Extensively Drug Resistant TB A return to the pre antibiotic era by sammyc2007

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									 Extensively Drug Resistant TB:
A return to the pre-antibiotic era?

             Susan Bacheller
         Tuberculosis Team Leader
             October 5, 2007

• Background
• MDR and XDR TB
   – Definitions
   – Current situation
• Outbreak and international
• Global response
                          22 Countries Account for 80% of Global TB Cases

Estimated number of new
TB cases (all forms)

     No estimate
     10 000–99 999
     100 000–999 999
     1 000 000 or more
                         Rates of new TB cases, 2005

Estimated new TB cases
per 100 000 population
     No estimate
     300 or more
Current Situation
                      Key Concepts

Primary (Initial) resistance
• TB patient’s initial Mycobacterium
   tuberculosis population resistant
   to drug

Secondary (Acquired) resistance
• Drug-resistant M. tuberculosis in initial
  population selected by inappropriate
  drug use (inadequate treatment or non-

Multidrug resistant (MDR) TB
  • TB patient’s M. tuberculosis isolate resistant
    to ≥ isoniazid and rifampicin

Extensively drug resistant (XDR) TB
  • MDR plus resistance to at least a fluoroquinolone
    and one second-line injectable drug (amikacin,
    kanamycin, capreomycin)
                  The Return to a Pre-antibiotic Era

 susceptible      MDR-TB         XDR-TB         Total DR
 TB*§             1990§          2006§          ?

*or limited    Resistance   Resistance    Resistance to
resistance     to H&R –     to 2nd line   all available
manageable                  drugs –       drugs –
with 4 drug    Treatable
regimen -      with 2nd
                            options       No
DOTS           line drugs
                            seriously     treatment
                 Factors Contributing to Development
                 and Spread of MDR and XDR TB

• Poor quality treatment
   – Inappropriate treatment regimens
   – Erratic drug taking
   – Poor quality drugs
• Weak TB programs (DOTS)
   –   Low completion/cure rates
   –   Lack of treatment follow up and patient support
   –   Unreliable drug supply
   –   Diagnostic delay
• Absent or inadequate infection control measures
• Uncontrolled use of 2nd line drugs
                   Can MDR-TB Case Management
                    Generate Additional XDR TB?

Message: the higher the % of MDR-TB managed
with current outcomes,
the higher the % of XDR-TB generated

                Blower S, Supervie V. Predicting the future of XDR tuberculosis. Lancet 2007
                    Drug Sensitive vs. Drug Resistant TB

Drug Sensitive TB                   Drug resistant TB – Challenges

•   Diagnosis - smear microscopy    •   Diagnosis – smear, culture and drug-
                                        resistance testing
•   Standardized treatment
                                    •   Treatment based on laboratory
•    4 drugs, 6-9 months                results and epidemiology information
•    Safe, effective, inexpensive   •   4-6 drugs, 2 years
•    95% cure, $20 (drug costs)     •    Less effective, ↑ toxicity and side
•    Based on evidence from ~ 30        effects ($)
    years of drug discovery and     •    <80% cure
    clinical trials
                                    •    Higher relapse rates (30 – 40%)
                                    •   Prolonged infectiousness
                                    •   $3,500 - $5,000 (drug costs)
                                    •    No clinical trials evidence to guide
                                        treatment or prevention
                      XDR TB – Challenges

• Same challenges as for
  MDR TB plus
• Cure rates of only 50 –
  60% in well supported
  programs (among
  predominantly HIV-
• Particularly lethal in PLWA
• Heightened stigma
                          MDR-TB Prevalence in new TB
                          cases 1994-2003

14.2   Kazakhstan

14.2   Israel

13.7   Russia (Tomsk)

13.2   Uzbekistan

12.2   Estonia

10.4   China (Liaoning)

9.4    Lithuania

9.3    Latvia

9.0    Russia (Ivanovo)

7.8    China (Henan)

6.6    Dominican Rep

5.3    Ivory Coast

5.0    Iran

4.9    Ecuador
                                                          % MDR TB in Previously Treated Cases

                                                                                                         Lithuania 53.3%
                                                                                                         Kazakhstan 56.4%
                                                                                                         Russia (Ivanovo) 58.1%

                 < 6%
                6 – 20%
                 20 – 40%
                 > 40 %
                No estimate

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization
concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent
approximate border lines for which there may not yet be full agreement.  WHO 2006. All rights reserved
              Estimated rates of MDR-TB among
              new TB cases, 2005

< 3%
> 6%
No estimate
                                          Countries with confirmed XDR-TB
                                          cases as of September 2007

                                                                                                                      border lines for which there may not yet be full agreement.  WHO 2005. All rights reserved
                                                                                                                      authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate
                                                                                                                      whatsoever on the part of the WHO concerning the legal status of any country, territory, city or area or of its
                                                                                                                      The boundaries and names shown and the designations used on this map do not imply the expression of any opinion
Argentina        Japan

Armenia          Latvia

Azerbaijan       Lithuania

Australia        Mexico

Bangladesh       Mozambique

Brazil           Netherlands

Canada           Norway

Chile            Peru

China, Hong Kong SAR

Czech Republic        Poland

Ecuador          Portugal

Estonia          Republic of Korea

France           Romania

Georgia          Russian Federation

Germany          Slovenia

Ireland          South Africa

India            Sweden

                 of Iran
Islamic RepublicSpain

Israel           Thailand       USA         Based on information provided to WHO Stop TB Department   13 September 2007
Italy            UK             Vietnam
                      Global Estimates

