mdr tb and xdr tb


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multidrug resistant tuberculosis and extensively drug resistant tuberculosis

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mdr tb and xdr tb

  2. 2. INTRODUCTION <ul><li>Tuberculosis is an ancient disease & it remains the leading cause of death of human being. </li></ul><ul><li>It is mainly caused by Mycobacterium tuberculosis </li></ul><ul><li>Mycobacteria causing human disease may be classified as follows: </li></ul><ul><li>Mycobacteria </li></ul><ul><li>1.CULTIVABLE MYCOBACTERIA: </li></ul><ul><li>a). Typical tubercle bacilli. </li></ul><ul><ul><li>Human type M.tuberculosis. </li></ul></ul><ul><ul><li>Bovine type M.bovis. </li></ul></ul><ul><ul><li>Vole type M.microti. </li></ul></ul><ul><ul><li>Human type M.africanum. </li></ul></ul>
  3. 3. <ul><li>b). Atypical mycobacteria (Runyon’s classification) </li></ul><ul><li>Group 1 Photochromogen </li></ul><ul><li>M. kansasii </li></ul><ul><li>M.marinum </li></ul><ul><li>M. simiae </li></ul><ul><li>M. asiaticum </li></ul><ul><li>Group 2 Scotochromogen </li></ul><ul><li>M.Scrofulsceum </li></ul><ul><li>M. Szulgai </li></ul><ul><li>M. Xenopi </li></ul><ul><li>M.Gordonae </li></ul><ul><li>M. Celatum </li></ul>
  4. 4. <ul><li>Group 3 Non photochromogens </li></ul><ul><li>M.avium-intracellular complex </li></ul><ul><li>M. Paratuberculosis </li></ul><ul><li>M.terrae-triviale </li></ul><ul><li>M.Shimoidae </li></ul><ul><li>Group 4 Rapid growers </li></ul><ul><li>M.fortuitum/chelonae complex </li></ul><ul><li>M.thermoresistible </li></ul>
  5. 5. <ul><li>C). Saprophytic mycobacteria. </li></ul><ul><li>M.smegmatis </li></ul><ul><li>M.phlei </li></ul><ul><li>M.stercoris </li></ul><ul><li>M. thermo </li></ul><ul><li>2) NON CULTIVABLE MYCOBACTERIA: </li></ul><ul><li>M.leprae (cause leprosy in human) </li></ul>
  6. 6. <ul><li>It is estimated that yearly about 9 millions people in the world are attacked with TB, with 1.7 million deaths. [1] </li></ul><ul><li>Airborne disease that is transmitted only after prolonged exposure to someone with active disease. </li></ul><ul><li>TB usually infects the lungs but other organs can be involved </li></ul>
  7. 7. TRANSMISSION Transmission of Tuberculosis <ul><li>The spread of M. tuberculosis involves a 3-step process: </li></ul><ul><ul><li>Transmission of bacteria, </li></ul></ul><ul><ul><li>Establishment of infection, and </li></ul></ul><ul><ul><li>Progression to disease. </li></ul></ul>
  8. 8. EPIDEMIOLOGY <ul><li>The average prevalence of tuberculosis in India is estimated to be 5.05 per thousands. </li></ul><ul><li>Prevalence of smear positive cases 2.7 per thousand. </li></ul><ul><li>Annual incidence of smear positive cases at 84 per 1, 00,000 annually. [2] </li></ul><ul><li>The recent survey of WHO Says 98% of cases in developing countries with an increase of ~3% annually, 10% in African countries . </li></ul><ul><li>80% of cases seen in 22 countries; about half in 5 countries: India, China, Indonesia, Nigeria and Bangladesh. </li></ul><ul><li>In India every day more than 5,000 develop TB disease and more than 1,000 people die. [3] </li></ul>
  9. 9. JUSTIFICATION OF STUDY <ul><li>Find out prevalence of Tuberculosis in South Gujarat region. </li></ul><ul><li>Identification and characterization of MDR & XDR TB cases. </li></ul><ul><li>Effectivity of Herbal Drug on MDR & XDR TB Strains. </li></ul>
  10. 10. HIV –TB CO-INFECTION <ul><li>Tuberculosis is the most common life threatening opportunistic infection in patient with HIV. </li></ul><ul><li>About 25 to 65 % patient with HIV/AIDS having tuberculosis of any organ. [6, 7, 8] </li></ul><ul><li>About 11.5 million people were co-infected with HIV and M.tuberculosis globally at the end of 2000. [4, 9] </li></ul><ul><li>HIV reactivates latent TB by weaking the natural defences of infected persons </li></ul><ul><li>In India 5.1 million HIV infected people, about half of them are co infected with M.tuberculosis [10] </li></ul><ul><li>Thus tuberculosis is a leading cause of morbidity and mortality in patient with HIV/AIDS [4, 5] </li></ul>
