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  1. Pediatric Tuberculosis Update Dr. George McSherry Audio Conference July 27, 2005

  2. Tuberculosis in Children and Adolescents 2005 • Epidemiology • Public Health Aspects & TB Control • Targeted Tuberculin Skin Testing • Contact Investigations • BCG Vaccine • Treatment of Latent TB Infection and TB Disease

  3. Global Epidemiology of TB • Tuberculosis remains the leading infectious disease in the world • More than 40% of the world’s population (>2 billion people) are infected with M. tuberculosis • In the 1990s: • 90 million new cases • 30 million deaths • Among children <15 years of age: • Approximately 13 million cases • 5 million deaths

  4. Reported TB Cases United States, 1982-2003 28,000 24,000 No. of Cases 20,000 16,000 12,000 1983 1987 1991 1995 1999 2003 Year

  5. Number of TB Cases inU.S.-born vs. Foreign-born Persons United States, 1993-2003 No. of Cases CDC

  6. Trends in TB Cases in Foreign-born Persons, United States, 1986-2003 No. of Cases Percentage 00 01 02 03 CDC

  7. Percentage of TB Cases Among Foreign-born Persons, United States 1993 2003 DC DC >50% 25% - 49% <25%

  8. Countries of Birth for Foreign-born Persons Reported with TB: United States (New Jersey), 2003 Mexico* 26% (9%) Other Countries 36% (52%) Philippines* 12% (11%) S. Korea 2% (2%) Haiti 3% (5%) Viet Nam* 8% (2%) China 5% (1%) Peru (9.4%) Ecuador (8.1%) India 8% (17%)

  9. Pediatric TB case rates by race/ethnicity, 1993-2001 Nelson, L. J. et al. Pediatrics 2004;114:333-341

  10. Reported TB Cases by Age Group United States, 2003 <15 yrs (6%) 65+ yrs (20%) 15 - 24 yrs (11%) 25 - 44 yrs (34%) 45 - 64 yrs (29%)

  11. Number and Percent of All TB Cases Occurring Among Children <15 Years CDC

  12. TB case rates by age group, 1993-2001 Nelson, L. J. et al. Pediatrics 2004;114:333-341

  13. Summary of Epidemiology of TB • Cases and case rates are on the decline • Foreign born persons account for more than 50% of U.S. cases • New Jersey: 70% • TB in children: • Highest risk for disease: • <5 years of age • Foreign born children • 60% of cases develop within 18 months of arrival in U.S. • Most common countries of birth: Mexico, Philippines, Vietnam • Varies depending on immigration patterns, i.e., recent increases in case among children from Sub-Saharan Africa and Eastern Europe • Racial and ethnic minorities

  14. Significance of Tuberculosis in Children A case of tuberculosis in a child is considered a “sentinel healthcare event” representing recent transmission of TB within the community

  15. Children <15 years with TBby Site of Disease

  16. Children <15 years with TB:Extrapulmonary Disease

  17. TB Control In the United States • Identification of new cases of TB • Initiation of appropriate treatment • Directly observed therapy • Contact Investigations • Identify persons at risk for infection • Targeted tuberculin testing • Identifies persons at high risk for TB who would benefit by treatment of LTBI • Treatment of latent TB infection (LTBI)

  18. Mantoux Tuberculin Skin Test • Specificity of the test varies depending on the prevalence of LTBI and the frequency of cross-reactions to the PPD antigen in a given population • In a population with relatively high frequency cross-reactions the specificity of the PPD is <95% • Decreases the positive predictive value of positive test in a low risk population • If the specificity is 90% in a low risk population with a prevalence of LTBI of 1%: • Positive predictive value of TST: 8% • 92% of positives are false positives • As prevalence of LTBI increases the PPV increases Huebner RE. Clin Infect Dis 1993;17:968

  19. AAP Recommendations: Targeted Tuberculin Skin Testing • Risk of exposure to TB should be assessed at routine healthcare evaluations • Only children with an increased risk of acquiring TB infection or disease should be considered for testing • Frequency of testing should be according to the degree of risk of acquiring infection • “Screening” is an inefficient way to control tuberculosis

