Tuberculosis in Children and Adolescents

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1 Tuberculosis in Children and Adolescents Ritu Banerjee, MD, Ph.D TB Clinical Intensive April 8, MFMER slide-1

2 Disclosures None 2014 MFMER slide-2

3 Objectives Describe the epidemiology of pediatric TB Describe the clinical presentation of pediatric TB Describe the evaluation for pediatric LTBI and active TB 2014 MFMER slide-3

4 TB disease in a young child marks recent acquisition and ongoing TB transmission within the community 2014 MFMER slide-4

5 Epidemiology MFMER slide-5

6 Global perspective 1 million cases/year 200 deaths/day Swaminathan, CID 2010, 50 (S3): S184-S194; MFMER slide-6

7 TB cases in the US 9945 TB cases among all ages in (4.9%) TB cases in children < 15 years 260 (2.6%) ages 0-4 years 226 (2.3%) ages 5-14 years MFMER slide-7

8 TB Case Rate per 100, TB Case Rates by Age Group, Overall US < 15 yrs yrs yrs yrs 65+ yrs Year Note: Rates presented on a logarithmic scale 2014 MFMER slide-8

9 Pediatric TB Cases by Race/Ethnicity, (N=19,840) White, non-hispanic Hispanic Asian Black, non-hispanic American Indian/Alaskan Native Year Note: Unknown, multiple race/ethnicity, and Native Hawaiian and Other Pacific Islander not shown 2014 MFMER slide-9

10 States with the Greatest Percent of the U.S. Total Pediatric TB Cases, N=19,840 California 23.9% All others 41.3% Texas 12.4% Illinois 4.4% Georgia 4.4% Florida 5.3% New York 8.2% 2014 MFMER slide-10

11 Number of Pediatric TB Cases Percent of Pediatric TB Cases 1,800 Number and Percent of Pediatric TB Cases by U.S. and Foreign Birth, (%) 100 1,600 1,400 1,200 1, Foreign-born U.S.-born Percent foreign-born Year 2014 MFMER slide-11

12 % Pediatric TB cases by age group (n = 19,840) Age (18.6%) Age < 1 (10.0%) Age 5 9 (22.5%) Age 1 4 (48.9%) MFMER slide-12

13 Clinical presentation 2014 MFMER slide-13

14 Features of pulmonary TB by age Clinical Feature Infants Children Adolescents Fever common uncommon common Night Sweats rare rare uncommon Cough common common common Productive cough rare rare common Dyspnea common rare rare Rales/wheezing common uncommon rare Dim.breath sounds common rare uncommon Pulm+Extrapulm common uncommon uncommon Cruz and Starke, Pediatric Tuberculosis, Pediatrics in Review 2010; 31: MFMER slide-14

15 Risk of progression to disease by age Age at infxn (yrs) No disease (%) Pulmonary TB (%) Miliary/CNS TB (%) < <0.5 > <0.5 Cruz and Starke, Pediatric Tuberculosis, Pediatrics in Review 2010; 31: MFMER slide-15

16 Pediatric TB Cases by Site of Disease, Extrapulm. 22.2% Both 7.2% Pulmonary 70.6% Any extrapulmonary involvement* (totaling 29.4%) Extrapulmonary site (%) Lymphatic 18.8% Meningeal 3.4% Miliary 1.4% Bone & Joint 1.5% Other 4.3% *Any extrapulmonary involvement which includes cases that are extrapulmonary only and both. Patients may have more than one disease site but are counted in mutually exclusive categories for surveillance purposes MFMER slide-16

17 Radiographic patterns: pulmonary TB TB pattern Reactivation Primary Infiltrate 85% upper Upper:lower 60:40 (can be anywhere) Cavitation Common Rare Adenopathy Rare Common in children Effusion May be present May be present 2014 MFMER slide-17

18 Primary complex 2014 MFMER slide-18

19 Hilar Lymphadenopathy 2014 MFMER slide-19

20 Pleural TB 2014 MFMER slide-20

21 Miliary TB 2014 MFMER slide-21

22 Miliary TB Most common in infants or IC Occurs shortly after infxn Usually insidious CXR normal early on Associated with hepatosplenomegaly, lymphadenopathy, cutaneous lesions TST negative in up to 50% Gastric aspirate, bronchoscopy, biopsy of lung liver, bone marrow, urine cx, bld cx, LP 2014 MFMER slide-22

23 Cavitary, pulmonary TB in adolescent Committee on Infectious Diseases et al. Red Book Online MFMER slide-23

24 Lymphadenitis (Scrofula) Committee on Infectious Diseases et al. Red Book Online MFMER slide-24

25 Skeletal TB Cruz and Starke, Pediatric Tuberculosis, Pediatrics in Review 2010; 31: MFMER slide-25

26 Young children with TB disease are rarely contagious CXR findings are immune response Rarely have cavitary disease Harbor few organisms (Paucibacillary) Do not generate forceful cough 2014 MFMER slide-26

