RNTCP Pediatric Guidelines 2019

RNTCP Updated
Pediatric TB
Guidelines 2019
Developed by
REVISED NATIONAL TUBERCULOSIS CONTROL
PROGRAM and
INDIAN ACADEMY OF PEDIATRICS
Guidance document
Draft as on 04th February 2019
Central TB Division, Ministry of Health and Family Welfare,

New Delhi, India.
Draft Updated IAP RNTCP Ped TB Guidelines 2019
Contents
Chapter 1 - Magnitude of problem ......................................................................................................... 2
Chapter 2 - Natural history of disease .................................................................................................... 4
Chapter 3 - Case Definitions TB ............................................................................................................ 10
Chapter 4 - Diagnosis of TB in Children................................................................................................. 11
Skin Test for TB ............................................................................................................................. 14
Chest Radiograph .......................................................................................................................... 15
Bacteriological Diagnosis .............................................................................................................. 16
Diagnosis of Extra pulmonary TB (EPTB) ........................................................................................... 18
Pleural effusion ............................................................................................................................. 20
Abdominal TB ................................................................................................................................ 21
Neurological TB ............................................................................................................................. 22
Bone and Joint TB.......................................................................................................................... 26
Chapter 5 - Treatment of Tuberculosis ................................................................................................. 28
Basis of pharmacotherapy ................................................................................................................ 28
Anti-tubercular therapy .................................................................................................................... 28
Pyridoxine Supplementation ............................................................................................................ 32
Monitoring and Follow up................................................................................................................. 32
Paradoxical upgrading reactions ................................................................................................... 37
Chapter 6 -TB in special situations ........................................................................................................ 38
Drug Resistant TB including MDR ..................................................................................................... 38
Management of TB with HIV co-infection ........................................................................................ 48
MANAGEMENT OF A NEONATE BORN TO A MOTHER WITH TUBERCULOSIS .................................. 56
Chapter 7 - PREVENTION OF TB ............................................................................................................ 59
Contact screening ............................................................................................................................. 59
Isoniazid Preventive Therapy ............................................................................................................ 60
BCG VACCINATION ............................................................................................................................ 61
Chapter 8 - Programme Management .................................................................................................. 65
Annexure 1 Tuberculin Skin test (TST) .......................................................................................... 69
Annexure 2: Method to collect gastric aspirate ........................................................................... 72
Annexure 3: Method to collect induced sputum .......................................................................... 73
Annexure 4: Needle aspiration of LN and similar swellings .......................................................... 75
Annexure 5 Treatment Recommendation for Delamanid in Children:......................................... 76
Annexure 6 Nikshay Poshan Yojana Scheme ……………………………………………………………………………80
Annexure 7 Private provider incentive …………………………………………………………………………… 83
1
Chapter 1 - Magnitude of problem
Global TB report 2018 reports that in India, an estimated 2.2 lakh children become ill with
tuberculosis (TB) each year (22% of global TB burden), with a slightly higher burden among
males. Pulmonary TB is the most common form in children but the extra-pulmonary TB forms
a larger proportion of cases than in adults. It is also known that about 10% of the cases
reported to RNTCP are from children under 14 years of age.
Challenges of managing Paediatric TB in public health
Childhood Tuberculosis (TB) is a formidable problem. Although the principles of

diagnosis and treatment remain the same in child and adults, yet the dissimilarities in the
pathology and the host bring up challenges when dealing with pediatric TB. Just as children
are not miniature adults, the TB among children is also not a miniature version of the adult
form. Adults and older children more often have the infectious form of TB which can be
detected by testing of sputum while in general, children have forms of TB which may be more
easily picked up on chest radiograph. Children upto 14 years constitute about 35% of the
population in our country and are expected to contribute about 10% of the case load. There
are many more numbers of adults presenting with TB as the adulthood span is far longer.
Furthermore, the disease in adults is more often infectious; and death due to TB among adult
bread winners constitutes a major catastrophe for the rest of the family including children.
Pulmonary TB in adults is relatively easier to diagnose due to their capacity to bring up sputum
which can be subjected to a simple and low-cost test like sputum smear examination which
also has much better sensitivity in this age group. Therefore, the desirous focus of any TB
control activity thus is largely oriented towards adult disease in mind and the efforts for
inclusion of the children are largely concerted around retrofitting the pediatric management
pathways over the much-established algorithms for adult TB. Difficulty to access the specimen
as children would more often swallow then bring up sputum and lower sensitivity of the
microbiological tests in children further add to this difficulty.
The general child survival strategies are expectedly focussed around the diseases with
highest mortality among the under-five and they include Pre-mature birth, perinatal asphyxia
and injuries, Pneumonia and Diarrhoea. (WHO & MCEE 2017). About 10% of these are due
to other causes, of which one cause is TB. Mycobacterium perhaps is one singular organism
contributing to most death of under-five among world’s middle & lower-income nations, but
it does not find place in the list of causes of death as it is difficult to diagnose and there is a
large detection gap. Exact contribution by TB to ‘Under 5 Mortality’ is unknown. Many TB
related deaths are possibly reported as pneumonia deaths due to similar respiratory
symptoms and autopsy studies from some African nations support this contention.
2
Focus on Children with TB thus seems to be lost somewhere between the two
stakeholders differing priorities. Though vertical approach for TB is providing singular
expertise for the disease but the pprogrammatic focus is oriented towards adults focusing on
controlling the pool of infectious cases and heavily relying on smear microscopy. The program
is usually retrofitting the adult type strategies to children with same disease but a different
problem e.g. the diagnostic strategies of the children and adults antithesis to each other i.e.
smear to radiology vs radiology to smear.
Lack of standard definitions, absence of simple/reliable diagnostic test and more EP

TB cases add to lack of data on pediatric TB. There is also gross under estimation of magnitude
of problem. It’s contribution to child mortality is lost as there are difficulties in its diagnosis.
TB remains in the penumbra due to missed diagnosis in SAM and ALRI. Sophistication of
diagnosis makes it difficult to decentralize the diagnosis to community level. These challenges
have led to a poor coordination between child survival strategies and TB control.
Since the global strategy has shifted to achieving ‘Zero death by TB’, this obviously
cannot happen without adding focus to TB in children. Countries are reporting on average 7%
cases of TB among children, mostly clinically diagnosed and EP. Numbers may be low as many
children are treated outside National TB programmes. RNTCP treats children reporting to
them and has introduced child -friendly dispersible FDC medication in 2017 to ensure
treatment compliance. Consistently about 6-7% of all patients treated under RNTCP annually
are children with TB. There are some variations in the reporting across different states which
may be reflection of the differences in burden of disease, health seeking behaviour and
availability of services, etc.
Current decade has perhaps witnessed most frenzied activity in the field of TB with a
renewed commitment to eliminate the disease from the world. The understanding about
disease, drug therapy and its pharmacokinetics, resistance amplification and newer
diagnostics and drugs has created an opportunity to use this knowledge for improving child
TB care in specific and child health care in particular There is a strong need for child specific
packages for TB management which are integrated with the child survival interventions. The
present updated guidelines are an effort to fast track the use of newer diagnostics and
therapy modifications for managing TB in children to achieve the goal of early diagnosis,
prompt and effective therapy so that the impact of the disease on lung health and child
mortality can be mitigated.
3
Chapter 2 - Natural history of disease

TB is a continuum which starts from susceptible to cured and each transition has a measurable
probability. TB is usually an airborne infection. It is also to be emphasized that children can
be infectious as well; especially older children and adolescents.
An imbalance between mycobacterial virulence and host immunity determines the progress
of infection/disease. It is the interaction of both these factors that would decide whether the
contacts would have an infection, whether the infection would remain latent or lead to a
primary disease and as the child grows older, reactivation of the latent infection. Risk of
progression of the TB infection to disease is about 5-10% over lifetime in a healthy individual
but this is higher in young children, nearly >50% in infants and 25% in 1-5 years. Rapid
progression can occur in presence of severe malnutrition or HIV-TB co-infection, etc. The risk
factors for TB infection and disease progression are described in the table below.
Source Case Contacts
30% 70%
Infection No Infection
Risk
5-10% lifetime
>50% in infants & 25% in 1-5 y 90-95%
Primary Disease
Persistent “Latent” No Disease
• Smear-positive: infectious Infection
• Smear-negative: can also
be Infectious Variabl
• Extra-Pulmonary Disease:
Non- Infectious
e
Late Reactivation Disease
Mycobacterial
Host Immunity
4
Table- -------Risk factors for TB infection and disease in children
For TB infection For TB disease

• Increased exposure • Young age
– Living in high TB endemic – Especially 0-2 years
communities
– Children of families living with HIV • HIV infection
– Overcrowding & poor sanitation – Risk of infection and disease
condition
– Air pollution including
environmental
– Tobacco smoke
• Source case • Other immune-suppression
– Cavitary disease /Smear positivity – Malnutrition
– Cough frequency / Cough hygiene – Post-measles, post-viral
– Delay in treatment of adult case – Diabetes
• Lack of contact screening • Lack of prophylaxis
• Contact with source case • Not BCG vaccinated
– Closeness of contact – Risk of disseminated disease with
– Duration of contact increased severity
The time for the events and complications of primary tuberculosis infection in infants and
children is fairly predictable with Wallgren Time Table of TB disease shown below. The time
table although might vary e.g. adolescents can have a primary complex.
Years 1 2 3 5 10 >10
Months 0 1 2 3 4 5 6 7 8 9 10 11 12
Immune
conversion
Primary
complex
Local lung
complications
Pleural effusion
(usually
adolescents)
Miliary /
meningeal
Bone
Skin
Secondary
breakdown
Renal
5
Younger children are the most vulnerable and can have a disseminated disease: Tubercular
meningitis (TBM), miliary, or a lymph node disease with complications. The school-going age
is the safest period. Thereafter, the risk would again increase as the second peak appears at
adolescence. They would have more of adult type disease and pleural effusions.
Childhood TB transition
Infection to disease transition in children can be a continuum and the distinction between the
two is made on the basis of presence of symptoms reaching the threshold of clinical
significance. Symptoms determine access to care and recognition as TB suspect. Based on the
transition, the disease can be classified into primary, progressive primary and secondary or
reactivation disease.
Classification of childhood TB
Primary complex can be formed at any place from where the organism enters. Primary
pulmonary involvement is the commonest (98%) and that only is being detailed further.
Primary / Progressive Primary Pulmonary tuberculosis typically manifests radiologically as
• Primary complex (Parenchymal lesion with draining lymphadenopathy)

• Consolidation with or without cavitation
• Atelectasis
• Emphysema, unilateral hyperinflation
• Pleural and/or pericardial effusion
• Miliary pattern
Primary Infection (LUNG)
Ghon’s Complex
Progress Contained
Treated
Progressive Primary
Disease
Naturally Heal
Reactivation disease
Risk much higher with natural healing as
compared to those treated
6
Three features common to primary infection are
(1) Patient may have non-specific mild symptoms which can go un-recognised,
(2) Primary lung foci are usually quite small relative to large hilar nodes, and
(3) Primary foci may resemble pneumonia & can be in any lobe Parenchymal disease in
primary TB typically involves areas of greatest ventilation e.g. middle lobe, superior
segments of lower lobes, anterior segment of upper lobes.
In primary infection, chest radiograph shows paratracheal and/or hilar nodes. There can be
associated direct signs (airway narrowing or deviation) or indirect signs of airway compression
(collapse, emphysema).
Right paratracheal node and a Parenchymal lesion is well In some cases, there might
right hilar node. seen with the associated be a consolidation but no
draining node. discernible node.
Fig Progression of a primary TB to progressive primary disease
Progression of
Ghon’s Complex
Regional LN Ghon’s Focus
Airway Partial or Complete Parenchymal Cavitation with

Involvement Obstruction Intra-Bronchial Spread
Intra Bronchial Spread

Contiguous rupture
Pleural Effusion
Pericardial Effusion
Miliary TB
Bronchopneumonic
Consolidation
Cavitation
7
Progressive primary TB usually appears as lymph node disease with airway compression; No
signs of obstruction/collapse.
The following set of chest skiagrams show the various way the Primary and progressive
primary disease can present in a child.
Airway compression. PPC and also the The PA chest x-ray shows an area of
No radiological sign compression of consolidation on the right-side lower zone
of obstruction like airway with silhouetting of the right cardiac border.
emphysema or Right lateral film of the same case is
collapse. showing the shadow in the middle lobe area
overlying the cardiac shadow.
The x-ray shows a Parenchymal cavitation with TB suspect with Miliary

lymph node shadow Consolidation shadows is highly
in the aorto suggestive of TB in the
pulmonary window Indian set up
with an
accompanying area
of consolidation
Reactivation or Post Primary tuberculosis
It is a disease of adolescence and adulthood. 50%- 90% of TB cases result from reactivation of
a previously dormant primary infection. Usually, it has a predilection for apical or posterior
segment of upper lobes or superior segment of lower lobes. It usually appears as focal or
patchy heterogeneous consolidation, consolidation with cavitation or pleural extension.
Tuberculomas are also seen but rare.
8
An area of consolidation in the left upper Extensive disease with multiple areas of
lobe with a cavity inside breakdown, more on the left side
It is important to remember that classifications of primary and reactivation TB (also referred

to as post-primary TB), which have been shown to be inaccurate and confusing. In settings in
which TB is endemic, the first infection is likely to occur in childhood but is unlikely to be a
single lifetime event. In all likelihood, ongoing TB transmission within endemic areas would
result in repeated episodes of infection. More recent studies have shown the reinfection is as
frequent as re-activation in endemic settings and therefore a preferred terminology may be
recurrent disease instead of labelling all of these as reactivation disease. Cavitary TB may be
a manifestation of recent primary infection or, more commonly in endemic settings, of re-
infection. From a management point of view, the important distinction is between cavitary
and noncavitary disease because the presence of cavities correlates with organism load,
treatment outcome, risk of acquiring drug resistance, and infection risk posed to the
community.
9
Chapter 3 - Case Definitions TB
Presumptive Paediatric TB: refers to children with persistent fever and/or cough for more
than 2 weeks, loss of weight*/no weight gain and/ or history of contact with infectious TB
cases**
*History of unexplained weight loss or no weight gain in past 3 months; loss of weight is
defined as loss of more than 5% body weight as compared to highest weight recorded in last
3 months.
** In a symptomatic child, contact with a person with any form of active TB within last 2 years
may be significant.
Presumptive Extra Pulmonary TB: refers to the presence of organ specific symptoms and
signs like swelling of lymph nodes, pain & swelling in joints, neck stiffness, disorientation etc
and/or constitutional symptoms like significant weight loss, persistent fever for >_2 weeks,
night sweats.
Presumptive DR TB: refers to those TB patients who have failed treatment with first line
drugs, paediatric TB non-responders, TB patients who are contact of DR-TB (or Rif resistance).
TB patients who are found positive on any follow up sputum smear examination during
treatment with first line drugs, previously treated TB cases, and, TB patients with HIV co-
infection.
10
Chapter 4 - Diagnosis of TB in Children
The conventional gold standard for the diagnosis of TB is demonstration of AFB on smear or
isolation of M.Tb on culture of an appropriate specimen. However, the performance of this
tool in primary TB and among children is poor. Cartridge based nucleic acid amplification test
(CBNAAT) have been the game changer as they have far higher sensitivity than smear and it
almost reaches the culture. While CBNAAT is a good test yet it fails to pick nearly a half of the
cases overall. In the absence of any other alternative fool proof, easy, patient friendly
diagnostic tool, the diagnosis of TB in children is often based on the combination of indirect
clues like suggestive symptomatology, suggestive radiology, history of contact, and positive
TST in combination.
In children with presumptive paediatric TB, every attempt must be made to microbiologically
prove diagnosis through examination of appropriate respiratory/non-respiratory specimens
with quality assured diagnostic tests.
• Diagnosis of tuberculosis should not be made only on clinical features and further
investigations are always necessary to establish diagnosis.
• In case of suspicion of pulmonary TB, sputum examination for Mtb using CBNAAT.
should be carried out among children who are able to give quality specimens
• CBNAAT is the preferred investigation of choice over smear examination but its best
yield as a test is when it is not ordered based on chest symptoms but on the basis of a
positive chest skiagram.
• If CBNAAT is not readily available or testing is not possible even by referral, smear
microscopic to be performed.
• For CBNAAT and LPA, only one specimen should be collected. LPA can be performed
directly on sputum specimen if it is smear positive or on culture isolates of specimens
which were negative on microscopy. Additional sample may be used for determining
the resistance to additional drugs.
• If M. Tuberculosis is detected by either of methods, child is diagnosed as
microbiologically confirmed pulmonary TB.
• If M. Tuberculosis is not detected or specimen is not available, diagnosis is inferred
from Chest X-Ray (CXR) and Tuberculin Skin Test (TST) by Mantoux technique using 2
TU of PPD RT23.
• Children with non-specific radiological shadows with a negative gastric
aspirate/induced sputum (GA/IS) by CBNAAT, should be sent for specialist opinion for
further evaluation as these children could have a large range of differential diagnosis
• All children with TB should be offered HIV testing
11
Diagnostic algorithm for paediatric pulmonary TB
• Persistent Fever >2wk, without a known cause and/or

Algorithm for • Unremitting Cough for >2w and/or
Pediatric • Wt loss of 5% in 3m or no wt gain in past 3 months or Poor weight gain despite nutritional
Pulmonary TB rehabilitation in children with SAM
among children • Contact with patient with Pulmonary TB in past 2 years
with no risk
Chest X-ray & Skin test for TB1,2
factors for drug
resistance
CXR Non specific CXR Normal CXR Normal
CXR highly shadows4 Skin Test - ve
Skin Test + ve
suggestive3
Microbiologically
Expectorated sputum/ Give course of
confirmed TB Case
GA/IS for WRDT5 Antibiotics6
Evaluate for EPTB

Refer to expert
WRDT -ve Persistent shadow
WRDT -ve and symptoms
Skin Test + ve Skin Test - ve Look for
WRDT alternate
cause
+ ve Refer to
Expert Expectorated sputum/
GA/IS for WRDT
Skin test +ve/-ve
No other likely alternative diagnosis
Clinically Diagnosed TB case Refer to expert
for work up of
WRDT WRDT
persistent
+ ve -ve pneumonia
HIV testing should be offered to all children with diagnosed TB 106
Draft Guidelines as on 04.02.19
12
Important Notes to the Algorithm

