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Extreme Drug Resistant TB and the Work Place

Extreme Drug Resistant TB and the Work Place. Dr Jennifer Coetzee Ampath. Outline. The “ABC” of TB drug resistance Current anti-TB drugs available What is MDR? What is XDR? How does TB drug resistance develop? Epidemiology of XDR TB XDR TB in the work place?

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Extreme Drug Resistant TB and the Work Place

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  1. Extreme Drug Resistant TB and the Work Place Dr Jennifer Coetzee Ampath

  2. Outline • The “ABC” of TB drug resistance • Current anti-TB drugs available • What is MDR? • What is XDR? • How does TB drug resistance develop? • Epidemiology of XDR TB • XDR TB in the work place? • Prevention and management of TB transmission in the occupational setting

  3. 1st Line Drugs: INH Rifampicin PZA Ethambutol Streptomycin 2nd Line Drugs Capreomycin Kanamycin Ethionamide PAS Cycloserine Quinolones Thiacetazone Anti TB Drugs Currently Available

  4. The ABC of TB Drug Resistance • MDR TB: Resistance to INH and Rifampicin • XDR TB: MDR TB that is also resistant to quinolones (e.g. ciprofloxacin) and one other of 2nd line injectable drug • Thus Extreme Drug resistance • Laboratory diagnosis based on susceptibility testing • Cure rate for MDR TB +/- 50% • XDR TB 64% more likely to die than if MDR TB

  5. How does TB drug resistance develop? • Spontaneous and random mutations in the bacterial • chromosome: • INH - 1 X 106 organisms • Rif - 1 x 108 • EMB - 1 x 106 • Strep - 1 x 105 • Probability of spontaneous mutants being simulta- neously resistant to 2 or more drugs is product of individual frequencies… • INH + Rif = 106 + 108 = 1014

  6. MDR: Global Perspective • 50 million people infected worldwide • Low prevalence of MDR: • well functioning TBCP with DOTS, low prevalence of TB, resource rich • High prevalence of MDR TB: • high TB rates, poor countries, limited medication available • MDR rates estimated to be 3 - 4% • Primary MDR: 1 - 3% • Acquired: 7 - 17%

  7. Implications of MDR TB • 100 X more expensive to treat • Duration of Rx up to 24 months • Patient hospitalised for 4 - 6 months • Extensive laboratory monitoring required • Side effects of 2nd line drugs significant • Inconvenient routes of administration • >30% default rate • Treatment failure > 10% if optimally Mx • Mortality rate: • 30 - 40% if HIV uninfected • 70 - 80% if HIV infected

  8. XDR TB • Hot off the press • Term coined in March 2006 • Report published in MMWR 24/03/06 • 350 cases worldwide between 2000 and 2004 • Primarily in South Korea, Eastern Europe and western Asia • 74 cases in USA

  9. Current Situation XDR • USA: 4% of MDR cases meet criteria for XDR • Latvia: 19% of MDR cases considered XDR • Australia, Belgium, Canada, France, Germany, Ireland, Portugal, Spain, Britain: • XDR TB increased from 3% of drug resistant cases to 11% (2000 to 2004) • Pandemic threat!

  10. RSA: The Tugela Ferry Event • In Tugela Ferry HIV/TB co-infected patients, respon- ding to ARV but not to ATT, were identified early 2005 • This prompted culture and susceptibility testing • Infection with highly resistant M.tuberculosis

  11. South African Situation (Tugela Ferry) Surveillance at District Hospital: 1428 Patients with sputum sent 921 Culture-Negative 475 (34%) Culture-Positive for M.tb Lancet 2006, 368:1575-1580

  12. 475 patients Culture-Positive for M.tb 290 Susceptible or Resistant but not MDR 185 (39%) Resistant to Isoniazid & Rifampin (MDR TB) 30 (6%) Resistant to all tested drugs (XDR TB) Prof. W. Sturm

  13. Overall Data for the Area • 52 of 53 people with XDR TB died • 44 were co-infected with HIV • Average survival was 16 days after sputum collection • 55% of the patients were primary XDR! • At least 2 HCWs were infected, died. A further 4 were suspected to have contracted XDR TB • Strain resistant to all 7 anti-TB drugs available in SA • Impact of 5.5 million people infected with HIV/AIDS

  14. Susceptibility Pattern • Isoniazide R • Rifampicin R • Pyrazinamide R • Ethambutol R • Streptomycin R • Kanamycin/amikacin R • Ciprofloxacin/ofloxacin R • Ethionamide S • Cycloserine ? • Capreomycin S • PAS ?

  15. XDR TB and the Work Place • Health care workers from KZN only published proven transmission of XDR TB to have occurred to date • Recent case of patient with XDR TB on aero- plane in US • Outbreaks of MDR TB has been well described • No evidence to suggest that MDR or XDR TB is more easily transmitted than drug susceptible TB

  16. Principles of TB Transmission • Inhalation of microscopic, aerosolised particles containing TB bacilli • Vast majority: particles elaborated by coughing, sneezing or singing • Alveolar deposition thought to be essential • Tiny enough to drift with inspired air rather than impact on mucous membranes • Droplet nuclei of 0.5-5 µm usually vectors of infection • Patients with extensive pulmonary TB pose greatest risk • Study form Alabama, gradient of skin-test reactivity of contacts: • HHCs to smear (+) cases: 46% • Non-HHCs to smear (+) cases: 34% • HHCs to smear (-), culture (+) cases: 28% • Non-HHCs to smear (-), culture (+) cases: 24%

  17. Environmental Factors That Increase the Risk of Transmission of TB • Exposure to TB in small, enclosed spaces • Inadequate local or general ventilation that results in insufficient dilution or removal of infectious nuclei • Recirculation of air containing infectious droplet nuclei • Inadequate cleaning and disinfection of medical equipment • Improper procedure for handling specimens

  18. Risk for Health-Care Associated Transmission of TB • Transmission and outbreaks well described • Magnitude of risk varies by: • Setting • Occupational group • Prevalence of TB in the community • Patient population • Effectiveness of TB infection-control measures

  19. Outbreaks in Health-Care Settings • Multiple outbreaks involved transmission of MDR TB strains to both patients and HCWs • Majority of patients and HCWs were HIV infected • Also outbreaks described in outpatient settings • Factors contributing to outbreaks: • Delayed diagnosis of TB disease • Delayed initiation and inadequate airborne precautions • Inadequate precautions for cough-inducing and aerosol-generating procedures • Lack of adequate respiratory protection

  20. Principles of Management of TB Contacts • Earliest possible identification of index cases • Rapid laboratory detection of MDR TB if indicated • Duration / time-line of exposure often unknown • Baseline CXR, symptom screening • Diagnosis of latent TB infection • Role of blood assays, incl. TB Spot, Quantiferon Gold • Skin testing? • Counseling, HIV testing imperative • Risk of reactivation disease • Treatment of latent TB infection • If exposed to MDR/XDR TB, to be referred to infectious disease specialist. Optimal therapy unknown.

  21. Conclusion “After 25 years working in TB treatment, I’m extremely concerned - we see very little progress, and there seems to be complacency in general about TB” Dr Karin Weyer, August 2006

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