1

DR.T.V.RAO MD

Dr.T.V.Rao MD

an update

3/13/16

MDR-TB

Dr.T.V.Rao MD

The

2
3/13/16

HOW DOES TUBERCULOSIS

OCCUR?

tuberculosis (TB) bacteria are spread

through the air from a person who is ill with
active TB that involves the lungs or airways.
The bacteria are contained in small, airborne
droplets created by coughing or sneezing.
Anyone who inhales these droplets is called a
"contact." A contact can be someone you
spend a lot of time with, such as a family
member, friend, or co-worker

Dr.T.V.Rao MD
3/13/16

ministry of Health
and Family Welfare
says that two deaths
occur every three
minutes from
tuberculosis (TB) in
India. It is also the
leading infectious
cause of death among
adults. Let us hope
this move serves as a

Dr.T.V.Rao MD

The

3/13/16

Tuberculosis is a Indias great 4

Concern

ACTIVE TUBERCULOSIS

Dr.T.V.Rao MD

tuberculosis (TB)
disease occurs when the
TB bacteria become
"active"; they
overwhelm the immune
system and cause a
person to become ill.
This usually occurs in
the lung, although TB
can affect any part of
the body, including the
lymph nodes, brain,

3/13/16

Active

Dr.T.V.Rao MD

Drug

3/13/16

Beginning of Drug Resistance in6

Tuberculosis

resistance was first

noted in the 1940s when
streptomycin was
formally studied as
monotherapy for the
treatment of
tuberculosis . As a
result, subsequent
therapeutic
interventions utilized
multidrug regimens to
decrease the risk of drug

Mycobacterium tuberculosis

Dr.T.V.Rao MD

tuberculosis is an ancient
human pathogen, which
has plagued countless
human societies despite
the introduction of
curative and preventive
therapy in the last
century. In recent years,
international attention
has turned toward the
evolving burden of

3/13/16

Mycobacterium

8
Multi-drug-resistant tuberculosis

tuberculosis (MDR-TB,
also known as Vank's
Disease) is defined as a
form of TB infection
caused by bacteria that
are resistant to
treatment with at least
two of the most powerful
first-line anti-TB drugs
isoniazid (INH) and

Dr.T.V.Rao MD

3/13/16

Multi-drug-resistant

9
Increasing incidence of MDR TB
Dr.T.V.Rao MD

3/13/16

Five

percent (5%) of
all TB cases across
the globe in 2013
were estimated to be
MDR-TB cases,
including 3.5% of
newly diagnosed TB
cases, and 20.5% of
previously treated

Magnitude of MDR/XDR

10

500,000 cases/year

Approximately

100,000 cases/year

in China
Approximately

40,000 cases/year

in Russia
Only

5% were diagnosed and

treated

About

3% of all cases were treated

Dr.T.V.Rao MD

3/13/16

Approximately

or Initial drug resistant

Secondary
Drug

or Acquired drug resistant

resistant (DR)

Mono-drug
Poly-drug

resistant

resistant

Multi-drug

drug resistant (MDR)

Extensively
Totally

drug resistant (XDR)

drug resistant (TDR)

Dr.T.V.Rao MD

Primary

11
3/13/16

Classification of Drug
Resistant Tuberculosis

Dr.T.V.Rao MD

Multidrug-

12
3/13/16

Definition of MDR
Tuberculosis

resistant
tuberculosis (MDRTB) is defined as
laboratoryconfirmed
resistance to the
two most potent
first-line

What is XDR Tuberculosis

Dr.T.V.Rao MD

2007, extensively
drug-resistant
tuberculosis (XDR-TB) has
been defined as
resistance to both
isoniazid and rifampin
with additional resistance
to at least one
fluoroquinolone and one
injectable agent
(amikacin, kanamycin, or

