Fundamentals of Tuberculosis

1
Fundamentals of Tuberculosis
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Reported TB Cases United States, 1981-2001
No. of Cases
1981
1989
1993
2001
1985
1997
Year
3
TB Case Rates, United States, 2001
D.C.
lt 3.5 (year 2000 target)
3.6 - 5.6
gt 5.6 (national average)
Rate cases per 100,000
4
Trends in TB Cases in Foreign-born Persons,
United States, 1986-2001
Percentage
No. of Cases
5
TB Case Rates in U.S.-born vs. Foreign-born
Persons, United States, 1991-2001
Cases per 100,000
Note Case rates for 2000 and 2001 based on an
extrapolation from the March 2000 U.S. Census
Bureau Current Population Reports.
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Completion of TB Therapy United States, 1993-1999
Percentage
Note Persons with initial isolate resistant to
rifampin and children under 15 years old with
meningeal, bone or joint, or miliary disease
excluded.
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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)

10
Not Everyone Exposed Becomes Infected

• Probability of transmission depends on
• - How Contagious
• - Kind of Environment
• Length of Exposure

11
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

13
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

• gt5 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

• gt 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

• gt 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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Boosting

• 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)

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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
  patients 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