All about pediatric tuberculosis in nutshell

1. Treatment Guidelines of
Childhood Tuberculosis and
RNTCP
Presenter: Dr. Chinmoy Lath
1st June’12

2. Aims of Therapy in Tuberculosis
The main objectives of anti-TB treatment are to:
• Cure the patient of TB (by rapidly eliminating most of the
bacilli).
• Prevent death from active TB or its late effects.
• Prevent relapse of TB (by eliminating the dormant bacilli).
• Prevent the development of drug resistance (by using
combination of drugs).
• Decrease TB transmission to others.

3. Evolution in Treatment of TB
Classical (long course) chemotherapy regimen :
• 18 months duration daily regimens
• Used INH with one or two bacteriostatic drugs
• High failure and relapse rate
• Poor compliance
Short course chemotherapy regimen
• Combination of 3-4 drugs used in intensive phase (2 mths)
• Drugs give either daily / intermittently
• Minimum duration of treatment – 6 months
• Drugs – preferably given together and as single dose

4. Advantages
• Faster, powerful bactericidal and sterilizing action
• Patient exposed to toxic drugs for shorter duration
• Less expensive
• Reduction in emergence of drug resistant bacilli
• Good tolerance and adherence

5. Results of six month treatment regimen for TB
Author, country
& year
Diagnostic
Criteria
No. of
children
Regimen Results
Al Dossary et
al, USA, 2002
Clinical and
radiological
175 2 weeks daily
HRZ f/b 6 wks
HRZ2 / 4RH2
81% t/t
completion 1
relapse
Te Water Naude
et al, S. Africa,
2000
Clinical &
radiological
89
117
2 RHZ2/4RH2
6RHZ
t/t outcome &
adherence
equivalent 1
relapse
Varudkar, India,
1985
Clinical &
radiological
100
40
45
2 HRE/4HE
2 HZE/4HE
6 HRE3
0 failures,
0 relapses
Kumar et al,
India, 1990
Clinical &
bacteriological
37
39
2 HRZ / 4HR2
9 HR
2 deaths not
related to TB 0
relapse
Ramachandran
et al, India, 1998
Clinical &
bacteriological
68
69
2 HRZ3 / 4RH2 3 (2%) died, 0
failures, 3
relapses

6. TRC studies on extrapulmonary TB
Studies Rx regimen Duration
(mon)
No.
of
pts
Follow-
up period
(months)
Overall
favourable
response
%
TB spine 6 HR7 + modified
HongKong Surgery
6 78 120 90
6HR7 6 78 120 94
TBM 2 HRS7/ 4HE7S2 /
6HE7
12 69 24 33
2R2 HZS7/ 10HE7 12 70 24 36
Pott’s
paraplegia
2SHER7 / 7HR2 9 11 60 73
Abd TB 2HRZ7/4HR7 6 85 60 94
Brain
tubeculoma
3HRZ7 / 6HR2 9 47 24 89

7. • Tuberculosis Research Centre (TRC) studies have clearly
established efficacy of short course treatment.
• Intermittent regimens proven as effective as daily regimen
• Overall favourable response varied from 87-99% except in
TBM (33%) and Pott’s spine (73%)
• In TBM, outcome is related to stage of disease at the start
of treatment and duration of symptoms prior to admission
• Similarly in Pott’s spine recovery influenced by factors like
initially motor power, presence or absence of bed sores and
duration of kyphosis
• Therefore early diagnosis and treatment is recommended
for these two conditions

8. Management of pediatric TB under RNTCP –
Diagnosis
Suspected cases of pulmonary TB include
• Fever and/or cough > 2 wks
• Weight loss or failure to thrive
• H/o contact with suspected / diagnosed case of active TB in
last 2 yrs
• Suspect TBM in child with neurological symptoms,
irritability, refusal to feed, headache, vomiting, altered
sensorium

9. Bacteriological testing
• Sputum examination whenever possible
• Gastric lavage if sputum not available (yield is 20%)
• Multiple samples to be taken
Tuberculin Test
• Mantoux test using 1 TU PPD RT 23 Tween 80
• +ve test >10 mm induration at 48-72 hrs
Radiology
• CXR – suggestive findings mediastinal / hilar lymphadenitis
with / without parenchymal lesions, pleural effusion, miliary
and fibro-caseous pictures
• Persistent pneumonia >4 wks inspite of antibiotic therapy

