Current tuberculosis management in short

Management of Pulmonary
Tuberculosis

Overview
• Burden of tuberculosis(TB)
• Pathogenesis, Risk factors and clinical presentation of TB
• Investigations, Diagnosis and Recent developments
• Management of TB and MDRTB including Newer Drugs
• MDR TB in Pregnancy
• Role of Surgery in MDR TB
• Latent TB
• Antibodies and Tuberculosis

Burden Of tuberculosis
• Tuberculosis is a major health problem globally, with increased mortality and
morbidity
• Globally, 1.4 million deaths was due to TB in the year 2015
• In India, the prevalence on TB is more in elderly, people (0.9%), illiterate (0.4%) and
people belonging to the poorest wealth quintile (0.53%)
• In door second hand smoke exposure, mud walls and poor sanitation, are other
factors for the rise of TB in India
Singh S, Kashyap G, Puri P. BMC Pulm Med. 2018;18(1).

Cont.….
Number of persons per 100,000 usual household residents suffering from any tuberculosis by state,
India (2005-06, 2015-16)
NFHS: National Family and Health Survey
Singh S, Kashyap G, Puri P. BMC Pulm Med. 2018;18(1).

Pathogenic Life Cycle of M. Tuberculosis
Cambier C, Falkow S, Ramakrishnan L. Cell. 2014;159(7):1497-1509.

Cont.…..Tuberculosis As A 3 Act Play
Hunter R.Tuberculosis. 2016;97: 8-17

Risk Factors For Acquiring TB Infection & Clinical Features
1. Narasimhan P, Wood J, Macintyre CR, et al. Risk factors for tuberculosis. Pulm Med 2013;2013:828939
2. 2. Kumar K, Kon O. Ann Res Hosp. 2017;1:1-1.
Clinical features of TB: Depends on the
site of infection 2
 Pulmonary TB is characterised by a history of
chronic cough, sputum production,
haemoptysis, fever, night sweats and weight
loss
 Other presentation of TB include :
• TB Meningitis,
• TB of skeletal system (pott’s spine)
• TB peritonitis
• TB pericarditis
• Plural TB
• Genitourinary TB
• TB lymphadenitis

Investigation, Diagnosis Algorithm And Recent
Developments

RNTCP Acceptable Methods For Microbial Diagnosis Of TB
• Sputum smear microscopy: Zeihl –neelson staining and LED-FM – light emitting diode based
fluorescent microscopy
• Culture:
• Rapid molecular diagnostic testing:
TOG-Chapter 3-Case finding & diagnosis strategy :: Ministry of Health and Family Welfare. Tbcindia.gov.in. https://tbcindia.gov.in/showfile.php?lid=3216.

Cont.…
• Radiography: CXR, as a screening tool, any abnormality should be confirmed with microbial
confirmation. Diagnosis of TB based on x-ray will be termed as clinically diagnosed TB
• Tuberculin skin test(TST) & Interferon gamma release assay(IGRA): As complementary test in
children in combination with microbial investigation, history of contact, radiology and
symptoms. IGRAs used in low prevalence countries to detect TB instead of TST, IGRA not
recommended in adult diagnosis of TB in India
• Serological test: Banned in India for manufacturing, importing , distribution and use of
commercial available kit for diagnosis of TB. Not recommended for diagnosis of TB

Accuracy Of Screening Tools For Pulmonary TB
Recommendations For Vulnerable Groups To Be Screened

Cartridge – Based Nucleic Acid Amplification Test (CBNAAT), programmatic management of drug-resistant TB (PMDT), PLHIV- people living with HIV, CXR- chest x ray, Rif- rifampicin, EPTB- extra
pulmonary tuberculosis, Tuberculin skin tests (TST), LPA- line probe analysis

Technologies Reviewed By WHO For TB Case Detection
Culture ( growth based): Mycobacterial culture on
solid agar (e.g., Lowenstein- Jensen [LJ]) or in liquid
culture (e.g., Mycobacterial Growth Indicator Tube [MGIT;
Becton Dickinson, Franklin Lakes, NJ] or BacT/ALERT MB
[bioMérieux, Durham, NC]) remains the gold standard
test for diagnosis of TB
WHO recommendations on mycobacterial cultures :
• Liquid culture is feasible for implementation in lower-
income settings. Liquid culture has a higher rate of
mycobacterial
• Isolation and a shorter time to detection compared with
solid culture.
• Rapid differentiation of M. tuberculosis from other acid-
fast organisms recovered in culture is essential.
Pai M, Nicol MP, Boehme CC. Microbiol Spectr.2016:4(5);363 -378.
The BACTEC TM MGIT 960 instrument (Becton Dickinson) and culture tubes for broth-based mycobacterial growth