3/13/16

Since

13

Dr.T.V.Rao MD

MDR-TB

3/13/16

MDR-TB infection

14

infection may be classified as either

primary or acquired. Primary MDR-TB occurs
in patients who have not previously been
infected with TB but who become infected
with a strain that is resistant to treatment.
Acquired MDR-TB occurs in patients during
treatment with a drug regimen that is not
effective at killing the particular strain of TB
with which they have been infected. Rates of
primary MDR-TB are low in North America and
Western Europe: in the US in 2000, the rate

Trends on MDR
As of 2013, 3.7% of new tuberculosis cases
tuberculosis
have MDR-TB.
Levels are much higher in those
15
Dr.T.V.Rao MD

3/13/16

previously treated for tuberculosis - about

20%. WHO estimates that there were about 0.5
million new MDR-TB cases in the world in 2011.
About 60% of these cases occurred in Brazil,
China, India, the Russian Federation and South
Africa alone. In Moldova, the crumbling health
system has led to the rise of MDR-TB. In 2013,
the MexicoUnited States border was noted to
be "a very hot region for drug resistant TB",

Dr.T.V.Rao MD

Cell

16
3/13/16

Mechanism of M. tuberculosis
drug resistance

wall: The cell wall of M. tuberculosis consists of

complex lipids, and it acts as a permeability barrier
from drugs.

2.Drug

modifying & inactivating enzymes: The M.

tuberculosis genome codes for certain enzymes that
make it drug resistant. The enzymes usually
phosphorylate, acetylate, or adenylate the drug
compounds.

3.Drug

efflux systems

4.Mutations:

Spontaneous mutations in the M.

Dr.T.V.Rao MD

3/13/16

17
Examples of mutations that
make M. tuberculosis drug
resistant
An example of this is the mutation in the rpoB gene,
which encodes the beta subunit of the bacteria's RNA
Polymerase. This mutation makes the bacillus
resistant to Rifampicin. Non-resistant TB is sensitive
to Rifampicin because this drug binds to the beta
subunit of the RNA Polymerase, and hence disrupts
transcription elongation. When the rpoB gene is
mutated, the resulting beta subunit protein has
different amino acids, and thus a different
conformation. Rifampicin can no longer bind to the
beta subunit and prevent transcription.

Dr.T.V.Rao MD

18
3/13/16

Mutations initiate Drug

Resistance in Tuberculosis

Other mutations make the bacterium resistant to other

drugs. For example, there are many mutations that can
make M. tuberculosis resistant to Isoniazid. Mutations
leading to INH resistance have been identified in different
gene targets including katG, inhA, ahpC and other genes
that remain to be established. Amino acid replacements in
the NADH binding site of InhA apparently result in INH
resistance by preventing the inhibition of mycolic acid
biosynthesis, which the bacterium uses in its cell wall.
Mutations in the katG gene causes the enzyme catalase
peroxidase unable to convert INH to its biologically active
form. Hence, INH is not able to affect M. t

Impact of MDR, XDR-TB

19

No effective treatment
Increasing morbidity and
mortality ( some report
show survival time in days)

Transmissible and spread

disease in general
population
( especially in

Dr.T.V.Rao MD

3/13/16

Risk Factors to Carry Drug

Resistant TB
20

Previous history of
treatment
* Failure
* Relapse

Dr.T.V.Rao MD

3/13/16

* HIV co-infection
*
Addictions
*
Contact with drug
resistant patient

When to suspect MDR

TB
In All Re-treatment

21

patients
All

treatment
failures

Treatment

adherent
patient whose
condition deteriorates

Patient

whose smear
does not convert after
three months of

Dr.T.V.Rao MD

3/13/16

Compliance with
management guidelines
as laid by NTCP
Excellent adherence
during the intensive
phase and continuation
phase

Dr.T.V.Rao MD

Ensuring cure of new

smear positive patients
the first time Ensure
that Re-treatment cases
complete their treatment

