Pediatric Tuberculosis 2011 - Global TB...
Transcript of Pediatric Tuberculosis 2011 - Global TB...
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Pediatric Tuberculosis 2011
Dwight A. Powell, MD, FAAP Professor Emeritus of Pediatrics
The Ohio State University College of Medicine Member, Section of Infectious Diseases
Nationwide Children’s Hospital, Columbus, Ohio
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25-44 yrs (34%)
Reported TB Cases by Age Group, United States, 2009 - CDC
<15 yrs (6%)
15–24 yrs (11%)
45–64 yrs (30%)
>65 yrs (20%)
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Groups at higher risk of developing disease after infection
• Immunosuppressed patients:
Prolonged steroids; immune suppressants; malignancy
• HIV infected patients
• Underlying poor health:
Diabetes, renal failure, silicosis, chronic lung disease, malnutrition
• Substance abuse
• Persons < 4 years of age
Groups at high-risk of exposure and infection
• Close contacts of cases of reactivation TB
• Foreign-born from high risk countries
• Residents of high-risk institutions
• Medically underserved, low-income persons
• Injection drug users
• Persons exposed to high-risk adults
~35% of household
contacts are infected
95%
NEJM 345:189, 2001
Bacteremia and dissemination to
multiple body organs
“LTBI” Major focus for PPD screening
- 15%
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Adolescent with Latent TB
LTBI in a child is a sentinel event indicating contact with a case of active TB
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Age Distribution of TB disease in children
Burroughs, M et al. PIDJ 18:440, 1999
0
5
10
15
20
25
30
35
40
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
No. of Cases
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Major site of TB disease in 11,480 children ≤ 15 yrs old in the U.S. 1993-2001
Site Number (%) Pulmonary 8824 (76.9) Lymphatic 1778 (15.5)
Meningeal 249 (2.1) Bone/Joint 156 (1.4) Pleural 132 (1.1)
Miliary 125 (1.1) Other 223 (1.9)
Nelson LJ et al Pediatr 2004;114:333
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Symptoms in Children with TB disease
Burroughs, M et al. PIDJ 18:440, 1999
Symptom Frequency (%) Symptom (156 children < 20 yrs)
Cough 62 Fever 55
Weight Loss 32 Night Sweats 26 Hemoptysis 12
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Primary pulmonary TB in children
10 yr old female with segmental RLL infiltrate and paratracheal lymphadenopathy
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Progressive primary pulmonary TB in children
4 mo female with RLL consolidation and R hilar lymphadenopathy
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Cavitary TB in an adolescent
17 yr old BF, 2 mo cough, night sweats and 10# wt loss. Born in Virgin Islands; in U.S. x 10 yrs. PPD >20mm; sputum (+) M. tuberculosis
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Miliary tuberculosis
3 year old female exposed to her grandfather with pulmonary TB
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13 month old Honduran male whose grandfather has cavitary tuberculosis
diagnosed after this child presented with fever,
irritability and nuchal rigidity
CSF: Glucose 50, prot 108, RBC 13, WBC 39, 100%
mononuclear cells.
Tuberculous meningitis
Gadolinium enhanced T1 weighted MRI
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Tuberculous meningitis
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13 yr old BM. 2 mo hx neck swelling, fever & 4# wt loss. Born in Somalia; moved to U.S. 9 mo PTA. PPD (+) but no Rx. PPD 25mm
Lymphatic TB in children TB Lymphadenitis in children
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Pott’s Disease (TB of vertebral bodies)
T6
L2
S1,2
T2 weighted MRI
T1 weighted MRI with
gadolinium
18 yr old college student from Ghana; known PPD positive in 2001; no RX. Developed 2 mo. back pain and leg weakness during football practice in 2005.
PPD 30 mm
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Inadequately treated Pott’s disease
10 yr old Somali female with severe kyphoscoliosis who was treated with one medication and coining at age 2-3 yrs
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Inadequately treated Pott’s disease
T1 weighted MRI showing destruction and fusion of
C5,6,7 &T1 vertebral bodies.
