TUBERCULOSIS

Dr. MUNNI LAL

Dr. MANISH KHANDELWAL
MU-7
 TUBERCULOSIS
• Tuberculosis (TB), which is caused by bacteria of
the Mycobacterium tuberculosis complex, is one
of the oldest diseases known to affect humans and
the top cause of infectious death worldwide.
• This disease most often affects the lungs,
although other organs are involved in up to one-
third of cases.
• Transmission usually takes place through the
airborne spread of droplet nuclei produced by
patients with infectious pulmonary TB.
 TUBERCULOSIS
• TB is classified as pulmonary, extrapulmonary, or both.
• Pulmonary TB is conventionally categorized as primary
or post primary (adult-type secondary)
• Extrapulmonary TB may occur in 10–40% of patients.
• The extrapulmonary sites most commonly involved in TB
are the lymph nodes, pleura, genitourinary tract, bones
and joints, meninges, peritoneum, and pericardium.
However, virtually any organ system may be affected.
 National Tuberculosis Elimination
Programme (NTEP)

• In 2020 the RNTCP was renamed the National

Tuberculosis Elimination Program (NTEP) to
emphasize the aim of the Government of India to
eliminate TB in India by 2025.
 Global TB Burden -2020
Global India
Incidence 9.96 million 26,40,000
(130/lakh) (193/lakh)
Deaths 1.21 million 4,36,000 *
(16/lakh) (32/lakh)
HIV TB cases 8,15,000 71,000
(8.2/lakh) (2.7/lakh)
HIV-TB deaths 2,08,000 9,500
(2.7/lakh) (0.69/lakh)
Estimated 4,65,000 1,24,000
MDR/RR cases (6.1 cases/lakh population) (9.1 cases/ lakh
population)
 Presumptive Pulmonary TB
A person with any of the symptoms and signs :
• Cough for > 2 weeks
• Fever >2 weeks
• Significant weight loss
• Haemoptysis
• Any abnormality in chest radiograph
Note: In addition, PLHIV, Diabetics, Malnourished,
cancer patients, patients on immuno- suppressants
or steroids & contacts of microbiologically
confirmed TB patients should be regularly screened
for sign and symptoms of TB .
 Presumptive extrapulmonary tb

• 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.
 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.

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 Case Definitions
• Clinically diagnosed TB case :
– Presumptive TB patient who is not
microbiologically confirmed, but diagnosed 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.
Microbiologically confirmed or clinically diagnosed cases
of TB are also classified according to:
• Anatomical site of disease
• History of previous treatment
• Drug resistance

10
 Classification by anatomical site
• 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.11
 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.

12
 Classification based on drug resistance
• Mono-resistant (MR): resistant to one first-line
anti-TB drug only.
• Poly-Drug Resistant (PDR): resistant to more
than one first-line anti-TB drug, other than both
INH and Rifampicin.
• Multi-Drug Resistant (MDR): resistant to both
Isoniazid and Rifampicin with or without
resistance to other first line drugs, based on the
results from a quality assured laboratory.

13
 Classification based on drug resistance
• Rifampicin Resistant (RR): resistance to
rifampicin 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 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. 14
 Diagnostic Tools
• Sputum Smear Microscopy (for AFB):
- Zeihl -Neelson Staining
- Fluorescent Staining
• Culture:
- Solid (Lowenstein Jensen) media
- Automated Liquid Culture System
eg.BACTEC, MGIT 960
• Rapid Molecular diagnostic testing:
- Line Probe Assay
- Nucleic Acid Amplification testing ( NAAT)
 Line Probe Assay
• The Line Probe Assay is
a DNA strip test that
allow simultaneous
molecular
identification of TB
and the most common
genetic mutation
causing resistance to
rifampicin and isoniazid

• Faster result available

 CBNAAT :Xpert MTB/RIF assay

• Specific for MTB, sensitivity

close to liquid culture
• Detection of Rifampicin-
resistance via rpoB gene
• Faster then LPA - 2 hrs
• Level of detection = 130 cfu /
ml
 Uses of CBNAAT under NTEP
• For Diagnosis of Rif Resistance in presumptive
DR-TB cases
• To detect MTB in presumptive TB cases among
key populations:
• People living with HIV / AIDS
• Paediatric cases
• Extra Pulmonary TB
• Fluid (Not done for Blood, Stool and
Urine)
• Tissue
 Other Diagnostic Tools