3/13/16

Prevention of MDR
TB

22

Prevention of MDR-TB cont

23

supply of TB
drugs to
treatment
points

is crucial

Treatment

is
free of charge

Supervision

therapy

of

Dr.T.V.Rao MD

3/13/16

Uninterrupted

Management Principles

24

done before treatment

is commenced
Patient sign consent form
MDR TB is treated for 18 -24
months Six months initial phase
hospitalisation
Patients are diagnosed

Dr.T.V.Rao MD

3/13/16

Counselling

Management Principles
cont
25

MDR TB wards

Management teams
with clear management
responsibilities Management
teams to have capacity and
expertise
Treatment logistics should be in
place

Dr.T.V.Rao MD

3/13/16

Dedicated

Dr.T.V.Rao MD

3/13/16

26
How can MDR TB be
The most important
thing a person can do to
prevented?

prevent the spread of MDR TB is to take all of

their medications exactly as prescribed by their
health care provider. No doses should be
missed and treatment should not be stopped
early. Patients should tell their health care
provider if they are having trouble taking the
medications. If patients plan to travel, they
should talk to their health care providers and
make sure they have enough medicine to last
while away

providers can help

prevent MDR TB by
quickly diagnosing
cases, following
recommended
treatment
guidelines,
monitoring patients
response to

Dr.T.V.Rao MD

3/13/16

27 Help Prevent the spread of MDR

TB
Health care

 Patient

whose smear
becomes positive again

after

Dr.T.V.Rao MD

3/13/16

When to suspect MDR TB 28

cont
initial conversion

Patient

whose smear is
negative but not

responding

to treatment

Symptomatic

contacts
of an MDR TB patient

29
How can MDR TB be prevented?

Another way to prevent

getting MDR TB is to avoid
exposure to known MDR
TB patients in closed or
crowded places such as
hospitals, prisons, or
homeless shelters. If you
work in hospitals or
health-care settings
where TB patients are
likely to be seen, you
should consult infection
control or occupational
health experts. Ask about
administrative and

Dr.T.V.Rao MD

3/13/16

Diagnosis of MDR-TB

30

In All Re-treatment
patients culture and
DST needs to taken

Treatment failures
on new TB cases

HCW are at riskwhen

Infection Control
measures are not in
place

MDR TB contacts

* A rare photograph of

Dr.T.V.Rao MD

3/13/16

technique
Hemi-nested

PCR of
rpoBgenes with 5
different color primers

Result

will be known
in 2 hours

Sensitivity

of 96.7%,
Specificity of 98.6%
with PPV of 93.6% and
NPV of 99.3%

Dr.T.V.Rao MD

Semi-automated

3/13/16

Xpert MTB/RIF

31

Xpert MTB/RIF

Dr.T.V.Rao MD

3/13/16

Xpert

32

MTB/RIF and reduce the cost of its use. An

innovative private-public partnership is a part of this
project and two external implementers will roll out
the activities via the non-governmental and private
sector. While UNITAID funding will allow Xpert to be
rolled out in 21 recipient countries, a novel financing
collaboration led by UNITAID and other partners has
achieved a 40 percent price reduction for this rapid
TB test. The project will assist in timely procurement
of 225 GeneXpert instruments in project sites in 21
low- and middle-income countries, utilising
1,444,960 Xpert MTB/RIF tests in 2013-2015

33
WHO Initiatives on TB Xpert
Dr.T.V.Rao MD

the leadership of Global TB Programme of

the World Health Organization (WHO), and the
Stop TB Partnerships Global Drug Facility (GDF),
the TBXpert Project will provide approximately 1.4
million Xpert MTB/RIF test cartridges and over 225
Xpert instruments instruments for the rapid
detection of TB and rifampicin resistance in 21
recipient countries (see map by clicking data
visualization on the right-hand column).
Currently all 21 countries have agreements with
the Project for the roll out. All countries placed
orders and all 21 countries received their
supplies. Number of cases detected with TB and
3/13/16

Under

MDR-TB diagnostics

Dr.T.V.Rao MD

3/13/16

The

34

Xpert assay represents a major advance for TB

diagnosis. Most current TB testing involves a centuryold technique where sputum samples are examined
under a microscope to check for the tuberculosis
bacillus. The gold standard diagnostic test for TB
diagnosis is the laboratory culture of Mycobacterium
tuberculosis but it can take up to two months to
provide results. Xpert provides dependable results
directly from sputum samples in less than two hours
and also detects resistance to rifampicin, one of the
most commonly used first-line drug for the treatment
of TB.