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Diagnosis of TB infection in Children
• Tuberculin skin test (TST) or Interferon gamma release assay (IGRA)
• CXR if one of the above is positive • Complete physical exam • Search for contact source • Treat for LTBI if CXR and PE are negative • Pursue further evaluation if CXR or PE are
abnormal
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Further diagnosis of TB disease in Children
• Attempt to Isolate organism • induced sputum x2 – AFB smear, culture
(cx) and nucleic acid analysis (NAA) • gastric washings x 2-3 – Cx and NAA • biopsy or fluid aspiration – Cx and NAA • lumbar puncture in infants of if signs of
meningitis – cells, prot, gluc, cx, NAA • HIV testing
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Definitions of Positive PPD Results in Children Induration ≥5 mm Children in contact with known active TB Children with clinical or radiographic illness consistent with TB Children who are immunocompromised Induration ≥10 mm Children at increased risk of disseminated disease
• Age < 4 yrs or underlying medical illness Children with increased exposure to TB
• Born or parents born in high-prevalence countries • Frequent exposure to adults with high-risk of TB • Travel to high-prevalence countries
Induration ≥15 mm Children >4 yrs old without any risk factors Redbook, 2009
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BCG scar after vaccination at birth
Santiago EM et al. Pediatr 2003;112:e298
7.5 wks after birth 6 mos after birth
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PPD skin test results in persons without known exposure to TB; those with BCG
were vaccinated as infants
Wang L et al. Thorax. 2002;57:804–809.
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BCG vaccine site - Japan
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Interferon-γ release assays for detection of M. TB infection
QuantiFERON-Gold In Tube (QFT-GIT) and TSPOT.TB
Antigens used: ESAT-6, CFP-10, and TB7.7
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CDC updated guidelines for using intereron gamma release assays to detect Mycobacterium
tuberculosis infection – U.S. 2010
Use of QFT-GIT and T-SPOT for testing children: • Assessing the accuracy of IGRAs has been
more difficult in children than in adults • This is especially true for children < 5 yrs old • Use of IGRAs in children is subject to several
limitations: • Studies in children are scant • Indeterminant results are more common in
children than adults • Some studies have raised concern that
IGRAs may have lower sensitivity that TSTs in children Mazuek GH et al. MMWR 2010;59:RR-5
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Sensitivity of IGRAs in culture confirmed TB disease in children
Ling DI et al. Pediatr Resp Rev 2010;12:9
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Specificity of IGRAs in culture confirmed TB disease in children
Ling DI et al. Pediatr Resp Rev 2010;12:9
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Retrospective review of TST vs IGRAs in 49 children in the UK with culture confirmed TB
Test No. tested No. positive (%) TST >15 mm 45 37 (82) TSPOT 25 16 (64) QFT-GIT 43 35 (81) TST or TSPOT (+) 25 24 (96) TST or QFT-GIT (+) 43 39 (91)
Bamford AR et al. Arch Dis Child 2010;95:180
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Summary of evidence from 12 studies comparing IGRAs vs TST for LTBI in children
IGRA type IGRA (+) TST (+) QFT-G 33/195 (17) 47/195 (24) QFT-GIT 60/334 (18) 58/334 (17) QFT-GIT 16/210 (8) 98/227 (43) QFT-GIT 11/105 (10) 10/105 (10) QFT-GIT 31/204 (15) 116/207 (56) QFT-GIT 65/192 (34) 57/193 (57) QFT-GIT 61/184 (33) 80/184 (43) TSPOT 36/120 (30) 84/120 (70) QFT-GIT 29/97 (30) 46/95 (48) TSPOT 25/95 (26) 46/95 (48) BOTH 71/215 (33) 57/215 (27) Ling DI et al. Pediatr Resp Rev 2010;12:9
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Results in 217 immigrant children from Africa or Asia screened in Australia with TST, QFT-GIT and TSPOT
NONE of the children had known household exposure to TB
Lucas M et al. Thorax 2010;65:442
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Results in 22 immigrant children from Africa or Asia screened in Australia with TST, QFT-GIT and T.SPOT.TB .
