CHILDHOOD TUBERCULOSIS: NEW WRINKLES IN AN OLD DISEASE [FOR THE NON-TB EXPERT]

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1 CHILDHOOD TUBERCULOSIS: NEW WRINKLES IN AN OLD DISEASE [FOR THE NON-TB EXPERT] QUESTION: : Which children in the United States should get a tuberculin skin test? Do questionnaires really work? Jeffrey R. Starke, M.D. Professor and Vice-Chairman of Pediatrics Baylor College of Medicine TUBERCULOSIS CASES IN THE UNITED STATES CHILDREN 0-14 YEARS OLD SOME REASONS WHY TUBERCULOSIS RESURGED IN THE U.S ,800 1,600 1,400 1,200 1, HIV co-epidemic Immigration and visitation Transmission in congregate settings Poor tuberculosis control IMMIGRATION-RELATED RELATED TUBERCULOSIS IN THE UNITED STATES IMMIGRATION AND PEDIATRIC TUBERCULOSIS About 1 million annual legal immigrants 30-40% have latent tuberculosis infection (LTBI) Pool of infected individuals increases by K per year 2% - 5% risk of disease: 6,000 20,000 future cases per year Immigrants > 15 years old CXR only Immigrants < 15 years old no services Visitors, all ages no services California study: receipt of foreign visitors in the home was an independent risk factor for LTBI in a child

2 MANTOUX TUBERCULIN SKIN TEST uses 5 TU of purified protein derivative (PPD) interpret in hours record size of induration in mm if it makes a reaction at >72 hrs, it counts! false negatives: 10% to 20% in disease TUBERCULIN SKIN TEST PROBLEMS CREATED BY FALSE POSITIVE TUBERCULIN SKIN TEST RESULTS Assume sensitivity = specificity = 95% When the prevalence of infection is 90%, the positive predictive value is 99% When the prevalence of infection is 1%, the positive predictive value is 15% [85% false positives] 1. There is no way to distinguish false from true positive results, so all positives should be evaluated and treated 2. Costs of evaluation: doctor/clinic time, xrays, medications, adverse reactions, evaluation of family members 3. Anxiety who has TB??? TUBERCULIN SKIN TEST UTILITY INDURATION SIZE POSITIVE TUBERCULIN SKIN TEST > 5 mm > 10 mm Accurate and useful for high-risk persons Inaccurate and, perhaps, harmful for low-risk persons HIV co-infection Foreign-born from a HR Immune compromise country Recent contact to TB Drug users Suspected disease Living in HR congregate setting Specific HR groups Children < 4 yrs old (AAP) >15 mm No risk factors

3 NYCDOH QUESTIONNAIRE FOR LTBI - RESULTS TARGETED TST TESTING KAISER PERMANENTE GROUP 23/413 (5.6%) of children with at least one risk factor had a reactive TST 4/2507 (0.16%) of children with no risk factors had a reactive TST ¾ children not identified were > 11years old 33,553 children in 18 offices Validated Risk Factors : Any Child Who was born outside the United States received a BCG vaccine lived outside the United States lives with someone with TB history LTBI RISK ASSESSMENT QUESTIONNAIRE FOR CHILDREN All risk assessment questionnaire should ask: QUESTION: : Should I repeat the TST when the result is borderline? 1. Was your child born outside the U.S? Where? 2. Has your child traveled (non-tourist, 1 wk) outside the U.S.? Where? 3. Has your child been in contact with anyone with TB? 4. Does your child have contact with anyone with a positive tuberculin skin test? REPEATING THE TST The TST does not get more accurate as one repeats it; it is more difficult to interpret Boosting: : tendency for increased induration with serial TSTs; ; in children, most often associated with previous receipt of a BCG vaccine The most accurate TST is the first one: do it right and do it well! CDC definition of a conversion of a TST is an increase in induration of 10 mm QUESTION: : Should I repeat the TST if the child has risk factors for LTBI?

