Report of National Consultation On Diagnosis and Treatment of Pediatric TB
Report of National Consultation On Diagnosis and Treatment of Pediatric TB
Report of National Consultation On Diagnosis and Treatment of Pediatric TB
The National consultation on diagnosis and treatment of pediatric TB was conducted on 31st
January 2012 and 1st February 2012 at LRS Institute of TB and Respiratory Diseases with the
following objectives:
To review the evidence base and advances in pediatric TB diagnosis and treatment
The list of the participants who attended the consultation and the agenda of the meeting
isannexed at the end of the report. After extensive deliberations and detailed discussions on
various issues related to the management of tuberculosis in children, the following key decisions
were taken.
1. Diagnosis of Pediatric TB*:A new diagnostic algorithm was developed for pulmonary
TB and the commonest type of extra pulmonary TB (Lymph node TB) addressing the
concerns of RNTCP and pediatricians. For other types of extra-pulmonary TB, it was
decided that the existing guidelines in the IAP consensus statement 2010 would be
adopted and used in RNTCP.
a. The pulmonary TB suspect and Lymph Node (LN) TB suspect definitions were
revisited and amended for greater clarity and updated guidance. Clear definitions
of weight loss/no weight gain were agreed upon. Loss of weight was defined as
a loss of more than 5% of the highest weight recorded in the past three
months.The algorithms for the diagnosis of pulmonary TB and Lymph node
tuberculosis are provided in Annexure 1. The consultation accepted to derive the
guidelines for diagnosis of other types of extra pulmonary TB from the existing
IAP guidelines (Detailed at Annexure 1).
b. The group recommended that all efforts should be made to demonstrate
bacteriological evidence for the diagnosis of pediatric TB. In cases where sputum
is not available for examination or sputum microscopy fails to demonstrate AFB,
alternative specimens (Gastric lavage, Induced sputum, broncho-alveolar lavage)
should be collected, depending upon the feasibility, under the supervision of a
pediatrician. It was decided that RNTCP will enhance the capacity of the
microscopy centres at the district hospital to process these alternative samples.
*0-14 years
2. Intermittent versus Daily regimen: The available scientific evidence, advantages and
disadvantages, risks and benefits were deliberated extensively and it was decided that
intermittent therapy will remain the mainstay of treating pediatric patients till emergence
of evidence against this mode of therapy. The group agreed that the missing doses in
thrice weekly regime can adversely affect its efficacy. The group also emphasized that
amongseriously ill admitted children or those with severe disseminated disease/neurotuberculosis, the likelihood of vomiting or non-tolerance of oral drugs is high in the
initial phase. There was, therefore, an agreement that this select group of seriously ill
admitted patients should be givendailysupervised therapy during their stay in the
hospitalusing daily drug dosages.After discharge they will be taken on thrice weekly
DOT regimen (with suitable modification to thrice weekly dosages). The mechanism to
make the necessary drugs available would be developed by RNTCP.
The group identified the urgent need to generate data on intermittent versus daily
therapy.Though there is no strong evidence, anecdotal clinical experiences and initial
findings from pharmacokinetic studies conducted at National Institute for Research on
Tuberculosis (NIRT) suggest that daily TB treatment may be of benefit in HIV-infected
children, at least in the intensive phase. This issue was widely debated, though, a
consensus could not be achieved; this issue was flagged as an issue of concern which
requires further discussion in future meetings involving pediatricians involved in care of
HIV-infected children.
3. Case definitions for pediatric patients were discussed and it was agreed that following
definitions will be incorporated in the RNTCP manuals.
a. Failure to respond: A case of pediatric TB who fails to have bacteriological
conversion to negative status or fails to respond clinically / or deteriorates after 12
weeks of compliant intensive phase shall be deemed to have failed response
provided alternative diagnoses/ reasons for nonresponse have been ruled out.
b. Relapse: A case of pediatric TB declared cured/completed therapy in past and has
(clinical or bacteriological)evidenceof recurrence.
c. Treatment after default: A case of pediatric TB who has taken treatment for at
least 4 weeks and comes after interruption of treatment for 2 months or more and
has active disease (clinical or bacteriological).
3
more, above the upper limit of the existing weight band. The group also agreed upon the
following daily doses (mg per kg of body weight per day) Rifampicin 10-12 mg/kg (max
600mg/day), Isoniazid 10mg/kg (max 300mg/day), Ethambutol 20-25mg/kg (max
1500mg/day), PZA 30-35mg/kg (max 2000mg/day) and Streptomycin 15 mg/kg (max
1gm/day).
