# Presentation: 719525

## This is an archived document.

**This is an archived document.**

## Core Curriculum Contents

-  Introduction
-  Transmission and Pathogenesis
-  Epidemiology of TB in the U.S.
-  Testing for TB Disease and Infection
-  Diagnosis of TB
-  Treatment of Latent TB Infection (LTBI)
-  Treatment of TB Disease
-  Infection Control in Health Care Settings
-  BCG Vaccination
-  Community TB Control

## Introduction

## Areas of Concern

- TB cases continue to be reported in every state
- Drug-resistant cases reported in almost every state
- Estimated 10-15 million persons in U.S. infected
- with *M. tuberculosis*
-  Without intervention, about 10% will develop
-   TB disease at some point in life

## Transmission and Pathogenesis

## Transmission of M. tuberculosis

- Spread by droplet nuclei
- Expelled when person with infectious TB coughs,
- sneezes, speaks, or sings
- Close contacts at highest risk of becoming infected
- Transmission occurs from person with infectious
- TB disease (not latent TB infection)

## Probability TB Will Be Transmitted

- Infectiousness of person with TB
- Environment in which exposure occurred
- Duration of exposure
- Virulence of the organism

## Pathogenesis

- 10% of infected persons with normal immune
-  systems develop TB at some point in life
- HIV strongest risk factor for development of TB if
- infected
-  Risk of  developing TB disease 7% to 10% each
-    year
- Certain medical conditions increase risk that TB
- infection will progress to TB disease

## Conditions That Increase the Risk of 

- Progression to TB Disease

- HIV infection
- Substance abuse
- Recent infection
- Chest radiograph findings suggestive of previous TB
- Diabetes mellitus
- Silicosis
- Prolonged corticosteriod therapy
- Other immunosuppressive therapy

## Conditions That Increase the Risk of 

- Progression to TB Disease (cont.)

- Cancer of the head and neck
- Hematologic and reticuloendothelial diseases
- End-stage renal disease
- Intestinal bypass or gastrectomy
- Chronic malabsorption syndromes
- Low body weight (10% or more below the ideal)

## Common Sites of TB Disease

- Lungs
- Pleura
- Central nervous system
- Lymphatic system
- Genitourinary systems
- Bones and joints
- Disseminated (miliary TB)

## Drug-Resistant TB

- Drug-resistant TB transmitted same way as
- drug-susceptible TB
- Drug resistance is divided into two types:
-  Primary resistance develops in persons initially
-      infected with resistant organisms
-  Secondary resistance (acquired resistance)
-      develops during TB therapy

## Classification System for TB

- No TB exposure
- Not infected

- No history of exposure
- Negative reaction to tuberculin skin test

- TB exposure
- No evidence of infection

- History of exposure
- Negative reaction to tuberculin skin test

- TB infection
- No disease

- Positive reaction to tuberculin skin test
- Negative bacteriologic studies (if done)
- No clinical, bacteriological, or radiographic
- evidence of active TB

- TB, clinically active

*M. tuberculosis* cultured (if done)
- Clinical, bacteriological, or radiographic
- evidence of current disease

- TB
- Not clinically active

- History of episode(s) of TB
**or**
- Abnormal but stable radiographic findings
- Positive reaction to the tuberculin skin test
- Negative bacteriologic studies (if done)
**and**
- No clinical or radiographic evidence of
- current disease

- TB suspected

- Diagnosis pending

**Class**

**Type**

**Description**

**0**

**1**

**2**

**3**

**4**

**5**

## Slide 14

## TB Morbidity Trends in the United States

- From 1953 to 1984, reported cases decreased by an
- average of 5.6% per year
- From 1985 to 1992, reported TB cases increased by
- 20%
- Since 1993, reported TB cases have been declining
- again
- 18,361 cases reported in 1998

## Reported TB Cases

- United States, 1953 - 1998

- Year

- 10,000

- 20,000

- *

- *

- 30,000

- 50,000

- 70,000

- 100,000

- Cases
- (Log Scale)

- *Change in case definition

- 53

- 60

- 70

- 80

- 90

- 98

## Factors Contributing to the Increase 

- in TB Morbidity: 1985-1992

- Deterioration of the TB public health infrastructure
- HIV/AIDS epidemic
- Immigration from countries where TB is common
- Transmission of TB in congregate settings

