TB Intensive Houston, Texas November 10-12, 12 2009 Childhood Tuberculosis Kim Connelly Smith MD, MPH November 12, 2009 Childhood Tuberculosis Kim Connelly Smith MD, MPH November 12, 2009 1
OUTLINE Stages of tuberculosis Differences of disease in children and adults Clinical cases interspersed Diagnostic challenges of pediatric TB Treatment of TB in children Time for questions 2
Stages of Tuberculosis Exposure to Contagious Adult with Pulmonary Disease Household contacts 20-30% Latent TB Infection LTBI 5-10% Adult Active TB Disease Risk varies by age 5-50% Child Active TB Disease Percent Risk of Disease by Age Age at Infection Risk of Active TB Birth 1 year* 43% 1 5 years* 24% 6 10 years* 2% 11 15 years* 16% Healthy Adults 5-10% lifetime risk HIV Infected Adults + 30-50% lifetime *Miller, Tuberculosis in Children Little Brown, Boston, 1963 + WHO, 2004 3
Risk of Progression to TB Disease by Age Age @ primary infection Birth-12months 1-2 years Risk of Disease Disease 50% Pulmonary Dis 30-40% Miliary or TBM 10-20% Disease 20-25% 25% Pulmonary Dis 75% Miliary of TBM 2-5% Marais BJ. Int J Tuberc Lung Dis 2004;8:392-402 TREATMENT Pediatric Tuberculosis OF TUBERCULOSIS Treatment IN CHILDREN Table Stages of TB Exposure Child < 4 years of age Household contact with adult with active pulmonary disease Latent TB infection (LTBI) Disease Pulmonary Disease Extrapulmonary other than meningitis, miliary or bone/joint Skin Test or IGRA Negative Positive CXR Normal Normal SXs None None Treatment Meds: INH Duration: 3 months Skin Test: in 3 months if positive, see LTBI Meds: INH Duration: 9 months 90% positive Abnormal +/- Meds: INH, RIF, PZA (consider EMB or an aminoglycoside) Duration: 6 months total stop PZA after 2 months continue INH & RIF 90% positive +/- Yes Same as pulmonary Obtain cultures if possible Disease Meningitis, miliary, or bone/joint Often negative early in meningitis and miliary disease 90% positive by end of tx +/- Yes Meds: INH, RIF, PZA and an aminoglycoside or Ethionamide (meningitis) or EMB (miliary, bone/joint) Duration: 12 months total. Stop PZA and aminoglycoside or Eth/EMB after 2 months. Steroids recommended for meningitis 4
Daycare Exposure Daycare Exposure Index case, teacher assistant with AFB smear positive pulmonary disease and cough for 6 weeks 135 children < 4 years of age, plus adult staff members exposed Who is at risk? Who needs TST? Who needs CXR? Who needs treatment? Smith, KC. Southern Medical Journal 93(9):877-880, 2000 5
Daycare Exposure Management Who is at risk? Children and staff Who needs TST? Everyone with significant contact with source case Who needs CXR? All children less than 4 years of age even if TST negative Any contacts with positive TST (> 5mm) Who needs treatment? LTBI (positive TST >5mm and normal CXR) INH for 9 months Exposed children less than 4 years of age need INH window prophylaxis for 3 months Follow up? Repeat TST 3 months after exposure If negative and contact broken, stop INH prophylaxis TB Prevention After Exposure Household contact with contagious person Teen or adult with pulmonary TB disease Usually > 4 hours of contact Initial TST negative Window period for TST conversion (2-12 weeks) CXR and physical exam normal INH prophylaxis recommended: For children <4 yrs of age Immunosuppressed patients Patients on tumor necrosis factor-alpha alpha blockers May prevent progression to disease during window period Repeat TST 2-3 months after exposure May stop INH if 2 nd TST negative <5mm in immunocompetent patients 6
Preventable Case With permission Pediatric TB Case a Missed Opportunity 15 mo old 10 days fussiness & decreased appetite 3 days inability to walk or sit up CSF: 96 WBC (NL <7), 72% Lymphs, 198 Protein (NL <45) Diagnosis: TB meningitis Family history Mom with pulmonary TB diagnosed 5 mo earlier on appropriate treatment Dad diagnosed with LTBI on INH Baby initial TST 0mm @ 10 months of age no CXR no treatment lost to follow up 7
Outcome Child treated with RIPE, completed 12 months Steroids for 1 month with 2-3 week taper to decrease CNS inflammation Developed seizures and hydrocephalous requiring VP shunt Otherwise did well with normal neurologic examination and development Case potentially preventable if treated with window prophylaxis when parent diagnosed Differences In Adult and Pediatric TB 8
Reactivation Disease Occurs years after primary infection Typical of adult disease Occasionally seen in teens Often cavitary disease High numbers of organisms (AFB +) Usually symptomatic and contagious Primary Disease Typical of childhood TB Usually not cavitary Classic x-ray: pulmonary infiltrate with or without hilar adenopathy, but may be nonspecific Low numbers of organisms AFB smears negative in 95% of cases Culture negative in 60% of cases Most children <12 yrs not contagious Often asymptomatic (50%) 9