1. Chest X-ray shall be done upfront in cases who are TB Suspects. This is a major change
from the earlier guidelines. If a recent good quality chest x-ray is available, it need not be
repeated.
2. The term Skin test for TB has been used instead of TST to cover any newer skin tests like
C-TB which might be available in near future.
3. Highly suggestive Chest X-ray refers to a) Miliary shadows, b) Lymphadenopathy (hilar or
mediastinal), or c) Chronic fibro-cavitary shadows.
4. Non-Specific Chest X-ray refer to patterns other than highly suggestive like consolidations,
in-homogenous shadows or bronchopneumonia, etc.
5. WHO approved Rapid diagnostic tests (WRDT) shall be preferred over smear examination
in all children?
a) When a child cannot self-expectorate and invasive methods are used for accessing
specimen, the specimen should be divided into two aliquots and one of them is
submitted for WRDT (Smear, if WRDT not available)
b) Available WRDT include CB NAAT, LPA and LAMP.
c) Whenever smear is used for diagnosis at least 2 samples should be tested while a
single sample is sufficient for more sensitive WRDT.
d) If a specimen is positive by any of these methods, the disease is labelled as
microbiologically confirmed TB.
e) At the initial step, if self-expectorated sputum is available and imaging is not
available or delayed, smear may be done (for ease of availability and low cost).
f) If a specimen is negative by WRDT (or smear), the second aliquot or a fresh
specimen should be submitted for liquid culture
6. Antibiotics of choice include amoxycillin or co-Amoxyclav. Antibiotics like Linezolid or any
quinolone should not be used as they have anti-TB action. In case antibiotic trial has
already been done in adequate dose and duration, it may not be repeated.
Proper characterization of symptoms is a very important starting point. Weight loss or not
gaining weight should always be documented with appropriate and proper weighing. The
patient should always be weighed with minimal clothing and without shoes using a tared
scale. Highly suggestive chest X-ray findings refer to skiagrams showing either military
13
mottling or lymphadenopathy (hilar or mediastinal) or chronic fibro-cavitatory shadows. If

radiological picture is highly suggestive of TB, then proceed to do further investigations
irrespective of the TST results as the sensitivity of the test is not 100%. In patients with non-
specific shadows like consolidations, in-homogenous shadows or bronchopneumonia, etc. a
trial of antibiotics like Amoxycillin should be given before microbiological testing for TB.
CBNAAT is the initial test of choice for microbiological confirmation. A good sputum sample
consists of recently discharged material from the bronchial tree with minimum amount of
oral or nasopharyngeal material, presence of mucoid or mucopurulent material and should
be 2-5 ml in volume. It should be collected in a sterile container after rinsing of the oral cavity
with clean water. The collected specimens should be transported to the laboratory as soon
as possible after collection. If delay is unavoidable, the specimens should be refrigerated up
to one week to inhibit the growth of unwanted micro-organisms. In case the patient does not
spontaneously expectorate, any other available respiratory specimen like Gastric lavage/
Induced sputum/ broncho-alveolar lavage can be collected by a skilled health care provider,
depending upon available infrastructure and sample should be subjected to CBNAAT.
Many children with TB may have concomitant extra-pulmonary disease. Specimen form the
EP site can also be used to establish diagnosis. No preservative should be used for any extra-
pulmonary specimen for culture. Necessary instructions are to be given to the concerned staff
for sending the biopsy specimen in normal saline for culture and not in ‘FORMALIN’’ as it kills
bacilli.
Children with persistent symptoms, non-specific shadows and negative results of smears and
other samples (GA/IS) by CB NAAT should be referred to experts for further work up of
persistent pneumonia. For new patients (those who do not fit in the definition of presumptive
DR-TB case) diagnosed as TB with RR by CBNAAT, a second test will be offered along with
liquid culture DST. However, it is expected that the newer generation CBNAAT e.g. Xpert
Ultra™, which has better performance, will not necessitate retesting for RR in a new case.
Skin Test for TB

The term skin testing has been used instead of TST since newer skin tests like C-TB might be
available in near future.
Tuberculin Skin Test is an intra-dermal injection of PPD. It is an immunological test which
elicits delayed type hypersensitivity. A positive test indicates present or past infection with
MTB but cannot distinguish infection from disease. TST is used as adjunct to other tests; in
the diagnosis of TB- has the same connotation as history of contact, screen children exposed
to TB or at increased risk of M. tuberculosis infection among contact with people with
contagious TB and HIV-infected children. TST is given as an intra-dermal injection and is the
recommended skin test while evaluating a child with presumptive TB. (See Annexure 1 for TST
technique)
Current recommendation is to use 2TU PPD RT23 for all diagnostic purposes. Mantoux’s test
or PPD skin test is considered positive if the induration is 10 mm or more, In HIV co-infected
14
cases 5 mm may be taken as the cut off. Due to non-availability of 2 TU, un-standardized TST
with 5, 10 TU RT23 is in practice which can cause problems in reading of test results. Cut offs
for higher strengths are not established. Higher strengths increase false positive reactions.
The standard cut off of 10 mm can actually not be justified for any higher strength of PPD
used Instructions for administering PPD test is given in (Annexure 1). All TB cases diagnosed
must be offered testing for HIV.
There is no role for inaccurate/ inconsistent diagnostics like serology (IgM, IgG, IgA antibodies
against MTB antigens), various in-house or non-validated commercial PCR tests & BCG test.
Currently there is no role of IGRAs in clinical practice for the diagnosis of TB. ESR is another
test often used as a supportive investigation but is of no value in ruling in or ruling out the
diagnosis of TB due to its non-specificity, and possibility to be affected by many variables
other than the disease.
Chest Radiograph
Primary childhood TB being paucibacillary, makes microbiological diagnosis (gold standard)
difficult. Hence, chest radiograph is an important tool to support the diagnosis of pulmonary
TB in children in the absence of microbiological confirmation. Several factors can lead to
errors in TB diagnosis on chest radiology leading to both under & over diagnosis. Issues
associated with chest radiology includes quality of films, technical issues, inter and intra-
individual variations, and artefact thymic shadow etc.
In relevant clinical setting, certain radiological lesions may be highly suggestive of

tuberculosis: miliary pattern, hilar and/or paratracheal lymph-adenopathy with or without
parenchymal involvement and fibro-cavitatory lesions. It should be remembered that all
these patterns do have other differential diagnosis. Specificity of these radiological findings
increases in a child with TB symptoms and positive TST. All presumptive TB cases with these
radiological patterns are considered to be probable TB and should be subjected to
microbiology to confirm the diagnosis. In case microbiological investigations are negative
these children can be considered to be cases of clinically diagnosed tuberculosis (TB).
Other radiological patterns like consolidations, non-homogenous opacity/infiltrates, thin

walled cavities etc. are classified as non-specific radiology. These radiological findings if non-
resolving despite adequate antibiotic therapy in a symptomatic child, needs to be evaluated
with IS/GA for CBNAAT and if negative then, further evaluation like CT chest, flexible
bronchoscopy for persistent pneumonia are required. The differential diagnosis in such
situations is large, of which TB might be one of the possibilities. These children need to be
referred for further evaluation and a trial of ATT is not justified.
Chest radiographs after completion of anti-tubercular drugs can have post TB changes like
opacities secondary to pleural thickening, fibro-atelectatic changes or areas of bronchiectasis.
These children are usually asymptomatic except in children with post TB bronchiectasis where
15
they may show symptoms of suppurative lung disease. Such cases also need expert
evaluation.
Ultrasonography of chest is helpful to assess pleural fluid collection. It is useful to

differentiate thymus and anterior lymph nodes, and identifying best place for aspiration/
FNAC/ biopsy in a peripheral lesion. CT scan is sometimes necessary but is costly and gives
significant radiation. This should hence be used judicially and is an important tool for
evaluation of children with persistent pneumonia. Certain CT patterns can be highly
suggestive of TB although not diagnostic like necrotic mediastinal lymphadenopathy,
centrilobular nodules with tree-in-bud pattern and cavities with surrounding consolidations.
Chest CT scan, also, may offer an opportunity for CT guided biopsy for tissue diagnosis.
Bacteriological Diagnosis
Bacteriological diagnosis includes microbiological diagnosis (smear/cultures) and molecular
diagnosis (CBNAAT).
Bacteriological diagnosis is the only confirmatory method of diagnosis of TB. Smear for AFB
is a simple test with high level of agreement between observers. Though easily said but has
been difficult to achieve because of difficulty in collection of sputum and paucibacillary nature
of pediatric TB in young children leading to poor sensitivity (10% or less with most pediatric
series). Most young children are not able to expectorate sputum and alternatively the
swallowed sputum is collected from stomach after a period of fasting (usually 4-6 hrs,
preferably overnight) as gastric aspirate. Extra-pulmonary TB is a significant problem in
children which also usually is low bacillary load disease and therefore smear negative. Till
recently cultures were not routinely done, and took a long time for the result.
The felt need was to have a sample which is easy to collect and process and a test which works
even with low bacillary load in specimen and which is not very complex and can be done close
to the patient or community.
Early morning gastric aspirate is a preferred specimen for most young children with
presumptive TB. It needs overnight fasting; requires hospitalization and skilled staff. It
requires centrifugation. It must be emphasized that gastric aspirates must be collected
properly. Increasing evidence now suggest that GA can be collected in ambulatory settings
after 4-6 hours of fasting with some compromise of the yield. (annexure 2 for method to
collect gastric aspirate)
Induced sputum is another sample which can be obtained in children who are unable to
produce sputum. Induction of sputum can be easily performed in young children including
infants with acceptable yield of the sample. It does not require any pre-processing but carries
the risk of transmission to provider as it provokes cough. (annexure 3 for method to collect
induced sputum)
16
Various studies have shown that the two tests are perhaps comparable in yield to diagnosis
while some consider GA to be a better test. Studies have also shown that the yield of two
consecutive GA samples is equivalent to one GA and IS taken on the same day.
Bronchoscopy and bronchoalveolar lavage are required in select cases of persistent

pneumonia for diagnosis, performed if routine investigations for TB are inconclusive or for
children who are drug resistant TB suspects and it is useful to rule out alternative diagnosis.
One specimen positive of the two is enough to declare a patient as smear-positive. Though
no evidence is available on the optimal number of specimens of GA/GL needed for best yield,
for programmatic uniformity, this may be two samples. However now with the newer
generation tests like CBNAAT (Xpert Rif™), a single good quality specimen is adequate.
CBNAAT is a real-time PCR rapid technique for diagnosis of TB and detection of rifampicin-
resistance conferring mutations within 2 hours. CBNAAT can be performed on both
respiratory and non-respiratory specimens (GA, BAL, IS, pleural fluid, CSF, lymph node
aspirate etc). The sensitivity and specificity of CBNAAT in sputum samples is around 98% and
99% for smear positive patients and 72 % for smear negative culture positive patients. The
sensitivity and specificity on GA have been 68% and 99% respectively.
CBNAAT is now recommended in all children for diagnosis of TB. Drawback of CBNAAT
includes negative test does not rule out TB in children as the sensitivity is a little less than the
culture which itself detects about a third to about half the cases. To maximise the yield from
this useful but expensive test, it is recommended that the test is performed in samples
collected from presumptive TB cases who show a lesion on chest skiagram. The yield of the
test falls significantly to under 10%, if it is offered purely on clinical basis (symptom basis).
While it performs well with CSF and LN aspirates, its yield is very poor with pleural or ascitic
fluid.
Being a nested PCR, CBNAAT provides additional information about Rifampicin resistance in
the Mtb detected. A new paediatric TB case, diagnosed by upfront CBNAAT, without any risk
factor for DRTB is currently retested with a fresh specimen. If the repeat sample is also
showing Rifampicin resistance, then the case is classified as ‘MDR Case’. This repeat testing
perhaps will not be necessitated with newer generation Xpert Ultra™. Further, if the repeat
sample is showing Rifampin sensitive, then we start on first line drugs pending confirmation
by liquid culture.
As a gold standard for diagnosis and for phenotypic DST, currently liquid cultures like
Mycobacterium Growth Indicator tube™ (MGIT) cultures are used and recommended. These
relatively rapid cultures have replaced the traditional solid culture like LJ culture. Cultures
should be sent in all children who are CBNAAT negative and all presumptive DR TB
17
Diagnosis of Extra pulmonary TB (EPTB)

EPTB refers to any microbiologically confirmed or clinically diagnosed case of TB involving
organs other than lungs e.g. lymph nodes, pleura, bones, joints, intestine, genitourinary tract,
meninges of the brain etc.
An effort should be made to establish microbiological confirmation in case of presumptive

EPTB. Appropriate specimens from the presumed sites of involvement must be obtained from
all the presumptive EPTB patients for CBNAAT/smear microscopy/culture & DST for M. tb/
histo-pathological examination etc based on type of specimen & availability of facilities.
CBNAAT is preferred over other tests. Chest X ray, USG etc are other investigations which can
be used as supporting tools for diagnosing EPTB.
Sensitivity of CBNAAT for TB diagnosis when compared to liquid culture as a ‘Gold Standard’
is high in FNAC/biopsy specimen from lymph nodes/ other tissues and CSF but lower in
pericardial, ascetic & synovial fluid samples and still lower in pleural fluid. Result provides
useful confirmation but a negative test does not always rule out TB, since the sensitivity of
liquid culture itself in extra-pulmonary specimen is not very high.
In case CBNAAT is not available, liquid culture needs to be performed.
If investigations like CBNAAT/smear microscopy/culture etc turn out to be negative or if

appropriate specimen is not available for these investigations, consultation with a specialist
followed by other tests e.g. histo-pathology, radiology, cytology etc may be undertaken.
TB lymphadenitis
Lymph node TB is one of the most common forms of EPTB and cervical lymph nodes are the
most common site with or without associated disease of other lymphoid tissue. It usually
occurs in 5-9 years of age. The presenting features are enlarging masses over weeks to
months. Cervical lymph nodes in particular jugular, posterior triangle and supraclavicular are
affected; axillary and inguinal are involved sometimes. Systemic symptoms may be seen as
this is local manifestations of a systemic disease. TB bacilli can affect hilar and mediastinal LN
by entry through pulmonary route.
Clinical correlate of diagnosis includes progressive enlargement of lymph node for more than
2 weeks, firm, minimally tender or non-tender, with or without fluctuation, further may get
matted and develop chronic sinus formation.
Fine needle aspiration cytology (FNAC) is usually adequate for accurate diagnosis and it
correlates well with biopsy in more than 90% of cases. Histopathology, typically shows
necrosis and epithelioid granuloma. It is important to look for AFB in FNAC specimen and
smear/culture may be positive in 20-80% of patients. Xpert for MTB Rif™ yield is 35%. Pus, if
18
aspirated can be sent for CBNAAT upfront if the facility is available. CBNAAT offers advantage
as this sophisticated test if positive, decreases the need for an expert pathologist. (Annexure
4 for Needle aspiration of LN and similar swellings) When FNAC is inconclusive, biopsy and
pathologist opinion is necessary for confirmation of diagnosis.
Fig. 2 Diagnostic algorithm for tubercular lymphadenitis
Lymph node enlargement

Enlarged lymph node - Matted, of > 2 cm in one or more
cold abscess with or without a sites
discharging Sinus
Prescribe a course of antibiotics for 7

days (Do not use uinolones).
Review after 2 weeks
In case of non-response, suspect TB as the

cause for lymphadenitis
Smear examination for CBNAAT / 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
Diagnosis confirmed if the pus / aspirate If no granulomatous changes and no AFB,
from FNAC show: (i) Mtb detected by consider alternative diagnosis
CBNAAT, (ii) ZN stain +ve for AFB, and/ Go for lymph node biopsy
or (iii) granulomatous changes
Isolated Mantoux test positivity without
suggestive findings on FNAC should not be
treated with ATT
Treat as
Case
Mantoux’s test is positive in a significant proportion (>70%) of patients. On chest X-Ray, 5-

40% of patients may have pulmonary/ pleural abnormalities, hilar/ mediastinal lymph nodes,
parenchymal lesions or pleural effusion. Utility ultrasonography is in guiding for FNAC in non-
palpable or deep-seated nodes. Central hypoechogenecity on USG where present is
considered suggestive of TB.
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
19
by CBNAAT, FNAC or histopathology etc. Figure 2 depicts the new diagnostic algorithm for
tubercular lymphadenitis. There has been no significant change in the diagnosis of lymph
node TB in children except the addition of CB NAAT in the diagnostic algorithm.
Pleural effusion
Pleural effusion usually appears secondary to rupture of a sub-pleural TB focus or mediastinal
lymph node leading to a granulomatous reaction. This triggers an inflammatory response
mediated by T cells leading to production of pleural fluid.
Children usually would present with fever, chest pain, anorexia and weight loss. While longer
duration symptoms may make TB more likely, many a times TB PE can present acutely. TB
effusion can present with high grade fever. Clinical examination would reveal signs of
effusion.
In the absence of a pleural fluid examination it is not possible to infer a diagnosis based on
radiology alone. If chest X-ray is suggestive of pleural effusion, pleural aspiration should be
performed for biochemical, cytological and smear examination by Ziehl-Neelsen stain to
confirm the diagnosis. Typically, a tubercular effusion fluid is straw coloured (pus, if aspirated,
is very rarely due to TB etiology) has large numbers of cells (in hundreds; predominantly
mononuclear), with high proteins (>3g/dL). Because of the high protein content of the
exudative effusion in tuberculosis it forms a cob-web on standing.
CBNAAT can also be performed on pleural fluid but the yield has been found to be low.
Induced sputum/GA should always be done since there can be associated pulmonary TB. Delhi
Pediatric TB study group showed that about 28% of the children with PE, GA or IS were
positive on culture. On the other hand, the culture yield for M. tb in Pleural fluid is about 5%.
There is a wide variation of tuberculin test sensitivity among children with pleural TB and TST
can be negative. A positive TST is supportive but not diagnostic, should be interpreted along
with microbiological and other investigations. Complete Blood Count within normal range
makes empyema or a complicated para-pneumonic effusion unlikely. ESR has no role as
described earlier as it is non-specific.
Although Adenosine Deaminase (ADA) has been used extensively for the diagnosis of TB
effusion in adults but utility in children appears limited. Adults based studies have compared
TB effusions with malignant effusions. There are very limited studies comparing TB effusion
with parapneumonic effusions, which is the commonest scenario in children. Limited data
suggests that there is a significant overlap between the ADA values in TB effusion and
pyogenic effusions.
Pleural biopsy may be performed, where available, in unclear situations with use of a Cope’s
or Abraham’s pleural biopsy needle. The pleural tissue can be subjected to histopathology,
ZN staining and MGIT cultures. The findings of granulomas with caseous necrotic tissue in the
20
pleural biopsy make the diagnosis of tuberculosis highly probable. Yield of pleural biopsy is
more than 80%.
Role of CT Chest is very limited as rarely does it provide any clue to clinch diagnosis. Pleural
diseases are best imaged with an USG but the benefit relates to establishing the presence and
extent of PE and not in establishing an etiological diagnosis.
In most circumstances, the diagnosis can be made by a combination of a long history, non-
sick child, an exudative lymphocytic effusion and a positive TST.
Abdominal TB
Abdominal TB can be present in intestinal, nodal, peritoneal, visceral and disseminated forms
and almost, one third patients would have more than one site involved. Symptoms and signs
vary. However, common symptoms are abdominal pain, fever, distension, weight loss and
anorexia and hepatomegaly and ascites are common signs. Isolated recurrent or chronic pain
without any other symptom is usually not due to TB.
Tubercular bacilli enter the gut through any of four routes i.e. haematogenous spread from
active pulmonary or miliary TB or Ingestion of contaminated milk or Contiguous spread from
adjacent organs or swallowing of infected sputum in patients with active pulmonary TB,
traverse the mucosa and lodge in submucosa. It follows with inflammatory changes, followed
by Lymphangitis, endarteritis, and fibrosis, mucosal ulceration and stricture.
Multimodality evaluation including clinical, laboratory, radiology, endoscopy, microbiology,

histopathology is needed to reach to definitive diagnosis of abdominal TB; tissue diagnosis
remains the main stay though.
Plain X-Rays are not the diagnostic tool. It may show enteroliths, perforation and features of
intestinal obstruction. Ultrasonography (USG) is recommended as initial modality of choice
and may pick up lymphadenopathy, peritoneal thickening, omental thickening and bowel wall
thickening, and ascites. Contrast enhanced CT and CT enterography provide adequate cross-
sectional imaging in depicting various forms of abdominal TB. Barium studies are gold
standards in diagnosing strictures, fistulae, erosions etc.
Abdominal TB imaging
CT Ileocecal area is the commonest involved region
enteropathy Uniform and concentric bowel thickening
Contracted and pulled up caecum
Ileocecal angel is distorted and often obtuse,
Short strictures of less than 3 cm.
USG / CECT Abdominal lymph node with central necrosis,
conglomerate, peripheral enhancement
Mesentery thickening of more than 15 mm
Caked omentum, multiple SOL liver / spleen, loculated
ascites
21
For diagnosis of peritoneal TB, peritoneoscopy have a very high sensitivity (93%) and
specificity (98%). There are three types of findings on peritoneoscopy. Hyperemic peritoneum
with ascites and whitish miliary nodules of less than 5%, thickened, hyperemic peritoneum
with ascites and adhesions and markedly thickened parietal peritoneum with yellowish
nodules and multiple thickened adhesions.
Many times, there are insufficient evidence to start ATT. Diagnosis of abdominal TB is a
challenge because: non-specific variable symptoms, low microbiological yield, need for
multimodality investigations, complications of wrong diagnosis. One should keep following
presentation in mind which commonly leads to error in diagnosing abdominal TB.
• Mild grade fever

