Download Dr Jennifer Coetzee

Extreme Drug Resistant TB and the
Work Place
Dr Jennifer Coetzee
Ampath
Page 1
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 2
Anti TB Drugs Currently Available
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1st Line Drugs:
INH
Rifampicin
PZA
Ethambutol
Streptomycin
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2nd Line Drugs
Capreomycin
Kanamycin
Ethionamide
PAS
Cycloserine
Quinolones
Thiacetazone
Page 3
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 4
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 simultaneously resistant to 2 or more drugs is product of
individual frequencies…
• INH + Rif = 106 + 108 = 1014
Page 5
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 6
Implications of MDR TB
• 100 X more expensive to treat
• Duration of Rx up to 24 months
– Patient hospitalised for 4 - 6 months
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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 7
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 8
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 9
RSA: The Tugela Ferry Event
• In Tugela Ferry HIV/TB co-infected patients, responding to ARV but not to ATT, were identified early
2005
• This prompted culture and susceptibility testing
• Infection with highly resistant M.tuberculosis
Page 10
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
Page 11
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
Page 12
Overall Data for the Area
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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 13
Susceptibility Pattern
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Isoniazide
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin
R
R
R
R
R
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Kanamycin/amikacin
Ciprofloxacin/ofloxacin
Ethionamide
Cycloserine
Capreomycin
PAS
R
R
S
?
S
?
Page 14
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 aeroplane 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 15
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 16
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 17
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 18
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 aerosolgenerating procedures
– Lack of adequate respiratory protection
Page 19
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.
Page 20
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
Page 21