## Factors Contributing to the Decrease in 

- TB Morbidity Since 1993

- Increased efforts to strengthen TB control
- programs that
- Promptly identify persons with TB
- Initiate appropriate treatment
- Ensure completion of therapy

## Reported Cases of TB by Country of Birth - 

-  United States, 1986-1998

- 86

- 87

- 88

- 89

- 90

- 91

- 92

- 93

- 94

- 95

- 96

- 97

- 98

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

- 40

- U.S.-born

- All Cases

- Foreign-born

- Recent Cases per 100,000 population

- Year

## Resistance to INH 4% in 46 states and District

- of Columbia (DC) during 1993-1998
- 45 states and DC reported at least one MDR TB
- case during 1993-1998

- Multidrug-Resistant TB (MDR TB) Remains a
- Serious Public Health Concern

## MDR TB Cases, 1993 - 1998

**None**

_**>**_** 1 case**

## Persons at Higher Risk for Exposure 

- to or Infection with TB

- Close contacts of person known or suspected to
- have TB
- Foreign-born persons from areas where TB is
- common
- Residents and employees of high-risk congregate
- settings
- Health care workers (HCWs) who serve high-risk
- clients

## Persons at Higher Risk for Exposure 

- to or Infection with TB (cont.)

- Medically underserved, low-income populations
- High-risk racial or ethnic minority populations
- Children exposed to adults in high-risk categories
- Persons who inject illicit drugs

## Persons at Higher Risk of Developing 

- TB Disease once Infected

- HIV infected
- Recently infected
- Persons with certain medical conditions
- Persons who inject illicit drugs
- History of inadequately treated TB

## Testing for 

- TB Disease and Infection

## Purpose of Targeted Testing

- Find persons with LTBI who would benefit from treatment
- Find persons with TB disease who would benefit from treatment
- Groups that are not high risk for TB should not be tested routinely

## All testing activities should be accompanied 

**by a plan for follow-up care.**

## Groups That Should Be Tested for LTBI

- Persons at higher risk for exposure to or infection with TB
- Close contacts of a person known or suspected
-  to have TB
- Foreign-born persons from areas where TB is
- common
- Residents and employees of high-risk
- congregate settings
- Health care workers (HCWs) who serve high-
- risk clients

## Groups That Should Be Tested 

- for LTBI (cont.)

- Persons at higher risk for exposure to or infection with TB
- Medically underserved, low-income populations
- High-risk racial or ethnic minority populations
- Children exposed to adults in high-risk categories
- Persons who inject illicit drugs

## Groups That Should Be Tested 

- for LTBI (Cont.)

- Persons at higher risk for TB disease once infected
- Persons with HIV infection
- Persons recently infected with *M. tuberculosis*
- Persons with certain medical conditions
- Persons who inject illicit drugs
- Persons with a history of inadequately treated TB

## Administering the Tuberculin Skin Test

- Inject intradermally 0.1 ml of 5
- TU PPD tuberculin
- Produce wheal 6 mm to 10 mm
- in diameter
- Do not recap, bend, or break
- needles, or remove needles from syringes
- Follow universal precautions for infection control

## Reading the Tuberculin Skin Test

- Read reaction 48-72 hours after
- injection
- Measure only induration
- Record reaction in millimeters

## Classifying the Tuberculin Reaction

** ******5 mm is classified as positive in
- HIV-positive persons
- Recent contacts of TB case
- Persons with fibrotic changes on chest radiograph
- 	consistent with old healed TB
- Patients with organ transplants and other
- 	immunosuppressed patients

## Classifying the Tuberculin 

- Reaction (cont.)

****10 mm is classified as positive in
- Recent arrivals from high-prevalence countries
- Injection drug users
- Residents and employees of high-risk congregate settings
- Mycobacteriology laboratory personnel
- Persons with clinical conditions that place them at high risk
- Children <4 years of age, or children and adolescents
- 	exposed to adults in high-risk categories

## Classifying the Tuberculin 

- Reaction (cont.)