• USG abdomen showing sub-centrimetric lymph nodes
• Failure to gain weight
• Functional abdominal pain
• Chronic diarrhoea without proper evaluation
Neurological TB
TB meningitis
TBM most commonly presents in 6 months to 4 years age. It is most severe form of TB in
children and uniformly leads to mortality, if not treated timely and effectively. Lympho-
hematogenous dissemination of the bacilli during the initial infection leads to formation of
caseous lesions in the meninges/cerebral cortex. These caseous lesions (Rich focus)
discharges bacilli in the subarachnoid space and produces exudates. It Infiltrates the cortical
and meningeal blood vessels and leads to inflammation, obstruction and finally, infarcts. It
may sometimes hinder the normal flow of CSF in the ventricular system and leads to
hydrocephalus.
The clinical presentation is divided in three stages. The disease usually progresses over several
weeks from stage one to three. Infants and young children may progress rapidly over days.
The stage at which treatment begins predicts the prognosis.
22
Typically lasts 1 to 2 weeks Begins abruptly Coma, hemiplegia or

Stage I
Stage II
Stage III
Nonspecific symptoms Characterized by increased paraplegia, decerebrate
intracranial pressure, posturing, deterioration in
Fever, headache, irritability vital signs
/ drowsiness, malaise, meningeal irritability, and
anorexia, inadequate vasculitis without marked
weight gain or weight loss, changes in sensorium
stagnation or regression of Clinical constellation,
development milestornes lethargy, nuchal rigidity,
Kerning and Brudzinski
signs, seizures, hypertonia,
vomiting, cranial nerver
palsies with basal
meningitis and other focal
neurological deficits
CSF is mostly clear, leucocyte counts ranges from 10 to 500 cells /mm3 (occasionally higher),
and majority are lymphocytes, glucose usually remains below 40mg/dl (CSF glucose / blood
glucose below 0.5, protein is elevated (more than 100 mg/dl). Tuberculin Skin Test may be
not reactive in 50% cases. Chest X-ray found normal in 20-50% cases. Nevertheless, every
effort should be made to look for other evidences since many a time extracranial lesions
clinches diagnosis of TBM.
CECT heads is the initial modality of diagnosis. It may have one or more of basal meningeal
enhancement, hydrocephalus, tuberculoma, infarcts in different areas, especially the basal
ganglia and pre-contrast basal hyper density. It sometimes even found normal. Contrast MRI
has higher sensitivity than CECT for the abnormalities such as meningeal enhancements,
infarcts and tuberculomas especially of lesions involving the brains stems. Usually MRI is
preferred when CT is inconclusive and suspicion is high. Cryptococal meningitis, CMV
encephalitis, toxoplasmosis, sarcoidosis, meningeal metastases, and lymphoma can result in
similar radiological findings.
23
Fig 3. Algorithm for diagnosis of TBM
Suspect TBM if: Immediate investigation

Insidious onset of fever and neurological CXR, TST
abnormality with or without Hg, LFT, Glucose, ESR, CECT cranium
• Headache/Vomiting HIV
• Poor feeding/Weight Lumbar puncture: Cytology (including AFB
loss staining), Biochemistry, CBNAAT, MTB and
• Irritability/lethargy pyogenic culture
• Seizures
• Confusion/Coma
• Neck Stiffness
• Cranial Nerve palsy AFB seen or CBNAAT +ve in CSF
• Hemiparesis NO
Check for the following three criteria
Criterion 1 Criterion 2 Criterion 3 YES
> 3 Clinico-investigative features >2 Risk factors for TBM Evidence of TB

strongly suggestive of TBM a) HIV or other elsewhere
a)>5 days of symptoms immunocompromised
9 b) SAM
b)WBC in Blood<15x10 /Lit
3 c) Recent contact with active
c)CSF 10-500 WBC/mm pulmonary TB
d)CSF Lymphocytes > 50%
e)CSF/ plasma gluc< 50%
YES
f)Imaging evidence of; Start treatment for TBM
2 or more Criterion fulfilled ?
Basal meningeal
enhancement
No
Hydrocephalous
Cerebral Infarct
Suggestive of Tuberculoma
24
Continue workup and management for alternative

diagnosis (e.g. Antibiotics for PTPM)
Review assessment within 48 to 72 hours

Consider repeat LP
Expand search for TB elsewhere
Consider MRI head (Contrast)
Again review criterion 1,2,3.

YES
Now 2 or more Criterion fulfilled?
NO
YES
Does the patient have unexplained
meningitis with low CSF glucose,
falling GCS or new focal neurology?
Start treatment for

NO TBM
Continue to investigate
Keep low threshold for starting
empirical ATT PTPM: Partially treated pyogenic meningitis
CNS tuberculosis other than TBM

Tuberculoma
It presents as intracranial space occupying lesion (ICSOL). Its location, size and peri-lesional
edema predisposes the manifestations like seizures, headache and neurological focal
deficits.
Imaging for Tuberculoma

Parameters Tuberculoma
CECT Appearance >2 cm, irregular thick outline, marked perilesional
edema
Location Infratentorial or supratentorial
Midline shift More likely
25
Contrast Appearance T2 - usually hypointense core

MRI MRS Lipid peak present
T2 relaxation Shorter (83-290 ms)
time
Bone and Joint TB

Bone and Joint TB roughly accounts for 5-15% of all EPTB and 2-5% of all TB in children and
adults. It occurs due to reactivation of bacilli which had seeded the bones during the initial
mycobacteremia. Symptomatic disease usually develops within 1-3years of infection but TB
dactylitis can have an early manifestation (usually 1month).
Common presentations of Bone and Joint TB are Potts spine (50% of osteoarticular TB),
Dactylitis, Arthritis (as extension from the metaphysitis), Osteomyelitis. A few uncommon
ones are reactive arthritis (Poncets), tenosynovitis and bursitis.
Dactylitis (spina ventosa)
Tuberculous osteitis, the dactylitis form, often affects children. It may involve multiple or
consecutive bones. Short tubular bones of the hands and feet in children are usually affected;
typically, the proximal phalanx of the index/middle fingers and middle/ring finger
metacarpals. It often follows a benign course without pyrexia and acute inflammatory signs.
On X-Ray, the involved bones show a diaphyseal expansile lesion, a periosteal reaction is
uncommon and healing is by sclerosis.
Potts spine
Most common site of Potts Spine is thoracic, followed by lumbar/ cervical. Pain may be
localized over the involved vertebra or could be referred due to root pains. There can be local
tenderness or deformity. Fever and constitutional symptoms present in one among three
cases. Neurological complications include paraparesis in 20-50% cases, cauda equina
syndrome, 15% of patients have a paradoxical response with increased neurologic deficit
following therapy, there is a risk of kyphosis later in life; especially in children below 7-10
years. Plain X-Ray can abnormal only when 30-50% of bone loss has occurred. It shows end
plate erosion, decrease height of vertebra, collapse and narrowing of discal space and
paravertebral soft tissue shadow. MRI is the most sensitive (nearly 100%). Features in MRI
are marrow edema, destruction of adjacent vertebral bodies and opposing end plates,
destruction of intervening disc, occurrence of prevertebral, paravertebral, and epidural
abscesses. Microbiology should always be attempted for definitive diagnosis and to pick up
MDR-TB. One should look for coexistence of pulmonary TB. If surgery is not planned then CT
guided biopsy of the paravertebral soft tissue/ vertebral body should be carried out and
should be subjected to HPE or culture or CBNAAT. Diagnostic yield will vary in various methods
from 50-70%.
26
TB Arthritis
TB arthritis occurs from intra articular spread from osteomyelitis. Usually, it involves weight
bearing joints such as hip and knee (90%) and less commonly SI / sterno clavicular joint. There
is single joint involvement commonly. Pain is the first symptom (usually at night) later
followed by local tenderness and restriction of joint movement. Fever and constitutional
symptoms may be absent. It may be confused sometimes with oligoarticular JRA. Plain X ray
shows soft tissue swelling, osteopenia, periarticular bone destruction and periosteal
reactions. MRI is very sensitive. For definitive diagnosis, aspiration of joint fluid / synovial
biopsy should be carried out and subjected to HPE or culture or CBNAAT.
TB Osteomyelitis
The usual sites of involvement are bones of hands and feet, long bones, skull, ribs, pelvic and
pectoral girdle etc. Multiple sites are often involved. It presents as pain and swelling of the
affected area. Diagnosis are usually done by X ray/ MRI. TB osteomyelitis should be
differentiated from chronic pyogenic osteomyelitis, Brodies abscess, tumors and chronic
recurrent multifocal osteomyelitis (CRMO). For definitive diagnosis, biopsy should be
subjected to HPE or culture or CB NAAT.
Laboratory Recording & Reporting

Results of the smear, culture and DST / LPA/ CBNAAT results are entered in the culture and
DST register, held at the laboratory. All results must be communicated to the concerned DTO,
DR-TBC/ private provider through Nikshay as soon as results are available so that patient
treatment decisions can be smoothly managed. However, for providers without access to
Nikshay, alternative means (email, SMS etc.,) for communicating the results must be utilized.
If the culture result shows early contamination (within 4 days), the same is informed to the
DTO within 24 hours and s/he is expected to arrange sending a repeat specimen (one early
morning and one spot) to the laboratory within 3 days.
If LPA is found to be invalid or the sputum is smear negative, the sputum specimen is
inoculated on solid or liquid culture immediately. If the culture result is found to be positive,
the culture isolate is subjected to LPA test for confirming MDR-TB / RR-TB.
Management of patients while DST results are awaited

Any TB patient whose RR-TB result is awaited, would be initiated on first-line anti-TB
treatment and continued on the same if found to be RS-TB. If RR-TB is detected, the patient
is immediately referred for pre-treatment evaluation and treatment initiation for DR-TB.
However, the first-line treatment should be stopped as applicable. Moreover, all presumptive
TB among key/vulnerable population would be initiated on RR-TB or RS-TB regimen based on
the results of CBNAAT. Patients must be counselled to practice covering the cough and other
infection control measures like provision of personal protective equipment and support to
prevent the transmission of infection.
27
Chapter 5 - Treatment of Tuberculosis
Basis of pharmacotherapy
Choice of anti-TB drugs is based on several determinants such as bacillary and metabolic
subpopulation, bacillary load, drug resistant strains, lag period of bacterial population,
pharmacokinetic profile and pathological factors etc. There are different types of bacillary
population in every case of tuberculosis and hence, drugs are selected in a combination to
attack entire (extra-cellular and intracellular, slow and rapidly growing) bacillary population
for successful chemotherapy. Isoniazid (INH) and rifampicin (RMP) kill the fast-growing bacilli,
pyrazinamide (PZA) acts against intracellular organisms in acidic medium while extracellular
slow growing bacilli are best killed by RMP. Thus, every case of tuberculosis must be treated
at least with these four drugs.
TB treatment is biphasic. The chances of naturally occurring mutants are higher if the bacillary
load is more and therefore, such cases need more drugs like in initial stage of disease.
Intensive phase is for early and rapid killing of Mtb, prevents deterioration and death, reduces
infectivity, sputum conversion is achieved in 80-90%. Addition of Z reduces duration to 6
months due to its sterilizing effect and addition of E is useful if initial drug resistance to INH is
high. Continuation phase eliminates most residual bacilli, reduces failures and relapses. Small
number of bacilli left and so, fewer drugs are required. But, in presence of background
resistant to the companion drugs; more drugs needed to prevent amplification of drug
resistance
As dividing time of TB bacilli is about 21 hours, all the drugs are administered in such a way
that they achieve peak concentration all at one time so as to hit bacilli hard. The drug
concentration is poor in caseum and sequestrated tissue, so these should be removed
surgically wherever feasible.
Anti-tubercular therapy
The appropriate management of tuberculosis requires assessment of the patient correctly
with respect to the site of disease, bacteriological status, treatment type of patient and the
severity of disease. These new case definitions are detailed in Table ------
Table ------
Category I -New Cases

• A TB patient who has never had treatment for TB or has taken anti-TB drugs for less
than one month is considered as a new case.
Category II- Previously Treated
• Recurrent TB case-A TB patient previously declared as successfully treated
(cured/treatment completed) and is subsequently found to be microbiologically
confirmed TB case
• Treatment After Failure Case- patients are those who have previously been treated
for TB and whose treatment failed at the end of their most recent course of
treatment.
28
• Treatment After Lost to Follow UP Case- A TB patient previously treated for TB for 1
month or more and was declared lost to follow up in their most recent course of
treatment and subsequently found microbiologically confirmed TB case.
• Other Previously Treated Case- are those who have previously been treated for TB
but without outcome after their most recent course of treatment is unknown or
undocumented
Evolution of TB drug therapy under RNTCP in the past few years
Ethambutol is recommended as fourth drug in intensive phase and as a third drug in the
continuation phase due to high INH resistance (around 13%) in new cases.
More recently a WHO commissioned systematic review that pooled results of 33 trials, nearly
2,000 patients with isoniazid mono-resistance, showed failure rates ranged from 9% to 45%.
Lower relapse, failure, and acquired drug resistance rates were seen with Longer duration of
rifampicin treatment, Daily therapy early in the treatment, and Regimens that included a
greater number of drugs to which the M. Tuberculosis carried by the patient were sensitive.
This led to shift to daily therapy.
There were also concerns about managing TB with Cat II as it was associated with poor
outcomes. While individuals receiving category II, treatment showed mixed results in multiple
observational studies; notably worse outcomes were seen among patients who failed after
their initial treatment episode. There was also an Increased incidence of DR TB among those
treated with cat II , suggesting amplification of R resistance in presence of INH resistance. As
we are shifting to U-DST, empiric retreatment regime like cat 2 has become redundant and
has since been withdrawn
Furthermore, the early detection of DR TB among the new cases has changed the threshold
for investigation for DRTB. No extension of IP is done at the end of 2 months for a patient with
non response; instead investigations for DRTB are carried out again.
Studies have also shown that most of the non-rifampicin resistance having poor outcomes is
due to INH mono/poly resistance. In case a Rifampicin sensitive case fails to improve on
therapy, tests for INH resistance are carried out using first line drug line probe assay (FLLPA)
either directly on a clinical sample if it is smear positive or on the isolate obtained through
lisuid culture. A new regime for INH mono-poly resistance is advised.
29
IAP RNTCP guidelines 2019
Type of patienta Regimens

New microbiologically confirmed Pulmonary TB 2HRZE+
4HREb
New Clinically diagnosed Pulmonary TB
New microbiologically confirmed extra-pulmonary TB
New Clinically Diagnosed Rifampicin Sensitive extra-pulmonary TB
Drug sensitive Previously Treated TBc (Recurrence, Treatment after loss
to follow up, Treatment after Failure)
aMolecular testing shall be done in all new cases in children with suspected TB at diagnosis.
B In case of Neuro and spinal TB the continuation phase is extended to 8 months
cAll these category of children shall be evaluated as DR TB suspects and evaluated as per DR TB Algorithm. DST
based treatment shall be followed. In case they are found to be Drug sensitive they shall be started on the above
regimen as for a new case. This group was earlier treated with CAT II regimen which is now withdrawn from RNTCP.
196
Draft Guidelines as on 04.02.19
The newer data on pharmacokinetics of ATT drugs has raised the issue of poor dosing and
now the drug dosages have been rationalised as shown in the Table below:
Range Average Maximum dose(mg)

mg/kg/day mg/kg/day
Rifampicin R 10-20 15 600
Isoniazid H 7-15 10 300
Pyrazinamide Z 30-40 35 2000
Ethambutol E 15-25 20 1500
Streptomycin S 15-20 20 1000
Other change has been the use of fixed dose combinations (FDCs) for therapy. FDCs
ncorporating the multi-drug therapy for TB are preferred due to safety, simplified treatment,
No errors in missing one or more of the combination drugs, and Reduced risk of emergence
of drug-resistant strains. From programmatic view point it can simplify drug supply
management, shipping and distribution. FDC tablets of good quality and proven
30
bioavailability of rifampicin and in appropriate dosing combination should be used in the

treatment of TB.
There are two types of FDCs available under RNTCP
• 3 Drugs FDC DT (H 50, R 75, Z150) (10:15:30) for children, + non-DT Ethambutol 100
• 4 drugs FDC Adult (H 75, R 150, Z 400, E 275)
The therapy recommended as per body weight is detailed below:
Recommended Drug dosages and FDC Pill

combination from 0-18 yrs
Weight band (kg) Dose
4-7 1 P +1 E
8- 11 2 P+ 2E
12-15 3 P+ 3E
16-24 4 P+ 4E
25-29 3 P + 3E+ 1 A
30- 39 2 P + 2E+2 A
Adjunct treatment along with anti tuberculosis drugs
Steroids in tuberculosis
Interaction between the microbial factors and host immunological factors in lung, lymph
nodes, intracranial tuberculosis lesions may cause paradoxical worsening of symptoms due to
release of pro-inflammatory markers like IL 2 and Interferon gamma. Majority recovers with
continuation of therapy. But,a few circumstances may have severe life threatening
manifestations and sequelae. In some of these circumstances, there may be relief in
symptoms if inflammation can be suppressed by steroids. Definite indications for concomitant
steroid therapy include TBM, pericarditis, addison’s disease, miliary TB with alveolo-capliiary
block and TB uveits. The evidence in other forms of intracranial TB like tuberculomas is
unclear. They may be used in endobronchial tuberculosis, bronchial compression, mediastinal
compression syndrome, pleurisy with severe distress, laryngeal TB, TB IRIS and miliary disease
with alveolo-capillary block. All children with TBM should be treated with adjuvant steroids
regardless of the disease severity. Dosage of predinsolone 1-2 mg/kg/day or dexamethasone
0.6 mg/kg/day or its equivalent is used for 4 weeks and then tapered over next 4 weeks. Any
steroid in equipotent doses can be used.
31
Pyridoxine Supplementation
Isoniazid interferes competitively with pyridoxine metabolism by inhibiting the formation of
the active form of the vitamin, and hence often results in peripheral neuropathy. Earlier
supplementation was recommended for high risk groups like HIV, alcohol abuse,
malnutrition, DM, Renal/liver failure, MDR treatment only. It was not recommended routinely
for children. However now there has been a rethink on this and supplementation with 10mg
per day is recommended to all those receiving INH therapy. The justification for Pyridoxine
supplementation is based on the fact that now INH dose has increased to 10-15 mg/kg for
treatment and prophylaxis and it can potentially increase the dose related adverse effects.
We also have a high prevalence of malnutrition in children with TB – so most of our patients
are “at risk” proportion. It is difficult to recognise or diagnose peripheral neuropathy in young
children whose unrecognised and untreated peripheral neuropathy can result in severe &
prolonged morbidity. This is why the expert group felt that the supplementation should be
provided. It is worth mentioning that earlier every child on continuation phase of Intermittent
DOT regime was getting Pyridoxine on drug holidays. Low cost, safety and lack of any
interference with INH action in the small prophylactic dose used favour it use for its potential
benefit.
Otherwise, no supplemental treatment in form of multivitamin or multi-mineral is advised as

there is no evidence of any of these improving outcome of these patients.
Monitoring and Follow up

