The document provides recommendations for the management of pediatric tuberculosis. It discusses the need to revise guidelines given new evidence on appropriate drug dosages in children. The key recommendations are: 1) Dosage amounts for common antituberculosis drugs like isoniazid, rifampicin, and pyrazinamide. 2) A four-drug regimen for 2 months followed by a two-drug regimen for 4 months is recommended for children in high HIV/drug resistance settings or those with extensive lung disease. 3) A three-drug regimen for 2 months followed by a two-drug regimen for 4 months can be used for other children with suspected pulmonary TB or lymph node TB and low HIV/drug

1. MANAGEMENT OF PEDIATRIC TUBERCULOSIS..
WHAT’S NEW??
DR. PUJA JAIN
SR, PEDIATRICS,FEHJ

2. INTRODUCTION
 Tuberculosis is a single major infectious disease
causing significant morbidity and mortality in
children.
 Children account for approx 40% of all cases of
tuberculosis being treated.
 Confirmation of the disease is difficult in children
because of paucibacillary nature of the disease and
difficulty in obtaining the sputum.
 Therefore most cases of pediatric TB are
categorized as either sputum smear negative PTB
or extra pulmonary TB cases, which are not
recorded and reported by NTPS.

3. NEED FOR REVISION??
 Since the publication of the Guidance in
2006, novel evidence has become available
concerning the correct dosages of medicines for the
treatment of tuberculosis in children.
 The aim of this revised guideline is to establish
standards for high-quality treatment of tuberculosis
in children by providing evidence-based
recommendations while considering the risks and
benefits, acceptability, feasibility, cost and financial
implications.

4. WHAT DO THEY SAY?? THE RECOMMENDATIONS..

5. GUIDING PRINCIPLES
1. Do no harm
 Introducing changes that preserve access for those
children who are sickest and most in need.
2. Ensure access and equity
 Ensuring that all children with tuberculosis have access
to treatment with fair and equitable distribution of
diagnostic and treatment services.
3. Promote quality and efficiency
 Delivering the highest standards of care within a public
health approach so as to achieve the greatest health
impact with the optimal use of available human and
financial resources.
4. Ensure sustainability
 Understanding the long-term consequences of change
with the vision of providing continued access to anti-TB
medicines for those in need.

6. PULMONARY TUBERCULOSIS WHEN TO SUSPECT??
 Fever and cough of recent onset > 2weeks duration.
 Recent loss of appetite, recent loss of weight .
 h/o contact.
 Presence of risk factors- h/o measles/whooping
cough ,immunocompromised states.
 Persistent lower respiratory infection not responding
to antibiotic therapy.
 No role of therapeutic trial with anti-TB drugs.

8. INVESTIGATIONS

9. TUBERCULIN TEST
o 1,2,or 5TU. (RT23)
o I.D , wheal of6mm
o Read after 48-72hrs by palpatory /
ballpoint pen method.
o >10 mm induration is positive
o 72hrs-7days- positive test can still be read.
o Positive test s/o tuberculosis, negative test
does not rule it out.

10. CHEST RADIOGRAPH
 Chest radiograph merely localizes the site of pathology
and not etiology.
 There are no pathognomonic radiological signs of
tuberculosis.
 In relevant clinical setting, certain radiological lesions may
strongly suggest tuberculosis and they include
 miliary, hilar or paratracheal lymphadenopathy with or
without parenchymal involvement.
 Fibrocaceous cavitatory lesions.

11. CONT..
 Rarely chest X-ray may be normal, such cases
should be referred to an appropriate center for
further detailed investigations if the clinical
suspicion is high.
 In clinical practice, non-resolving chest shadows
despite adequate antibiotic therapy in a
symptomatic child raises the possibility of
tuberculosis.
 all persistent radiological lesions are not
necessarily due to TB.
 Imaging like USG and CT are helpful in estimating
pleural fluid collection.

12. BACTERIOLOGY
 Demonstration of AFB from any body fluid or tissue
is the gold standard for diagnosis.
 Sputum positivity rate is 33%.
 Early morning gastric aspirate after 4-6hrs overnight
fasting.
 Induction of sputum with 3% hypertonic saline
nebulization.
 ZN stain can reveal only >10,000 bacilli/ml.
 Culture methods available are- LJ media, bactec
and non radiometric methods.