Cont.…
Xpert MTB- RIF: WHO recommendation:
• Should be used as the initial diagnostic test in all adults or children having TB, or in those suspected of
having MDR-TB or HIV-associated TB
• Should be used in the initial diagnosis for CSF analysis of those suspected to have TB meningitis, and
replacement test for usual practice for testing specific non respiratory specimens (lymph nodes and
other tissues) from patients suspected of having extrapulmonary TB
An important limitation of Xpert
MTB/RIF is its inability to
distinguish between live and
dead bacilli. The assay may
remain positive even after
treatment completion and
should not be used to monitor
response to treatment

Cont….
 The TB-Loop- Mediated Amplification Test (LAMP) assay: (Eiken Chemical Co., Japan) is based on an
isothermal amplification protocol (using a simple heating block) and produces a result that can be seen with
the naked eye
WHO recommendations on LAM are:
• LAM testing should only be used to assist in the diagnosis of TB in persons with HIV infection with low CD4
counts (<100 cells/μl) or HIV infected patients who are seriously ill
• LAM testing should not be used as a screening test for TB
 Urine Lipoarabinomannan Rapid Test: Lipoarabinomannan (LAM) is a component of the cell wall of M.
tuberculosis that may be found in urine of patients with TB
• Urine LAM testing lacks sensitivity for diagnosis of TB in HIV-uninfected patients, and should only be used
for diagnosis of HIV-associated TB in patients with low CD4 counts (<100 cells/μl), or HIV-infected patients
who are seriously ill.
• The test is not able to distinguish between infection with M. tuberculosis and other mycobacterial species

Technologies Reviewed By WHO For Drug- Susceptibility Testing
WHO recommendations on liquid
culture-based DST are:
• As a minimum, national TB control programs should
establish laboratory capacity to detect MDR-TB.
• Automated liquid systems and molecular line probe
assays (see “Genotypic Tests for DST,” below) for first-
line DST are recommended as the current gold
standard.
• DST for aminoglycosides, polypeptides, and
fluoroquinolones has been shown to have relatively
good reliability and reproducibility

Cont….
Genotypic Tests for DST
 WHO recommendations on molecular LPAs( 2008) are:
• LPAs are validated for direct testing of sputum in smear-positive specimens and on isolates of smear-positive
specimens and on isolates of MTB. They are not recommended for use on smear-negative samples
• Adoption of LPAs does not eliminate the need for conventional culture and DST capability (for diagnosis of patients
with smear-negative TB and for further DST for patients with MDR-TB)
• Appropriate laboratory infrastructure and appropriately trained staff are necessary to ensure adequate precautions
for biosafety and prevention of contamination
 A rifampin-resistant Xpert MTB/RIF( 2010) : result should therefore be confirmed with a second (different)
test. Furthermore, the correlation between genotypic and phenotypic testing is sometimes complex. Xpert MTB/RIF may
miss some locally prevalent Rifampin resistance-conferring mutations, which are detectable by phenotypic testing
 WHO recommendations on second-line molecular line probe assays(2016) are:
• For patients with confirmed rifampin-resistant TB or MDR-TB, SL-LPA may be used as the initial test, instead of
phenotypic culture-based DST, to detect resistance to fluoroquinolones or second-line injectable drugs

Cont….
Non-commercial DST Methods:
• Microscopic observation of drug susceptibility (MODS) - based on microscopic observation of
microcolonies of MTB in liquid media (with and without antibiotics). Microtiter plates may be inoculated with
sputum specimen (direct testing) or cultured isolates (indirect testing)
• Nitrate reductase assay (NRA) - based on colorimetric change in solid agar caused by reduction of nitrate
by MTB, and is suitable for direct or indirect testing
• Colorimetric redox indicator (CRI) - based on colour change due to reduction of an indicator dye that is
added to liquid media containing viable MTB that has been exposed to antibiotics (indirect testing only)
WHO recommandations on non- commercial DST methods:
• MODS, CRI, and NRA methods may be used under clearly defined program and operational conditions, in
reference laboratories, and as an interim solution while capacity for genotypic or automated liquid culture is
being developed.

