Childhood TV & 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

35. CHOROID TUBERCLES

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

46. X-ray showing destruction

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

59. APPROACH TO DIAGNOSIS

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