures. There are several potential explanations for this 

occurrence, including the possibilities that the acid-fast organisms are nontuberculous and difficult 

to culture, that they are nonviable tubercle bacilli, or that there was laboratory error. The approach 

taken in such cases should be individualized on the basis of clinical and radiographic findings. If 

suspicion of TB disease is high and the patient has positive AFB smears, even with negative cultures, 

the patient should be treated as if culture positive, using one of the recommended regimens.
Chapter 6: Treatment of Tuberculosis Disease

174

Study Questions

6.32 Which drug is harmful to the fetus and should NOT be used with pregnant women 

during the initial treatment phase? 

(choose the one best answer)

A. Isoniazid

B. Rifampin

C. Ethambutol

D. Streptomycin

6.33 Which of the following statements about infants and children is true? 

(choose the one best answer)

A. Anti-TB drugs in breast milk can be considered effective treatment for TB disease or for 

LTBI in a nursing infant.

B. EMB is routinely used to treat children for TB disease.

C. Young children should be treated with three (rather than four) drugs in the initial phase.

D. TB disease is less likely to disseminate in children than in adults.

6.34 For HIV-infected patients, which of the following statements is true? 

(choose the one best answer)

A. The minimum duration of treatment of TB disease for HIV-infected adults is 6 months.

B. If there is evidence of a slow or suboptimal response, the continuation phase should be 

prolonged to 7 months (a total of 9 months of treatment).

C. DOT and other adherence promoting strategies should be used in all patients with HIVrelated TB disease. 

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 6: Treatment of Tuberculosis Disease

175

TB patients can have additional medical problems or presentations. Match the problem or 

presentation with the appropriate type of TB disease treatment.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Additional Medical Problems 

or Presentations Type of Treatment

____ 6.35 End-stage renal disease

____ 6.36 Hepatic disease

____ 6.37 Extrapulmonary TB disease

A. Consider a regimen with fewer potentially 

hepatotoxic agents.

B. Alteration in dosing anti-TB drugs is 

commonly necessary. Do not decrease dose 

of anti-TB drugs. Dosing interval should be 

increased to 3 times a week.

C. Use the same principles as for pulmonary 

TB disease. A 6-month treatment regimen 

is recommended, unless the organisms are 

known or strongly suspected to be resistant 

to the first-line drugs.

6.38 Drug resistance in a patient with newly diagnosed TB disease may be suspected on the 

basis of which of the following? 

(choose the one best answer)

A. Time spent in a region in which drug resistance is common

B. Contact with a known drug-resistant case

C. Previous TB treatment

D. A, B, and C are all correct.

E. Only A and B are correct.

6.39 Joanne has an M. tuberculosis strain that is resistant to both isoniazid and rifampin. 

What is Joanne at high risk for? 

(choose the one best answer)

A. Treatment failure

B. Relapse

C. Further acquired resistance

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 6: Treatment of Tuberculosis Disease

176

Patient Monitoring

Adverse reactions to anti-TB drugs are relatively rare, but in some patients they may be severe. 

Clinicians who treat TB disease should be familiar with the methods of monitoring for adverse 

reactions and patients’ response to treatment. In some situations (drug-resistant TB disease, 

pregnancy, HIV-infected patients), expert consultation should be sought. 

Baseline Monitoring

Before starting treatment, adult patients should have certain baseline blood and vision tests to help 

detect any underlying problems that may complicate treatment. For children, only vision tests are 

necessary unless there are other medical conditions that may complicate treatment. Recommended 

examinations for baseline monitoring are included in Table 6.9.

Before starting treatment, adult patients should have 

certain baseline blood and vision tests to help detect any 

underlying problems that may complicate treatment.

For children, only vision tests are necessary unless there are 

other medical conditions that may complicate treatment.

Table 6.9

Recommended Examinations for Baseline Monitoring

Patient Recommended Test

All patients Measure aminotransferases (i.e., AST, ALT), 

bilirubin, alkaline phosphatase, and serum 

creatinine and a platelet count

Patients at risk for hepatitis B or C 

(e.g., injection drug user, born in Asia 

or Africa, or HIV infected)

Conduct serologic tests

Patients who are taking EMB Test visual acuity (Snellen chart) and color 

vision (Ishihara)

HIV-infected patients Obtain CD4+ lymphocyte count
Chapter 6: Treatment of Tuberculosis Disease

177

Monitoring During Treatment

Patients with TB disease should have clinical evaluations at least monthly to identify possible adverse 

reactions to medications and to assess adherence (Table 6.10). 

As a routine practice, it is not necessary to monitor liver or renal function or platelet count for 

patients being treated with first-line anti-TB drugs unless there were abnormalities at baseline or 

there are clinical reasons to obtain measurements. Patients who have stable abnormalities of hepatic 

or renal function at baseline should have repeat measurements early in the course of treatment, then 

less frequently to ensure that conditions have not worsened.

Monthly repeat testing of visual acuity (Snellen) and color vision (Ishihara) is recommended for 

patients receiving an EMB dose exceeding 15– 20 mg/kg (the recommended range) and for patients 

receiving EMB for more than 2 months. Patients receiving EMB should be questioned regarding 

visual disturbances at monthly intervals. Patients should be educated regarding the possible visual 

side effects of EMB and should be instructed to immediately report vision changes to their healthcare provider.

Table 6.10

Monitoring During Treatment

Patient Recommended Test

All patients Repeat at least monthly clinical evaluations to

• Identify possible adverse reactions to 

medications 

• Assess adherence

Patients who are taking EMB • Question monthly regarding visual 

disturbances 

• Repeat monthly testing for visual acuity 

(Snellen chart) and color vision (Ishihara) for 

patients whose dose exceeds 15– 20 mg/kg

and those who have been receiving EMB for 

>2 months 

Patients who have 

extrapulmonary TB disease

Evaluation depends on 

• Sites involved

• Ease with which specimens can be obtained
Chapter 6: Treatment of Tuberculosis Disease

178

Study Questions

6.40 For baseline monitoring, children only need vision tests unless there are other medical 

conditions that may complicate treatment.

(circle the one best answer)

A. True

B. False

Match the patient with the type of monitoring that should occur during treatment.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.)

Patients Monitoring During Treatment

____ 6.41 Pauline is being treated with 

first-line anti-TB drugs. 

She had no abnormalities 

at baseline and no clinical 

problems.

____ 6.42 Don had stable 

abnormalities of hepatic 

function at baseline.

____ 6.43 Percy has been on first-line 

anti-TB drugs that include 

ethambutol for greater than 

2 months.

A. Repeat measurements early in the course 

of treatment, then less frequently to ensure 

that condition does not worsen. 

B. Repeat visual acuity and color vision.

C. Not necessary to monitor liver or renal 

function or platelet count.

Evaluating Response to Treatment

It is important for clinicians to evaluate a patient’s response to treatment to determine the efficacy 

of the treatment and to identify any adverse reactions. Clinicians use three methods to determine 

whether a patient is responding to treatment:

1. Clinical evaluation

2. Bacteriological examination

3. Chest radiograph

It is important for clinicians to evaluate a patient’s response to treatment to 

determine the efficacy of the treatment and to identify any adverse reactions.
Chapter 6: Treatment of Tuberculosis Disease

179

Clinical Evaluation

Patients should have clinical evaluations at least monthly to 

• Identify possible adverse reactions to medications;

• Assess adherence; and

• Determine treatment efficacy. 

Although each patient responds to treatment at a different pace, all TB symptoms should gradually 

improve and eventually go away. Patients whose symptoms do not improve during the first 2 

months of treatment, or whose symptoms worsen after improving initially, should be reevaluated for 

adherence issues and development of drug resistance.

Adverse Reactions to Anti-TB Drugs

In addition to the microbiological evaluations, it is essential that patients have clinical evaluations to 

identify possible adverse effects of the anti-TB drugs (Table 6.11). Monitoring for adverse reactions 

must be individualized. The type and frequency of monitoring should depend on the drugs used and 

the patient’s risk for adverse reactions (e.g., age or alcohol use). At minimum, patients should be seen 

monthly during therapy and questioned by health-care providers concerning adverse reactions, even 

if no problems are apparent. 

Adverse reactions to anti-TB drugs are relatively rare, but in some patients they may be severe. 

Mild adverse effects can generally be managed with symptomatic therapy. The drug or drugs must 

be discontinued for more severe effects. It is important that first-line drugs not be stopped without 

adequate justification. Proper management of serious adverse reactions often requires expert 

consultation. 

Patients should be specifically instructed to look for symptoms associated with the most common 

reactions to the medications they are taking. They should also be instructed to seek medical 

attention immediately should these symptoms occur. All patients receiving INH, RIF, or PZA 

should immediately report any symptoms suggestive of hepatitis (nausea, loss of appetite, vomiting, 

persistently dark urine, yellowish skin or eyes, malaise, unexplained elevated temperature for more 

than 3 days, or abdominal tenderness). If the symptoms suggest adverse reactions, the patient should 

be instructed to stop the medication, and appropriate laboratory testing should be performed.

Patients should be specifically instructed to look for symptoms 

associated with the most common reactions to the medications 

they are taking. They should also be instructed to seek medical 

attention immediately should these symptoms occur.
Chapter 6: Treatment of Tuberculosis Disease

180

Table 6.11

Common Adverse Reactions to TB Drugs

Caused 

by Adverse Reaction Signs and Symptoms Significance 

of Reaction*

Any 

drug

Allergic • Skin rash May be serious 

or minor

EMB Eye damage • Blurred or changed vision

• Changed color vision

Serious

INH

PZA

RIF

Hepatic toxicity • Abdominal pain

• Abnormal liver function test results

• Dark urine

• Fatigue

• Fever for 3 or more days

• Flu-like symptoms

• Lack of appetite

• Nausea

• Vomiting

• Yellowish skin or eyes

Serious

INH Nervous system 

damage

• Dizziness; tingling or numbness 

around the mouth

Serious

Peripheral neuropathy • Tingling sensation in hands and feet Serious

PZA Stomach upset • Stomach upset

• Vomiting

• Lack of appetite

May be serious 

or minor

Gout • Abnormal uric acid level**

• Joint aches

Serious

RIF Bleeding problems • Easy bruising

• Slow blood clotting

Serious

Discoloration of body 

fluids

• Orange urine, sweat, or tears

• Permanently stained soft contact lenses

Minor

Drug interactions • Interferes with certain medications such as 

birth control pills, birth control implants, 

and methadone treatment

May be serious 

or minor

Sensitivity to the sun • Frequent sunburn Minor

 * Patients should stop medication for serious adverse reactions and consult a clinician immediately.

Patients can continue taking medication if they have minor adverse reactions.

** Asymptomatic elevated uric acid levels are expected with PZA treatment. Acute gouty arthritis, which is rare 

without preexisting gout, is a contraindication to PZA use.
Chapter 6: Treatment of Tuberculosis Disease

181

Common Adverse Reactions to TB Disease Treatment

The items listed below are common adverse reactions to TB treatment: 

• Gastrointestinal problems 

• Hepatitis

• Rash 

• Drug fever 

Gastrointestinal Problems

Gastrointestinal reactions to the anti-TB drugs are common, particularly in the first few weeks of 

therapy. These reactions include:

• Upset stomach

• Nausea

• Poor appetite

• Abdominal pain

In the presence of gastrointestinal symptoms, measure

• Serum aminotransferases (i.e., AST, ALT) and 

• Bilirubin 

Hepatic Toxicity

Liver injury can be caused by three of the first-line TB disease drugs, INH, RIF and PZA. Significant 

liver toxicity is indicated by AST ≥3 times the upper limit of normal in the presence of symptoms, 

or ≥5 times the upper limit of normal in the absence of symptoms (Table 6.12). If the AST and ALT 

are <5 times the upper limit of normal, toxicity can be considered mild; an AST or ALT of 5–10 

times normal defines moderate toxicity; and >10 times normal is severe. In addition to elevation 

of the AST and ALT, occasionally there are disproportionate increases in bilirubin and alkaline 

phosphatase. This pattern is more consistent with RIF hepatotoxicity. 

Table 6.12

Hepatic Toxicity

AST and ALT Level Levels of Toxicity

AST and ALT <5 times the upper limit of normal Mild

AST or ALT 5– 10 times the normal limit Moderate

AST or ALT >10 times the normal limit Severe
Chapter 6: Treatment of Tuberculosis Disease

182

Rash 

All drugs used in treating TB disease can cause a rash. The response to a patient with a rash depends 

upon its severity. The rash may be minor, affecting a limited area or being predominantly manifested 

as itching. In this case, antihistamines should be given for symptomatic relief, but all TB disease 

medications can be continued. 

All drugs used in treating TB disease can cause a rash.

Drug Fever

Recurrence of fever in a patient who has been receiving therapy for several weeks should suggest drug 

fever, especially if the patient is showing microbiologic and radiographic improvement. It should 

be noted, however, that fever from TB may persist for as long as 2 months after therapy has been 

initiated.

Bacteriologic Examination

Important treatment decisions concerning the continuation-phase regimen are based on the 

microbacteriological status at the end of the initial phase of treatment (i.e., at least 2 months). 

Patients whose cultures have not become negative after 3 months of therapy should be reevaluated 

for potential drug-resistant disease, as well as for potential failure to adhere to the regimen. Patients 

who have positive cultures after 4 months of treatment should be considered as having failed 

treatment and managed accordingly.

Patients whose cultures have not become negative after 3 months of 

therapy should be reevaluated for potential drug-resistant disease, 

as well as for potential failure to adhere to the regimen.

Positive Sputum Cultures Prior to Treatment

For patients whose sputum culture is positive prior to treatment, the best way to measure the efficacy 

of therapy is to obtain specimens for culture at least monthly until two consecutive specimens are 

negative on culture (Table 6.13). Patients with multidrug-resistant TB should have sputum AFB 

smears and cultures performed monthly for the entire course of treatment.

Negative Sputum Cultures Prior to Treatment

For patients with negative sputum cultures prior to treatment for pulmonary disease, the major 

indicators of response to therapy are the chest radiograph and the clinical evaluation (Table 6.13). 

The intervals at which chest radiography should be repeated depend on the clinical circumstances 

and the differential diagnosis that is being considered. If the radiograph does not improve after the 

patient has received 2 months of treatment, the abnormality may be the result of either previous 

(not current) TB disease or another reason.
Chapter 6: Treatment of Tuberculosis Disease

183

Table 6.13

Response to Treatment for Pulmonary TB Disease

Bacteriologic

Status

Recommendations for 

Response to Treatment

Positive sputum cultures prior 

to treatment

• Obtain specimens for culture at least monthly until two 

consecutive specimens are negative on culture

• Perform monthly sputum AFB smears and cultures on MDR 

TB patients for entire course of treatment 

• A repeat chest radiograph after 2 months of treatment may 

be useful but is not essential

Negative sputum cultures 

prior to treatment

• Repeat chest radiograph at intervals based on clinical 

circumstances and differential diagnosis

• If radiograph does not improve after patient has received 2 

months of treatment, abnormality may be due to

» Previous (not current) TB disease

» Another reason

Cultures have not become 

negative after 3 months 

of therapy

Reevaluate for 

• Potential drug-resistant disease

• Potential failure to adhere 

Cultures are still positive after 

4 months of treatment

Consider as having failed treatment and manage accordingly

Chest Radiograph

For patients with positive cultures at diagnosis, a repeat chest radiograph at completion of 2 months 

of treatment may be useful, but is not essential. For patients with culture-positive TB, a chest 

radiograph at completion of treatment provides a baseline for comparison with any future films. 

For patients with cultures that are initially negative, a chest radiograph is necessary after 2 months 

of treatment, and a radiograph at completion of treatment is desirable. Generally, follow-up after 

completion of therapy is not necessary. 

For patients with cultures that are initially negative, a chest 

radiograph is necessary after 2 months of treatment, and a 

radiograph at completion of treatment is desirable.
Chapter 6: Treatment of Tuberculosis Disease

184

Study Questions

6.44 How often should patients have clinical evaluations to identify possible adverse reactions 

to medications and to assess adherence and to determine treatment efficacy?