10. PCR
• Low sensitivity for gastric aspirates
• Routine use not recommended
• May be useful in neuro TB
• Sensitivity ranges from 4-80% & specificity 80-100%
Serology
• Low sensitivity, specificity and positive predictive value

11. RNTCP
diagnostic
algorithm for
pediatric
pulmonary TB

12. Standard Case Definitions
New case
• Pt. who never had treatment for TB / or taken ATT <4 wks
Relapse
• Pt. declared cured of TB in past after one full course of
ATT, and has become sputum smear +ve
Treatment failure
• A pt. who while on treatment remained or become again
smear positive 5 months or more after starting therapy
• A pt. initially smear negative become sputum +ve after 2nd
month of therapy

13. Treatment after interruption
• Patient who interrupts t/t for 2 months or more, and return
with smear +ve
Chronic case
• Patient who remained or become smear +ve after
completing fully supervised re-treatment regimen
Smear positive pulmonary TB
• One or more initial sputum smear +ve for AFB

14. Smear negative pulmonary TB
• At least 2 sputum specimen –ve for AFB
• Radiological abnormality consistent with active pulm TB
• No response to a coarse of broad spectrum antibiotics
• Decision by clinician to treat with full course of ATT

15. Treatment Outcomes
Cure
• Initially sputum smear-positive patient who
• has completed treatment and
• had negative sputum smears on two occasions, one of
which was at the end of the treatment.
Treatment completed
• Pt. who has completed t/t without proof of cure.
Treatment failure
• Pt. who remaining or becomes again smear +ve at 5 month
/ later during t/t
Transfer out
• Pt. transferred to other reporting unit

16. Treatment Regimen
Treatment
category
Type of patients TB treatment regimens
Intensive
phase
Continuation
phase
Category I New sputum smear-positive PTB
Seriously ill sputum smear-negative PTB
Seriously ill extrapulmonary tuberculosis
(EPTB)
2H3R3Z3E3 4H3R3
Category II Sputum smear-positive relapse,
Sputum smear-positive treatment failure,
Sputum smear-positive treatment after
default
2S3H3R3Z3E3/
1H3R3Z3E3
5H3R3E3
Category III Sputum smear-negative and EPTB not
serious ill
2H3R3Z3 4H3R3

17. New RNTCP Classification

18. • Seriously ill sputum smear negative pulm. TB: all forms of
PTB other than primary complex
• Seriously ill EPTB: TBM, disseminated miliary TB, TB
pericarditis, TB peritonitis and intestinal TB, B/L or
extensive pleurisy, spinal TB with or without neurological
complications, genitourinary tract TB, bone & joint TB
• Not seriously ill EPTB: lymph node TB and U/L pleural
effusion
• In pts with TBM on category I treatment, 4 drug use during
intensive phase should be HRZS instead of HRZE.
Continuation phase to be given for 7 months. Total duration
of treatment 9 months
• Steroids to be used initially in hospitalized cases of TBM
and TB pericarditis for 6-8 weeks.

19. Suggested pediatric dosages for intermittent therapy
Drug Dosage
(mg/kg)
Weight range in kg
6-10 11-17 18-25 26-30
Isoniazid 10 75 150 225 300
Rifampicin 10 75 150 225 300
Pyrazinamide 30-35 250 500 750 1250
Ethambutol 30 200 400 600 1000
Streptomycin 15

20. • During intensive phase, patient swallows drug under
supervision of Health worker 3 times a week
• In continuation phase, pt is issued medicine for 1 wk in
multiblister combipack of which 1st dose swallowed in
presence of health worker
Chemoprophylaxis
• Asymptomatic children <6 yrs exposed to infectious TB
should be given 6 month of INH (5 mg/kg daily)
Monitoring & evaluation
• Sputum examined after 2 month of intensive phase in
Category I, after 3 months in Category II, if +ve IP given for
1 more month.

21. Lacunae in RNTCP
• Children can’t appreciate symptoms / bring out sputums 
difficulty in diagnosis
• CXR – intra and interreader variations, not available at
primary health centres
• Tubeculin test, gastric lavage and FNAC – limited to
hospitals, not available in primary health centres
• Problem in direct observation of t/t – non-availability of child
due to clash with school timing, non-availability of parents
due to work
• Social stigma, especially for female pts

22. Consensus
Statement
Recommendations
of IAP, 2010

23. Diagnostic algorithm for tubercular lymphadenitis

24. Recommended doses of antitubercular drugs
• All drugs to be given empty stomach single dose
• Vit B6 – not needed in children taking INH
• Daily treatment regimen is advised
• Fixed dose combination of INH and rifampicin acceptable
• Use pyrazinamide separately

25. Prednisolone
Indications
• Tubercular meningitis.
• Tubercular pericarditis.
• Mediastinal compression syndrome due to Tuberculosis.
• Endobronchial tuberculosis.
• Pleurisy with severe dystress.
• Milliary disease with alveolocapillary block.
• Dose:2-4 mg/kg/day for 2-4 wks then tapper over 2 weeks.