  11. 11. TREATMENT & CONTROL <ul><li>There are various ways to prevent tuberculosis. </li></ul><ul><li>BCG Vaccine </li></ul><ul><li>The use of BCG stimulates partial immunity </li></ul><ul><li>The effectiveness of BCG in preventing tuberculosis in adult is limited. </li></ul><ul><li>Tuberculosis can be treated effectively by a combination of anti-tubercular drugs. </li></ul><ul><li>First line drugs Isoniazid, Rifampicin, Streptomycin, Pyrazinamide and Ethambutol.[11] </li></ul><ul><li>Anti-tubercular drugs </li></ul><ul><li>Second line drugs Amikacin,Levofloxacin, Gatifloxacin, PAS [Para amino Salicyclic acid], Ethionamide, Kanamycin Cycloserine, Capreomycin and Ofloxacin. </li></ul><ul><li>Majority of these drugs are bacteriostatic than bactericidal, therefore causes of MDR </li></ul><ul><li>& XDR more. </li></ul><ul><li>Patient with tuberculosis, who fail to complete ‘Standard’ course or irregular intake of drug are at increased risk for treatment failure and they may play a role in both the emergence of drug resistant strains of M.tuberculosis and further spread of tuberculosis in the society. [11] </li></ul>
  12. 12. MDR-TB & XDR TB CAUSES OF DRUG RESISTANCE <ul><li>Inadequate dosage or treatment with too few drugs. </li></ul><ul><li>Lack of compliance </li></ul><ul><li>Patients fail to take medication consistently for 6-12 months necessary for cure. </li></ul><ul><li>Patients feel better after 3 or 4 weeks </li></ul><ul><li>Drugs have unpleasant side effects </li></ul>
  13. 13. <ul><li>WHAT IS MDR-TB & XDR TB </li></ul><ul><li>Drug resistant TB is widespread and found in all countries surveyed. It emerges as a result of treatment mismanagement and is passed from person to person in the same way as drug sensitive TB. </li></ul><ul><li>Multidrug resistant TB [MDR-TB] is a form of TB that does not respond to the standard six month treatment using first line drugs [i.e. resistant to Isoniazid and Rifampicin]. It can take two years to treat with drugs that are more toxic, and 100 times more expensive. If the drugs to treat MDR-TB are mismanaged. Further resistance can occur. </li></ul><ul><li>Extensively drug resistant [XDR TB] is a form of TB caused by bacteria resistant to all the most effective drugs [i.e. MDR-TB plus resistance to any fluoroquinolone and any of the second line anti-TB injectable drugs: Amikacin, Kanamycin or Capreomycin]. </li></ul>[18]
  14. 14. [19]
  15. 15. MDR-TB AND HIV <ul><li>MDR-TB and XDR-TB are associated with an extremely high mortality, especially in the HIV co infected person [14] </li></ul><ul><li>According to the 4th WHO report [2008] on anti tuberculosis drug resistance; MDR-TB has been shown to be almost twice as common in TB patient living with HIV as compared to TB patient without HIV [12] </li></ul><ul><li>To resolve the problem of TB the National Tuberculosis Programme [NTP] in India was implemented in 1962 </li></ul><ul><li>To improve & strengthen tuberculosis control activities, the Government of India launched the Revise National Tuberculosis Control Programme [RNTCP] in 1997 and cover almost the whole country with excellent results by the end of 2005. [3] </li></ul><ul><li>Directly Observed Treatment, Short Course Chemotherapy [DOTS] means that the patient swallows short course anti TB drugs in the presence of health worker or other trained individual. [3] </li></ul>There are two phases in the treatment of tuberculosis, -The intensive phase which is of 3 months, -The continuation phases for 4 and 5 months.