****15 mm is classified as positive in
- Persons with no known risk factors for TB
- Targeted skin testing programs should only be
-     conducted among high-risk groups

## Occupational Exposure to TB, 

- Appropriate Cutoff Depends on

- Individual risk factors for TB
- Prevalence of TB in the facility

## Factors that May Affect the 

- Skin Test Reaction

**Type of Reaction**      **Possible Cause**
- False-positive	       Nontuberculous mycobacteria
-                                    BCG vaccination
- 	                          Anergy
- False-negative	       Recent TB infection
-                                    Very young age (< 6 months old)
-                                    Live-virus vaccination
-                                    Overwhelming TB disease

## Anergy

- Do not rule out diagnosis based on negative skin test result
- Consider anergy in persons with no reaction if
-  HIV infected
-  Overwhelming TB disease
-  Severe or febrile illness
-  Viral infections
-  Live-virus vaccinations
-  Immunosuppressive therapy.
- Anergy skin testing no longer routinely recommended

## Boosting

- Some people with LTBI may have negative skin
- test reaction when tested years after infection
- Initial skin test may stimulate (boost) ability to react
- to tuberculin
- Positive reactions to subsequent tests may be
- misinterpreted as a new infection

## Two-Step Testing

- Use two-step testing for initial skin testing of adults
- who will be retested periodically
- If first test positive, consider the person infected
- If first test negative, give second test 1-3 weeks
- 	later
- If second test positive, consider person infected
- If second test negative, consider person
- 	uninfected

## Diagnosis of TB

## Evaluation for TB

- Medical history
- Physical examination
- Mantoux tuberculin skin test
- Chest radiograph
- Bacteriologic or histologic exam

## Symptoms of Pulmonary TB

- Productive, prolonged cough
- (duration of ****3 weeks)
- Chest pain
- Hemoptysis

## Systemic Symptoms of TB

- Fever
- Chills
- Night sweats
- Appetite loss
- Weight loss
- Easy fatigability

## Medical History

- Symptoms of disease
- History of TB exposure, infection, or disease
- Past TB treatment
- Demographic risk factors for TB
- Medical conditions that increase risk for TB
- disease

## Mantoux Tuberculin Skin Test

- Preferred method of testing for TB infection
- in adults and children
- Tuberculin skin testing useful for
-  Examining person who is not ill but may be
-    infected
-  Determining how many people in group are
-    infected
-  Examining  person who has symptoms of TB

## Chest Radiograph

- Abnormalities often seen in apical
- or posterior segments of upper
- lobe or superior segments of
- lower lobe
- May have unusual appearance in
- HIV-positive persons
- Cannot confirm diagnosis of TB

- Arrow points to cavity in
- patient's right upper lobe.

## Specimen Collection

- Obtain 3 sputum specimens for smear examination
- and culture
- Persons unable to cough up sputum, induce
- sputum, bronchoscopy or gastric aspiration
- Follow infection control precautions during
- specimen collection

## Smear Examination

- Strongly consider TB in patients with smears
- containing acid-fast bacilli (AFB)
- Results should be available within 24 hours of
- specimen collection
- Presumptive diagnosis of TB

## AFB smear

**AFB (shown in red) are tubercle bacilli**

## Cultures

- Use to confirm diagnosis of TB
- Culture all specimens, even if smear negative
- Results in 4 to 14 days when liquid medium
- systems used

**Colonies of *****M. tuberculosis***** growing on media**

## Drug Susceptibility Testing

- Drug susceptibility testing on initial *M. tuberculosis *
- isolate
- Repeat for patients who
-  Do not respond to therapy
-  Have positive cultures despite 2 months of  therapy
- Promptly forward results to the health department

## Persons at Increased Risk for 

- Drug Resistance

- History of treatment with TB drugs
- Contacts of persons with drug-resistant TB
- Foreign-born persons from high prevalent drug
- resistant areas
- Smears or cultures remain positive despite
- 2 months of TB treatment
- Received inadequate treatment regimens for
- >2 weeks

## Treatment of Latent TB Infection (LTBI)

## Candidates for Treatment of LTBI

- Positive skin test result ****5 mm
- HIV-positive persons
- Recent contacts of a TB case
- Persons with fibrotic changes on chest radiograph
- 	consistent with old TB
- Patients with organ transplants and other
- 	immunosuppressed patients