13. SERODIAGNOSTICS
 Non specific.
 Not recommended in the diagnosis of tuberculosis.

14. INTERFERON GAMMA RELEASE ASSAYS
 A newer generation of tests which measure the
production of interferon gamma by the peripheral
mononuclear cells have been developed to identify
the patients with TB disease or latent infection.
 These use two antigens, early secretion antigen
target (ESAT 6) and culture filtrate protein 10
(CFP10), which are specifically present only in
Mycobacterium tuberculosis and not in other
mycobateria or the BCG vaccine strain.

15. CONT..
 These tests though have a principle similar to skin
test but do away with the need for a repeat visit by
the patient for reading purposes.
 Quantiferon Gold and T spot are two of the
commercially available IGRAs.
 These are being used in place of the skin test in low
prevalence countries to detect latent TB infection.
 However, these expensive tests do not differentiate
the TB infection from disease.
 Its exact utility in high burden situation is still not
clear.

16. PCR TEST
 PCR cannot differentiate living from dead bacilli and
continues to be positive even after successful
treatment.
 PCR is positive in 95% to 100 % of culture positive
cases but only in 50% to 60% of culture negative
cases.
 It may be false positive in 1% to 30% of cases.
 Thus, no decisions can be made only on the basis
of PCR tests and hence these tests are not
recommended in clinical practice.

17. TUBERCULOSIS LYMPHADENITIS
 Clinical correlate of diagnosis includes progressive
enlargement of lymph node for more than 2 weeks,
firm, minimally tender or non-tender, fluctuating,
further may get matted and develop chronic sinus
formation.
 Mantoux test is positive in a significant proportion.
 Fine needle aspiration cytology (FNAC)is usually
adequate for accurate diagnosis and it correlates
well with biopsy in >90% of cases.

18. CONT..
 Histopathology, typically shows necrosis and
epitheloid granuloma.
 It is important to look for AFB in FNAC specimen
and it may be positive in 20-70% of patients.
 When FNAC is inconclusive, biopsy is necessary for
confirmation of diagnosis.
 In children lymphadenopathy is common due to
recurrent tonsillitis and upper respiratory tract
infections.
 Reactive lymphadenitis may clinically mimic
tuberculosis but do not warrant anti-TB drugs.
 Hence, anti-TB drugs should not be given unless
the diagnosis of TB is confirmed by FNAC or
histopathology.

20. TUBERCULOSIS MENINGITIS
 Typically CSF is clear, usually does not show very
high cell count (under 500 cells/cumm) with
lymphocytosis.
 Biochemical investigations reveal increased proteins
and mild reduction in glucose.
 The typical CSF picture described above can also be
mimicked by partially treated pyogenic meningitis. In
such a situation, CSF can be repeated after 48-72
hours of treatment with a fresh set of broad spectrum
potent antibiotics to evaluate change in clinical status
as well as in CSF

21. CONT..
 During this time, efforts are made to establish the
diagnosis by collecting more evidence using
PPD, chest skiagrams, and bacteriological
diagnosis from appropriate samples including CSF.
 Many a time concomitant TB lesions elsewhere in
the body co-exist and can clinch the diagnosis.
 Mycobacterial culture from CSF should also be
attempted but CSF culture has poor sensitivity
(16%) though specificity is high (90%).

22. CONT..
 Neuroimaging is an important diagnostic modality. It
may reveal one or more of the following findings:
 Basal meningeal enhancement;
 Hydrocephalus with or without peri-ventricular ooze;
 Tuberculoma(s); or infarcts may be seen in different
areas, especially in basal ganglia.
 Normal CT scan does not rule out TBM and in case
of strong clinical suspicion of diagnosis, a repeat
follow-up CT scan after few days may show

23. TUBERCULOMA
 Often seen in older children, it may present as a
focal seizure in supra-tentorial cortical lesion or with
symptoms and signs of raised intracranial tension
with multiple localizing signs and hydrocephalus in
posterior fossa lesion.
 It may sometimes also be seen as a part of TB
meningitis.

24. CONT..
 Differentiation from other ring lesions,especially
neurocysticercosis (NCC) is difficult incortical
lesion.
 A ring enhancing lesion is not pathognomonic of
tuberculoma.
 A larger lesion >20 mm, disc lesion or ring lesion
with thicker rim with central nodule favors
tuberculoma; while multiple, smaller, thin rim with
epicentric nodule favor NCC.
 MR spectroscopy may help in diagnosis of
tuberculoma as it shows lipid peak.

25. ABDOMINAL TUBERCULOSIS
 It may present as localized disease such as
mesenteric lymphadenopathy, intestinal
disease, peritoneal involvement or systemic
disseminated disease presenting as
hepatosplenomegaly.
 Large matted lymph node mass may be clinically
evident and ultrasound guided biopsy may help in
confirming the diagnosis.