26. Microbiological Basis of Treatment
Types of bacterial population
• Group I – metabolically active continuously growing bacilli
in neutral pH present extracellularly, killed by INH f/b
rifampicin and streptomycin
• Group II – intermittent multiplying organisms (semidormant)
in hypoxic environment of cacious material killed by
rifampicin
• Group III – intracellular bacilli in acidic pH killed by
pyrazinamide
• Group IV – drug resistant mutants, acted upon by rifampicin
and INH

27. Pharmacological principles
• Drugs are divided in three categories
1. Early bactericidal activity – ability to kill bacilli in first few
days of t/t, max. in INH f/b Etham. and Rifampicin
2. Sterilizing activity – ability to eradicate persisters -
intracellular bacilli, seen with Rifampicin & Pyz
3. Prevention of drug resistance to companion drug, seen
in INH and Rifampicin

28. CLASSIFICATION
OF
ANTITUBERCULAR DRUGS

29. Tuberculocidal Tuberculostatic
Isoniazid, Rifampicin
Streptomycin, Amikacin
Pyrazinamide
Capreomycin, Quinolones,
Rifamycin
Ethambutol (except in inflamed
meninges)
Thiacetazone, Ethionamide
Para-aminosalicyclic acid
Cycloserine

30. TRADITIONAL
CLASSIFICATION
FIRST LINE DRUGS:
INH (H)
RIFAMPICIN (R)
PYRAZINAMIDE (Z)
ETHAMBUTOL (E)
STREPTOMYCIN (S)
SECOND LINE DRUGS:
AMIKACIN, KANAMYCIN
FLUOROQUINOLONES
PAS, CYCLOSERINE

31. RECENT WHO CLASSIFICATION
GROUP 1 (FIRST LINE ORAL AGENTS)
– INH
GROUP 2 (INJECTABLE AGENTS)
– KANAMYCIN
GROUP 3 (FLUOROQUINOLONES)
– LEVOFLOXACIN
GROUP 4 (ORAL BACTERIOSTATIC AGENTS)
– ETHIONAMIDE
GROUP 5 (AGENTS WITH UNCLEAR EFFICACY)
– LINAZOLID, AMX-CLV

32. ANTI-TB DRUGS USED IN
RNTCP
FIRST LINE DRUGS:
INH (H)
RIFAMPICIN (R)
PYRAZINAMIDE (Z)
ETHAMBUTOL (E)
STREPTOMYCIN (S)
SECOND LINE DRUGS:
AMIKACIN, KANAMYCIN,
FLUOROQUINOLONES,
CAPREOMYCIN,
ETHIONAMIDE
PAS, CYCLOSERINE, etc…

33. Adverse effects of ATT drugs
Drug Adverse effects
Isoniazid Hepatotoxicity, peripheral neuritis, hypersensitive
reactions may precipitate epilepsy, drug induced lupus,
psychotic changes
Rifampicin Hepatotoxicity, gastrointestinal, autoimmune reactions
(more with intermittent administration), which include flu
syndrome, thrombocytopenias, purpura, respiratory
shock syndrome, acute hemolytic anemia, ARF)
Pyrazinamide Hepatotoxicity, arthralgia, hyperuricemia,
gastrointestinal, allergic reactions
Ethambutol Optic neuritis, colour blindness, gastrointestinal, allergic
reactions, hyperuricemia
Streptomycin Vestibular dysfunction, deafness, nephrotoxicity,
neuromuscular blockade, peripheral neuritis

34. Adverse effects of ATT drugs (contd…)
Drug Adverse effects
Thioacetazone Exfoliative dermatitis, Steven Johnson syndrome
Quinolones GI symptoms, CNS, phototoxicity, tendinopathy &
tendinitis, nephrotoxicity, skin rash
Ethionamide GI symptoms, psychiatric (hallucination & depression),
hepatitis, hypothyroidism, Gynaecomastia
Cycloserine CNS (convulsions), psychiatric (depression, suicidal
tendency)
PAS GI symptoms, hepatic dysfunction, hypokalemia,
hypothyroidism

