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TB (Infection) or not TB? Who should we screen and treat?

TB (Infection) or not TB? Who should we screen and treat?. Primary Care Conference August 31, 2005 K. Mae Hla, M.D., M.H.S. Learning Objectives. Review guidelines for testing and treatment of LTBI using case examples Evaluate the rationale for targeted TST

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TB (Infection) or not TB? Who should we screen and treat?

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  1. TB (Infection) or not TB? Who should we screen and treat? Primary Care Conference August 31, 2005 K. Mae Hla, M.D., M.H.S.

  2. Learning Objectives • Review guidelines for testing and treatment of LTBI using case examples • Evaluate the rationale for targeted TST • Discuss factors influencing TST results and interpretations • Assess the evidence of current treatment recommendations for LTBI • Updates on new tests and treatment recommendations

  3. Case #1 43 year old female physician who underwent routine annual testing at UWHC: PPD was 10 mm. Previous year’s PPD was 0 mm. No known history of exposure but works with high risk patients No history of BCG No history of cough, low grade fever, night sweats or weight loss

  4. What would you do with this patient? • Consider the test positive • Consider the test negative • Consider a Chest X-ray • Disregard test results if chest x-ray is negative since she’s older than 35 years  

  5. Case #2 • 32 year old man arrived from India 2 years ago • TB tested during pre-employment exam • 23 mm induration • H/o BCG in childhood • No symptoms of active TB

  6. What would you do with this patient? • Positive TST is due to BCG • Old positive PPD • No need to consider for INH treatment since due to either of the above • Disregard BCG and recommend INH 

  7. What would you do now? • Positive TB test is due to BCG • Old positive PPD • No need to consider for INH treatment since due to either of the above • Disregard BCG and recommend INH –end of story • Test further 

  8. Case # 3 • 28 y.o. woman with SLE, ESRD, S/P kidney transplant on immunosuppressive therapy • PPD placed during hospitalization with acute lung infiltrate was 6 mm • Is this PPD positive or negative?

  9. Case # 4 36 y.o. diabetic male, PPD 13 mm, recently in prison, known exposure to INH resistant TB, no known prior PPDs, no acute symptoms, CXR-negative. • Is this person at risk of developing TB? • What are his risk factors? • What would you recommend he be treated with?

  10. Case # 5 • 30 y.o. male seen in clinic for naturalization physical • Country of origin: England • Hx of BCG at age 13 • PPD: 11 mm induration, never been tested in past • CXR normal

  11. Case # 5 • Consider his PPD positive • Consider his PPD negative • Consider his pos PPD to be due to BCG and not recommend INH • Disregard BCG and consider 9 months of INH 

  12. Case # 6 35 y.o. HIV positive male, PPD negative for past 2 yrs, tested 6 mm now; no known exposure history, no acute symptoms, CXR negative for active or old TB. • Is his PPD negative or positive? • How likely is he to develop active TB?

  13. General Principles in Screening • The disease is common (prior probability) • The test is both accurate and reliable • Treating the disease at an early phase will lead to improved outcome compared to that of treating it only when it manifests itself as active disease • Treatment is feasible and not harmful

  14. Reported TB Cases United States, 1953 - 1998 100,000 70,000 * 50,000 Cases (Log Scale) * 30,000 20,000 10,000 53 60 70 80 90 98 Year *Change in case definition

  15. Reported Cases of TB by Country of Birth - United States, 1986-1998 40 35 30 Foreign-born 25 Recent Cases per 100,000 population 20 15 All Cases 10 5 U.S.-born 0 86 98 87 88 89 90 91 92 93 94 95 96 97 Year

  16. Areas of Concern • TB cases continue to be reported in every state • Drug-resistant cases reported in almost every state • Estimated 10-15 million persons in U.S. infected with M. tuberculosis • Without intervention, about 10% will develop TB disease at some point in life

  17. Targeted TB Testing • Identify persons with LTBI who would benefit by treatment of LTBI • Find persons with TB disease who would benefit from treatment • Groups that are not high risk for TB should not be tested routinely • All testing activities should be accompanied by plan for follow-up care

  18. Who should we screen?High Risk Groups for LTBI Groups that should be tested for LTBI regardless of age: • Persons at higher risk for exposure to or infection with TB • Persons at higher risk for TB once infected

  19. Persons at Higher Risk for Exposure to or Infection with TB • Close contacts of person known or suspected to have TB • Foreign-born persons from areas where TB is common • Residents and employees of high-risk congregate settings • Health care workers (HCWs) who serve high-risk clients

  20. Persons at Higher Risk for Exposure to or Infection with TB (cont.) • Medically underserved, low-income populations • High-risk racial or ethnic minority populations • Children exposed to adults in high-risk categories • Persons who inject illicit drugs

  21. TB Case Rates* according to the length of Residence in the U.S. for Foreign-Born Persons, 1986-1993 * Rates are per 100,000 person-years, adjusted for age.