26. CONT..
 Echogenic thickened mesentery with lymph nodes
>15mm in size.
 dilated and matted bowel loops.
 thickened omentum, and ascites.
 Barium follow-through examination may be
suggestive of intestinal disease but is not
confirmatory.
 Exudative peritoneal disease presents as ascites
that is often clinically evident.
 The ascetic tap should always be done in such
situations and the fluid tapped is an
exudate, typically showing lymphocytic predominant
cellular response with high proteins (>3g/dL

27. PRINCIPLES OF TREATMENT
 The combination regimens used to treat active
disease aim to eliminate actively replicating and
dormant or near-dormant mycobateria using a
combination of drugs with different actions whilst
preventing the emergence of drug-resistant
organisms, and all being achieved with a minimum
of toxicity.
 Bactericidal drugs that kill actively metabolizing and
replicating organisms are important to achieve a
rapid reduction in microbial load which leads to
clinical improvement, contains disease progression
and terminates transmission.

28. CONT..
 Isoniazid (H) and rifampicin (R) are important first-
line bactericidal drugs with isoniazid having the
most potent early bactericidal activity.
 Sterilizing drugs aim to eradicate those organisms
that are less active metabolically and those that are
in an acidic environment in order to prevent
relapse.

29. CONT..
 Rifampicin and pyrazinamide (Z) are important first-
line sterilizing drugs.
 Protection against emergence of drug-resistant
organisms is achieved by the combination of
effective early bactericidal activity to reduce
microbial load combined with effective sterilizing
activity of more slowly replicating organisms, and
strengthened by the addition of a fourth drug such
as ethambutol or steptomycin.

30. CONT..
 The most common TB diagnostic category in
children is smear-negative PTB and so the
commonest regimen used in children is 2HRZ 4HR.
 A fourth drug is important for cure of disease with a
large microbial load such as sputum smear-positive
PTB or PTB with extensive parenchymal
involvement, and to reduce the risk of development
of drug-resistance.
 The recommended treatment of TB meningitis and
osteoarticular TB are also under review and 12
months regimen is the preferred option.

31. CONT..
 The WHO guidelines of 2003 included 6HE as an
alternative to 4HR for the continuation phase of
new patient regimens.
 Rifampicin is important in the continuation phase to
kill slowly metabolizing organisms whilst isoniazid is
less potent for bactericidal activity in that context
and when combined with rifampicin, is added to
provide protection against drug resistance.
 relapse was more common in those in the 6HE arm
than for those in the 4HR.
 4HR is now the only recommended option for the
continuation phase.

32. A WORD ABOUT ETHAMBUTOL.
 Studies show that toxicity is related to the dose
and duration of therapy.
 WHO-ethambutol is safe and the risk of toxicity
negligible for children of all ages if the
recommended dosages were adhered to.
 Further, the abovementioned removal of 6HE as an
alternative to 4HR for the continuation phase also
reduces the potential of toxicity because duration of
ethambutol usage is now usually limited to the
initiation phase of two months.

33. ROLE OF STERIODS
 Definite indications for concomitant steroid therapy
 TBM and pericarditis.
 Steroids are routinely not indicated in lymphadenitis
and pleural effusion.
 They may be used in endobronchial tuberculosis or
mediastinal compression syndrome due
totuberculosis, pleurisy with severe distress
andmiliary disease with alveolo-capillary block.
 Predinsone 2-4 mg/kg/d or its equivalent is used
for2-4 weeks and then tapered over next 2 weeks.

40. RECOMMENDATIONS
Recommendation 1
 Given the risk of drug-induced hepatotoxicity, WHO
recommends the following dosages of
antituberculosis medicines for the treatment of
tuberculosis in children:
 Isoniazid (H) – 10 mg/kg (range 10–15 mg/kg);
maximum dose 300 mg/day
 Rifampicin (R) – 15 mg/kg (range 10–20 mg/kg);
maximum dose 600 mg/day
 Pyrazinamide (Z) – 35 mg/kg (30–40 mg/kg)
 Ethambutol (E) – 20 mg/kg (15–25 mg/kg)
 (Strong recommendation, moderate-quality
evidence)

41. RECOMMENDATION 2
Children living in settings where the
 prevalence of the HIV is high or
 where resistance to isoniazid is high,
 or both,
 with suspected or confirmed pulmonary
tuberculosis or peripheral lymphadenitis;
 or children with extensive pulmonary disease living
in settings of low HIV prevalence or low isoniazid
resistance
 should be treated with a four-drug regimen (HRZE)
for 2 months followed by a two-drug regimen (HR)
for 4 months at the following dosages

