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Tuberculosis Powered By Docstoc

Mark B. Stephens, MD MS FAAFP
         CDR MC USN
   Assoc Prof Fam Med USU
         Cap Conf 2008
       6 Key Learning Points
1.   Assess for TB Risk
2.   If risk present, perform TST/IGF test
3.   If TST +, r/o active TB
4.   If no active TB, treat LTBI
5.   Ensure completion of LTBI
6.   If active TB, isolate and treat

                           *IGT = interferon gamma testing
   Which one of the following is true
regarding PPD testing for tuberculosis?
  1. Patients who have converted within the past
     year should be treated, regardless of age
  2. In patients who previously received a BCG
     vaccination, the threshold for a positive test
     is 25 mm of induration
  3. Patients who test positive only on the second
     step of a two-step PPD test, given 2 weeks
     after the first test, are at high risk for
     development of active disease
  4. PPD testing is contraindicated in patients
     who are HIV positive
   A health-care worker has a negative
tuberculin skin test. A second test 10 days
             later is positive.
This result indicates

  1.    previous vaccination with BCG
  2.    a false-positive skin test
  3.    recent conversion
  4.    long-standing, latent infection
  5.    probable immunodeficiency
 Which persons are at increased
risk of contracting active TB once
  infected with m. tuberculosis?

1.   Persons with HIV infection
2.   Persons who live in dry climates
3.   Persons who inject illicit drugs
4.   Persons with a history of inadequately
     treated TB
1, 3, 4
  1/3 of the World Population is
    infected with tuberculosis
1. True
2. False
     How many worldwide deaths
         annually from TB?
1.   2 million
2.   500,000
3.   6 million
4.   10 million
5.   20 million
 How many people develop active
        TB annually?

1.   6 million
2.   9 million
3.   12 million
4.   15 million
5.   18 million
1. Assess for TB risk
2. Determine criteria for screening tests
   and interpretation
3. Analyze factors associated with active

                      Primary resource
  Which one of these increases a
 person’s risk of exposure to TB?
1. Adolescents participating in outdoor
2. Family members living with someone
   who has TB
3. Employees of a correctional facility
4. Foreign-born persons from areas that
   have a high TB prevalence
2, 3, 4
           Who is at risk?
1. Close contacts of persons known or
   suspected to have TB
2. Foreign-born persons, including children,
   from areas that have a high TB prevalence
3. Residents and employees of high-risk
   congregate settings
4. Some medically underserved, low-income
   populations as defined locally
1, 2, 3, 4
            Who is at risk?
1. High-risk racial or ethnic minority
   populations, defined locally as having an
   increased prevalence of TB
2. Infants, children, and adolescents exposed
   to adults in high-risk categories
3. Persons who inject illicit drugs
4. Health care workers who serve high-risk
1, 2, 3, 4
           Who needs TST?

1.   20 yo school teacher
2.   54 yo diabetic
3.   43 yo Indonesian immigrant
4.   55 yo inmate
5.   ALL of the above
3, 4*
Targeted Tuberculin Skin Test
• Best screening tool available
• Useful for
  – Determining how many people in a group
    are infected (e.g., contact investigation)
  – Examining persons who have symptoms of
• Multiple puncture tests (e.g., Tine Test)
  are inaccurate and not recommended
    QuantiFERON®-Gold Test

• Whole-blood test used to detect M.
  tuberculosis infection
• Cells recognize tubercle protein-
  specific antigens and release
  interferon-γ (IGT)
• LTBI preferred to “PPD Converter”
• LTBI is the presence of M. tuberculosis
  organisms without symptoms or
  radiographic evidence of TB disease
• Finding and treating persons at high risk
  for latent TB infection (LTBI) is a priority
• Without treatment 10-15% LTBI
  proceed to active TB
A 26-year-old female nurse has had recent contact with
patients with AIDS and tuberculosis (TB), and now has
 a positive tuberculin skin test. Her test was negative a
year ago. She has no other medical complaints. Testing
to exclude which one of the following is most important
before starting latent TB therapy with isoniazid (INH)?

 1.   Active TB
 2.   Previous hepatitis
 3.   Diabetes mellitus
 4.   Neuropathy
 5.   Pregnancy
 Who is at risk to develop active
1. Those who have been recently
2. Those with clinical conditions that
   increase their risk of progressing
   from LTBI to TB disease
       1. Recent Infections
• Close contacts to person with infectious
• Skin test converters (within past 2
• Recent immigrants from TB-endemic
  regions of the world (within 5 years of
  arrival to the U.S.)
       2. Clinical Conditions
• Children ≤ 5 years with a positive TST
• Residents and employees of high-risk
  congregate settings (e.g., correctional
  facilities, homeless shelters, health care
• Underweight or malnourished persons
• Injection drug users
         RR for Active TB
  Clinical Condition     Relative Risk
Silicosis                      30
DM                          2.0-4.1
ESRD                      10.0-25.3
RRT / Dialysis                 37
Solid organ Transplant       20-74
Carcinoma H&N                  16
HIV+                        35-162
Recent LTBI (<1 yr)           12.9
IV Drug Use                    40
Fibrosis on CXR             2-13.6
Underweight                    2
        LTBI Regimens

9-month INH is preferred
 • 6-month regimen is less effective but may
   be used if unable to complete 9 months
 • May also be given intermittently (twice
   • Use directly observed therapy (DOT) for
     intermittent regimen
     Completion of Therapy
Completion of therapy is based on the
 total number of doses administered, not
 on duration alone.
    • INH daily for 9 months
          (270 doses within 12 months)
    • INH twice/week for 9 months
          (76 doses within 12 months)
    • INH daily for 6 months
          (180 doses within 9 months)
    Managing missed doses
• Extend or restart treatment if
  interruptions frequent or prolonged
• When treatment has been interrupted
  for more than 2 months, re-examine and
  rule out active TB disease
• Recommend and arrange for DOT as
Is routine laboratory monitoring
 necessary for patients on INH?

