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![ Rapid detection of M.tb and Rif resistance
Sensitivity: 95-99.5%; specificity: 95%
For sputum smear (+)/(-)
Minimal training
Minimal space requirements
Fully automated
Results in 2 hours
Cartridge Based Nucleic Acid Amplification Test
4 Newer Techniques
Bacteriologic confirmation
4
Gene Xpert Mtb/Rif [CBNAAT]](https://image.slidesharecdn.com/tbinpediatrics-210909074447/85/TB-in-pediatrics-46-320.jpg)
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TB in pediatrics
This document discusses tuberculosis (TB) in children. It begins with an overview of the clinical spectrum of TB in children, which can include pulmonary, visceral, cutaneous, neuro, and perinatal manifestations. Pulmonary TB lesions in children typically include primary complexes and intrathoracic lymphadenopathy. Extrapulmonary TB involves sites like bone, joints, the gastrointestinal tract, and the central nervous system. The document then covers the diagnosis of TB in children, which involves clinical judgment based on exposure history and symptoms, the tuberculin skin test, chest x-ray, and bacteriological confirmation via sputum sampling or gastric aspiration. Interpretation of diagnostic tests and their limitations are also discussed.
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TB in pediatrics
- 1. Tuberculosis in Children •Dr.C.S.N.Vitta l Roadmap towards ending TB in children and adolescents
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- 4. Attack of microbeson Humanity I wanna Kill - Plague Kill ya … - COVID 19 My turn … - SARS I too wanna Kill - Cholera Me too… - MERS
- 5. I wanna Kill- Plague Kill ya … COVID 19 My turn …- SARS I too wanna Kill - Cholera Me too… - MERS Throughout the 1600-1800s in Europe& United States, TB caused 25% of all deaths. “If the number of victims that a disease claims is the measure of its significance then all the diseases particularly the most dreaded infections such as bubonic plague, Asiatic cholera, etc. must rank far behind tuberculosis” -- Die Ätiologie der Tuberculose, Robert Koch (1882) Ha Ha Ha … TB
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- 9. RNTCP (Revised National Tuberculosiscontrol Program) The initial objectives of the RNTCP in India were: to achieve and maintain a TB treatment success rate of at least 85% among new sputum positive (NSP) patients. to achieve and maintain detection of at least 70% of the estimated new sputum positive people in the community. The national goal was now the elimination of TB in India by 2025.
- 10. RNTCP Gets AName Change This implies targeting an 80 per cent reduction in incidence and 90 per cent reduction in mortality (base line 2015)
- 11. Tuberculosis: in adultsvs in children Massive global disease burden that is well quantified; excellent awareness Massive global disease burden that is poorly quantified; minimal awareness Usually “adult-type” lung disease Usually intrathoracic lymph node disease, but extrapulmonary disease common Multibacillary; high infection risk Paucibacillary; low infection risk, unless cavities or extensive lung involvement; Difficult to differentiate acquired from primary drug resistance Nearly always primary drug resistance indicating recent transmission Infection Control Drug resistance Epidemiology Pathogenesis Well established facilities + Very much Inadequate facilities, formulations,etc Diag/Tt/Prevent
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- 18. Clinical Manifestations –Pulmonary TB Primary Pulmonary Disease Progressive primary pulmonary disease Reactivation TB Pleural Effusion Upper Respiratory tract Disease Lymph node disease Lympho hematogenous (Disseminated TB) Spread • Incubation period varies between 4 and 8 weeks
- 19. Bone & jointTB • Pott’s disease • Spondylitis • Spina ventosa Visceral TB • Renal • GI • Lymphnodes • Phlycten Perinatal TB • Congenital CNS TB • Tuberculoma • Meningitis Cutaneous TB • Lupus vulgaris • Scrofula derma • Verrucis cutis • Tuberculids Extra Pulmonary Tuberculosis
- 20. Clinical Spectrum -Pulmonary TB Ghon focus Uncomplicated— apex of the left lower lobe, lower part of upper lobe Place where the “eagle has landed,” rarely seen because it is usually transient. (Gie 2003; Marais et al. 2004b). •Ranke’s complex – Ghon’s focus with fibrosis and calcification •Simon focus – Tuberculous nodule in lung apex Lesions of Primary TB
- 21. Clinical Spectrum -Pulmonary TB Intrathoracic lymph node disease (anteroposterior view) Primary Complex: 1. Ghon focus 2. Lymphatics 3. Hilar lymph nodes
- 22. Clinical Spectrum –Pulmonary TB Complicated Ghon focus Poor disease containment at the point of entry; infants and severely immune- compromised individuals are particularly vulnerable. (Gie 2003; Marais et al. 2004b). Lesions of Secondary TB Puhl’s lesion (Aschoff-Puhl reinfection)– lesion in the lung apex and supraclavicular Assman focus – Infraclavicular lesion of pulmonary tuberculosis Progressive Primary Disease
- 23. Clinical Spectrum –Pulmonary TB Airway obstruction with “check valve” effect Hyperinflation (ball valve effect) of left lung. See remnant of Ghon focus and large left-sided perihilar nodes (Gie 2003; Marais et al. 2004b).
