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Moving Forward in Diagnosis of Infectious Diseases in Developing Countries - A focus on Tuberculosis - 1st Meeting of the Global Laboratory Initiative (GLI) 1st Meeting of the Global Laboratory Initiative (GLI) World Health Organization & Fondation Mérieux MDR and XDR-TB: the new challenge f di i for diagnosis Paul Nunn on behalf of Kitty Lambregts Chair MDR Working Group Paul Nunn on behalf of Kitty Lambregts, Chair, MDR Working Group Les Pensières, Veyrier-du-Lac, France, 8 - 9 May 2008
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MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

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Page 1: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Moving Forward in Diagnosis of Infectious Diseases in Developing g g p gCountries

- A focus on Tuberculosis -1st Meeting of the Global Laboratory Initiative (GLI)1st Meeting of the Global Laboratory Initiative (GLI)

World Health Organization & Fondation Mérieux

MDR and XDR-TB: the new challenge f di ifor diagnosis

Paul Nunn on behalf of Kitty Lambregts Chair MDR Working GroupPaul Nunn on behalf of Kitty Lambregts, Chair, MDR Working Group

Les Pensières, Veyrier-du-Lac, France,8 - 9 May 20088 9 ay 008

Page 2: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Latest global TB Estimates - 2006

Estimated number of

cases

Estimated number of

deathscases deaths

1.65 million1.65 million9.15 million9.15 millionAll forms of TB Greatest number of cases in Asia;

120 000489 000

Greatest number of cases in Asia; greatest rates per capita in Africa

Multidrug-resistant 120,000489,000TB (MDR-TB)

Extensively drug-y gresistant TB (XDR-TB) 40,000 20,000

HIV-associated TB00 000 200 000700,000 200,000

Page 3: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

MDR-TB among new cases 1994-2007g* Sub-national averages applied to China, Russia, Indonesia

< 3%3-6 %> 6 %> 6 %No data MDR-TB is resistance to isoniazid and rifampicin

Drug susceptible TB Cure rate 95+%MDR-TB Cure rate 67%

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

Page 4: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

% MDR among new and retreatment cases (1994-2006)

