2. ⚫Revised National TB Control
Programme (RNTCP) nomenclature
changed
To
⚫National TB Elimination
Programme (NTEP)
from January 2020
3. ◾ India has highest burden of both TB and MDR
TB and second highest of HIV associated TB
based on estimates reported in Global TB
report 2015.
◾ An estimated 71,000 cases of MDR TB emerge
annually from the notified cases of Pulmonary
TB in India.
◾ 3% among new TB cases, 12-17% among
previously treated TB cases have MDR
TB.
◾ An estimated 1.1 Lac HIV associated TB
occurred in 2014 & 31,000 estimated
number of patient died among them.
5. CASE DEFINITIONS
⚫Microbiologically confirm TB case – Biological
specimen positive for AFB or positive for
Mycobacterium tuberculosis on culture or positive
for tuberculosis through quality assured rapid
diagnostic molecular test.
6. Clinically diagnosed TB case
⚫A presumptive TB patients who is not
microbiologically confirmed but diagnosed with
active TB by a clinician on the basis of X-ray
abnormalities, Histopathology or Clinical signs
with a decision to treat the patient with a full
course of ATD.
7. Presumptive Paediatric TB
⚫Persistent fever > 2 weeks
⚫Cough > 2 weeks
⚫Loss of weight / no weight gain
⚫History of contact with infectious TB case
Loss of weight is define as loss of > 5% body weight
as compared to highest weight recorded in last 3
months
8. Presumptive DRTB (As per TOG
2016)
⚫Patients who are found positive on any follow up
sputum smear examination during treatment with
FLD, previously treated TB cases
⚫ TB patients with HIV co–infection
⚫TB patients who failed treatment with FLD
⚫Paediatric TB non responders
⚫TB patients who are contact of DR-TB (or Rif
resistance)
9. It is same as the old one
Previously called relapse
Previously called only failure
11. Diagnostic Tools
Tools for microbiological confirmation of TB
All efforts should be undertaken for microbiologically
confirming the diagnosis in presumptive TB patients. Under
NTEP, acceptable methods for microbiological diagnosis of
TB are:
Sputum Smear
Microscopy (for AFB)
Culture Rapid Molecular
diagnostic testing
Zeihl -Neelson
Staining
Fluorescent Staining
- Solid (LJ) media
- Liquid Culture
System
- Line Probe Assay
- CBNAAT/TrueNat/ Ultra
NAAT
Drug Sensitivity Testing:
Modified PST for MGIT 960 system (for both first and second line
drugs)
Economic variant of Proportion sensitivity testing (1%) using LJ
medium (as a back up when indicated)
12. CXR: Radiological manifestations of TB
⚫Patterns like
⚫Hilar / mediastinal
Lymphadenopathy
⚫Chronic
fibrocavitary
disease
⚫Miliary pattern
⚫Patterns like
⚫Consolidations
⚫Non homogenous
opacity
⚫Ground glassing
⚫Thin walled
cavities
13.
14.
15. Role of Mtb culture
Solid
culture -LJ
Not routinely available
Long TAT
Cost, an issue
Liquid culture
Mycobacterium
Growth indicator
Tube™ (MGIT)
Now available through
NTEP lab network and
other accredited
laboratories
Short TAT
Under current Universal DST strategy
may be used upfront with specimens like
IS/ GA/BAL, if molecular tests are
negative
In the past
Now
Diagnostic yield can be
improved with MTb
culture
16. Newer Rapid Molecular Tests for Tuberculosis
Xpert MTB/RIF
UltraTM
Truenat™ MTB-
RIF Dx ™
Developed by the Indian firm
MolBio Diagnostics Pvt Ltd
Goa
Battery operated
2-step testing, not fully
automated, may need
centrifuging of samples like GA
Requires a two step process:
DNA extraction and then
addition to the chip
Newer generation Nested PCR
cartridge used in the same
equipment
Ultra has lower detection limit (16
bacilli per ml sputum) as
compared to 131 per ml
for Xpert® MTB/RIF
Especially useful for paucibacillary
disease: children, HIV TB-coinfection
Ultra may replace Xpert® MTB/RIF
in near future
18. • Persistent Fever >2wk, without a known cause and/or
• Unremitting Cough for >2wk and/or
• Weight loss of 5%; or, no wt gain in past 3 mo despite adequate nutrition;
or, failure of nutritional rehabilitation in babies with severe acute
malnutrition
With or without Contact with patient with Pulmonary TB in past 2 years
Chest X-ray
Microbiologically
confirmed TB Case.