- 24. Clinical Spectrum –Pulmonary TB Pleural effusion Follows rupture of subpleural focus. Also by hematogenous spread from primary focus . Hypersensitivity to tuberculoproteins Asymptomatic (minor), Fever, cough, dyspnea, pleuritic chest pain
- 25. Clinical Spectrum –Pulmonary TB Disseminated (miliary) disease Heavy hematogenous spread of tubercle bacilli causing disease in 2 or more organs Miliary Tuberculosis: CXR - SNOW STROM appearance
- 26. Clinical Spectrum –Pulmonary TB Adult-type disease At 8–10 yr of age Associated with an excessive and poorly regulated immune response Any child with cavitary disease is infectious (as infectious as an adult sputum smear-positive case) and should be regarded as a potential source case.
- 27. Symptoms - PulmonaryTB Primary complex – mild fever, anorexia, weight loss, decreased activity, cough Progressive primary complex – high grade fever, cough, expectoration and hemoptysis – cavity and ulceration of bronchus Endobronchial TB – wheeze, fever, troublesome cough, dyspnea, cyanosis. Wheezing child not responding to bronchodilators, less than 2 yrs age
- 28. Symptoms Cough (2weeks) Fever (2 weeks) Night sweats (drenching) Weight loss or poor weight gain Malaise and fatigue Loss of appetite Shortness of breath Chest pain
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- 30. Diagnosis of TBin children Bacteriologic confirmation 4 Clinical judgment - based on exposure history & clinical features 1 Tuberculin Skin Test (TST) 2 Chest x-ray (CXR) 3
- 31. Definitions in treatmentof TB in children • Children with persistent fever and/or cough, • loss of weight (loss of > 5% body weight as compared to highest weight recorded) • No weight gain in last 3 months and or • History of contact with infectious TB cases. Presumptive pediatric TB 01 02 03 • Based only on X-ray / Bacteriology Clinically diagnosed TB • Monoresistance: resistance to one 1st anti-TB drug only; • Poly-drug resistance (PDR) resistance to more than one first-line ATD, other than both INH and Rifampicin. • Multi-drug resistant (MDR) • Extensively-drug resistant (XDR) TB. Drug resistant TB
- 33. Clinical judgment ExposureHistory Closeness of contact - living in the same household or in frequent contact with a source case with smear-positive PTB. Sputum smear result of index case (if known) - Children are infectious if smear (+) or with cavitary TB Timing of contact children usually develop TB within 2 years after exposure and most (90%) within the 1st year If no source case is identified, always ask about anyone in household with cough – if so, request assessment of that person for possible TB 1
- 34. Check weight,record weight and compare to previous weight Clinical judgment 1 Clinical Features
- 35. PEDISATC ON 2007 Varinder Singh Hassan, Aug 2007 MantouxTest A standard dose of 5 tuberculin units (TU - 0.1 ml) of PPD Tuberculin Skin Test (TST) 2
- 36. Mantoux Test Tuberculin SkinTest (TST) 2
- 37. Tuberculin Skin Test(TST) – Interpretation > 5 mm > 10 mm > 15 mm • Immunocompromised • HIV-infected children • severely malnourished; • Immunosuppressed patients • Organ transplnts • In presence of history of close contact, • Findings suggestive of TB • Persons with nodular or fibrotic changes on chest X- ray (old healed TB) • Patients with organ transplants, and other • In all other children (whether they have received BCG vaccination or not) • Persons with clinical conditions that place them at high risk • Children less than four years of age, or children and adolescents exposed to adults in high-risk categories • Persons with no known risk factors for TB
- 38. – False Positive Causedby atypical tuberculous mycobacteria Previous administration of BCG vaccine. When the injected area is touched, causing swelling & itching Allergic reaction or hypersensitivity Infection at the site of test Tuberculin Skin Test (TST) 2
- 39. False negative result RecentTB infection (less than 8–10 weeks) Recent Viral infection (EBV, measles, HIV, mumps, chicken pox) Chronic renal failure, Liver failure Hodgkin's disease, Lymphomas, Leukemia, Sarcoidosis Corticosteroid therapy/steroid use Immunological compromised state (malnutrition) Recent Live Viral Vaccine (3 weeks gap mandatory) Tuberculin Skin Test (TST) 2