35. Second-line anti-TB drugs for t/t of MDR-TB in children
Drug Mode of action Recommended daily dose
Range (mg/kg bw) Max
(mg)
Ethionamide or
prothionamide
Bacteriostatic 15-20 1000
Fluoroquinolones
Ofloxacin Bactericidal 15-20 800
Levofloxacin Bactericidal 7.5-10 -
Moxifloxacin Bactericidal 7.5-10 -
Gatifloxacin Bactericidal 7.5-10 -
Ciprofloxacin Bactericidal 20-30 1500
Aminoglycosides
Kanamycin Bactericidal 15-30 1000
Amikacin Bactericidal 15-22.5 1000
Capreomycin Bactericidal 15-30 1000
Cycloserine terizidone Bacteriostatic 10-20 1000

36. Contraindications for anti TB drugs
Isoniazid
• Known hypersensitivity to isoniazid
• Active hepatic disease
Rifampicin
• Hypersensitivity to rifampicin
• Hepatic dysfunction
Pyrazinamide
• Known hypersensitivity to
pyrazinamide
• Severe hepatic impairment
• Gout
Streptomycin
• Hypersensitivity
• Auditory nerve impairment
• Myasthenia gravis
• Pregnancy
Ethambutol
• Hypersensitivity
• Preexisting optic neuritis
• Pts with creatinine clearance
of <50 ml/min

37. Important side effects with clinical implications
Hepatotoxicity
• Hepatotoxicity drugs include INH, rifampicin, PYZ
• Chances if higher doses / combination are used
• Children with severe disease like TBM, miliary TB are at
greater risk
• Children with preexisting liver dysfunction and malnutrition
more predisposed
• Routine lab monitoring needed in high risk cases

38. Hepatotoxicity (clinically evident jaundice / ALT >5 times normal)
Stop IHN, Rifamp & Pyz, start Etham & Strepto
Repeat AST, ALT If they stay as normal / or
show a declining trend
Rifamp 10. mg/kg/day +
add INH 2.5 mg/kg/d
(repeat LFT)
PZA (30 mg/kg/d)
+ INH (5 mg/kg/d)
(7 days)

39. Ocular toxicity
• Seen in 5%, if doses of Ethambutol b/w 25-50 mg/kg/d.
• Rare in dose of 15 mg/kg/day.
• Result in reversible optic neuritis, blurred vision, scotoma,
colour blindness.
• Literature review suggests it is safe in children at a dose of
15-25 mg/kg/day.
Peripheral neuritis
• Clinically manifest peripheral neuritis is rare in children.
• Manifest and pins and needle sensation in hands and feet.
• More common in malnourished children, HIV +ve,
breastfeeding infants.
• Supplemental pyridoxine 5-10 mg/kg/day is recommended
in the predisposed population.

40. Role of Surgery in TB
Pulmonary TB
Indications
• Major airway obstruction due to
– Extraluminal LN compression – nodal curettage
– Intraluminal granulation tissue - bronchoscopy
• Post-TB pulmonary destruction – lung resection
• Late pleural fibrosis – decortication
• Release of post-tubercular constrictive pericarditis
• Drainage of active TB lung abscess

41. Neuro TB
Indications
• Failure of medical management
• TB with hydrocephalus and uncontrolled raised ICT
• Cerebral abscess
• Tuberculoma – for diagnosis of difficulty cases / features of
SOL
• Tubercular spinal arachnoiditis compressing cord
Early VP shunts for mild to mod. Hydrocephalus,
morbidity & mortality, no effect on stage III pts prognosis

42. Abdominal TB
Indications
• Diagnostic in case of peritoneal abd. TB
• Exploratory laparotomy in acute abdomen
• Management of complications like stricture, adhesion,
fistula, bleeding
Peritoneal
Wet / Ascitic Dry / Sclerosing
Laparoscopy and biopsy Open biopsy

43. Intestinal
Ulcers MassStricture Perforation
Local
resection
Local resection
(ileoceocotomy)
Minimal
narrowing
Local
resection /
enterostomy
(rarely)
Significant
narrowing
Multiple or very
long stricture
ATT Stricturoplasty Local resection