Children should be closely monitored for treatment progress and disease response. Most of
the children in their early ages, are unable to produce sputum, the response to treatment
among them therefore may be assessed clinically. The help of radiological and other relevant
investigations may also be taken
There are two components of follow up: (1) Clinical follow up and (2) Laboratory follow up
1. Clinical follow up should be done every every month during treatment. After completion
of treatment it may be every 6 months for 2 years. every 1 month till completion. An Initial
visit with in 2 weeks of starting therapy to re-check that patient is on correct dose and
combination and is tolerating all drugs is desirable, where possible.
2. On each follow up child should be assessed for following:
a. Improvement in clinical symptoms including cough, fever, appetite or other clinical
symptoms. These will be assessed as no improvement, partial improvement or
improved after asking parents/attendants. Most patients will show amelioration of
symptoms by the end of 4 weeks of therapy.
b. Physical examination: This will include individualised relevant examination for
respiratory rate, heart rate, temperature (if fever), blood pressure if needed, chest
indrawing, recording of lymphnode size, anemia, abdomen for
organomegaly/distenstion, chest examination for breath sound, crepitations, evidence
of pleural effusion, examination of cardiovascular system if pericardial TB, examination
32
of central nervous system if CNS TB was diagnosis. Physician will record his/her
assessment as no improvement, partial improvement or improvement.
Treating physician should also record weight of the child nearest to 0.1 Kg by using
appropriate weighing scale (Bassinette type electronic weighing scale for infants and
lever type scale for children who can stand) and check for weight gain in comparison
to weight on last visit.
Causes of poor weight gain may be poor intake, vomiting, side effect of medications,
wrong diagnosis, co morbid conditions, concomitant infections such as diarrhea/
pneumonia or poor response to treatment. Various causes will be assessed by asking
history and performing examination. If assessment suggests no clinical deterioration,
family will be counselled for increasing food intake.
If child is losing weight or assessed to be unresponsive to treatment, he should be
revaluated for TB/ drug resistant TB or alternative diagnosis by seeking expert advice.
c. Side effects of medications: Common side effects of ATT are given in table V. Most of
these are minor and consist of vomiting, rashes, pain abdomen etc. Important side
effects of ATT include hepatotoxicity manifesting as nausea, vomiting, pain abdomen,
poor appetite or clinically evident jaundice. The treating physician will also assess for
rashes, visual acuity, color vision for older children. Will ask for any other problem, if
cannot be explained by drugs, will provide appropriate treatment.
d. Treatment of Co-morbid conditions like HIV, SAM, DM etc should be monitored during
each visit. Decongestive measure and anti-convulsants are often prescribed in
neurological TB and should be monitored at followup. Any co morbidities If respiratory
difficulty and assessed to have pneumothorax, collapse etc, refer for pediatric
consultation. If subacute intestinal obstruction, refer for gastroenterology/ surgical
opinion.
e. Revisit adherence to therapy at each visit. Use Pill count, Social support, family based
DOT and Treatment supervisor as needed.
In case the patient has interrupted treatment:
Interruption upto 4 weeks are managed by resuming the therapy but if the drugs are
interrupted for over 4 weeks, the patient is investigated for acquisition of DRTB. If on
testing Rif resistance is not detected, re-treat with first line 4 drugs, AND Check for
INH resistance then treat appropriately as DS or INH mono-poly resistance case. If
Rifampicin resistance is detected – then treat as MDR TB.
2. Monitoring by Laboratory investigations will include sputum examination, imaging X ray
film of chest, Ultrasound abdomen, ECHOcardiography, CT scan of organ involved (Head,
Chest, Abdomen) or MRI (spine). Lab investigation for side effects of medications,
33
monitoring of drug levels for antiepileptic drugs, liver function tests if hepato toxicity is
considered or developed.
2.1 Microbiological: Tested at end of IP and end of treatment (Bacterial
negativity- sputum, GA etc with smear and culture; repeat CBNAAT for any
acquisition of Rif Resistance if followup smear is positive)
2.2 MGIT culture: should be performed if child is not responding even after 4
weeks of therapy.
2.3 Liver function test: No routine LFT testing for patients on first line drugs.
2.4 Follow up Chest radiographs should be performed only at end of therapy; or,
earlier if assessed to be clinically non improvement or has any complication or
deterioration.
Other imaging including Ultrasound of abdomen, echo cardiography, CT/MRI scan
of affected organ system at completion of treatment or assessed to be unresponsive
or deterioration while on treatment.
Adverse Effects of Anti TB Drugs

Drug Main Effects Rare Effects
Isoniazid Peripheral neuropathy, skin rash, Convulsion, Psychosis, Arthralgia,
Hepatitis, Sleepiness & lethargy Anaemia
Rifampicin Gastrointestinal (Abdominal pain, Osteomalacia,
nausea, vomiting), Pseudomemberanous colitis,
Hepatitis,generalized cutaneous Pseudoadrenal crisis, Acute Renal
reactions, thrombocytopenic purpura failure, Haemolytic anaemia
Pyrazinamide Arthralgia, hepatitis, Gastrointestinal Cutaneous reactions,
Sideroblastic anaemia
Ethambutol Retrobulbar neuritis Generalised cutaneous reactions,
Arthralgia, peripheral
neuropathy, hepatitis
Side Effects of Second line Anti-TB drugs

Drugs Side Effects
Injectables- • Ototoxicity
Kanamycin/Capreomycin • Nephrotoxicity
• Vertigo
• Electrolyte imbalance
Quinolones-Ofloxacin, • Gastro-intestinal-Abdominal pain, nausea,
Levofloxacin, Moxifloxacin vomiting
• CNS- dizziness, convulsions
• Phototoxicity, photosensitivity
• Tendinopathy, tendinitis
• Skin rash
• Cardiotoxicity-QT prolongation
• Arthralgia
34
Ethionamide • Gastro-intestinal- epigastric discomfort, anorexia,

metallic taste, nausea, vomiting
• Excessive salivation, sulfurous belching
• Hepatitis,
• Hypothyroidism and goiter with prolonged
administration
• Gynaecomastia, menstrual disturbance
impotence, acne, headache, peripheral
neuropathy
Cycloserine • CNS- dizziness, slurred speech, convulsion,
headache, tremor, insomnia
• Psychiatric- confusion, depression, altered
behaviour, suicidal tendency
• Hypersensitivity reactions
Management of Adverse Drug Reactions (ADR)
What to do if symptoms of adverse effects occur- the following should be done
❖ The dose of the drugs should be checked

❖ All the other causes of symptoms should be excluded
❖ The seriousness of the adverse effects should be estimated
❖ The adverse effects should be registered
❖ The drugs may need to be stopped and should eventually be reintroduced gradually
when symptoms disappear
❖ Development of drug resistance should be avoided
A symptom based approach to the management of the most common adverse effects is adopted.
These side effects are classified as major and minor. In general, a patient who develops minor
adverse effects should continue the TB treatment and be given symptomatic treatment. If a
patient develops major side effects, the responsible drug or the entire regimen may need to be
stopped and the patient should urgently referred to a clinician or health care facility for further
assessment and treatment. Patients with major adverse reactions should be managed in a
hospital. In DR-TB patients, the DR-TB Committee needs to be involved in the management and
modification of the regimen if required.
ATT drug induced liver injury
Hepatotoxicity occurs usually within weeks to months. Approximately, 60% in the first 3
months of treatment. It may be different for Indian setting due to high prevalence of
hepatotropic infections like Hepatitis A in paediatric age group. Clinical features are nausea,
vomiting, anorexia, pain abdomen, jaundice, unexplained fatigue, new onset hepatomegaly
and bleeding manifestation. Risk factors for ATT induced liver injury are malnutrition,
hypoalbuminemia, associated HIV, Hepatitis B, Hepatitis C infection, extensive TB disease,
35
increases with age, ±slow acetylators of INH, Presence of HLA-DQB1*0201, gene

polymorphisms at loci of genes coding for cytochrome P450 2E1 and for glutathione S-
transferase.
Asymptomatic increases in serum liver transaminases can be managed with continue ATT,
monitoring for symptoms -anorexia, malaise, vomiting, or jaundice and may repeat liver
enzymes after a week.
Drug induced liver injury which is defined as presence of atleast rise of >5 times the upper
limit of normal levels of ALT and /or AST, even when has no symptoms or rise in ALT and/or
AST >3 times when has nausea, vomiting, diarrhoea or rise in level of serum total bilirubin
above 1.5 mg/dl.
In such cases, stop all hepatotoxic ATT drugs - R, H, Z immediately. Symptomatic treatment
should be given. Look for other causes of hepatitis- viral markers in all cases (A, E). Consider
starting alternative drugs if seriously ill: Ethambutol, Streptomycin, & Levofloxacin. Re-
introduce primary drugs once symptoms subsided & liver enzymes <2 upper limit of normal
(ULN) (2-6 weeks). Start with full dose of rifampicin (after LFT is < 2ULN). The drugs (in full
dose) are to be added every 3-days, with regular LFT monitoring. A new drug is re-instituted
only if the ALT is less than twice the upper limit of normal. In case the patient is sick, drowsy
or have any abnormal bleeds, the case should be referred to an in-patient facility.
For deciding the final duration of therapy; do not take into account the days when full
complement of treatment was not given.
Clinical or radiological deterioration during follow up

The causes for a clinical non-response could be
a. Incorrect diagnosis (particularly if clinically diagnosed case of TB)
b. Lack of adherence to therapy
c. Incorrect drugs or dosages
d. not retaining drugs- children often may vomit out drugs due to the bad taste or
due to forceful medication
e. Secondary infection or a comorbidity
f. Drug resistance
g. Paradoxical upgrading reactions
The further steps of investigations are decided based on clinical clues for the above
conditions. Detailed investigations for drug resistance should be sent for MGIT DST or LPA or
CBNAAT. Drug resistance should not be labeled without microbiological confirmation in most
circumstances. Diagnosis of drug resistant TB in bacteriological diagnosis is often untenable,
with few notable exceptions where access to appropriate specimen may be an issue. DST or
LPA or CBNAAT needed as confirmatory test for DRTB. History of contact with a proven case
of MDR or prolonged or irregular therapy in a case with in household or peer groups of the
child is a good clue for investigating for DRTB. Often such history is provided later on followup
36
by the family as they become more aware about the disease and may check around for such
a case.
Radiological deterioration alone without clinical symptoms should be reviewed with a skilled
radiologists. Often the difference in phase of respiration, rotation, difference in radiological
factors may affect the assessment of followup images.
Paradoxical upgrading reactions

It refers to enlargement of old lesions or unexpected appearance of new lesions during
apparently adequate ATT. It usually occurs 3–12 weeks after beginning of therapy; most
frequently after treatment for 6- 7 weeks, & lasts for ∼2 months. Generally, it is self-limiting;
resolves without serious sequelae. It usually regresses without a change of initial drug
regimen. It may occur post treatment (as late as two years) in cases of lymph node TB.
Active TB can result in depression of immunity. After successful ATT focal immune response
improves. Accumulation of inflammatory exudates at previously invisible microscopic
tuberculous foci elsewhere, appearing as new lesions. Reversible roentgenographic
progression in initial treatment of TB may be more common than previously expected if there
is frequent monitoring by chest radiograph. In fact, it is for this very reason, routine
monitoring by radiographs is not recommended.
Types of paradoxical reactions reported
• Increase in size of mediastinal lymph nodes or areas of pulmonary infiltration in pediatric

patients with primary TB
• Appearance of new lung infiltrates in patients with extrapulmonary TB
• Development of TB pleural effusion
• Increase in size of effusion/appearance of effusion on the contra lateral side
• Appearance of new lymph nodes/ enlargement of original nodes
• Increase in size or number of tuberculoma/ infarctions / hydrocephalus on treatment of
intracranial TB
It might be difficult to distinguish a paradoxical reaction from a true drug resistance and it is
always a diagnosis of exclusion. Absence of any systemic symptoms is a useful indicator for
PUR. Absence of systemic symptoms is usually seen in paradoxical reactions (non-HIV
settings).
Long term follows up: After completion of treatment, the patients should be followed up
every 6 months after completing treatment for 2 years to assess fr relapse of illness.
Monitoring on each visit will include same as described above. Lab tests required only if
indicated.
37
Chapter 6 -TB in special situations
Drug Resistant TB including MDR
MDR-TB is defined as M. tuberculosis resistant to isoniazid and rifampicin with or without

resistance to other drugs. Currently, WHO estimated incidence of Rifampicin and MDR TB in
India is estimated to be around 147000. This translates to be around 11 patients per 100 000
population annually as per the Global TB Report, WHO 2017.
Very limited data is available for MDR-TB in children. It is mainly from transmission of drug-
resistant TB from adults to child contacts and less likely to be acquired from previous exposure
to TB treatment. Thus MDR TB in children mirrors MDR TB in adult so MDR TB is common in
children in settings where MDR TB is common in adults. MDR TB in children like in adults is
associated with higher morbidity and mortality compared to drug-sensitive disease.
Presumptive case of MDR-TB in children- Children who are contacts of adults with MDR TB/
drug resistant TB, who are lost to follow up after initiating treatment, those who present with
recurrence of disease after previous treatment, those who do not respond to therapy with first
line drugs and those living with HIV (CLHIV)
Children usually have paucibacillary disease and are often sputum negative. So, these
definitions are to be used in conjunction with the clinico-radiological picture.
Approach to diagnose DR TB in children
Careful history of patients is most important. This includes contact with a suspect MDR, drug
and dose history as well as adherence. Causes of non response to anti-TB therapy including
incorrect diagnosis of TB, poor adherence, associated immunodeficiency such as HIV,
paradoxical reactions. Intercurrent infections should also be ruled out. Clinical examination
and investigations relevant for pulmonary TB or EP-TB patients need to be carried out. It is
important to try and get appropriate samples from children.
Bacteriological confirmation and drug susceptibility testing are mandatory. For this, sputum
(or other relevant samples e.g. gastric aspirate, induced sputum, bronchoscopic lavage, lymph
node aspiration, CSF analysis, tissue biopsies) must be collected in all children with presumed
DR-TB for CB NAAT (e.g. Xpert MTB/RIF) or LPA AND culture and drug sensitivity testing. This
may even imply referral to a higher center to facilitate invasive testing.
Diagnosis of DR-TB in the absence of microbiological confirmation must be thoroughly

reviewed as it may often be untenable. In presumptive DR-TB, if there is no microbiological
38
confirmation, bacteriologically negative clinically diagnosed DR-TB can be considered after

ruling out alternative diagnosis.
Probable MDR-TB among children: The case definitions of presumptive DR-TB and variety of
DR-TB patients used for adults would also apply to children. However, the term probable
MDR-TB in children would be applied to children wherein bacteriologic confirmation is not
available/ negative and the decision regarding diagnosis and initiation of treatment is taken
by the NDR-TBC committee.
Criteria for diagnosis of “Probable MDR-TB” include children with sign and symptoms of active
TB disease who in addition have the following risk factors. They should be considered as
having ‘probable’ MDR-TB and started on MDR-TB treatment, even in the absence of
bacteriological confirmation. They include children who have:
➢ Close contact with a known case of MDR-TB;
➢ Close contact with a person who died whilst on TB treatment;
➢ Close contact with a person who failed TB treatment;
➢ Non response or Failure of a first-line regimen, recognizing that both
bacteriological and Clinical definitions of failure should be used; and
➢ Previous treatment with second-line medications
All patients considered to have ‘probable’ MDR-TB should be presented to and discussed with
a DR-TBC Committee followed by a decision to treat which ought to be made in consultation
with the paediatrician. This consideration of initiation of appropriate DR-TB regimen without
bacteriological confirmation does not replace the need for a thorough and ongoing diagnostic
evaluation, including consideration of non-TB causes, prior to initiation of DR-TB treatment.
Children with a central nervous system disease and/or those with other life-threatening
manifestations with risk factors for DRTB may be treated as probable MDRTB even when their
DST tests are awaited. They should be initiated on therapy immediately, in consultation with
the paediatrician in the NDR-TBC committee, given the high risk of mortality. Further
continuation of therapy can be decided based on their test results when available.
Presumptive DRTB is a patient who needs to be subjected to genotypic (CBNAAT, LPA) or
phenotypic (LC-DST) DSTs while probable MDR TB is a patient, who after getting the results
of the above tests, cannot be microbiologically confirmed and needs to be started DRTB
regimen based on their clinical and /or radiological deterioration (clinically diagnosed case of
MDR TB).
‘A patient is confirmed to have drug resistant TB, only when the results are from a RNTCP
quality assured Culture & DST Laboratory and by a RNTCP endorsed testing method’
Mono-resistance TB (MR)- A TB patient, whose biological specimen is resistant to one first-

line anti-TB drug only
Poly-drug resistance TB (PDR)-A TB patient, whose biological specimen is resistant to more

than one first-line anti-TB drugs, other than both H & R.
39
Rifampicin resistance (RR)- A TB patient, whose biological specimen is resistant to R, detected

using phenotypic or genotypic methods, with or without resistance to other anti-TB drugs. It
includes any resistance to R, in the form of mono-resistance, poly-resistance, MDR or XDR.
Multidrug resistance TB (MDR)- A TB patient whose biological specimen is resistant to both

H & R with or without resistance to other first-line anti-TB drugs. MDR TB patients may also
have additional resistance to any/all FQ OR any/all SLI anti-TB drugs.
Extensive drug resistance (XDR)- A MDR TB patient whose biological specimen is additionally
resistant to at least a FQ (Ofx, Lfx, Mfx) and SLI anti-TB drugs (Km, Am, Cm).
NOTE-It is to be noted that R resistance is quite rare without H resistance. Majority of DST
results with R resistance will also be H resistant, i.e., MDR-TB. This has been substantiated in
the National Drug Resistance Survey (2014-16). Therefore, RNTCP has taken the
programmatic decision that patients, who have any R resistance, should be managed as if
they are an MDR-TB patient and this is in line with WHO global guidelines for PMDT.
The algorithmic approach to diagnose DR-TB in children is shown in Figure below.
Figure Algorithmic approach to diagnosis of DR-TB in children

New child TB patient
Treat as DR-
TB DR-TB DS-TB
Contact with infectious TBpatient ?

