Overview of this presentation Burden of TB, TB/HIV, MDR-TB Progress towards international targets Challenges in 2011 Actions needed.

Overview of this presentation

• Burden of TB, TB/HIV, MDR-TB

• Progress towards international targets

• Challenges in 2011

• Actions needed

Overview of this presentation

• Burden of TB, TB/HIV, MDR-TB

• Progress towards international targets

• Challenges in 2011

• Actions needed

Estimated number of

cases

Estimated number of

deaths

1.7 million(range: 1.5–2.0 million)

9.4 million(range: 8.9–9.9 million)

440,000(range: 390,000–510,000)

All forms of TB

Multidrug-resistant TB (MDR-TB)

HIV-associated TB

1.1 million (12%) (range: 1.0–1.2 million)

380,000(range: 320,000–450,000)

The Global Burden of TB -2009

about 150,000

0–24

25–49

50–99

100–299

300 and higher

No estimate available

0–24

25–49

50–99

100–299

300 and higher

No estimate available

0–24

25–49

50–99

100–299

>300

No estimate

• Highest burden in Asia (55% of 9.4 million cases)

• Highest rates in Africa, due to high HIV infection rate

~80% of HIV+ TB cases in Africa

Per 100 000 population

TB Incidence Rates - 2009

Africa 30%

West Pacific 20%

SE Asia 35%

Europe 4%

East Mediterranean 7%

Americas 3%

Impact of HIV on TB in Africa

Notified cases per 100,000 pop. 1980-2008

Percentage of global estimated HIV-positive TB cases

EMR

Cameroon

Thailand

Brazil

Democratic Republic of the Congo

China

Myanmar

EUR

Côte d'Ivoire

Malawi

United Republic of Tanzania

AMR

Zambia

WPR

Ethiopia

Mozambique

Kenya

Uganda

Zimbabwe

Nigeria

India

SEA

South Africa

AFR

1% 5% 10% 20% 50% 90% 0

100

200

300

400

500

600

700

1980 1984 1988 1992 1996 2000 2004 2008

Botswana

Côte d'Ivoire

DR Congo

Gabon

Guinea

Kenya

Malawi

Mozambique

South Africa

UR Tanzania

Zimbabwe

• 79% of all TB/HIV cases world-wide are in Africa• 50% of all TB/HIV cases world-wide in 9 African countries• 23% of the estimated 2 million HIV deaths due to TB

% MDR-TB among new TB cases,1994-2009

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 2010. All rights reserved

Australia, Democratic Republic of the Congo, Fiji, Guam, New Caledonia, Solomon Islands and Qatar reported data on combined new and previously treated cases.

0-<3

3-<6

6-<12

12-<18

>=18

No data available

Subnational data only

13 top settings with highest % of MDR-TB among new cases, 2001-2010

16.5

19.2

19.3

19.4

20.0

22.3

23.8

27.3

28.3

15.4

14.8

16.0

16.1

0 5 10 15 20 25 30

Tashkent, Uzbekistan (2005)

Estonia (2008)

Donetsk Oblast, Ukraine (2006)

Mary El Republic, Russian Federation (2008)

Dushanbe city and Rudaki district, Tajikistan (2009)

Belgorod Oblast, Russian Federation (2008)

Kaliningrad Oblast, Russian Federation (2008)

Republic of Moldova (2006)

Ivanovo Oblast, Russian Federation (2008)

Baku city, Azerbaijan (2007)

Arkhangelsk Oblast, Russian Federation (2008)

Pskov Oblast, Russian Federation (2008)

Murmansk Oblast, Russian Federation (2008)

