Childhood tuberculosis & Revised RNTCP guidelines
- 1. Childhood Tuberculosis & Revised RNTCP guidelines Topic presentation by : Dr. Saurav Kumar Upadhyay 1st Year, Junior resident Dept. of Pediatrics SVPPGIP SCBMCH,Cuttack
- 2. TUBERCULOSIS • Chronic infectious disease caused by Mycobacterium tuberculosis. • Caused human disease for more than 4000 years • First recognized as clinical entity by Schonlein who used the term Tuberculosis • The term derived from english term “tubercle” or lesion of consumption
- 3. BURDEN OF TB • In India , every day more than 6000 develop TB disease more then 600 people die of TB ie. 2 deaths every 5 minutes • India has highest burden of both TB and MDR TB and second highest of HIV associated TB • Approx 3 % among new TB cases and 12to17 % among previously treated TB cases have MDR TB
- 4. • 10% disease burden is assigned to children. • Annual risk of tuberculosis infection in developing countries in children is 2-5%. • Estimated lifetime risk of developing TB as indicated by positive tuberculin test is 10%. • In India, over 1,00,000 children die from TB every year.
- 5. TERMINOLOGY • EXPOSURE : Significant contact with an adult or adolescent with infectious TB but lacks proof of infection . • INFECTION : Occurs when the individual inhales droplet nuclei containing M.tb which survive intracellularly within the lung and associated lymphoid tissue . Hallmark is +TST +/- CXR . Signs, symptoms and Physical examination normal .
- 6. • DISEASE : Signs or symptoms becomes apparent • Not all infected individual have the same risk of developing disease • Immunocompetent adult : 5 to 10 % life time risk • Younger than 1yr : 40% within 9 months • HIV infected : 30 times higher risk
- 7. TRANSMISSION • Inhalation of air borne mucus droplet nuclei 1-5 micron in diameter • Chance of transmission increases with Positive AFB strain Extensive UL infiltrates / cavity Copious production of thin sputum Severe and forceful cough • Environmental factors
- 9. AT RISK • Exposed to high risk adults • Slum dwellers • Street children • IV drug abuser • Malnutrition
- 10. CLINICAL MANIFESTATIONS • PRIMARY PULMONARY DISEASE • Progressive primary Pulmonary disease • Reactivation TB • Pleural Effusion • Pericardial Disease • Lympho hematogenous (Disseminated TB ) Spread • Upper Respiratory tract Disease • Lymph node disease • CNS Disease • Cutaneous disease
- 11. • Bone and joint disease • Abdomen and GI disease • Genitourinary Disease • Perinatal disease
- 12. PRIMARY PULMONARY DISEASE • PRIMARY FOCUS : Ghon’s : Usually at the site of first implantation • Usually single and subpleural • Most cases : heals and disappears or fibrosis or calcifies.
- 13. • PRMARY COMPLEX : Parenchymal Pulmonary focus and Hilar lymph nodes and draining lymphadenitis • Complication arises more commonly from regional adenitis than primary focus • HALLMARK : relatively large size Regional lymphadenitis compared with relatively small size of initial lung focus
- 15. CHILDREN vs ADULTS • In adults , • Regional lymphadenitis is less marked • Bronchial erosion less frequent • Less risk of dissemination • Cavity formation • Thus in adults primary infection tends to be more local and pulmonary
- 16. PROGRESSIVE PRIMARY PULMONARY DISEASE • Rare but serious • Primary focus enlarges steadily and develops large caseous center • Enlarging focus Can slough necrotic debris into adjacent bronchus leading to intrapulmonary dissemination
- 17. COMPLICATIONS OF PRIMARY FOCUS • Rupture into plueral space • Rupture into bronchus : cavity • Enlarged focus , laminated or coin shadow
- 18. COMPLICTIONS OF REGIONAL NODE • Incomplete ( ball valve ) bronchial obstruction , emphysema of middle and lower lobes • Complete : collapse of lower lobe • Rupture into pericardium : TB pericardial effusion