5. Drug formulations: Since the number of tablets is too many to consume and younger
patients have difficulty in swallowing tablets,the group strongly recommended using
dispersible tablet formulations under the programme.In the interim, DOT centres will
be provided with pestle and mortars for crushing the drugs. It will be the responsibility of
the DOT provider to supervise the process of drug consumption by the child and in case
any child vomits within half an hour of period of observation, fresh dosages for all the
drugs vomited will be provided to the caregiver. The issue of using fixed dose
combinations (FDC) under RNTCP was debated, but a consensus could not be reached
due to concerns on bioavailability of individual drugs in FDC especially Rifampicin. This
was flagged for further discussions in future meetings.
6. Cat III regimen: Though, there is utility of Cat III regimen in some pediatric TB cases,
in view of: the fact that the programme has already implemented the new treatment
categories; evidence of a relatively high INH resistance in studies from NIRT and
increasing evidence of safety of Ethambutol in the doses used under RNTCP, the group
agreed that the decision of abolishing Cat III need not be revisited. Hence, there will be
only two treatment categories one for treating new cases and another for treating
previously treated cases. The treatment regimens are summarized in Annexure 2 (Table
3).
7. TB Meningitis (TBM) : The group felt that Streptomycin can be safely replaced by
Ethambutol in intensive phase of TBMbecause of (a) current evidence favoring safety
and efficacy of Ethambutol, (b) lack of any value addition in efficacy using Streptomycin
over Ethambutol, and (c) need to avoidproblems of injection based treatment (lack of
adequate muscle mass in malnourished, risks of unsafe Injections, need for a trained
personnel, unpleasantness of the treatment). While ethambutol was considered a better
option than streptomycin in the treatment of new cases of childhood TB, streptomycin
continues to be recommended as the additional fifth drug in the retreatment regime.
8. Extending intensive and continuation phase: Children who show poor or no response
at 8 weeks of intensive phase shouldbe given benefit of extension of IP for one more
month. In patients with TB Meningitis, spinal TB,miliary/disseminated TB and osteoarticular TB, the continuation phase shall be extended by 3 months making the total
duration of treatment to a total of 9 months. It may be further extened for 3 more months
in continuation phase (making the total duration of treatment to 12 months) on a case to
case basis in case of delayed response and at the discretion of the treating physician/
pediatrician.
9. Making DOT patient-friendly: The group recommended that RNTCP may explore and
pilot test the feasibility and effectiveness of alternate approaches like Mother or care
giver at home as DOT provider in selected areas and if found useful can be accepted as
strategy and scaled up.
10. TB preventive therapy: The dose of INH for chemoprophylaxis was recommended to be
10 mg/kg (instead of currently recommended dosage of 5 mg/kg) administered daily for 6
months. TB preventive therapy should be provided to:
a. All asymptomatic contacts (under 6 years of age) of a smear positive case, after
ruling out active disease and irrespective of their BCG or nutritional status.
b. Chemoprophylaxis is also recommended for all HIV infected children who either
had a known exposure to an infectious TB case or are Tuberculin skin test (TST)
positive (>=5mm induration) but have no active TB disease.
c. All TST positive children who are receiving immunosuppressive therapy (e.g.
Children with nephrotic syndrome, acute leukemia, etc.).
d. A child born to mother who was diagnosed to have TB in pregnancy should
receive prophylaxis for 6 months, provided congenital TB has been ruled out.
BCG vaccination can be given at birth even if INH chemoprophylaxis is planned.
The suggestion of introducing syrup formulations for infants due to difficulty in breaking
tablets was debated. Given issues of bioavailability in syrup formulations and in the light
of increased dose, it was decided to manage with 100 mg tablets instead of syrup
Annexure 1
Diagnostic Algorithm for Pediatric Pulmonary Tb
Flowchart 1
AND/ OR
AND / OR
Sputum Examination
Child has:
1. Already received a complete course of
appropriate antibiotics, OR
2. Sick look,
OR
3. Severe Respiratory Distress, OR
4. Any other reason for X-Ray chest
Yes
Smear positive
No
Follow Flowchart 2
Smear negative
History of unexplained weight loss or no weight gain in past 3 months; Loss of weight defined as loss of more than 5% body weight as compared to
highest weight recorded in last 3 months.
2
Radiological changes highlysuggestive of TB are Hilar/paratracheal lymphadenitis with or without parenchymal lesion, Miliary TB, fibrocavitary
pneumonia,.
3
If the radiological picture is highly suggestive of TB, then proceed to do further investigations irrespective of the TST result as the sensitivity of the
test is not 100%.
4
All efforts including Gastric Lavage (GL)/ Induced sputum (IS) or Bronchoalveolar lavage (BAL) should be made to look for Acid fast bacilli (AFB)
1
depending upon the facilities.