Yes or No
Yes
DRT/DST of source patient not known &
Source is a Source is a known DS-TB patient
Source is retreatment TB patient &/or
child is failing 1st line treatment or not known or no risk factor
Do DRT/DST of child or source’s specimen

Do DRT/DST on an appropriate
specimen from the child.
Consult pediatrician to treat as If poor response to

treatment, consult DS-TB, treat as DR-TB, treat as
OR source’s isolates, if child’s pediatrician to treat DS- TB DR- TB
as probable DR-TB
40
If an appropriate specimen is available from the child, the specimen processing will be in
accordance to the Pediatric DR-TB diagnostic algorithm shown below.
Pediatric Drug Resistant TB Diagnostic Algorithm

All microbiologically diagnosed TB patients
Source’s sample of
CBNAAT
contacts subjected to
DST, if child’s specimen
not available
For discordance on
RR TB LPA for RR-TB – repeat RS TB
CBNAAT at LPA lab
RR-TB among new patients

SL - LPA** – repeat CBNAAT in fresh
sample $
FL-LPA*
FQ and SLI FQ and/or SLI H H

Sensitive Resistance Resistant Sensitive
* LPA may be done directly if smear positive else send for MGIT foll by FLPA to evaluate for H mono/poly resistance
** SLLPA may be done directly if smear positive else send for MGIT foll by SLLPA or LC DST (Mfx 2.0, Km, Cm, Lzd)
$ - With availability of X-pert ultra-cartridges in the near future, the reconfirmation of RR-TB among new TB patients
will no longer be required. If Rif Resistant on repetition, DRTB regimen is initiated; If Rif sensitive on repetition or If
result is unavailable, DSTB regimen is initiated
Methods for drug susceptibility testing

Drug Resistance Tests (DRT) using molecular methods: This can be performed on sputum
specimen (direct) or on culture isolates (indirect) for diagnostic purpose. Presently the
following technologies are available for diagnosis of DR-TB through rapid molecular diagnostic
testing:
1) CBNAAT (Xpert MTB)/Rif testing using the Gene-Xpert platform / TruNat. These tests
can be performed on smear positive, smear negative and extra pulmonary specimen.
The test detects TB and resistance to R
2) Line Probe Assay (LPA) for detection of MTB complex and resistance to first line drugs R,
H and second-line drugs class FQ and class SLID.
LPA provides rapid diagnosis of R and H resistance as well as resistance to class FQ and
class SLID. When performed on smear positive specimen. It can be used directly and
41
can yield results in 72 hours. Else it can be used on culture isolates from smear
negative specimen for rapid DST.
These methods are PCR-based and cannot be used for determining response to
treatment.
Growth-based phenotypic drug susceptibility testing: Culture though a highly sensitive and
specific method for TB diagnosis, requires 2-8 weeks to yield results and hence does not help
in early detection. However, culture will be used for long-term follow-up of patients on DR-
TB treatment and help detect early recurrence in both drug sensitive and drug-resistant TB.
The growth-based phenotypic culture methods include automated Liquid culture systems
e.g., BACTEC MGIT 960, BacTAlert or Versatrek etc., and solid (Löwenstein Jensen) media.
Mycobacteria growth indicator tube (MGIT) is the commonest system used under RNTCP at
present, and can test both pulmonary and EP specimen. Most commonly used method for
testing is the economic variant of the proportion sensitivity. MGIT is preferred method for
DST and both first and second-line anti-TB drugs can be tested. Following drugs can be tested
for susceptibility by liquid culture:
- First-line drugs: R, H, Z
- second-line drugs: Lfx, Mfx, Km, Cm, Am
- other drugs: Lzd, Cfz, Bdq*, Dlm etc.
Choice of Diagnostic Technology
DR diagnostic technology Choice

CBNAAT/LPA First
Liquid culture isolation and LPA DST Second
Liquid culture isolation and liquid DST Third
Laboratory recording and reporting

Results of the smear, culture and DST / LPA/ CBNAAT are entered in the culture and DST
register available at the laboratory. All results must be communicated to the concerned DTO,
DR-TBC/ private provider through Nikshay as soon as results are available so that patient
treatment decisions can be smoothly managed. However, for providers without access to
Nikshay, alternative means (email, SMS etc.,) for communicating the results must be utilized.
If the culture result shows early contamination (within 4 days), the same is informed to the
DTO within 24 hours and s/he is expected to arrange sending a repeat specimen (one early
morning and one spot) to the laboratory within 3 days. If LPA is found to be invalid or the
sputum is smear negative, the sputum specimen is inoculated on solid or liquid culture
immediately. If the culture result is found to be positive, the culture isolate is subjected to
LPA test for confirming MDR-TB / RR-TB.
42
Group of drugs for treatment of drug resistant TB in children
Very recently WHO has regrouped the second line drugs and given a draft guidance for using
these. The following table is from their guidance of Dec 2018.
Grouping of drugs recommended for use in longer MDR-TB regimen

(Based on WHO Dec 2018 guidelines)
RNTCP Treatment Expert group has agreed to the following regimes for our country, keeping
in view the WHO advice.
43
RNTCP Regimens for Drug Resistant TB case
Integrated Pediatric Drug Resistant TB Algorithm

All microbiologically diagnosed TB
patients
Source’s sample of
contacts subjected to DST,
if child’s specimen not
CBNAAT available
For discordance on LPA for RR-

RR TB TB – repeat CBNAAT at LPA lab RS TB
Shorter MDR TB RR-TB among new patients – First line
Regimen (9-11 m)# repeat CBNAAT in fresh sample treatment
$
SL - LPA** FL-LPA*
Non
FQ and SLI Sensitive FQ and/or SLI Resistance H Resistant H Sensitive response t
therapy
H mono/poly
Continue shorter MDR All oral longer Continue First line
resistant TB
regimen regimen (18-20 m) treatment
regimen (6 m)
In case of addl resistance, failing regimen, drug intolerance, return after interruption (>1 m) or
emergence of any exclusion criteria
* LPA may be done directly if smear positive else send for MGIT foll by FLPA to evaluate for H mono/poly resistance
** SLLPA may be done directly if smear positive else send for MGIT foll by SLLPA or LC DST (Mfx 2.0, Km, Cm, Lzd)
$ - With availability of X-pert ultra-cartridges in the near future, the reconfirmation of RR-TB among new TB patients will no longer be
required. If Rif Resistant on repetition, DRTB regimen is initiated; If Rif sensitive on repetition or If result is unavailab le, DSTB regimen is
initiated
DST to Z, Cfz, Bdq & Dlm would be considered for policy in future, whenever available, standardized & WHO endorsed.
44
Principles of DRTB regimen:
➢ Always be treated in consultation with an expert

➢ Include at least 4-6 bactericidal medications to which the strain is known or likely to
be susceptible
➢ Do not add a single drug to a failing regimen
Treatment Recommendation for Delamanid in Children are detailed in the Annexure 5.
The monitoring of DR-TB treatment in children would be as per the suggested schedule by
regimen type in Table 8.1. However, the paediatrician of the Nodal/District DR-TBC must
regularly evaluate the progress of the child on treatment and initiate any other investigations
as suggested
Pre-treatment Evaluation for DR-TB patient:

• Detailed history including screening for mental illness, seizer disorder, drugs/alcohol
abuse etc
• Weight
• Height
• CBC with platelets counts
• Blood sugar to screen for DM
• LFT
• KFT (Blood urea, S. Creatinine etc)
• TSH & other thyroid functioning tests
• Urine examination- routine & microscopic
• Chest X Ray
• ECG
• Serum electrolytes
Table ----------- Standard Regimen for Initiating Treatment of MDR/RR TB or H Mono-poly DR-
TB
** Eligibility for Shorter MDR Regimen: patients not exposed to second line drugs for more
than 1 month/no additional resistance to FQ/SLI, those who are resistant to drugs used in
the regime and in those where there is documented/ possible resistance to FLQ and PZA
45
10mg/kg od
*Children at risk for peripheral neuropathy (e.g. malnutrition or HIV co-infection) should
also receive pyridoxine 50-100 mg/day depenfding on the dose of Cycloserine if used.
therapeutic dose..
Monitoring of MDR-TB patients in children
46
47
Management of TB with HIV co-infection
The HIV epidemic can potentially drive a second epidemic such as Tuberculosis – and vice
versa. HIV greatly increases number of TB patients, which in turn increases TB transmission.
The intersection of both epidemics could potentially spawn a third – such as Multiple Drug
Resistant Tuberculosis. About 1,10,000 people in India are estimated to be HIV-TB co-infected
annually, with the national average for HIV prevalence among incident TB cases at 5% , ranked
second in the world and accounts for about 10% of the global burden of HIV associated TB
(Source WHO. 2015. Global TB Report) It is recognized that HIV and TB make for a fatal
combination with extremely high death rates (15–18%) reported among HIV infected TB cases
notified under the RNTCP. Further, even among cured TB cases with HIV infection, the risk of
recurrent TB is quite high. Overall, TB is estimated to cause about 25% of all deaths among
PLHIV in India (Source NACO. 2013. National Framework for Joint HIV/TB Collaborative
Activities, MoHFW, Government of India).
Since the co-infection rate is high, it is important from a public health standpoint to screen all
those children with HIV, for TB, and vice-versa. Thus all patients who have TB should be tested
for HIV after counselling. This is a simple antibody test in children above 18 months of age.
Rapid HIV tests that are reliable are available at all ICTC centres around the country.
Sign & Symptoms in CLHIV for screening for TB:
48
Specific problems in diagnosis & treatment of TB in children infected with HIV
Overlapping symptoms
• Chronic pulmonary symptoms due to other HIV related condition eg. GERD,
bronchiectasis mimic TB
• Weight loss and failure to thrive are both features of HIV and tuberculosis
Radiology
• CXR interpretation- difficult with presence of other HIV related conditions pneumonia,
LIP, bronchiectasis
• HIV infected patients with active TB proven on sputum culture can have normal chest
radiographs
Tuberculin Sensitivity Testing (TST)
• Induration >5 mm is read as positive TST
• Extremely low sensitivity in culture confirmed TB with HIV cases despite taking cut-offs
of 5 mm
• No consistent evidence that IGRA was more sensitive than TST for active TB diagnosis
Sputum microscopy
• Has poor sensitivity in detecting TB in PLHIV due to fewer organisms in sputum (Source-
WHO. 2014. Xpert MTB/RIF for people living with HIV)
• As the HIV disease progresses and the individual become more immune-compromised,
the clinical presentation is proportionately more likely to be EP or smear negative than
in HIV-uninfected TB patients. This can result in misdiagnosis or delays in diagnosis and
in turn, higher morbidity and mortality.
Treatment
• Is more difficult and adverse events are more common. Deaths during treatment are
partly due to TB itself and partly due to HIV related diseases, particularly in the
advanced stages of immunodeficiency. Further, due to increased frequency of adverse
drug reaction, rigorous monitoring in this particular group of patients is required in
order to ensure adherence to treatment, early identification and treatment of adverse
events and to reduce default.
CBNAAT is the frontline test for diagnosis of TB among CLHIV. If CBNAAT is not available,
arrangements have to be made for collection and transportation of specimen to the nearest
CBNAAT site.
49
Diagnostic Algorithm of TB in CLHIV
HIV infected child
Intensified TB case finding
Presumptive TB
Presumptive Pulmonary TB Presumptive Extra Pulmonary TB
CBNAAT/2 smears/ + X-Ray chest CBNAAT /culture / Cytology X-Ray chest and
smear positive Histopathological other radiological
specimen from extra examination examinations
Pulmonary pulmonary
Smear or Xpert Smear and CBNAAT Smear and CBNAAT
positive negative + X-ray negative + X-ray negative Any one or more suggestive of TB
suggestive of TB for TB
Bacteriologically positive Clinically diagnosed TB Non TB

TB Extra pulmonary TB
Strategy for HIV-TB coordination to reduce mortality
Prevention Early Detection of HIV-TB

• Isoniazid preventive therapy (IPT) for all CLHIV 100% coverage of provider-initiated HIV
(on ART+ Pre-ART) testing and counselling (PITC) in TB patients
• Robust Airborne infection control (AIC) PITC in presumptive TB cases
activities Rapid diagnostics for detecting TB and DR-TB
• Awareness generation in PLHIV
Early Care & Prompt Treatment of HIV-TB Intensive Case Finding (ICF) activities at all
❖ Promotion of ‘Single Window Delivery Services’ HIV settings (ICTCs, ART centres, Link ART
i.e. ATT from ART centre along with ART drugs Centre (LACs), and Targeted Intervention (TI
❖ Prompt initiation of TB treatment settings): all ICTC clients should be screened
❖ Early initiation of ART (within first 8 wks) & for presence of TB and vice-versa
monitoring of timeliness of ART initiation
through expanded ART reporting formats
❖ Strengthened linkage of HIV-TB patients to ART
centres through travel support by RNTCP
❖ ART for HIV-TB cases irrespective of CD4 count
At all ART centres, NACO ensures strengthening of ‘3Is’ strategy i.e. Intensive Case Finding
(ICF), Airborne infection control (AIC) and Isoniazid preventive therapy (IPT) along with
provision of daily anti-TB treatment (ATT) for PLHIV.
50
TB treatment recommendations
Treatment regimen is same as in HIV non infected children. 6 months duration of therapy
(with intensive and continuation phases) is optimal. At end of continuation phase, give 6
months of INH preventive therapy for 6 months. In case of spinal TB and CNS TB- continuation
phase to be prolonged (9-10 months); thus total duration of therapy is 12 months. Pyrodoxine
supplementation (10mg/day) should be given till the time INH is prescribed in DSTB co-
infected children.
Giving ART and ATT together is however not without problems.
Rifampicin is a potent inducer of cytochrome P450, thus increasing metabolism of NNRTI and
protease inhibitors, and therefore reducing the therapeutic drug levels. There can also be
adverse events especially hepatotoxicity. The possibility of development of IRIS is always
there more so when ART is initiated early. High pill count may also affect patients’ acceptance
and lead to high lost to follow ups. NACO ART guidelines of 2018 recommend any child with
active TB disease should begin TB treatment immediately and begin ART as soon as tolerated
(2-8 weeks into TB therapy), irrespective of clinical stage & degree of immuno-suppression.
This “two weeks” guideline is to have the patient to get adjusted to the effects and to the side
effects of anti TB drugs and also to have reduced the antigenic load of M. tuberculosis as much
as possible at the time of ART initiation to reduce ART related complications, including IRIS.
Treating physicians can deviate from this general guideline of “two weeks”, in cases of
moribund patients, severe forms of TB or disseminated TB. The initiation can be decided on
case to case basis and is advisable to initiate ART in all cases at least within 8 weeks of starting
anti-TB treatment. In children with CD4 count <50/cumm, the ART should be initiated as early
as possible within the first 2 weeks of starting the ATT.
51
ART among CLHIV with TB co-infection
Management of HIV-TB co-infection in infants and children
Management of HIV-TB co-infection in infants, children and

adolescents in relation to Age groups and bodyweight
NB Nevirapine is no more part of first line ART.
52
Monitoring during treatment

• HIV-infected children on ATT: LFTs at baseline, day 15, month 1 and month 3. After 3
months, a symptom-directed approach is useful.
• If symptoms of drug toxicity develop, a physical examination and liver enzyme
measurement should be repeated.
• Guidelines for ATT induced liver disease remain the same (ATS guidelines).
Initiating ART in patients with DR- TB
The use of ART in HIV infected patients with TB improves survival for both drug-resistant and
susceptible disease. However, HIV infected DR-TB patients without the benefit of ART may
experience mortality rates exceeding 90%. The likelihood of adverse effects could
compromise the treatment of HIV or DR-TB if both treatments are started simultaneously.
Second-line anti-TB drugs should be initiated first, followed by ART as soon as second-line
anti-TB drugs are tolerated. Generally this should be within the first two weeks of initiating
DR-TB treatment. On the other hand, undue delay in starting ART could result in significant
risk of HIV related death amongst DR-TB patients. Co-trimaxazole can be provided to all
patients with HIV to reduce mortality by preventing opportunistic infections as per WHO
recommendation
Patients who are already on ART at the time of DR-TB diagnosis can be continued on ART
when DR-TB therapy is initiated.
Concomitant therapy with ART or other medicines: Rifampicin (R) is not used in DR-TB
treatment; they are used in the treatment of R-sensitive poly- and mono-resistant TB, which
has drug interaction with Protease Inhibitor (PI). Newer drug like Bdq are metabolized by the
CYP3A4 having multiple drug interactions with protease inhibitors and non-nucleoside
reverse-transcriptase inhibitors (NNRTI)
TB IRIS (Immune reconstitution inflammatory syndrome)
After the initiation of ART, HIV-1 replication is greatly reduced and viral load rapidly falls,
resulting in increased CD4 cell function & improved immunity. The host immune response to
the pathogen then produces the clinical manifestations in subset of patients. These are of two
types. In paradoxical IRIS, a diagnosis of TB is already made, ATT is started, and a good initial
response to TB therapy is observed before the patient started on ART. In unmasking IRIS: the
diagnosis of TB was not made, and usually there are no clinical features before starting ART.
After ART is initiated a good initial response (CD4, viral load) is seen, and then the TB
manifestations become manifest.
53
IRIS can manifest in several ways. Onset of TB-associated IRIS should be within 3 months of
starting ART with at least 1 major criterion & 2 minor criteria:
Major criteria Minor criteria
• New/enlarging lymph nodes or other • New/worsening constitutional

