Download - Multi-drug resistant Tuberculosis
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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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561
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10
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5
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21
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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