Management of TB 2019

TECHNICAL AND OPERATIONAL GUIDELINES OF
RNTCP
Tuberculosis Management
Dr. Harish Bhatia
Consultant Chest Specialist & Interventional Pulmonologist
MBBS DTCD DNB MNAMS FSM MERS

DELHI RNTCP
• Delhi ranks First in the country in terms of
TB incidence over the last decade
– Delhi TB Incidence-414/lakh/year (2018)
– India TB Incidence- 138/lakh/year(2017)
• Key Risk Factors-
– Migratory Population
– Overcrowding
– JJ clusters and unauthorized colonies in slums

Presumptive Pulmonary TB
Presumptive Pulmonary TB refers to a person with any of the
symptoms and signs suggestive of TB including:-
-Cough for > 2 weeks
-Haemoptysis
-Fever >2 weeks
-Significant weight loss
-Any pulmonary abnormality in chest radiograph
Note: In addition , contacts of microbiologically confirmed TB patients, PLHIV ,
Diabetics, Malnourished, cancer patients, patients on immuno- suppressants or
steroids should be regularly screened for sign and symptoms of TB

Diagnostic Tools
Tools for microbiological confirmation of TB
All efforts should be undertaken for microbiologically
confirming the diagnosis in presumptive TB patients. Under
RNTCP, 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
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)

Presumptive pediatric TB
Diagnostic Algorithm for Pediatric TB

Presumptive Extra Pulmonary TB
Presumptive Extra Pulmonary TB refers to the
presence of organ specific symptoms and signs like
swelling of lymph node, pain and swelling in joints,
neck stiffness, disorientation , etc.,
and/or
constitutional symptoms like significant weight loss,
persistent fever for ≥ 2 weeks, night sweats.

Diagnostic Algorithm for Extra-Pulmonary TB

DR-TB DIAGNOSTIC ALGORITHM
*Offer molecular testing for H mono/poly resistance to TB patients prioritized by risk as per the available lab capacity
**LC DST (Mfx 2.0, Km, Cm, Lzd) will be simultaneously done. Culture Isolates would be preserved for future DST to Cfx &
BDQ when available & WHO endorsed.
$ States to advance in phased manner as per PMDT Scale up plan for universal DST based on lab capacity and policy on
use of diagnostics
All diagnosed TB patientsPresumptive TB
Key/Vulnerable
populations
• Paediatric age group
• People living with HIV
• EPTB sites
• Smear negative/NA with
X-ray suggestive of TB
• Non responders to
treatment
• DR-TB contacts
• Previously treated TB
• TB-HIV co-infection
• New TB patients $
CBNAAT
RR TB RS TB
FL-LPA*SL - LPA**
FQ and SLI
Sensitive
FQ and/or SLI
Resistance
H SensitiveH Resistant
For discordance on LPA for RR-TB
– repeat CBNAAT at LPA lab

All diagnosed TB patientsPresumptive TB
Key/Vulnerable populations
• Paediatric age group
• People living with HIV
• EPTB sites
• Smear negative/NA with X-ray
suggestive of TB
• Non responders to
treatment
• DR-TB contacts
• Previously treated TB
• TB-HIV co-infection
• New TB cases $
CBNAAT
RR TB RS TB
FL-LPA*SL - LPA**
FQ and SLI Sensitive FQ and/or SLI Resistance H SensitiveH Resistant
For discordance on LPA for RR-TB –
repeat CBNAAT at LPA lab
Integrated Drug Resistant TB Algorithm
*Offer molecular testing for H mono/poly resistance to TB patients prioritized by risk as per the available lab capacity
**LC DST (Mfx 2.0, Km, Cm, Lzd) will be simultaneously done. Culture Isolates would be preserved for future DST to Cfx & BDQ when
available & WHO endorsed.
$ States to advance in phased manner as per PMDT Scale up plan for universal DST based on lab capacity and policy on use of diagnostics

Case definitions
• Microbiologically confirmed TB :
– presumptive TB patient with biological specimen positive for AFB,
or positive for MTB on culture, or positive for TB through Quality
Assured Rapid Diagnostic molecular test.
• Clinically diagnosed TB case :
– presumptive TB patient who is not microbiologically confirmed,
but diagnosed with active TB by a clinician on the basis of X-ray,
histopathology or clinical signs with a decision to treat the patient
with a full course of Anti-TB treatment.
– In children, this is based on the presence of abnormalities
consistent with TB on radiography, history of exposure to an
infectious case, evidence of TB infection (positive TST) & clinical
findings suggestive of TB in event of negative or unavailable
microbiological results
12