- 40. CXR The commonestpicture: persistent opacification in the lung together with enlarged hilar or sub-carinal lymph glands. A miliary pattern of opacification children is highly suggestive of TB. Adolescents: Large pleural effusions and apical infiltrates with cavity formation being the most common forms of presentation (similar to adults). May also develop primary disease with hilar adenopathy and collapse lesions visible on CXR. Chest x-ray 3
- 41. Diagnosis of TB SmearTest: AFB Staining The acid-fast bacilli will stain bright red, and the background will stain blue. Reagents used in the procedure include Ziehl–Neelsen carbolfuchsin solution, 1% acid alcohol, and methylene blue solution Bacteriologic confirmation 4
- 42. Diagnosis of TB Culture – Gold standard. Bacteriological confirmation is the exception rather than the rule with only 10- 15 % of sputum samples revealing acid fast bacilli (AFB) Bacteriologic confirmation 4
- 43. Gastric aspirate vsinduced sputum Gastric aspirate 30% to 50% yield Stain and culture yield from 3 GW higher than BAL1 Induced sputum Inhalation of 3-5% hypertonic saline Bronchospasm possible side effect Yield of 1 induced sputum equivalent to 3 GW • Lighter Curr Probl Pediatr Adolesc Health Care 2009 2Zar Lancet 2005 Bacteriologic confirmation 4
- 44. Principle: T-cellsof individuals with TB infection secrete IFN-γ in response to re-stimulation with M. tb-specific antigens • Newton SM, Brent AJ, Anderson S, Whittaker E, and Kampmann B; Paediatric Tuberculosis - Lancet Infect Dis. 2008 Aug; 8(8): 498–510. • QuantiFERON-TB Gold is FDA-approved in the United State • T-SPOT.TB is another IGRA; it uses the ELISPOT method. Interferon Gamma Release Assay (IGRA) Newer Techniques Bacteriologic confirmation 4
- 45. Identifies M.tband genetic mutations associated with INH and RIF resistance Specificity is excellent for INH resistance but sensitivity estimates are modest and variable Can be used directly on sputum specimens, or on isolates Results within 1-2 days Complex to perform Geographical variation in prevalence of mutations associated with rifampicin and INH resistance *GenoType MTDBRplus strips (Hain Lifescience) 4 Newer Techniques Bacteriologic confirmation 4 Molecular Line Probe Assay (LPA)
- 46. Rapid detectionof M.tb and Rif resistance Sensitivity: 95-99.5%; specificity: 95% For sputum smear (+)/(-) Minimal training Minimal space requirements Fully automated Results in 2 hours Cartridge Based Nucleic Acid Amplification Test 4 Newer Techniques Bacteriologic confirmation 4 Gene Xpert Mtb/Rif [CBNAAT]
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- 48. to cure thepatient of TB prevent death from TB disease prevent its late effects prevent relapse of TB prevent dt & transmission of drug-resistance reduce transmission of TB to others achieve all this with minimal toxicity Aims of Treatment of TB in children 1 2 3 4 5 6 7
- 49. Recommended treatment regimensfor new cases of TB in children TB diagnostic category Anti-TB drug regimens Intensive phase Continuation phase Low HIV prevalence (and HIV-negative children and low isoniazid resistance settings Smear-negative pulmonary TB Intrathoracic lymph node TB Tuberculous peripheral lymphadenitis 2 HRZ 4 HR Extensive pulmonary disease Smear-positive pulmonary TB Severe forms of extrapulmonary TB (other than tuberculous meningitis/osteoarticular TB) 2 HRZE 4 HR High HIV prevalence or high isoniazid resistance or both Smear-positive PTB Smear-negative PTB with or without extensive parenchymal disease All forms of EPTB except tuberculous meningitis and osteoarticular TB 2 HRZE 4 HR Tuberculous meningitis and osteoarticular TB (All regions) 2 HRZE 10 HR
- 50. Doses of AntiTB Drugs Drug Suggested daily dose Isoniazid 10 (7-15) mg/kg/d Rifampicin 15 (10-20) mg/kg/d Pyrazinamide 35 (30-40) mg/kg/d Ethambutol 20 (15–25) mg/kg/d • The higher end of the range for isoniazid dose applies to younger children; as the children grow older the lower end of the dosing range becomes more appropriate.