CXR highly
suggestive
Expectorated sputum/ GA/IS
for NTEP approved NAAT for
Mtb
NAAT +
ve
NAAT -ve
CXR Non specific
shadows
Persistent shadow and
symptoms
Give course of appropriate
antibiotics
Skip this step if already received an appropriate
antibiotic course
NAAT+ ve
HIV
testing
should be
offered to
all
children
diagnosed
with TB
CXR
Normal
Algorithm for
Pediatric
Intrathoracic
TB among
children with
no risk
factors for
drug
resistance
37
RIF
resistance
not detected
Treat with
first line
drugs
NAAT -ve
or repeat test not
indicated or feasible
RIF
resistance
detected,
Re-confrim
and
follow the
DRTB
No other likely alternative diagnosis
Treat as Clinically Diagnosed
Probable TB case
• Evaluate for
EPTB
• Consider
referral to a
higher centre for
detailed
investigation for
an alternate
cause
• Look for any other site like a significantly enlarged
peripheral enlarged lymphnode and test the LN aspirate for
Mtb
• Consider Repeat NAAT from a better quality specimen or
alternative specimen like BAL or aspirate depending upon
the availability and feasibility
• May seek review from a higher centre
19.
20. DRUG REGIMEN FOR DRUG
SENSITIVE TB
⚫The principal of treatment of tuberculosis
(other than DR-TB) with daily regimen with
daily fixed dose combination of First
Line Antitubercular Drugs in appropriate
weight bands.
21. FDCs – Potential Advantages
⚫Simplicity of treatment
⚫Increased patient acceptance
⚫Fewer tablets to swallow
⚫Prevents ‘concealed’ irregularity
⚫Increased health worker compliance
⚫Fewer tablets to handle, hence quicker supervision of
DOT
⚫Easier drug management
⚫Reduced use of monotherapy
⚫Lower risk of misuse of single drugs
⚫Lower risk of emergence of drug resistance
⚫Easier to adjust dosages by body weight
22. ⚫INH resistance
⚫Pre-treatment INH resistance is high (>10%)
⚫pre-treatment INH resistance lead to amplification of
resistance (acquired rifampicin resistance), leading
to MDR
24. No Extension of IP
⚫For new TB cases the treatment in intensive
phase will be of 8 weeks.
⚫There will be no need for extension of IP.
25.
26. The revised weight band for standard first line
regimen for TB in adults and children is
given below-
27. Pediatric formulation
H50, R75, Z150
E100(separate tab)
Adult formulation
H75, R 150, Z400,
E275
Children up to the weight of 39 kg would be
managed as per the various weight bands
available for children
Children ≥ 40 kg would be managed as per
the various weight bands available for adults
≥ 40 kg
Weight
band (kg)
Dose from 0-18
years
4-7 1 P + 1E
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
Pediatric Drug Formulations
and Dosages
29. Follow up of Treatment
Monthly
Symptoms
ADR
Weight
Comorbidity
CXR*
ClinicalLaboratory
Smear microscopy
Culture
DST*
Investigation for ADR*
Investigation for comorbidity*
* If required
30. Clinical Follow up
⮚ At least monthly - Patient visits the clinical facility
or the MO reviews during home visit
⮚ Improvement on chest symptoms, increase
in
weight etc. may indicate good prognosis
⮚ Control of co-morbid conditions like HIV
and diabetes
⮚ Symptoms and signs of adverse
reactions to drugs should be specifically
asked
31. Clinical follow up
⮚ Chest x-ray to be offered to drug sensitive pulmonary
TB patients whenever required and available.
⮚ Response to treatment in extra-pulmonary TB may be
best assessed clinically. Help of radiological and other
relevant investigations may be taken.
⮚ Response to treatment in children may be assessed
clinically (who are unable to produce sputum). Help of
relevant investigations may be taken.
32. Laboratory follow up
IP CP 6 12 18 24
In case of pulmonary tuberculosis, smear microscopy
examination on one sputum specimen should be done at
the end of IP and end of treatment.