(circle the one best answer)

A. Weekly

B. Twice a month

C. Once a month

D. Every 6 weeks

6.45 LaRue has been receiving TB treatment for 2 months. She is experiencing nausea, 

vomiting, abdominal pain, malaise, and persistently dark urine. What could be the cause? 

(circle the one best answer)

A. TB disease has spread to her abdomen.

B. She has hepatic toxicity due to adverse reaction to TB medications. 

C. She has an adverse reaction to EMB. 

Match the characteristic of an adverse reaction to TB therapy with the type of adverse reaction.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Characteristic Adverse Reaction

____ 6.46 Can be caused by three of 

the first-line TB drugs. 

____ 6.47 Can cause a recurrence of 

fever in a patient who has 

been receiving therapy for 

several weeks.

____ 6.48 Is common particularly 

in the first few weeks of 

therapy.

____ 6.49 Can be caused by all drugs 

used in treating TB disease.

A. Gastrointestinal problems

B. Hepatic toxicity

C. Rash

D. Drug fever
Chapter 6: Treatment of Tuberculosis Disease

185

Match the patient with the type of measures that should be taken to determine how the patient 

is responding to treatment.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.) 

Patients Measures for Determining the 

Patient’s Response to Treatment

____ 6.50 Carol had a positive sputum 

cultures prior to treatment 

and has multidrug-resistant 

TB disease.

____ 6.51 Tom’s culture has not 

become negative after 3 

months of treatment.

____ 6.52 Roxanne had negative 

sputum cultures prior to 

treatment.

____ 6.53 Burl had positive sputum 

cultures prior to treatment.

____ 6.54 Mike had positive sputum 

cultures after 4 months of 

treatment.

A. Obtain specimens for culture at least 

monthly until 2 consecutive specimens are 

negative on culture. 

B. Repeat chest radiographs at intervals 

based on clinical circumstances and the 

differential diagnosis.

C. Perform sputum AFB smears and cultures 

monthly for the entire course of treatment.

D. Reevaluate for potential drug-resistant TB 

disease, as well as for potential failure to 

adhere to the regimen.

E. Consider as having failed treatment and 

manage accordingly.
Chapter 6: Treatment of Tuberculosis Disease

186

Chapter Summary

The major goals for treatment of TB disease include 

• Cure the individual patient;

• Minimize risk of death and disability; and

• Reduce transmission of M. tuberculosis to other persons. 

To ensure that these goals are met, TB disease must be treated for at least 6 months or longer. 

Most of the bacteria are killed during the first 8 weeks of treatment; however, there are persistent 

organisms that require longer treatment. If treatment is not continued for a long enough duration, 

the surviving bacteria may cause the patient to become ill and infectious again.

There are several options for daily and intermittent therapy, but the goal of treatment for TB disease 

should be to provide the safest and most effective therapy in the shortest period of time. Given 

adequate treatment, almost all patients will recover and be cured. 

Regimens for the treatment of TB disease must contain multiple drugs to which the bacteria are 

susceptible. The standard of care for initiating treatment of TB disease is a four-drug regimen. 

Treatment with a single drug can lead to the development of a bacterial population resistant to that 

drug. Likewise, the addition of a single drug to a failing anti-TB regimen can lead to additional 

resistance. When two or more drugs to which in vitro susceptibility has been demonstrated are given 

together, each helps prevent the emergence of tubercle bacilli resistant to the others.

Responsibility for successful treatment is assigned to the health-care provider, not the patient. 

Health-care professionals should consult their health department’s TB control program to ensure 

their TB patients are able to adhere to a prescribed treatment regimen. The TB control program 

should assist the health-care professional in evaluating patient barriers to adherence and recommend 

directly observed therapy (DOT) and the use of incentives and enablers that may assist the patient in 

completing the recommended therapy. 

Currently, there are 10 drugs approved by the U.S. FDA for the treatment of TB disease. In 

addition, the fluoroquinolones (levofloxacin, moxifloxacin, and gatifloxacin), although not

approved by the FDA for TB disease, are commonly used to treat TB disease caused by drugresistant organisms or for patients who are intolerant of some first-line drugs. Rifabutin, approved 

for use in preventing Mycobacterium avium complex disease in patients with HIV infection but not

approved for TB disease, is useful for treating TB disease in patients concurrently taking drugs that 

interact with rifampin (e.g., certain antiretroviral drugs). Amikacin and kanamycin, nearly identical 

aminoglycoside drugs used in treating patients with TB disease caused by drug-resistant organisms, 

are not approved by the FDA for treatment of TB.

Of the approved drugs, INH, RIF, EMB, and PZA are considered the first-line anti-TB drugs 

and form the core of standard treatment regimens. RBT and RPT may also be considered firstline drugs under certain circumstances. RBT is used as a substitute for RIF in the treatment of 

all forms of TB caused by organisms that are known or presumed to be susceptible to this agent. 

The drug is generally reserved for patients who have intolerance to RIF or for whom drug-drug 

interactions preclude the use of rifampin. SM was formerly considered to be a first-line drug and, in 

some instances, is still used in the initial treatment regimen. However, an increasing prevalence of 
Chapter 6: Treatment of Tuberculosis Disease

187

resistance to SM in many parts of the world has decreased its overall usefulness. The remaining drugs 

are reserved for special situations such as drug intolerance or resistance. 

There are four basic treatment regimens recommended for treating adults with TB disease caused 

by organisms that are known or presumed to be susceptible to INH, RIF, PZA, and EMB. Each 

treatment regimen consists of an initial 2-month treatment phase followed by a continuation phase 

of either 4 or 7 months. The 4-month continuation phase is used for the majority of patients. 

Although these regimens are broadly applicable, there are modifications that should be made under 

specified circumstances.

Adverse reactions to anti-TB drugs are relatively rare, but in some patients they may be severe. 

Clinicians who treat TB disease should be familiar with the methods of monitoring for adverse 

reactions and patients’ response to treatment. In some situations (drug-resistant TB disease, 

pregnancy, HIV-infected patients), expert consultation should be sought. 

References

CDC. Controlling tuberculosis in the United States: Recommendations from the American Thoracic 

Society, CDC, and the Infectious Diseases Society of America. MMWR 2005; 54 (No. RR-12).

www.cdc.gov/mmwr/preview/mmwrhtml/rr5412a1.htm

CDC. National action plan to combat multidrug-resistant tuberculosis. MMWR 1992; 41 (RR-11): 

1–48. www.cdc.gov/mmwr/preview/mmwrhtml/00031159.htm

CDC. Notice to Readers: Updated guidelines on managing drug interactions in the treatment of 

HIV-related tuberculosis. MMWR 2008; 57 (04): 98.

www.cdc.gov/mmwr/preview/mmwrhtml/mm5704a4.htm?s_cid=mm5704a4_e

CDC. Treating opportunistic infections among HIV-exposed and infected children. MMWR 2004; 

53 (No. RR-14). www.cdc.gov/mmwr/preview/mmwrhtml/rr5314a1.htm

CDC. Treating opportunistic infections among HIV-infected adults and adolescents. MMWR 2004; 

53 (No. RR-15). www.cdc.gov/mmwr/preview/mmwrhtml/rr5315a1.htm

CDC. Treatment of tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society 

of America. MMWR 2003; 52 (No. RR-11). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm

Errata (January 7, 2005)

www.cdc.gov/MMWR/preview/MMWRhtml/mm5351a5.htm

Chapter 7 – Tuberculosis Infection Control

189

Table of Contents

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191

Infectiousness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192

TB Infection Control Measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196

TB Infection Control Program................................................ 199

TB Infection Control in Nontraditional Facility-based Settings . . . . . . . . . . . . . . . . . . . . . . 218

TB Infection Control in the Home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226

Chapter Objectives

After working through this chapter, you should be able to 

• Describe the factors that determine the infectiousness of a tuberculosis (TB) patient;

• Explain the main goals of a TB infection control program;

• Discuss the three levels of an effective TB infection control program;

• Explain the purpose and the characteristics of a TB airborne infection isolation room; and

• Describe the circumstances when respirators and surgical masks should be used.

Chapter 7 

Tuberculosis Infection Control

Chapter 7 – Tuberculosis Infection Control

191

Introduction

M. tuberculosis can be transmitted in virtually any setting. Clinicians should be aware that 

transmission has been documented in health-care settings where health-care workers (HCWs) and 

patients come in contact with persons with infectious TB who 

• Have unsuspected TB disease,

• Have not received adequate or appropriate treatment, or

• Have not been separated from others.

Health-care settings in this context include clinics and hospitals, as well as nontraditional facilitybased settings such as emergency medical services, correctional facilities, home-based health-care 

and outreach settings, long-term care facilities, and homeless shelters. People who work or receive 

care in health-care settings (as referenced above) are at higher risk for becoming infected with 

M. tuberculosis; therefore, it is necessary to have a TB infection control plan as part of a general 

infection control program designed to ensure the following:

• Prompt detection of TB;

• Airborne precautions; and

• Treatment of persons who have been suspected or confirmed to have TB disease 

(see Chapter 2, Transmission and Pathogenesis of Tuberculosis). 

People who work or receive care in health-care settings are at 

higher risk for becoming infected with M. tuberculosis; therefore, 

it is necessary to have a TB infection control plan.

Study Question

7.1 In which of the following health-care settings can TB be transmitted? 

(circle the one best answer)

F. Where TB patients have not received adequate and appropriate treatment.

G. Where TB patients have not been separated from others. 

H. Where persons who have unsuspected TB disease come into contact with others.

I. A, B, and C are all correct.

J. Only A and B are correct.
Chapter 7 – Tuberculosis Infection Control

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Infectiousness

The infectiousness of a TB patient is directly related to the number of droplet nuclei carrying 

M. tuberculosis (tubercle bacilli) that are expelled into the air. Depending on the environment, these 

tiny particles can remain suspended in the air for several hours. M. tuberculosis is transmitted through 

the air, not by surface contact. Infection occurs when a person inhales droplet nuclei containing 

M. tuberculosis, and the droplet nuclei traverse the mouth or nasal passages, upper respiratory 

tract, and bronchi to reach the alveoli of the lungs. Persons with extrapulmonary TB disease may 

have concurrent unsuspected pulmonary or laryngeal TB disease. Except for laryngeal TB disease, 

extrapulmonary TB disease is rarely infectious; however, transmission from extrapulmonary sites has 

been reported to occur during aerosol-producing procedures such as autopsies and tissue irrigation. 

The characteristics of a patient with TB disease that are associated with infectiousness include, but 

are not limited to, those listed in Table 7.1. 

The infectiousness of a TB patient is directly related to the number of droplet 

nuclei carrying M. tuberculosis (tubercle bacilli) that are expelled into the air.

Infection occurs when a person inhales droplet nuclei containing 

M. tuberculosis, and the droplet nuclei traverse the mouth or nasal passages, 

upper respiratory tract, and bronchi to reach the alveoli of the lungs.
Chapter 7 – Tuberculosis Infection Control

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Table 7.1

Infectiousness of People Known to

Have or Suspected of Having TB Disease* 

Factors Associated with 

Noninfectiousness

Factors Associated with

Infectiousness

No cough Presence of a cough

No cavity in the lung Cavity in the lung

No acid-fast bacilli on sputum smear Acid-fast bacilli on sputum smear

Extrapulmonary (non-pulmonary) TB disease TB disease of the lungs, airway, or larynx

Receiving adequate treatment for 2 weeks or 

longer

Not receiving adequate treatment

Not undergoing cough-inducing procedures Undergoing cough-inducing procedures 

(e.g., bronchoscopy, sputum induction, and 

administration of aerosolized medications)

Negative sputum cultures Positive sputum cultures

 * Infectiousness depends on a variety of factors. Clinicians should consider all of these factors when 

determining whether a TB patient should be considered infectious.

In general, young children with pulmonary TB disease are less likely than adults to be infectious, 

because children are sometimes unable to produce sputum when they cough, or may have 

paucibacillary TB. However, it is still possible for children to transmit M. tuberculosis to others if 

they have infectious characteristics, such as a positive AFB smear or cavity on a chest radiograph.

In general, young children with pulmonary TB disease are less likely 

than adults to be infectious, because children are sometimes unable to 

produce sputum when they cough, or may have paucibacillary TB.

For most patients, infectiousness appears to decline rapidly after adequate and appropriate 

treatment is started; however, the rate of decline varies from patient to patient. Some patients with 

unrecognized or inadequately treated drug-resistant TB disease may remain infectious for weeks or 

even months. Patients with drug-resistant TB disease may not respond to the initial drug regimen, 

acquire further drug resistance, and remain infectious until they receive adequate treatment.

Infectiousness appears to decline rapidly after adequate and appropriate 

treatment is started; however, the rate of decline varies from patient to patient.
Chapter 7 – Tuberculosis Infection Control

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Persons with extrapulmonary TB disease are usually noninfectious unless they also have pulmonary 

disease, TB disease located in the oral cavity or the larynx, or extrapulmonary disease that includes 

an open abscess or lesion in which the concentration of organisms is high. Pulmonary TB should be 

ruled out when there is a diagnosis of extrapulmonary TB disease. Table 7.2 indicates the criteria for 

patients to be considered noninfectious. 

Table 7.2 

Criteria for Patients to Be Considered Noninfectious

Criteria

Patients can be considered noninfectious when they meet all of the following three criteria:

1. They have three consecutive negative AFB sputum smears collected in 8- to 24-hour intervals 

(at least one being an early morning specimen);

2. Their symptoms have improved clinically (for example, they are coughing less and they no

longer have a fever); and

3. They are compliant with an adequate treatment regimen for 2 weeks or longer. 

It is important to consider the environmental factors that enhance the probability that M. tuberculosis

will be transmitted (Table 7.3). 

Table 7.3

Environmental Factors that Enhance the Probability that 

M. tuberculosis Will Be Transmitted

Factor Description

Concentration of 

infectious bacilli

The more bacilli in the air, the more probable that 

M. tuberculosis will be transmitted

Space Exposure in small, enclosed spaces

Ventilation Inadequate local or general ventilation that results in 

insufficient dilution or removal of infectious droplet nuclei

Air circulation Recirculation of air containing infectious droplet nuclei

Specimen handling Improper specimen handling procedures that generate 

infectious droplet nuclei

Air pressure Positive air pressure in infectious patient’s room that causes 

M. tuberculosis organisms to flow to other areas
Chapter 7 – Tuberculosis Infection Control

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Study Questions

Indicate if the following statements about infectiousness are true or false. 

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.)

Patients True or False

____ 7.2 Children are more likely than adults to be infectious.

____ 7.3 For most patients, infectiousness appears to decline 

rapidly after adequate treatment is started.

____ 7.4 Some patients with unrecognized or inadequately treated 

drug-resistant TB disease may remain infectious for 

weeks or even months.

____ 7.5 Patients with drug-resistant TB disease may not respond 

to the initial drug regimen, acquire further drug 

resistance, and may remain infectious until they receive 

adequate treatment.

A. True

B. False

7.6 Patients can be considered noninfectious when they meet which of the following criteria? 

(choose the one best answer)

A. They are compliant with an adequate regimen for 2 weeks or longer. 

B. Their symptoms have improved clinically.

C. They have three consecutive negative sputum smears collected in 8- to 24-hour intervals 

(at least one being an early morning specimen).

D. A, B, and C are all correct.

E. Only A and B are correct.

7.7 Which of the following environmental factors can enhance the probability that 

M. tuberculosis will be transmitted? 

(choose the one best answer)

A. Concentration of infectious bacilli in the air

B. Exposure in small, enclosed spaces

C. Inadequate local or general ventilation that results in insufficient dilution or removal of 

infectious droplet nuclei

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 7 – Tuberculosis Infection Control

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TB Infection Control Measures

TB infection control measures should be based on a careful assessment of risk for transmission of TB 

in the facility or setting. The goals of effective TB infection control programs are to 

• Detect TB disease early and promptly;

• Isolate those who have or are suspected of having TB disease (airborne precautions); and

• Treat people who have or who are suspected of having TB disease.

TB infection control measures should be based on a careful 

assessment of risk for transmission of TB in the facility or setting.

