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DR.T.V.RAO MD
Dr.T.V.Rao MD
an update
3/13/16
MDR-TB
Dr.T.V.Rao MD
The
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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
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3/13/16
Classification of Drug
Resistant Tuberculosis
Dr.T.V.Rao MD
Multidrug-
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