44. Genitourinary TB
For complications like
• Ureteral stricture, abscesses and non-functioning kidneys
Radical procedures
• Nephrectomy
• Partial nephrectomy
• Epididymectomy
Reconstructive procedures
• Strictures
– For PUJ obstruction: Pyeloplasy, percutaneous nephrostomy
– Ureteric strictures: Double J stenting, resection anastomosis
– Vesicoureteric junction obstruction: ureteric reimplantation

45. Potts spine
Indications for surgery
• Paraplegia despite conservative treatment
• Sudden acute paraplegia
• Paraplegia accompanied by uncontrolled spasticity
• Paraplegia in flexion
• Flaccid paraplegia
• Surgical procedure – anterolateral decompression

46. MDR-TB
An MDR TB SUSPECT Whose SPUTUM Is CULTURE POSITIVE
for M.Tb that are invitro resistant to Isoniazide AND rifampicin
with or without resistant to other drugs from an RNTCP
accredited laboratory.

47. Treatment of Multi-Drug Resistant TB
• Prevalence of primary MDR in India – <3%
• Prevalence of MDR TB among treated cases – 12-17%
(Paramsivan et al, IJMR 2004; 277-86)
Initial drug resistance
• INH – 20-30%, Streptomycin <10%, Rifampicin – 2-3%
Acquired drug resistance
• INH – 50-60%, Rifampicin – 20-30%, Streptomycin – 15-
30%
(Amdekar YK. Indian Pediatr 1998; 35: 715-18)

48. Drug-resistant TB should be suspected if any of the
features are present
• Features in the source case suggestive of drug-restating
TB
– Contact with a known case of drug-resistant TB
– Remains sputum smear-negative after 3 months of t/t
– H/o previously treated TB
– H/o treatment interruption
• Features of child suspected of having drug-resistant TB
– Contact with a known case of drug-resistant TB
– Not responding to the anti-TB treatment regimen
– Recurrence of TB after adherence to treatment

49. Types of resistance
Natural resistance
• Species specific resistance to drug without strain being
ever exposed to it
Primary resistance
• Pt infected with drug-resistant population without having
received prior treatment
Secondary (acquired) drug resistance
• Pt harbous organisms which were previously drug
susceptible but resistance developed during course of t/t

50. Alternative method of grouping ATT drugs
Grouping Drugs (abbreviation)
Group 1: First line oral Anti TB
agents
Isoniazid (H); Rifampicin (R); Ethambutol
(E); Pyrazinamide (Z)
Group 2: Injectable Anti TB
agents
Streptomycin (S); Kanamycin (Km);
Amikacin (Am); Capreomycin (Cm); Viomycin
(Vi)
Group 3: Fluoroquinolones Ciprofloxacin (Cfx); Ofloxacin (Ofx);
Levofloxacin (Lfx); Moxifloxacin (Mfx);
Gatifloxacin (Gfx)
Group 4: Oral bacteriostatic
second-line anti TB agents
Ethionamide (Eto); Protionamide (Pto);
Cycloserine (Cs); Terizidone (Trd); p-
aminosalicylic acid (PAS); Thioacetazone
(Th)
Group 5 – Anti TB agents with
unclear efficacy (not
recommended by WHO for
routine use in MDR-TB pts)
Clofazimine (Cfz); Amoxicillin / Clavulanate
(Amx / Clv); Clarithromycin (Clr); Linezolid
(Lzd)

51. Principles of Treatment
• Never add one drug to a failing regimen.
• Treat child according to the drug susceptibility pattern and
using t/t history of source case strain if isolate from child is
not available
• Use at least 4 drugs with certain effectivity
• Use daily treatment, directly observed
• Use bactericidal drugs as far as possible
• Use all oral 1st line drug to which isolate is sensitive
• An injectable agent is used for minimum of 6 months after
culture conversion

52. Principles of Treatment contd..
• Oral quinolone used for entire duration of therapy
• t/t to be given for at least 18 months after cultures are –ve
• Drug dosing to be determined by body weight
• Counsel caregiver regarding adverse events & compliance
• Follow-up is essential – clinical, radiological and
bacteriological
• Monitor LFT, KFT, hearing periodically

53. Concept of DOTS plus
Individualized treatment regimen
• Regimen designed as per resistance pattern of strain
infecting pt.
• Heavily dependent on drug sensitivity testing
• Unlikely to fail
• Less applicable in resource poor countries
Standardized regimen
• Based on common resistance pattern identified in a given
population
• Low cost, simpler implementation, less dependent on
laboratories