Detection of TB Disease

The primary risk to health-care workers (HCWs) and the general population is the undiagnosed or 

unsuspected patient with TB disease. Within health-care settings, protocols should be implemented 

and enforced to promptly identify, isolate, separate, and either transfer or manage persons who have 

suspected or confirmed TB disease. Personnel who admit patients to facilities should be trained to 

detect signs and symptoms of TB disease. People suspected of having TB disease should be given 

a diagnostic evaluation as soon as possible (see Chapter 4, Diagnosis of Tuberculosis Disease). 

Clinicians and other HCWs should suspect TB disease in people who have any of the symptoms 

listed in Table 7.4 and isolate them until TB is excluded.

Table 7.4 

Symptoms of TB Disease

Symptoms

People who have any of the following symptoms should 

be evaluated for TB disease:

• Persistent cough (3 weeks or longer);

• Chest pain;

• Bloody sputum;

• Weight loss or loss of appetite;

• Fever; 

• Chills; 

• Night sweats;

• Malaise; or

• Fatigue
Chapter 7 – Tuberculosis Infection Control

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The primary risk to health-care workers (HCWs) and the general 

population is the undiagnosed or unsuspected patient with TB disease.

Airborne Precautions

TB airborne precautions should be initiated for any patient who has signs or symptoms of TB disease 

(suspected TB), or who has documented infectious TB disease and remains infectious in spite of 

treatment.

TB airborne precautions should be initiated for any patient who has 

signs or symptoms of TB disease (suspected TB), or who has documented 

infectious TB disease and remains infectious in spite of treatment.

Persons who have or are suspected of having infectious TB disease should be placed in an area 

away from other patients, preferably in an airborne infection isolation (AII) room. An AII room is 

a single-occupancy patient-care room in which environmental factors are controlled to minimize 

transmission of infectious agents. If a facility does not have an AII room, patients should be placed 

in a room that has been designated for isolation of persons with suspected or known infectious TB 

disease and, if possible, referred to a facility with an AII room.

A patient who has drug-susceptible TB of the lung, airway, or larynx, who is on standard multidrug 

antituberculosis treatment, and who has had a substantial clinical and bacteriologic response to 

therapy (e.g., reduction in cough, resolution of fever, and progressively decreasing quantity of AFB 

on smear result) is probably no longer infectious. However, because culture and drug-susceptibility 

results are not usually known when the decision to discontinue airborne precautions is made, all 

patients with suspected TB disease should remain under airborne precautions until they have had 

three consecutive negative AFB sputum smear results, each collected in 8- to 24-hour intervals, with 

at least one being an early morning specimen; have received standard multidrug antituberculosis 

treatment (minimum of 2 weeks); and have demonstrated clinical improvement.

Airborne precautions in a health-care or congregate setting may 

be discontinued when a patient has been on adequate therapy 

for 2 weeks or longer, symptoms improve, and there have been 

three consecutive, negative AFB sputum smear results. 

Treatment 

Patients who have confirmed TB disease, or who are considered highly probable to have TB disease, 

should promptly start appropriate treatment (see Chapter 6, Treatment of Tuberculosis Disease).
Chapter 7 – Tuberculosis Infection Control

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Study Questions

7.8 Which of the following is NOT a goal of an effective TB infection control program?

(choose the one best answer)

A. Detect TB disease early and promptly.

B. Isolate from others those people who have or are suspected of having TB disease.

C. Ensure everyone wears a personal respirator.

D. Treat people who have or are suspected of having TB disease.

7.9 The primary risk to health-care workers and the general population is the undiagnosed or 

unsuspected patient with TB disease. 

(choose the one best answer)

A. True

B. False

7.10 TB airborne precautions should be initiated for which of the following patients? 

(choose the one best answer)

A. Any patient who has signs or symptoms of TB disease

B. Any patient who has documented infectious TB disease and remains infectious 

in spite of treatment

C. Any patient who has TB meningitis

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 7 – Tuberculosis Infection Control

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TB Infection Control Program

A TB infection control program should be based on the following three levels of hierarchy (Table 7.8):

1. Administrative controls, which reduce risk of exposure;

2. Environmental controls, which prevent spread and reduce concentration of droplet nuclei; 

and

3. Respiratory-protection controls, which further reduce risk of exposure in special areas and 

circumstances.

1. Administrative Controls

The first and most important level of a TB infection control program is the use of administrative 

measures to reduce the risk of exposure to persons who might have TB disease. Administrative 

controls consist of implementing the following activities:

• Assigning someone the responsibility and authority for TB infection control in the health-care 

setting;

• Conducting a TB infection control risk assessment of the setting;

• Developing and instituting a written TB infection control plan to ensure prompt detection, 

separation from others (into an AII room if possible), and treatment of persons who have 

suspected or confirmed TB disease;

• Ensuring the availability of recommended laboratory processing, testing, and reporting of 

results;

• Implementing effective work practices for managing patients who may have TB disease;

• Ensuring proper cleaning, sterilization, or disinfection of equipment that might be 

contaminated (e.g., endoscopes); 

• Educating, training, and counseling HCWs, patients, and visitors about TB infection and 

disease;

• Testing and evaluating workers who are at risk for exposure to TB disease;

• Applying epidemiology-based prevention principles, including the use of setting-related TB 

infection control data;

• Using posters and signs to remind patients and staff of proper cough etiquette (covering mouth 

when coughing) and respiratory hygiene; and

• Coordinating efforts between local health department and high-risk health-care and congregate 

settings.

The first and most important level of a TB infection control 

program is the use of administrative measures to reduce the 

risk for exposure to persons who might have TB disease.
Chapter 7 – Tuberculosis Infection Control

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Health-Care Worker Education and Training

Health-care worker (HCW) education and training on TB infection and disease is an essential part 

of a TB infection control program and can increase adherence to TB infection control measures. 

Education and training should emphasize the increased risks posed by an undiagnosed person with 

TB disease in a health-care setting and the specific measures to reduce this risk. Health-care settings 

should document that all HCWs, including physicians, have received training relevant to their work 

setting. Resources for TB education and training can be found on the following websites:

• CDC DTBE website (www.cdc.gov/tb);

• Find TB Resources website (www.findtbresources.org); and

• Regional Training and Medical Consultation Centers’ TB Training and Education Products 

website (https://sntc.medicine.ufl.edu/rtmccproducts.aspx.)

All health-care settings should conduct an annual evaluation for follow-up education and training 

based on the

• Number of untrained or new HCWs;

• Changes in the organization and services of the health-care setting; and 

• Availability of new TB infection control information. 

Facility Risk Assessment

Health-care and congregate settings should conduct an annual evaluation of the risk for transmission 

of M. tuberculosis. The risk assessment determines the type of administrative, environmental, and 

respiratory-protection controls needed by examining the

• Number of patients with TB disease in the setting; 

• Promptness of detection, isolation, and evaluation of patients with suspected or confirmed TB 

disease;

• Evidence of transmission of M. tuberculosis in the setting; and

• Community rate of TB disease.

Health-care and congregate settings should conduct an annual 

evaluation of the risk for transmission of M. tuberculosis.

Risk Classification

The purpose of the risk classification is to determine the need for a TB testing program for HCWs 

and the frequency of testing. The risk classification, or risk level, will vary; however, all settings 

should perform risk classification as part of risk assessment to determine the need for and frequency 

of a HCW testing program, regardless of the likelihood of encountering persons with TB disease. 

Baseline TB testing should be conducted for HCWs upon hiring (see Chapter 3, Testing for 

Tuberculosis Infection and Disease). The three TB risk classifications are indicated in Table 7.5. 
Chapter 7 – Tuberculosis Infection Control

201

Table 7.5

TB Risk Classifications

Risk

Classification

Need for

Testing

Frequency of 

Testing

Low risk Should be used for settings in 

which persons with TB disease are 

not expected to be encountered.

Exposure to M. tuberculosis in 

these settings is unlikely, and 

further testing is not needed 

unless exposure has occurred. 

Medium risk Should be used for facilities in 

which the risk assessment has 

determined that HCWs will possibly 

be exposed to persons with TB 

disease.

Repeat testing should be done 

annually.

Potential ongoing 

transmission

Should be temporarily assigned to 

any setting where there is evidence 

of person-to-person transmission of 

M. tuberculosis in the past year.

Testing should be repeated 

every 8 to 10 weeks until there 

is no evidence of ongoing 

transmission.

2. Environmental Controls

The second level of hierarchy is the use of environmental controls to prevent the spread and reduce 

the concentration of droplet nuclei and includes:

• Primary environmental controls; and

• Secondary environmental controls (Table 7.6).

The second level of hierarchy is the use of environmental controls to 

prevent the spread and reduce the concentration of droplet nuclei.
Chapter 7 – Tuberculosis Infection Control

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Table 7.6 

Environmental Controls

Primary Environmental

Control

Secondary Environmental 

Control

Controls the source of infection by diluting 

and removing contaminated air and by using 

general ventilation

• Uses natural ventilation (e.g., open doors, 

windows)

• Uses mechanical ventilation equipment to 

circulate and move air in a building 

• Uses local exhaust ventilation (e.g., hoods, 

tents, or booths) 

Controls airflow in areas adjacent to the 

source and cleans air

• Controls the airflow to prevent 

contamination of air in areas adjacent to 

the source (AII rooms) 

• Cleans the air by using high efficiency 

particulate air (HEPA) filtration or 

ultraviolet germicidal irradiation (UVGI)

Primary Environmental Controls

Primary environmental controls consist of controlling the source of infection by using local exhaust 

ventilation (e.g., hoods, tents, or booths) and diluting and removing contaminated air by using 

general ventilation.

Ventilation is the movement and the replacement of air in a building with air from the outside or 

with clean, recirculated air. When fresh air enters a room, it dilutes the concentration of particles in 

room air, such as droplet nuclei. There are two types of ventilation:

• Natural ventilation 

• Mechanical ventilation

Natural Ventilation

Natural ventilation relies on cross ventilation in a building designed for good air exchange; for 

example, the use of open doors and windows to bring in air from outside. Natural ventilation can be 

useful for nontraditional facility-based and congregate settings that do not have a central ventilation 

system. In these settings, waiting rooms, shelter dormitories, or other rooms in which people 

congregate should have an operable window, door, or skylight that is kept open as often as possible. 

Fans can be used to help distribute the air (Figure 7.1). If the direction of airflow is unknown, staff 

should sit near the fresh air source and clients should sit near the exhaust location (Figure 7.2). 

This can help protect staff from droplet nuclei expelled by patients with unidentified TB disease. 

In addition to these environmental measures, cough etiquette and respiratory hygiene should be 

encouraged to further reduce risk (Figure 7.3).
Chapter 7 – Tuberculosis Infection Control

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Figure 7.1

Exhaust Fan Used for Distributing Air
Chapter 7 – Tuberculosis Infection Control

204

Figure 7.2

Natural Ventilation in TB Exam or Counseling Room

TB Exam 

or 

Counseling Room

Air out through 

open window

Chair for

health-care 

worker

Chairfor 

patient

Exam or 

counseling 

table

Air in through 

vent in door
Chapter 7 – Tuberculosis Infection Control

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Figure 7.3

Person with Infectious TB in Waiting Room

Mechanical Ventilation

Mechanical ventilation refers to the use of equipment to circulate and move air in a building. 

Mechanical ventilation should be used by hospitals, TB clinics, and other health-care and congregate 

settings expecting to see a confirmed or suspected TB patient. Mechanical ventilation consists of

• Local exhaust ventilation; and 

• General ventilation.

Local exhaust ventilation stops airborne contaminants before they spread into the general 

environment. Local exhaust ventilation includes the use of

• External hoods;

• Booths; and

• Tents. 

Local exhaust ventilation should be used for cough-inducing and aerosol-generating procedures 

(Figure 7.4). If local exhaust ventilation cannot be used, cough-inducing and aerosol-generating 

procedures should be performed in an AII room. If an AII room is not available, the procedures 

should be performed outdoors and away from

• People;

• Windows; and

• Air intakes. 
Chapter 7 – Tuberculosis Infection Control

206

Figure 7.4

Local Exhaust in Sputum Collection Booth

Air in through 

vent in door

Prefilter

HEPA filter

Exhaust to 

room or outside

Sputum 

Collection 

Booth

General ventilation systems maintain air quality in health-care settings by the 

• Dilution of contaminated air;

• Removal of contaminated air; and 

• Control of airflow patterns in the patient’s procedure room or setting 

(e.g., negative pressure in AII rooms) (Figure 7.5). 
Chapter 7 – Tuberculosis Infection Control

207

Figure 7.5

Airborne Infection Isolation (AII) Room

10’

12’

Corridor

TB Patient Room

• 10’x 12’ (120 sq. ft. per patient)

• 8’ 6” high ceiling

Negative air flow

Minimum 

210 CFM

exhaust

Supply air system

160 CFM

supply

50 CFM

≥ 12 air changes per hour

Window

Patient

bed

Private 

Bathroom

TB AII rooms are designed to prevent the spread of droplet nuclei expelled by a patient with TB 

disease. In TB clinics, hospitals, and other inpatient settings, patients known to have TB disease or 

suspected of having TB disease should be placed in a TB AII room immediately. Health-care facilities 

that provide care for patients with suspected or confirmed TB disease should have at least one AII 

room. Medical facilities in correctional settings should also have at least one AII room. The need for 

additional AII rooms should be based on the TB risk assessment for the setting. 

In TB clinics, hospitals, and other inpatient settings, patients 

known to have TB disease or suspected of having TB disease 

should be placed in a TB AII room immediately.
Chapter 7 – Tuberculosis Infection Control

208

Health-care facilities that provide care for patients with 

suspected or confirmed TB disease and medical facilities in 

correctional settings should have at least one AII room.

One characteristic of AII rooms is their negative pressure relative to other parts of the facility. 

Negative pressure causes air to flow from the corridors into the AII room. The air from the AII room 

cannot escape to the other parts of the health-care setting when the door is closed and the ventilation 

system is operating properly. The doors and windows of AII rooms must be kept closed as much as 

possible in order to maintain negative pressure, and the pressure must be checked periodically to 

make sure that it remains negative. Air from the AII room can be exhausted directly to the outdoors, 

where the droplet nuclei will be diluted in the outdoor air, or passed through a special high efficiency 

particulate air (HEPA) filter that removes most (99.97%) of the droplet nuclei before it is returned 

to the general circulation. If a HEPA filter is not used, the air should be exhausted directly to the 

outside away from air-intake vents, persons, and animals, in accordance with applicable federal, state, 

and local regulations on environmental discharges. 

One characteristic of AII rooms is the negative pressure 

relative to other parts of the facility. Negative pressure allows 

air to flow from the corridors into the AII room.

Air from the AII room can be exhausted directly to the outdoors, where 

the droplet nuclei will be diluted in the outdoor air, or passed through a 

special high efficiency particulate air filter that removes most (99.97%) 

of the droplet nuclei before it is returned to the general circulation.

In existing health-care settings, AII rooms should have airflow of six or more air changes per hour 

(ACH). In new or renovated health-care settings, AII rooms should have airflow of at least 12 ACH. 

When feasible, the airflow in existing health-care setting AII rooms should be increased to 12 ACH by

• Adjusting or modifying the ventilation system; or

• Using air-cleaning methods: room-air recirculation units containing HEPA filters or ultraviolet 

germicidal irradiation (UVGI) systems that increase the equivalent ACH. 

It is important that AII rooms be single-patient rooms with a private bathroom. Entry of visitors 

and HCWs should be restricted and monitored to minimize the transmission of M. tuberculosis. 

All HCWs who enter an AII room should wear N95 disposable filtering facepiece respirators (see 

Respiratory-Protection Controls). An N95 respirator should be fitted correctly before using. Visitors 

should be offered and encouraged to use respiratory protection (i.e., N95 respirator) and instructed 

by HCWs on how to use it.