4 HOW OFTEN SHOULD A TST BE GIVEN? Must separate previous risk from on-going risk Receipt of foreign visitors from high prevalence countries into the home was a risk factor for one California study for a positive TST in a child Frequent problem: summer trips abroad Sharing the air with indigenous people. For foreign travel, wait 3 months until after return QUESTION: : What really is the effect of a previous BCG vaccination on a subsequent TST? INTERACTION OF BCG VACCINES WITH THE TUBERCULIN SKIN TEST 50% of vaccinated infants do not react to a TST; most of the rest stop reacting within 5 years most non-infants who get one or more BCG vaccinations will react to a TST (usually < 15 mm), but effect wanes over 5 10 years outside infancy, positive TST more likely to indicate infection with M. tuberculosis than be residual from BCG QUESTION: : How do I handle tuberculin skin testing of foreign-born adopted children? TUBERCULIN SKIN TESTING OF FOREIGN-BORN ADOPTEES On one hand, most children have received a BCG vaccine within the past year, which can cause reaction to a TST On the other hand, many have lived in conditions conducive to transmission of M. tuberculosis and we can t t do an investigation

5 TUBERCULIN SKIN TESTING OF FOREIGN-BORN ADOPTEES General Guidelines 1. Assess for symptoms of tuberculosis disease prolonged (>2 wk) cough, weight loss, fevers QUESTION: : Should I (or someone) do a TST on family members of children who have a positive TST? 2. Note a BCG scar and/or immunization records 3. Place and read a 5 TU TST without controls 4. Delay the TST if the child is significantly malnourished 5. Positive TST reaction is 10mm, though this will result in some overtreatment due to recent BCG vaccination 6. Treat LTBI with isoniazid unless specific evidence of INH- resistance is uncovered ASSOCIATE INVESTIGATION CHILDREN WITH LTBI Associate investigation: identification and evaluation of close contacts of children and adolescent with LTBI can be considered a form of targeted testing although often recommended (AAP-Red Book), many health departments have limited/no resources yield of finding cases of tuberculosis is low yield of finding LTBI is 30% to 40% effective only if index child was tested because of risk QUESTION: : Is there any role currently for the new interferon-gamma release assays in diagnosing LTBI in infants and children? INTERFERON-GAMMA RELEASE FOR DIAGNOSIS OF LTBI IN CHILDREN - SEPTEMBER, 2006 Only commercially available (5/05) test in the U.S. is QuantiFERON-TB Gold Measures release of interferon-gamma into whole blood after stimulation of lymphocytes with ESAT-6 6 and CFP-10, proteins fairly specific for M. tuberculosis Unfortunately, data for children ware very limited. Despite this, CDC (12/05) states tests can be used in children.

6 Comparison of Tuberculin Skin Test and Interferon- ٢ Release Assays Antigens studied Cross-reactivity reactivity with BCG Cross-reactivity reactivity with NTM Estimated sensitivity, TB in immunocompetent adults Estimated specificity, TB in immunocompetent adults Distinguish between TB infection and TB disease Boosting No. of patient visits required Tuberculin Skin Test Many -PPD Yes Yes 75-90% 70-95% No Yes Two IFN- ٢ Release Assay ESAT-6, CFP-10 Unlikely Less Likely 75-95% % No No One QUESTION: : What are some pearls for treatment for LTBI in infants and children? TREATMENT OF LTBI IN CHILDREN 9 months of isoniazid (daily or twice weekly under DOT) is only accepted regimen INH-resistance or intolerance rifampin for 6 months Multidrug-resistance resistance consult an expert Use isoniazid unless there is documented exposure to a specific case of drug-resistant resistant TB PEARLS OF WISDOM FOR TREATING LTBI IN CHILDREN Use INH suspension only in children 5 kg Compliance with 9 months of INH averages 50% - be vigilant and skeptical Use DOPT for: recent contacts, infants, immune compromised When children aren t t tolerating INH, the problem is more often with the parent than the child Route LFTs only for: other liver toxic drugs, liver disease, signs or symptoms of hepatitis