Baku, Azerbaijan

Arkhangelsk Oblast, RF

Kaliningrad Oblast, RF

Tomsk Oblast, RF

Donetsk, Ukraine

Pskov Oblast, RF

Estonia

Kazakhstan*

Tashkent, Uzbekistan

Latvia

Ivanovo Oblast, RF*

Mary El Oblast, RF

Armenia

Lithuania

Liaoning Province, China*

Latvia

I M li P i Chi

Henan Province, China*

Orel Oblast, RF

Armenia

0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0

Heilongjiang Province, China

Inner Mongolia Province, China

Page 5: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

0.25

0.30

0.35

80

100

120

200

250

300

350

0.05

0.10

0.15

0.20

0.25

p=0.0750

20

40

60

Arkhangelsk oblast

56 59 69 85

0

50

100

150

200

0.001997 1999 2001 2003 2005

p 0.075

0.35

01998 2000 2002 2004 2006

01999 2000 2001 2002 2003 2004 2005

400 120

0.15

0.20

0.25

0.30

150

200

250300

350

40

60

80

100

0.00

0.05

0.10

1997 1999 2001 2003 2005

p=0.0068

10 11 19 23 28

0

50100

1999 2000 2001 2002 2003 2004 2005 20060

20

40

1998 2000 2002 2004 2006

Orel oblast

0 25

0.30

0.35

400

500

600

100

120

0 05

0.10

0.15

0.20

0.25

p=0.00557 48 57 73 59

95 77100

200

300

400

20

40

60

80

Tomsk oblast

0.00

0.05

1997 1999 2001 2003 2005

p 0.0055

27 48 5 5

0

100

1999 2000 2001 2002 2003 2004 2005

New DST, New MDR TB notification rate % MDR among new

01998 2000 2002 2004 2006

Page 6: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

300350400450

0 20

0.25

0.30

0.35

0 20

0.25

0.30

0.35

40

50

60

70

53

75

50 53 64 51 51 4250100150200250

0 00

0.05

0.10

0.15

0.20

p=0.62130 00

0.05

0.10

0.15

0.20

p=0.621310

20

30

40

Estonia0

1998 1999 2000 2001 2002 2003 2004 20050.00

1997 1999 2001 2003 2005

9001000

0.001997 1999 2001 2003 2005

01997 1999 2001 2003 2005 2007

90100

0.35

400500600700800900

405060708090

0.15

0.20

0.25

0.30

71 86 83 99 95 80 114

91

0100200300

1998 1999 2000 2001 2002 2003 2004 20050

102030

1997 1999 2001 2003 2005 2007

Latvia0.00

0.05

0.10

1997 1999 2001 2003 2005

p=0.3260

700800900

1000

0.25

0.30

0.35

60708090

100

64 61 75 84 86 104 12

7

100200300400500600

0.05

0.10

0.15

0.20

p=0.0169102030405060

Lithuania

0100

1999 2000 2001 2002 2003 2004 2005

0.001997 1999 2001 2003 2005

p

New cases tested, New MDR % MDR among new

01997 1999 2001 2003 2005

TB notification rate

Page 7: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

2006: eXtensively Drug Resistant Tuberculosis XDR TB

XDR = Resistance to at least INH and

Tuberculosis - XDR-TB

RIF (MDR) PLUS resistance to fluoroquinolones, AND one of the second-line injectable drugs (amikacin, kanamycin, or capreomycin)

Of 17,690 isolates from 49 countries d i 2000 2004 20% MDR during 2000-2004 20% were MDR and 2% were XDR

XDR found in: XDR found in: USA: 4% of MDRLatvia: 19% of MDRS Korea: 15% of MDRS Korea: 15% of MDR

MMWR Morb Mortal Wkly Rep 2006; 55:301-5

Page 8: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Denmark

Croatia

Armenia

Lithuania

Poland

Norw ay

Tomsk Oblast, RF

Rep. Georgia

Armenia

UK

Belgium

Sw itzerland

Baku Azerbaijan

Latvia

Kaliningrad Oblast, RF

Netherlands

France

UK

Donetsk, Ukraine

Pskov Oblast, RF

Baku, Azerbaijan

Israel

Romania

0.0 20.0 40.0 60.0 80.0 100.0

Estonia

Ireland

Spain, Barcelona

Sw eden

% XDR-TB among MDR in Europe n = 27

Spain, Aragon

Czech Republic

Ireland Europe n = 27* Reporting periods vary generally 3 year average

0.0 20.0 40.0 60.0 80.0 100.0

Slovenia

Page 9: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

TB Treatment Outcomes, by Selected Drug Resistance Patterns, Latvia, 2000-2003*

Cure Completion Death Default Failed Continue Tx HIV+

HR+AG+FQ

Cure Completion Death Default Failed Continue Tx HIV+

HR+INJ+FQ

HR+3SLD

MDR-TB All

0 10 20 30 40 50 60 70

Percent

* Leimane V, et al. First Global XDR TB Task Force Meeting. Oct 9, 2006(from N = 820 evaluated)

Percent

Page 10: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics
Page 11: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

What no amount of congressional lobbying

could have achieved. And in the end – no harm

done.

Page 12: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Estimated HIV prevalence in new TB cases, 2006

No estimate

HIV prevalence in TB cases, (%)

0–4

20–49

50 or more

5–19

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

Page 13: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

MDR-TB & HIV in institutions in the WestWest

Patients with MDR-TB

T l Di dReference

Totalno.

HIV infected %

Died%

Time to death, median, weeks

Hospital (Florida), 1988–1990 MMWR 1991;40:585-91 65 93 72 7

Hospital (New York City),1989–1990

MMWR 1993;42:427-34JAMA 1996;276:1229-35

51 100 89 16

Hospital (New York City), 1990–1991

JAMA 1996;276:1229-35NEJM 1992;326:1514 21

70 95 77 41990–1991 NEJM 1992;326:1514-21

Hospital (New York City),1991–1992

JAMA 1996;276:1229-35 JID 1993;168:1052-5 32 91 83 4

Two hospitals (Italy), AIDS 1998;12:1095 102 116 98 95 6-81991–1995 AIDS 1998;12:1095-102 116 98 95 6-8

Hospital (Madrid, Spain),1991–1995 EID 1996;2:125-9 48 100 98 7

Hospital (Buenos Aires Argentina)Hospital (Buenos Aires, Argentina), 1994–1995 JID 1997;176:637-42 68 100 93 5

Prison system (New York State), 1990–1991 JID 1994; 170:151-6 42 98 79 4

JID 2007;196 Suppl 1:S86-107

Page 14: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Epidemiology of MDR and HIV in AfricaPatients Place Association

between tested for HIV statusbetween tested for HIV status and any R HIV and DR

Githui, 1989 271 Nairobi, Kenya No associationGithui, 1989 271 Nairobi, Kenya No associationChum, 1996 1164 Tanzania No associationKenyon, 1999 240 Botswana No association Churchyard, 2000 1913 South Africa No association Warndorff, 2000 836 Malawi No association Espinal 2001 463 Multicentre No associationEspinal, 2001 463 Multicentre No association Mac-Arthur, 2001 709 Mozambique Association with HSWeyer, unpublished 762 South Africa No association

Association with MDR among retreatments

Page 15: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics
Page 16: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