## Candidates for Treatment of LTBI (cont.)

- Positive skin test result ****10 mm
- Recent arrivals from high-prevalence countries
- Injection drug users
- Residents and employees of high-risk congregate settings
- Mycobacteriology laboratory personnel
- Persons with clinical conditions that make them high-risk
- Children < 4 years of age, or children and adolescents
- 	exposed to adults in high-risk categories

## Candidates for Treatment of LTBI (cont.)

- Positive skin test result ****15 mm
- Persons with no known risk factors for TB may be
- 	considered
- Targeted skin testing programs should only be
- 	conducted among high-risk groups

## Treatment of LTBI with Isoniazid (INH)

- 9-month regimen considered optimal
- Children should receive 9 months of therapy
- Can be given twice-weekly if directly observed

## Treatment of LTBI with a Rifamycin 

- and Pyrazinamide (PZA)

- HIV-Positive Persons
- A rifamycin and PZA daily for 2 months
- May be given twice weekly
- Administration of rifampin (RIF) contraindicated with some
- protease inhibitors (PIs) and nonnucleoside reverse
- transcriptase inhibitors (NNRTIs)
- HIV-Negative Persons
- Clinical trials have not been conducted
- Daily RIF and PZA for 2 months
- May be given twice weekly

## Contacts of INH-Resistant TB

- Treatment with a rifamycin and PZA
- If unable to tolerate PZA, 4-month regimen of daily RIF
- HIV-positive persons: 2 month regimen with a rifamycin and
- PZA
- Contacts of Multidrug-Resistant TB
- Use 2 drugs to which the infecting organism has
- demonstrated susceptibility
- Treat for 6 months or observe without treatment
-  (HIV-negative)
- Treat HIV-positive persons for 12 months
- Follow for 2 years regardless of treatment

## Fibrotic Lesions

- Acceptable regimens include
- 9 months of INH
- 2 months RIF plus PZA
- 4 months of RIF (with or without INH)

- Pregnancy and Breast-feeding
- INH daily or twice weekly
- Pyridoxine supplementation
- Breast-feeding not contraindicated

## Monitoring Patients

- Before treatment for LTBI is started, clinicians should
- Rule out possibility of TB disease
- Determine history of treatment for LTBI or disease
- Determine contraindications to treatment
- Obtain information about current and previous
- 	drug therapy
- Recommend HIV testing if risk factors are present

## Monitoring Patients (cont.)

- Establish rapport with patient and emphasize
- Benefits of treatment
- Importance of adherence to treatment regimen
- Possible adverse side effects of regimen
- Establishment of optimal follow-up plan

## Monitoring Patients (cont.)

- Baseline laboratory testing
- Not routinely indicated
- Baseline hepatic measurements for
-  Patients whose initial evaluation suggests a liver disorder
-  Patients with HIV infection
-  Pregnant women and those in immediate postpartum period
-  Patients with history of chronic liver disorder

## Monitoring Patients (cont.)

- At least monthly, evaluate for
- Adherence to prescribed regimen
- Signs and symptoms of active TB disease
- Signs and symptoms of hepatitis (if receiving
-        isoniazid alone, and at 2, 4, and 8 weeks if
-        receiving RIF and PZA)

## Treatment of TB Disease

## Basic Principles of Treatment

- Provide safest, most effective therapy in shortest time
- Multiple drugs to which the organisms are susceptible
- Never add single drug to failing regimen
- Ensure adherence to therapy

## Adherence

- Nonadherence is a major problem in TB control
- Use case management and directly observed
-  therapy (DOT) to ensure patients complete treatment

## Case Management

- Assignment of responsibility
- Systematic regular review
- Plans to address barriers to adherence

## Directly Observed Therapy (DOT)

- Health care worker watches patient swallow each
- dose of medication
- Consider DOT for all patients
- DOT should be used with all intermittent regimens
- DOT can lead to reductions in relapse and acquired
- drug resistance
- Use DOT with other measures to promote adherence

## Treatment of TB for HIV-Negative Persons

- Include four drugs in initial regimen
-  Isoniazid (INH)
-  Rifampin (RIF)
-  Pyrazinamide (PZA)
-  Ethambutol (EMB) or streptomycin (SM)
- Adjust regimen when drug susceptibility results are
- known

## Treatment of TB for HIV-Positive Persons

- Management of HIV-related TB is complex
- Care for HIV-related TB should be provided
- by or in consultation with experts in management
- of both HIV and TB

## Treatment of TB for 

- HIV-Positive Persons (cont.)

