Transcript MDR- and XDR-TB

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MDR- and XDR-TB:
prevention, treatment and control
J-P Zellweger
ERS/TB PAN NET ToT, Barcelona 2010
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Objectives
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To familiarise with the new documents available on
MDR- and XDR-TB management and with the
specific components of the Stop TB Strategy
To analyse the main findings on drug resistance
trends, improvement of laboratory services and
treatment delivery process, and the actions
undertaken to tackle MDR- and XDR- TB
To identify priorities and proposed solutions to
further prevent the emergence of drug resistance
and improve the management of MDR- and XDRTB
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Causes of DR
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Guidelines for the programmatic management of
drug-resistant tuberculosis (1)
1 Background information on DR-TB
2 Framework for effective control of DR-TB
3 Political commitment and coordination
4 Definitions: case registration, bacteriology and treatment
outcomes
5 Case-finding strategies
6 Laboratory aspects
7 Treatment strategies for MDR-TB and XDR-TB
8 Mono- and poly-resistant strains
9 Treatment of DR-TB in special conditions and situations
10 DR-TB and HIV infection
11 Initial evaluation, monitoring of treatment and management of
adverse effects
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Guidelines for the programmatic management of
drug-resistant tuberculosis (2)
12 Treatment delivery and community-based DR-TB support
13 Management of patients with MDR-TB treatment failure
14 Management of contacts of MDR-TB patients
15 Drug resistance and infection control
16 Human resources: training and staffing
17 Management of second-line antituberculosis drugs
18 Category IV recording and reporting system
19 Managing DR-TN through patient-centered care
ANNEX 1
Drug information sheets
ANNEX 2
Weight-based dosing of drugs for adults
ANNEX 3
Suggestions for further reading
ANNEX 4
Legislation, human rights, and patient’s right in TB
care prevention and control
ANNEX 5
Use of experimental drugs outside of clinical trials
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ANNEX 5
Methodology
New STB strategy
and Update on
XDR epidemiology
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DOTS
FUNDING: Government
Commitment (10$/ case)
DIAGNOSIS: SS microscopy,
QA and safety measures
MDR-TB
> money
Up to 20,000 $/ case
+C, DST, SRL, QA,
infection control
TREATMENT: SCC,DOT, 6-8
months, no hospitalization
24 months, mandatory DOT
& hospitalization in
reference facilities
TB drugs only, no AE
relevant toxicity, need
special drugs + expertise
TREATMENT MONITORING:
SS, standard outcome
definitions
C, DST, special outcome
definitons
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Who needs DST?
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Cat I, II failures, chronics
Failure anti-TB TX in the private sector
Contacts of DR-/MDR-TB
HCW at risk, prisoners, homeless, etc.
No SS/C conversion Month 2,3
Residence in very high DR-prevalence settings
Exposure to poor quality drugs
Previous treatment by poor programmes
Co-morbidities favouring rapid transit/ malabsorbtion
HIV+
If available: for ALL TB patients!
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Algorithm for rapid DST testing
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DST testing in routine conditions
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How to design a regimen for MDR-TB cases
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XDR= extensively drug-resistant TB
Definition
Resistance to at least rifampicin and
isoniazid, in addition to any
fluoroquinolone, and to at least one of the
three following injectable drugs used in
anti-TB treatment: capreomycin,
kanamycin and amikacin.
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What was known
• Operational definition, proposed without
solid evidence
• SRLs’ survey on XDR-TB isolates (“ a
posteriori”, no outcomes)
• Anecdotal description of virtually
untreatable TB patients
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What was not known on XDR?
• Is the risk of death/ probability of success
different from that of MDR?
• Are their clinical characteristics different? in
HIV-negative patients?
• Is their infectiousness different?
• Has the XDR definition a clinical relevance?
Which is the role of susceptibility to first-line
drugs different from HR?
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ERS and TBNET studies contributed
to answer
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Time to SS and C conversion double than MDR-TB
Risk of death 5.5 times higher
Higher failure and default rates than MDR-TB
Lower success rate than MDR-TB
High proportion of adverse events due to 2°-line TB
drugs
• XDR-TB definition has both clinical and operational
significance
Migliori GB et al, ERJ 2007
Sotgiu et al, ERJ 2008
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Global Policy: MDR-TB and XDR-TB
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Strengthen basic TB control, to prevent M/XDR-TB
Scale-up programmatic management and care of
MDR-TB and XDR-TB
Strengthen laboratory services for adequate and
timely diagnosis of MDR-TB and XDR-TB
Ensure availability of quality drugs and their
rational use
Expand MDR-TB and XDR-TB surveillance
Introduce infection control, especially in high HIV
prevalence settings
Mobilize urgently resources domestically and
internationally
Promote research and development into new
diagnostics, drugs and vaccines
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Conclusions
• MDR/XDTR-TB is one of the major threats for
the future control of TB
• MDR/XDR-TB is basically a man-made problem
• The main issues are:
– Stopping the source: control of all ERRORS which
sustain the creation of new cases
– Accessing second-line drugs
– Managing medical, human and economical
problems associated with the treatment
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