  22. Persons at Higher Risk of Developing TB Disease once Infected • HIV infected • Recently infected (converted within 2 yr) • Persons with certain medical conditions • Persons who inject illicit drugs • History of inadequately treated TB

  23. Incidence of active TB in persons with a positive PPD by selected risk factors Risk Factor TB Cases/1,000 person-years Recent TB infection Infection <1 yr past 12.9 Infection 1-7 yr past 1.6 Human immunodeficiency virus (HIV) infection 35.0-162 Injection drug use HIV seropositive 76.0 HIV seronegative or unknown 10.0

  24. Relative risk* for developing active TB by selected clinical conditions Clinical Condition Relative Risk Silicosis 30 Diabetes mellitus 2.0-4.1 Chronic renal failure/hemodialysis 10.0-25.3 *Relative to control population; independent of TB test status

  25. Relative risk* for developing active TB by selected clinical conditions Clinical Condition Relative Risk Gastrectomy 2-5 Jejunoileal bypass 27-63 Solid organ transplantation Renal 37 Cardiac 20-74 Carcinoma of head or neck 16 *Relative to control population; independent of TB test status

  26. Are HCWs at high risk of LTBI? • Prevalence of TB in the community, facility, institution • Contact with high risk patients (HIV positive pts., injection drug users, homeless pts.) • Increased risk in certain occupational groups (respiratory therapists) • Individual risk factors (diverse workforce)

  27. Test accuracy and reliability • Prior probability of disease • Method of administration • Timing of reading • Interpretation

  28. Administering the Tuberculin Skin Test • Inject intradermally 0.1 ml of 5 • TU PPD tuberculin • Produce wheal 6 mm to 10 mm • in diameter • Do not recap, bend, or break • needles, or remove needles from syringes • Follow universal precautions for infection control

  29. Reading the Tuberculin Skin Test • Read reaction 48-72 hours after injection • Measure only induration • Record reaction in millimeters

  30. Classifying the Tuberculin Reaction>5 mm is classified as positive in • HIV-positive persons • Recent contacts of TB case • Persons with fibrotic changes on chest radiograph consistent with old healed TB • Patients with organ transplants and other immunosuppressed patients

  31. >10 mm is classified as positive in • Recent arrivals from high-prevalence countries • Injection drug users • Residents and employees of high-risk congregate settings (hospitals, prison, NH) • Mycobacteriology laboratory personnel • Persons with clinical conditions that place them at high risk • Children <4 years of age, or children and adolescents exposed to high-risk adults

  32. Classifying the Tuberculin Reaction (cont.) • >15 mm is classified as positive in • Persons with no known risk factors for TB • HCWs otherwise at low risk for TB disease and who received baseline testing at start of employment

  33. Factors that May Affect the Skin Test Reaction

  34. Boosting • Some people with LTBI may have negative skin test reaction when tested years after infection • Initial skin test may stimulate (boost) ability to react to tuberculin • Positive reactions to subsequent tests may be misinterpreted as a new infection

  35. Two-Step Testing Use two-step testing for initial skin testing of adults who will be retested periodically • If first test positive, consider the person infected • If first test negative, give second test 1-3 weeks later • If second test positive, consider person infected • If second test negative, consider person uninfected

  36. BCG Vaccination and TST • Tuberculin skin testing is not contraindicated in BCG-vaccinated persons • Treatment for LTBI should be considered for any BCG- vaccinated person whose skin test reaction is >10 mm, if any of these circumstances are present: • Was contact of person with infectious TB • Was born or has resided in a country with high TB prevalence • Is continually exposed to populations where TB prevalence is high

  37. BCG Effect vs. LTBI • Case # 2 • Likely LTBI given country of origin and recent arrival • Case # 5 • Likely BCG effect

  38. New Test for Detecting LTBI • QuantiFERON (QFT)– FDA approved in 2001 • in vitro cytokine assay • quantification of interferon-gamma released from sensitized lymphocytes in whole blood incubated overnight with PPD from M.TB • will not detect M. Bovis strains used in BCG • QFT results: % Tuberculin response: cut point of 15% for people with identified risk, 30% for people with no identified risk for infection

  39. QuantiFERON-TB Test • Advantages • Less subjective than interpretation of the TST • Requires single patient visit • Helps in detecting LTBI in patients who have had BCG • Does not boost anamnestic immune responses • Maybe more efficient and cost effective than TSTs in screening HCWs for infection with M.TB

  40. QuantiFERON-TB Test (QFT) • Disadvantages • limited laboratory and clinical experience • process within 12 hours after blood collection • ability of QFT in predicting progression to TB disease not evaluated • confirmation of a positive QFT with TST recommended especially if probability of LTBI low • active TB still needs to be ruled out

  41. Who Should We Treat? • Persons who are at very high risk of developing TB once infected should be given treatment regardless of age

  42. Patients who should be treated if their TST result is >5, regardless of age • HIV-positive persons • Recent contacts of TB case • Persons with fibrotic changes on chest radiograph consistent with old healed TB • Patients with organ transplants and other immunosuppressed patients

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