27 Diagnosis Committee on Infectious Diseases et al. Red Book Online MFMER slide-27

28 Diagnosis Positive TST, epidemiologic factors, clinical and radiographic findings Up to 15% of children with TB disease have negative TST Only 30-40% of children with pulmonary TB have positive cultures 2014 MFMER slide-28

29 Pediatric TB Cases by Case Verification Criterion*, N=19,840 Provider Diagnosis 23% Laboratory Confirmed 26% Clinical Case 51% *Based on the public health surveillance definition for TB [MMWR 1997:46(No. RR-10):40-41] 2014 MFMER slide-29

30 Laboratory-confirmed pediatric TB cases 60% 50% 40% 30% 20% 10% 0% < 1 y 1-4 y 5-9 y y MFMER slide-30

31 Role of IGRAs in children IGRAS cannot distinguish LTBI from TB disease IGRAs preferred in BCG-vaccinated, asymptomatic children > 5 Y of age In young children, performance of IGRAs is variable and utility is unclear TST preferred/igra acceptable in children <5 Y Both TST and IGRA can be used sometimes Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection --- United States, 2010; MMWR, 59(RR05);1-25; American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. Pickering LK, ed. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; MFMER slide-31

32 Evaluation of child with suspected TB Evaluate contacts TST or IGRA Radiographs Sputum AFB stain, culture 3 early morning gastric aspirates LP if < 1 year Bronchoscopy Notify public health 2014 MFMER slide-32

33 Pediatric TB Cases by HIV Status, * N=19,354 Information on HIV results are not available for the majority of pediatric TB cases (75.9%) Pediatric TB cases with HIV-positive test results, minimum estimate** Pediatric cases with HIV-positive test results of those patients with known results 0.9% 3.7% *California HIV data missing from ; Vermont HIV data through 2006 only. **Pediatric TB cases with positive HIV test results divided by all pediatric TB cases. Note: Through 2004, California only reported positive HIV test results based on TB and AIDS registry matching; all other California TB cases were classified as Unknown MFMER slide-33

34 Treatment 2014 MFMER slide-34

35 Treatment of young children exposed to TB Window prophylaxis (INH) if: Exposed to TB Neg. TST/CXR < 4 years of age Immunocompromised If second TST negative, stop medication 2014 MFMER slide-35

36 Treatment of children with LTBI Drug-susceptible strain INH x 9 months Rifampin x 6 months ( 4 months) INH plus RIF x 3 months (UK) INH/Rifapentene weekly x 12 (>2 yo) MDR strain No data PZA plus EMB Fluoroquinolone Fluoroquinolone plus EMB or PZA 9-12 months 2014 MFMER slide-36

37 Treatment of drug-susceptible TB disease in children Drug Dose Toxicity (mg/kg/day) Isoniazid Hepatitis, neuropathy Rifampin Hepatitis Ethambutol 20 Optic neuritis Pyrazinamide Gout, rash * Baseline labs not necessary unless underlying liver disease 2014 MFMER slide-37

38 Treatment of MDR TB disease in children Drug Dose (mg/kg/day) Toxicity Monitoring Amikacin Nephrotoxicity, ototoxicity Baseline, monthy Cr, drug conc, hearing Levofloxacin Arthropathy Ethionamide Hepatotoxicity, GI, hypersens., hypothyroidism, neuropathy, optic neuritis Baseline ALT, TSH Cycloserine Rash, seizures, psychosis neuropsych eval monthly PAS Hepatotoxicity, GI, hypersens., hypothyroidism Baseline ALT, TSH 2014 MFMER slide-38

39 Number of cases that are drug resistant Percent of cases that are drug resistant Number and Percent of Culture-Confirmed Pediatric TB Cases with Drug Resistance, Year Resistance to any 1st line drug MDR TB Percent with resistance to any 1st line drug Percent with MDR TB First line drugs are isoniazid, rifampin, pyrazinamide and ethambutol MDR TB = resistance to at least isoniazid and rifampin 2014 MFMER slide-39

40 Take home points Children with TB (vs. adults with TB) fewer symptoms more culture-negative and extrapulmonary TB rapid progression from infection to disease different CXR findings less contagious TST conversion and TB disease in a child signify recent infection and ongoing transmission Children with TB should be offered HIV testing 2014 MFMER slide-40

41 Young children with TB disease are rarely contagious? A. True B. False 50% 50% True False 2014 MFMER slide-41

42 TB disease in a young child marks recent acquisition and ongoing TB transmission within the community. A. True B. False 50% 50% True False 2014 MFMER slide-42

43 Which age child has the highest likelihood of progression from TB infection to TB disease? A. 6 months B. 4 years C. 10 years D. 14 years 25% 25% 25% 25% A. 6 months B. 4 years C. 10 years D. 14 years 2014 MFMER slide-43

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