• Radiography
• Tuberculin Skin Test (TST) & Interferon Gamma
Release Assay (IGRA): gives evidence of
infection, Not disease
- Currently there is no role of IGRAs in clinical
practice for the diagnosis of TB.
• Serological test
- Not recommended for diagnosis of TB
• ESR is not specific
Treatment of Drug Sensitive TB
 New Anti TB Treatment (Daily)
Type of TB Case Type of Patient Regimen

1. Microbiologically confirmed (positive for AFB,

New or positive for MTB on culture, or positive for
(H/O ATT TB through Quality Assured Rapid Diagnostic
< 1Month) molecular test) 2 HRZE
2. Clinically diagnosed +
4 HRE

Previously treated
1. Microbiologically confirmed
(H/O ATT
> 1Month) 2. Clinically diagnosed

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 Dosage
• Frequency of dosage : DAILY (7 day/week)
• Single daily dosage (morning after meals)
• 4 weeks per month, i.e. 28 doses
• No extension of Intensive Phase
• Continuous Phase (CP) can be extended by
– 12 to 24 weeks in certain forms like
– CNS TB, Skeletal TB and Disseminated TB
 Recommended Daily Dosage of
Essential first-line anti-TB drugs
Name of Drug Adult Daily Dose (mg/kg body wt.)

5 mg/kg
Isoniazid
(4–6 mg/kg) daily
10 mg/kg
Rifampicin
(8–12 mg/kg) daily
25 mg/kg
Pyrazinamide
(20–30 mg/kg) daily
15 mg/kg
Streptomycin
(15–20 mg/kg) daily
15 mg/kg
Ethambutol
(12–18 mg/kg) daily 24
 FDC
4 FDC
• Isoniazid 75 mg
• Rifampicin 150 mg
• Pyrazinamide 400 mg
• Ethambutol 275 mg
3 FDC
• Isoniazid 75 mg
• Rifampicin 150 mg
• Ethambutol 275 mg
25
 Daily Dose Schedule for Adults
(as per weight bands)
Number of tablets
Inj. Streptomycin
Intensive phase Continuation phase

Weight band HRZE HRE

(2019)

75/150/400/275 mg 75/150/275 mg gm

25-34 kg 2 2 0.5 gm
Change in drug dosages when patient shifts in weight band with ±5 Kg
 Tab Pyridoxine

• Tab pyridoxine not required for all TB patients

• Tab pyridoxine required for TB patients who are:
Malnourished
HIV co-infected
Diabetics
Pregnant women
Treatment of Drug Resistant (DR) TB
 Classes of Anti TB Drugs for treatment of DR-TB
New Grouping of Drugs
Group A Levofloxacin Or Lfx
Include all three medicines Moxifloxacin Mfx
Bedaquiline Bdq
Linezolid Lzd
Group B
Add one or both medicines Clofazimine Cfz
Cycloserine / Terizidone Cs/Trd

Group C Ethambutol E
Add to complete the Delamanid Dlm
regimen and when Pyrazinamide Z
medicines from Group A Imipenem-cilastatin OR Ipm-Cln/
and B cannot be used Meropenem Mpm
Amikacin Am
(OR Streptomycin) (S)
Ethionamide / Prothionamide Eto/Pto
p-aminosalicylic acid PAS
 DR-TB Regimen
Regimen class Intensive phase Continuation phase
H mono/poly DR TB (R resistance not detected and H resistance)

All oral H mono-poly DR (6) Lfx R E Z

TB regimen@
MDR / RR TB
Shorter MDR TB (4-6) Mfxh Km/Am* Eto (5) Mfxh Cfz Z E
regimen@ Cfz Z Hh E
All oral longer MDR TB (18-20) Bdq(6) Lfx Lzd# Cfz Cs
regimen@

*If the intensive phase is prolonged, the injectable agent is only given three times a
week in the extended intensive phase.
# Reduce Lzd to 300 mg/day after 6 to 8 months.
@ Pyridoxin to be given to all DR TB patients as per weight band.
 Features of Shorter MDR-TB Regimen

• It should be used as a package and neither

replacement of drug (except the use of Am instead
of Km) nor extension of treatment duration
(beyond 11 month) is permitted.