42. CONT..
 isoniazid (H) – 10 mg/kg (range 10–15 mg/kg);
maximum dose 300 mg/day
 rifampicin (R) – 15 mg/kg (range 10–20 mg/kg);
maximum dose 600 mg/day
 pyrazinamide (Z) – 35 mg/kg (30–40 mg/kg)
 ethambutol (E) – 20 mg/kg (15-25 mg/kg)
 (Strong recommendation, moderate-quality
evidence)
 High prevalence is defined as countries, sub
national administrative units, or selected
facilities, where the HIV prevalence among adult
pregnant women is ≥1% or among TB patients is
≥5%.

43. RECOMMENDATION 3
 Children with suspected or confirmed
 Pulmonary tuberculosis or
 Tuberculous peripheral lymphadenitis
 with low HIV prevalence
 low resistance to isoniazid
 children who are HIV-negative can be treated with a
three drug regimen (HRZ) for 2 months followed by
a two-drug (HR) regimen for 4 months

44. CONT..
Dosages:
 isoniazid (H) – 10 mg/kg (range 10–15 mg/kg);
maximum dose 300 mg/day
 rifampicin (R) – 15 mg/kg (range 10–20 mg/kg);
maximum dose 600 mg/day
 pyrazinamide (Z) – 35 mg/kg (30–40 mg/kg)
 (Strong recommendation, moderate-quality
evidence)

45. RECOMMENDATION 4
 Children with suspected or confirmed pulmonary
tuberculosis or tuberculous peripheral lymphadenitis
living in settings with high HIV prevalence (or with
confirmed HIV infection) should not be treated with
intermittent regimens (that is, twice-weekly or thrice-
weekly doses).
 (Strong recommendation, low-to-moderate-
quality evidence against the use of intermittent
treatment in children)

46. RECOMMENDATION 5
 During the continuation phase of treatment, thrice-
weekly regimens can be considered for children
known to be HIV-uninfected living in settings with
well-established directly-observed therapy (DOT).
 (Weak recommendation, very low-quality
evidence for use of intermittent treatment in
children in specific settings)

47. RECOMMENDATION 6
 Infants (aged 0–3 months) with suspected or
confirmed pulmonary tuberculosis or tuberculous
peripheral lymphadenitis should be promptly treated
with the standard treatment regimens, as described
above.
 (Strong recommendation, low-quality evidence)

48. RECOMMENDATION 7
 Streptomycin should not be used as part of first-line
treatment regimens for children with
 pulmonary tuberculosis or
 tuberculous peripheral lymphadenitis.
 (Strong recommendation, moderate-quality
evidence).

49. RECOMMENDATION 8
 Children with suspected or confirmed tuberculous
meningitis should be treated with a
 four-drug regimen (HRZE) for 2 months, followed
by a two-drug regimen (HR) for10 months; the total
duration of treatment being 12 months.
 The dosages recommended for the treatment of
tuberculous meningitis are the same as those
described for pulmonary tuberculosis.
 (Strong recommendation, low-quality evidence)

50. RECOMMENDATION 9
 Children with suspected or confirmed osteoarticular
tuberculosis should be treated with a four-drug
regimen (HRZE) for 2 months followed by a two-
drug regimen (HR) for 10 months; the total duration
of treatment being 12 months.
 The doses recommended for the treatment of
osteoarticular tuberculosis are the same as those
described for pulmonary tuberculosis.
 (Strong recommendation, low-quality evidence)

51. RECOMMENDATION 10
 Children with proven or suspected pulmonary
tuberculosis or tuberculous meningitis caused by
multiple drug-resistant bacilli can be treated with a
fluoroquinolone in the context of a well-functioning
MDR-TB control programme and within an
appropriate MDR-TB regimen.
 The decision to treat should be taken by a clinician
experienced in managing paediatric tuberculosis.
 (Strong recommendation, very low-quality
evidence)

52. CHEMOPROPHYLAXIS
 Six months of chemopropylaxis is recommended for
all under 6 years age contacts of an
infectiouscase, irrespective of their BCG or
nutritional status.
 PPD positive children over 6 years of age and who
donot have any evidence of active disease but are
planned for immunosuppressive therapy
(e.g.children with nephrotic syndrome, acute
leukemias, etc) may also be given the benefit of
chemoprophylaxis.
 While there is evidence that HR combination can
make the prophylaxis shorter (3months) but the
group does not recommend this dueto the risk of
misuse of rifampicin.

54. THANK YOU