Annexure 1
Flowchart 2
Further investigations in Pediatric pulmonary TB suspect who HAS PERSISTENT
SYMPTOMS and does not have highly suggestive Chest skiagram
XRC Normal
TST Negative
Review for an
alternative diagnosis
XRCNormal
TST positive
YES,
Give Specific therapy
NO
Smear positive
Smear negative
Annexure 1
When to suspect pulmonary TB?
The above flowcharts depict the diagnostic algorithm for childhood pulmonary TB. Fever and / or
cough of recent onset lasting for > 2 weeks should arouse suspicion of tuberculosis. It is important to
document fever and not depend merely on impression. Fever can be of any type and the oftendescribed evening rise of temperature is neither specific to this etiology.
Cough can be dry or moist and may be severe. Cough persisting beyond 2 weeks, particularly as an
only symptom in an otherwise healthy child can be due to viral infection and is often not due to TB.
Such children, therefore, do not always warrantextensive investigations. As cough and fever are
otherwise also common, it is the unabated persistence of these symptoms for over 2 weeks which
makes TB more likely. Recurrent symptoms with normal intervening period are less likely to be due
to tuberculosis.
Recent unexplained loss of weight is an important pointer to the suspicion of tuberculosis.
History of exposure to an infectious TB patient (smear positive) should always prompt detailed
examination for presence of the disease. However, in a symptomatic child, contact with a person with
any form of active tuberculosis within last two years may be significant as many a times there can be
a coexisting pulmonary involvement which went unrecognized due to lack of chest symptoms.
Diagnosis is also more likely in presence of risk factors such as recent history of measles or
whooping cough and immunocompromised state including steroid therapy. TB remains an important
cause of persistent pneumonia not responding to antibiotic therapy in our country.
Significant superficial lymphadenopathy must be specially looked for, as it may often coexist.
Diagnosis of tuberculosis can never be reliably made only on clinical features. The subject with
abovementioned clinical features- in isolation or in combination -is only a TB suspect. Further
investigations are always necessary to establish the diagnosis. Therapeutic trial with anti-TB drugs is
therefore, not recommended and instead every attempt must be made to prove the diagnosis.
Bacteriology
Demonstration of AFB from any body fluid or tissue is confirmatory of tuberculosis. Such a proof is
often lacking in childhood tuberculosis because of difficulty in collection of sputum and due to
paucibacillary primary disease in children. However, studies do report that the yield of a positive test
in advanced cases may be as high as in adults. Therefore, every attempt must be made to
bacteriologically prove the diagnosis in every case of suspected tuberculosis.
Sputum smear examination is the primary investigation of choice if sputum specimen is available
from the child. If sputum smear is positive, patient is diagnosed as smear positive pulmonary TB and
should be initiated on TB treatment.
If sputum smear is negative or not available, then the patient is prescribed a course of antibiotics for
duration of seven days, and in case symptoms persist, Chest X-ray and Tuberculin skin test (TST /
Mantoux test) should be performed. Care should to be taken to use antibiotics which do not have
anti-TB activity.Fluoroquinolones should not be used as antibiotics at this point in time. In case the
symptoms continue unabated despite antibiotics, then chest X-ray and TST should be done.
However, in a sick looking or distressed child with persistent symptoms of >2weeks duration, chest
skiagram and TST test should be performed immediately along with other workup for non-TB
infections.
Annexure 1
Even where the XRC is highly suggestive of TB (Hilar/paratracheal lymphadenitis with or without
parenchymal lesion, Miliary TB, fibrocavitary pneumonia) AND TST is positive, an attempt should
be made for establishing bacteriological diagnosis using alternative specimens like Gastric Lavage
(GL)/ Induced sputum (IS) or Bronchoalveolar lavage (BAL) depending on the facilities available.
Given that the sensitivity of TST is not 100%, in any case with highly suggestive radiology, one must
attempt bacteriological diagnosis (as mentioned above) even if the TST is negative. Based on the
bacteriological results, case may be labeled as smear positive or negative TB and treated
appropriately.
Inpediatric pulmonary TB suspect who HAS PERSISTENT SYMPTOMS and / or non-specific
radiological shadows but efforts for a bacteriological diagnosis havefailed, further investigative
scheme is detailed in Flowchart 2. It is broadly divided into three possible situations.
1. If both TST and X-ray findings are negative, then TB is highly unlikely and an alternative
diagnosis should be looked for.
2. In situations where the CXR has persistence of non-specificshadows despite a course of
antibiotics, alternative samples for TB (GA/IS/BAL) should be sent to establish
bacteriological diagnosis irrespective of the TSTpositivity.In case the alternative sample is
AFB positive, then classify and treat as smear positive case. In case these samples are
negative, then an alternative diagnosis should be diligently looked for. If no alternative
diagnosis is established, the case may be classified and treated as smear negative TB.