Classification by Anatomical site of Disease
• Pulmonary tuberculosis (PTB) : any microbiologically
confirmed or clinically diagnosed case of TB involving lung
parenchyma or tracheo-bronchial tree.
• Extra Pulmonary tuberculosis (EPTB) : any
microbiologically confirmed or clinically diagnosed case of
TB involving organs other than lungs e.g. pleura, lymph
nodes, intestine, genitourinary tract, joint and bones,
meninges of the brain etc.
• Miliary TB classified as PTB because there are lesions in
the lungs. A patient with both pulmonary and
extrapulmonary TB should be classified as a case of PTB. 13

Classification by H/O previous TB treatment
• New case - A TB patient who has never had treatment for TB or has taken anti-TB
drugs for less than one month.
• Previously treated patients have received 1 month or more of anti-TB drugs in the
past.
• 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 those patients who have previously been treated for TB
and whose treatment failed at the end of their most recent course of treatment.
• Treatment after loss to follow-up 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 patients are those who have previously been treated for
TB but whose outcome after their most recent course of treatment is unknown or
undocumented.
14

Classificationbasedondrugresistance
• Mono-resistant (MR) : A TB patient, whose biological specimen is
resistant to one first-line anti-TB drug only.
• Poly-Drug Resistant (PDR): A TB patient, whose biological specimen
is resistant to more than one first-line anti-TB drug, other than both
INH and Rifampicin.
• Multi Drug Resistant (MDR): A TB patient, whose biological specimen
is resistant to both isoniazid and rifampicin with or without resistance
to other first line drugs, based on the results from a quality assured
laboratory.
• Rifampicin Resistant (RR): resistance to rifampicin detected using
phenotypic or genotypic methods, with or without resistance to other
anti-TB drugs excluding INH. Patients, who have any Rifampicin
resistance, should also be managed as if they are an MDR TB case.
• Extensively Drug Resistant (XDR): A MDR TB case whose biological
specimen is additionally resistant to a fluoroquinolone (ofloxacin,
levofloxacin, or moxifloxacin) and a second-line injectable anti TB drug
(kanamycin, amikacin, or capreomycin) from a quality assured
laboratory.
15

DRUG SENSITIVE TB TREATMENT REGIMENS
Type of TB
Case
Treatment
regimen in IP
Treatment
regimen in CP
New (2)HRZE (4)HRE
Previously
Treated
(2)HRZE (4)HRE
+ Prefix to the drug stands for the number of months

Key Points
National Guidance on Regimen
• Daily treatment
• 2 HREZ -------4HRE (continuation phase includes
Ethambutol)
• Weight Band wise drug dosage (5 weight bands in
adults)
• FDC
• Comprehensive approach (including ADR Mx, improved
recording reporting, ICT enabled treatment adherence)

Fixed Dose Combinations (FDCs) Potential Advantages
• Simplicity of treatment
• Increased patient acceptance
– Fewer tablets to swallow
– Prevents ‘concealed’ irregularity / selective drug avoidance
• 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 bodyweight
18

Dosage
• Frequency of Dosage: DAILY (7 day/week)
• Single daily dosage
• 4 weeks per month, i.e.: 28 doses
• No extension of Intensive Phase
19

Single vs FDC Blister Pack
Single-Dose Blister Pack FDC Blister Pack
20

Daily Dose Schedule for Adults
(as per weight bands)
Weight band
Number of tablets
Inj. Streptomycin
(Intensive Phase
only)
Intensive phase
Continuation
phase
HRZE HRE
75/150/400/275 mg 75/150/275 mg gm
25-34 kg 2 2 0.5 gm
35-49 kg 3 3 0.75 gm
50-64 kg 4 4 1 gm
65-75 kg 5 5 1 gm
>75 KG 6 6
23

Doses in RNTCP Daily Regimen
Type of TB Case Doses in IP Doses in CP
New/Previously
treated
56 doses
(8 weeks x 7
days/week) or
28x2
112 doses
(16 weeks x 7
days/week) or 28x4
24