54. Management of MDR TB under RNTCP
• RNTCP will be using a Standardized Treatment regimen
RNTCP CATEGORY IV REGIMEN:
6 (9) Km Lvx Eto Cs Z E / 18 Lvx Eto Cs E
• Minimum recommendation is that intensive phase to be
given for 6 months
• After 6 months – continuation phase started if 4th month
culture are negative
• If 4th month culture is still awaited after 6 months of t/t, IP is
extended
• After maximum of 9 months CP started for 18 months

55. MDR patient referred to state level DOTS plus site with DTS
result
DOTS plus site decides on whom to start Rx
Pt admitted at DOTS plus site for 1 month
Discharged with 1 wk drug supply
Given treatment at a facility near to home

56. Indications for Surgery in MDR-TB
• As adjuvant may improve results of chemotherapy in
selected cases
• Ideally operate early in therapy, b/w 6-9 month
• After surgery continue therapy for 18 months
• If disease is resectable, surgery considered in following
– Absence of response despite 6-9 mon of t/t
– High risk of failure or relapse due to high degree of resistance
– Morbid complications e.g. haemoptysis, bronchiectasis,
bronchopleural fistula
– Recurrence of positive smear or culture during t/t
– Relapse after completion of anti-TB treatment

57. MDR TB in special situations
MDR-TB in pts with renal failure
• Drugs requiring dose or interval adjustment in renal failure
are – ethambutol, quinolones, aminoglycosides,
cycloserine, PAS, ethionamide
• Monitor blood urea, nitrogen and creatinine frequently
• In mild renal failure – dose of aminoglycoside reduced
• In severe renal failure – aminoglycosides are discontinued

58. Drug Method of
modi-
fication
GFR (ml/min)
>50 10-50 <10
Kanamycin D, I 7.5-15 mg/kg/24 hr 4-7.5 mg/kg/24 hr 3 mg/kg/48 hr
Ethambutol I 20 mg/kg/24 hr 20 mg/kg/24-36 hr 20 mg/kg/48 hr
Pyrazinamide D 30 mg/kg/24 hr 30 mg/kg/24 hr 15-30 mg/kg/24 hr
Ofloxacin D 100% 50-75% 50%
Ethionamide D 100% 100% 50%
Cycloserine D 100% 50-100% 50%
PAS D 100% 50-75% 50
D = dose adjustment; I = interval adjustment; *%age of recommended dose to be given

59. MDR-TB in pts with pre-existing liver disease
• In category IV regimen, PYZ, PAS and ethionamide are
hepatotoxic
• Most of the 2nd line drugs can be safely used in mild
impairment as they are less hepatotoxic than 1st line drugs
• PYZ should be avoided in such patients
MDR-TB in pts with seizure disorders
• If seizures are not under control, initiation of anti-seizure
drugs will be needed prior to start of MDR-TB therapy
• Cycloserine, ethionamide, quinolone have been associated
with seizures, use carefully
• Pyridoxine should be given with cycloserine to prevent
seizures

60. • Avoid cycloserine in pts with uncontrolled seizures
• Anti-epileptic drugs may have interaction with cycloserine
and quinolones, monitoring of serum levels may be needed
MDR-TB in pts with psychosis
• High baseline incidence of depression and anxiety in pts
with MDR-TB due to chronicity and socioeconomic factors
• Quinolones, ethionamide – associated with psychosis
• Pyridoxine prophylaxis recommended
• Cycloserine causes severe psychosis but not abs. C/I
• If pt. on cycloserine develop psychosis, stop cycloserine
and start anti-psychotics
• Resume cycloserine once pt is stabilized

61. XDR TB
(extensively drug resistance TB)
• XDR TB is resistance to at least INH and rifampicin (i.e.
MDR TB) + resistance to any fluoroquinolones and any one
of the second line anti-TB injectable drugs (Am, Cm, Km)
• Worldwide noted in 41 countries till date
• Isolated reports indicate existence of XDR TB in India, but it
is not possible to estimate its magnitude from present data
• Effective treatment of MDR pts through DOTS plus can
prevent XDR TB generation
• Extremely difficult to treat with poor outcomes

62. SUMMARY(RNTCP)
DIAGNOSIS OF PTB
• DURATION OF COUGH
3 WEEKS  2 WEEKS
– NUMBER OF SPUTUM SMEARS TO BE
COLLECTED
3 SMEARS  2 SMEARS
– NUMBER OF + SMEARS REQUIRED FOR DX OF
PTB+
2 SMEARS  1 SMEAR

