14 th Meeting of the Core Group of the TB/HIV Working Group Addis Ababa, Ethiopia November 12, 2008 MDR and XDR-TB in the context of HIV: What next? Paul.

14th Meeting of the Core Group of the TB/HIV Working GroupAddis Ababa, EthiopiaNovember 12, 2008

MDR and XDR-TB in the context of HIV: What next?

Paul Nunn, Abby WrightErnesto Jaramillo

Matteo Zignol

Stop TB Department, WHO, Geneva

Latest global TB Estimates - 2006

Estimated number of

cases

Estimated number of

deaths

1.65 1.65 millionmillion

9.15 9.15 millionmillion

120,000 489,000

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

Multidrug-resistant TB (MDR-TB)

Extensively drug-resistant TB (XDR-TB)

40,000 20,000

HIV-associated TB700,000 200,000

MDR-TB among new cases 1994-2007

< 3%

3-6 %

> 6 %

No data

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

* Sub-national averages applied to China, Russia, Indonesia.

MDR-TB is resistance to isoniazid and rifampicinDrug susceptible TB Cure rate 95+%MDR-TB Cure rate 67%

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

Henan Province, China*

Orel Oblast, RF

Armenia

Lithuania

Liaoning Province, China*

Latvia

Ivanovo Oblast, RF*

Mary El Oblast, RF

Estonia

Kazakhstan*

Tashkent, Uzbekistan

Tomsk Oblast, RF

Donetsk, Ukraine

Pskov Oblast, RF

Baku, Azerbaijan

Arkhangelsk Oblast, RF

Kaliningrad Oblast, RF

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

0

50

100

150

200

250

300

350

400

450

1998 1999 2000 2001 2002 2003 2004 2005

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

1997 1999 2001 2003 2005

p=0.6213

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

1997 1999 2001 2003 2005

p=0.62130

10

20

30

40

50

60

70

1997 1999 2001 2003 2005 2007

Estonia

0

100

200

300

400

500

600

1999 2000 2001 2002 2003 2004 2005

Tomsk oblast

0

20

40

60

80

100

120

1998 2000 2002 2004 2006

TB notification rate

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

1997 1999 2001 2003 2005

p=0.0055

New DST, New MDR % MDR among new

Tomsk oblast

XDR = Resistance to at least INH and 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 during 2000-2004 20% were MDR and 2% were XDR

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

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

2006 - eXtensively Drug Resistant Tuberculosis - XDR-TB

Countries with confirmed cases of XDR-TB as of November 2008

Anti-TB Drug resistance:Status as of 2008

Highest rates in FSU, with MDR rates among new cases higher - up to 29% - as DRS expands

Across all patients in FSU – 1 in 5 has MDR-TB Up to 10% MDR in new cases in parts of China and India China, India and Russia account for 60% global MDR-TB

burden – but response in all 3 is inadequate Baltics reducing the problem with targeted investment,

Estonia reducing all cases and % MDR-TB Mortality of M and XDR-TB remains very high What is the impact of HIV on MDR?

1980's and 1990's outbreaks in Buenos Aires, London, Milan, New York City etcPeriodic surveys, especially in Africa, did not detect significantly higher rates of drug resistance among those with HIV

HIV-associated MDR TB outbreaks

XDR-TB in Tugela Ferry, South Africa

Study characteristics (53 patients) No. (%)

No prior TB Treatment 26 (51) Prior TB treatment

– Cure or Completed treatment 14 (28)

– Treatment Default or Failure 7 (14) HIV-infected (44 tested) 44 (100) Health care workers 2 Dead (includes 34% on ARV) 52 (98) Median survival 16 days Number of TB strains 4+

Ghandi N et al. Lancet 2006; 368:1575-80

MDR and XDR-TB casesby month in CoSH 2005-2008

Monthly MDR and XDR cases (2005 - 2008)

0

5

10

15

20

25

30

35

Janu

ary

Febr

uary

Mar

ch

Apr

il

May

June

July

Aug

ust

Sep

tem

ber

Oct

ober

Nov

embe

r

Dec

embe

r

2005

2006

2007

2008

By Dec 2007 – MDR cases 286

XDR cases 382

010203040506070

MD

R c

ase

s/1

00

k p

op

n.

200520062007

0%

10%

20%

30%

40%

50%

60%

XD

R /

MD

R

200520062007

MDR cases per 100 000 population (top)

XDR/MDR (bottom)

(Data for Uthungulu for 2005 excluded)

MDR-TB and HIV in Ukraine

Independent predictors for MDR-TBHistory of previous treatment: OR: 4.0 (95%CLs 3.1-5.1)

Imprisonment: OR: 1.5 (95%CLs 1.1-2.0)

New casesPreviously

treated casesNew cases

Previously treated cases

n=924 n=369 n=78 n=12515.5 41.5 21.8 52.8

(13.1 to 17.8) (36.4 to 46.5) (12.4 to 31.2) (43.9 to 61.7)MDR rates (95% CLs)

Civilian sector Penitentiary sector

• HIV status: OR: 1.7 (95%CLs 1.3-2.3)

Summary situation of MDR and HIV HIV is causing outbreaks of MDR-TB HIV probably increasing community

transmission of MDR-TB where prevalence of infection with MDR-TB is high,

Epidemics of HIV (focus Africa) and MDR (focus Eastern Europe) now overlap

http://whqlibdoc.who.int/publications

Prevention of MDR TB in context of HIV Involve community representatives in

design of care and prevention Ensure high quality basic TB control Infection control

– HIV and ART clinics– Guidelines, and WHO policy January

2009

Preventive therapy problematic

Management of MDR-TB in context of HIV Ensuring rapid diagnosis and

management of TB in HIV clinics– Intensified case finding– Laboratory capacity for MDR-TB diagnosis

• Culture, solid and liquid• Molecular tests, eg line probe assays, now

WHO policy• DST for all patients?

Empirical treatment for MDR-TB– Avoid thiacetazone

Management of MDR-TB in context of HIV - II

ART

– When to start– Drug interactions– Immune reconstitution inflammatory syndrome

HIV care and support, but remember infection control

Centres of excellence Isolation facilities Involuntary detention Care in the community Special teams

Policy decisions confronting many countries in MDR-TB Move from pilot phase to national scale up of

MDR-TB Sources of finance eg GFATM Expansion of laboratory capacity – national

laboratory plan National airborne infection control plan Sourcing of 2nd line drugs – GLC/GDF or

national pharmaceutical industry Quality assurance of 2nd line drugs Involvement/regulation of the private care

delivery sector