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Adult TB Disease 85% Pulmonary Pulmonary Extrapulmonary 15% Extrapulmonary CDC Adult Extrapulmonary TB Disease (15%) 4% Meningeal 13% Other 9% Miliary 10% Bone/Joint 16% GU 25% Lymphatic 23% Pleurall Lymphatic Pleural GU Other Bone/Joint Miliary Meningeal CDC 11
Pediatric TB Disease 25% Extrapulmonary 75% Pulmonary Pulmonary Extrapulmonary CDC Extrapulmonary TB Disease in Children (25%) 5% Other 6% Pleural 5% Miliary 4% Bone/Joint 14% Meningeal 67% Lymphatic Lymphatic Bone/Joint Other Miliary Pleural Meningeal CDC 12
*Feigin & Cherry, Text of Pedi ID Common symptoms of TB disease in children Cough and/or respiratory distress Pulmonary findings on examination Lymphadenopathy or lymphadenitis S/SxSx of meningitis including seizures Persistent fever (FUO) Weight loss or failure to thrive Unlike adults, up to 50% of children with TB disease have no symptoms 13
Work Up for TB Disease In Children Hospital admission for cultures Gastric aspirates vs BAL When to get CT scans When to biopsy When adult case known with + MTB cultures Unique Challenges of TB in Children More difficult diagnosis Nonspecific signs and symptoms Fewer mycobacteria Fewer positive bacteriologic tests Increases risk of progression to active disease Higher risk of extrapulmonary and TB meningitis 14
Lymphadenopathy Clinical Case Cervical Lymphadenopathy 8 yr old with cervical lymphadenopathy History: LAN for 3 months PMHx: Healthy BCG vaccine at birth TB skin test 15 mm Physical Exam: 3 cm anterior cervical LAN 1.5 cm supraclavicular lymphadenopathy CXR: Hilar LAN, no infiltrates Is this TB disease? What else could it be? 15
Hilar & Cervical Lymphadenopathy Differential Dx Tuberculosis Non TB mycobacteria (NTM) Lymphoma/Leukemia HIV Other causes Diagnostic tests Biopsy (FNA or surgical for culture and path) Interferon Blood test for TB infection Results Fine needle aspirate of node: Pathology: lymphoma, no TB by culture or microscopy Interferon Blood test for TB Positive Diagnostic for latent TB infection or disease Diagnoses: LTBI (TB lymph node disease usually localized) AND Lymphoma Treatment: Chemotherapy for lymphoma AND INH daily for 9 months for LTBI consider prolonged treatment during immunosuppresion 16
Diagnosis for TB in Children Gold Standard Positive TB Culture OR, Clinical Diagnosis: Abnormal CXR, laboratory, or physical examination consistent with TB AND 1 or more of the following: Positive tuberculin skin test Contagious adult source case identified Clinical course consistent with TB disease Improvement on TB therapy AFB smears and Cultures in Children and Infants AFB smear usually negative In 95% of patients <12 years of age Low yield on TB culture Only 40% positive in children 1-1212 yrs of age with pulm TB Obtaining cultures from children with pulmonary TB Early morning gastric aspirates (x3) Broncho alveolar lavage (BAL) Sputum in children >5yrs sometimes Teens similar to adults if cavitary TB Infants with pulmonary TB 60-70% cultures pos Adult source case important 17
Tuberculosis Meningitis Higher risk in infants Gradual onset over days or 1-2 weeks compared to bacterial meningitis Cerebral Spinal Fluid (CSF) Normal to moderately high WBC (20 s-100 s), lymphocytic predominance 75% with very high protein, usually >100-300 Typical MRI Brain stem & basal ganglion enhancement Hydrocephalous and infarcts may be seen Sometimes no findings on MRI Tuberculosis Meningitis, cont Possible complications Hydrocephalous Stroke/infarcts Cognitive impairment Normal outcome possible if treated in early stages (50% in my experience) Treatment 4 TB meds until susceptibilities known, INH/Rif for 12 months steroids (1-2 months) to decrease inflammation and scar formation Symptoms often get worse before better, treat in hospital until clinically improving 18
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Expected Clinical Course for TB Disease in Children Pulmonary CXR takes months to improve Hilar lymphadenopathy May take year or more to regress on x-ray Lymphadenitis Gets worse before improvement over months Meningitis Inflammation increases initially with treatment Steroids important for 1 st month Hospitalization recommended until clinically stable or improving 20
Monitoring Children on TB Treatment Risk of drug toxicity low Monitor clinical signs regular clinical visits (4-6 wks) patient education Routine blood work not necessary unless symptoms risk factors for toxicity Monitor and reinforce adherence When to follow up CXR s for pulmonary TB Clinical change End of therapy Completion of therapy certificate Management of TB Medication Reactions Hepatotoxicity Medication refusal in children Vit B6 Missed doses or interruption in tx Drug rashes 21
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