Summary of Diagnostic tests For TB
Diagnostics for TB. Source:
Heemskerk D, Caws M,
Marias, Ben &F, Jeremy.
Tuberculosis in adults and
children. Available at
http://www.SpringerLink.com
• √= Recommended
• X=not
recommended
with more
evidence
• XX=clearly not
recommended.
• NTMa=Non-
Tuberculosis
Mycobacteria

Pipeline Of Future Diagnostics
Classes of TB biomarkers under development and validation
Translational challenges for developing innovative TB technologies that can meet the needs

The Three Tiers Of The Network Of TB Laboratories And The
Responsibilities And The Tests Offered At Each Level
World Health Organization (WHO). (2015a) Implementing the End TB Strategy: The Essentials Geneva: WHO.
World Health Organization (WHO) Multidrug-resistant (MDR),extensively drug-resistant (XDR)-TB, drug susceptibility testing (DST), MTB/RIF Mycobacterium tuberculosis complex (MTBC) and
resistance to rifampin (RIF), Ziehl-Neelsen (ZN) smear microscopy. LED fluorescence microscopy, Line Probe Assay (LPA)

Management Of Tuberculosis: Anti – Tubercular
Drugs

Vision, Goals, And Targets Of National Strategic Plan For TB
Vision
TB-Free India with zero deaths, disease, and poverty due to TB
Goal
To achieve a rapid decline in the morbidity and mortality due to TB, while working toward
elimination of TB in India by 20251
Case Registration: The government has also proactively engaged the private practitioners, number
of private organizations, NGOs, professional bodies such as Indian Medical Association, to enhance
notification of TB cases. Central TB Division, in collaboration with National Informatics Centre, has
developed a case-based web-based platform-“NIKSHAY” in 2012, which has now been scaled up
nationally2
1. RNTCP National Strategic Plan for TB Elimination in India (2017-2025)Central TB Division, DGHS, MOHFW, Government of India.
2. Purty A. Indian Journal of Community Medicine. 2018;43(1):1.

RNTCP National Strategic Plan for TB Elimination in India (2017-2025)Central TB Division, DGHS, MOHFW, Government of India.
National Strategic Plan 2017-2025 Results Framework (Impact And
Outcome Indicators And Targets

The “Detect – Treat – Prevent – Build” approach of National
Strategic Plan 2017-2025. How do we do it?
RNTCP: Revised National Tuberculosis Control Programme, STDC: State TB Training and Demonstration Centres, COE: Centers of excellence, NRTI: Nucleoside reverse transcriptase inhibitors,
LTBI: Latent TB infection, TP: Tuberculosis, DST: Drug susceptibility testing, NTI: National Tuberculosis Institute, HR: Human Resources
RNTCP National Strategic Plan for TB Elimination in India (2017-2025)Central TB Division, DGHS, MOHFW, Government of India.

Case definition Of Tuberculosis:
Presumptive TB : Refers to a person with any of the symptoms or signs suggestive of TB:
• Cough >2 Weeks,
• Fever >2 Weeks,
• Significant Weight Loss,
• Haemoptysis,
• Any Abnormalities In Chest Radiography.
In addition, contact of microbiologically confirmed TB patients, PL HIV, diabetics, malnourished, cancer
patients, patients on immunosuppressive therapy or steroid should be regularly screened for signs and
symptoms of TB.
Drug resistant TB: TB patients who have failed treatment with first-line anti-tubercular drugs (ATD),
who are contacts of DRTB, are found positive on any follow-up sputum smear examination during
treatment with first-line ATD, previously treated TB cases, with HIV co-infection. Also, Paediatric TB non-
responder
Chaudhuri A. The Journal of Association of Chest Physicians. 2017;5(1):1.

Cont....
• New case – A TB patient who has never had treatment for TB or has taken ATD for <1 month. (No change
in new guidelines.)
• Previously treated patients have received one month or more ATD in the past. This may be:
• Recurrent TB case – TB patient previously declared as successfully treated (cured/treatment
completed) and who is subsequently found to be microbiologically confirmed TB case is a recurrent
TB case. (Previously called relapse.)
• Treatment after failure – TB Patients who have previously been treated for TB and whose treatment
failed at the end of their most recent course of treatment.
Previously, it was called failure where a TB patient is sputum-positive at 5 months or more after initiation of
treatment.
• Treatment after loss to follow-up – TB patient previously treated for one month or more and was
declared lost to follow-up in their most recent course of treatment and subsequently found
microbiologically confirmed TB cases.
Previously called treatment after default – a patient who has received treatment for TB for a month or more from any source and
return for treatment after having defaulted, that is, not taking ATD consecutively for 2 months or more and found to have smear-
positive.