- 19. SEQUELAE OF BRONCHIAL COMPLICATIONS • Stricture of bronchus at site of erosion • Cylindrical bronchiectasis in area of old collapse • Wedge shadow : contracture and fibrosis of segmental lesion • Linear scar of fibrosis following segmental lesion
- 20. SYMPTOMS • Primary complex – mild fever , anorexia , wt 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 consider
- 21. PLEURAL EFFUSION • Follows rupture of subpleural focus. Also by hematogenous spread from primary focus . • Hypersensitivity to tuberculoproteins • Fever, cough, dyspnea, pleuritic chest pain
- 23. MILIARY TB • First 3 to 6 months after infection • Heavy hematogenous spread of tubercle bacilli causing disease in 2 or more organs • CXR : SNOW STROM apperance
- 25. CUTANEOUS TB • Associated with primary complex – direct inoculation into traumatized area ; painless nodule , leading to non healing ulcer with regional lymphadenitis • Associated with hematogenous dissemination- Papulonecrotic tuberculids – papules with soft centres on trunk , thighs and face • Lupus Vulgaris : Well demarcated annular plaque with central scarring • Verrucosa cutis – large tuberculids on arm and legs
- 26. LUPUS VULGARIS Well demarcated annular plaque with central scarring
- 27. VERRUCOSA CUTIS
- 28. • Associated with hypersensitivity – ERYTHEMA NODOSUM painful indurated nodules on shins , elbows , forearms that subside in 2-3weeks
- 29. ERYTHEMA NODOSUM
- 30. SCROFULA • TB of superficial LNs • Mc form of extrapulmonary TB in children • Tonsillar / submandibular – paratracheal nodes • Supraclavicular – primary lesion of UL lung • Inguinal , epitrochlear , axillary – TB skin or skeletal system causing regional lymphadenitis • U/L , discrete , non tender , firm . Systemic signs and symptoms except low grade fever are absent , TST usually reactive . CXR : Normal in 70% • Respond well to ATT
- 31. D/D TB LYMPHADENITIS • Non Tuberculous Mycobacteria • Cat scratch disease • Tularemia • Brucellosis • Toxoplasmosis • Pyogenic infections • Tumor • Brachial cleft cyst • Cystic hygroma
- 32. SCROFULODERMA Firm asymptomatic subctaneous nodule
- 33. SCROFULODERMA ULCER Shallow, undermined bluish margins floor with granulation tissue
- 34. OCULAR TB • Primary TB Conjuctivitis – after trauma , yellowish gray nodules on palpebral conjuctiva with preauricular adenopathy • PHLYCTENULAR CONJUCTIVITIS – Hypersensitivity – nodules on limbus recurring in crops • CHOROID TUBERCLES – Miliary TB Highly specific
- 36. TB OTITIS MEDIA • Primary with preauricular adenitis • Metastatic from elsewhere • Painless otorrhea +/- blood , perforated TM • Complications - secondary infection ,deafness ,TB meningitis
- 37. GI and ABDOMINAL TB • Painless ulcer on mucosa , palate , tonsil with enlargement of LNs . • TB Esophagus : TEF in infants , Rare • TB peritonitis : young men . Rare in children • Generalized : from miliary hematogenous spread • Localized – direct extension from abdominal LN , Intestinal focus , genitourinary focus • Doughy feel abdomen , low grade fever , anorexia • Confirmed by paracentesis
- 38. • TB ENTERITIS – Hematogenous / swallowing • Jejunum and ileum near payers patch and appendix are most commomly involved • Ulcerative , hypertrophic , ulcerohypertrophic • D/D : Crohns disease
- 39. • Intestinal TB • Fever++ • Hypertrophic lesions • Caseating conglomerate granulomas, AFB + ve • Anorectal fistula & anal lesion less common • Excellent response to ATT • Crohn’s disease • Fever+ • Cobblestone appearance & aphthous ulcers • Non caseating granuloma, AFB – ve • Common • No response to ATT, requires immunosuppresive therapy
- 40. Transverse ulcers of TB
- 41. Longitudinal Ulcers of CROHNS
- 42. Renal TB • Tubercles in glomeruli leads to shedding of tubercle bacilli into tubules • Caseous mass / cavity between cortex and pyramids • TB cystitis • Symptoms : Dysuria , hematuria , sterile pyuria