3. If only TST is positive and X-ray chest is not suggestive, then look forTB at an extrapulmonarysite or an alternative diagnosis. Cases with persistent symptoms with TST positive
but no evidence of TB at pulmonary/ extra-pulmonary site thus far, often need expert help
and detailed investigations like CT chest, etc.
Bacteriological Investigations using following alternative specimens can be attempted:
1. Early morning gastric aspirate is a preferred specimen for most young children with
suspected TB for detecting AFB or isolating Mycobacterium tuberculosis. The child is kept
fasting for about 6 hours (at night) and an appropriate size intra-gastric tube is passed in the
morning. Initially the aspirate is drawn from the stomach and then a further washing with 1530 mL saline is taken. The contents so recovered are then immediately transferred to the
laboratory. This specimen can also be collected as an ambulatory procedure after 4-6 hours
fasting with some loss of yield.
2. Sputum collection is possible in older children with extensive and cavitatory disease,
particularly if the patient has a wet cough.
3. Induction of sputum by 3% nebulized hypertonic saline can be tried in other children. The
patient is pretreated with nebulized bronchodilators like salbutamol prior to induction.
Following saline nebulisation, chest physiotherapy is done to loosen up the secretion and the
samples are collected from the throat or nasopharynx using a collector attached to a suctionat
one end and a catheter/tube to the other. The suction catheter provokes cough and the
secretions brought up are collected via suction.
4. Bronchial washings / bronchoalveolar lavage (BAL) can also be used as a diagnostic tool
though the availability is limited. Bronchoscopy and BAL is often needed for evaluatingcases
of persistent pneumonia. Sometimes, there may be a co-existent peripheral lymphadenopathy,
which is easily accessible and the aspirates from these can be used for bacteriological/
cytological diagnosis.
The experience shows that one needs to collect at least two samples of whatever type of the
respiratory specimens one decides to choose to get the optimal yield. If the facilities are limited,
these tests may be prioritized and atleast be done in all children with wet cough or children who have
definite parenchymal lesion on chest skiagram.
Annexure 1
Ziehl-Neelsen stain can reveal AFB only if sample contains > 10,000 bacilli per ml. Various culture
methods such as LJ medium, Radiometric (Bactec) and Non-radiometric (MGIT) can be used for
confirming diagnosis in paucibacillary state. The newer methods are capable of giving faster results
and may be used if available. Mycobacterial culture and drug sensitivity assumes special significance
in case of suspected drug resistance and should be attempted in cases needing retreatment
(particularly the defaulters and failures but preferably in all cases).
Radiology
Chest radiograph merely localizes the site of pathology and does not define 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, pleural effusion and
fibrocaseouscavitatory lesions. Rarely chest X-ray may be normal, such cases should be referred to
an appropriate center for further detailed investigations, if the clinical suspicion and epidemiological
risk (e.g. close contact of an infectious case, etc.) is high. In clinical practice, non-resolving chest
shadows despite adequate antibiotic therapy in a symptomatic child raises the possibility of
tuberculosis. It is worth mentioning that all persistent radiological lesions are not necessarily due to
TB. Asymptomatic patients may have persistent shadows due to parenchymal scarring, pleural
thickening, and healed fibro-atelectatic changes. On the other hand, a child with bronchiectasis or an
interstitial lung disease may have presence of non-resolving shadows with persistent symptoms.
Ultrasonography of chest is helpful to assess pleural fluid collection; although decubitus chest Xray
film may also reveal similar information.
CT scan is rarely necessary and is not cost and radiation effective. ChestCT scan, however, may
offer an opportunity for CT guided biopsy for tissue diagnosis.
Tuberculin test
The standard tuberculin skin test recommended for use is the Mantouxs test. Commercially available
tuberculin in the country are of the strength of 1, 2 and 5 Tuberculin Unit (TU) PPD (RT23
equivalent). It is important to raise a wheal of about 6 mm after the intra-dermal injection and the
test is read 48-72 hours after an injection. Ballpoint or palpatory methods are used to read the
induration. The width of reaction (induration) in the horizontal plane is noted for interpretation.
Mantouxs test or PPD skin test is considered positive if the induration is 10 mm or more. This
cutoff was recommended using a 1 TU PPD RT23. It is recommended that the 10mm cutoff may
be continued to use for strengths of PPD only up to 5TU, however,2TU PPD RT23 was
considered to be the most suitable strength. In no case strength higher than 5 TU should be used.
Degree of reaction, including necrosis and ulceration, may not necessarily differentiate infected from
diseased. Prior BCG vaccine has minimal influence on PPD reaction.