Dr.T.V.Rao MD

3/13/16

)35
Rapid Drug Susceptibility Test
(DST

Carry over contamination is not a problem because format

of PCR reaction is not sensitive and can be done in smear
positive

Interpretation

Hybridization band should be positive

M.tb band should be positive

All wild type bands are positive and no mutant band is

positive : sensitive

All wild type bands are positive and any one mutant band
is positive : resistance

Any one of wild type band is missing : resistance

36
Rapid Drug Susceptibility Test (DST)
Dr.T.V.Rao MD

Risk

for rapid DST

3/13/16

Indication

factor(s) to carry drug resistance strains

Closed

contact to MDR-TB patient and develop

TB
Smear

positive at 2(3) months after treatment

Smear

positive at 5 months after treatment

Before

changing regimen or adding any drug to

treatment regimen

Suspected

patient

of NTM infection in smear positive

Stop TB Reach Everyone 37

Dr.T.V.Rao MD

3/13/16

The rapid and accurate

diagnosis of symptomatic
patients is the cornerstone
of global strategies for TB
control. TB is challenging to
diagnose and difficult to
treat, especially in the
developing world which
bears 95% of the global
disease burden. Inaccurate
diagnosis has spurred the
rapid spread of TB and drug
resistance especially in

Dr.T.V.Rao MD

38
3/13/16

The need for improved TB

diagnostics

ultimate goal of providing a more upto-date TB diagnostic tool for the 21st
century is the focus of ongoing research
and development. However, the
expanding TB/HIV epidemics and the
increasing of drug resistant TB, have led
to a need for improved diagnostics that
complement each other. While no single
diagnostic test provides all the
information needed for patient care over
the disease progression, several

Dr.T.V.Rao MD

The

3/13/16

What is goal of everyone in39

Control of Tuberculosis

40
Great plan to control tuberculosis
Dr.T.V.Rao MD

3/13/16

comes as a shot in the arm for

India's fight against tuberculosis, as
the government of India plans to
introduce 300 powerful diagnostic
machines which are capable of
conducting a highly sensitive
molecular test. The GeneXpert TB
test machines can detect five times
more cases of drug resistant

Dr.T.V.Rao MD

It

41
3/13/16

Indian Government To Tackle

Tuberculosis With 300 New GeneXpert
Diagnostic Machines

Attention of Viewers

42

II

Dr.T.V.Rao MD

3/13/16

am thankful to many in the world who made me to achieve my desired goals faster than I
thought, having > 3-5 million health professionals share and utilize my knowledge for the
benefit of mankind, Today I wish to be freelancer to the world to create interest in Medical,
Clinical and Diagnostic Microbiology with more emphasis on Infectious diseases and Hospital
associated Infection wish to be your partner in educating many millions who know well the
importance of Infectious diseases

You can visit many web sites of mine

www.medmicrobes.com

www.slidehsare.com

www.authourstream.com

www,scribd.com

Be a friend on Facebook with tummalapalli venkateswararao access

Raos Microbiology

Raos Infection care

Microbiology connected Travancore Medical College

For any assistance on INFECTION REALTED ISSUES CONTACT ME AT doctortvrao@gmail.com

Mob

+91 7204113154

43
Dr.T.V.Rao MD

Created by Dr.T.V.Rao MD for

Benefit of Medical and Paramedical
Professionals in the Developing World
Created from World Wide Resources
Email
doctortvrao@gmail.com
3/13/16

Program