• If any modification in composition of regimen is

warranted, patient should be switched to
appropriate longer regimen
Integrated DR-TB Algorithm
 NAAT (CBNAAT/TruNAAT)
MTB D MTB ND

RR RS

Shorter All oral longer

Rx for DSTB

FL, SL- LPA & LC-DST

Sensitive to Resistant to FQ & / or

FQ & SLI SLI, Drug Intolerance

Cont. same Rx All oral longer

 NAAT (CBNAAT/TruNAAT))
MTB D MTB ND

RR RS

Rx for DSTB

1st line LPA for H

Sensitive to H Resistant to H

SL- LPA & LC-DST

Cont. Rx for DSTB Rx for all oral
H mono/poly DRTB
 Newer anti-TB drugs

• Bedaquiline The new drug with anti-TB effect,

was approved for treatment of multidrug resistant
TB by US FDA in late 2012 .
• Strong bactericidal and sterilizing activities
against M.tb.
• The drug has an extended half-life up to 5.5
months post stopping BDQ due to high volume
of distribution, with extensive tissue distribution,
highly bound to plasma proteins.
 Newer anti-TB drugs
Delamanid (Dlm)
• Delamanid is the first approved drug in the class of
nitro-dihydro-imidazo-oxazoles for the treatment of
MDR-TB
• Potent anti-bactericidal activity in vitro against
drug-susceptible and drug-resistant strains
• No cross-resistance seen with tested anti-TB drugs
• Delamanid inhibited mycobacteria growth under
both aerobic and anaerobic conditions
 Dosage of DR-TB drugs for adults
S.No Drugs 16-29 Kgs 30-45 Kgs 46-70 Kgs >70 Kgs
1 Rifampicin(R)1 300mg 450mg 600mg 600mg
2 High dose H (Hh) 300 mg 600 mg 900 mg 900 mg
3 Ethambutol(E) 400 mg 800 mg 1200 mg 1600 mg
4 Pyrazinamide(Z) 750 mg 1250 mg 1750 mg 2000 mg
5 Levofloxacin(Lfx) 250 mg 750 mg 1000 mg 1000 mg
6 Moxifloxacin (Mfx) 200 mg 400 mg 400 mg 400 mg
7 High Dose Mfx (Mfxh) 400mg 600mg 800mg 800mg
8 Bedaquiline (Bdq) Week 0–2: Bdq 400 mg daily
Week 3–24: Bdq 200 mg 3 times per week
9 Linezolid (Lzd) 300 mg 600 mg 600 mg 600 mg
10 Clofazimine (Cfz) 50 mg 100 mg 100 mg 200 mg
11 Cycloserine(Cs)4 250 mg 500 mg 750 mg 1000 mg
12 Delamanid (Dlm) 50 mg twice daily (100 mg) for 24 weeks in 6-11 years of age
100 mg twice daily (200 mg) for 24 weeks for ≥12 years of age
13 Imipenem/cilastatin (Ipm/Cls) 4 1000 mg imipenem /1000 mg cilastatin twice daily
14 Meropenam (Mpm) 1000 mg three times daily (alternative dosing is 2000 mg twice daily)
15 Amikacin (Am) 2 500 mg 750 mg 750 mg 1000 mg
16 Kanamycin(Km) 2 500 mg 750 mg 750 mg 1000 mg
17 Ethionamide(Eto) 4 375 mg 500 mg 750 mg 1000 mg
18 Na-PAS (60% weight/vol) 3,4 10 gm 14 gm 16 gm 22 gm
19 Amoxyclav(Amx/Clv) 875/125 mg 875/125 mg BD 875/125 mg 875/125
(In child: WHO 80mg/Kg in 2 divided BD (2 morning +1 (2 morning +1
doses) evening) evening)
20 Pyridoxine(Pdx) 50 mg 100 mg 100 mg 100 mg
TB in special conditions
 TB in Pregnant women
• Pregnancy is not a contraindication for Tt of TB.
• With the exception of streptomycin, the first line
anti-TB drugs are safe for use in pregnancy.
• The 6 month regimen with pyrazinamide safe
during pregnancy and recommended by
who(2HRZE+ 4HR).
• If pyrazinamide is not included in the initial
regimen ,than minimal duration of therapy is 9
months(2HRE+7HR).
• Thioamides,bedaquiline ,and delamanid should be
avoided in pregnancy
 TB in Lactating women
• A breastfeeding woman should receive a full
course of TB treatment.
• After ruling out active TB, the baby should be
given 6 months of isoniazid preventive therapy,
followed by BCG vaccination. Breast feeding
should not be discouraged.
• The mother should be advised about cough
hygiene measures
• Mothers receiving INH and their breastfed infants
should be supplemented with vitamin B6
(pyridoxine), recommended dose of Pyridoxine in
 HIV-Associated TB
• TB is one of the most common diseases among
HIV-infected persons worldwide.
• Responsible for an estimated 20–25% of all HIV-
related mortality.
• All HIV-infected tb patients ,regardless of CD4 +T
cell count,are candidates of ART,which is initiated
as soon as possible after the diagnosis and within
first 8 week of ATT.
• In case of profoundly immunosuppressed patinets
with CD4 +T cell count <50/µL ,ART should be
started within first 2 week of ATT
The immune reconstitution inflammatory syndrome
(IRIS)
• This syndrome has been associated with the
administration of ART and occurs in ~10% of HIV-
infected TB patients.
• Usually developing 1–3 months after initiation of
ART, more common among patients with advanced
immunosuppression and extrapulmonary TB
• Exacerbations in systemic manifestations
(lymphadenopathy, fever) or respiratory signs
(worsening of pulmonary infiltrations, pleural
effusion) as well as laboratory or radiographic
manifestations of TB
The immune reconstitution inflammatory syndrome
(IRIS)
• Firstly ensure that the clinical syndrome does not
represent a failure of TB treatment or the
development of another infection.
• ART should not be initiated during the first 8
weeks of TB treatment in patients with TB
meningitis.
• Prednisolone given for 4 weeks at a low dosage
(1.5 mg/kg per day for 2 weeks and half that dose
for the remaining 2 weeks) has reduced the need
for hospitalizatization.
 ATT in chronic liver disease