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
• While treating NTM
25

ICT Based monitoring: 99 DOTS
• Adherence tracking E tool
• Will be rolled out for some more states
• Randomly distributed missed call numbers
behind pill blisters

99DOTS: ACCURATE MONITORING AT VERY LOW COST
Combination of Caller ID and
numbers called shows that
doses are in patient’s hands.
28
Courtesy: Mr. Bill Thies

Key Product Information (Paediatric)
(Dispersible FDC)
• Rifampicin 75 mg + Isoniazid 50 mg + Pyrazinamide 150 mg
• Rifampicin 75 mg + Isoniazid 50 mg
• Formulation: Dispersible; flavor
• Ethambutol 100 mg
• Formulation: Dispersible
31

WT BAND COMBI INH RIF PZA EMB
4 TO 7 C+E 50 75 150 100
8TO 11 2C+2E 100 150 300 200
12 TO 15 3C+3E 150 225 450 300
16TO 24 4C+4E 200 300 600 400
25TO 29 A+3C+3E 225 375 850 575
30 TO 39 2A+2C+2E 250 450 1100 750
C: HRZ paediatric base dose (dispersible)
A: Adult 4FDC base dose
E: Ethambutol 100mg (dispersible)
Daily Dispersible FDCs Paediatric Anti-TB drugs
32

SHORTER MDR-TB REGIMEN
• Standardized shorter MDR-TB regimen with seven drugs
and a treatment duration of 9-12 months
• Indicated conditionally in MDR-TB or Rifampicin resistant-
TB, regardless of patient age or HIV status
• Exclusion criteria:
A. Second line drug resistance
B. EP Cases
C. Pregnancy

SHORTER MDR-TB REGIMEN
• 4-6 Km-Mfx-Pto-Cfz-Z-Hhigh-dose-E / 5 Mfx-Cfz-
Z-E
• Km=Kanamycin; Mfx=Moxifloxacin;
• Pto=Prothionamide; Cfz=Clofazimine;
• Z=Pyrazinamide; Hhigh-dose= high-dose
• Isoniazid; E=Ethambutol

The total duration of treatment will be 9 to 12 months. The Intensive Phase
(IP) is for 3 months with scope for extension to a maximum of 6 months.
The Continuation phase (CP) is for a fixed duration of 6 months.
The patient is initiated on treatment at DR-TB Centre, and then sent back
for ambulatory treatment to the DTO for continuation of treatment regimen
and regular follow-up.
Treatment regimen for Mono/Poly DR TB

Standard regimen for initiating treatment of MDR/RR-TB or H mono-poly
DR-TB at district DR-TB centre based on CBNAAT or FL-LPA
(6) LfxREZ

• Whenever DST pattern of extended pannel of drugs
would be available to guide the treatment like at six
sites where Bedaquiline is introduded initially.
• The management protocol will follow essentially
optimized regimen in case patients are diagnosed
with drug resistance other than or in addition to
MDR and XDR.

Contact Investigation
• 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”.
• The patient will be initiated on regimen for new or
previously treated case based on their history of previous
anti-TB treatment.
• Simultaneously two sputum samples will be transported for
culture and DST to a RNTCP-certified C&DST laboratory.

Bedaquiline Conditional Access Programme: Introduction of new anti TB drug under RNTCP
• Bedaquiline (BDQ): is a new class of drug, diarylquinoline that
specifically targets mycobacterial ATP synthase, an enzyme
essential for the supply of energy to Mycobacterium tuberculosis and
most other mycobacteria.
• Strong bactericidal and sterilizing activities against M. tuberculosis
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 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.