1. Yes
2. No
       Routine monitoring?
Instruct patient to report signs or
  symptoms of adverse drug reactions
  • Rash
  • Anorexia, nausea, vomiting, or abdominal
    pain in right upper quadrant
  • Fatigue or weakness
  • Dark urine
  • Persistent numbness in hands or feet
        Routine Monitoring?
Baseline liver function tests (e.g.,
 AST, ALT, and bilirubin) are not
 necessary except for high risk
  •   HIV disease
  •   History of liver disease
  •   Alcoholism
  •   Pregnancy or in early postpartum period
           Stopping INH?
• Asymptomatic elevation of hepatic
  enzymes seen in 10%-20% of people
  taking INH
  • Levels usually return to normal after
    completion of treatment
• Expert opinion:
  • Withhold INH if transaminase level 3x
    ULN if patient symptomic and 5x ULN if
    patient is asymptomatic
         LTBI: Bottom Line

• Assess patient for TB risk factors
• If risk is present, perform TST (or IGT)
• If TST (or IGT) is positive, rule out active
  TB disease
• If active TB disease is ruled out, initiate
  treatment for LTBI
• If treatment is initiated, ensure completion
       6 Key Learning Points
1.   Assess for TB Risk
2.   If risk present, perform TST/IGT* test
3.   If TST +, r/o active TB
4.   If no active TB, treat LTBI
5.   Ensure completion of LTBI
6.   If active TB, isolate and treat

                            *IGT = interferon gamma testing
Case Studies
             Case Study 1
29-year-old African-American female
• Diabetes
• 35 weeks pregnant
• TST = 20 mm of induration
• No symptoms of TB disease
• CXR, CBC, LFTs normal
• No known contact with TB patient
    What are her primary risk

1. Diabetes
2. Pregnancy
3. Both
           Case Study 1

• Persons with diabetes mellitus are
  2 to 4 times more likely to develop
  TB disease than those without
• Risk may be higher in insulin-
  dependent diabetics and those
  with poorly controlled diabetes
              Case Study 1
• Pregnancy has minimal influence on the
  pathogenesis of TB or the likelihood of
  LTBI progressing to disease
• Pregnant women should be targeted for
  TB testing only if they have specific risk
  factors for LTBI or progression to
When would you treat her?

1. Now
2. After delivery
3. Doesn’t matter
           Case Study 1

 OK to delay treatment until after
 the early postpartum period,
 unless the person has recent TB
 infection or HIV infection
           Case Study 2
47-year-old Hispanic male
• Moved to U.S. from Bolivia 4 years ago
• Known contact of infectious TB case
• TST = 5 mm of induration
• 3 months later TST = 23 mm of induration
• No symptoms of TB disease
• Normal CXR, CBC, AST, and bilirubin
What are this patients risk factors
             for TB?

1.   Hispanic
2.   Immigration from Bolivia
3.   5mm TST on arrival
4.   Exposure to active TB
           Case Study 2

• Patient is a contact of an infectious
  TB case
• Recent immigrant to the U.S. from a
  country with a high prevalence of TB
             Case Study 2
• Persons from TB-endemic countries
  have increased rates of TB
• Rates of TB similar to country of origin
  for 5 years after arrival in the U.S.
• Increased rates most likely due to M.
  tuberculosis infection in native country
Was his 5mm TST positive on

1. Yes
2. No
            Case Study 2
• Normal immigrant positive is ≥ 10
  mm of induration
• As a contact of an active TB case,
  however, 5 mm of induration is
  considered positive for this patient
• Should have been treated for LTBI
  immediately after the first TST
             Case Study 3
36-year-old Asian female
  • Moved to U.S. from Philippines > 15 years
  • Works in a correctional facility
  • TST result negative 1 year ago
  • TST employment physical = 26 mm
  • CXR normal
  • No symptoms of TB disease
  • No known contact with a TB patient
What are this patients risk factors
             for TB?

1.   Female
2.   Philippines
3.   Correctional work
4.   Recent TST conversion
           Case Study 3
• Recent TST conversion (within a 2-
  year period)
• TST conversion increases risk for
  progressing from LTBI to TB disease
• Foreign-born status is less of a risk
  factor (immigrated > 5 years ago)
• Correctional work
             Case Study 3
• Patient is a recent ‘converter’ and, as
  such, is a candidate for treatment of
  LTBI with INH
  A 36-year-old male who recently immigrated
  from Rwanda presents with a several-month
  history of cough accompanied by hemoptysis
    and weight loss. He is afebrile, and a lung
   examination is normal. A chest radiograph
shows a cavitary lesion in his left upper lobe. He
     is admitted to the hospital and placed in
     respiratory isolation. A tuberculin test is
 positive, but three induced sputum smears are
 negative for acid-fast bacillus. Cultures are still
  pending. Which one of the following INITIAL
    treatment regimens is most appropriate?
1. No treatment until culture results are
2. Isoniazid for 9 months
3. Rifampin and pyrazinamide for 8 weeks
4. Rifampin and/or isoniazid for 18 weeks
5. Rifampin, isoniazid, ethambutol, and
   pyrazinamide for 8 weeks
•High incidence in sub-Saharan Africa.
•Positive AFB smear/culture for M. tb to
confirm active disease,
•Treatment should begin without delay if
suspicion is high (four drugs)
•Initial treatment for previously untreated is
8 weeks of rifampin, isoniazid, ethambutol,
and pyrazinamide.
•If the likelihood of active tuberculosis is low,
treatment can be deferred until the results of
mycobacterial cultures are known.

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