All of these children had KNOWN household exposure to TB
Lucas M et al. Thorax 2010;65:442
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Progression to active TB in 104 German children <16 yrs old followed for 2-4 yrs without treatment after > 40 hrs
contact with an adult with active TB
QFT
-GIT
Diel R et al. Am J Resp Crit Care Med 2011;183:88
♦ active TB ♦ no BCG O BCG
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Our current policy for tuberculin skin testing and IGRA testing for children
• Screening for active TB • Use TST, QFT-GIT, and T-Spot.TB • Further evaluate and treat if any positive • If clinical evidence of miliary TB meningitis,
malnutrition, or compromised immunity, further evaluate and treat even if all are negative
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Our current policy for tuberculin skin testing and IGRA testing for children
• Screening for LTBI in asymptomatic children • Initial PPD skin test • If known TB exposure and TST ≥ 5mm, obtain
QFT-GIT and T-Spot.TB (if age < 5 yrs) • If no known TB exposure but high exposure risk:
• TST > 15 mm – No IGRA – start RX • TST 10-15 mm, obtain QFT-GIT and T-
Spot.TB (if age < 5 yrs). If IGRA (+) treat; if IGRA (-) do not treat
• TST < 10 mm – no IGRA
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Directly observed therapy of TB Disease Stage of TB RX Duration Pulmonary TB ♦ Non HIV (+), US born INH/Rif/PZA* 6 mo** ♦ HIV(+) or foreign INH/rifabutin/PZA/eth 6mo** born Extrapulmonary TB meningitis INH/RIF/PZA/eth 9-12 mo** bone, joint, miliary Same as pulmonary 6-9 mo** *if INH resistance >4% or high risk of drug resistance in source, add ethambutol until drug susceptibility confirmed. **PZA for only first 2 months
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Treatment of LTBI or contact of child with adult case of TB disease
Drugs Dosage Duration, mo Interval INH 10-15 mg/kg 9 Daily INH 20-30 mg/kg 9 2-3x/wk, DOT For know exposure to INH resistant case Rifampin 10-20 mg/kg 6 Daily For children who are contacts of adults with TB disease - Tuberculin skin test and CXR; repeat in 8-10 weeks if (-) - If child < age 4 years begin INH as above; continue INH
until repeat TST is (-) and index case is on DOT and confirmed to be sputum (-)
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Importance of therapy for LTBI
• New cases of active tuberculosis in the United States, as in other low prevalence countries, generally occur as re-activation of LTBI.
• Children are estimated to have a 5-15% lifetime risk of conversion from LTBI to active disease.
• Monotherapy with isoniazid (INH) for 9 months has been demonstrated to reduce risk of conversion to active disease in children by greater than 90%.
• A primary objective in the US strategy for tuberculosis (TB) control is to achieve successful completion of a course of treatment for ≥ 85% of high-risk individuals.
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NCH LTBI clinic 2005-present • Persons ≤ school age screened by school nurses, refugee center,
or Columbus Public Health • Persons with (+) TST sent for CXR at NCH • CXR read within 15 minutes
• Those with (+) CXR admitted to full evaluation • Those with (-) CXR sent to LTBI clinic
• CPNP obtains full Hx and PE, orders IGRA if indicated, and initiates therapy in those with (+) IGRA or > 15 mm TST
• CPNP provides educational material in English, Spanish, or Somali
• CPNP follows patients monthly with pill count and incentives • Patients on INH are considered to have completed therapy
with 270 doses taken over 12 months
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0%10%20%30%40%50%60%70%80%90%
100%
Mexico, Central& South America
Sub-SaharanAfrica
Northern Africa &Middle East
Eastern Europe United States Asia
Completion of therapy for LTBI in 545 children from 54 different nationalities (overall completion rate = 54.4%
Powell DA et al. PIDJ 2008;28:272
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Powell DA et al. PIDJ 2008;28:272
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Evaluation of 1521 children from 91 different countries enrolled in the NCH LTBI clinc from
6/1/06 to 12/31/09 and offered treatment based on TST ≥ 10 mm
• Therapy was refused by 138 (9.1%) patients • Only patients from countries in Pacific Asia (47.6%),
Eastern Europe (38.9%), and North Africa and the Middle East (19.0%) had greater than 10% rate of treatment refusal.
• Therapy was initiated by 1383 patients (mean age = 10.9 years, median = 11.5) and completed by 1000 (72.3%).
• Patients who initiated therapy were given the option to follow up monthly in the main NCH LTBI clinic or in one of two NCH Close to Home Clinics
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Completion of therapy by clinic location
Variable CTH clinic NCH clinic p (N=188) (N=1195) Completed therapy 88.3% 69.8% < .001 Foreign born 98.4% 89.3% < .001 Birth region < .001 SSA 67% 46.2% MSCA 18.6% 26.8% NA/WE 1.6% 11.5%
Data analysed by Kevin Spicer MD, PhD, MPH
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Completion of therapy by clinic location analyzed by propensity score matching
Variable CTH clinic NCH clinic p (N=179) (N=179) Completed therapy 88.8% 75.4% .001 Foreign born 98.3% 99.4% 0.67 Birth region 0.86 SSA 65.4% 65.9% MSCA 19.6% 22.9% NA/WE 1.7% 1.1%
Data analysed by Kevin Spicer MD, PhD, MPH
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Take home messages regarding Pediatric Tuberculosis
• Childhood TB is most often pulmonary and may appear like many other forms of pneumonia
• Interferon-γ release assays are currently used to complement PPD skin testing pending future research
• Identification and treatment of LTBI should remain a key focus of TB control in the US
• LTBI treatment requires intense efforts to maximize completion of therapy