- 44. SKELETAL TB • In order of frequency • Vertebrae > knee > hip> elbow • Upper extremities and non weight bearing bones ( skull , clavicle ) rarely involved • TB SPONDYLITIS – Thoracic / lumbar / both in order of frequency • SPINA VENTOSA : Pic next slide • Xray : narrowing of disc space, collapse of vertebral body , extensive destruction with kyphosis (POTTS DISEASE ) • COMPLICATIONS – Paravertebral abscess , psoas abscess , paraplegia ,quadriplegia
- 45. SPINA VENTOSA of 4th metacarpals thickening , soft tissue swelling and discharging wound
- 47. GENITAL TB • Uncommon Mostly seen in prepubescent boys and girls • Lymphohematogenous spread / direct spread • Adolescent girls – Fallopian tubes 90 to 100% , endometritis , oophoritis , cervicitis . • INFERTILITY – sequel • Adolescent boys – epididymitis / orchitis
- 48. NEUROTUBERCULOSIS MENINGOVASCULAR TBM and Meningoencephalitis Spinal arachnoiditis Radiculomyelitis / myelitis PARENCHYMAL Tuberculoma Tubercular abscess SECONDARY Spinal cord disease (compression) milairy TB of brain
- 49. TB MENINGITIS • PATHOPHYSIOLOGY • Rupture of subcortical focus (rich ) into Subarachnoid space • Inflammatory exudates Form over base of brain and along cerebral vessels as they pass over hemispheres • Adhesions along base and roof of 4th ventricle lead to obstruction and hydrocephalus • Involvement of CN 3 , 6 , 7 and optic chiasma
- 50. STAGES • STAGE 1 : lasts 1-2 wks , non specific symptoms • STAGE 2 : Begins abruptly , lethargy , meningeal signs , , hypertonia , FND , Cranial nerve palsy • STAGE 3 : Coma , hemi/ paraplegia , hypertension , decerebrate posturing , deterioration of vitals
- 51. Diagnosis • Signs of meningeal irritation • CXR • CT BRAIN – basal exudates , inflammatory granulomas • Tuberculin testing • Retinoscopy for choroid tubercles • LP : elevated pressure – 30 to 40 cm h20 cobweb coagulum 100-500 cells sugar <40mg/dl rarely <20 protein 400-5000mg/dl AFB Smear and culture
- 52. TUBERCULOMAS • Adults : supratentorial , children : infratentorial , base near cerebellum • Usually singular but may be multiple also . • CT/ MRI Brain : discrete lesions with significant surrounding edema . Contrast enhancement : ring like lesion • D/D Neurocysticercosis
- 53. • Tuberculoma • May present at any age • Progressive neurological deficit • Ring size is usually >20mm Irregular with significant cerebral edema • May be supratentorial / Infratentorial • Likely to cause midline shift • MRS has lipid peak. • T2 relaxation time shorter. • Neurocysticercosis • Rare before the age of 3 years • Generally no neurological deficit,postictal focal deficits of varying severity resolves within a matter of days /weeks. • Usuall smaller,regular outline, less cerbral edema • Usually supratentorial • No midline shift • No lipid peak • T2 relaxation time longer.
- 55. PREGNANCY AND NEWBORN • Prematurity , IUGR , LBW and prenatal mortality . • Congenital TB is rare because mc result of female genital tract TB is infertility • Occurs from lesion of placenta – primary focus is fetal liver with periportal LN involvement • Aspiration or ingestion of infected amniotic fluid – primary focus is liver • However mc route of infection for neonate is postnatal airborne transmission from adult with infectious pulmonary TB
- 56. PERINATAL DISEASE • Symptoms may present at birth but commonly begin by 2nd/3rd week of life . • Signs : respiratory distress , fever , HSM , poor feeding , lethargy , irritability , LN , failure to thrive , ear discharge and skin lesions • Generalized LN and meningitis occur in 30-50 % • CXR : Miliary pattern • TST : Often neg . Can become positive in 1-3 months . • Gastric aspirate and other specimens yields good results • Mortality rate remains high because of delayed diagnosis .
