page 1 extreme drug resistant tb and the work place dr jennifer coetzee ampath
TRANSCRIPT
Page 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
Page 3
Anti TB Drugs Currently Available
• 1st Line Drugs:
• INH
• Rifampicin
• PZA
• Ethambutol
• Streptomycin
• 2nd Line Drugs
• Capreomycin
• Kanamycin
• Ethionamide
• PAS
• Cycloserine
• Quinolones
• Thiacetazone
Page 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
Page 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
Page 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%
Page 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
Page 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
Page 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!
Page 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
Page 11
South African Situation (Tugela Ferry)
1428 Patients with sputum sent
475 (34%)Culture-Positive for M.tb
921 Culture-Negative
Lancet 2006, 368:1575-1580
Surveillance at District Hospital:
Page 12
475 patientsCulture-Positive for M.tb
185 (39%)Resistant to Isoniazid & Rifampin
(MDR TB)
290 Susceptible or Resistant
but not MDR
30 (6%) Resistant to all tested drugs
(XDR TB) Prof. W. Sturm
Page 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
Page 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 ?
Page 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
Page 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%
Page 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
Page 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
Page 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
Page 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.