XDR-TB in Tugela Ferry, South AfricaSouth Africa

544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB

Study characteristics (53 patients) No (%)Study characteristics (53 patients) No. (%)

No prior TB Treatment 26 (51) Prior TB treatmentPrior TB treatment

Cure or Completed treatment 14 (28) Treatment Default or Failure 7 (14)

HIV infected (44 tested) 44 (100) HIV-infected (44 tested) 44 (100) Health care workers 2 Dead (includes 34% on ARV) 52 (98)

M di i l 16 d Median survival 16 days Number of TB strains 4+

Lancet 2006; 368:1575-80

Page 17: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

506070

0k p

opn. 2005

20062007 MDR cases

10203040

case

s/10

0

per 100 000 population

010

hekwini

21 U

gu ndlovu

thuke

la zin

yathi

Amajuba

ululand

yaku

de hungulu

iLembe

Sisonke

ro

vince

MD

R

(top). XDR/MDR

20 eT

he 2

22 U

mgungun23

Uth

24 U

mzin25

Am

26 Zul

27 U

mkhan

ya28

Uthu29

iL43

SisKZN pro (bottom)

(Data for

40%

50%

60%

R

200520062007

(Uthungulu for 2005 excluded)

10%

20%

30%

XDR

/ M

D

0%

10%

hekwini

21 U

gu ndlovu

thuke

la inya

thi maju

ba ululan

d ya

kude

hungulu iLem

be Siso

nke

rovin

ce

20 eT

he 21

22 U

mgungun23

Uth

24 U

mzin25

Am

26 Zul

27 U

mkhan

ya28

Uthu29

iL43

SisKZN pro

Page 18: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics
Page 19: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Gl b l l lGlobal level response

Coordination of Partnership activities – the MDR Working Group

Global strategy and policies directed at better prevention and control of MDR/XDR-TB

Regional and country support Monitoring and evaluation Advocacy and resource mobilisation for

countries and partners

Page 20: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Partnership activitiesPartnership activities

MDR Working Group Tbilisi meeting, September 2007Tbilisi meeting, September 2007 New Chair and Vice Chair Core Group meetings Core Group meetings Sub-groups

• Drug management• Drug management• Advocacy and resource mobilization• ResearchResearch• Green Light Committee (Expanded and reformed)

NewsletterNewsletter

Page 21: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Challenges posed by MDR/XDR-TBg p y1st Global XDR-TB Task Force, 2006

M ff ti b i TB More effective basic TB management

Expansion of management ofExpansion of management of MDR and XDR-TB

Infection control Laboratory strengthening Expanded surveillance of MDR

d XDR TB i l di HIVand XDR-TB, including HIV Advocacy and resource

mobilisationmobilisation New tools

Page 22: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Notified cases of MDR-TB (2004–2006) and j t d ti t t b t t d (2007 2008)50 GLC

projected patients to be treated (2007–2008)4647

40

50 non-GLCGLC

4647

Global plan target for number of MDR-TB

3023

patients to be enrolled on treatment:2006: 14 thousand2007: 48 thousand2008: 98 thousand

10

20 1818

0

10

2004 (101,25%)

2005 (106,48%)

2006 (108,78%)

2007 (112,80%)

2008 (116,86%)

Page 23: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

ConclusionsConclusionsMDR i id d i i d b i MDR is widespread, increasing, and being fuelled now by HIV

XDR-TB is ubiquitous and likely rising XDR-TB is ubiquitous, and likely rising Management of patients with MDR or XDR-TB

requires drug susceptibility testsrequires drug susceptibility tests Rapid tests are life saving in HIV associated

MDR-TB Problem is how to resurrect a stunted, starved,

demoralised, laboratory network and establish a vibrant effective responsive accurate purveyorvibrant, effective, responsive, accurate purveyor of DST data in all the places MDR is found

Page 24: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

AcknowledgementsAcknowledgements

Katherine Floyd Chris DyeChris Dye Lynne Harrop Abby Wright Ernesto Jaramillo Ernesto Jaramillo Matteo Zignol Karin Weyer

Page 25: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

II Meeting of the WHO Task Force on XDR-TB 9-10 April, Geneva, Switzerland9 10 April, Geneva, Switzerland

Page 26: MDR and XDR-TB: the new challenge fdi ifor diagnosis...XDR-TB in Tugela Ferry, South AfricaSouth Africa 544 Culture +ve, of which 221 MDR-TB (41%) and 53 XDR-TB Study characteristics

Main Recommendation

WHO and Stop TB Partnership to convene aWHO and Stop TB Partnership to convene a meeting with ALL 27 high priority countries early in 2009early in 2009

to increase political commitment at the highest country level,

hi d i th i it t i assess progress achieved in these priority countries, and

agree on actions to tackle the main factors hampering agree on actions to tackle the main factors hampering progress