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Multi drug resistant T.B. (MDR)Dr. Gopalrao M.D. Ph.D.Professor of Community MedicineCAR Medical College

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Global Fact sheet: T.B. Incidence: 8.8 million people are affected by TB annually world wide. 1.4 million deaths occur annually world wide. MDR-TB is defined as disease having resistance to two or more of the anti T.B. drugs with or without resistance to other anti TB drugsIt is a major threat to TB control program world wide.

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Countries having problem of MDR T.B.

RussiaPeoples Republic of ChinaIndiaWestern EuropeUnited statesUnited KingdomGermanyCentral EuropeLithuaniaLatviaEstonia

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Indian ScenarioPrevalence of MDR T.B. in new smear +ve cases

is less than 3% and 12 to 17% amongst previously treated PTB cases. • India is the highest TB burden country in the world.

• India is 17th among 22 high burden countries in terms of incidence rate • Accounts for 20% of global burden of TB.• Every year 1.8 million persons develop TB • There are point eight million new smear positive cases. • The annual risk of becoming infected with TB is 1.5 %

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Case study from Andhra PradeshStudy conducted on 75 MDR T.B. cases.

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Reported MDR cases from 18 districts of Andhra Pradesh

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2

561

9

5

5

10

3

2

2

5

2

21

1

14

8

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NO. OF PATIENTS

% OF PATIENTS

SOB, Cough, fever

38 50%

Cough, fever 20 27%

SOB, cough 6 8%

Cough, fever, loss of appetite

2 3%

SOB, cough, fever, loss of

appetite

2 3%

cough 2 3%

SOB, Haemoptysis

1 1%Cough, loss of appetite

1 1%

Cough, fever, haemoptysis

1 1%

SOB 1 1%

SOB, cough,haemoptysis

1 1%

Cough, fever,chest pain

1 1%

Complaint

s among

MDRTB

Patients

Clinical factors promoting resistanceDelayed diagnosis and isolationInappropriate drug regimen.

Inadequate initial therapy Incomplete course of treatment Inappropriate treatment modificationsAdding single drug to a failing regimen Inappropriate use of chemoprophylaxis

Poor adherence and incomplete Follow upFailure to isolate MDR TB patientsFailure to employ DOTOver the counter anti TBFaked drugs

Mechanism of ResistanceTB specific drugs

INH, PZA, ETH

Antibiotics with activity against TBRIFAminogycosidesFlouroquinolones

INHChromosomally mediatedLoss of catalase/peroxidaseMutation in mycolic acid synthesisRegulators of peroxide response

Mechanism of resistance

RifampinReduced binding to RNA polymerase

Clusters of mutations at “Rifampin Resistance Determining Region” (RRDR)

Reduced Cell wall permeability

Mechanism of resistance

Treatment of MDR TBFactors determining Success

Culture of MDR TBReliable susceptibilityReliable history of previous drug regimensProgram to assure delivery of prescribed drugs

(DOT)Correct choice of modified treatment regimenReliable follow up

New Chemotherapeutic AgentsNot many. Low interest from pharmaceutical

industryDerivatives of Rifamycin

Rifabutin: Sensitive subset of Rifampin resistant strainsRifapentine: Extended half-life but more mono-

resistance to rifamycinsKRM-1648. benzoxazinorifamycin. In vitro and animal

models.New flouroquinolones

Gatifloxacin, Moxifloxacin, levofloxacin, sparfloxacinNitroimidazoles

related to metronidazole. May work better against latent bacilli

Avoiding pro-drug problems

ChemoprophylaxisDeterminants of intervention

Likelihood of infection with MDR TB Low Intermediate High

Likelihood of developing MDR TB Immune suppression

Global TB control targets

2005: World Health Assembly:- To detect at least 70% of infectious TB cases- To treat successfully at least 85% of detected cases

2015: 50% reduction in TB prevalence and death rates by 2015

2015: Goal 6: Combat HIV/AIDS, malaria and other diseases Target 8: to have halted by 2015 and begun to reverse the incidence… Indicator 23: prevalence and deaths associated with TB

Indicator 24: proportion of TB cases detected and cured under DOTS

Stop TB Strategy to reach the 2015 MDGs

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Thank You