If the patient returns for reading beyond 72 hours but by 7th day, a positive test can still be read. A
repeat test may be needed, if there is an induration less than 10mm and the suspect reports for
reading beyond the stipulated time of 72hours post injection.Repeat tuberculin test when required
should preferably be done on the other arm. The reading of the repeat test should be interpreted as in
any other individual.
Status of othertests in vogue for diagnosing active tuberculosis in children:
Annexure 1
1. BCG Test: BCG test is not recommended in diagnosis of tuberculosis.
2. Serodiagnostic Tests: As mycobacterial antigens overlap in different stages of infection and
disease, there are no specific antigens that can confirm natural infection or active disease.
Commercial antigen tests are not easily available or well evaluated. Commercial TB
antibody tests share similar problems of interpretation and as they cannot differentiate natural
infection from BCG vaccine induced infection and active disease from old healed disease.
These tests are not recommended for use.
3. Interferon Gamma Release Assays (IGRAs): Newer generations 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 (CFP 10), which are
specifically present only in mycobacterium tuberculosis and not in other mycobateria or the
BCG vaccine strain. 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.QuantiferonGoldTM and TspotTM 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. Theexact advantage of these tests in
high burden situation is still not clear. Hence, these are not recommended for use in the
diagnostic algorithm for Tuberculosis in India.
4. PCR Tests and Gene Expert : The inhouse Nucleic acid amplification tests (NAAT) and
several commercial tests have poor sensitivity for diagnosing TB in smear negative samples.
The laboratory contamination is a real risk. Thesetests are, therefore, not recommended for
the diagnosis of childhood TB. NAATs are preferred for rapid identification of the culture
isolates rather than using them directly over clinical specimens.
However, Heminested, cartridge based real time PCR marketed as Xpert MTB/RIF is now
endorsed by WHO as a likely point of care test using clinical specimens. This may be used,
where available, particularly in previously treated cases or cases who are contacts of chronic/
MDR TB adults. The test has ability to detect Mtb as well as rifampin resistance in a matter
ofhours. Being cartridge based, real time technology, and the risk of cross contamination is
also less. The utility of this test for extra-pulmonary specimens is being established.
Extra-pulmonary Tuberculosis
TB lymphadenitis
This is most common form of extra pulmonary tuberculosis. Clinical correlate of diagnosis includes
progressive enlargement of lymph node for more than 2 weeks, firm, minimally tender or not tender,
sometimesfluctuating, may be matted and may have chronic sinus formation.
The diagnostic algorithm is shown below. Fine needle aspiration cytology (FNAC) is usually
adequate for accurate diagnosis and it correlates well with biopsy in >90% of cases. 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 URIs as well. Such reactive lymphadenitis may clinically mimic tuberculosis but does
not warrant anti-TB drugs. Persistent lymphadenopathy of significant size (say more than 2cm in the
neck) should however, be investigated.TST is mostly positive in a significant proportion, but isolated
skin test positivity is not enough to establish a diagnosis of TB. Hence anti-TB drugs should not be
given unless the diagnosis of TB is confirmed by FNAC or histopathology.
Annexure 1
Smear examination for AFB by ZN Staining of the pus from discharging sinus / aspirate from lymph node
Aspirate for fine needle aspiration for cytology (FNAC), where facilities exist.
Treat as Case
Pleural Effusion
If chest X-ray is suggestive of pleural effusion, pleural aspiration should always be performed for
biochemical, cytologicaland smear examination by ZN stain to confirm the diagnosis. Typically, a
tubercular effusion fluid is straw colored (pus, if aspirated, is very rarely due to TB etiology) has
large numbers of cells (in hundreds; predominantly mononuclear), with high proteins (>3g/dL).
Adenosine Deaminase (ADA) levels over 60 IU/L may be suggestive of tuberculous pleural effusion
but is not diagnostic of TB.Pleural biopsy may be performed, where available, particularly when the
fluid aspirate findings are inconclusive.
Tubercular meningitis (TBM)
Children with TBM present with a rather longer (>1 week) duration of fever, with vague CNS
symptoms such as behavior changes, irritability, drowsiness, headache, vomiting and seizures.
Physical examination reveals typically global encephalopathy with focal deficits, hydrocephalus and
movement disorder. Risk factors for TBM include age < 5 years, contact with an adult suffering from
tuberculosis, PEM grade III and IV, and HIV infection.
Annexure 1
1. Typically CSF is clear to opalescent, usually does not show very high cell count (under 500
cells/mm3) with lymphocytosis. Biochemical investigations reveal increased proteins and mild
reduction in glucose. The typical CSF picture may, however, not always be seen. Furthermore,
the typical CSF picture described above can also be mimicked by partially treated pyogenic
meningitis. In such a situation, reassessing after 48-72 hours of treatment with a fresh set of
broad spectrum potent antibiotics to evaluate improvement in clinical status as well as in CSF
can be useful.