  20. Targeted Tuberculin Testing Risk-Assessment Questionnaire • Was your child born outside the United States? • Africa, Asia, Eastern Europe, Latin America • Has your child traveled outside the United States? >1 week • Has your child been exposed to anyone with TB disease? TB or LTBI, nature of contact • Does your child have close contact with a person who has a positive TB skin test? Pediatrics 2004;114:1175, supplement

  21. Targeted Tuberculin Testing Risk-Assessment Questionnaire • Depending on local epidemiology and priorities other possible questions include: • Does your child spend time with anyone who has been in jail or a shelter, uses illegal drugs or has HIV? • Has your child had raw milk or eaten unpasteurized cheese? • Is there a household member born outside the U.S.? • Is there a household member who has traveled outside the U.S.? Pediatrics 2004;114:1175, supplement

  22. AAPRecommendations: Tuberculin Skin Testing • Children for whom immediate TST is indicated: • Contacts of persons with confirmed or suspected infectious tuberculosis (contact investigation) • Children with CXR or clinical findings suggesting TB • Children immigrating from endemic countries (e.g., Asia, Middle East, Africa, Latin America) • Children with histories of travel to endemic countries and/or significant contact with indigenous persons from such countries Red Book 2003

  23. AAP Recommendations: Tuberculin Skin Testing • Children who should have an annual TST: • Children with HIV infection • Incarcerated adolescents Red Book 2003

  24. AAP Recommendations: Tuberculin Skin Testing • Some experts recommend that these children should be tested every 2-3 years: • Children exposed to the following persons: • HIV-infected • Homeless • Residents of nursing homes • Institutionalized or incarcerated adolescents or adults • Users of illicit drugs • Migrant farm workers • Foster children with exposure to adults in the preceding high risk groups

  25. AAP Recommendations: Tuberculin Skin Testing • Children who should be considered for TST at 4-6 and 11-16 years of age: • Children whose parents immigrated (with unknown TST status) from regions of the world with high prevalence of tuberculosis • Children with continued potential exposure by travel to endemic areas and/or household contact with persons from endemic areas (with unknown TST status)

  26. Administering the Tuberculin Skin Test • Inject intradermally 0.1 ml of 5 TU PPD tuberculin • Produce wheal 6mm to 10mm in diameter • Placed and read by experienced health professionals

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

  28. Parental Reading of Tuberculin Skin Testing • TST was placed on 37 children from different families • Parents were instructed verbally about • The importance of the test • When and how to read induration • Given written instructions • Had the date stamped on their hands • Site was marked with permanent marker and a bracelet with the reading date was placed on the child’s hand • Results: 36/37 returned for reading • Only 22% of families (8/36) were able to both read and document skin test results appropriately Cheng TL, PIDJ 1996

  29. Positive TST in Children:Definitions • Takes into account the following: • Risk of infection (exposure) • Risk of progression to disease • Immune status • Age

  30. Positive TST Results: Infants, Children, and Adolescents • TST considered positive at >5 mm induration when: • In close contact with known or suspected contagious cases of tuberculosis • Suspected to have tuberculosis disease: • CXR consistent with active or previously active tuberculosis • Clinical evidence of tuberculosis • Receiving immunosuppressive therapy • With immunosuppressive conditions • With HIV infection

  31. Positive TST Results: Infants, Children, and Adolescents • TST considered positive at >10 mminduration in children: • At increased risk of disseminated disease: • Young age: <4 years of age • Other medical conditions: Hodgkin disease, lymphoma, diabetes mellitus, chronic renal failure, malnutrition • With increased exposure to tuberculosis disease • Born or whose parents were born in high-prevalence regions of the world • Frequently exposed to adults who are HIV-infected, homeless, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized persons, migrant farm workers • Travel and exposure to high-prevalence regions of the world

  32. Positive TST Results: Infants, Children, and Adolescents • TST considered positive at >15 mminduration: • In children >4 years of age without any risk factors

  33. Evaluation of the Child with a Positive TST • Evaluation of all children with a positive TST should include: • A careful history • Household investigation • Physical examination • Chest radiographs (PA & lateral)

  34. Treatment of Latent Tuberculosis Infection in Children • INH 10 mg/kg (max., 300 mg) PO daily for 270 doses • Alternative: Twice weekly directly observed (DOT) INH 20-40 mg/kg (max., 900 mg) PO for 72 doses • Monitor index case isolate sensitivities • Hepatotoxicity from INH is rare in children: • A monthly assessment for clinical evidence of hepatotoxicity should be made: loss of appetite or weight, nausea, vomiting, abdominal pain, jaundice • Routine monitoring of LFTs is not indicated

  35. Tuberculosis Control in the United States • Contact Investigations “The most reliable TB control program is based upon aggressive and expedient contact investigations, rather than routine screening of large populations with low risk.” Can be complex, require experience and often a lot of detective work.