- RIF-based regimens generally recommended for persons
- Who have not started antiretroviral therapy
- For whom PIs or NNRTIs are not recommended

- Initial treatment phase should consist of
- Isoniazid (INH)
- Rifampin (RIF)
- Pyrazinzamide (PZA)
- Ethambutol (EMB)

- RIF may be used with some Pls and NNRTIs

## Treatment of TB for 

- HIV-Positive Persons (cont.)

- For patients receiving PIs or NNRTIs,** **initial treatment
- phase may consist of
-  Isoniazid (INH)
** **Rifabutin (RFB)
-  Pyrazinamide (PZA)
-  Ethambutol (EMB)
- An alternative nonrifamycin regimen includes INH,
- EMB, PZA, and streptomycin (SM)

## Extrapulmonary TB

- In most cases, treat with same regimens
- used for pulmonary TB

- Bone and Joint TB, Miliary TB,
- or TB Meningitis in Children

- Treat for a minimum of 12 months

## Pregnant women 

- 9-month regimen of INH, RIF, and EMB
- PZA and SM are contraindicated
- PZA not contraindicated in HIV-positive pregnant
-      women

- In most cases, treat with same regimens used for
-      adults

**  **
- Treat as soon as diagnosis suspected

- Children

- Infants

## Treatment Regimens for TB 

- Resistant Only to INH

- HIV-Negative Persons
- Carefully supervise and manage treatment to avoid
- 	development of MDR TB
- Discontinue INH and continue RIF, PZA, and EMB
- 	or SM for the entire 6 months
- Or, treat with RIF and EMB for 12 months
- HIV-Positive Persons
- Regimen should consist of a rifamycin, PZA, and EMB

## Multidrug-Resistant TB (MDR TB)

- Presents difficult treatment problems
- Treatment must be individualized
- Clinicians unfamiliar with treatment of MDR TB should
- seek expert consultation
- Always use DOT to ensure adherence

## Monitoring for Adverse Reactions

- Baseline measurements
- Monitor patients at least monthly
- Monitoring for adverse reactions must be
- individualized
- Instruct patients to immediately report adverse
- reactions

## Monitoring Response to Treatment

- Monitor patients bacteriologically monthly until
- cultures convert to negative
- After 3 months of therapy, if cultures are positive
- or symptoms do not resolve, reevaluate for
-  Potential drug-resistant disease
-  Nonadherence to drug regimen
- If cultures do not convert to negative despite 3
- months of therapy, consider initiating DOT

## Infection Control in Health Care Settings

## Infectiousness

- Patients should be considered infectious if they
- Are coughing
- Are undergoing cough-inducing or aerosol-generating
-        procedures, or
- Have sputum smears positive for acid-fast bacilli and they
- Are not receiving therapy
- Have just started therapy, or
- Have poor clinical response to therapy

## Infectiousness (cont.)

- Patients no longer considered infectious if they meet **all** of these criteria:
-     Are on adequate therapy
-     Have had a significant clinical response to therapy,
**      **and
-    Have had 3 consecutive negative sputum smear
-      results

## Infection Control Measures

- Administrative controls to reduce risk of exposure
- Engineering controls to prevent spread and reduce
- concentration of droplet nuclei
- Personal respiratory protection in areas where
- increased risk of exposure

## Administrative Controls

- Reduce risk of exposing uninfected persons to infectious disease:
- Develop and implement written policies and protocols to ensure
-  Rapid identification
-  Isolation
-  Diagnostic evaluation
-  Treatment
-   Implement effective work practices among HCWs
-   Educate, train, and counsel HCWs about TB
-   Test HCWs for TB infection and disease

## Administrative Controls (cont.)

- Perform risk assessment and classification of facility based on
-    Profile of TB in community
-    Number of infectious TB patients admitted
-    Analysis of HCW skin test conversions

