Fundamentals of Tuberculosis

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10000120001400016000180002000022000240002600028000

Reported TB Cases United States, 1981-2001

Year

1981 1985 1989 1993 1997 2001

No

. of

Ca

ses

3

TB Case Rates, United States, 2001

< 3.5 (year 2000 target)

3.6 - 5.6

> 5.6 (national average)

D.C.

Rate: cases per 100,000

4

Trends in TB Cases in Foreign-born Persons, United States, 1986-2001

0

2,000

4,000

6,000

8,000

10,000

1986 1988 1990 1992 1994 1996 1998 20000

10

20

30

40

50

60

No. of Cases Percentage of Total Cases

No. of Cases Percentage

5

TB Case Rates in U.S.-born vs. Foreign-born Persons, United States, 1991-2001

0

10

20

30

40

1991 1993 1995 1997 1999 2001

U.S. Overall U.S.-born Foreign-born

Cas

es p

er 1

00,0

00

Note: Case rates for 2000 and 2001 based on an extrapolation from the March 2000 U.S. Census Bureau Current Population Reports.

6

Completion of TB Therapy United States, 1993-1999

0

20

40

60

80

100

1993 1994 1995 1996 1997 1998 1999

Completed Completed in 1 yr or less

Note: Persons with initial isolate resistant to rifampin and children under 15 years old with meningeal, bone or joint, or miliary disease excluded.

Per

cen

tag

e

7

TB in the United States

• From 1953 to 1984, reported cases decreased by approximately 5.6% each year

• From 1985 to 1992, reported cases increased by 20%

• 25,313 cases reported in 1993

• Since 1993, cases are steadily declining

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Transmission & Pathogenesis of TB

• Caused by Mycobacterium tuberculosis

• Spread person to person through the airborne particles that contain M. tuberculosis, called droplet nuclei

• Transmission occurs when an infectious person coughs, sneezes, laughs, or sings

• Prolonged contact needed for transmission

• 10% of infected persons will develop TB disease at some point in their lives

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Common Sites of TB Disease

• Lungs (85% of all cases)

• Pleura

• Central nervous system

• Genitourinary system

• Bones and joints

• Disseminated (miliary TB)

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Not Everyone Exposed Becomes Infected

Probability of transmission depends on:

- How Contagious

- Kind of Environment

- Length of Exposure

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Development of TB Disease

• 10% of infected persons will develop TB disease at some point in their lives

• Certain conditions increase the risk that TB infection will progress to disease

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Factors Contributing to the Increase in TB Cases

• HIV epidemic

• Increased immigration from high-prevalence countries

• Transmission of TB in congregate settings (e.g., correctional facilities, long-term care)

• Deterioration of the public health care infrastructure

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Factors That Increase the Risk of TB Disease Once Infected

• HIV infection • Substance abuse (especially drug injection)• Recent infection with M. tuberculosis• Chest radiograph findings suggestive of previous

TB (in a person inadequately treated)• Low body weight (10% or more below the ideal)• Certain Medical Conditions, such as…..

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Medical Conditions that Increase the Risk of TB Disease

• Diabetes mellitus• Silicosis• Cancer of the head and neck• Hematologic and reticuloendothelial diseases• End-stage renal disease• Intestinal bypass or gastrectomy• Chronic malabsorption syndromes• Prolonged corticosteroid therapy• Other immunosuppressive therapy

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Groups at High Risk for TB Exposure

• Close contacts of a person with infectious TB• Foreign-born persons from areas where TB is

common• Residents of congregate settings• Persons who inject drugs• Locally identified high-burden groups, such

as farm workers or homeless persons• Children

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Clinical Manifestations of TB

• Chest pain

• Productive prolonged cough

• Hemoptysis

• Fever, chills, night sweats

• Easy fatigability

• Loss of appetite

• Weight loss

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TB Diagnostic Tests

• Mantoux Tuberculin Skin Test• Chest X-ray• Sputum examination

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Latent TB Infection (LTBI) • Occurs when person inhales bacteria and it reaches air sacs (alveoli) of lung • Immune system keeps bacilli encapsulated

• Person is not infectious and has no symptoms

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TB Disease

• Occurs when immune system cannot keep bacilli contained

• Bacilli begin to multiply

• Person develops symptoms

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LTBI vs. TB Disease• LTBI

– Asymptomatic – PPD negative– Chest X-ray

normal– Sputum negative– Not infectious

• TB Disease– Cough, fever, night

sweats– PPD positive– Chest X-ray

abnormal– Infectious before

treatment initiated

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Targeted Testing

• Not everyone should be routinely tested for TB

• Testing should be done only if there is an intent to treat

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Groups to Target with the Tuberculin Skin Test

• Persons with or at risk for HIV infection

• Close contacts of persons with infectious TB

• Persons with certain medical conditions

• Persons who inject drugs

• Foreign-born persons from areas where TB is common

• Medically underserved, low-income populations

• Residents of congregate settings

• Locally identified high-prevalence groups

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Performing the Tuberculin Skin Test

• Use Mantoux tuberculin skin test

• 0.1 ml of 5-TU PPD injected intradermally

• Read within 48-72 hours by healthcare worker

• Measure transverse diameter of induration

• Record results in millimeters of induration

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Classifying the TST Reaction - 1

>5 mm is positive in• Persons known to have or suspected of having

HIV infection• Close contacts of a person with infectious TB• Persons who have a chest radiograph suggestive of

previous TB• Persons who inject drugs (if HIV status unknown)

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Classifying the TST Reaction - 2

> 10 mm is positive in• Person with certain medical conditions, excluding HIV

infection• Persons who inject drugs (if HIV negative)• Foreign-born persons from areas where TB is common• Medially underserved, low-income populations• Residents of long-term care facilities• Children younger than 4 years of age• Locally identified high-prevalence groups