63. • CATEGORY III HAS BEEN PHASED
OUT
• NEW (DOTS)
• PREVIOUSLY TREATED (DOTS)
• CATEGORY IV FOR MDRTB
• CATEGORY V FOR XDRTB
SUMMARY(RNTCP)
TREATMENT OF PTB

64. Treatment of Congenital TB
As per IAP
• Continue breastfeeding
• BCG given at birth
• If CXR normal – 6 HR
• If CXR abnormal – 2 HRZ/7HR
• Congenital TB – 2 HRZ/7 HR

65. As per WHO – active pulm TB diagnosed after delivery
<2 months after >2 months after
Treat mother, breastfeed, INH x 6 m
(5 mg/kg/d), BCG after stopping INH
Treat mother, breastfeed, INH x 6 m
(5 mg/kg/d), if BCG not given at birth
give after stopping INH
>2 month <2 month before
Smear-ve just before delivery Smear +ve just before
delivery
Treat mother,
breastfeed, INH x 6
m (5 mg/kg/d), BCG
after stopping INH
Treat mother, breastfeed, no
preventive CT, BCG at birth
Treat mother, breastfeed,
INH x 6 m (5 mg/kg/d),
BCG after stopping INH
As per WHO – active pulm TB diagnosed before delivery

66. As per RNTCP
Treat mother
Continue breast feeding
Mother
Sputum +ve Sputum -ve
Chemotherapy to
infant x 3 months
BCG given
No chemotherapy
MTx at 3 months
+ve -ve
BCG givenBCG not given 
continue CT x 6 mths

67. As per National Neonatology Forum (NNF)
If child has clinical features of perinatal TB
Start ATT
• 2 HRZ + 7 HR
• May add streptomycin for first 2 months
• HIV co-infection – 2 HRZS + 7 to 10 HR
• Extra pulmonary TB – 2 HRZS + 7 to 10 HR
• MDR TB – 12 to 18 HRZS or RHZE
Add steroids (prednisolone 1-2 mg/kg/d for 4-8 wks) if
• Meningitis, neuro TB, miliary TB, TB involving serous
layers, endobronchial / segmental lesions, genitourinary
TB, sinus formation
Breastfed infants / neonates on INH must be supplemented
with B6

68. If the child is clinically normal but mother high risk
Mother Mx negative (induration <10 mm)
Symptomatic Asymptomatic
CXR abnormal CXR normal Presumed uninfected
Investigate &
treat mother
No investigations
No t/t
Investigate &
treat mother,
no t/t of baby
Screen baby
Normal
Abnormal
Chemoprophylaxis (6 HR)
T/t as perinatal TB

69. If the child is clinically normal but mother high risk
Mother Mx Positive (induration >10 mm)
Abnormal Normal
CXR
No active TB Active TB
Screen mother
Continue breastfeed
Follow-up
T/t mother
Screen baby
Normal
Abnormal
Chemoprophylaxis (6 HR)
T/t as perinatal TB
Symptomatic Asymptomatic
Screen mother Breastfeed, no t/t

70. High risk mothers
• Old case of TB and on irregular t/t
• Sputum +ve
• Having signs and symptoms
• Miliary TB or CXR
• TBM
General instructions
• Continue breastfeeding
• Give BCG at birth
• Separation not needed
• Follow-up both mother and child

71. Discontinue breastfeeding + separation
• Mother so sick to need admission
• MDR TB suspected
• Proven default
• Sputum +ve mother not put on ATT

73. TB and HIV
• 60% of PLHA develop TB
• 16-18% of children with TB have HIV
• Active TB is commonest OI among HIV infected individuals
Diagnosis of TB in HIV infected children
3 or more of following
• Chronic symptoms s/o TB
• Physical signs s/o TB
• CXR s/o TB
• Positive Mx >5 mm induration

74. Problems in treatment
• Potential for drug interactions, esp. b/w rifampicin and anti-
retroviral agents
• Problems of drug toxicity and adverse effects
• IRIS
• Pill burden, adherence
Key therapeutic principles
• Treatment of TB takes precedence over t/t of HIV infection
• In pts already on HAART, continue same with modification
in both HAART and ATT
• If pt. not receiving HAART, timing of initiation of ART
decided on basis of immune suppression and CD4 counts
and type of TB