Health-care settings with AII rooms should observe the policies and practices indicated in Table 7.7. 
Chapter 7 – Tuberculosis Infection Control

209

Table 7.7 

Policies and Practices for Airborne Infectious Isolation 

(AII) Rooms in Health-Care Settings

Policies and Practices

• Keep doors and windows closed as much as possible;

• Maintain an adequate number of AII rooms;

• Check negative pressure by monitoring and recording the direction of airflow 

on a daily basis;

• Perform diagnostic and treatment procedures in the AII room;

• Ensure patients adhere to AII precautions;

• Group AII rooms in one part of the health-care setting;

• Schedule patients with suspected and confirmed infectious TB disease for 

procedures when few HCWs and no other patients are present; 

• Provide a surgical mask for patients with suspected or confirmed infectious TB 

disease during transport, in waiting areas, and when others are present; and

• Review environmental control maintenance procedures and logs to determine 

if maintenance is being conducted properly and regularly.

Secondary Environmental Controls

Secondary environmental controls consist of controlling the airflow to prevent contamination of air 

in areas adjacent to the source (AII rooms) and cleaning the air by using HEPA filtration (Figure 7.6) 

or ultraviolet germicidal irradiation (UVGI) (Figure 7.7). HEPA filters can be used to filter droplet 

nuclei from the air and must be used when discharging air from: 

• Local exhaust ventilation booths or enclosures directly into the surrounding room or area; and 

• An AII room (or other negative-pressure room) into the general ventilation system (e.g., in 

settings in which the ventilation system or building configuration makes venting the exhaust to 

the outside impossible). 

Secondary environmental controls consist of controlling the airflow 

to prevent contamination of air in areas adjacent to the source 

(AII rooms) and cleaning the air by using HEPA filtration or UVGI.

UVGI is an air-cleaning technology that consists of the use of special lamps that give off germicidal 

ultraviolet irradiation (wave length=254 nm). The lamps are used to inactivate the tubercle bacilli 

contained in the droplet nuclei. Overexposure to UV light can be harmful to the skin and eyes; 

lamps must be installed in the upper part of rooms or corridors or placed in exhaust ducts. Regular, 

appropriate maintenance is essential to ensure UVGI lamps are operating correctly.
Chapter 7 – Tuberculosis Infection Control

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Figure 7.6

HEPA Filter

Figure 7.7

Ultraviolet Germicidal Irradiation (UVGI)

3. Respiratory-Protection Controls

Respiratory-protection control is the third level of a TB infection control program and consists of the 

use of personal protective equipment in situations that pose a high risk for exposure to TB disease 

(Figure 7.8). Use of respiratory protection can further reduce risk for exposure of HCWs to droplet 

nuclei expelled into the air. The following measures can be taken to reduce risk for exposure:

• Implementing a respiratory-protection program;

• Training HCWs on respiratory protection; and

• Educating patients on respiratory hygiene and the importance of cough etiquette.

Respiratory-protection control is the third level of a TB infection 

control program and consists of the use of protective equipment 

in situations that pose a high risk for exposure to TB disease.
Chapter 7 – Tuberculosis Infection Control

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Figure 7.8

Health-Care Worker and Infectious TB Patient

Using Respiratory Protection

All health-care settings that use respiratory-protection controls are required by the Occupational 

Safety and Health Administration (OSHA) to develop, implement, and maintain a respiratoryprotection program. 

Administrative and environmental controls minimize the number of areas in which exposure to 

M. tuberculosis might occur and therefore minimize the number of persons exposed. These control 

measures also reduce, but do not eliminate, the risk for exposure in limited areas. In these settings, 

respiratory protection should be used by all persons, including HCWs and visitors. These settings 

include:

• TB AII rooms;

• Rooms where cough-inducing or aerosol generating procedures are done;

• Ambulances and other vehicles transporting infectious TB disease patients; and

• Homes of infectious TB disease patients (for HCWs; other persons should not visit the homes 

of infectious persons).

The effectiveness of a respiratory-protection program requires the development of written standard 

procedures. Standard procedures should include information and guidance for the proper selection, 

use, and care of respirators. Settings where HCWs use respiratory protection to prevent transmission 

of M. tuberculosis should develop, implement, and maintain a respiratory-protection program. The 

program should provide HCWs with annual training on TB control, TB infection control, and 

respiratory protection, including fit-testing.

Settings where HCWs use respiratory protection to prevent 

transmission of M. tuberculosis should develop, implement, 

and maintain a respiratory-protection program.
Chapter 7 – Tuberculosis Infection Control

212

The minimum respiratory protection is a filtering face-piece respirator and must be selected from 

those approved by CDC/National Institute for Occupational Safety and Health (NIOSH) under 

Title 42 CFR, Part 84. It must meet one of the following specifications:

• Nonpowered air-purifying respirators (N95, N99, N100, R95, R99, R100, P95, P99, and 

P100), including disposables; 

• Powered air-purifying respirators (PAPRs) with high-efficiency filters; or

• Supplied-air respirators.

It is important that respirators fit different face sizes and features properly. It is also important to 

understand the difference between respirators and surgical masks.

Respirators are designed to protect HCWs and other individuals from inhaling droplet nuclei (Figure 

7.9). Surgical masks are designed to reduce the number of droplets being exhaled into the air by 

persons with infectious TB disease when they breathe, talk, cough, or sneeze (Figure 7.10). Persons 

suspected or confirmed to have infectious TB disease should be given, and encouraged to use, a 

surgical mask to minimize the risk of expelling droplet nuclei into the air. 

Respirators are designed to protect HCWs and other 

individuals from inhaling droplet nuclei. 

Surgical masks are designed to reduce the number of droplets 

being exhaled into the air by persons with infectious TB 

disease when they breathe, talk, cough, or sneeze. 
Chapter 7 – Tuberculosis Infection Control

213

Figure 7.9

Respirator for

Health-Care Workers

Figure 7.10

Surgical Mask for 

Persons with Infectious TB Disease

Health-care worker wearing

a respirator

Infectious TB patient wearing

a surgical mask

Respirators

• Designed to filter out droplet nuclei from 

being inhaled by the health-care worker 

and other individuals.

• Should properly fit different face sizes and 

features.

• Should NOT be worn by the patient.

Surgical masks

• Designed to stop droplet nuclei from 

being spread (exhaled) by the patient.

• Should NOT be worn by the health-care 

worker
Chapter 7 – Tuberculosis Infection Control

214

Table 7.8

TB Infection-Control Program: Level of Controls

Administrative Controls

• Assign responsibility for TB infection control 

• Conduct TB risk assessment 

• Develop and institute a written TB infection-control plan 

• Ensure the timely availability of recommended laboratory processing, testing, and 

reporting of results

• Implement effective work practices for the management of patients with suspected 

or confirmed TB disease

• Ensure proper cleaning and sterilization or disinfection of potentially contaminated 

equipment 

• Train and educate health-care workers 

• Test and evaluate health-care workers for TB infection and disease

• Apply epidemiology-based prevention principles 

• Use posters and signs demonstrating and advising respiratory hygiene and cough 

etiquette

• Coordinate efforts with the local or state health department.

Environmental Controls

• Reduce concentration of infectious droplet nuclei through the following technologies:

» Ventilation technologies, including

− Natural ventilation

− Mechanical ventilation

» High efficiency particulate air filtration (HEPA) 

» Ultraviolet germicidal irradiation (UVGI)

Respiratory Protection Controls

• Implement a respiratory-protection program 

• Train health-care workers on respiratory protection

• Educate patients on respiratory hygiene and the importance of covering their cough

• Test HCWs for mask fit and functionality
Chapter 7 – Tuberculosis Infection Control

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Study Questions

Case study–Jose

Jose, the Harris County TB Control Manager, is conducting a risk assessment to determine 

the type of administrative, environmental, and respiratory-protection controls that are 

needed in his area.

7.11 What things should Jose examine? 

(choose the one best answer)

A. Number of patients with TB disease in the setting and the community rate of TB disease

B. Evidence of transmission of M. tuberculosis in the setting

C. Promptness of detection, isolation, and evaluation of patients with suspected or confirmed 

TB disease. 

D. A, B, and C are all correct.

E. Only A and B are correct.

Match the setting and testing characteristics for each type of TB risk classification.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.)

Setting and Testing Characteristics TB Risk Classification

____ 7.12 Temporarily assigned to any setting with evidence 

of person-to-person transmission of M. tuberculosis

in the past year.

____ 7.13 Setting where persons with TB disease are not

expected to be encountered.

____ 7.14 Facilities in which the risk assessment has 

determined that health-care workers will 

possibly be exposed to persons with TB disease.

____ 7.15 Repeat testing is not needed unless exposure 

has occurred.

____ 7.16 Repeat testing should be done every 8 to 10 weeks 

until there is no evidence of ongoing transmission. 

____ 7.17 Repeat testing should be done annually.

A. Low-risk 

classification

B. Medium-risk 

classification

C. Potential ongoing 

transmission 

classification
Chapter 7 – Tuberculosis Infection Control

216

Indicate whether the types of environmental controls below are primary or secondary controls.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.)

Environmental 

Controls

Primary/Secondary 

Controls

____ 7.18 HEPA filtration

____ 7.19 Natural, mechanical, and local exhaust ventilation

____ 7.20 Ultraviolet germicidal irradiation 

____ 7.21 Controls airflow in areas adjacent to the source and 

cleans air

____ 7.22 Controls the source of infection by diluting and 

removing contaminated air and by using general 

ventilation

A. Primary control

B. Secondary control

Indicate if the following statements about TB airborne infection isolation (AII) rooms are true 

or false. (Choose the one best answer and write the letter for the correct answer on the line next to 

the question number.)

Statements about TB AII Rooms True or False

____ 7.23 Designed to prevent the spread of the droplet nuclei 

to other rooms in the facility.

____ 7.24 Have positive pressure relative to other parts of the 

facility.

____ 7.25 Air from the AII room is exhausted directly to the 

outdoors, or passes through a special filter that 

removes all of the droplet nuclei.

____ 7.26 Entry of visitors and health-care workers should 

be restricted and monitored to minimize the 

transmission of M. tuberculosis.

____ 7.27 Patients staying in AII rooms should wear N95 

disposable filtering face-piece respirators.

____ 7.28 AII rooms can be used for multiple patients.

A. True

B. False
Chapter 7 – Tuberculosis Infection Control

217

7.29 Which of the following respiratory protection measures reduces risk for exposure to TB 

disease? (choose the one best answer)

A. Implementing a respiratory-protection program

B. Training health-care workers on respiratory protection

C. Educating patients on respiratory hygiene and the importance of cough etiquette

D. A, B, and C are all correct.

E. Only A and B are correct.

7.30 Which of the following statements about respiratory protection is true? 

(choose the one best answer)

A. Respirators are designed to protect health-care workers and other individuals from 

inhaling droplet nuclei.

B. Surgical masks are designed to reduce the number of droplets being exhaled into the air by 

persons with infectious TB disease. 

C. Health-care workers can wear surgical masks for protection against droplet nuclei, and 

persons with infectious TB disease can wear respirators to prevent the spread of TB.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 7 – Tuberculosis Infection Control

218

Match the activities with the type of TB infection control.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.)

Activities TB Infection Controls

____ 7.31 Use natural exhaust ventilation and mechanical 

ventilation to remove contaminated air.

____ 7.32 Use personal protective equipment in situations that 

pose a high risk for exposure to TB disease.

____ 7.33 Assign someone the responsibility and authority for 

TB infection control in the health-care setting.

____ 7.34 Ensure the availability of recommended laboratory 

processing, testing, and reporting of results.

____ 7.35 Control the airflow to prevent contamination of air 

in areas adjacent to the source and clean the air by 

using HEPA filtration or UVGI.

____ 7.36 Conduct a TB infection control risk assessment of 

the setting.

A. Administrative 

controls

B. Environmental 

controls

C. Respiratory 

protection controls

TB Infection Control in 

Nontraditional Facility-Based Settings

All nontraditional facility-based settings where patients with TB disease receive care should establish 

and follow a TB infection control program. These settings include but are not limited to

• Correctional facilities;

• Homeless shelters;

• Long-term care facilities; 

• Home-based health-care and outreach settings; and

• Emergency medical services (EMS) (Table 7.9).

All nontraditional facility-based settings where patients with TB disease 

receive care should establish and follow a TB infection control program.
Chapter 7 – Tuberculosis Infection Control

219

Correctional Facilities

TB disease can be a substantial health concern in correctional facilities. TB outbreaks in correctional 

facilities can lead to transmission in surrounding communities. Health-care settings in correctional 

facilities should be classified as at least medium risk based on the possibility of exposure to persons 

with TB disease. Correctional facilities overall are classified as minimal risk or non-minimal risk 

based on the TB risks of the population housed in the facility. A respiratory-protection program 

should be implemented with at least one AII room available where inmates with suspected or 

confirmed TB disease can be isolated immediately. Those inmates who must be transported should 

wear a surgical mask during transport. Correctional facilities should maintain a tracking system for 

inmate TB testing and treatment, and establish a mechanism for sharing this information with state 

and local health departments and other correctional facilities. 

Homeless Shelters

TB disease is more common in the homeless population than in the general population. Several 

factors in the shelter environment can influence the likelihood of M. tuberculosis transmission, 

including crowding and the state of the ventilation system. The absolute number and population 

density of persons sharing the same breathing space is important. If all other factors are constant, 

the size of the shelter population is directly proportional to the likelihood that someone with 

infectious TB will be present and that someone else will become infected. Conversely, the smaller 

the population and less crowded the shelter, the lower the risk. Homeless shelters should implement 

a tracking system for clients and establish a mechanism for sharing this information with state and 

local health departments when appropriate.

Long-Term Care Facilities

TB disease poses a health risk in long-term care facilities (LTCFs) such as hospice and skilled-nursing 

facilities. Transmission of M. tuberculosis has occurred in LTCFs and pulmonary TB disease has been 

documented in HIV-infected patients and other immunocompromised patients residing in hospices. 

LTCFs must have adequate administrative and environmental controls if they accept patients with 

suspected or confirmed infectious TB disease. These include airborne precaution capabilities and a 

respiratory-protection program. People most at risk in LTCFs include

• Patients;

• HCWs;

• Visitors; and

• Volunteers

Home-Based Health-Care and Outreach Settings

Transmission of M. tuberculosis has been documented in home-based health-care and outreach 

settings. HCWs in these settings should be able to

• Evaluate signs and symptoms of TB disease for early detection and treatment;

• Educate patients on the importance of reporting symptoms and signs of TB disease; and

• Wear an N95 personal respirator when entering homes of persons with suspected or confirmed 

infectious TB disease or when transporting such persons in an enclosed vehicle.
Chapter 7 – Tuberculosis Infection Control

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Emergency Medical Services (EMS)

Although the overall risk is low, there has been documented transmission of M. tuberculosis in EMS 

occupational settings. EMS personnel should be included in

• Comprehensive training, education, and testing programs for TB infection; and

• Follow-up testing as indicated by the risk classification of the setting. 

Drivers, HCWs, and other staff transporting patients with suspected or confirmed TB should wear 

an N95 respirator, and the patients should wear a surgical mask. In addition, ambulances should 

allow for the maximum amount of outdoor air to be circulated in the vehicle.