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Classifying the TST Reaction - 3

> 15 mm is positive in

• All persons with no known risk factors for TB

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Classifying the TST Reaction - 4

For persons who may have occupational exposure to TB, the appropriate cutoff depends on:

• Individual risk factors for TB

• The prevalence of TB in the facility or

place of employment

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BCG Vaccination and Tuberculin Skin Test

• There is no reliable method of distinguishing tuberculin reaction caused by BCG from those caused by TB infection

• Evaluate all BCG-vaccinated persons who have a positive skin test result for treatment of latent TB infection

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Anergy• The inability to react to skin tests due to weakened immune system• Do not rule out diagnosis of TB on basis of negative PPD• Consider anergy in non-reactors who:

- Are immunocompromised (e.g., HIV+, cancer chemotherapy) - Have overwhelming TB disease

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• Some people with history of LTBI lose their ability to react to tuberculin

• Baseline test may be negative (immune system “forgets” how to react to TB-like substance)

• Another test 1-3 weeks later will be positive (baseline test stimulated/ “boosted” immune system)

Boosting

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Two-Step Testing

• A strategy for differentiating between boosted reactions and reactions caused by recent infections

• 2nd test given 1 - 3 weeks after baseline

• Used in many residential facilities for initial skin testing of new employees who will be re- tested (with single test) on a regular basis

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Two-Step Testing

Baseline PPD test Repeat PPD 1-3 weeks later

NEGATIVE: POSITIVE:Person probably does not This is a “boosted” reaction have TB infection due to TB infection a long

time ago

Negative Result

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Assessing Infectiousness of a TB Patient

• Patients should be considered infectious if they:– Are undergoing cough-inducing procedures– Have sputum smears positive for acid-fast

bacilli and:• Are not receiving therapy

• Have just started therapy, or

• Have a poor clinical or bacterial response to therapy

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Assessing Infectiousness of a TB Patient

• Patients are not considered infectious if they meet all these criteria:– Adequate therapy received for 2-3 weeks– Favorable clinical response to therapy, and – 3 consecutive negative sputum smears results

from sputum collected on different days

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Techniques to Decrease the Possibility of TB Transmission

• Instruct patient to:– Cover mouth when coughing or sneezing– Wear mask as instructed– Open windows to assure proper ventilation– Do not go to work or school until instructed by

physician– Avoid public transportation– Limit visitors

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Evaluation for TB

• Medical history

• Physical examination

• Mantoux tuberculin skin test

• Chest radiograph

• Bacteriologic exam (smear & culture)

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Symptoms of TB• *Productive prolonged cough

• *Chest pain

• *Hemoptysis

• Fever

• Chills

• Night sweats

• Easy fatigability

• Loss of appetite

• Weight loss *commonly seen in cases of pulmonary TB

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Chest X-Ray

• Chest X-rays should be done in patients with positive skin test results

• Abnormal chest X-ray cannot itself confirm the diagnosis of TB but can be used in conjunction with other diagnostic indicators

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Sputum Collection

• Sputum specimens are essential to confirm TB

• Mucus from within lung, not saliva

• Collect 3 specimens on 3 different days

• Spontaneous morning sputum more desirable than induced specimens

• Collect sputum before drug therapy initiated

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Smear Examination

• Strongly consider TB in patients with smears containing acid-fast bacilli (AFB)

• Use follow-up smear examinations to assess patient’s infectiousness and response to therapy

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Cultures

• Used to confirm diagnosis of TB

• Culture all specimens, even if smear is negative

• Initial drug isolate should be used to determine drug susceptibility

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Treatment of Latent TB Infection

• Daily INH therapy for 9 months – Monitor patients for signs and symptoms of

hepatitis and neurotoxicity

• Alternate regimen – Rifampin for 4 months

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High Priority Candidates for Treatment of Latent TB Infection

Regardless of age Over age 35

- HIV + or suspect - Foreign-born- Close contact - Medically underserved,- Abnormal chest x-ray low-income

- Medical conditions - Long term care facilities

- Recent converters - Other populations (homeless, HCWs)

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Treatment of TB Disease

• Include four drugs in initial regimen– Isoniazid (INH)

– Rifampin (RIF)

– Pyrazinamide (PZA)

– Ethambutol (EMB)

• Adjust regimen when drug susceptibility results are shown

• Never add a single drug to a failing regimen• Ensure adherence to therapy

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Monitoring for Adverse Reactions

Instruct patients taking INH, RIF and PZA to report immediately the following:– nausea– loss of appetite– vomiting– persistently dark urine– yellowish skin– malaise– unexplained fever for 3 or more days– abdominal pain

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Monitoring for Drug Resistance

• Primary - Becoming infected with a strain of M. tuberculosis which is already resistant to one or more drugs

• Acquired - Becoming infected with a strain of M. tuberculosis which becomes drug resistant due to inappropriate or inadequate drug treatment

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Barriers to Adherence

• Stigma

• Extensive duration of treatment

• Side effects of medications

• Concerns of toxicity

• Lack of knowledge of the disease process and necessary treatment

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Improving Adherence

• Case management

• Directly Observed Therapy (DOT)

• Patient education

• Incentives/enablers

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Directly Observed Therapy (DOT)

• Health care worker watches patient swallow each dose of medication

• DOT is the best way to ensure adherence

• Should be used with all intermittent regimens

• Reduces relapse of TB disease and acquired drug resistance

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Other Measures to Promote Adherence

• Develop an individualized treatment plan for each patient

• Work with outreach staff from same cultural and linguistic background as patient

• Educate patient about TB, medication dosage, and possible adverse reactions

• Use incentives and enablers to remove barriers to adherence

• Facilitate access to health and social services