Classification   Estimated Number of   Estimated Number
                        Cases              of Deaths

All forms TB         8.8 million          1.6 million

  MDR TB               424,000             116,000

  XDR TB               27,000               16,000

Latent TB
XDR Outbreak
                                 XDR among MDR-TB isolates:
                                 XDR-TB Present in All Regions

     Geographic Region                            Total MDR    XDR TB
                                                    TB (n)      n (%)
     Industrialized nations                             821    53 ( 6 )
     Latin America                                      543    32 ( 6 )
     Eastern Europe                                     406    55 ( 14 )
     Africa and Middle East                             156     1 ( <1 )
     Asia                                             1,572   204 ( 13 )
                                      Total           3,418    345 (10)

   Source: US CDC, MMWR, March 24, 2006, vol. 55, no. 11

Source: MMWR March 2006
  XDR TB in Rural South Africa
  Patient Characteristics*

Characteristic                                                                            No. (%)
No prior TB treatment (n=47)                                                              26 ( 55)
Prior hospitalization [last 2 yrs] (n=42)                                                 28 ( 67)
Previous TB treatment (n=47)
   Cured or completed                                                                     14 ( 30)
   Failure or default                                                                       7 ( 15)
HIV infection (n=44)                                                                     44 (100)
Dead: includes 15 (34%) on ARVs                                                           52 ( 98)
Identical genotype (n=46)                                                                 39 ( 85)

* Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, Zeller K, Andrews J, Friedland G.
Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis
and HIV in a rural area of South Africa. Lancet 2006;368:1575-1580
                            MDR and XDR-TB and HIV/AIDS:
                            The Perfect Storm

      • Immune compromised people more vulnerable to TB
      • Diagnosis of TB is more difficult in HIV positive people
         – Smear negative; Extra-pulmonary
      • Treatment is challenging
         – Drug interactions
         – Intolerance and adherence
      • Protecting health care workers (HCWs) is important
         – Special risk for HIV+ HCWs
      • Increased burden on health care system
         – Need for hospitalization, heavier workload, stricter infection control
      • Fear and stigma
         – Alarmist messages  increase stigma
         – Negative impact on health seeking behaviour

Source WHO/CDC
Who is this man?
 TB Patient Is Isolated After Taking Two Flights

Published: May 30, 2007
Federal and international officials are tracking down
passengers and crew members on two trans-Atlantic flights
earlier this month who may have been exposed to a man
infected with an exceptionally dangerous form of tuberculosis.
Global Response
By 2005 sustain or exceed by 2015
 Detect 70% of new sputum smear (SS) + cases
       2005 Global 60%
 Successfully treat 85% of these cases
       2004 Global 84%
By 2015
 Reduce TB prevalence and deaths by 50% (relative to 1990)
       Reducing prevalence to ≤ 155 per 100,000
                      2005 Global 217/100,000
       Reducing deaths to ≤ 14 per 100,000
                      2005 Global 24/100,000
Stop TB Strategy
  Sub Regional Response: Expert Consultation,
         Johannesburg, SA, Sept. 2006

• Organized by SA Medical Research Council (MRC) to
  develop strategy to address MDR TB / XDR TB in
  Southern Africa
• Key stakeholders with experience in drug-resistant
  TB response – WHO, CDC (DTBE and RSA GAP),
• Representatives from all 9 provinces of RSA (TB,
  HIV, TB lab)
• Representatives from 10 SADC countries (TB, HIV,
  TB lab)
                         Sub-Regional: 7-point Action Plan
                         for Immediate Response

• Develop national emergency response plans
    – Lesotho, Namibia, Malawi, Mauritius, Mozambique, South Africa,
      Swaziland and Zimbabwe

• Conduct rapid surveys of MDR TB and XDR TB

• Strengthen and expand current national TB labs

• Urgently implement broad infection control measures

• Establish capacity to manage and treat MDR/XDR TB

• Promote universal access to ARVs for all TB patients

• Support and increase development research for new anti-TB
  drugs and rapid diagnostic tests for drug resistance
Source: CDC
                          Global Response: Priority Activities
                          for MDR and XDR-TB

•    Strengthen basic TB and HIV/AIDS
•    Scale-up programmatic management
     of MDR/XDR-TB
•    Strengthen lab services for diagnosis
•    Expand MDR/XDR TB surveillance
•    Strengthen infection control
     measures to avoid transmission
•    Increase advocacy, communication
     and social mobilization
•    Mobilize resources at all levels
•    Promote research and development-
     new diagnostics, drugs and vaccines

    Estimated cost of next two years for MDR TB and
    XDR TB operational plan is U$2.15 billion
25 Priority MDR XDR TB Countries
                      MDR/XDR-TB – Take Home Messages

• Present in all regions – but
  distribution and magnitude
• The Global Response Plan for
  MDR/XDR TB = consensus on
  priorities and actions
• Prevention of MDR/XDR TB is
   – Strong DOTS programs are key
• Management of MDR and XDR
  TB must be integrated into TB
  control programs
• New tools are urgently needed

Source: WHO
Thank you

•   www.who.int/tb/xdr/en/
•   www.stoptb.org
•   www.cdc.gov
•   www.usaid.gov

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