Table 7.9

TB Infection Control for Nontraditional Settings

Setting Transmission of 

M. tuberculosis Screening/testing Recommendations

Correctional 

facilities

• Substantial health 

concern

• TB outbreaks in 

these settings can 

lead to transmission 

in surrounding 

communities

• Heath-care settings 

in these facilities are 

at least medium risk

• All correctional 

staff should be 

screened and 

tested for TB 

annually

• Implement a respiratoryprotection program with at 

least one AII room or have a 

transfer policy

• Inmates with suspected or 

confirmed TB disease should 

be isolated immediately and 

wear a surgical mask when 

being transported outside of 

an AII room

• Facilities should maintain a 

tracking system for sharing 

information with state and 

local health departments and 

other correctional facilities

Homeless 

shelters

• Occurs in these 

settings

• More common in 

homeless shelters 

than in general 

population

• Frequent visitors are 

at risk of exposure

• Symptom 

screening

• Evaluate the resident for 

signs and symptoms of TB 

disease for early detection and 

treatment

• Educate staff on importance of 

reporting signs and symptoms 

of TB disease
Chapter 7 – Tuberculosis Infection Control

221

Setting Transmission of 

M. tuberculosis Screening/testing Recommendations

Longterm care 

facilities

• Occurs in these 

settings

• Poses a health 

risk to patients, 

health-care workers, 

visitors, and 

volunteers

• New employees 

and residents 

should receive 

symptom 

screening and 

possibly testing 

upon entry

• Must have adequate 

administrative and 

environmental controls that 

include 

» Airborn precaution 

capabilities

» Respiratory-protection 

program

• Patients with suspected 

or confirmed infectious TB 

disease should not stay 

in LTCFs unless adequate 

administrative and 

environmental controls 

are in place

Homebased 

healthcare and 

outreach 

settings

• Occurs in these 

settings

• Symptom 

screening

• Employees should 

receive annual 

screening and/or 

testing

• Evaluate the resident for 

signs and symptoms of TB 

disease for early detection and 

treatment

• Educate patients and staff on 

importance of reporting signs 

and symptoms of TB disease 

• Wear an N95 respirator when 

entering homes of persons 

suspected of having infectious 

TB disease

Emergency 

medical 

services

• Low health concern • Include a 

comprehensive 

employee 

screening 

program to test 

for TB infection

• Conduct followup testing as 

indicated by the 

risk classification 

of the setting

• Drivers, health-care workers, 

and other staff should wear an 

N95 respirator in a high-risk 

situation

• Persons with suspected TB 

who are transported in an 

ambulance should wear a 

surgical mask

• Ambulances should allow for 

maximum amount of outdoor 

air to circulate in the vehicle
Chapter 7 – Tuberculosis Infection Control

222

Study Question

7.37 Which of the following statements about TB infection control in nontraditional 

settings is true? 

(choose the one best answer)

A. All nontraditional settings where patients with TB disease receive care should establish and 

follow a TB infection control program.

B. Nontraditional settings include correctional facilities, homeless shelters, long-term care 

facilities, home-based health-care, and emergency medical services. 

C. Emergency medical services has a documented overall high level of transmission of M. 

tuberculosis. 

D. A, B, and C are all correct.

E. Only A and B are correct.

TB Infection Control in the Home

Patients who are suspected to have, or have, confirmed TB disease are frequently sent home after 

starting treatment, even though they may still be infectious. Patients with TB disease can be sent 

home even if they do not have three negative sputum smears, if the following criteria are met:

• A follow-up plan has been made with the local TB program;

• The patient is on standard TB treatment, and directly observed therapy (DOT) has been 

arranged;

• No infants or children less than 5 years of age or persons with immunocompromising 

conditions are present in the household; and

• The patient is willing to remain isolated in the home except for health-care associated visits 

until the patient has negative sputum smear results.

Patients who have suspected or confirmed TB disease are more likely to have already transmitted 

TB infection to members of their household before their TB disease was diagnosed and treatment 

was started. However, TB patients and members of their household should take steps to prevent the 

further spread of TB infection after they return home (Table 7.10). Patients with TB disease should

• Be instructed to cover their mouth and nose when coughing or sneezing;

• Sleep alone and not in a room with other household members; and

• Refrain from having visitors in the home until they are noninfectious.
Chapter 7 – Tuberculosis Infection Control

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HCWs who visit TB patients in their homes should take the following precautions to protect 

themselves from exposure to M. tuberculosis (Table 7.10):

• Instruct patients to cover their mouth and nose with a tissue when coughing or sneezing;

• Wear a respirator when visiting the home of a patient with infectious TB disease or when 

transporting a patient with infectious TB disease in a vehicle; and

• Collect specimens in a well ventilated area, away from other household members

In addition, HCWs whose responsibilities include visiting infectious patients should participate in 

an annual TB testing program.

Table 7.10

TB Infection Control in the Home

Steps that

Patients Can Take to Prevent the

Further Transmission of TB 

in the Home

Precautions for

Health-Care Workers to

Take to Protect Themselves from

Exposure to M. tuberculosis

• Cover their mouth and nose when coughing 

or sneezing 

• Sleep alone and not in a room with other 

household members

• Refrain from having visitors in the home 

until they are noninfectious.

• Instruct patients to cover their mouth 

and nose with a tissue when coughing or 

sneezing

• Wear a respirator when visiting the home of 

a patient with infectious TB disease or when 

transporting a patient with infectious TB 

disease in a vehicle

• Collect specimens in a well-ventilated area, 

away from other household members

Study Questions

7.38 Elton was just diagnosed with TB and is considered infectious. Lilian, his nurse, is 

instructing him about steps he can take to prevent the spread of TB infection to others 

when he returns home today. Which of the following steps should Lilian mention?

(choose the one best answer)

A. Cover his mouth and nose when coughing or sneezing.

B. Do not have visitors until he is noninfectious.

C. It is ok to sleep in the same room with his wife.

D. A, B, and C are all correct.

E. Only A and B are correct.
Chapter 7 – Tuberculosis Infection Control

224

Lilian will be conducting DOT at Elton’s home starting tomorrow. Which of the following 

precautions should Lilian take to protect herself from exposure to TB?

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.)

Precautions for Health-Care Workers 

Visiting the Home of a TB Patient 

Who May Be Infectious

Yes or No

____ 7.39 Spray the room where they will meet with a 

disinfectant before Elton enters it.

____ 7.40 Wear a respirator when visiting Elton’s home.

____ 7.41 Wear a surgical mask when visiting Elton’s home.

____ 7.42 Collect specimens in a well-ventilated area, away 

from other household members.

____ 7.43 Refrain from touching any surfaces in the home.

A. Yes

(take this precaution)

B. No

(this is not an 

effective precaution)

Chapter Summary

M. tuberculosis can be transmitted in virtually any setting. Clinicians should be aware that 

transmission has been documented in health-care settings where HCWs and patients come in 

contact with persons with infectious TB who 

• Have unsuspected TB disease,

• Have not received adequate treatment, or

• Have not been isolated from others.

The infectiousness of a TB patient is directly related to the number of droplet nuclei carrying 

M. tuberculosis (tubercle bacilli) that are expelled into the air. Depending on the environment, 

these tiny particles can remain suspended in the air for several hours. M. tuberculosis is transmitted 

only through the air, not by surface contact. Infection occurs when a person inhales droplet nuclei 

containing M. tuberculosis, and the droplet nuclei traverse the mouth or nasal passages, upper 

respiratory tract, and bronchi to reach the alveoli of the lungs. Persons with extrapulmonary 

TB disease may have concurrent unsuspected pulmonary or laryngeal TB disease. Except for 

laryngeal TB disease, extrapulmonary TB disease is rarely infectious; however, transmission from 

extrapulmonary sites has been reported to occur during aerosol-producing procedures such as 

autopsies and tissue irrigation.

For most patients, infectiousness appears to decline rapidly after adequate and appropriate 

treatment is started; however, the rate of decline varies from patient to patient. Some patients with 

unrecognized or inadequately treated drug-resistant TB disease may remain infectious for weeks or 

even months. Patients with drug-resistant TB disease may not respond to the initial drug regimen 

and may remain infectious until they receive adequate treatment.
Chapter 7 – Tuberculosis Infection Control

225

TB infection control measures should be based on a careful assessment of risk for transmission of TB 

in the facility or setting. The goals of effective TB infection control programs are to

• Detect TB disease early and promptly;

• Isolate those who have or are suspected of having TB disease (airborne precautions); and

• Treat people who have or are suspected of having TB disease. 

The primary risk to HCWs and the general population is the undiagnosed or unsuspected patient 

with TB disease. Within health-care settings, protocols should be implemented and enforced to 

promptly identify, isolate, and either transfer or manage persons who have suspected or confirmed 

TB disease. Personnel who admit patients to facilities should be trained to detect signs and 

symptoms of TB disease.

A TB infection control program should be based on the following three levels of hierarchy:

1. Administrative controls, which reduce risk of exposure;

2. Environmental controls, which prevent spread and reduce concentration of droplet 

nuclei; and

3. Respiratory-protection controls, which further reduce risk of exposure in special 

areas and circumstances.

The first and most important level of a TB infection control program is the use of administrative 

measures to reduce the risk for exposure to persons who might have TB disease.

The second level of hierarchy is the use of environmental controls to prevent the spread and reduce 

the concentration of infectious droplet nuclei and includes primary and secondary controls.

Respiratory-protection control is the third level of a TB infection control program and consists 

of the use of protective equipment in situations that pose a high risk for exposure to TB disease. 

Use of respiratory protection can further reduce HCW risk of exposure to droplet nuclei expelled 

into the air.

All nontraditional facility-based settings where patients with TB disease receive care should establish 

and follow a TB infection control program. These settings include but are not limited to

• Correctional facilities;

• Homeless shelters;

• Long-term care facilities; 

• Home-based health-care and outreach settings; and

• Emergency medical services;
Chapter 7 – Tuberculosis Infection Control

226

Patients who are suspected to have, or have, confirmed TB disease are frequently sent home after 

starting treatment, even though they may still be infectious. Patients with TB disease can be sent 

home even if they do not have three negative sputum smears, if the following criteria are met:

• A follow-up plan has been made with the local TB program;

• The patient is on standard TB treatment, and DOT has been arranged;

• No infants or children less than 5 years of age or persons with immunocompromising 

conditions are present in the household unless they have been evaluated and started on 

treatment; and

• The patient is willing to remain isolated in the home except for health-care associated visits 

until the patient has negative sputum smear results.

References

CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care 

settings, 2005. MMWR 2005; 54 (No. RR-17).

www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e

CDC. Prevention and control of tuberculosis in correctional and detention facilities: 

Recommendations from CDC. MMWR 2006; 55 (No. RR-09): 1– 44. 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5509a1.htm

Curry International Tuberculosis Center (US). Tuberculosis Infection Control: A Practical Manual 

for Preventing TB; 2007. www.currytbcenter.ucsf.edu/products/a-z_list.cfm
Chapter 8: Community Tuberculosis Control

227

Table of Contents

Chapter Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229

Roles and Responsibilities of the Public Health Sector Providers . . . . . . . . . . . . . . . . . . . . . 229

Roles and Responsibilities of Specific Private Health Sector Providers . . . . . . . . . . . . . . . . . 236

Chapter Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248

Chapter Objectives

After working through this chapter, you should be able to 

• Describe the roles and responsibilities for tuberculosis (TB) control and prevention 

in the public health sector; and

• Describe the roles and responsibilities for TB control and prevention in the private 

health sector.

Chapter 8 

Community Tuberculosis Control

Chapter 8: Community Tuberculosis Control

229

Introduction

State and local health departments have the primary responsibility for preventing and controlling 

TB. However, TB control is a complex undertaking and requires the collaborative efforts of a broad 

range of persons, organizations, and institutions both inside and outside the public health sector. 

These various persons and organizations have a role in improving the detection of TB cases, one of 

the most important responsibilities of TB control, and include

• Clinicians;

• Community health centers;

• Hospitals;

• Academic institutions;

• Medical professional organizations;

• Community-based organizations;

• Correctional facilities;

• Civil surgeons; and

• Pharmaceutical and biotechnology industries.

State and local health departments have the primary responsibility 

for preventing and controlling tuberculosis (TB).

Roles and Responsibilities of the Public Health Sector Providers

The essential role of the public health sector in TB control is to plan, coordinate, and evaluate TB 

control and prevention efforts. This role requires that state and local health departments focus and 

provide oversight on the following critical elements:

• Planning and policy development;

• Contact investigation; 

• Clinical and diagnostic services for patients with TB and their contacts;

• Training and education;

• Surveillance data and information management; and

• Monitoring and evaluation.

The essential role of the public health sector in TB control is to plan, 

coordinate, and evaluate TB control and prevention efforts.
Chapter 8: Community Tuberculosis Control

230

Planning and Policy Development

State and local TB control programs have the responsibility for developing TB control policies and 

procedures. A TB control plan should be developed in collaboration with community stakeholders 

and experts in medical and nonmedical TB management. Laboratory directors and professional 

organizations also make excellent partners to collaborate with when developing TB control policies. 

A TB control plan should be developed in collaboration with community 

stakeholders and experts in medical and nonmedical TB management.

The plan should be based on an understanding of local epidemiologic data and on the capabilities 

and capacities of clinical and support services for clients. Fiscal resources available for TB control 

also determine the plan’s scope and direction, as well as ongoing indicators of program performance 

(program evaluation). Policies and procedures should reflect national, state, and local standards of 

care and should offer guidance in the management of LTBI and TB disease. 

A written TB control plan should be updated regularly and distributed widely to partners. The TB 

control plan should

• Assign specific roles and responsibilities; 

• Define essential pathways of communication between providers, laboratories, and the public 

health system;

• Assign sufficient resources, both human and financial, to ensure its implementation, including 

a responsible case manager for each suspected and verified case of TB disease;

• Provide provisions for expert consultation and oversight for TB-related matters to clinicians, 

institutions, and communities;

• Provide special guidance to local laboratories that process TB-related samples;

• Assist local authorities in conducting contact or outbreak investigations and directly observed 

therapy (DOT); and 

• Provide culturally appropriate information to patients, persons at risk, and the community.

A written TB control plan should be updated regularly 

and distributed widely to partners.

Systems to minimize or eliminate financial and cultural barriers to TB control should be integral 

to the plan. Persons with TB disease and persons at high risk for TB should receive culturally 

appropriate education about TB and clinical services, including treatment, without consideration for 

their ability to pay. 

The plan should be consistent with current legal statutes related to TB control. Relevant laws 

and regulations should be reviewed periodically and updated as necessary to ensure consistency 

with currently recommended clinical and public health practice (e.g., mandatory reporting laws, 

institutional infection control procedures, hospital and correctional system discharge planning, 

and involuntary confinement laws). The health department is legally responsible for ensuring that 
Chapter 8: Community Tuberculosis Control

231

a complete and timely contact investigation is done for the TB cases reported in its jurisdiction. 

Health departments should work closely with providers in the nonpublic health sector to ensure 

prompt reporting of suspected TB cases. They should understand the public health aspects of TB, 

including the need for prompt reporting and the facilitating role of the jurisdictional health agency 

in case management. Federal agencies should take the lead in resolving interstate TB-control issues, 

including movement of TB patients across state lines and multistate TB outbreaks. 

The health department is legally responsible for ensuring that a complete 

and timely contact investigation is done for the TB cases reported in its area. 

Health departments should work closely with providers in the nonpublic 

health sector to ensure prompt reporting of suspected TB cases. 

Clinical and Diagnostic Services for Patients with TB Disease 

and Their Contacts

TB control programs should ensure that patients with suspected or confirmed TB disease have ready 

access to diagnostic and treatment services that meet national standards. These services are often 

provided by state and/or locally supported TB specialty clinics and staffed by health department 

personnel or by contracted service providers. However, persons may seek medical care for TB 

infection or disease in the private medical sector. Regardless of where a person receives medical 

care, the primary responsibility for ensuring the quality and completeness of all TB-related services 

rests with state and local public health agencies. To ensure that standards of care are met, health 

departments should develop and maintain close working relationships with 

• Local laboratories; 

• Pharmacies; and 

• Health-care providers.

Regardless of where a person receives medical care, the primary 

responsibility for ensuring the quality and completeness of all 

TB-related services rests with state and local public health agencies.

Clinical facilities should provide screening, diagnostics, and monitoring tests, including 

radiology services.

Radiology services include access to radiograph equipment, trained radiograph technicians, 

and radiograph interpretation by a qualified person. Radiograph findings and reports should be 

available within 24 hours.

Radiograph findings and reports should be available within 24 hours.
Chapter 8: Community Tuberculosis Control

232

Coordinating care with other health-care providers and facilities is crucial to the prevention and 

control of TB. TB patients often receive care in a variety of settings, including

• Private practices;

• Hospitals;

• HIV clinics; 

• Community clinics;

• Correctional facilities; and 

• Nursing homes. 

Treatment plans must be specific to individual patient needs. As patients move among these settings, 

continuity of care may be compromised unless a system is in place to provide coordination of care.