- 57. HIV and TB • 30 times increased risk • Diagnosis is difficult – TST neg , culture confirmation is difficult , C/F are similar to many other HIV related infections . • Treatment is difficult- More often severe , progressive and likely to be extrapulmonary , high rates of drug resistance , recurrent disease are more common • Mortality rate depends on CD4 count . Increased mortality rates are attributed to progressive HIV disease than TB . • Hence HIV infected children with potential exposures should be promptly evaluated ,conversely all child with TB should be tested for HIV
- 58. IRIS • Immune reconstitution inflammatory syndrome • Starting of HAART • Transient worsening of symptoms such as fever increasing LN , exacerbation of intracerebral tuberculoma , pleural effusions • Reason : effects of immune reconstitution , although hypersensitivity reaction to antigens released by TB bacilli may also contribute
- 60. PRESUMPTIVE PAEDIATRIC TB • Children with persistent fever and / or cough for more than 2 weeks • Loss of weight * / no wt gain • History of contact with infectious TB cases ** *unexplained past 3 months / No wt gain 3 months . Loss of wt more than 5% as compared to highest wt recorded in last 3 months **In a symptomatic child , contact with a person with any form of active TB with in last 2 yrs
- 61. PRESUMPTIVE DR TB • Failed treatment with first line drugs • TB non responders • Contacts with DR TB • Found positive on any follow up sputum smear • Previously treated TB • HIV Co-infection
- 62. CASE DEFINITIONS • MICROBIOLOGICALLY CONFIRMED TB : AFB +/ culture+/ positive through quality assured rapid diagnostic molecular test • CLINICALLY DIAGNOSED TB :Presumptive TB pt who is not microbiologically confirmed but diagnosed with Active TB by a clinician on basis on Xray /history of exposure to infectious case/ Evidence of TB infection (TST+) / clinical signs
- 63. CLASSIFIED ACCORDING TO • Anatomical site of disease • H/O previous treatment • Drug resistance
- 64. ANATOMICAL SITE • PULMONARY TB : Any microbiologically or clinically diagnosed TB Involving lung parenchyma or the tracheobronchial tree . • EXTRAPULMONARY TB : Other organs
- 65. H/O TREATMENT • NEW CASE : never had treatment or taken ATT Less than one month • PREVIOUSLY TREATED PATIENTS : one month or more treatment in the past 1. RECURRENT TB Case : A TB patient previously declared as successfully treated and is subsequently found to be microbiologically confirmed TB 2.TREATMENT AFTER FAILURE : Patients are those who have previously been treated for TB and whose treatment failed at the end of their most recent course of treatment
- 66. 3.TREATMENT AFTER LOSS OF FOLLOW UP A TB patient previously treated for TB for 1 month or more and was declared loss to follow up in their most recent course of treatment and subsequently found microbiologically confirmed TB 4.OTHER PREVIOUSLY TREATED PATIENTS : are those who have previously been treated for TB but whose outcome is unknown or undocumented
- 67. DRUG RESISTANCE • MR : One first line Anti TB drug • PDR : More than one first line Anti TB drug other than both H and R • MDR : Resistance to both H and R With or without resistance to other first line drugs based on results from quality assured lab • RR : Resistance to R detected using phenotypic or genotypic methods , with or without resistance to other Anti TB drug excluding INH . Managed as MDR TB • XDR : MDR +Resistance to a FQs (oflox, levo or moxi) +second line injectable AntiTB drug (Kanamycin, amikacin, capreomycin)
- 68. DIAGNOSTIC TOOLS TESTS FOR MICROBIOLOGICAL CONFIRMATION • All efforts should be undertaken for microbiologically confirming Presumptive TB pts . • Under RNTCP acceptable methods are • SPUTUM SMEAR MICROSCOPY(AFB) Zeihl-Neelson staining Fluroscence staining
- 69. ZIEHL-NEELSEN STAINING GRADING FINDING NO OF FIELDS GRADING RESULT No AFB in 100 oil immersion field 100 0 Neg 1-9 AFB per 100 oil immersion field 100 scanty Pos 10-99 AFB per 100 oil immersion fields 100 1+ Pos 1-10 AFB per oil immersion field 50 2+ Pos >10 AFB per oil immersion field 20 3+ Pos
- 70. • CULTURE Solid : Lowenstein Jensen media Automated liquid culture system ex : BACTEC MGIT 960 , BactiAlert etc . Drug sensitivity testing Modified PST for MGIT 960 system • RAPID MOLECULAR DIAGNOSTIC TESTING Line probe assay CBNAAT
- 71. RADIOGRAPHY • Used as screening tool to increase sensitivity of diagnostic algorithm • Any abnormality should further be evaluated for microbiological confirmation • Diagnosis based on CXR will be termed as CLINICALLY DIAGNOSED TB