• CP A or MELD<18 : Two hepatotoxic drugs

regime(9HRE)
• CP B or MELD 18-25 : One hepatotoxic drugs
regime(2SHE+10HE)
• CP C or MELD >25 : No hepatotoxic drugs
regime(18-24 LES)
 ATT in chronic liver disease
• Two hepatotoxic drug regime
-9HRE( Preferred)
-2HRSE+7HR
-6-9 ZRE( if H Res.)
• One hepatotoxic drug regime
-2SHE + 10HE
• No hepatotoxic drug regime
-18-24 LES
 ATT in renal disease
• Isoniazid and rifampicin are eliminated by biliary
excretion so no change in dosing necessary.
• Ethambutol and metabolites of pyrazinamide has
renal excretion so doses should be
adjusted.patients with stage 4 and 5 chronic renal
disease and on haemodialysis, dosing interval
increased three time weekly (Not daily ) ,similarly
in case of aminoglycosides dosing interval
increased three time weekly (Not daily ). .
 Side effects of anti TB Drugs
• Drug induced hepatitis
 Up to 20% of patients have small increases (up to
three times the upper limit of normal) in serum
levels of aminotransferase ,not accompanied by
symptoms.
 For patients with symptomatic hepatitis ,at least
three fold increase in serum level of AST and /or
ALT and for those without symptoms five- to
sixfold elevations in serum levels of AST and /or
ALT,than treatment should be stopped and drugs
reintroduce at a time after liver function has
 Resume ATT with R and E after LFT returned to baseline or <2 normal

If tolerated after 3-5 days then resume H

If not tolerated after 3-5

If tolerated after 3-5 days days

Suspect H as cause of
Suspect Z as cause of hepatotoxicity
hepatotoxicity

Discontinue
Continue HRE H ,continue R and E
Regimen

Resume Z
-follow LFT closely

If not tolerated
If tolerated after 3-5
Discontinue Z ,continue
days,continue Z, R and E
R and E,add FQ
 Side effects of anti TB Drugs
• . Hypersensitivity reactions usually require the
discontinuation of all drugs
• Hyperuricemia and arthralgia caused by
pyrazinamide ; however, pyrazinamide treatment
should be stopped if the patient develops gouty
arthritis.
• autoimmune thrombocytopenia secondary to rifampin
therapy should not receive the drug thereafter.
• Similarly, the occurrence of optic neuritis with
ethambutol is an indication for permanent
discontinuation of this drug.
 Side effects of anti TB Drugs

• QT interval prolongation-
Bedaquiline ,clofazimine,delamanid,fluoroquinolo
nes.
• Patient with QTc interval >500 ms or history of
ventricular arrhythmia should not given these
drugs.
• Patient taking amikacin should undergo serial
audiometry to detect any hearing loss early on