Expert medical consultation in TB should be available to the health-care community, especially 

for pediatric TB cases and for patients who have drug-resistant disease. Consultants may be health 

department employees or clinicians with TB expertise who are under contract with the health 

department.

Laboratory services should also be readily accessible to perform and provide results of AFB smear 

examinations within 24 hours of specimen collection. TB prevention and control programs should 

work closely with laboratories to ensure the rapid delivery of specimens to the laboratory and prompt 

reporting of AFB smear results, culture results, and results of drug-susceptibility tests to the clinician 

and health department. Laboratory services should also be available to provide monitoring of 

bacteriologic response to therapy.

Laboratory services should be readily accessible to 

perform and provide results of acid-fast bacilli (AFB) smear 

examinations within 24 hours of specimen collection.

Training and Education

TB control programs should provide education and training in the clinical and public health 

aspects of TB to all program staff. Staff members should receive education at regular intervals on 

their particular responsibilities in the program and should demonstrate proficiency in those areas. 

Based on the local epidemiology and needs, TB programs should also educate health-care providers 

(both public and private), community members, public health officials, and policy makers on TB 

prevention and control.

Based on the local epidemiology and needs, TB programs should educate 

health-care providers (both public and private), community members, 

public health officials, and policy makers on TB prevention and control.
Chapter 8: Community Tuberculosis Control

233

To ensure the availability of a competent TB workforce that understands and meets the needs of its 

community, state TB programs should use resources from CDC, the CDC-funded Regional Training 

and Medical Consultation Centers (RTMCCs), National Institutes of Health (NIH)-supported TB 

curriculum centers, the National TB Controllers Association (NTCA), and other national and local 

agencies to create and implement education activities. State and local TB programs should develop 

education and training programs with groups such as those listed in Table 8.1.

Table 8.1

Groups Needing TB Education and Training Programs 

Agencies and Other Organizations Schools

• Local health-care providers

• Community-based organizations

• Health-care institutions

• Medicine

• Nursing

• Pharmacy

• Dentistry

• Public health

Surveillance and Information Management 

Surveillance and information management systems should be a priority of all TB control programs. 

Information technology can improve care of patients with TB disease through standardized 

collection of data and tracking of test results. Other benefits include ready access to details of 

treatment regimens, administration of DOT, and drug-drug interactions. Advancements in 

information technology allow for the analysis and rapid distribution of epidemiologic data, as 

well as management of individualized treatment plans.

Monitoring and Evaluation 

The systematic monitoring and evaluation of TB program activities is a critical factor in enhancing 

program performance. Evaluation techniques provide TB programs with an evidence-based means of 

assessing and improving their TB-control strategies by helping them understand what causes good or 

bad program performance. Evaluation can also be used for the following:

• Program advocacy;

• Assessing staffing needs;

• Focusing training and capacity building;

• Directing limited resources to the most productive activities;

• Accounting for available resources;

• Generating additional resources; and

• Recognizing achievement. 
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TB control programs should develop priorities for program evaluation based on the TB issues or 

challenges in their jurisdiction and the way services are organized. In general, the first priority for 

evaluation efforts should be to focus on those activities and outcomes that relate most directly to the 

key strategies of TB control, which include:

• Identifying patients with infectious TB disease and administering a complete course 

of treatment; 

• Finding TB patient contacts and other persons at high risk with LTBI and treating them; and

• Interrupting transmission of M. tuberculosis in high-risk settings. 

TB control programs should develop priorities for program 

evaluation based on the TB issues or challenges in their 

jurisdiction and the way services are organized.

Targets for program performance have been established by CDC to assist TB control programs in 

treating TB patients, identifying and examining their contacts, and improving the quality of case 

reporting for national surveillance. In addition, national objectives have been set for completing 

treatment for LTBI among contacts of infectious cases of TB disease. These national objectives 

for program performance provide a starting point for state and local TB control programs to use 

for program evaluation, but each TB control program should establish methods to evaluate its 

performance; for additional information, go to www.cdc.gov/tb/ .

Targets for program performance have been established by CDC to assist TB 

control programs in treating TB patients, identifying and examining their 

contacts, and improving the quality of case reporting for national surveillance.

National objectives have been set for completing treatment for 

LTBI among contacts of infectious cases of TB disease.

Other program areas that should be monitored through formal evaluation methods are

• Timeliness and completeness of reporting of TB cases and suspected cases;

• How often a recommended treatment regimen for patients with TB disease and 

LTBI is used; and

• The quality of the program’s databases for surveillance and case management.
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Study Questions

8.1 What should a written TB control plan be based on? 

(choose the one best answer)

A. Local epidemiologic data and ongoing indicators of program performance.

B. Fiscal resources available for TB control.

C. Capabilities and capacities of clinical and support services for clients.

D. A, B, and C are all correct.

E. Only A and B are correct.

8.2 Which of the following is legally responsible for ensuring that a complete and timely 

contact investigation is done for the TB cases reported in its area/agency? 

(choose the one best answer)

A. Health department

B. Hospitals 

C. Private physicians

D. A, B, and C are all correct.

E. Only A and B are correct.

8.3 What should clinical facilities provide for TB patients and their contacts? 

(choose the one best answer)

A. Screening, diagnosis, and monitoring tests. 

B. Radiology services including access to radiograph equipment, trained radiograph 

technicians, and radiograph interpretation by a qualified person.

C. Radiograph findings and reports within 24 hours.

D. A, B, and C are all correct.

E. Only A and B are correct.

8.4 Laboratory services should provide results of AFB smear examinations within what time 

period? (choose the one best answer)

A. 24 hours

B. 72 hours

C. 1 week

D. 2 weeks
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8.5 TB programs are responsible for educating health-care providers (both public and 

private), community members, public health officials, and policy makers on TB 

prevention and control. (choose the one best answer)

A. True

B. False

8.6 Surveillance data and information management systems should be a priority for all TB 

programs. (choose the one best answer)

A. True

B. False

Roles and Responsibilities of 

Specific Private Health Sector Providers

The private health sector plays an important role in TB prevention and control and includes the 

following stakeholders: 

• Clinicians;

• Community health centers;

• Hospitals;

• Academic institutions;

• Medical professional organizations;

• Community-based organizations;

• Correctional facilities;

• Civil surgeons; and

• Pharmaceutical and biotechnology industries.

To the extent possible, this varied group of providers should look for new ways to educate medical 

practitioners, and promote clinical and public health expertise necessary for TB elimination.

To the extent possible, this varied group of providers should look 

for new ways to educate medical practitioners, and promote clinical 

and public health expertise necessary for TB elimination.

Clinicians 

Clinicians in medical practice in the non-public health sector play a vital role in TB control 

throughout communities in the United States. Hospital or clinic-based medical practitioners, 

including those working in emergency departments, are usually the first source of medical care for 

persons with TB disease. These providers may also provide ongoing management of TB patients. 
Chapter 8: Community Tuberculosis Control

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The role of medical practitioners in TB control will increase as TB morbidity in the United States 

decreases and jurisdictions reduce or even eliminate public health clinical services for TB. Private 

medical providers should strive for the following goals:

• Understand prevalent medical conditions, including those with public health implications, of 

populations within their practice; 

• Be aware of applicable state laws and regulations for reporting diseases and the need to report 

TB cases; 

• Recognize the range of responsibilities that arise when TB disease is suspected in a patient 

under medical evaluation, including the following:

» The need for prompt establishment of diagnosis; 

» Use of consultants and hospitalization if indicated; 

» Reporting the suspected TB case to the state and local public health agency and 

cooperating with subsequent public health activities; and 

» Developing, in partnership with the public health agency, a treatment plan that optimizes 

the likelihood that the patient will complete the recommended course of therapy; 

• Incorporate current recommendations for diagnosis, standard treatment of TB disease, and 

targeted testing and treatment of LTBI;

• Be able to place and read tuberculin skin tests or administer blood tests for TB infection, rule 

out suspected TB disease, and administer and monitor treatment for LTBI;

• Screen all new patients for symptoms of TB disease and risk factors for LTBI and give those 

with risk factors a TB skin or blood test; and

• For patients receiving treatment, review risk factors that can suppress the immune system 

Expert medical consultation in TB should be available to the health-care community, especially for 

patients who have drug-resistant disease or medical diagnoses that might affect the course or the 

outcome of treatment. Consultants may be employees of the health department or clinicians with 

expertise who are under contract with the health department. 

The role of medical practitioners in TB control will increase as TB 

morbidity in the United States decreases and jurisdictions reduce 

or even eliminate public health clinical services for TB.

Community Health Centers

Community health centers typically provide primary health-care services to populations 

that encounter barriers to those services at other sites in the health-care system, and include 

persons who are

• Low-income and their families; 

• Immigrants and refugees;

• Uninsured;

• Homeless; and

• Poor women and children. 
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Patients at high risk for TB disease often receive primary and emergency health care in emergency 

rooms or in community health centers. For example, community health centers in certain inner-city 

areas might serve primarily homeless persons, whereas centers in neighborhoods in which certain 

racial and ethnic populations are concentrated might become predominant health-care providers 

for immigrants and refugees. Newly arriving refugee families are frequently directed to community 

health centers to receive federally supported health-screening services, which might include targeted 

testing and treatment for LTBI. Persons with symptoms of TB disease might go first for evaluation 

and care to a community health center. For these reasons, community health centers are a critical 

part of efforts to control and prevent TB disease, and, therefore, need to perform the following tasks:

• Provide their medical staff with the skills and knowledge needed to conduct a TB risk 

assessment of their clients, diagnose and initiate treatment for TB disease, and diagnose 

and treat LTBI;

• Develop close working relationships with consultant physicians, hospitals, and clinical 

laboratories;

• Develop close working relationships with the public health agency that serves their jurisdiction; 

• Arrange for reporting patients with suspected TB disease, ensuring availability of diagnostic 

services (e.g., sputum smears for acid-fast bacilli, cultures for M. tuberculosis, and chest 

radiographs), and providing consultation and referral of patients for diagnosis, treatment, 

and hospitalization, as indicated; 

• Understand federal and state programs that support screening, diagnostic, and treatment 

services for patients at high risk and make prevention, diagnosis, and treatment of TB disease 

a high priority; 

• Educate patients about the personal and public health implications of TB disease and LTBI, 

and motivate them to accept prevention and curative services; and

• Establish recommended TB infection control practices to protect patients and staff.

Community health centers typically provide primary healthcare services to populations that encounter barriers to receiving 

those services at other sites in the health-care system.

Community health centers are a critical part of 

efforts to control and prevent TB disease.
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Hospitals 

Hospitals play a critical role in TB control and prevention and provide multiple services that are 

instrumental to the diagnosis, treatment, and control of TB infection and disease. Hospitals with 

active outpatient and emergency room services often serve as sites of acute and primary medical 

care for homeless persons, inner-city residents, immigrants and refugees, and other persons at high 

risk for TB disease. Also, hospital staff members often provide medical consultation services for the 

diagnosis and management of TB disease by public health and community clinicians. Laboratory 

services provided by hospitals for community-based medical care providers might include key 

diagnostic tests for TB disease. To prevent further spread of infection, hospitals should perform the 

following tasks:

• Develop TB infection control policies to ensure that patients suspected of having infectious TB 

disease are isolated in airborne infection isolation (AII) rooms and that effective TB infection 

control measures are implemented;

• Report any patient with a suspected or confirmed diagnosis of TB disease to their state and 

local public health agency promptly;

• Develop a written policy and plan for prevention of the nosocomial transmission of TB disease 

in their facility; 

• Provide training and ongoing education of their medical and house staff in the prevailing 

diseases of the populations to which they provide care; and

• Ensure patients with TB are discharged on a standard anti-TB regimen with advance 

arrangements coordinated between the hospital and the jurisdictional public health agency to 

enhance patient follow-up.

Hospitals with active outpatient and emergency room services 

often serve as sites of acute and primary medical care for 

homeless persons, inner-city residents, immigrants and 

refugees, and other persons at high risk for TB disease.

Academic Institutions 

Academic institutions (including schools of medicine, pharmacy, public health, and nursing) 

have the obligation and the opportunity to contribute to TB control in the United States and 

worldwide. Students from diverse disciplines, including the clinical and laboratory sciences, nursing, 

epidemiology, and health services, should be introduced to applicable concepts of public health in 

general and, because TB is a major cause of preventable illness and death in developing countries, to 

TB in particular. 

Academic institutions can provide benefits to other participants in TB control. Conferences, 

grand rounds, and other presentations are a source of continuing education for private medical 

practitioners and other community-based health-care workers. Also, trained specialists and 

researchers at academic institutions can provide clinical, radiographic, and epidemiologic 

consultation to medical practitioners and public health agencies. A majority of academic institutions 

manage university-based hospitals, which often serve populations at high risk for TB infection and 
Chapter 8: Community Tuberculosis Control

240

disease. University hospitals can become models for TB risk assessment of patients, inpatient care, 

and infection-control practice, and they can serve as tertiary care sites for an entire community or 

region. To aid communities in the fight against TB, academic institutions have a responsibility to 

perform the following tasks:

• Incorporate TB education into their curricula;

• Serve as repositories of expertise in the treatment and management of TB infection and 

disease, and as a resource for public health and community-based clinicians and other 

health-care workers;

• Partner with public health agencies to improve TB control, which can include providing 

additional sites for education and training, opportunities for clinical research, and, for patients 

with TB disease, a systematic transition from hospital to outpatient care, including DOT; and

• Provide leadership in conducting research in diagnostics, drugs, and vaccines for TB infection 

and disease. 

University hospitals can become models for TB risk assessment of 

patients, inpatient care, and infection-control practice, and they can 

serve as tertiary care sites for an entire community or region.

Medical Professional Organizations 

Medical professional organizations are critical partners in TB control efforts owing to their 

involvement with medical practice, research, education, advocacy, and public health. Greater 

participation of the nonpublic health medical sector is needed to maintain clinical expertise in 

the diagnosis and management of TB in an era of declining incidence. Organizations whose 

memberships include primary-care medical practitioners can make significant contributions to the 

control, prevention, and elimination of TB by performing the following tasks:

• Training and educating their members and other health professionals regarding the clinical and 

public health aspects of the risk assessment, diagnosis, treatment, control, and prevention of 

TB disease;

• Providing professional leadership on clinical practice and control of TB by participating in 

the development or endorsement of guidelines, influencing professional school curricula, and 

establishing and supporting fellowship training programs, as applicable;

• Providing support for adequate funding for TB control and research through public education 

campaigns; and

• Endorsing the importance of greater U.S. involvement in global control of TB by linking U.S.-

based health professionals with those from other parts of the world.

Greater participation of the nonpublic health medical sector 

is needed to maintain clinical expertise in the diagnosis and 

management of TB in an era of declining incidence.
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Community-Based Organizations

Community-based organizations (CBOs) can be particularly effective in providing information and 

education on TB disease to their constituencies. As part of the communities they serve, CBOs are 

often highly regarded, and their messages might be accepted more positively than those delivered by 

the state and/or local health department. Organizations providing services to populations at risk for 

TB disease should perform the following tasks:

• Partner with the state and local public health TB program and medical care providers from 

the community to facilitate access to diagnostic, treatment, and prevention services for the 

target population;

• Become involved in support initiatives, such as state and local TB advisory committees and 

coalitions; and

• Coordinate with public health agencies and educational institutions to develop education 

programs that are tailored culturally and linguistically to their populations. 

As part of the communities they serve, CBOs are often highly 

regarded, and their messages might be accepted more positively than 

those delivered by the state and/or local health department.

Correctional Facilities 

Correctional facilities are common sites of TB transmission. Prevalence of TB disease and LTBI are 

substantially higher in prisons and jails than in the general population. TB disease is believed to be 

the leading cause of death for prisoners worldwide. 

Targeted testing and treatment of LTBI in correctional facilities have been demonstrated to have 

a substantial public health impact. Testing and treatment activities for LTBI are carried out more 

easily in prisons because the length of stay is generally sufficient to permit completion of a course 

of treatment. Jails are convenient sites for targeted testing, but subsequent treatment of LTBI has 

proved challenging. 