75. WHO recommends ART be given to
• All pts with extrapulmonary TB (stage 4)
• All those with pulm TB unless CD4 count >350 cells/mm3
• ART recurrence and fatality rates in TB
Classification of HIV-associated immunodeficiency in
children
Classification of
HIV-associated
immunodeficiency
Age-related CD4 values
11 months
(%)
12-35
months (%)
35-59
months (%)
5 years
(cells/mm3)
Not significant >35 >30 >25 >500
Mild 30-35 25-30 20-25 350-499
Advanced 25-30 20-25 15-20 200-349
Severe <25 <20 <15 <200

76. Initiation of first-line ART in relation to anti-TB therapy
WHO pediatric
clinical stage
Timing of ART following
start of anti-TB t/t
Recommended ART regimen
4 (extrapulm TB
other than LN
TB)
Start ART soon after anti-TB
t/t (b/w 2 & 8 wks following
start of anti-TB t/t)
In children aged <3 yrs
• preferred: triple NRTI first line
regimen – d4T or AZT + 3 TC
+ ABC
• Alternative: standard first-line
regimen – two NRTIs + NVP
In children aged 3 yrs
• Preferred: triple NRTI first-line
regimen – two d4T or AZT +
3TC + ABC
• Alternative: standard firstline-
line regimen – two NRTIs +
EFV
3 (pulm TB and
LN TB)
With clinical management
alone
•Start ART soon after start of
anti-TB t/t (b/w 2-8 wks
following start of ATT)
•Consider delaying start of
ART until anti-TB t/t is
completed – if excellent
clinical response to ATT in first
2-8 wks and child is stable

77. WHO pediatric
clinical stage
Timing of ART following
start of anti-TB t/t
Recommended ART regimen
3 (pulm TB and
LN TB)
When CD4 values are
available
• Severe immunodeficiency
CD4 <200 – start ART b/w 2-
8 wks as soon as ATT
tolerated
• Advanced immunodeficiency
(CD4 200-350) – start ART 8
wks after starting ATT
• Mild or no immunodeficiency
(CD4 >350) – consider
delaying start of ART until
ATT completed
Regimens as recommended
above

78. • EF V is not currently recommended for <3 yrs / <10 kg and
not given to postpubertal adolescent girls who are sexually
active and not using contraception
ART recommendations for pts who develop TB within 6
months of starting a first-line ART regimen
1st line or 2nd
line ART
regimen
ART regimen at the time of
TB occurs
Management options
1st line ART (AZT or D4T) + 3TC + EFV Continue with two NRTIs + EFV
(AZT or D4T) + 3TC + NVP Substitute NVP with EFV, or
Substitute with triple NRTI
regimen
AZT + 3TC + TDF Continue with triple NRTI
regimen
2nd line ART Two NRTIs + PI Substitute or continue with LPV/r
– containing regimen and adjust
the dose of RTV

79. Immune reconstitution inflammatory syndrome
• Characterised by clinical deterioration after initial
improvement
• Occurs in 1/3rd of pts on ATT who have started ART
• Presents within 3 months of ART initiation
• Fever, worsening of pre-existing LAP + resp disease
• Most cases resolve without intervention
• Serious reactions may require use of steroids
ART failure
• If TB occurs within 6 months of initiation of ART, it should
not be considered as failure of t/t
• If episode occurs after 6 months of ART, with no other
clinical / immunological evidence of disease progression, it
should not be considered ART failure
• Extrapulm TB should be considered ART failure

80. Drug interactions and toxicity
• Thiacetazone is contraindicated in HIV pts
• HIV pts more prone to develop INH induced peripheral
neuritis therefore given pyridoxine supplementation
• Both ATT and NVP – cause hepatotoxicity  close
monitoring needed
• Rifampicin induces cyt p450 enzymes and reduces conc of
PI by 80%, NVP level by 20-58%, EFV level by 25%
• PI resistant mutants of HIV may emerge if unboosted PIs
are used with rifampicin

81. Chemoprophylaxis (6HR)
• All HIV pts with MTx >5 mm given prophylaxis
• Also in anergic pts exposed to active TB
BCG vaccination
• WHO recommends all asymptomatic HIV infected children
should receive BCG except those with symptoms of AIDS
related complex / AIDS. This is especially true for high TB
prevalent countries like India
• BCG should not be given to HIV-infected children in low TB
prevalence countries