2. Efforts should be made to establish the diagnosis by collecting more supportive evidence using
TST, chest skiagrams. Bacteriological diagnosis from appropriate samples including CSF is
diagnostic. Many a time concomitant TB lesions elsewhere in the body (say, pulmonary) coexist 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%).
3. 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.
4. 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 newly developing lesions. CSF
abnormalities in TBM may take variable time up to few months to return to normal.
5. Besides routine CSF examination, CSF ADA is high in TBM. Various studies have a cut-off
point between 7 and 11.3 IU/L for diagnosis. This may offer supportive evidence in favor of
TBM but should not be taken in isolation.
6. CSF antigen and PCR tests are neither routinely available nor reproducible. They are, therefore,
not recommended. CSF antibody tests have poor sensitivity and specificity and hence are not
useful.
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. Differentiation from
other ring lesions, especially neurocysticercosis (NCC) is difficult in cortical 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.
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.
1. There are no standard guidelines for sonography diagnosis of abdominal tuberculosis.
However, corroborative evidence includes: echogenic thickened mesentery with lymph nodes
> 15mm in size; dilated and matted bowel loops; thickened omentum, and ascites. None of
these findings, however, is specific to TB alone.
2. Barium follow-through examination may be suggestive of intestinal disease but is not
confirmatory.
3. Exudative peritoneal disease presents as ascites that is often clinically evident. The ascitic 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).
******
Annexure 2
Table 1: New weight bands and generic patient wise boxes with drug dosage delivered and pill burden
Body
Weight
INH
PZA
6
7
8
100
100
100
100
100
100
250
250
250
9
10
11
12
150
150
150
150
150
150
150
150
400
400
400
400
13
14
15
16
200
200
200
200
200
200
200
200
500
500
500
500
17
18
19
20
250
250
250
250
250
250
250
250
650
650
650
650
21
22
23
24
300
300
300
300
300
300
300
300
750
750
750
750
25
26
27
28
29
30
400
400
400
400
400
400
400
400
400
400
400
400
1000
1000
1000
1000
1000
1000
ETB
Product 1
200
200
200
Product 2
300
300
300
300
Product 3
400
400
400
400
Product
1+2
500
500
500
500
Product
2+2
600
600
600
600
Product
3+3
800
800
800
800
800
800
PILL BURDEN
3 drug
individual
FDC
drugs
2 drug
FDC
17
14
13
17
14
13
42
36
31
33
29
25
3
3
3
2
2
2
4
4
4
17
15
14
13
17
15
14
13
44
40
36
33
33
30
27
25
3
3
3
3
2
2
2
2
4
4
4
4
15
14
13
13
15
14
13
13
38
36
33
31
31
29
27
25
3
3
3
3
2
2
2
2
4
4
4
4
15
14
13
13
15
14
13
13
38
36
34
33
29
28
26
25
6
6
6
6
4
4
4
4
8
8
8
8
14
14
13
13
14
14
13
13
36
34
33
31
29
27
26
25
6
6
6
6
4
4
4
4
8
8
8
8
16
15
15
14
14
13
16
15
15
14
14
13
40
38
37
36
34
33
32
31
30
29
28
27
6
6
6
6
6
6
4
4
4
4
4
4
8
8
8
8
8
8
Annexure 2
Table 2: Revised Dosing and Weight bands according to existing Pediatric Patient wise boxes (PWB)
Weight
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
New
PC13
PC13
PC13 + half of PC13
PC13 + half of PC13
PC13 + half of PC13
PC13 + half of PC13
PC14
PC14
PC14
PC14
PC14 + half of PC13
PC14 + half of PC13
PC14 + PC13
PC14 + PC13
PC14 + PC13
PC14 + PC13
PC14 + PC13
PC14
PC14
PC14
PC14
PC14
PC14
PC14
PC14
Tab
1
1
1.5
1.5
1.5
1.5
1
1
1
1
1 +1/2
1 +1/2
1 each
1 each
1 each
1 each
1 each
2
2
2
2
2
2
2
2
Rif delr
75
75
112.5
112.5
112.5
112.5
150
150
150
150
187.5
187.5
225
225
225
225
225
300
300
300
300
300
300
300
300
INH delr
75
75
112.5
112.5
112.5
112.5
150
150
150
150
187.5
187.5
225
225
225
225
225
300
300
300
300
300
300
300
300
PZA delr
250
250
375
375
375
375
500
500
500
500
625
625
750
750
750
750
750
1000
1000
1000
1000
1000
1000
1000
1000
ETHAM delr
200
200
300
300
300
300
400
400
400
400
500
500
600
600
600
600
600
800
800
800
800
800
800
800
800
RIF/ kg
13
11
14
13
11
10
13
12
11
10
12
11
13
12
11
11
10
13
13
12
12
11
11
10
10
INH/ kg
13
11
14
13
11
10
13
12
11
10
12
11
13
12
11
11
10
13
13
12
12
11
11
10
10
PZA/ kg
42
36
47
42
38
34
42
38
36
33
39
37
42
39
38
36
34
43
42
40
38
37
36
34
33
ETHAM / kg
33
29
38
33
30
27
33
31
29
27
31
29
33
32
30
29
27
35
33
32
31
30
29
28
27
Annexure 2
TABLE 3: Treatment Categories and Regimens for Childhood Tuberculosis
Category of treatment
Type of patients
TB treatment regimens
Intensive phase
Continuation phase
New cases
2H3R3Z3E3*
4H3R3
2S3H3R3Z3E3
+1H3R3Z3E3
5H3R3E3
Annexure 2
In patients with TB meningitis on Category I treatment, the four drugs used during the intensive phase can either be HRZE or HRZS.