Correctional facilities have the responsibility of limiting the transmission of TB within the 

institution and protecting their inhabitants and staff from exposure because of their communal 

living arrangements. This is a particular challenge in jails because of the short lengths of stay for the 

majority of detainees. Abrupt and unexpected transfers of detainees among institutions might occur 

with little consideration for health issues; therefore, correctional facilities have a responsibility in the 

community to perform the following tasks:

• Coordinate with the jurisdictional public health agency to develop and maintain an accurate 

epidemiologic profile of the risk for TB infection and disease in the inmate population;

• Develop written polices based on the local epidemiology of TB, establish effective programs to 

screen for TB disease, respond promptly when cases occur within the facility, provide targeted 

testing and treatment programs for inhabitants and detainees with LTBI, and provide ongoing, 

competency-based education for all staff members;
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• Establish ongoing working relations with public health agencies, hospitals, and other 

community partners for policy development, consultation and referral;

• Develop firm linkages for referral of persons under treatment for TB disease and LTBI 

upon discharge;

• Develop TB infection control programs to protect inhabitants, detainees, staff, and visitors 

from exposure to TB disease following requirements of the Occupational Safety and Health 

Administration (OSHA) and other regulatory agencies; 

• Evaluate, in coordination with the local health department, the effectiveness of the institutional 

TB-control program to eliminate transmission within the facility on a continual basis; and

• Develop ongoing education programs for staff and inmates regarding TB.

Correctional facilities have the responsibility of limiting the transmission of TB 

within the institution and protecting their inhabitants and staff from exposure.

Civil Surgeons 

Civil surgeons are licensed physicians who are certified by the U.S. Citizenship and Immigration 

Services (CIS) to conduct a required health screening examination, including testing for LTBI and 

TB disease, of foreign-born persons living in the United States who apply for permanent residency. 

CDC has responsibility for providing guidance on screening and treatment, but has no regulatory 

role in monitoring the quality or outcomes of these examinations. 

Civil surgeons are a critical component of TB control because of their access to a high-risk 

population. U.S.-based immigration screening can identify foreign-born persons with LTBI for 

whom treatment is indicated and detect TB disease. Although civil surgeons receive immigrationfocused training, little information is available on the knowledge, attitudes, and practices of civil 

surgeons. To further the cause of TB elimination, civil surgeons should perform the following tasks:

• Understand current guidelines for the diagnosis and treatment of TB disease and LTBI;

• Establish a working relationship with state and local public health agencies, and report 

suspected and confirmed cases of TB; and

• Develop a referral mechanism for evaluation for TB disease and LTBI of persons seeking 

adjustment of immigration status.

Because of their access to foreign-born persons at high risk, 

civil surgeons are a critical component of TB control.
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Pharmaceutical and Biotechnology Industries

Pharmaceutical and biotechnology industries are partners in TB control because of their essential 

role in developing new diagnostics, drugs, and vaccines. Although development of new tools for 

diagnosis, treatment, and prevention of TB has been deemed essential to the effort to combat the 

disease globally and to move toward its elimination, progress in these fields has been slow. New nonprofit organizations are working with public and private partners to facilitate the development of 

essential new tools. These organizations include 

• The Global Alliance for Tuberculosis Drug Development (www.tballiance.org);

• The Aeras Global Tuberculosis Vaccine Foundation (www.aeras.org); and 

• The Foundation for Innovative New Diagnostics (www.finddiagnostics.org).

Although development of new tools for diagnosis, treatment, and prevention 

of TB has been deemed essential to the effort to combat the disease globally 

and to move toward its elimination, progress in these fields has been slow.

These organizations have provided venues for identifying and addressing obstacles to the 

development of new tools against TB among private industry, public and academic researchers, 

and philanthropic organizations. To further contribute to TB control and prevention efforts, the 

pharmaceutical and biotechnology industries should perform the following tasks:

• Understand the dimensions of the global TB epidemic and realize their key role in developing 

the necessary tools for diagnosis, treatment, and prevention of TB disease; 

• Respond to the current surge of interest in TB globally by reexamining the costs of new 

product development and by considering potential new public and private funding and the 

markets for such products in developing countries; 

• Contribute their perspectives and become involved in coalitions such as the Global Partnership 

to Stop Tuberculosis, the Global Alliance for Tuberculosis Drug Development, and the 

Foundation for Innovative New Diagnostics; and 

• Coordinate with other stakeholders to ensure access to essential products for those whose 

lives are at stake. 
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Study Questions

8.7 The role of medical practitioners in TB control will decrease as TB morbidity in the 

United States decreases and jurisdictions reduce or even eliminate public health clinical 

services for TB.

(choose the one best answer)

A. True

B. False

8.8 Why do community health centers play a critical role in efforts to control and 

prevent TB disease? (choose the one best answer)

A. They provide primary health-care services to populations that may encounter barriers to 

those services at other sites in the health-care system.

B. Persons with symptoms of TB disease might go there first for evaluation and care.

C. They have the primary responsibility for coordinating TB program integration 

in their area.

D. A, B, and C are all correct.

E. Only A and B are correct.

8.9 Which of the following tasks should hospitals perform to prevent the further 

spread of infection? 

(choose the one best answer)

A. Develop a written policy and plan for prevention of the nosocomial transmission of TB 

disease in their facility.

B. Develop TB infection control policies to ensure that patients suspected of having 

infectious TB disease are isolated in AII rooms.

C. Report any patient with a suspected or confirmed diagnosis of TB disease to their state 

and local public health agency promptly.

D. A, B, and C are all correct.

E. Only A and B are correct.
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8.10 Which of the following is NOT a responsibility of academic institutions? 

(choose the one best answer)

A. Incorporate TB education into their curricula.

B. Serve as repositories of expertise in the treatment and management of TB infection and 

disease.

C. Develop questionnaires for screening all new patients in the community.

D. Partner with public health agencies to improve TB control.

E. Provide leadership in conducting research in diagnostics, drugs, and vaccines for TB 

infection and disease.

8.11 Why are medical professional organizations critical partners in TB control efforts? 

(choose the one best answer)

A. They are involved with medical practice and research.

B. They provide TB education.

C. They provide support for adequate funding for TB control and research. 

D. A, B, and C are all correct.

E. Only A and B are correct.

8.12 Why are community-based organizations particularly effective in providing information 

and education on TB disease to their constituencies?

(choose the one best answer) 

A. They are often highly regarded by the populations they serve.

B. Their messages might be accepted more positively than those delivered by the state 

and/or local health department.

C. They have unlimited funds to purchase quality educational materials.

D. A, B, and C are all correct.

E. Only A and B are correct.

8.13 TB is believed to be the leading cause of death for prisoners worldwide. 

(choose the one best answer)

A. True

B. False
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8.14 Which of the following statements about civil surgeons is true? 

(choose the one best answer)

A. Are a critical component of TB control because of their access to foreign-born 

persons at high risk for TB.

B. Conduct required health screening examinations, including testing for LTBI 

and TB disease in foreign-born persons living in the United States who apply for 

permanent residency.

C. Provide treatment for all TB patients that they identify.

D. A, B, and C are all correct.

E. Only A and B are correct.

8.15 Which of the following statements is true about pharmaceutical and biotechnology 

industries involved in TB? 

(choose the one best answer)

A. Their essential role is to develop new diagnostics, drugs, and vaccines.

B. New public-private partnerships can help identify and address obstacles to developing new 

tools for TB.

C. New tools for diagnosis, treatment, prevention and elimination of TB are being developed 

quite rapidly to meet the need both domestically and internationally. 

D. A, B, and C are all correct.

E. Only A and B are correct.

Match the primary responsibility with the appropriate health sector.

(Choose the one best answer and write the letter for the correct answer on the line next to the 

question number.)

Primary Responsibility Health Sector 

____ 8.16 Plan, coordinate, and evaluate TB control 

and prevention efforts.

____ 8.17 Ensure the quality and completeness of all 

TB-related services.

____ 8.18 Are usually the first sources of medical care 

for persons with TB disease and need to be 

able to provide appropriate diagnostic and 

treatment services or referral.

A. Public health sector (TB 

programs, state and local 

public health agencies)

B. Private health sector 

(clinicians, community 

health centers, hospitals, 

academic institutions, 

correctional facilities, 

homeless shelters, etc.)
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Chapter Summary

State and local health departments have the primary responsibility for preventing and controlling 

TB. However, TB control is a complex undertaking and requires the collaborative efforts of a broad 

range of persons, organizations, and institutions both inside and outside the public health sector. 

These various persons and organizations have a role in improving the detection of TB cases, one of 

the most important responsibilities of TB control, and include:

• Clinicians;

• Community health centers;

• Hospitals;

• Academic institutions;

• Medical professional organizations;

• Community-based organizations;

• Correctional facilities;

• Civil surgeons; and

• Pharmaceutical and biotechnology industries.

The essential role of the public health sector is to plan, coordinate, and evaluate TB control and 

prevention efforts. This role requires that state and local health departments focus on the following 

critical elements:

• Planning and policy development;

• Clinical and diagnostic services for patients with TB and their contacts;

• Training and education;

• Surveillance data and information management; and

• Monitoring and evaluation.
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References

CDC. Controlling tuberculosis in the United States: Recommendations from the American Thoracic 

Society, CDC, and the Infectious Diseases Society of America. MMWR 2005; 54 (No. RR-12): 1–81.

www.cdc.gov/MMWR/preview/MMWRhtml/rr5412a1.htm

CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care 

settings, 2005. MMWR 2005; 54 (No. RR-17). 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e

CDC. Prevention and control of tuberculosis in correctional and detention facilities: 

Recommendations from CDC. MMWR 2006; 55 (No. RR-09): 1–44.

www.cdc.gov/mmwr/preview/mmwrhtml/rr5509a1.htm

CDC. Tuberculosis elimination revisited: Obstacles, opportunities, and a renewed commitment. 

MMWR 1999; 48 (No. RR-9). www.cdc.gov/MMWR/preview/MMWRhtml/rr4809a1.htm
Appendix A: Glossary

249

Appendix A

Glossary

Acid-fast bacilli (AFB) smear

An examination of a specimen (e.g., sputum) that has been spread onto a glass slide, stained, washed 

in an acid solution, and then placed under the microscope for examination; used to detect acid-fast 

bacilli in a specimen. Acid-fast bacilli are not decolorized by acid-alcohol after having been stained 

with dyes such as basic fuchsin. 

Active case finding

Identifying unreported cases of TB disease by actively searching for them (e.g., laboratory and 

pharmacy audits). 

Adenopathy

Swelling or enlargement of the lymph nodes. 

Adult-type TB

A clinical presentation of TB disease more typical of an adult. Characterized by upper lobe 

infiltration and cavitation associated with sputum production. 

Airborne infection isolation (AII)

Isolation of patients infected with organisms that are spread via airborne droplet nuclei <5 microns 

in diameter. 

Airborne infection isolation (AII) room

Single-occupancy patient-care room in which environmental factors are controlled to minimize the 

transmission of infectious agents that are usually spread from person to person by droplet nuclei 

associated with coughing or aerosolization of contaminated fluids. AII rooms typically have specific 

requirements for controlled ventilation, air pressure, and air filtration. 

Alveoli

The small air sacs at the end of airways in the lung. 

Amikacin

An injectable second-line drug in the aminoglycoside class that is used for patients with drugresistant tuberculosis whose isolate has demonstrated or presumed susceptibility to the drug. 

Aminoglycoside

A class of broad-spectrum antibiotics active against gram-negative bacteria; can cause renal toxicity 

and ototoxicity. Aminoglycosides used to treat TB include streptomycin, amikacin, and kanamycin. 
Appendix A: Glossary

250

Amprenavir

An inhibitor of HIV-1 protease. It is used in combination with other antiretroviral agents for the 

treatment of HIV-1 infection. 

Anergy

Inability to react to skin-test antigens because of a weakened immune system. (Anergic) 

Anergy testing

Conducted by giving skin tests using two substances other than tuberculin; done to determine 

whether a person is anergic. People who do not react to any of the substances, including tuberculin, 

after 48 to 72 hours (that is, people who have less than 5 mm of induration to all of the skin tests) 

are considered to have cutaneous anergy to those antigens. 

Antiretroviral agents

The categories of antiretroviral agents currently available for the treatment of HIV-1 infection 

are nucleoside reverse transcriptase inhibitors (NRTI), nucleotide reverse transcriptase inhibitors 

(NtRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI). 

Apex

The narrow, somewhat conical upper part of a lung. (Plural: apices) 

Bacille Calmette-Guérin (BCG) vaccine

Vaccine made from biologic substances derived from a strain of Mycobacterium bovis that was 

attenuated by Calmette and Guérin at the Pasteur Institute in Lille, France. An early version of BCG 

was first administered to humans in 1921. It is widely used in the World Health Organization’s 

(WHO) immunization programs in highly TB-prevalent countries to reduce risk of life-threatening 

TB meningitis and disseminated disease in children and adolescents. 

Boosted reaction

An increased response of the immune system to a second or subsequent occasion on which it 

encounters a specific antigen. 

Bronchiectasis

Persistent and progressive dilation of bronchi or bronchioles as a consequence of inflammatory 

disease, obstruction, or congenital abnormality. Symptoms include fetid breath and paroxysmal 

coughing, with the expectoration of mucopurulent matter. 

Bronchoscopy

An examination of the interior of the tracheo-bronchial tree with a flexible fiberoptic device; it is 

used for inspection, performance of endobronchial diagnostic tests, taking of specimens for biopsy 

and culture, or removal of foreign bodies. 

Capreomycin

A second-line injectable drug that is used for patients with drug-resistant tuberculosis.

Cavity

A hollow space within the lung, visible on a chest radiograph, which may contain many tubercle 

bacilli; often occurs in people with severe pulmonary TB disease. 
Appendix A: Glossary

251

Close contacts

Persons who had prolonged, frequent, or intense contact with a person with TB while he or she was 

infectious. Close contacts are more likely to become infected with M. tuberculosis than contacts who 

see the person with TB less often. 

Creatinine

A waste product of protein metabolism that is found in the urine. It can be measured to assess overall 

kidney function. An abnormally elevated blood creatinine level is seen in those individuals with 

kidney insufficiency and kidney failure. 

Culture

Organisms grown on or in media (liquid or solid substances containing nutrients) so that they can 

be identified; a positive culture for M. tuberculosis contains tubercle bacilli, whereas a negative culture 

contains no detectable tubercle bacilli. 

Cycloserine

A second-line drug that is used for treating patients with drug-resistant tuberculosis.

Delavirdine

A nonnucleoside reverse transcriptase inhibitor of the human immunodeficiency virus type 1 (HIV-1). 

It is used in combination with other antiretroviral agents for the treatment of HIV-1 infection. 

Delayed-type hypersensitivity

An increased reactivity to specific antigens mediated by lymphocytes and not by antibodies. 

Demographic factors

Factors such as country of origin, age, gender, ethnic or racial group, and occupation. 

Directly observed therapy (DOT)

A strategy used to help patients adhere to treatment; it means that a health-care worker or another 

designated person watches the TB patient swallow each dose of the prescribed drugs. 

Droplet nuclei

Very small droplets, 1 to 5 microns in diameter, that may be expelled when a person who has 

infectious TB coughs or sneezes; they can remain suspended in the air for several hours, depending 

on the environment. 

Drug-resistant TB

TB disease caused by Mycobacterium tuberculosis organisms that are resistant to at least one first-line 

antituberculosis drug. 

Efavirenz

A nonnucleoside reverse transcriptase inhibitor of the human immunodeficiency virus type 1 (HIV-1). 

It is used in combination with other antiretroviral agents for the treatment of HIV-1 infection. 

Ethambutol (EMB)

A first-line drug for treating all forms of TB. It is included in initial treatment regimens primarily 

to prevent emergence of rifampin (RIF) resistance when primary resistance to isoniazid (INH) 

may be present. 
Appendix A: Glossary

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Ethionamide

A second-line drug used for patients with drug-resistant tuberculosis disease. 

Extensively drug-resistant TB (XDR TB)

Extensively drug-resistant TB is a rare type of MDR TB that is resistant to isoniazid and rifampin, 

plus any fluoroquinolone and at least one of three injectable second-line drugs. 