focal tissue enlargement symptoms such as fever
• New/worsening radiological features • New/worsening respiratory
• New/worsening CNS tuberculosis symptoms such as cough
• New/worsening serositis • New/worsening abdominal pain
IRIS is also a diagnosis of exclusion. It is important to rule out other causes of the clinical
presentation like poor adherence to TB therapy, failure of TB therapy due to drug resistance,
another opportunistic infection or neoplasm, drug toxicity or drug reaction.
Anti-tuberculosis therapy and ART should be continued in every case. Mild IRIS should be
managed with symptomatic treatment, aspiration of large fluctuant lymph nodes or
subcutaneous abscess may provide relief. In moderate to severe IRIS, oral prednisolone (1-2
mg/kg for 1-2 weeks, then gradually decreasing doses) may be given for paradoxical IRIS (after
excluding all other differential diagnosis).
BCG in children with HIV
BCG is useful for children born in TB-endemic countries but in high prevalence of HIV, it is
associated with disseminated BCG disease in vaccinated HIV-infected infants. Disseminated
BCG is associated with all-cause mortality in excess of 75% among CLHIV.
WHO recommendations of BCG in children with HIV are as follows
- Benefits outweigh risks for BCG vaccination for infants born to women of unknown HIV
status. These infants should be immunized.
- Benefits usually outweigh risks for BCG vaccination for infants whose HIV infection
status is unknown & who demonstrate no signs or reported symptoms suggestive of HIV
infection but who are born to known HIV-infected women. These infants should be
immunized after consideration of the aforementioned locally determined factors
- Risks outweigh benefits for BCG vaccination for infants who are known to be HIV
infected with or without signs or reported symptoms of HIV infection. These infants
should not be immunized
- Risks usually outweigh benefits for BCG vaccination for infants whose HIV infection
status is unknown but who have signs or reported symptoms suggestive of HIV infection
and who are born to HIV-infected mothers. These children should not be immunized.
54
Implementation of the WHO recommendation on BCG: Indian context
BCG vaccine is usually given at birth in India. Recognition of HIV infection at birth is difficult
as HIV infected infants are usually asymptomatic at birth. Most PMTCT recommends
diagnosis of HIV infection by PCR at 6 weeks of age. As PMTCT programmes are strengthened
and access to maternal HAART improves the number of paediatric HIV infections will decline.
It will cause more HIV exposed but HIV non-infected cases. If these children are non-
vaccinated, they will have greater chance of disseminated TB. The BCG Working Group
supported the revised WHO BCG vaccination policy, but recommends that current universal
BCG immunisation of infants continue in countries highly endemic for TB until countries have
all programmes in place for implementing selective deferral of HIV-exposed infants. IAP also
recommends - BCG vaccination at birth in all asymptomatic HIV exposed infants.
Isoniazid Preventive Therapy (IPT) for children living with HIV
IPT is one of the “3 I’s” globally recommended for prevention of incident TB among HIV
infected individuals/children. In 2011, The World Health Organization issued specific
recommendations regarding the use of IPT in its guidelines on ‘Intensified TB Case Finding &
& IPT for PLHIV in resource constrained settings’. The recommendations are:
✓ Children living with HIV (CLHIV) who do not have poor weight gain, fever, current cough
are unlikely to have active TB
✓ CLHIV who have any of the above symptoms may have TB and should be evaluated for
TB and other conditions. If evaluation shows no TB, such children should be offered IPT
regardless of their age.
✓ CLHIV, who are more than 12 months of age, and who are unlikely to have active TB on
symptom based screening, and have no contact with TB case should receive six month of
IPT (10mg/kg/day) as a part of a comprehensive package of HIV prevention and care
services.
✓ All CLHIV who have successfully completed treatment of TB disease should receive INH
for an additional six months.
✓ Although, IPT is more effective among TST positive individuals/children, it is not a
requirement for initiating IPT intervention among the CLHIV considering difficulty in
logistics and administration of the TST
✓ Providing IPT to CLHIV does not increase risk of developing INH resistance TB later.
Therefore, concerns regarding development of INH resistance should not be a barrier to
provide IPT.
55
Algorithm for use of IPT for children living with HIV
Aged less than 6 years and living with HIV
Screen for TB with any one of the following

symptoms:
Yes Investigate for TB
• Poor weight gain
and other diseases
• Fever
• Current cough
Give appropriate Other
treatment diagnosis
No
TB Contact present Not TB
Yes No
TB
Give IPT
Treat
Age < 12 m Age > 12 m
for TB
No IPT Give IPT
Give additional 6 months IPT after

Screen for TB Regularly completion of TB treatment*
Infants diagnosed as HIV infected at 3-4 months of age should be monthly screened for
contacts and screened for active TB (do not start INH prophylaxis). If contact is positive, INH
prophylaxis should be given for 6 months (after ruling out active TB) and if contact is negative,
monthly screening should be continued without INH prophylaxis.
INH prophylaxis is given in dose of 10 mg/kg orally every day for 6 months duration as per
current recommendations. Pyrodoxine supplementation may be given with IPT. Hepatitis and
peripheral neuropathy are the contraindications to start INH prophylaxis.
MANAGEMENT OF A NEONATE BORN TO A MOTHER WITH TUBERCULOSIS

There may be several ways a newborn can be exposed Safety of ATT during pregnancy
to TB with definitive but variable risk of transmission
of infection. These situations include when mother • FLDs Safe (except
has active TB (both pulmonary/ extrapulmonary) aminoglycosides), particularly after
first trimester
when baby is born or mother has completed
• Aminoglycosides are unsafe and
treatment but was having any form of TB disease (
not recommended
pulmonary or extra-pulmonary) while carrying this
• Offers no transplacental effect on
baby or neonate exposed to a Health care foetus
worker/other contact with Pulmonary TB. The
newborn should first be evaluated for the presence of disease as early as possible. As the
symptoms can be subtle, a good clinical examination and chest radiograph is needed. Other
investigations including USG abdomen or gastric aspirate may be indicated based on
symptoms and examination. Risk of transmission of infection to new born is affected by many
56
factors like maternal disease (high with miliary, meningeal or pulmonary disease; low with
pleural effusion or lymph node and unknown with HIV co-infection) and therapy (low risk if
completed treatment or even if taken 2 weeks of treatment), use of chemoprophylaxis,
closeness of contact, isolation and barrier nursing.
Preventive therapy to neonate
Preventive therapy is recommended for those neonates whose whom mother has any form
of active TB whether pulmonary or extrapulmonary detected in pregnancy or after birth or if
the neonate exposed to any infectious case of TB after birth. Active disease should be ruled
out in neonates. INH preventive therapy is given in a dose of 10 mg/kg for duration of 6
months. Pyridoxine may be given.
Chemoprophylaxis is not recommended in MDR contacts since the efficacy of 2nd line drugs
in preventing TB is not unequivocally established and also because these drugs can be fairly
toxic.
Modern chemotherapy is so efficacious that separation of the mother and infant is no longer
considered mandatory, once the mother’s therapy is started and if baby is on IPT. Separation
should occur only if the mother is ill enough to require hospitalization, if she has been or is
expected to become non-adherent to her treatment, or if she is infected with a drug resistant
strain of M. tuberculosis. Also, consideration should be given to sick mother’s health,
nutrition and rest.
Vaccination with BCG appears to decrease the risk of tuberculosis in exposed infants, and
hence all children born to mother’s with TB should receive BCG at birth even if they are
isoniazid preventive therapy.
The mother can continue to breast feed the baby. The ATT excreted in small amount in the
milk has no therapeutic or adverse effect on the baby. Appropriate cough hygiene and cough
etiquette should be observed by the mother. TST has a limited role in neonates and young
infants and testing is hence not recommended.
Perinatal tuberculosis
Congenital TB is acquired during intrauterine life or before complete passage through the
birth canal. Perinatal TB is preferred term which encompasses true congenital and neonatal
forms of disease. Distinction between true congenital cases & those acquired postnatally is
purely of epidemiological significance and modes of presentation, treatment, and immediate
prognosis do not differ between two groups and may be difficult to differentiate at times.
There are two main infectious routes for congenital TB. Transplacental route, forming a
primary complex in liver of infant with secondary hematogenous spread and by aspiration or
ingestion of infected amniotic fluid, leading to a primary focus in lungs or GIT.
Diagnostic criteria for congenital TB
Cantwell described presence of proven tuberculous disease with at least one of the following
57
• Lesions in newborn baby during the Limitation to Cantwell criteria

first week of life
• A primary hepatic complex or • Presentation may be late; after 2-3 weeks of birth
• Difficulty in demonstration of AFB in neonates if GA is
caseating hepatic granulomata
negative
• Tuberculous infection of placenta or
• Inadequate opportunities / facilities for examination
maternal genital tract
of placenta / endometrium
• Exclusion of possibility of postnatal • Percutaneous liver biopsies are also difficult to
transmission by investigation of perform, especially in sick neonates with multiple co
contacts, including hospital staff. morbid factors
Congenital and perinatal forms of TB • Incomplete evaluation of mother, especially if
mimic common neonatal illnesses and symptoms of TB are not florid and inadequate
have a uniform poor outcome. Many evaluation of contacts, including hospital attendants
patients die without diagnosis, especially compounds the problem
in conditions where the index of
suspicion is low or the GA examination is unyielding. Extensive and invasive investigations
are difficult to carry out especially in small hospitals and sick patients.
Treatment regimen of perinatal TB is similar to pediatric TB.
58
Chapter 7 - PREVENTION OF TB
Factors that predict likely transmission of TB are anatomical site of disease, positive sputum
bacteriology, radiographic findings, behaviours that increase aerosolisation of respiratory
secretions, age, HIV status and administration of effective therapy.
The risk of infection with tuberculosis (as measured by TST) is greatest if the contact is close
and with a case of sputum smear-positive disease. This illustrates that child contact screening
is important especially for close contacts of sputum smear-positive cases because they have
such a high risk of infection. Contact history (including closeness and type of source case of
TB disease) is important for children with suspected TB disease. In resource-limited settings,
the focus of contact screening is on contacts of smear-positive cases because of greater risk
and limited capacity for screening. However, cases of smear-negative pulmonary TB can also
transmit infection. Not only that, studies suggest that increased grades of smear positivity of
source case is associated with increased risk of infection in child contacts. It also shows that
closeness of contact is a risk for infection as risk of infection was much higher if the source
case was a primary care giver like mother, aunt or grandmother rather than a male relative.
Strategies to prevent TB
Following are the mainstay of strategies to prevent TB
1. Early detection and treatment of infectious cases

2. Airborne infection control practices
3. Contact screening and IPT
4. BCG vaccination
General measures to prevent spread of infections
• Keeping windows and doors open, as far as feasible, to allow fresh air into patients’ homes
• Maintaining spatial separation of at least 3 feet
• Using a surgical face mask/ cloth over mouth by the patient
• Covering mouth/nose when coughing/sneezing
• Using tissues and promptly disposing them in trash by the patient
• Performing hand hygiene if hands get spoiled with respiratory secretions by the patient
Contact screening
• All close contacts, especially household contacts should be screened for TB.
• In case of paediatric TB patients, reverse contact tracing for search of any active TB case
in the household of the child must be undertaken.
• Particular attention should be paid to contacts with the highest susceptibility to TB
infection
59
The highest priority contacts for active screening are:

• Persons with symptoms suggestive of tuberculosis
• Children aged upto 5 years age
• Contacts with known or suspected immune-compromised status particularly HIV infection
• Contacts with Diabetes Mellitus
• Contacts with other higher risks including pregnancy, smokers and alcoholics etc.
• Contacts of patients with DR-TB.
All close contacts of DR-TB cases should be identified through contact tracing and evaluated
for active TB disease as per RNTCP guidelines. If the contact is found to be suffering from
pulmonary TB disease irrespective of the smear results, he/she will be identified as an
“Presumptive MDR-TB”.
Preventive therapy
Isoniazid Preventive Therapy

Children are more susceptible to TB infection, more likely to develop active TB disease soon
after infection, and more likely to develop severe forms of disseminated TB. Children upto 5
years of age, who are close contacts of a microbiologically confirmed pulmonary TB patient
within the past 3 months, should be evaluated for active TB by a medical officer/
paediatrician. After excluding active TB he/she should be given INH preventive therapy
irrespective of their BCG or nutritional status. The dose of INH for preventive therapy is 10
mg/kg body weight administered daily for a minimum period of six months. The INH tablets
Index Case
Contacts
Smear Positive
Cavitation
Pulmonary Smear Negative
Symptomatic
Asymptomatic
Evaluate for Disease
Age of the Contact

No evidence of Disease
Age 5 years or more Age upto 5 years
Diagnose LTBI using appropriate

tests 6H
6H
60
should be collected on monthly basis. The contacts should be closely monitored for TB
symptoms.
In addition to above, INH preventive therapy should be considered in following situation:-
• 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.
• All TST positive children who are receiving immunosuppressive therapy (e.g. Children with
nephrotic syndrome, acute leukemia, etc.).
• 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 preventive therapy is planned.
12 dose weekly Rifapentine and INH regime is currently in focus for its ease and possibility of
supervised therapy and may be introduced on field trial basis in future.
Close contacts of index cases with proven DR-TB should be monitored closely for signs and
symptoms of active TB as isoniazid may not be prophylactic in these cases. Although
alternative prophylaxis treatments have been suggested, there is no consensus regarding the
choice of the drug(s) and the duration of treatment. Prompt treatment of MDR-TB is the most
effective way of preventing the spread of infection to others. The following measures should
be taken to prevent spread of DR-TB infection:
1. Early diagnosis and appropriate treatment of MDR-TB cases;

2. Screening of contacts as per RNTCP guidelines
Further research into effective and non-toxic chemoprophylaxis in areas of high MDR-TB
prevalence is required.
BCG VACCINATION
It is a live attenuated vaccine prepared from Mycobacterium bovis. Routinely given at birth or
soon thereafter based on tuberculosis risk. It is given as intradermal injections.
Efficacy is variable and ranged from substantial protection, in UK MRC trial (RR 0.22; 95% CI,
.16–.31), to absence of clinically important benefit in Chingleput trial (RR, 1.05; 95% CI, .88–
1.25). Efficacy is better in school age with prior testing (74%) and neonatal vaccination (60%).
There are marked differences in estimated efficacy according to latitude at which trials were
conducted. Greater efficacy in trials conducted at latitudes farthest from the equator. For
prevention of meningeal and military TB, overall protection by BCG is around 85% and with
neonatal vaccination it is around 90%.
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BCG lymphadenitis
BCG lymphadenitis appears as an isolated axillary (or supraclavicular/cervical) lymph node

enlargement with history of BCG on the same side. There is no tenderness and raised
temperature over swelling (except in impending rupture state) without fever or other
constitutional symptoms. TST is not helpful in distinguishing BCG lymphadenitis from TB LN.
Neither FNAC cytology nor presence of AFB or CBNAAT can distinguish between BCG or TB
adenitis as the results are similar. Though, clinical differentiation from TB lymphadenitis may
not be difficult, as cases of isolated axillary glandular TB are very rare BCG adenitis has the
following characteristic features:
✓ Preceding history of vaccination on the same side

✓ Can appear anytime with in first year
✓ More often with subcutaneous or injection high up on shoulder
✓ Injection given high up on the shoulder can cause ipsilateral cervical adenopathy
✓ Never has associated systemic issues in healthy children
Types of BCG lymphadenitis
- Simple or non-supurative
- Suppurative (Distinguished by development of fluctuations in swelling, with erythema & oedema
of overlying skin)
- Disseminated BCGiosis (seen in immunosuppressed HIV infected children)
Course of untreated lymphadenitis
Non suppurative lymphadenitis regresses spontaneously over a period of few weeks to

months; can take upto 6-8 months. In a few cases, progressive enlargement & evolution into
abscess formation can occur. Suppuration may develop in 30% to 80% of cases of BCG
lymphadenitis.
Suppurative lymphadenitis can regress spontaneously but most likely outcome in these cases
is development of spontaneous rupture and sinus formation. Finally, healing of sinus occurs
through cicatrisation, but process usually takes several months.
Management of lymphadenitis
Non-suppurative BCG lymphadenitis is allowed to regress spontaneously. If already

suppurated or suppuration develops, needle aspiration may be done to prevent rupture and
subsequent large ulceration. Repeated aspiration on refilling may be required, and gradually
the pus starts thinning out and decreasing in volume.
62
Surgical excision is resorted to if needle aspiration fails, as in cases with multiloculated or

matted glands. Erythromycin and ATT are ineffective in hastening regression or preventing
suppuration in BCG lymphadenitis and should not be used.
TREATMENT OUTCOMES
The treatment outcome definitions make a clear distinction between three types of patient
groups (cohort):
1. Patients treated for drug susceptible TB

2. Patients treated for RR/MDR-TB/XDR-TB
3. Patients treated for Mono/poly-DR-TB
Treatment Outcomes for Drug-susceptible TB patients
Cured: microbiologically confirmed TB patients at the beginning of treatment who was smear
or culture negative at the end of the complete treatment
Treatment Completed: A TB patient who completed treatment without evidence of failure

or clinical deterioration BUT no record to show that the smear or culture results of biological
specimen in the last month of treatment was negative, either because test was not done or
because result is unavailable or test is not feasible e.g. in some forms of EPTB there may
be practical difficulties of repeating the biologic specimen at the end of therapy
Treatment Success: TB patients either cured or treatment completed are accounted in

treatment success.
Failure: A TB patient whose biological specimen is positive by smear or culture at the end of
treatment.
Non-responder (Failure to Respond): A case of paediatric TB who fails to have microbiological

conversion to negative status or fails to respond clinically/ or deteriorates after 4 weeks of
compliant intensive phase shall be deemed to have failed response provided alternative
diagnoses/reasons for non-response have been ruled out
Lost to Follow Up: A TB patient for whom treatment was interrupted for 1 consecutive month
or more
Non-Evaluated: A TB patient for whom no treatment outcome is assigned. This includes

former ‘Transfer-out”
63
Treatment Regimen Changed: A TB patient who is on first line regimen and has been
diagnosed as having DRTB and switched to drug resistant TB regimen prior to being declared
as failed
Died: A patient who has died during the course of anti-TB treatment
Treatment Outcomes for RR-/MDR-TB and/or XDR-TB patients
Cure: Treatment completed as recommended by the national policy without evidence of

failure AND three or more consecutive cultures taken at least 30 days apart are negative after
the intensive phase.
Treatment Completed: Treatment completed as recommended by the national policy

without evidence of failure BUT no record that three or more consecutive culture taken at
least 30 days apart are negative after the intensive phase or sample not accessible.
Treatment Success: The sum of cured and treatment completed.
Treatment Failed: treatment terminated or need for permanent regimen change of at least
two or more anti-TB drugs in CP because of:
❖ Lack of microbiological conversion by the end of the intensive phase or

❖ Microbiological reversion in the CP after conversion to negative or
❖ Evidence of additional acquired resistance to fluroquinolones or second line injectable
drugs or
❖ Adverse drug reactions (ADR)
64
Chapter 8 - Programme Management

