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MDR-TBan update

DR.T.V.RAO MD

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2HOW DOES TUBERCULOSIS OCCUR?

The 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

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4Tuberculosis is a India’s great Concern

The 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 booster to tackle the TB endemic.

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5ACTIVE TUBERCULOSIS Active 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, kidneys, or bones.

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6Beginning of Drug Resistance in Tuberculosis

Drug 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 resistance.

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7Mycobacterium tuberculosis Mycobacterium

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 drug resistance.

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8Multi-drug-resistant tuberculosis

Multi-drug-resistant 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 rifampicin

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9Increasing incidence of MDR – TB 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 TB cases

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10Magnitude of MDR/XDRApproximately 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

with good quality drugs

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11Classification of Drug Resistant Tuberculosis

Primary or Initial drug resistant •Secondary or Acquired drug resistant •Drug resistant (DR) –Mono-drug resistant –Poly-drug resistant •Multi-drug drug resistant (MDR) •Extensively drug resistant (XDR) •Totally drug resistant (TDR)

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12Definition of MDR Tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) is defined as laboratory-confirmed resistance to the two most potent first-line medications, isoniazid and rifampin .

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13What is XDR – Tuberculosis Since 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 capreomycin) .

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14MDR-TB infection MDR-TB 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 of primary MDR-TB was 1% of all cases of TB nationally

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15Trends on MDR tuberculosis As of 2013, 3.7% of new tuberculosis cases

have MDR-TB. Levels are much higher in those 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 Mexico–United States border was noted to be "a very hot region for drug resistant TB", though the number of cases remained small

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16Mechanism of M. tuberculosis drug resistance

Cell 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.

tuberculosis genome can give rise to proteins that make the bacterium drug resistant, depending on the drug action.

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17Examples 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.

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18Mutations 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

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19Impact of MDR, XDR-TB No effective treatment

• Increasing morbidity and mortality ( some report show survival time in days) • Transmissible and spread disease in general population ( especially in compromised host) • Health care workers are risk to be infected

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20Risk Factors to Carry Drug Resistant TB

Previous history of treatment * Failure * Relapse * HIV co-infection * Addictions * Contact with drug resistant patient * Born in high prevalence country

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21When to suspect MDR TB

In All Re-treatment patients

•All treatment failures

•Treatment adherent patient whose condition deteriorates

•Patient whose smear does not convert after three months of treatment

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22Prevention of MDR TB

Ensuring cure of new smear positive patients the first time •Ensure that Re-treatment cases complete their treatment •Compliance with management guidelines as laid by NTCP •Excellent adherence during the intensive phase and continuation phase

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23Prevention of MDR-TB cont…

Uninterrupted supply of TB drugs to treatment

points is crucial •Treatment is

free of charge •Supervision of

therapy

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24Management Principles Counselling 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 at PHC centres and peripheral Hospitals •Management structures to be in place

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25Management Principles cont

Dedicated MDR TB wards •Management teams with clear management responsibilities •Management teams to have capacity and expertise •Treatment logistics should be in place •OPD Clinic conducted at MDR TB Unit •Patients to be accompanied to the clinic

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

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

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27Help Prevent the spread of MDR - TBHealth care

providers can help prevent MDR TB by quickly diagnosing cases, following recommended treatment guidelines, monitoring patients’ response to treatment, and making sure therapy is completed.

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28When to suspect MDR TB cont…

Patient whose smear becomes positive again

after initial conversion •Patient whose smear is

negative but not responding to treatment •Symptomatic contacts

of an MDR TB patient

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29How 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 environmental procedures for preventing exposure to TB

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30Diagnosis of MDR-TB 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

James Nachtwey

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31Xpert MTB/RIF Semi-automated

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%

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32Xpert MTB/RIF Xpert 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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33WHO Initiatives on TB Xpert Under the leadership of Global TB Programme of

the World Health Organization (WHO), and the Stop TB Partnership’s 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 with Rifampicin resistant TB has steadily increased with programme roll out.

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34MDR-TB diagnostics The Xpert assay represents a major advance for TB

diagnosis. Most current TB testing involves a century-old 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.

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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

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36Rapid Drug Susceptibility Test (DST) Indication for rapid DST –Risk 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 of NTM infection in smear positive

patient

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37Stop TB Reach Everyone

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38The need for improved TB diagnostics

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 HIV/AIDS patients.

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39What is goal of everyone in Control of Tuberculosis

The ultimate goal of providing a more up-to-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 technologies exist today that can help reduce the spread of TB and its mortality rate.

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40Great plan to control tuberculosis

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41Indian Government To Tackle Tuberculosis With 300 New GeneXpert

Diagnostic MachinesIt 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 tuberculosis as per various studies across the country.

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42Attention of Viewers II 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 Rao’s Microbiology Rao’s 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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Program 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