Transcript Pathogenesis

Fundamentals of
Tuberculosis
2
No. of Cases
Reported TB Cases
United States, 1981-2001
28000
26000
24000
22000
20000
18000
16000
14000
12000
10000
1981
1985
1989
1993
Year
1997
2001
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TB Case Rates, United States, 2001
D.C.
< 3.5 (year 2000 target)
3.6 - 5.6
> 5.6 (national average)
Rate: cases per 100,000
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Trends in TB Cases in Foreign-born
Persons, United States, 1986-2001
Percentage
No. of Cases
10,000
60
50
8,000
40
30
20
6,000
4,000
2,000
10
0
0
1986
1988
1990
1992
No. of Cases
1994
1996
1998
2000
Percentage of Total Cases
5
Cases per 100,000
TB Case Rates in U.S.-born vs. Foreignborn Persons, United States, 1991-2001
40
30
20
10
0
1991
1993
1995
U.S. Overall
1997
U.S.-born
1999
Foreign-born
Note: Case rates for 2000 and 2001 based on an
extrapolation from the March 2000 U.S. Census Bureau
Current Population Reports.
2001
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Completion of TB Therapy
United States, 1993-1999
100
80
60
40
20
0
1993
1994
Completed
1995
1996
1997
1998
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.
1999
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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
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
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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
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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
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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
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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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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 retested (with single test) on a regular basis
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Two-Step Testing
Baseline PPD test
Negative Result
Repeat PPD 1-3 weeks later
NEGATIVE:
POSITIVE:
Person probably does not
have TB infection
This is a “boosted” reaction
due to TB infection a long
time ago
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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:
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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
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*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
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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
- Close contact
- Abnormal chest x-ray
- Foreign-born
- Medically underserved,
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
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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:
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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
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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
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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