## Engineering Controls

- To prevent spread and reduce concentration of infectious droplet nuclei
-    Use ventilation systems in TB isolation rooms
-    Use HEPA filtration and ultraviolet irradiation with other
-       infection control measures

## Personal Respiratory Protection

- Use in areas where increased risk of exposure:
- TB isolation rooms
- Rooms where cough-inducing procedures are done
- Homes of infectious TB patients

## BCG Vaccination

## Recommendations for BCG Vaccination

- Not recommended in immunization programs or TB control programs in the U.S.
- BCG vaccination undertaken after consultation with health department

## Recommendations for BCG 

-    Is continually exposed to untreated or ineffectively
-      treated patient
-    Will be continually exposed to multidrug-resistant TB

- Recommendations for BCG
- Vaccination (cont.)

## Recommendations for BCG 

- Vaccination (cont.)

- HCWs considered on individual basis in settings    in which
-    High percentage of MDR TB patients has been
-      found
-    Transmission of drug-resistant TB strains and
-      subsequent infection are likely, _and_
-    Comprehensive TB infection-control precautions
-       implemented and not successful

## BCG Contraindications

- Contraindicated in persons with impaired immune response from
- HIV infection
- Congenital immunodeficiency
- Leukemia
- Lymphoma
- Generalized malignancy
- Receiving high-dose steroid therapy
- Receiving alkylating agents
- Receiving antimetabolites
- Receiving radiation therapy

## BCG Vaccination and 

- Tuberculin Skin Testing

- Tuberculin skin testing not contraindicated for BCG-vaccinated
-       persons
- LTBI diagnosis and treatment for LTBI considered for any BCG-
-      vaccinated person whose skin test reaction is ****10 mm, if any of
-      these circumstances are present:
-  Was contact of another person with infectious TB
-  Was born or has resided in a high TB prevalence
-   country
-  Is continually exposed to populations where TB
-               prevalence is high

## Community TB Control

## Preventing and Controlling TB

- Three priority strategies:
- Identify and treat all persons with TB disease
- Identify contacts to persons with infectious
- 	TB; evaluate and offer therapy
- Test high-risk groups for LTBI; offer therapy
-  	as appropriate

## Health care providers should work with health department 

- in the following areas:
- Overall planning and policy development
- Identification of persons with clinically active TB
- Management of persons with disease or TB suspects
- Identification and management of persons with LTBI
- Laboratory and diagnostic services
- Data collection and analysis
- Training and education

## Overall Planning and Policy

- Develop overall TB control strategy
- Review local laws, regulations, and policies
- Guide and oversee TB control efforts of local institutions and
- practitioners
- Provide consultations in TB treatment, contact investigations,
- and infection control practices
- Seek out necessary funding and resources
- Educate policymakers

## Identification of Persons Who Have Clinically Active TB

- Health department has ultimate responsibility for
- ensuring TB patients do not transmit TB

- Contact Investigation

- Purpose of a contact investigation is to find persons who

- Have TB disease so treatment can be given, and further
- 	transmission stopped
- Have LTBI so treatment can be given
- Are at high risk of developing TB disease and require
- 	treatment until LTBI excluded

## Management of Persons Who Have TB 

- Disease or TB Suspects

- Management involves range of services, which include
- Developing a treatment plan
- Promoting and ensuring adherence
- Providing a referral system for other medical problems
- Providing clinical consultation services
- Providing inpatient care when necessary
- Providing appropriate facilities to isolate and treat
- 	patients with infectious TB
- Maintaining an infection control program

## Identification and Management 

- of Persons with LTBI

- Establish working relationships with other health
- care providers
- Target testing to well-defined high-risk groups
- Flexibility needed in defining high-priority groups

## Laboratory and Diagnostic Services

- Readily accessible
- AFB results within 24 hours of specimen collection
- Clinicians promptly report all TB cases and
- suspected cases
- All TB smear and culture results reported by
- laboratories

## Data Collection and Analysis

- TB reporting required in every state
- All new cases and suspected cases promptly
- reported to health department
- All drug susceptibility results sent to health
- department

## Training and Education

- TB control programs should
- Provide training for program staff
- Provide leadership in TB education to the community
- Ensure community leaders, clinicians, and
-        policymakers are knowledgeable about TB
- Educate the public