Smear examination at end of
IP
Negative Positive
DST
At end of IP – Smear
positive – No
Extension of Intensive
Phase
33. Laboratory Follow up
At completion of treatment, a sputum
smear and/or culture
should be done for every patient
Smear examination at end of
treatment
Negative Positive
DST
At end of treatment –
Smear or Culture
positive – Treatment
Failure
34. Long term follow up for Drug
sensitive TB patients
• After completion of treatment patients
should be followed up at the end of
6,12,18 and 24 months.
• It will help to detect recurrence of TB at
the earliest.
35. Pyridoxine in TB Regimen
⚫Tab pyridoxine not required for all TB
patients
⚫To prevent INH related neuropathy in
persons at high risk of Vitamin B6 deficiency
⚫Alcoholics
⚫Malnourished persons
⚫Pregnant and lactating women
⚫Patients with conditions such as chronic renal
failure, diabetes,
⚫HIV infection
38. ⚫Prevalence of TB among COVID 19 0.03-4.4 in
different studies.
⚫Over all decline in TB notification by 26%
during January to June 2020 (compared to
previous year)
39. ⚫Active as well as latent TB are an important risk
factor for SARS- CoV-2 infection.
⚫TB is associated with a 2.1 fold increased risk of
severe COVID 19 disease
⚫Dual morbidity & mortality of TB and COVID 19
leading to poor outcome.
40. A. Bi -directional TB COVID screening
B. TB screening for ILI (influenza like illness)
cases.
C. TB screening for SARI (severe acute respiratory
illness) cases.
42. Ideally all presumptive TB patients have
to undergo HIV screening.
This is important to ensure all HIV positive TB
patients receive ART irrespective of CD4 count
and Chemo Prophylaxis (CPT).
HIV &
Tuberculosis
43.
44. First Line ART for HIV - TB
Second Line ART for HIV - TB
45. Adjustment of Anti TB drugs in renal insufficiency
Drugs Recommended dose and frequency for patients with creatinine
clearance <30 ml/min or for patients receiving haemodialysis (unless
otherwise indicated dose after dialysis)
Isoniazid No adjustment necessary
Refiampicin No adjustment necessary
Pyrazinamide 25-35 mg/kg per dose three times per week ( not daily)
Ethambutol 15-25 mg/kg per dose three times per week ( not daily)
Rifabutin Normal dose can be used, if possible monitor drug concentrations to avoid
toxicity.
Streptomycin 12-15mg/kg per dose two or three times per week (not daily)
Capreomycin 12-15mg/kg per dose two or three times per week (not daily)
Kanamycin 12-15mg/kg per dose two or three times per week (not daily)
Amikacin 12-15mg/kg per dose two or three times per week (not daily)
Ofloxacin 600-800mg/kg per dose three times per week (not daily)
Levofloxacin 750-1000mg per dose three times per week (not daily)
Moxifloxacin No adjustment necessary
Cycloserine 250mg once daily or 500mg/ dose three times per week
Terizidone Recommendations not available
46. Torizidone Recommendations not available
Prothinamide No adjustment necessary
Ethionamide No adjustment necessary
Para-
aminosalicylicaci
d
4g/dose twice daily maximum dose
Bedaquiline No dosage adjustments required in patients with mild to moderate renal
impairment (dosing not established in severe renal impairment, use with
caution)
Linezolid No adjustment necessary
Clofazimine No adjustment necessary
Amoxicilin
/clavulanate
For creatinine clearance 10-30ml/min dose 1000mg as amoxiciline
component twice daily
For creatinine clearance <10ml/min dose 1000mg as amoxicilin
component once daily
Imipenem
/cilastin
For creatinine clearance 20-40ml/min dose 500mg every hours
For creatinine clearance <20-40ml/min dose 500mg every 12 hours
Meropenem For creatinine clearance 20-40/ml/min dose 750mg every 12 hours
For creatinine clearance <20/ml/min dose 500mg every 12 hours
High dose
isoniazid
Recommendations not available
Adjustment of Anti TB drugs in renal insufficiency
52. Latent tuberculosis infection (LTBI): A
state of persistent immune response to
stimulation by M. tuberculosis
antigens with no evidence of clinically
manifest active TB.
53. ⚫ India: ~35-40% population infected with LTBI.
⚫ 10% lifetime risk of active TB (greater in PLHIV &
other risk groups) with half of the risk within two years
after infection.