  16. 16. <ul><li>According to the WHO, under this programme second line anti TB drugs are used to control the prevalence of MDR-TB & thus DOTS-PLUS should be implemented in selected areas with moderate to high levels of MDR-TB. [13] </li></ul><ul><li>There have been a number of reports on drug resistance in India including state level Drug Resistance Surveillance [DRS] surveys conducted in Gujarat & Maharashtra. </li></ul><ul><li>Data from these studies have found MDR-TB levels of about 3%in new cases and 12%-17% in re-treatment cases. [20] </li></ul><ul><li>As per the DOTS Plus strategy the diagnosis of MDR-TB will be made at the Intermediate Reference Laboratories (IRLs) accredited to perform culture and Drug Sensitivity Testing (DST). </li></ul><ul><li>RNTCP has initiated the establishment of the laboratory network in a phased manner </li></ul><ul><li>in all the states across the country with support from the four National reference </li></ul><ul><li>Laboratories. </li></ul>
  17. 17. PLAN OF WORK A. Sample collection Sputum samples <ul><li>2 Consecutive days Sputum samples </li></ul><ul><li>Normally sputum is non-sterile clinical sample and so it contains the organisms present as a normal flora of the respiratory tract. </li></ul>B. Staining <ul><li>The screening for the bacilli of M.tuberculosis will be done by acid fast staining. </li></ul>
  18. 18. C. Culture <ul><li>The sample which will show 8-10 bacilli per field will be further studies for the sputum culture. </li></ul>Liquefication and Decontamination <ul><li>For the target isolation of M.tuberculosis, the samples are to be treated with acid and alcohol. </li></ul><ul><li>Method used for Digestion & Decontamination of sputum sample will be N-Acetyl-l-cysteine sodium hydroxide. [15] </li></ul>Inoculation <ul><li>To perform the sputum culture the sample will be inoculated into Loweinstein Jenson [L-J] media along with Middle Brook 7H11 [16]. </li></ul>
  19. 19. Incubation <ul><li>All the inoculated media will be incubated for 3 to 4 weeks. </li></ul><ul><li>Isolated colonies will be studied in detail for their morphological, cultural and biochemical characteristics. </li></ul>Growth on L.J. Medium <ul><li>Rough, Buff and Tough Colony on L.J. Medium </li></ul>
  20. 20. D. Identification Tests <ul><li>PNB TEST [paranitrobenzoicacid], </li></ul><ul><li>Niacin production test, </li></ul>
  21. 21. <ul><li>Catalase quantitative test, </li></ul><ul><li>OTHER BIOCHEMICAL TEST: </li></ul><ul><li>Nacl tolerance test, </li></ul><ul><li>Nitrate reduction, </li></ul><ul><li>Pyrazinamide [15] </li></ul>
  22. 22. E. Drug Susceptibility Testing <ul><li>The drug susceptibility testing will be performed by Two method: </li></ul><ul><li>Direct Susceptibility Testing [ Gold Standard Method ] [16] </li></ul><ul><li>MTT. [3-4,5 dimethyithiazol – 2 yl-2-5-diphenyl tetrazolium bromide] tube method. [ Rapid Method ] [17] </li></ul><ul><li>List of drug to be tested </li></ul>Primary Drug <ul><li>Isoniazid, </li></ul><ul><li>Rifampicin, </li></ul><ul><li>Streptomycin, </li></ul><ul><li>Ethambutol, </li></ul><ul><li>Pyrazinamide </li></ul>
  23. 23. <ul><li>Those organisms showing resistance again more than two drugs will be considered as multi drug resistant </li></ul>F. Result <ul><li>Those organisms showing resistance again MDR TB plus resistant to any fluoroquinolone and any of the second line anti-TB injectable drugs will be considered as a XDR-TB [Extensively Drug Resistant TB] </li></ul>Secondary Drug <ul><li>Amikacin, </li></ul><ul><li>Kanamycin, </li></ul><ul><li>Ethionamide, </li></ul><ul><li>Levofloxacin, </li></ul><ul><li>Gatifloxacin, </li></ul><ul><li>Ofloxacin, </li></ul><ul><li>PAS </li></ul>
  24. 24. G. Effect of herbal extracts <ul><li>MDR and XDR strains are selected for the further studies. </li></ul>Herbal Compound Garlic [ Allium sativum ] <ul><li>Study will be done by MIC [Minimum Inhibition Concentration] method. [21,22] </li></ul>