Recording and Reporting:
The reporting system used for monitoring TB control is NIKSHAY – a case based, web based
surveillance tool, developed indigenously for the nation. This digital repository of program
data allows the program managers to make informed decisions on a real time basis for better
TB control activities. Nikshay is also the only recommended tool for private sector to notify
TB cases. Nikshay can be accessed via the web or conveniently through the mobile app for
ease of notification.
Directory Services are incorporated in Nikshay for ease of communication and patient linkage.
In addition to existing treatment adherence strategies, ICT enabled strategies that help
support treatment adherence reporting have been incorporated.
PHI Level:
At the PHI Level, after diagnosis of a case of TB, the patient is registered in TB notification
register and notified in Nikshay on a real-time basis. Subsequently, the patient is initiated on
treatment and a treatment card is opened. Each patient record consists of patient enrolment,
request for test and updating report details, filling up treatment card, follow up, contact
investigation, HIV status and treatment outcomes. All modules should be updated in a timely
manner during the course of anti-TB treatment of the patient. PHI wise patient registration
status can be monitored at the TU level by the Medical officer and DTO.
Private TB notifications are also entered in Nikshay. Facilities already registered under Nikshay
can either notify directly using the web or mobile portal, or report to the nodal officer ie the
DTO. The notifications received by the nodal officer are entered in Nikshay using the
respective PHI ID and password. At the PHI level, public health action is initiated by STS/Health
Visitor/General health system staff and details of the same like date of home visit, list of
household contacts, number of symptomatic contacts, chemoprophylaxis status, linkage to
HIV counselling and testing, linkage to CDST services are also entered. Public health action
must be undertaken and details entered within two weeks of date of notification.
Monthly Programme Management and logistics report (PMR) is prepared by the PHI Medical
officer and sent to the TU. This report is reviewed on a monthly basis at the TU level .The
monthly PHI PM reports are collated at the TU on a quarterly basis and simultaneously
entered in NIKSHAY as the quarterly TU PMR. This report gives details of the supervisory
activities, microscopy, case finding, referrals, treatment initiation, presumptive MDR, Quality
of DOTS implementation, drug and logistics and lab consumables.
65
TU Level:
Periodic reports generated from Nikshay include case notification reportand treatment
outcome report. The case-based entry at PHI level for the TU forms the basis for generation
of all reports at the TU level. In case of missed or delayed Nikshay entry, or incomplete
updating of the modules at the PHI level, the corresponding report does not reflect the true
performance of the PHI/TU. It is therefore mandatory that all modules be updated on real
time basis for accurate reporting.
Results of patients undergoing culture and drug susceptibility testing from an accredited lab
are available without delay for treatment decision making. Details of patients requiring
admission at the Drug resistant tb center are also available for further action.
District level:
District level periodic reports are also generated from Nikshay. These reports are monitored
periodically by the DTO and District Collector. The TB notification status from registered
private health facilities and prompt initiation of public health action is also monitored
periodically.
State Level:
The quarterly reports from all districts are monitored at state level. Areas requiring
intervention – for eg case finding, case holding based on the performance indicators are
identified. The district specific action plan is formulated to improve performance and address
gaps in program management. The reports from the districts can be reviewed for any given
time period from the state, as this is a real time program monitoring tool.
National Level:
Reports from all states are reviewed at CTD and timely feedback is provided to the states for
undertaking corrective action.
Supervision and monitoring:
In addition to routine supervisory activities as listed under RNTCP, the medical officer should
undertake the following activities with regard to pediatric TB patients:
Correct diagnosis and treatment initiation: The Medical Officer should elicit detailed history
and review all relevant records to ensure that a correct diagnosis has been made and
appropriate treatment initiated.
Completeness of treatment card: Medical officer should ensure that all details of the
treatment card are duly filled and simultaneously entered in Nikshay. Address and phone
66
numbers of patient, contact person, treatment supporter should be entered in relevant

records. Updating of patients’ weight, details of follow up visits, retrieval actions done in case
of missed doses are also to be supervised.
Efforts taken by the STS and Health visitor in tracing the index case and contact screening
should be closely supervised and documented in the remarks column of the treatment card.
Supervisory home visits should be undertaken frequently with aim to monitor adherence,
document adverse drug reactions and growth monitoring.
Public health actions initiated for privately notified pediatric patients should be given priority
and all efforts supervised to ensure a successful treatment outcome.
Chemoprophylaxis: Medical officers should monitor all children started on chemoprophylaxis

and verify correct dosage and timely refills.
Advocacy Communication and Social Mobilization
Advocacy, Communication and Social mobilization activities in the context of pediatric TB

should be carried out at individual and community level. Activities should be aimed at creating
awareness among people about childhood TB (signs and symptoms) diagnosis, and treatment
in order to increase accessibility and utilization of services. It should be remembered that
ACSM activities are not substitute to TB control activities. These are supportive services to
enhance the quality of services; widen the reach of activities and facilitate the process of
implementation of TB care services, mobilize the civil society and actively engage panchayat
raj institutions in the care and control of TB among children.
Inter sectoral coordination
RNTCP and Child Health Division are working together to develop a collaborative framework
between the two divisions in order to reduce morbidity and mortality of Tuberculosis among
paediatric population. Engagement with Rashtriya Bal Swasthya Karyakram (RBSK) is also
underway for incorporation of questions pertaining to TB in screening Tool and referral Card
for Children of RBSK. Indian Academy of Paediatrics have also been engaged to reach out to
pediatric patients being managed in the private sector, through involvement in policy
divisions and support in capacity building of all its members.
DEATH AUDIT
The Medical Officer should conduct an in-depth audit of all the deaths occurring amongst the
TB patients irrespective of initiation of treatment. Similarly, DTO should conduct death review
of all MDR-TB patients died. This would be beneficial in understanding the cause leading to
the deaths and guide the programme in taking appropriate action to prevent them.
67
Incentives to patients
“Nikshay Poshan Yojana”- It was Launched from 01st April 2018. Under this scheme,
Nutritional support through Direct Benefit Transfer of 500 INR per month for all patients on
TB treatment throughout duration of treatment. The patient needs to be registered in the
Nikshay portal (Annexure 6)
Tribal patient incentive – Under this scheme, 750 INR per patient in tribal areas for
transport support
Incentive to providers
Private Provider Incentive: Under this scheme, 500 INR at notification & 500 INR on
reporting treatment outcome is provider to the private provider who first notifies the case
to the programme (Annexure 7)
Informant incentive: Under this scheme, Incentive of 500 INR to informant for notification
of patients in public sector
Incentive for Treatment support: Under this scheme, a treatment supporter for a new Case
of TB receives 1000 INR at completion of treatment and for a Drug Resistant Case receives
2000 INR at completion of intensive phase, 3000 INR at completion of treatment
68
Annexures
Annexure 1 Tuberculin Skin test (TST)

Several studies were conducted in US and elsewhere in new recruits, using strengths 1, 5, 10,
250 units. Reaction to low doses was seen in persons with either history of contact, suspicion
of disease or those with active tuberculosis. The increasing strength when used, started losing
discrimination between infected (exposed) and non-infected (non-exposed). 5TU PPD-S had
the best discriminatory power and is therefore the recommended dose for clinical testing.
Later studies showed 1 TU PPD RT23 is equivalent to 2.5 TU of PPD-S, 2 TU RT 23 with Tween
80 is equivalent to 5 TU PPD-S. Lower doses were chosen due to fear of stronger reaction with
environmental mycobacteria and BCG vaccination. Current recommendation is to use 2TU
PPD RT23 for all diagnostic purposes in our country. Indigenous manufacturers available
formulations are products standardised against PPD RT 23 made by SSI, Copenhagen.
Commercially available tuberculins in the country are 1, 2 and 5 Tuberculin Unit (TU) PPD
(RT23 equivalent).
The width of reaction (induration) in the horizontal plane is noted for interpretation.
Mantoux’s test or PPD skin test is considered positive if the induration is 10 mm or more, In
HIV coinfected, 5mm may be taken as the cut off. 10 mm was considered the best anti-mode
cut off between the two populations using PPD-s 5TU (equivalent PPD RT23 2TU) to have
highest sensitivity and specificity for M tb infection. This validates the current
recommendations for using 10 mm cut off with 2 TU PPD RT23 in our country. Currently, the
laboratories more often use 5 TU PPD (RT23 equivalent), or sometimes even some other
higher strengths or types of PPD are used. There is no linear relationship between the reaction
obtained and strength of PPD used. Cut offs for higher strengths are not established. Higher
strengths increase false positive reactions. The standard cut off of 10 mm can actually not
be justified for any higher strength of PPD used. Degree of reaction, including necrosis and
ulceration, may not necessarily differentiate infected from diseased. Prior BCG vaccine has
minimal influence on PPD reaction.
The technique of administration of tuberculin and reading of the test is described in box #.
Preparation of site Record information

• 5–10 cm (2–4 inches) below elbow • Date and time of test
joint, on ventral forearm • Site location
• Forearm placed palm-up on a firm, • Lot number of tuberculin
well-lit surface • Tuberculin strength
• Skin should not have barriers e.g. scars,
sores, veins
• Clean with alcohol swab
Preparation of injection Instruction to the patient
• Expiry date and Tuberculin strength (2 • To avoid scratching the site,
TU of PPD RT23) checked
69
• A single-dose syringe with a short (1/4 • Keep it clean and dry, and avoid putting
to 1/2 inches) 27-gauge needle with a creams/ lotions, adhesive bandages
short bevel loaded with 0.1 ml • Mention that getting the site wet with
tuberculin water is not harmful, but the site should
not be wiped or scrubbed.
Injection of test drug
• Needle inserted slowly, bevel up, at
angle of 5–15°
• Needle bevel should be visible just
below skin
• PPD injected gently raising an Intra-
dermal wheal of at least 6 mm
diameter
• If not, repeated 2 inches away from the
original site
• Discard the used syringe in the sharp
container (as per BMW guidelines)
NOTE:
PPD must be kept refrigerated at 2-8*C (DO NOT FREEZE)
Check the expiry date and date that the vial was opened. The vial should be discarded if it has been
opened for more than 30 days or expiry date has passed. The vaccine vial should be taken if the VVM
(Vaccine Vial Monitor) on the box (of 10 vials) has changed its color.
NOTE: After use, the tuberculin vial should be returned to the refrigerator
Test reading: Induration should be measured and not erythema. Palpation with fingertips
or using ball point method should be done to find margins of the induration across
(horizontally). Induration may not always be visible, so palpation with fingertips should be
relied upon to discover it. The area is lightly touched with pads of fingertips. Using a light,
gentle motion, fingertips are swept over surface of forearm in a 2-inch diameter around
injection site in all four directions to locate the margins or edges of induration. The margin is
marked at the edges across the arm. The induration should only be measured using a
transparent ruler/scale. “0” of ruler line should be placed on left edge of the induration and
ruler line should be read on the right edge of the induration as identified (use lower
measurement if between two gradations on mm scale). Measurement should be recorded in
millimetres (mm) across the horizontal axis only. The test is not recorded as negative/positive.
Instead, no induration is 0 mm. In case there is huge erythema but no induration, it may be
due to an inadvertent subcutaneous leak. In such situations the test is repeated on the other
arm.
70
Ideally, the test should be read between 48 and 72 hours
Test is negative
Repeat in other forearm
If child comes beyond 72 hours

up to 7 days
Test is positive
Interpret as positive
If child comes beyond 7 days Repeat test in other forearm
Interpretation falacy
Degree of reaction, including local skin necrosis, vesiculation and ulceration does not
differentiate infected from diseased. Reactivity in BCG vaccine recipients generally wane over
time and about 10% may have reaction above 10mm; particularly in the first year after
vaccination. In high burden countries a positive TST results is likely due to TB infection if risk
factors are present even in a BCG vaccinated child.
Causes of false negative Causes of false positive
• Incorrect technique of administration or • Incorrect technique of
Interpretation Interpretation
• Improper storage of tuberculin • BCG vaccination
• Immunodeficiency/suppression • Infection with mycobacterium
– Primary other than TB
– Secondary like HIV infection, SAM,
Immunosuppressive (e.g. steroids)
• Infections
– Viral (e.g. measles, varicella)
– Bacterial (e.g. Typhoid, leprosy, pertussis)
• Vaccinated with live viral vaccine (within 6
weeks)
• Neonatal patients
• Severe forms of TB
71
Annexure 2: Method to collect gastric aspirate

Steps for GA sample collection procedure include-
1. Explain the procedure and take consent from the parent or guardian
2. Patient should be fasting for 4-6 hours prior to collection procedure. In an admitted child it
may be done early in the morning, while the child is still asleep and in-bed.
3. Place the patient in a supine position and restrain using the long-folded sheets.
4. The ryle’s tube needs to be placed in the body of stomach through the nose. The required
length of the tube to be inserted can be ascertained by measuring the distance from tip of
the nose to the tragus and then from the tragus to the midpoint between xiphisternum and
umbilicus. One could make this measurement directly using the tube or else using a
measuring tape.
5. Apply lubricant jelly to the tube
6. Gently insert the tube through the nose in the direction perpendicular to the face upto the
measured length. This can often be assisted by asking the patient to swallow.
7. Fix it to the nose with an adhesive tape.
8. It is important to confirm that the tube is correctly positioned in the stomach. This can be
ascertained by pushing some air with a syringe into the tube and simultaneously
auscultating for the gush of air over the epigastrium with a stethoscope. In case, the patient
starts choking or coughing while inserting the tube then the tube should be withdrawn and
re-inserted after the patient has settled.
9. Once the Ryle tube has been inserted into the stomach, its position can be checked by
hearing a gush of air over the epigastrium. One can also aspirate the stomach contents to
confirm the position.
10. Gently aspirate from the tube keeping the patient in the supine position.
11. If there is no aspirate or the quantity is inadequate, try re-aspiration after shifting the
patient in the left and right lateral positions.
12. If one still does not get adequate specimen in both supine as well as lateral positions, further
aspiration can be retried by shifting the tube a little in or out, in an effort to hit the stomach
contents. The repeat aspiration should be done while rotating the patient through supine
and lateral positions.
13. In case, direct aspiration fails to provide adequate specimen, one should instill about 10 ml
normal saline through the tube slowly. Align it to gravitate on its own.
14. After instilling, re-aspirate rotating the patient through supine as well as in left and right
lateral positions.
15. Repeat these steps till gastric aspirate is obtained
16. Collect the aspirate in a sterile container. A specimen is considered adequate if contains
about 10-15 ml of stomach contents.
17. After collection of gastric aspirate, gently remove the tube by closing its cap or pinching the
tube
72
Annexure 3: Method to collect induced sputum

Steps for IS sample collection procedure include-
1. Patient should be fasting for 2-3 hours prior to collection procedure.

2. Explain the procedure and take consent from the parent or guardian.
3. Procedure should be performed in a well-ventilated room having an exhaust fan while
wearing a N95 facemask
4. Baseline values of respiratory rate, pulse rate, chest retractions, wheeze and oxygen
saturation should be taken prior to the procedure
5. Priming with Salbutamol can either be done through Metered Dose Inhaler (i.e. MDI) or
nebulization using either respiratory solution or respule. MDI has an advantage that it takes
less time and is as effective as nebulization. However, nebulization facility is essential to give
3% hypertonic saline.
a. MDI: Salbutamol is administered by sequentially giving 2 puffs, i.e. 100 micrograms
through MDI with a spacer. This prevents bronchospasm from 3% hypertonic saline
nebulization in children predisposed to it.
b. Nebulization using respiratory solution or respule: The Neb respirator solution
contains 5 mg of Salbutamol per ml. The dosage for administration is 0.15 mg/kg.
Taking age in to consideration, the administered dosage varies. For neb respule, use
equivalent doses as respirator solution. Fill up the required amount of salbutamol
from respiratory solution or respule. Load the drug formulation to the nebulization
chamber. Add saline if required to ensure that volume of formulation in the
chamber is above its minimal fill volume.
6. Nebulize with 5 ml of 3% sterile hypertonic saline. Use a sterile commercially available
preparation. Nebulization can be done through a jet nebulizer attached to pressurized
oxygen or air supply, at the lowest flow rate needed to produce adequate mist which
USUALLY is 5 to 7 L per min.
7. While the child is being nebulized, give a container to the child to collect any expectorated
sputum.
8. Child may start expectorating while being nebulized with 3% saline. If the sample is
adequate, then the procedure may be wrapped here, and expectoration may be sent to lab
for further processing.
9. Few children will only produce or bring up saliva or no expectoration on their own after 3%
hypertonic saline nebulization. In such situations, one can loosen up secretions and assist
child in secreting sputum by chest percussion. The purpose of chest percussion is to bring
the secretions from the peripheral to central airways, from where the child can cough out
the secretions.
10. Palm of the hands while doing percussion should be made into a cup shape formed by the
fingers and the thumb, instead of flat open hand. This avoids hurting the child. For younger
children, it is ideal to percuss with fingers. Movement while doing percussion should be at
wrist and not elbow or shoulder. For percussion, we must cover all areas of chest in sitting,
supine and prone positions.
11. If there is sputum production and child can expectorate, collect this sputum in sterile
container
12. If still child is unable to expectorate or if it is a young child who needs assistance to collect
secretions, then sputum can be collected by suction through nasopharynx or oropharynx.
13. Use sterile mucus extractor or suction trap with the other end of the extractor connected to
gentle suction of around 100 cm of water. The catheter is inserted through the nose.
73
14. The length of tube to be inserted is measured from side of the nose to the angle of the
mandible.
15. Apply lubricant jelly or wet the tube.
16. The catheter is gently inserted into the nose in a direction perpendicular to the face.
17. Release suction. As the catheter touches the posterior pharyngeal wall, it can provoke
cough. The loosened secretions are brought up with the cough and suction will facilitate its
collection in mucus extractor or suction trap.
18. In this child, as you can see respiratory secretions have been collected. This should be
immediately transported to GeneXpert lab
19. Monitor for 30 mins after the procedure for respiratory complaints like respiratory rate,
pulse rate, chest retractions, wheeze etc.
20. Fresh sterile disposable tubing and chamber for nebulization should be used for each
patient.
74
Annexure 4: Needle aspiration of LN and similar swellings

1. Explain the procedure and take consent from the parent or guardian
2. Place the patient in a supine position and restrain using the long-folded sheets.
3. Disinfect the skin at the planned needle puncture site
4. Firstly, with alcohol (70%) followed by povidone-iodine and again with alcohol (70%).
5. Between each application, let the area dry.
6. The swelling or lymph node should be immobilized in between the fingers of one hand.
7. Pass the needle through the skin, avoiding any superficial veins
8. Direct the needle towards the center of the target.
9. Precautions must be taken to ensure that the needle tip is not pointing towards the
operator’s fingers immobilizing the lymph node or deep structures below the node.
10. Once in the target, the needle tip is moved within the target, while applying suction using
10- or 20-ml syringe.
11. Prior to withdrawal of the needle from the swelling, negative pressure must be released.
12. Remove the needle from the swelling by pulling straight out so as not to lacerate the skin.
13. Remove as much aspirate as possible from the swelling. Aspirate may be taken from multiple
swellings and pooled before sending to laboratory for bacteriological confirmation.
14. At the end of the procedure, dress the site after applying antiseptic
15. Send the aspirated collection to laboratory for further processing.
16. If the aspirate is too small for transferring to container, then one may collect the material
after aspirating and rinsing the syringe using minimal sterile normal saline. Avoid excess
dilution with saline as it can lead to false negative result.
75
Annexure 5 Treatment Recommendation for Delamanid in Children:

Source Guideline for use of Delamanid - print version.pdf-Guidelines for use of Delamanid in
the treatment of DR-TB in India 2018
Delamanid (Dlm) is the first approved newer drug in the class of nitro-dihydro-imidazo-
oxazoles for the
treatment of MDR-TB, indicated for use as part of an appropriate combination regimen for
pulmonary MDR-TB in adult and adolescent (6-17 years) patients when an effective
treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.
Its characteristics:
1) Chemical class: nitroimidazole
2) Mechanism of Action: Bactericidal (Half-life: 36 hours)
• By blocking the synthesis of mycolic acids (i.e. stopping the bacteria from
creating building blocks important for their cell walls).
• By poisoning them with nitric oxide, which the drugs release when
metabolized
3) Each film-coated tablet contains 50 mg Delamanid.
4) Excipient with known effect: each film-coated tablet contains 100 mg lactose (as
monohydrate).
WHO recommendations on use of Delamanid
Dlm may be added to a WHO-recommended regimen for patients in above mentioned age
group with pulmonary MDR-TB under the following conditions:
• When an effective treatment regimen containing four second-line drugs in
addition to pyrazinamide (Z) according to WHO recommendations cannot be
designed;
• When there is documented evidence of resistance to any FQ or second-line
injectable drug in addition to MDR.
• When there is higher risk for poor outcomes (eg. drug intolerance or
contraindication, extensive or advanced disease)
Add Dlm to a longer MDR-TB regimen when it cannot be composed according to WHO
recommendations. When an effective and well-tolerated longer MDR-TB regimen can be
otherwise composed, the addition of Dlm may not be warranted.
Use of Dlm in the shorter MDR-TB regimen under programmatic conditions is not
recommended by WHO given the lack of data.
Dlm may have a protective role in preventing the emergence of additional drug resistance.
Hence, the conditions for Dlm use in individual patients remain the same. Dlm should be
retained in country guidelines, national essential medicine lists and
procurement options.
76
The National PMDT Scale up Plan for 2017- 2020, an operational plan, was developed by
consolidating the state wise PMDT micro-plans developed during the series of regional PMDT
review meetings with 35 states organized by CTD at north, south, west, east and north east
zone in the year 2015-2016. Outputs include clarity and transparency on national training and
district appraisal needs, laboratory scale up requirements, national/state/district
responsibilities understood by all and scale up plan of Newer drugs (Bdq & Dlm), Shorter MDR-
TB Regimen and DST guided treatment.
Although, WHO has issued an interim guideline in 2016 for the use of Delamanid in this age
group with a dosage of 50 mg BID (6-11 years) and 100 mg BID (12-17 years) for 6 months, it
is yet to be approved by regulatory authorities including India. Once regulatory approval for
use of Delamanid in children and adolescent (6-17 years) are obtained, they would be
considered in the inclusion criteria.
Criteria for patients to receive Delamanid
1) Basic criteria
Inclusion criteria:
Adults, adolescent and children (≥6 yrs), including people living with HIV (PLHIV), not
eligible for a shorter MDR- TB regimen for reasons of resistance, contraindication or
tolerability
– MDR/RR-TB with resistance to any/all FQ OR any/all SLI
– XDR-TB
– Mixed Pattern DR-TB including patients who are failing any DR-TB regimen or have drug
intolerance or contraindications or who return after interruption or emergence of any
exclusion criteria for shorter MDR-TB regimen or with extensive or advanced disease and
others deemed at higher baseline risk for poor outcomes.
Special caution: HIV+ (in consultation with ART centres), 65yrs+, patients with diabetes,
hepatic or severe renal impairment, those with serum albumin <2.8 g/dL or those who
use alcohol or substances
Additional considerations:
• Delamanid may be considered with caution by the NDR-TBC committee under specialist
consultation in patients with baseline serum albumin <2.8 g/dL. Very frequent
monitoring serum albumin need to be done in such patients.
• Electrolyte imbalances (Serum K, Mg, Ca) to be corrected before initiating Delamanid.
• Females should not be pregnant, or should be using a non-hormone-based birth control
method. They should be willing to continue practicing birth control methods throughout
the treatment period, or have been post-menopausal for the past 2 years.
• Patients with controlled stable arrhythmia can be considered after obtaining cardiac
consultation.
• Delamanid film-coated tablets contain lactose. Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
can be considered after obtaining specialist consultation.
77
Exclusion Criteria:
• Children under 6 years
• Pregnant & breastfeeding women
• Patients with repeated demonstration of a QT interval >500 ms, history of torsades
de pointes or cardiac ventricular arrhythmias
• Hypersensitivity to the active substance or to any of the excipients
Extra-pulmonary TB:
Although, there is no regulatory approval for use of these drugs in EP MDR-TB patients as
the evidence is still evolving, there is no absolute contraindication for use in EP MDR-TB
patients if benefits offset any potential harm. Effectiveness of Dlm in central nervous
system TB is yet un-established.
Patient Education Booklet for Dlm-containing regimen
A detailed patient education booklet has been developed for educating the patient on the
use of Dlm (Appendix 1). The patient education booklet for Dlm (Appendix 1) must be
provided to the patient along with the RNTCP PMDT treatment book that contains the list of
drugs contraindicated or to be used with caution with Dlm. The patient must be motivated
to carry these documents at every visit to any health care provider throughout the
treatment course.
78
As per the programme guideline use of Delamanid in this age group 6-11 years with a
dosage of 50 mg BID and 100 mg BID of 12-17 years for 6 months is recommended
Use delamanid in children: (Source-Rapid Clinical Advice, 2014-The Sentinel Project )
a) Children with confirmed MDR-TB and additional resistance to one or more of the second-line agents (based on Drug
Susceptibility Testing - DST)
b) Children with probable MDR-TB and additional resistance to one or more of the second-line agents (i.e. children exposed to
a source case with such a drug resistance profile),
c) Children who are failing MDR-TB therapy (e.g. children with co-morbidities such as HIV, diabetes, or malnutrition or other
immune-compromising conditions and also children with extensive disease-defined as pulmonary disease with the presence of
bilateral involvement or the presence of cavities or those with severe forms of extrapulmonary disease). Delamanid should not
be added as a single drug to a failing regimen and careful adherence support must be provided to the child and his or her family
during treatment and should undergo close clinical monitoring.
NOTE-
1) There are currently only limited data on the use of delamanid in adults with HIV and limited PK data on drug-drug
interactions with anti-retrovirals; however there do not appear to be any significant interactions with antiretroviral
therapy. In adults, HIV infection is not a contraindication to receiving delamanid and no changes to antiretroviral therapy
are currently recommended with delamanid treatment.
2) There is no data on cerebrospinal fluid penetration of Delamanid, but its high protein binding suggests it may have
limited penetration; this should be considered when constructing a treatment regimen for persons with MDR-TB
meningitis.
Delamanid can be given to children with MDR-TB and the indications specified above, if they are aged 6 years and above and
their weight is 20kg or more, as PK and safety data to guide optimal dosing is available for this population
The PK and safety studies of Delamanid in children support the following dosing recommendations:
Weight Range Dose Duration
20-34kg 50 mg twice daily For 24 weeks

35 kg and above 100mg twice daily For 24 weeks
Children who have a known allergy to Delamanid should not receive the drug
Delamanid may not be effective in children who have been previously treated with Delamanid or another nitroimidazole agent
(i.e. pretomanid), however, there are likely to be v few children who have experience with either of these medications.
Delamanid can be considered for any child on MDR-TB treatment who develops significant intolerance to one or more of the
second-line drugs. The offending agent should be replaced with Delamanid at the earliest sign of intolerance
Safety Monitoring and Programmatic Recommendations for Delamanid in Children-
ECG monitoring to assess for QTc prolongation should be carried out at baseline and then on monthly basis for children on
Delamanid-
1) Children on Delamanid may be at risk for mild to moderate QTc prolongation therefore, the use of other QTc prolonging
TB medications (i.e. moxifloxacin, clofazimine, Bedaquiline) should be limited where possible, although this may be
challenging in the treatment of MDR-TB.
2) Other baseline and follow-up tests for children on Delamanid should follow guidelines for programmatic management
of MDR-TB and include, at a minimum, clinical assessment for adverse events, dose re-evaluation, monthly liver function
tests and potassium while the child is on Delamanid
Children with MDR-TB on Delamanid would likely benefit from nutritional support and protein supplementation, thus an
appropriate nutritional support should be provided
As is recommended for adults on Delamanid, all children who receive Delamanid should be carefully followed as a cohort and
be included in active Drug Safety Monitoring and Management (aDSM) planning and implementation- to ensure any serious
and severe adverse events experienced by child on new TB drugs are reported to a centralized monitoring body within the country
in order to continue building the safety database of these drugs.
79
80
Government of India
Ministry of Health & Family Welfare
(Central TB Division)
Nutritional Support to TB patients (Nikshay Poshan Yojana)
1. Scheme details / components:
Ministry of Health and Family Welfare, Government of India has announced the scheme
for incentives for nutritional support to TB patients. This scheme will be called “Nikshay
Poshan Yojana”.
2. Beneficiary:
All notified TB patients are beneficiaries of the scheme.
3. Eligibility:
All TB patients notified on or after 1st April 2018 including all existing TB patients under
treatment are eligible to receive incentives. The patient must be registered\notified on the
NIKSHAY portal.
4. Benefit:
Financial incentive of Rs.500/- per month for each notified TB patient for duration for
which the patient is on anti-TB treatment. For existing patients on treatment on 01/04/2018,
incentives shall be provided for the period of treatment remaining after 01/04/2018.
Provided that for existing patients on 01/04/18, only such patients for whom the remaining
period of treatment after 01/04/18 is more than or equal to one month, shall be eligible for
incentive. Also, existing patients on 01/04/18 shall be entitled to receive incentives only
for full months of remaining period of treatment (partial months shall be dropped).
The scheme is registered under Direct Benefit Transfer. The incentives can be distributed
in Cash (only via DBT preferably through Aadhaar enabled bank accounts) or in-kind. The
States that are already distributing incentives in-kind may continue to do so subject to the
condition that the total value of the food basket being distributed must not be less than Rs.
500 per month. Such states where such ‘in-kind’ support is provided by the state;
concurrence should be taken from Ministry of Health & Family Welfare, Government of
India.
5. Start date: 1st April 2018
5. Funding:
80
The scheme is a centrally sponsored scheme under National Health Mission (NHM).
Financial norms of NHM in terms of cost sharing, are applicable to the scheme.
6. Area of implementation:
This scheme is implemented across all States and UTs in India.
7. Schedule of payment:
 Each TB patient whether public or private sector notified must be notified on the
Nikshay, platform.
 For ease of transaction, following arrangement will be followed –
Type of patient New Previously treated Drug resistant TB

Usual duration of 6 months 8 months 24 months (9-12
treatment months for shorter
regimens)
First incentive On notification On notification On notification
Second incentive @ 2 months on End of @ 3 months on End of @ 2 months of follow-
IP follow-up result IP follow-up up result
Third incentive @ 6 months on End of @ 5 months of @ 4 months on follow-
treatment follow-up treatment up result
result
Fourth incentive --- @ 8 months on End of @ 6 months on follow-
treatment follow-up up result
result
Subsequent incentive --- --- @ every two months
till end of treatment
Exception handling For each extension of For each extension of For each extension of
treatment Rs.1000/- for treatment Rs.1000/- for treatment Rs.1000/- for
two months or if two months or if two months or if
extension is only for extension is only for extension is only for
one month then @ one month then @ one month then @
Rs.500/- pm Rs.500/- pm Rs.500/- pm
Note:
(i) The payment schedule for patients already notified on Nikshay as on 01/04/2018 will
also be the same. However, payment to such patient shall be for the remaining period
of treatment.
81
(ii) For paediatric TB patients where Bank accounts are not available, the money shall be
deposited in parents / guardians accounts whose details are to be sought and entered in
Nikshay against the patient’s records.
(iii)For patients not having Bank account or Aadhaar number, health staff will facilitate
opening of Bank a/c for the patient preferably under Jan Dhan Yojna and will also
facilitate his/her Aadhaar enrolment.
8. Timelines / Periodicity:
Beneficiary list creation and incentive payments will be done as per following schedule –
Entry of each TB patient with Bank a/c and Aadhaar in Realtime (same day)
Nikshay and its follow-up details
Preparation of beneficiary list (maker) 1st of every month
Checking of beneficiary details (checker) 3rd of every month
Approval of beneficiary list with details (approver) 5th of every month
Processing of payments 7th of every month
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Annexure 1
Scheme: Incentives for notification of TB patients by Private Providers
1. Incentives:
1.1. All private sector providers, including private health establishments, qualified medical
practitioners, private laboratory of pathology or microbiology and licensed private
pharmacies, registered on Nikshay will be eligible to receive the incentive of Rs. 1000/-
for notification and for reporting treatment outcome of a TB patient, subject to the
conditions presribed in para 2, as under –
1) Rs. 500/- for notification of TB patient.
2) Rs. 500/- for reporting treatment outcome of the patient. However, only the private
sector practitioners\hospitals that has notified a patient will only be eligible to receive
the incentive for reporting of treatment outcomes for that patient.
It may be noted that a private provider, if he so wishes, may authorise any staff of his
establishment to receive the incentives.
It may also be noted that a private provider may also choose to forego the incentives.
1.2. The Scheme will be effective from 01.04.2018
2. Conditions to be fulfilled for eligibility for incentives –
2.1. The provider must be registered on Nikshay. Registration of Health Facility is a one-
time requirement. A Health Facility can register itself through the online process or by
submitting the prescribed form, with full requisite information, to the DTO or by placing
a phone call at the Nikshay Sampark helpline at 1800 11 6666.
2.2. The provider must provide full details about the patient as precribed in the notification
No. Z-28015/2/2012-TB, dated March 19th, 2018 (copy enclosed), regarding madatory
notification of TB patients.
2.3. The provider must provide the contact details, preferefably a mobile phone number of
the patient or any of his near relatives or aquaintances.
2.4. In case a staff of the establishment (of provide provider) has been authorized to receive
incentive, details of the staff along with his\her bank account details must be provided.
2.5. The private provider must clearly express his option for foregoing the incentive at the
time of notification of patient.
3. Process for verification and payment:
3.1. Upon notification of a patient (either from public or private sector), Aadhar number or
details of the relevant alternative identity document of the patient, as precribed in sub-
clause (3) of clause 1 of notification No.Z-28015/24/2017-TB, dated June 19th, 2017,
published official gazzette (copy enclosed), will be seeded by the district RNTCP\public
health staff.
84
3.2. Nikshay software shall generate a list of probable duplicates, if any, for all new TB
cases notified since 01.04.2018. These lists will be generated on the basis of details of
identity documents and demographic details of the patients as entered in the Nikshay
database, in the reports section on Nikshay under the user ID of TB units concerned.
3.3. The STS or any other official autherised by the DTO or MO-TC of that TU, shall verify
the lsit of probable duplicates.
3.4. In case, there are no probable duplicates for a notified patient, no such verification shall
be necessary and the DTO shall proceed for making payment of incentives for such
cases.
3.5. In case it is found that there are duplicates for a patient in the database, the STS will
verify whether the patients in the list of probable duplicates are unique or not. In such
cases –
3.5.1. If the patient is found to be unique, the STS shall update such status on Nikshay
and the DTO will proceed for payment of incentive.
3.5.2. If it is found that a newly notified patient has already been notified on Nikshay in
past, i.e. there are multiple notifications for the same patient, then the STS shall
update the duplication status for such records on Nikshay. In such cases incentives
shall be paid for the earliest notification of the patient as per records available on
Nikshay.
3.6. All payments of incentives shall be done through the Nikshay-PFMS system following
the DBT process as being followed for other schemes under RNTCP.
4. Other points:
4.1. If the patient is not enrolled for Aadhar then apart from entering the details of
alternative identity documents, the concerned district RNTCP\public health staff should
also facilitate Aadhar enrolment.
4.2. Since all decisions for payments under the scheme are being taken on the basis of
information available on Nikshay, it is necessary to exercise due care while entering the
information at the time of notification of patients. In case it is found that an eligible
private provider is denied the incentive on account of incorrect data entry on Nikshay,
the concerned Nikshay user shall be held responsible.
85

RNTCP Pediatric Guidelines 2019

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RNTCP Pediatric Guidelines 2019

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RNTCP Updated

Central TB Division, Ministry of Health and Family Welfare,

Chapter 1 - Magnitude of problem

Challenges of managing Paediatric TB in public health

Childhood Tuberculosis (TB) is a formidable problem. Although the principles of

Lack of standard definitions, absence of simple/reliable diagnostic test and more EP

Chapter 2 - Natural history of disease

Source Case Contacts

Table- -------Risk factors for TB infection and disease in children

For TB infection For TB disease

Primary / Progressive Primary Pulmonary tuberculosis typically manifests radiologically as

• Primary complex (Parenchymal lesion with draining lymphadenopathy)

Three features common to primary infection are

Regional LN Ghon’s Focus

Airway Partial or Complete Parenchymal Cavitation with

Intra Bronchial Spread

The x-ray shows a Parenchymal cavitation with TB suspect with Miliary

Reactivation or Post Primary tuberculosis

It is important to remember that classifications of primary and reactivation TB (also referred

Chapter 3 - Case Definitions TB

Chapter 4 - Diagnosis of TB in Children

Diagnostic algorithm for paediatric pulmonary TB

• Persistent Fever >2wk, without a known cause and/or

Evaluate for EPTB

Important Notes to the Algorithm

mottling or lymphadenopathy (hilar or mediastinal) or chronic fibro-cavitatory shadows. If

Skin Test for TB

In relevant clinical setting, certain radiological lesions may be highly suggestive of

Other radiological patterns like consolidations, non-homogenous opacity/infiltrates, thin

Ultrasonography of chest is helpful to assess pleural fluid collection. It is useful to

Bronchoscopy and bronchoalveolar lavage are required in select cases of persistent

Diagnosis of Extra pulmonary TB (EPTB)

An effort should be made to establish microbiological confirmation in case of presumptive

In case CBNAAT is not available, liquid culture needs to be performed.

If investigations like CBNAAT/smear microscopy/culture etc turn out to be negative or if

Fig. 2 Diagnostic algorithm for tubercular lymphadenitis

Lymph node enlargement

Prescribe a course of antibiotics for 7

In case of non-response, suspect TB as the

Smear examination for CBNAAT / AFB by ZN Staining of

Mantoux’s test is positive in a significant proportion (>70%) of patients. On chest X-Ray, 5-

In children, lymphadenopathy is common due to recurrent tonsillitis and upper respiratory

Multimodality evaluation including clinical, laboratory, radiology, endoscopy, microbiology,

• Mild grade fever

Typically lasts 1 to 2 weeks Begins abruptly Coma, hemiplegia or

Fig 3. Algorithm for diagnosis of TBM

Suspect TBM if: Immediate investigation

Check for the following three criteria

Criterion 1 Criterion 2 Criterion 3 YES

> 3 Clinico-investigative features >2 Risk factors for TBM Evidence of TB

Continue workup and management for alternative

Review assessment within 48 to 72 hours

Again review criterion 1,2,3.

Start treatment for

CNS tuberculosis other than TBM

Imaging for Tuberculoma

Contrast Appearance T2 - usually hypointense core

Bone and Joint TB

Dactylitis (spina ventosa)

Laboratory Recording & Reporting

Management of patients while DST results are awaited

Chapter 5 - Treatment of Tuberculosis

Category I -New Cases