The present evidence suggests that Ethambutol can be used in children.
Children who show poor or no response at 8 weeks of intensive phase may be given benefit of extension of IP for one more month.
In patients with TB Meningitis, spinal TB, miliary/disseminated TB and osteoarticular TB, the continuation phase shall be extended
by 3 months making the total duration of treatment to a total of 9 months. A further extension may be done for 3 more months in
continuation phase (making the total duration of treatment to 12 months) on a case to case basis in case of delayed response and
as per the discretion of the treating physician.
Under Revised National Tuberculosis Program (RNTCP, all patients shall be covered under directly observed intermittent (thrice
weekly) therapy. The supervised therapy is considered as the most optimal treatment and is followed under RNTCP. It is important
to ensure completion of treatment in every case put on treatment to prevent emergence of resistance, particularly to Rifampicin. In
the rare circumstances where a patient is given daily therapy, observation and completion of therapy remains as important. It is
the duty of the prescriber to ensure appropriate and complete treatment in all cases.
Scientific research
Disease burden (Epidemiology)
1. Determine prospectively the incidence of childhood TB in different communities making use of
standardized consensus diagnostic criteria.
a. Geographically representative
b. covering all age groups (014) and socioeconomic strata
c. pulmonary (smearpositive and smearnegative) and extrapulmonary TB
d. HIVinfection
e. drugresistance
2. Epidemiologic studies (classical and molecular epidemiology) to study TB transmission in
community
3. Carry out a prospective evaluation of the incidence of disseminated BCG disease (in HIV high
prevalence districts)
Diagnosis
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Treatment
1. Investigate shorter, childfriendly regimen for both, infection and disease
2. Pharmacokinetic studies with newly revised RNTCP dosage schedule all ages, HIV positive and
neg, types of TB
3. Pharmacokinetic studies of secondline drugs.
a. Population PK (follow cohorts)
b. Outcomes important to document
4. Study drugdrug interactions and drug toxicity, particularly in HIVinfected children who
frequently receive multiple drugs other than antituberculosis agents.
5. Evaluate rates of treatment failure and recurrence (disaggregated by HIV status): multicentric
cohort study
6. Standard 6 month therapy: daily versus intermittent
7. Pilot the new dosing recommendations
8. Evaluate 3 and 4month treatment regimens in paucibacillary forms of childhood TB
9. Evaluate necessity for longer periods of treatment in HIVinfected children.
10. Participate in trials of new TB drugs/regimens
Prevention
1. Development of Vaccines to prevent infection and disease in children and adults
2. Assess the accuracy of classification of cases as smearpositive pulmonary TB, smear negative
pulmonary TB and extrapulmonary TB, and the quality of management of cases.
3. Carry out epidemiological studies to determine the numbers of HIVinfected and noninfected
children in contact with both sputum smearpositive and smear negative adults, both HIV
infected and noninfected, who might qualify for chemoprophylaxis in different communities.
4. Assess the value of standard isoniazid prophylaxis and compare it to shorter multidrug
chemoprophylaxis in both HIVinfected and noninfected children.