  25. 25. <ul><li>Study will determine the prevalence of MDR and XDR in south Gujarat region. </li></ul>EXPECTED RESULT <ul><li>Attempts will also be done to suggest the Herbal drugs and its concentration to combat the spread of drug resistant tubercle bacilli . </li></ul>
  26. 26. <ul><li>S.Singh: Scaling up Anti Mycobacterial drug susceptibility services in India. It is high time, Indian Journal of Medical Microbio. [2008] 26 [3] : 209-11 </li></ul>REFERENCES <ul><li>Epidemiology of Tuberculosis: Current status in India. A.K.Chakraborty.India J med Res. 120, oct-2004. p.p.248-276 </li></ul><ul><li>Module for Laboratory Technicians.oct-2005 Central TB Division – New Delhi – 110011 </li></ul><ul><li>Harries A, Maher D, Graham S.TB/HIV: A Clinical Manual. 2nd Edition. Geneva : WHO : 2004 WHO/HTM/TB/2004 : 329 </li></ul><ul><li>Raviglione MC, Narain JP, Kochi A. HIV Associated Tuberculosis in developing Countries : Clinical Features, Diagnosis & Treatment, Bull WHO 1992;70: 515-25 </li></ul><ul><li>Narain jp, Tripathy SP, Pontali E. TB & HIV Infection, Tuberculosis : Epidemiology & Control, New Delhi : WHO Regional office for South Ease Asia : 2002 </li></ul><ul><li>Gothi D, Joshi JM, Clinical & Laboratory observations or tuberculosis at a Mumbai [India] clinic post grad Med j 2004;80:97-100 </li></ul>
  27. 27. <ul><li>Corbett EL,Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, eta. The growing burden of tuberculosis; global trends & interactions with the HIV epidemic. Arch Intern. Med.2003;163 : 1009-21 </li></ul><ul><li>Khatri GR, Friden TR, Controlling tuberculosis in India. N Engl .J med 2002; 347: 1420-5. </li></ul><ul><li>Gandhi N R, Moll A, Sturm A W , Pawinski R, Govender T, Laloo U, Redeller K, Andrews J,Firdlnnd G,2006 Extensively drug resistant tuberculosis as a cause of death in patient co infected with HIV and TB in a rural area in a south Africa. Lancet 368: 1575/1580 </li></ul><ul><li>WHO [2006] Global Tuberculosis Control: Surveillance, Planning, Financing, WHO, Geneva, Switzerland. </li></ul><ul><li>Centres for Disease Control & Prevention [CDC] [2006] Emergence of M.tuberculosis with extensive resistance to 2nd line drugs world wide, 2000-2004. Morb,wkly Rep 55:301-305 </li></ul><ul><li>Sharma SK, Kadhiravan T, Banga A, Goyal T, Bhatia I, Saha PK, Spectrum of clinical disease in a cohort of 135 hospitalized HIV infected patients from north India, BMC Infec.Dis.2004;4:52 </li></ul>
  28. 28. <ul><li>Antimicrobials in laboratory medicine edited by Ashok Rattan, BI,Churchill Livingstone 1st Edition [156-166] </li></ul><ul><li>U Raut, P Narang, DK Mendiratta, R Narang P.Narang, V.Deotale: Evaluation of Rapid MTT tube Method for detection of Drug Susceptibility of M.tuberculosis to Rifampicin & Isoniazid. </li></ul><ul><li>Paramshivam CN :An overview on drug resistant tuberculosis in India, India J tuber.1998;45:73-81 </li></ul><ul><li>Anargyros, P., D. S. J. Astill, and I. S. Sim. 1990. Comparison of improved BACTEC and Lowenstein-Jensen media for culture of mycobacteria from clinical specimens. J. Clin. Microbiol. 28: 1288–1291 </li></ul><ul><li>R.Vijdea, M.Stegger, A.sosnovskaja, A.B.Anderson V.Thomson, D.Bang, MDR-TB – Rapid detection of resistance of RIF & high or low levels of INH in clinical specimens & isolates: EURJ Clinical Micro. Infec.Dis. [2008]27: 1079-1086 </li></ul><ul><li>Clinical Microbiology Procedures Handbook Editor in Chief, Henry D.Isenberg, Vol-I, American society for microbiology/WashingtonD.C. </li></ul>
  29. 29. 20. RNTCP Launches Cat IV (DOTS Plus) treatment for Multi-Drug Resistant TB[2008] 21. In vitro Antibacterial activity of Garlic Against isolates of Acinetobacter spp., Journal of Biological Sciences 7 [5]: 819-822,2007 ISSN 1727-3048 22. Delaha,E.C. AND V.F. Garaqusi, 1985. Inhibition of Mycobacteria by Garlic extract [ Allium sativum ]. Antimicrob agents Chemother.,27:485-486.