Extrapulmonary TB

TB disease that occurs in places other than the lungs, such as the lymph nodes, the pleura, the brain, 

the kidneys, the larynx, or the bones. 

False-negative reaction

A negative skin test reaction in a person infected with M. tuberculosis. 

False-positive reaction

A positive skin test reaction in a person not infected with M. tuberculosis. 

Fluorochrome staining

The use of any fluorescent dye (e.g., auramine, rhodamine) used to label or stain. Must be viewed 

using a fluorescence microscope. 

Fluoroquinolones

A class of synthetic broad-spectrum antibacterial drugs. Examples of fluoroquinolones used to treat 

TB are levofloxacin, moxifloxacin, gatifloxacin, and ofloxacin. 

Gatifloxacin

A fluoroquinolone used as a second-line drug in the treatment of TB. 

Granuloma

Chronic inflammatory lesion characterized by large numbers of cells of various types 

(e.g., macrophages, lymphocytes, fibroblasts, and giant cells). 

Hemoptysis

The expectoration of blood or of blood-stained sputum. 

Hepatotoxicity

Injury to the liver; can be a side effect of medications. 

High-risk congregate settings

Settings where there is a high risk of TB transmission; examples may include correctional facilities, 

nursing homes, homeless shelters, hospitals, residential facilities for persons living with AIDS, and 

other health care facilities. 

High-risk racial or ethnic minority populations

Populations that have higher rates of TB infection or disease. This may include Asians and Pacific 

Islanders, Hispanics, African Americans, Native Americans. 
Appendix A: Glossary

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Hilar

Relating to, affecting, or located near the depression in the medial surface of a lung that forms the 

opening through which the bronchus, blood vessels, and nerves pass. Seen in the center of a chest 

radiograph. 

Indinavir

An inhibitor of HIV-1 protease. It is used in combination with other antiretroviral agents for the 

treatment of HIV-1 infection. 

Induration

A palpable, raised, hardened area. 

Infectiousness

The infectiousness of a person with TB disease is directly related to the number of tubercle bacilli 

that he or she expels into the air. Persons who expel many tubercle bacilli are more infectious than 

patients who expel few or no bacilli. 

Interferon gamma release assay (IGRA)

A test that detects the presence of M. tuberculosis infection by measuring the immune response to the 

TB bacteria in whole blood. 

Isoniazid (INH)

A first-line drug for treatment of all forms of TB. 

Kanamycin

An injectable second-line drug in the aminoglycoside class that is used for patients with drugresistant tuberculosis. 

Latent TB infection (LTBI)

Persons with latent TB infection have M. tuberculosis organisms in their bodies but do not have TB 

disease, have no symptoms, and are noninfectious. Such persons usually have a positive reaction to 

the TST or IGRA. 

Levofloxacin

A fluoroquinolone used as a second-line drug in the treatment of TB. 

Lymphadenopathy

Swelling of the lymph nodes. 

Macrophage 

A type of white blood cell that ingests foreign material; found in the alveoli of the lungs. 

Mantoux tuberculin skin test (TST)

Skin test used to detect TB infection. In the United States, it is performed by using a 27-gauge 

needle and syringe to inject 0.1 ml containing 5 tuberculin units of purified protein derivative (PPD) 

between the layers of the skin (intradermally), usually on the forearm; the reaction to this test, the 

induration (palpable hardened area), is measured 48 to 72 hours after the injection and is classified as 

positive or negative depending on the size of the induration and the patient’s risk factors for TB. 
Appendix A: Glossary

254

Mediastinal

Pertaining to the space in the thoracic cavity behind the sternum and between the two pleural sacs 

(containing the lungs). 

Miliary TB

TB disease that occurs when tubercle bacilli enter the bloodstream and are carried to all parts of the 

body, where they grow and cause disease in multiple sites; so named because the chest radiograph of 

patients with miliary TB often looks as though millet seeds are scattered throughout the lung. 

Moxifloxacin

A fluoroquinolone used as a second-line drug in the treatment of TB. 

Multidrug-resistant TB (MDR TB)

TB disease caused by Mycobacterium tuberculosis organisms that are resistant to more than one antiTB drug. MDR TB is defined as resistance to at least isoniazid and rifampin. It is more difficult to 

treat than drug-susceptible TB. 

Mycobacterium avium

A nontuberculous mycobacteria (NTM) causing disease primarily in domestic fowl and other birds. 

This bacterium can also cause opportunistic infections in immunocompromised persons; often 

disseminated infections. 

Mycobacterium bovis

A type of tuberculous mycobacteria; the bovine variety of the tubercle bacillus. Before the 

pasteurization of milk became common practice, these mycobacteria were often spread to humans 

through contaminated milk; in the United States today, M. bovis rarely affects humans. 

Mycobacterium gordonae

A type of nontuberculous mycobacteria (NTM); M. gordonae is one of the least pathogenic of the 

mycobacteria. 

Mycobacterium intracellulare

A nontuberculous mycobacteria (NTM) found in lung lesions and sputum of humans; may cause 

bone and tendon-sheath lesions in rabbits; some strains are pathogenic for mice. 

Mycobacterium tuberculosis

A type of tuberculous mycobacteria; a gram-positive bacterium that causes tuberculosis. It is 

sometimes called the tubercle bacillus. 

Mycobacterium tuberculosis complex

The M. tuberculosis complex includes seven other TB-causing mycobacteria: M. bovis, M. africanum, 

M. microti, M. canetti, M. caprae, M. pinnipedii, and M. mungi. 

Nelfinavir

An inhibitor of HIV-1 protease. It is used in combination with other antiretroviral agents for the 

treatment of HIV-1 infection. 
Appendix A: Glossary

255

Nevirapine

A nonnucleoside reverse transcriptase inhibitor of the human immunodeficiency virus type 1 (HIV-1). 

It is used in combination with other antiretroviral agents for the treatment of HIV-1 infection. 

Nonnucleoside reverse transcriptase inhibitors (NNRTI)

Antiretroviral agents used for the treatment of HIV-1 infection. 

Nontuberculous mycobacteria (NTM)

Mycobacteria other than those comprising the M. tuberculosis complex. NTM may cause pulmonary 

disease resembling TB; however, NTM are NOT usually spread from person to person. Just how and 

why people become infected with NTM is not clear. Although the germs are found easily in water 

and soil, they do not affect most people. 

Nucleotide reverse transcriptase inhibitors (NtRTI)

Antiretroviral agents used for the treatment of HIV-1 infection. 

Palpating

A light feathery touch with the fingertips to feel for any induration. A sweeping motion is used to 

search the forearm for the indurated reaction. 

Para-amino salicylic acid (PAS)

An oral drug used in treatment of drug-resistant tuberculosis. 

Paradoxical reaction

A temporary exacerbation of symptoms, signs, or radiographic manifestations after initiation of 

treatment for TB disease. 

Pathogenesis

The origin and development of disease. 

Paucibacillary

Having or made up of few bacilli. 

Peripheral neuropathy

Injury to the nerves that supply sensation to the arms and legs, causing a tingling sensation or a 

weakened sense of touch in the hands and feet. 

Pleural effusion

The collection of fluid (including blood) in the pleural space. 

Polymerase chain reaction (PCR)

The first practical system for in vitro amplification of DNA and, as such, one of the most important 

recent developments in molecular medicine. 

Primary TB

TB disease occurring soon after the initial infection with M. tuberculosis. Occurs commonly in 

children or in immunocompromised hosts. Primary TB is characterized by intrathoracic adenopathy, 

mid- and lower-lung zone infiltrates, and the absence of cavitation. 
Appendix A: Glossary

256

Protease inhibitors (PI)

Antiretroviral agents used for the treatment of HIV-1 infection. 

Pyrazinamide (PZA)

A first-line drug for the treatment of all forms of TB. 

QuantiFERON-TB Gold In-Tube test (QFT-GIT)

A whole-blood test for diagnosing TB infection. QFT-GIT measures the patient’s immune reactivity 

to Mycobacterium tuberculosis, the bacterium that causes TB. 

Reticuloendothelial diseases

Diseases of the phagocytic system of the body, including the fixed macrophages of tissues, 

liver, and spleen. 

Rifabutin

Used as a substitute for rifampin (RIF) in the treatment of all forms of TB caused by organisms 

that are known or presumed to be susceptible to this drug. The drug is generally reserved for patients 

who are receiving any medication having unacceptable interactions with RIF or have experienced 

intolerance to RIF. 

Rifampin (RIF)

A first-line drug for treatment of all forms of TB. Rifamycins are an essential component of all 

short-course regimens. 

Rifamycin

A class of drugs that include rifampin, rifabutin, and rifapentine. 

Rifapentine (RPT)

May be used once weekly with INH in the continuation phase of treatment for HIV-seronegative 

patients with noncavitary, drug-susceptible pulmonary TB who have negative sputum smears at 

completion of the initial phase of treatment. 

Ritonavir

An inhibitor of HIV-1 protease. It is used in combination with other antiretroviral agents for the 

treatment of HIV-1 infection. 

Saquinavir

An inhibitor of HIV-1 protease. It is used in combination with other antiretroviral agents for the 

treatment of HIV-1 infection. 

Silicosis

A form of lung disease resulting from occupational exposure to and inhalation of silica dust over a 

period of years, usually associated with concurrent tobacco use; characterized by a slowly progressive 

fibrosis of the lungs, it results in impairment of lung function. 

Skin-test conversion

A negative tuberculin skin test reaction which increases in size by ≥10 mm within 2 years; indicative 

of recent infection with M. tuberculosis. 
Appendix A: Glossary

257

Streptomycin (SM)

An aminoglycoside used as a second-line drug in the treatment of TB. Among patients likely to have 

acquired M. tuberculosis in a high-incidence country, the relatively high rate of resistance to SM 

limits its usefulness. 

Symptoms suggestive of hepatitis or hepatotoxicity

Symptoms include nausea, loss of appetite, vomiting, persistently dark urine, yellowish skin, malaise, 

unexplained elevated temperature for more than 3 days, or abdominal tenderness.

T-SPOT®.TB test 

A cellular in vitro blood test for the diagnosis of active and latent TB infection that enumerates the 

response of effector T-cells that have been sensitized to Mycobacterium tuberculosis. 

Targeted testing

Targeting testing is the tuberculin skin testing of groups for which rates of TB are substantially 

higher than for the general population. 

Transmission

Transmission occurs when a person inhales droplet nuclei containing M. tuberculosis, and the droplet 

nuclei traverse the mouth or nasal passages, upper respiratory tract, and bronchi to reach the alveoli 

of the lungs. 

Tubercle bacilli

Mycobacterium tuberculosis organisms. 

Ultraviolet germicidal irradiation (UVGI)

A sterilization method that uses ultraviolet light to break down microorganisms. 

Virulence

The ability of any agent of infection to produce disease. The virulence of a microorganism (such as a 

bacterium or virus) is associated with the severity of the disease it is capable of causing. 

Volar surface

Palm-side-up surface of the forearm, about 2 to 4 inches below the elbow. 

Ziehl-Neelsen or Kinyoun

Methods for staining acid-fast bacteria; acid-fast organisms appear red, other tissue elements light 

blue; basic fuchsin dye.

Appendix B: Answers to the Study Questions

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Appendix B

Answers to the Study Questions 

Chapter 1

Overview of Tuberculosis Epidemiology in the United States

# Answer

1.1 B

1.2 B

1.3 B

1.4 A

1.5 A

1.6 C

1.7 E

1.8 D

1.9 C

1.10 E

1.11 D

1.12 E

1.13 C
Appendix B: Answers to the Study Questions

260

Chapter 2

Transmission and Pathogenesis

# Answer # Answer

2.1 B 2.18 B

2.2 E 2.19 B

2.3 A 2.20 B

2.4 B 2.21 A

2.5 E 2.22 A

2.6 B 2.23 E

2.7 C 2.24 D

2.8 B 2.25 B

2.9 C 2.26 A

2.10 B 2.27 B

2.11 A 2.28 A

2.12 B 2.29 C

2.13 B 2.30 F

2.14 A 2.31 E

2.15 A 2.32 B

2.16 B 2.33 A

2.17 B 2.34 D
Appendix B: Answers to the Study Questions

261

Chapter 3

Testing for Tuberculosis Infection and Disease

# Answer # Answer

3.1 E 3.17 A

3.2 E 3.18 A

3.3 A 3.19 B

3.4 C 3.20 A

3.5 B 3.21 B

3.6 C 3.22 A

3.7 A 3.23 B

3.8 D 3.24 A

3.9 A 3.25 A

3.10 E 3.26 A

3.11 B 3.27 A

3.12 C 3.28 B

3.13 A 3.29 A

3.14 D 3.30 A

3.15 C 3.31 A

3.16 B 3.32 B
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262

Chapter 4

Diagnosis of Tuberculosis

# Answer # Answer

4.1 A 4.18 D

4.2 B 4.19 B

4.3 A 4.20 A

4.4 B 4.21 A

4.5 B 4.22 A

4.6 A 4.23 B

4.7 A 4.24 A

4.8 A 4.25 C

4.9 A 4.26 A

4.10 A 4.27 B

4.11 B 4.28 A

4.12 A 4.29 A

4.13 C 4.30 D

4.14 D 4.31 D

4.15 E 4.32 D

4.16 B 4.33 B

4.17 A
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263

Chapter 5

Treatment of Latent Tuberculosis Infection

# Answer # Answer

5.1 B 5.15 E

5.2 B 5.16 D

5.3 A 5.17 B

5.4 B 5.18 A

5.5 B 5.19 B

5.6 A 5.20 C

5.7 A 5.21 E

5.8 C 5.22 D

5.9 B 5.23 E

5.10 B 5.24 D

5.11 A 5.25 A

5.12 B 5.26 E

5.13 E 5.27 D

5.14 D 5.28 E
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264

Chapter 6

Treatment of Tuberculosis Disease

# Answer # Answer

6.1 D 6.28 C

6.2 A 6.29 A

6.3 B 6.30 D

6.4 A 6.31 D

6.5 B 6.32 D

6.6 A 6.33 C

6.7 A 6.34 D

6.8 D 6.35 B

6.9 E 6.36 A

6.10 B 6.37 C

6.11 E 6.38 D

6.12 E 6.39 D

6.13 C 6.40 A

6.14 E 6.41 C

6.15 E 6.42 A

6.16 A 6.43 B

6.17 A 6.44 C

6.18 A 6.45 B

6.19 B 6.46 B

6.20 A 6.47 D

6.21 A 6.48 A

6.22 B 6.49 C

6.23 A 6.50 C

6.24 D 6.51 D

6.25 E 6.52 B

6.26 B 6.53 A

6.27 A 6.54 E
Appendix B: Answers to the Study Questions

265

Chapter 7

Tuberculosis Infection Control

# Answer # Answer

7.1 D 7.23 A

7.2 B 7.24 B

7.3 A 7.25 A

7.4 A 7.26 A

7.5 A 7.27 B

7.6 D 7.28 B

7.7 D 7.29 D

7.8 C 7.30 E

7.9 A 7.31 B

7.10 E 7.32 C

7.11 D 7.33 A

7.12 C 7.34 A

7.13 A 7.35 B

7.14 B 7.36 A

7.15 A 7.37 E

7.16 C 7.38 E

7.17 B 7.39 B

7.18 B 7.40 A

7.19 A 7.41 B

7.20 B 7.42 A

7.21 B 7.43 B

7.22 A
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266

Chapter 8

Community Tuberculosis Control

# Answer

8.1 D

8.2 A

8.3 D

8.4 A

8.5 A

8.6 A

8.7 B

8.8 E

8.9 D

8.10 C

8.11 D

8.12 E

8.13 A

8.14 E

8.15 E

8.16 A

8.17 A

8.18 B
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Appendix C 

PowerPoint Slide Set

PowerPoint Slide Set

The Core Curriculum is accompanied by a PowerPoint slide set for use in presentations and training 

programs. Images of the slides are included in this appendix. The slide set may be downloaded from 

the CDC DTBE website at www.cdc.gov/tb. 

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Notes
Notes