Tuberculosis

1
Tuberculosis
2
Objectives

• Know current epidemiologic trends in TB
• Know indications for testing for TB exposure and
  the tests available
• Be familiar with treatments for latent
  tuberculosis infections

3
Background Epidemiology
4
9 million Cases Annuallygt1/3 in India and China
9 million Cases Annually gt1/3 in India and China
lt 1 000
1 000 to 9 999
10 000 to 99 999
100 000 to 999 999
1 000 000 or more
No Estimate
5
Reported TB Cases United States, 19822006
No. of Cases
Year
6
TB Case Rates, United States, 2006
D.C.
lt 3.5 (year 2000 target)
3.64.6
gt 4.6 (national average)
Cases per 100,000.
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TB Case Rates by Age Group and Sex, United
States, 2006
Cases per 100,000


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Trends in TB Cases in Foreign-born Persons,
United States, 19862006
No. of Cases
Percentage
Updated as of April 6, 2007.
9
Drug Resistant TB Counted Cases defined on
Initial DST by Year, 19932006
Reported incident cases as of 7/18/07 Drug
Susceptibility Test
Case Count
Year of Diagnosis
10
TB in Children

• WHO estimate of TB in children
• 1.3 million annual cases
• 450,000 deaths
• 15 of TB in low-income countries children vs. 6
  in United States

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MAKING THE DECISION TO TEST FOR TB

• The Initial Test for TB Infection is the History

12
Who Should be Tested?

• Those at epidemiological increased risk of having
  TB infection
• Those at increased individual risk of developing
  TB disease if infected
• ONLY test if you are going to treat the patient
  a decision to test is a decision to treat

13
Questionnaire Risk Assessment for TB Infection in
Children - NYCDOH
Ozuah et al. JAMA285451

• Risk factor Sens. Spec. PPV NPV
  OR
• Contact to a case 26 99.6 38.9
  99.3 92
• Birth/travel to endemic area 63 89.7
  5.4 99.6 15
• Contact to HR adult 19 96.6
  4.9 99.2 7
• Age gt 11 yr 67 71.0 2.1
  99.6 5

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Epidemiologically-Defined Groups with HIGH
Prevalence of Tuberculosis Infection

• Immigrants from areas of world with a high
  incidence of TB
• Homeless persons, and other low income groups
  with poor access to health care
• Elderly persons
• Residents and employees in congregate living
  facilities serving persons at high risk of TB
  (correctional institutions, homeless shelters,
  health care facilities, nursing homes, assisted
  living facilities, AIDS housing)

15
Underlying Medical Conditions Which Increase
Risk for Progression to Active TB Disease

• HIV infection
• Chronic renal failure
• Immunosuppressive Rx
• Diabetes mellitus
• Malignancy
• TNF Alpha blocker therapy
• Transplant recipients
• gt 15 mg Prednisone/day
• Silicosis

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Incidence of Tuberculosis by Selected Risk
Factors in Persons with a Positive TST
Risk Factor
TB Cases/1000 person-years
Recent TB Infection Infection lt 1 year past
Infection 1-7 years past HIV/AIDS Injection Drug
Use HIV-positive HIV-negative or
unknown Silicosis Radiographic findings
consistent with old TB Weight Deviation from
Standard (?5 overweight ? ?15 underweight)
12.9 1.6 35.0-162 76.0 10.0 68.0 2.0-13.6 0.7-2.6
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HOW TO TEST
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Tuberculin Skin Testing
Tuberculin Skin Testing
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Induration of gt5mm Considered a Positive TST

• HIV positive persons
• Recent contacts of TB cases
• Fibrotic Changes on CXR c/w old (not treated) TB
• Patients with organ transplants or other
  immunosuppression
• Prednisone therapy 15 mg/day gt 1 month

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Induration of gt10mm Considered a Positive TST

• Recent arrivals (lt5 yrs) high prevalence
  countries
• Intravenous Drug Users
• Residents/employees - high-risk congregate
  facilities (health care, prisons, shelters, etc.)

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Induration of gt15mm Considered a Positive TST

• TB lab personnel
• Persons with high-risk medical conditions
• Children lt4 yrs or exposed to adults at risk

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Interferon Gamma Release Assays

• Quantiferon measure of interferon gamma in
  supernatant, currently at third generation test
  Quantiferon Gold In-tube
• Elispot measure of individual T-cells that
  produce interferon gamma.

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Positive Skin Test

• Now what?

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Before Treatment of LTBI Exclude Active
Tuberculosis

• Absence of symptoms
• Negative CXR
• Negative medical evaluation
• Order and wait for sputum culture if
• any question

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Hilar adenopathy with infiltrate and collapse
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Miliary TB in a child
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Chest Radiograph Pearls

• Hilar nodes, pleural disease extrapulmonary,
  few bacteria
• Cavitary disease many bacteria
• Parenchymal scars NOT active, only needs
  preventive therapy (LTBI) IF scar is gt 2.5 cm
• Calcified node is functionally like a normal
  chest radiograph (very very few live AFB)

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Childhood TB diagnosed by

• Combination of
• Contact with infectious adult case
• Symptoms and signs
• Positive tuberculin skin test
• Suspicious CXR or CT/MRI
• Bacteriological confirmation
• Serology?

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Treatment
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Treatment of LTBI

• Treatment regimens
• INH x 9 months
• Alternative Rifampin 600mg daily x 4 months for
  adults, 6 months for children and HIV
• Possible
• INH Rifampin x 3 to 4 months
• INH, Rifampin, EMB PZA x 2 months
• No longer used Rifampin/PZA x 2 months
• New? Rifapentine INH weekly x 12 weeks

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ISONIAZID PREVENTIVE THERAPYWorldwide Trials,
1955-1965
Tunisia Kenya India Philippines
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How Much Isoniazid Is Needed for the Prevention
of Tuberculosis?

• Longer durations of therapy corresponded to lower
  TB rates among those who took 0-9 mo
• No extra increase in protection among those who
  took gt9 months

Community based study, Bethel Alaska
Comstock GW, 1999. Int J Tuberc. Lung Dis
3847-850
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IUATLD Study of INH Therapy for LTBI

• Reduction in culture positive TB at 5 years all
  participants
• 6 months therapy 65
• 12 months therapy 75
• Reduction in culture positive TB at 5 years in
  the group of completer-compliers (took gt 80 of
  doses)
• 6 months therapy 69
• 12 months therapy 93

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Contacts Of INH Resistant TB

• Four month regimen daily Rifampin for
  adults
• Six month regimen daily Rifampin for HIV
  infected
• Six month regimen daily Rifampin for
  children

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Treatment of Latent TB Infection in Special
Situations

• For children and adolescents (lt18 years old)
• Isoniazid for 9 months
• For pregnant women
• Isoniazid for 9 or 6 months - may defer except
  for HIV- infected women and those recently
  infected with Mycobacterium tuberculosis
• For persons exposed to isoniazid resistant TB
• Rifampin for 4 months
• For persons likely infected with
  multidrug-resistant TB
• Pyrazinamide and ethambutol, or pyrazinamide
  and
• quinolone for 6-12 months (i.e., at least 2
  drugs to which the organism is susceptible)

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TB and BCG Vaccination

• Efficacy for adult pulmonary TB 0-80 in
  randomized clinical trials
• Best efficacy against serious childhood disease
• 64 protection against TB meningitis
• 78 protection effect against disseminated TB
• BCG important for young children, inadequate as
  single strategy

Colditz GA et al. JAMA 1994 271 698-702.