⚫ 16-21 times more risk in HIV co-infection ; 3-4 times
in diabetes/other immune -compromised.
54. Diagnostic Algorithm
* Algorithm accepted with an addition in the footnote 3 that in other high-risk groups, testing must
precede before TPT.
55. Recommendations for LTBI interventions under NTEP
3rd National Technical Working Group(TWG) on Latent TB Infection Management in India held
on 12th May, 2020
Eligible population Strategy Treatment option
• People living with HIV
(Adults and children >12
months)
• Infants <12 months in
contact with active TB
• Household contacts below 5 years
of pulmonary TB patients
Treating all
after ruling
out active TB
• 6-months daily
isoniazid
• Three months of daily
rifampicin plus isoniazid
(Alternative in household
contacts 0 - 14 years (up
to 25 kg weight) in limited
geographies)
• Household contacts 5 years
and above of pulmonary TB
patients (testing would be offered
whenever available)
Treating all
after ruling
out active
TB
3-month weekly Isoniazid
and Rifapentine
• Children/Adult on
immunosuppressive therapy
Testing and
3-month weekly Isoniazid
and Rifapentine
57. Bedaquiline (Bdq)
● Diarylquinoline that specifically targets
mycobacterial ATP synthase, an enzyme
essential for the supply of energy to
Mycobacterium TB.
● Strong bactericidal and sterilizing activities
against M.tb have been shown in pre-clinical,
laboratory and animal experiments.
● The drug has a high volume of distribution, with
extensive tissue distribution, highly bound to
plasma proteins and is hepatically metabolized.
● The drug has an extended half-life, which means
that it is still present in the plasma up to 5.5
months post stopping Bdq.
58. Bedaquiline(Bdq)-
● It will be given to children >5 years of age weighing
15kg or more.
● Child-friendly (i.e. dispersible and palatable)
formulations of the medications should be used
whenever available.
● Bedaquiline tablets suspended in water have been
shown to have the same bioavailability as tablets
swallowed whole, and can be used to treat DR TB in
children until a child-friendly formulation are available
under NTEP.
59. Delamanid (Dlm)
● Is the first approved drug in the class of nitro-
dihydro-imidazo-oxazoles for the treatment of
MDR-TB.
● It is bactericidal drug with 36 hours of half-life
and act with two different mechanisms of action.
It blocks the synthesis of mycolic acids (i.e.,
stopping the bacteria from creating building
blocks important for their cell walls) as well as
poison the bacilli with nitric oxide, which the
drugs release when metabolized.
● For children it will be given to children 6 years
onwards. Although the use of Dlm in the age
group of 3-5 years has been approved by WHO,
the regulatory approval in India is awaited.
60. Key Considerations for newer drugs:
● Take a light meal with Bdq and other anti-TB
drugs,
● Patients should not consume milk containing
products at the time of taking drugs, as the calcium
in these can decrease the absorption of FQs.
● Large fatty meals should be avoided, as these can
impair absorption of some of the other antiTB drugs
(Cs, H etc.).
61. The following medications are not allowed during the 24-week administration of
Bdq and up to one month after the last dose of Bdq because of potential drug–
drug interactions:
● Systemic use of moderate and strong CYP3A4 inhibitors, e.g. azole
antifungals: ketoconazole, voriconazole, itraconazole, fluconazole;
● ketolides such as telithromycin and macrolide antibiotics other than
azithromycin for more than 2 consecutive weeks.
● Systemic use of strong CYP3A4 inducers, e.g. phenytoin, carbamazepine,
phenobarbital.
● St. John’s Wort and Rifamycins (rifampin, rifabutin, rifapentine);
● Cholesterol lowering medications of the “statin” class.
● Bdq use in PLHIV infection should be with caution with ARVs that exhibit
drug-drug interactions with Bdq (efavirenz) or prolong the QT interval
(lopinavir/ ritonavir).
● Other second-line drugs that are likely to be administered with Bdq/ Dlm,
notably FQs and Cfz may potentially increase the risk of cardiotoxicity.
Therefore, monitoring of patients for cardiac dysrhythmias or QT interval
prolongation (i.e. using ECG), and for electrolyte imbalances (especially
serum potassium) that can predispose to cardiotoxicity is imperative.