5. Contact Tracing and Chemoprophylaxis
6. Study the effectiveness different strategies (treatment card, new register, training etc) for
improving contacttracing and chemoprophylaxis in children document outcomes
7. Collaborate in the establishment of vaccine trial sites for the evaluation of new TB vaccines.
Agenda
31st January 2012 (Tuesday)
Day 1
09.00 09.30
09.30 10.00
Registration
INAUGURAL SESSION
Welcome and Objectives
Address
Address
Address
Vote of thanks
10.00 10.30
SESSION 1:
OVERVIEW OF NATIONAL AND
GLOBAL GUIDELINES
Rapporteur: Dr. Ajay Kumar MV, CTD
Overview of Pediatric TB
management under RNTCP
Achievements and Challenges
10.30 11.00
11.00 11.30
11.30 12.00
Tea Break
SESSION 2:
DIAGNOSIS OF PEDIATRIC TB
Rapporteur:
Dr GR Sethi, Professor of Pediatrics,
LNJP, Delhi
Chairs:
Dr. D Behera, Director, LRS
Dr Piyush Gupta, Editor-in-chief, Indian
Pediatrics
Dr. RajeswarDayal, Professor of
Pediatrics, Agra
12.0012.30
12.30 13.00
13.0014.00
Lunch Break
SESSION 3:
TREATMENT OF PEDIATRIC TB
Rapporteur:
Dr GR Sethi, Professor of Pediatrics,
LNJP, Delhi
Chairs:
Dr. SoumyaSwaminathan, Senior
Deputy Director, NIRT
14.0014.30
14.30 14.40
14.40-15.00
15.00 15.30
15.30 16.00
16.00 17.00
17.30 20.30
Day 2
09.30 10.00
SESSION 3:
RECOMMENDATIONS TO RNTCP
Chairs:
Dr. Ashok Kumar, DDG-TB
Dr. SoumyaSwaminathan, NIRT
10.00 11.00
11.00 11.30
11.30 12.15
11.30 13.00
13.00 14.00
LunchBreak
14:00
14:30
14:30
15:00
15.00 15.30
15.30 16.30
Discussion
TeaBreak
Open Forum Discussion on any other
issues
Summary and Next steps
Name
Designation
Dr Ashok Kumar
Dr Devesh Gupta
Dr
SoumyaSwaminathan
Dr
GeethaRamachandran
DDGTB, Central TB
Division, Dte.GHS,
MoHFW
Addnl DDGTB, Central
TB Division, Dte.GHS,
MoHFW
Senior Grade Deputy
Director, NIRT, Chennai
Researcher in
Pharmacokinetics,
NIRT, Chennai
Director, LRS Institute
of TB and respiratory
diseases
Director, National TB
Institute
[email protected];
[email protected];
[email protected]
[email protected]
contact phone
number
01123063226
01123062781 /
09811033031
9444057478
[email protected];
[email protected]
04428369648 /
09790835712
Fax no:044
28362528
9790835712
Dr D Behera
Dr Prahlad Kumar
Dr Sangeeta Sharma
Dr Varinder Singh
Dr RakeshLodha
10
Dr SushilKabra
11
Dr Rewari BB
NPOART, NACO
12
Dr Rohit C Agarwal
Mumbai (IAPpresident)
13
Dr GR Sethi
14
15
Dr PuneetDewan
Dr Sreenivas A
16
17
18
Dr
RanjaniRamachandran
Dr Ajay Kumar MV
Dr. Santosh K. Talwar
Professor of Pediatrics,
LNJP, Delhi
MOTB, SEARO
NPOTB, WHOIndia
Office
MOTB Labs, SEARO
19
Dr. BhaskarShenoy
08023362431/
2344119293/
09341262352
9341262352 /
08023362431
9899666510
[email protected];
[email protected]
[email protected]
[email protected]
[email protected]
01126593621 /
09868397533
01126594610 /
Fax no:011
26588941
01143616667 /
09811267610
Fax no: 011
26429099
02225153643/
02225133062/
09821096353
01127867019,
9968604305
9871389967
9313058578
9650296363
[email protected]
[email protected]
9311384574
01123061175
08025023263 /
09845036174
Fax no:080
25266757
S.No
Name
Designation
20
Professor Pediatrics,
PGIMER Chandigarh
21
Dr RajeshwarDayal
22
Dr KiranRade
9810104609
23
Dr Piyush Gupta
9811597172
24
Dr AnandVasudev
Prof &HODpediatrics,
SN Medical College
Agra
Consultant
Epidemiologist, Central
TB Division
Editor in chief, Indian
Pediatrics
Executive Officer, IAP
contact phone
number
01722755306 /
9914208306,
9814117152
9837022899
25
Dr. RohitSarin
[email protected]
[email protected]
26
Dr. RupakSingla
27
DTCD.MD.FNCCP
Vice chairman
Tuberculosis
Association of India
MBBS, MD, DNB Head,
Deptt. Of TB & chest
Diseases
CST Dvsn , NACO
01122779484 /
09811074973
01126517827 /
01126854922
Fax no:011
26568227
01126517826/30
Fax no:011
26517834
9720192030