Cont.... Classification On The Basis Of Drug Resistance
• Mono resistance (MR) – A TB patient whose biological specimen is resistant to one first-line anti-TB
drug only.
• Poly resistance (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 resistance (MDR) – A TB patient whose biological specimen is resistant to both INH and
Rifampicin with or without resistance other first-line ATD, based on results from a Quality Assured
Laboratory. (No changes.)
• Rifampicin resistance (RR) – Resistance to Rifampicin detected by phenotypic or genotypic methods
with or without resistant to other ATD excluding INH. Patient with RR should be managed as if they
are in MDR TB case.
• Extensive drug resistance (XDR) – MDR TB case whose biological specimen was resistant to a
Fluroquinolone (FQ) and a second-line injectable ATD from a Quality Assured Laboratory. (No
changes.)

Difference Of RNTCP Regimen Between New And Previous Guidelines

Grouping Of Antitubercular Drugs
Guideline for PMDT in India 2017 :: Central TB Division. Tbcindia.gov.in. https://tbcindia.gov.in/index1.php?lang=1&level=2&sublinkid=4780&lid=3306.

Revised Grouping Of Anti-tuberculosis Drugs
XDR, extensively drug resistant; MDR, multi-drug resistant;; Rfb, rifabutin;Km, kanamycin; Amk,
amikacin; Cm, capreomycin; Lfx, levofloxacin; Mfx, moxifloxacin; Ofx, ofloxacin; Eto, ethionamide; Pto,
protionamide; Cs, cycloserine; Trd, terizidone; Bdq, bedaquiline; Dlm, delamanid; Lzd, linezolid; Cfz,
clofazimine; Amx/Clv, amoxicillin/clavulanate; Ipm/Cln, imipenem/cilastatin; Mpm, meropenem; Clr,
clarithromycin,PAS, para-aminosalicylic acid; Gfx, gatifloxacin
1. World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. WHO/HTM/TB/2016.04. Geneva: WHO; 2016.
2. Guideline for PMDT in India 2017 :: Central TB Division. Tbcindia.gov.in. https://tbcindia.gov.in/index1.php?lang=1&level=2&sublinkid=4780&lid=3306.
Regimen for MDR TB dosage and weight band
recommendations2

1. Chaudhuri A. The Journal of Association of Chest Physicians. 2017;5(1):1.
2. TOG-Chapter 4-Treatment of TB Part 1 :: Ministry of Health and Family Welfare. Tbcindia.gov.in. https://tbcindia.gov.in/showfile.php?lid=3219
Drug Dosage for Pediatric TB

Cont…
TOG-Chapter 4-Treatment of TB Part 1 :: Ministry of Health and Family
Welfare. Tbcindia.gov.in. https://tbcindia.gov.in/showfile.php?lid=3219.
FLD- first line Anti tubercular drugs
SLI- Second line injectables

Adverse Effect Of Anti Tubercular Drugs
TOG-Chapter 4-Treatment of TB Part 2 :: Ministry of Health and Family Welfare. Tbcindia.gov.in. https://tbcindia.gov.in/showfile.php?lid=3220

Follow-Up Of Treatment For TB
 Clinical follow-up – (new addition)
Should be at least monthly – review for improvement of chest symptoms, weight gain, control the co-morbid conditions
such as HIV and diabetes and to monitor any adverse reaction to ATD
 Follow-up laboratory investigation
For PTB cases – sputum smear examination at the end of IP and at the end of treatment. (In the previous guidelines,
follow-up sputum smear to be done at 2, 4 and 6 months for new cases and 3, 5 and 8 months in previously treated
cases.)
• In case of clinical deterioration, the Medical Office may consider repeat sputum smear even during CP. (New addition)
• At the completion of treatment, sputum smear and culture should be done for every patient
• CXR – to be offered whenever required and available.
 Long-term follow-up
After completion of treatment, the patient should be followed up at the end of 6, 12, 18 and 24 months. Any clinical
symptoms and/or cough, sputum microscopy and/or culture should be considered. (New addition) However, there was
no provision of long-term follow-up in the previous guidelines.
Chaudhuri A. The Journal of Association of Chest Physicians. 2017;5(1):1. c

