1 / 81

Pediatric Tuberculosis

Pediatric Tuberculosis. Ramona Sunderwirth , MD, MPH Global Health Fellowship Department of EM St Lukes /Roosevelt Hospital Center. Objectives. Epidemiology Pathophysiology Clinical Presentations Diagnostic Challenges Treatment. Epidemiology TB in 21 st Century.

carrie
Download Presentation

Pediatric Tuberculosis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PediatricTuberculosis Ramona Sunderwirth, MD, MPH Global Health Fellowship Department of EM St Lukes/Roosevelt Hospital Center

  2. Objectives Epidemiology Pathophysiology Clinical Presentations Diagnostic Challenges Treatment

  3. Epidemiology TB in 21st Century • 1/3 of world population infected w/ TB • 9.4 M new cases & 1.8M deaths/ yr worldwide (2008) • 15-20% global TB disease burden: children < 15 yrs • Indicates continued transmission in setting w/ poor epidemic control • 4% reported cases, but 95% cases in <12yr age are smear - • 80% in 22 highest burden countries • Increasing numbers developing world • HIV epidemic (> 34% co- infected) • Poverty, overcrowding, malnutrition. Travel • MDR-TB and XDR-TB /Incomplete treatments • Breakdown of TB control programs

  4. Pediatric TB • Recent transmission from infected adult • Measure of TB control in community, rarely transmit TB • Higher risk & more rapid progression to active disease • 95% of children who develop TB, w/in 12 mos (1ary infection) • Reflection of immature immune system • Innate (macrophages), DC (dendritic cells) & acquired T-cell (CD4) immunity • EPTB more common • Infants: high morbidity and mortality • Disseminated TB/meningitis: 10-20% • Pulmonary TB: 30-40%

  5. Pediatric TB stages • Exposure • Contact w/ infectious pulmonary TB • Child asymptomatic • TST -, CXR normal • Infection (LTBI) • Contact w/ infectious pulmonary TB (adult) • Child asymptomatic • TST +, CXR normal • Disease • Contact w/ infectious pulmonary TB • TST+/- • Child symptomatic or CXR positive for TB

  6. Pediatric TB – Epi challenges Diagnosis TB childhood difficult clinical presentation variable & nonspecific confirmation by culture < 40% absence productive cough , paucibacillary disease contact investigation of adults w/ infectious pulmonary TB 60-80% children infected when exposed to AFB + sputum 30-40% children infected when exposed to AFB - sputum most efficient method dx children w/ TB

  7. Factors influencing PedEpi in USA • Increasing rates of TB in foreign-born immigrants • Worldwide HIV epidemic & MRTB • Transmission of TB among undx individuals w/ limited access to health care, poor housing/nutrition • 80-87% childhood TB in USA among AA, Hispanics, Asians, Native Americans • 1 out of 4 children w/ TB is foreign born • Concentrated in cities w/ pop > 250,000

  8. TB in HIV + children • Important factor contributing to persistence TB • HIV adults horizontally transmit TB to children • HIV exposed /infected children • TB incidence 100 x higher (underestimation) • HIV + children • Weaker cell mediated immunity (CD4+Tcells) • Increased risk progressing from TB infection to TB disease • Similar presentation but more severe/extensive/EPTB/CNS • Higher recurrence/reinfection rates • Higher TB mortality

  9. Pathogenesis of Peds TB • 1st 2 months post infection • Primary Complex: Ghon focus + adenopathy (usually hilar) • Cell mediated response TST +, TB antibodies formed • Febrile reaction w/ onset of delayed hypersensitivity • Hematogenous/lymphatic seeded areas • Massive dissemination 1-3% cases (miliary/meningeal TB) • 10-15% live organisms persist (potential for reactivation)