- 72. TST • Complimentary in children in combination with microbiological investigation,contact history, CXR and symptoms • A positive Tuberculin skin test/Mantoux test was defined as an induration of 10 mm or more, measured 48-72 hours after Intradermal injection with 2 TU Tuberculin PPD RT 23 or 5 TU of PPD-S • <5mm : negative ; no active ds • 5to 10 mm : boderline ; postive in immunocompromised host, contact history • >10 mm : positive, suggests disease in presence of clinical features
- 73. • STORAGE:- stored in dark place at 2-200 C Opened vials should not be kept for >2days
- 75. False negative • Patient related:- Infection(measles,mumps,HIV) Heavy load of antigen in miliary TB,TBM. Live attenuated viral vaccines CRF PEM(gradeIII,IV) Intake of steroids,immunosuppresants Extremes of age Stress • Others Faulty technique Denatured tuberculin
- 76. False positive • Infection with non –tuberculous mycobacteria. • Recent BCG vaccination. • Infection at the site of test
- 77. IGRA • Low prevalence countries • Not recommended in diagnostic algorithm
- 78. SEROLOGICAL TESTS • Not done anymore
- 81. Drug regimen
- 93. FOLLOW UP • Clinical follow up • Laboratory follow up
- 94. CLINICAL • At least monthly . • Improvement of chest symptoms • Increase in weight • Control of co-morbid conditions
- 95. LABORATORY • Sputum smear examination in case of Pulmonary TB at the end of IP and end of treatment • Negative : good prognosis
- 96. CXR • End of IP • End of treatment • Whenever required
- 97. LONG TERM FOLLOW UP • After completion : End of 6, 12, 18 & 24 months • In presence of any clinical symptoms, sputum microscopy / culture should be considered
- 98. MDR/XDR TB FOLLOW UP • MICROBIOLOGICAL : One sputum will be collected and examined by culture at least 30 days apart from 3 to 7th month of treatment (i.e. At the end of months 3,4,5,6,7 ) and at 3 monthly intervals (ie. At the end of months 9,12,15,18,21,24) . • If any culture during CP / end of treatment is positive then it should be followed by monthly cultures for 3 months
- 99. • Weight : monthly • CXR : at the end of IP / end of treatment / whenever required • Physical examination : including ADR every monthly for 6 months then every 3 months for 2 yrs • S.creatinine : monthly for First 3 months then every 3 months during injectable phase
- 100. • ECG : once monthly if Moxifloxacin is used • TFT : Start and whenever required if PAS & Ethionamide is used. • CBC : weekly in first month then monthly • Electrolytes : monthly till Inj Capreomycin used • LFT : monthly in IP and 3 monthly in CP • CXR : every 6 monthly in XDR TB
- 101. EPTB FOLLOW UP • Treatment response best assessed clinically • If required imaging • Extension of IP/CP may be considered in consultation with the specialist concerned
- 102. Treatment Outcome
- 103. DRUG SENSITIVE TB • CURED : microbiologically confirmed TB at beginning of treatment who was smear negative or culture negative at end of complete treatment • TREATMENT COMPLETED : Completed treatment without evidence of failure or clinical deterioration but no record to show that the smear or culture results of biological specimen in last month of treatment was neg , either because test was not done or because result is unavailable
- 104. • TREATMENT SUCCESS : Cured / treatment complete • FAILURE : Biological specimen is postive by smear / culture at end of treatment • FAILURE TO RESPOND : A case of paediatric TB who fails to have microbiological conversion to negative status or fails to respond clinically / detoriates after 12wks of complaint IP shall be deemed to have failed response provided alternate diagnosis/ reasons for non responders have been ruled out
- 105. • LOST TO FOLLOW UP : Patient whose treatment was interrupted for 1 consecutive month or more • TREATMENT REGIMEN CHANGED : First line regimen to DRTB • DIED : During course of ATT
- 106. RR/MDR-TB/XDR-TB • CURE : Treatment completed as recommended without evidence of failure and 3 or more consecutive cultures taken atleast 30 days apart are negative after IP • TREATMENT COMPLETED : Completed as recommended without evidence of failure but no record • TREATMENT SUCCESS : Cured / treatment complete
- 107. • TREATMENT FAILED : Treatment terminated or need for permanent regimen change of atleast 2 or more ATT drugs in CP because of - Lack of microbiological conversion by end of IP OR - Microbiological reversion in CP after conversion to negative OR - Evidence of additional acquired resistance to FQs / second line injectables
- 108. • CONVERSION (To negative ) : Conversion to negative when two consecutive cultures taken at least 30 days apart are found to be negative • REVERSION (To negative ): 2 consecutive cultures taken atleast 30 days apart are found to be positive . For the purpose of defining TREATMENT FAILED , reversion is considered only when it occurs in the continuation phase
- 110. THANK YOU