- 53. Medicines Used forDrug Resistant Tuberculosis Group Drugs A — Levofloxacin ( Lfx) — Moxifloxacin (Mfx) — Gatifloxacin (Gfx) B 2nd Line Injectables — Amikacin — Kanamycin — Capreomycin C Other core 2nd line agents — Ethionamide/Prothionamide (Eto/Pto) — Cycloserine/Terezidone (Cs/Trd) — Linezolid (Lzd) — Clofazimine (Cfz) Group Drugs D Add-on agents D 1 • Pyrazinamide (Z) • Ethambutol (E) • High Dose Isoniazid (Hh)· D 2 • Bedaquiline (Bdq) • Delaminid (Dlm) D 3 • Para-amino salicylic acid (PAS) • Imipenem-Cilastatin (Ipm) • Meropenem (Mpm) • Amoxicillin-Clavulanate (AmxClv)
- 54. Treatment regimens forchildren with MDR-TB A shorter MDR-TB treatment regimen of 9–12 months is recommended for RR-/MDR-TB patients In case of failing regimen, drug intolerance, return after interruption >2 months, emergence of any exclusion criterion - Longer MDR-TB regimens 6-9 months of intensive phase with Kanamycin, Levofloxacin, Ethambutol, Pyrazinamide, Ethionamide and Cycloserine, and 18 months of continuation phase with Levofloxacin, Ethambutol, Ethionamide and Cycloserine. Delamanid: Children (6 – 11 years) - 50 mg – 2x /day for 6 months and • Adolescents (12-17 years) – 100mg 2x /day for 6 months in adolescents aged 12 to 17 • Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children. 2nd edition. WHO 2014
- 55. Adjunct Corticosteroids forEPTB • Mandal et al., Recent Changes in Tuberculosis Guidelines for Children; Mycobact Dis 2017, 7:2 DOI: 10.4172/2161-1068.1000237 a)TB meningitis-at least for 4 weeks in HIV negative and b) HIV+ve, no life threatening opportunistic infections c) TB pericarditis in both HIV -ve and HIV +ve patients d) Pleural TB : not routinely recommended.
- 56. Drug Resistance -Definitions Drug Redistant TB: Mycobacterium tuberculosis bacilli resistant to at least one of the 1st line anti TB drugs, INH, RMP, Pyrazinamide or Ethambutol Multidrug Resistant TB: Mtb resistant to INH and RMP Extensively Resistant TB: Mtb resistant at least to INH, RMP plus any resistance to fluroqunolones and injectable anti TB drugs.
- 57. TREATMENT OF CHILDHOODTUBERCULOSIS Drug Regimen – Follow up a) b) • no need to extend intensive phase (IP) • weight monthly • sputum microscopy at end of IP and end of treatment • chest X-ray only if required. New & previously treated drug sensitive PT • sputum smear monthly at 3,4,5,6 and 7 months in intensive phase and • at 3 months interval in continuation phase • extend IP by maximum 3 months total of 9 months. MDR-TB
- 58. Additional management issuesin the treatment of drug-resistant TB • In EPTB: • Immune Reconstitution Inflammatory Syndrome (IRIS) • TBM, • Pl effusion, • Pericardial effusion Corticosteroids Extremely crucial Infection control Very important Nutritional support • Pyridoxine 5-10 mg/kg/d • Co-trimoxazole Prophylaxis Therapy • Anti Retroviral Therapy HIV positive children with DR-TB Critical to prevent development of resistance Adherence
- 59. Treatment of LatentTuberculosis Infection (LTBI) • Recommended for adults and children aged >2 years, including HIV-positive persons 3 mo of once-weekly Isoniazid plus Rifapentine (RPT): • Recommended for HIV- negative adults and children of all ages. 4 mo of daily Rifampin • Recommended for adults and children of all ages and for HIV- positive persons 3 mo of daily Isoniazid + Rifampin(RIF) • for HIV-negative adults and children of all ages 6 or 9 mo of daily Isoniazid (10–15 mg/kg) Chemo prophylaxis P
- 60. New Anti TBInitiatives at National Level 1. NIKSHAY : Online monitoring tool for TB control 2. TB Notification: TB is notifiable disease from 2012 3. Ban on TB Serology 4. Direct benefit transfer schemes
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