Management Of Tb with Liver Disorders(New addition)
If the serum alanine amino transferase level is >3 times normal before initiation of treatment, the regime should be:
1. Containing two hepatotoxic drugs: INH + Rifampicin + Ethambutol for 9 months or INH + Rifampicin + Ethambutol +
Streptomycin for 2 months followed by INH and Rifampicin for 7 months or Rifampicin + Ethambutol + Pyrazinamide
for 6–9 months.
2. Containing one hepatotoxic drug: INH + Ethambutol + Streptomycin for 2 months followed by INH + Ethambutol for
10 months.
3. Containing no hepatotoxic drugs: Streptomycin + Ethambutol + FQ for 18–24 months.
ART and ATT
Start ATT first and when the patient tolerates the treatment for 2 weeks to 2 months, initiate ART for HIV
Isoniazid Preventive Therapy (IPT) for People living with HIV( PLHIV)
• Adult and adolescents living with HIV screened for TB and those who are unlikely to have active TB
should be offered IPT
• Children with HIV who have no TB symptoms and who are unlikely to have active TB on symptom-based
screening should be offered IPT regardless of their age
• All children with HIV who have successfully completed treatment for TB disease should receive IPT.
• Adult and adolescent: INH 300 mg + Pyridoxine 50 mg per day for 6 months.
• Children above 12 months: INH 10 mg/kg + Pyridoxine 25 mg per day for 6 months.

DR-TB Diagnostic Algorithm
Guidelines for use of Delamanid in the treatment of drug resistant TB in India. 2018. available at https://tbcindia.gov.in/showfile.php?lid=3343.
Integrated Drug Resistant TB Algorithm

Introduction Of New ATD Under RNTCP
 Bedaquiline (BDQ): New class of drug, diarylquinoline that targets mycobacterial ATP
synthase, and enzyme essential for supply of energy to mycobacterium TB. Strong bactericidal
and sterilizing activities against MTB
• It has no cross-resistance with first- and second-line ATD
• Significant benefit in improving the time to culture conversion in MDR TB patients
• Basic criterion – Adult aged ≥18 years having pulmonary MDR TB; Not to be used in
pregnant women.1
Delamanid : A nitroimidazole, 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
• 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
1. Chaudhuri A. The Journal of Association of Chest Physicians. 2017;5(1):1.
2. Guidelines for use of Delamanid in the treatment of drug resistant TB in India. 2018. available at https://tbcindia.gov.in/showfile.php?lid=3343

Algorithm for management of M/XDR patients who default and return for
treatment within 6 months of discontinuing Regimen for M/XDR TB
Algorithm for management of M/XDR patients who default and return for
treatment after 6 months

Role Of Surgery In Management Of MDR-TB
• In MDR-TB patients with localized disease, surgery, as an adjunct to chemotherapy, can
improve outcomes provided skilled thoracic surgeons and excellent post-operative care
are available.
• When unilateral resectable disease is present, surgery should be considered for the
following cases:
- Absence of adequate response to ATT, clinically or microbiologically for 6- 9months
- High risk of failure or relapse due to high degree of resistance or extensive parenchymal involvement
- Morbid complications of parenchymal disease e.g. haemoptysis, bronchiectasis, bronchopleural
fistula, or empyema;
- Recurrence of positive culture status during course of treatment; and
- Relapse after completion of ATT

Latent Tuberculosis Infection (LTBI)
• Presence of MTB in the body without any signs and symptoms, or radiographic or
bacteriological evidence of TB
• India with 1/4th of the global burden of TB, has 40% pf population infected with TB
• LTBI based on Tuberculin skin test or interferon gamma release assay is neither rational nor
practicable in the 40% of the population, hence focussed approach is needed
• Risk for LTBI: patients on long term corticosteroids, immunosuppressant, HIV infected and
juvenile contacts of sputum –positive index cases.1
WHO guidelines recommend any of the following treatment options for LTBI :
• 6 months of isoniazid monotherapy;
• 9 months of isoniazid monotherapy;
• 3 months of weekly rifapentine plus isoniazid;
• 3–4 months of isoniazid plus rifampicin;
• 3–4 months of rifampicin monotherapy.
1. TOG-Chapter 4-Treatment of TB Part 2 :: Ministry of Health and Family Welfare. Tbcindia.gov.in. https://tbcindia.gov.in/showfile.php?lid=3220
2. World Health Organisation. Guidelines on the management of latent tuberculosis infection. WHO, 2015

Antibodies and Tuberculosis
Jacobs A, Mongkolsapaya J, Screaton G, McShane H, Wilkinson R. Tuberculosis. 2016;101:102-113.
Factors Related To The Development Of Antibodies Against M.TB In Humans
Evidence suggestive of a role of antibody-mediated immunity in prevention of infection or
limiting severity of disease

Current tuberculosis management in short

Current tuberculosis management in short

Recommended

Recommended

More Related Content

Similar to Current tuberculosis management in short

Similar to Current tuberculosis management in short (20)

More from Subhajit Ghosh

More from Subhajit Ghosh (12)

Recently uploaded

Recently uploaded (20)

Current tuberculosis management in short

Editor's Notes