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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• 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 XDR- TB

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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-TB2 Framework for effective control of DR-TB3 Political commitment and coordination 4 Definitions: case registration, bacteriology and treatment

outcomes5 Case-finding strategies 6 Laboratory aspects 7 Treatment strategies for MDR-TB and XDR-TB 8 Mono- and poly-resistant strains9 Treatment of DR-TB in special conditions and situations10 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 failure14 Management of contacts of MDR-TB patients15 Drug resistance and infection control 16 Human resources: training and staffing17 Management of second-line antituberculosis drugs 18 Category IV recording and reporting system19 Managing DR-TN through patient-centered careANNEX 1 Drug information sheetsANNEX 2 Weight-based dosing of drugs for adultsANNEX 3 Suggestions for further readingANNEX 4 Legislation, human rights, and patient’s right in TB

care prevention and control ANNEX 5 Use of experimental drugs outside of clinical trials ANNEX 5 Methodology

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New STB strategy and Update on XDR epidemiology

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DOTS MDR-TB

FUNDING: Government Commitment (10$/ case)

> money

Up to 20,000 $/ caseDIAGNOSIS: SS microscopy, QA and safety measures

+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?

• 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

• 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 2007Sotgiu et al, ERJ 2008

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Global Policy: MDR-TB and XDR-TB

1. Strengthen basic TB control, to prevent M/XDR-TB2. Scale-up programmatic management and care of

MDR-TB and XDR-TB 3. Strengthen laboratory services for adequate and

timely diagnosis of MDR-TB and XDR-TB4. Ensure availability of quality drugs and their

rational use5. Expand MDR-TB and XDR-TB surveillance 6. Introduce infection control, especially in high HIV

prevalence settings7. Mobilize urgently resources domestically and

internationally8. Promote research and development into new

diagnostics, drugs and vaccines

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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