  10. Pathogenesis: Timetable • Symptomatic lymphohematogenous , miliary/meningitis • 2-6 mos • Endobronchial TB w/ segmental pul changes • 4-9 mos • Significant bone/joint lesions • 1 yr • Renal lesions • 5-25 yrs • Infants and young children • Rapid progression: 1 st yr/5yr post infection respectively • Reactivation of Pul TB • Function of age of primary infection • Cavitation, lung/bone/joint/renal lesions • HIV/measles/varicella co infection, malnutrition

  11. Pregnancy & NN • Congenital Infection Rare (risk higher if mother HIV+) • Transplacental, hematogenous spead via UV/placenta • Bacille: fetal liver (primary focus w/ periportal lymph nodes) or wide spread miliary disease. • Bacille: liver to main circulation (1ary focus in lung) active after birth. • Aspiration/ingestion infected amniotic fluid in utero • multiple 1ary foci (lung, gut, middle ear) • Postnatal infection by inhalation from TB + mother • Breastfeeding not CI if mother on treatment • NN needs treatment

  12. Clinical Forms Peds TB • Endothoracic • Lymphohematogenous • CNS • Other Extrapulmonary Sites • Adolescents • Neonates

  13. Clinical manifestations Most infected children asymptomatic • Lymphadenopathy • w/in 6 mos infection, ant cervical/submandibular • Primary Pulmonary TB (PTB) • Most common presentation • Children > 10 yrs age more like adult disease • Intra thoracic adenopathy & parenchymal changes • Progressive Pulmonary disease • Common in young children: TB broncho-pneumonia • Chronic Pulmonary Disease/ reactivation • Most common in adolescents (1ary infection > 7 yrs age) • Cavitation, typically upper lobe

  14. Endothoracic • Asymptomatic • 80-95% infected children, 40-50% infected infants • Pulmonary • 1ary pulmonary complex • Progressive pulmonary disease • Chronic pulmonary disease • Pleural effusion • Pericarditis

  15. EndothoracicPulmonary • 1ary pulmonary complex • Adenopathy large w/ small parenchymal foci • CXR • hilar adenopathy, • localized hyperaeration, atelectasis • localized pleural effusion • segmental infiltrate (foci) • Signs/symptoms infrequent (except in infants) • 1ary complex: fever + cough • Fever, cough, night sweats, FTT • Localized wheeze, diminished BS • Dysphagia, edema hand/arm

  16. Hilar Adenopathy

  17. Endothoracic: Progressive pulmonary disease • Rare but serious • CXR bronchopneumonia/lobar pneumonia w/ cavities • Signs/symptoms significant • Fever, night sweats, wt loss, cough • Diminished BS, rales, dullness, egophony • High fatality w/out treatment

  18. Endothoracic: Chronic pulmonary disease • “Adult reactivation” type/recent or reinfection • 6-7% pediatric patients (TB acquired > 7yrs age) • Most common pul sites • original parenchymal focus, regional lymph nodes, or apical seedings • Usually remains localized to lungs • Identical to Adult pulmonary disease

  19. Endothoracic: Pleural effusion • Subpleural 1ary pul focus /subpleural caseous lymph nodes • Small, localized or generalized • 4-30% of TB cases in young adults, rare children • Signs/symptoms abrupt • Fever, chest pain, SOB, dull percussion, decreased BS • Dx difficult • Acid fast stain pleural fluid-/cult + 30% biopsies • Prognosis good in treated children

  20. EndothoracicPericarditis • Rare in children (0.4-4%) • Direct invasion from subcarinal lymph nodes • Can lead to constrictive pericarditis • Signs/symptoms nonspecific • Fever, malaise, fatigue, wt loss, chest pain • friction rub distant HS/pulsus paradoxus • Dx: acid fast stain -/cx + 30-70% • Pericardectomy

  21. Lymphohematogenous • Clinical course acute/indolent/prolonged • Multiple organ involvement • HSM & adenitis (superficial/deep), Pulmonary, Meningitis • Papulonecrotictuberculides • Miliary • Massive # organisms released, > 2 organs affected • Early complication 1ary infection (2-6 mos) • Common infants/children: explosive or insidious onset • Fever, wt loss, anorexia, malaise, HSM, gen. lymphadenopathy, resp distress • CXR: tubercules • Dx difficult: TST -, liver/bone biopsy needed (33%+) • Prognosis w/ treatment excellent , resolution slow