Bedaquiline: Dosage
• Week 0–2: BDQ 400 mg (4 tablets of 100 mg) daily
(7 days per week) + OBR
• Week 3–24: BDQ 200 mg (2 tablets of 100 mg) 3
times per week (with at least 48 hours between
doses) for a total dose of 600 mg per week + OBR
• Week 25 (start of month 7) to end of treatment:
Continue other second-line anti-TB drugs only as
per RNTCP recommendations

Pregnancy
• Rifampicin, isoniazid, ethambutol, and
pyrazinamide can be used safely during
pregnancy.
• Addition of pyridoxine in the dose of 10
mg/day is recommended to prevent
isoniazid peripheral neuropathy.
CHEMOTHERAPY OF TB IN SPECIAL SITUATIONS

Pregnancy with MDR-TB
Duration of pregnancy
< 20 wks
Advise MTP
MTP
Start
/continue
treatment
> 20 wks
Start modified
regimen
1.Omit
Kanamycin,add
PAS till delivery
2.Repalce PAS with
Kanamycin after
delivery and
continued till end
of IP
Unwilling for MTP
Start modifid
regimen
1.<12 wks-omit
kanamycin
And
Ethionamide,add
PAS
2.>12 wks-omit
kanamycin only,
add PAS
3.Replace PAS wih
Kanamycin after
delivery and
continue till end of
IP

• Tight glycemic control is desirable.
• Doses of oral hypoglycemic agents may
have to be increased due to drug
interaction with rifampin.
• Prophylactic pyridoxine in the dose of 10
mg/day is recommended to prevent
isoniazid peripheral neuropathy
Diabetes mellitus

• 6-month course of therapy is recommended for treating
tuberculosis involving any site with the exception of the
meninges, for which a 9- 12-month regimen is
recommended.
• Prolongation of therapy also should be considered for
patients with tuberculosis in any site that is slow to
respond.
• The addition of corticosteroids is recommended for
patients with tuberculous pericarditis and tuberculous
meningitis.
American Thoracic Society, CDC, and
Infectious Diseases Society of America
Tuberculosis of the Central Nervous System

• Dosages may have to be adjusted according to the creatinine
clearance especially for ethambutol and isoniazid.
• In acute renal failure, ethambutol should be given 8 hours
before hemodialysis.
• Creatinine clearance should be estimated for adjustment of
some of the antituberculosis drugs.
• Creatinine clearance = (140 - Age) Weight / 72 Χ serum
creatinine, gives a rough estimate of the glomerular filtration
rate.
Renal failure

• Post transplant patients and other special situations
– Rifampicin-containing regimens are avoided as rifampicin
causes increased clearance of cyclosporin.
• Pre-existing liver disease
– In stable disease with normal liver enzymes, all anti-
tuberculous drugs may be used but frequent monitoring of
liver function tests is required.

– If patients are fed by nasogastric tube or
gastrostomy tube, usual doses and drugs
may be powdered and administered
avoiding feeds 2-3 hours before and after
the meal.
Treatment in unconscious patient/patients
unable to swallow

• Use of specific empiric anti-tuberculosis therapy (SEATT)
with isoniazid, ethambutol, pyrazinamide can be used as a
method for rapid presumptive diagnosis and treatment of
febrile patients with clinical and radiological suspicion of
TB, who are seriously ill and where no bacteriological or
histological proof is available. Fever is used as guide for
response to therapy.
• Rifampicin and aminoglycosides or quinolones are not used,
to ensure that defervescence of fever is due to action of
specific anti-TB drugs i.e. isoniazid, ethambutol and
pyrazinamide. Rifampicin may be added as soon as the
patient is afebrile.
Seriously Ill Patients with Suspected TB

BENEFITSOFIPT
• IPTaugmenttheeffectsofART onreducingtheincidenceofTB.
• Likelihoodof restorationofTB-specificimmunityby ART, andthe
beneficialeffectofIPT maybeprolonged.
• IPTdoesnotpromoteIsoniazidresistancewhenusedtotreatlatentTB
infection.InLTBI,theMTB bacilli arefewerinnumberandaredividing
slowly,resultinginanextremelylowriskofselectingdrug-resistant
mutants.
• A studyconductedin2010reflectedthatprevalenceofINHresistance
amongIPT-exposedpersonswassimilartothebackgroundpopulation.

ISONIAZIDPREVENTIVETHERAPYFORHIV
• Prevent progression of LTBI to prevent
progression to active TB disease.
• Isoniazid is one of the most effective bactericidal
anti-TB drugs that protectagainstprogressionoflatent
TBinfectiontoactivedisease (againstendogenous
reactivation).ItalsopreventsTBre-infectionpost exposure
toanopencaseofTB(againstexogenousre-infection/super
infection/nosocomialtransmission).

Thanks
TB HELP LINE NO. 1800-11-6666
(TOLL FREE)

Management of TB 2019

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