  36. Concentric-Circle Approach to Contact Tracing Home Environment Casual Close Index Case Leisure Environment Work/School Environment Adapted from Etkind S., Veen J., In Reichman-Hershfield: Tuberculosis: A Comprehensive International Approach, 2000

  37. Presenting Patient (Ppt.)(Index case) • 6/14/04 (Monday): 39 year-old female was admitted to a suburban New Jersey hospital with complaints of fever, decreased appetite, 23 lb weight loss, cough X 1-3 months, night sweats • Chest radiographs were done

  38. Presenting Patient (Index case) • 6/17 (Thursday): First sputum was obtained for AFB studies; AFB smear reported as (4+); AFB subsequently confirmed as M. tuberculosis • 6/19 (Saturday): Treatment initiated with INH, RIF, PZA, & ethambutol • 6/21 (Monday): Presumptive case of TB reported by telephone to local health department • Included in the report: Place of employment - a Daycare Center (DCC) • Same day: Health department nurse contacted TB controller for the county

  39. Contact Investigation Initiated • 6/21 (Monday): Maintaining confidentiality, TB controller calls asst. dir. of DCC to schedule CI management meeting and on-site assessment; asst. dir. volunteers that Ppt. is her aunt (“I know who this is…”): • Secretarial volunteer 1-2 hrs/week • Works at desk doing paperwork, filing • Little or no contact with children in the daycare • Asst. dir. also reveals that she has 6 mo. old infant, exposed to Ppt. socially on weekends (10 hrs/wk): • “Does not attend daycare” • “Diagnosed with pneumonia 4 weeks ago” • TB controller arranges with local health department to have TST placed that day on the infant; CXR scheduled • In subsequent TB Q & A sessions with other parents it is learned that infant was at daycare regularly

  40. Contact Investigation, cont. • 6/22: First of 4 interviews of Ppt. by 3 different interviewers is held in hospital • Infectious period: 3/17-6/14/04 (Contact broken) • May have spent more time daycare (2-3 hrs/day) than originally described by niece • Not much contact with children • 6/23: On-site assessment of DCC conducted by TB controller: • High priority contacts: 35 • 30 children attend: All <4 years of age • 5 staff members: Adults and adolescents • Daycare is in a church basement

  41. Church Basement-Daycare

  42. Contact Investigation, cont. • 6/23: Field visit by PHR to home of social contacts reveals a second 6 mo. old infant previously identified by Ppt. during an interview: • Significant social contact • History of pneumonia 3 weeks prior • PHR & TB controller consult with PNP and infant is referred to ER for evaluation • Chest radiographs are done

  43. Contact Investigation, Initial Results: Household and Social Contacts

  44. Contact Investigation, cont. • Continuing assessment and DCC parent notification • 6/29 & 6/30: TSTs placed, CXRs done • 6 extra clinic sessions, including 3 done at local health department • Multiple meetings by TB Center staff with DCC staff; follow-up interviews of Ppt.

  45. Results of Initial Skin Testing: Daycare

  46. Tuberculosis Exposure in Children • History, PE, TST, CXR done • CXR is done regardless of TST result • IF: • Asymptomatic and physical examination is normal • TST is negative • Chest X-ray is normal • AND IF <4 years of age START: Isoniazid (INH) 10 mg/kg (max., 300 mg) PO once daily

  47. Tuberculosis Exposure in Children • Why is INH given even if there is no evidence of infection or disease at initial visit: • May already be infected • Infection more likely to progress to disease • Infants and younger children are more likely to have disseminated disease or meningitis • TST repeated 12 weeks after contact broken with infectious adult: • If TST (-), discontinue INH • If TST (+), re-evaluate child and treat accordingly

  48. Contact Investigation, Initial Results: Infection and Disease at Daycare

  49. Contact Investigation, Initial Results: Household and Social Contacts

  50. Contact Investigation Results: Totals After Initial Testing