  22. CNS Manifestations • Rich focus, vessels infiltrated by exudate • Inflamation/infarction • Brain stem: CN III,VI,VII dysfunction • Basilar cisterns obstructed: hydrocephalus • TB meningitis • Children < 4 yrs age, most w/in 3-6 mos of 1ary infection • Gradual onset, rapid in infants Hydrocephalus • Tuberculomas (20-37%) • Mortality (<10% w/ Rx) Morbidity high (MR, Sz, hemiparesis) • TST – in 40%, CXR nl 50% • CSF: cell # 10-100, glucose low, protein high • Tuberculoma • Most common in < 10yrs age • Infratentorial: headaches, Seizures, increased ICP

  23. Tuberculomas

  24. CN palsy 3, 6, 7

  25. Fever of Unknown Origin • Common in developing countries • Few clinical findings • Primary infection: cellular immune response • Reactivation old/hidden focus

  26. Other Extrapulmonary Sites • More common, not infectious • Infants • HIV + children • Scrofula • Skeletal • Vertebrae most common: Pott’s Disease • Knee, hip, elbow, smaller joints • Abdominal/peritoneal TB • Adolescents • Eye, middle ear, sinuses, kidneys, skin • Rare in children

  27. Osseous Clinical manifestations • TB osteitis • Synovitis/epiphysitis, destructive arthritis, fusion in deformed positions • Abscesses may track through tissues (psoas) • TB arthritis (Ponchet’s Disease) • 1-5% children if TB untreated • Knee/hip/elbow/dacylitis • Thick, inflammatory synovium, invades articular surface, w/ erosion and fibrosis joint

  28. Pott’s Disease

  29. TB osteitis

  30. GI & GU Manifestations • Abdominal/peritoneal TB • Thickened gut, peritoneal lymph nodes • Obstruction, fistula formation, ascitis, perforation, malapsorption • Palpation doughy abdomen w/ masses of adherent lymph nodes • R/o malignancy (laparoscopic biopsy) • Poor prognosis, long term intestinal problems • Renal TB • Uncommon in children • Sterile pyuria • TB epididymitis and orchitis

  31. GI TB

  32. Adolescents • Acquired as initial infection during adolescence • Chronic pulmonary TB w/in 1-3 yrs • Acquired in early childhood • Rare if acquired as infant • More likely if acquired 1ary infection from 7-10 yrs age • Propensity to progress to contagious TB • Target group for TST & case finding

  33. Neonates • Clinical symptoms 2-3wk • FTT, respiratory distress, fever, HSM, meningitis lymphadenopathy, sepsis, lethargy • Dx difficult • TST -, CXR nl or miliary • AFB in gastric aspirate, urine, BM, liver biopsy, ear • TB in mother • Infants of + mother TB • INH & BCG to newborn, treat mother /contacts • Breastfeed if mother on Rx

  34. Diagnosis TB in ChildrenGeneral Principles • Triad • TST+ • History of recent exposure to adult w/ probable /definitive TB • CXR abnormal • Symptom based scoring systems • Immunocompetent children • Definitive diagnosis • Acid fast smear of sputum/gastric secretions microscopy • Isolation of TB • Automated liquid culture systems (gold standard now)

  35. Challenge of Childhood TB diagnosis • Establishing accurate diagnosis • Challenges collecting adequate sample for micro • <15% of cases are sputum AFB smear + (paucibacillary) • Mycobacterial cx yields: 30-40% • Case detection & contact tracing not routine • Most individuals acquire infection childhood/adolescence • CXR nl in significant proportion of children w/ confirmed pul TB • Most new Dx not validated in children • No widely available gold standard dx of TB in children

  36. TST • Hallmark of 1ary TB infection • Appears 3wks-3mos after initial infection, lasts yrs • Infants less enduration, more anergy • Sensitivity/Specificity 95% • PPV – function of TB prevalence in community • AAP/CDC recommendations in USA • Screen w/ questionnaire • TST only for high risk children • BCG • <50% infants TST + at 9-12 mos post vaccination • 80-90% TST- by 3-5yrs post vaccination

  37. TST + interpretation • > 5 mm • Persons w/ contact w/ infectious persons • Persons w/ abnl CXR • HIV infected/immunocompromised • < 10mm • Infants • Children in contact w/ adults at high risk • Foreign born persons from hi prevalence countries, IVDU, residents prisons, institutions • >15 mm • No risk factors

  38. Specimen collection Methods • Sputum • Induced Sputum • Gastric aspirate • Nasopharyngeal aspiration • String Test • BAL • Urine/stool • Blood/BM • CSF • Find needle aspiration adenitis

  39. Diagnosis TB in ChildrenDirect smears, acid fast stains & Cultures • Sputum smears • Sputum rarely produced <10yrs age, paucibacillary TB • Insufficient alone to dx or r/o TB • Induced sputum w/ 5% saline neb, serial collections in infants • Gastric washings (x3): acid fast stains/cultures • Sensitivity Cx: 30-50% children, 70% infants • Better than BAL • Other body fluids/tissue specimens • Sensitivity Cx: 30-50% children, 70% infants • Difficulty isolating TB in children should not greatly influence approach to therapy • Attempt to isolate • no source case, source case MDR TB, child has suspected extrathoracic TB

  40. Diagnostics • Traditional direct smear microscopy • sputum • Solid culture • Chest radiography • Tuberculin skin testing (TST)

  41. Traditional Approaches to Diagnose TB in Children • TB culture • CXR • Symptom-based • TST

  42. New diagnostic approaches • Organism – based • Colorimetric culture systems (TK-Medium) • Phage-based tests (FASTPlaque-TB) • Microscopic observation drug susceptibility (MODS) • Assay PCR based test • Antigen- based essays • LAMdetection assay • Immune-based • Antibody-based assays • MPB-64 skin test • T-cell assays • T-Spot.TB (IGRA) • QuantiFERON-TB Gold • Symptoms-based: Refined symptom based diagnosis

  43. TB Research Movementinitiated by the Stop TB Partnership & WHO • engaging TB researchers, programme managers, & affected communities in a • collaborative & concerted strategic effort to • ↑ scope, scale, & speed of TB research across the continuum • linking basic research development of new methods, & operational research

  44. New Diagnostics since 2007 • Liquid media for culture & DST • Def of a new sputum-smear-positive TB case • one acid fast bacilli in at least one sputum sample in countries • ↓ of number of smears for diagnosis of pul TB • WHO recommends the number ↓ from three to two • Molecular line-probe assays for rapid screening pt at risk of MDR TB • Same day dx by microscopy • LED-based microscopy • conventional fluorescence microscopy replaced by LED microscopy using auramine staining • LED microscopy phased in as alternative for conventional Ziehl-Neelsen light microscopy • Non-commercial culture DST methods • Microscopically observed drug susceptibility • Nitrate reductase assay, • Colorimetric redox indicator methods

  45. New Diagnostics 2009 • Xpert MTB/RIF • First automated molecular test for TB (NAAT assay) • Excellent performance in Smear + & - pts • Hi accuracy for determination rifampicin resistance • Simple to use system • Detects M tuberculosis directly from sputum in <2 hrs • IGRAs (interferon-γ release assays) • T-cell assays • T-Spot.TB (IGRA) • QuantiFERON-TB Gold • Blood test • Results in 24hr • Blood test • Results in 24h

  46. TBDST: drug-susceptibility test MODS: microscopic observation drug susceptibility NRA: nitrate reductase assay CRI: colorimetricredox indicator assay LPA: line-probe assay NAAT: nucleic acid amplification test LED: light-emittingdiode POC: point of care LTBI: latent tuberculosis infection

More Related