35.3Minsk, Belarus (2010)Preliminary results

Time trends in TB and MDR-TB: reverting, controlling, and alarming…

1

10

100

1000

1996 1998 2000 2002 2004 2006 2008

0.3% per year

19.4% per year

____ TB ____ MDR-TB

1

10

100

1999 2001 2003 2005 2007 2009

2.4% per year

-2.4% per year

____ TB ____ MDR-TB

1

10

100

1998 2000 2002 2004 2006 2008

-6.7% per year

-5.1% per year

____ TB ____ MDR-TB

Botswana

Tomsk Oblast, Russia

Estonia

Countries that had reported at least one

XDR-TB case by end March 2011

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 2011. All rights reserved

Argentina Bhutan France Japan Namibia Republic of Korea ThailandArmenia Cambodia Georgia Kazakhstan Nepal Republic of Moldova TogoAustralia Canada Germany Kenya Netherlands Romania TunisiaAustria Chile Greece Kyrgyzstan Norway Russian Federation UkraineAzerbaijan China India Latvia Pakistan Slovenia United Arab EmiratesBangladesh Colombia Indonesia Lesotho Peru South Africa United KingdomBelgium Czech Republic Iran (Islamic Rep. of) Lithuania Philippines Spain United States of AmericaBotswana Ecuador Ireland Mexico Poland Swaziland UzbekistanBrazil Egypt Israel Mozambique Portugal Sweden Viet NamBurkina Faso Estonia Italy Myanmar Qatar Tajikistan

Overview of this presentation

• Burden of TB, TB/HIV, MDR-TB

• Progress towards international targets

• Challenges in 2011

• Actions needed

The global response: Stop TB Strategy & Global Plan

To save lives, prevent suffering, protect the vulnerable, &

promote human rights

1. Pursue high-quality DOTS expansion

2. Address TB-HIV, MDR-TB, and needs of the poor and vulnerable

3. Contribute to health system strengthening

4. Engage all care providers

5. Empower people with TB and communities

6. Enable and promote research

2015: Goal 6: Combat HIV/AIDS, malaria and other diseases Target 6c: to have halted by 2015 and begun to reverse the

incidence…

*Indicator 6.9: incidence, prevalence and mortality associated with TB*Indicator 6.10: proportion of TB cases detected and cured under DOTS

2015: 50% reduction in TB prevalence and deaths by 20152050: elimination (<1 case per million population)

The Global TB Control Targets

Achievements thus far

• 41 million patients cured, 1995-2009

• 6 million deaths averted compared to 1995 care standards

• Mortality reduced by 35% since 1990 and 50% mortality targets on track globally

• Cure rates >85%, care for TB/HIV improving

• 2015 MDG target on track: global TB incidence peaked in 2004

• But…. TB incidence declining too slowly, case detection stagnating, and MDR-TB care only now starting scale-up

Prevalence and mortality: global estimates

2015

Mortality

1990

35

25

15

0

target

Prevalence

1990

300

200

100

0

2015

target

shaded area = uncertainty band

Incidence rates falling globally after peak in 2004, but only at <1%/year

Peak in 2004

Incidence (all forms, incl. PLHIV)

TB Notifications

Incidence TB in PLHIV

shaded area = uncertainty band

Notification gap

Overview of this presentation

• Burden of TB, TB/HIV, MDR-TB

• Progress towards international targets

• Challenges in 2011

• Actions needed

What are the challenges in 2011 if we target "elimination"?1. Funding not secure

2. Only 63% of all estimated cases reported

3. TB/HIV major impact in Africa

4. MDR-TB, with high burden in former USSR and China

5. Weak health policies, systems and services

6. Un-engaged non-state practitioners

7. Un-aware, un-involved communities

8. R&D and transfer of tools/technology: Xpert MTB-RIF, and soon new drugs

Funding required, Global Plan

Plan component

US$ billions, 2011–15

% total

IMPLEMENTATION

36.9 79%

DOTS 22.6 48%

MDR-TB 7.1 15%

TB/HIV 2.8 6%

Lab strengthening

4.0 8%

Technical assistance

0.4 1%

R&D 9.8 21%

TOTAL 46.7 100%

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

2010 2011 2012 2013 2014 2015

US$

mill

ions

(nom

inal

)

Funding available

Funding needed

Treatment success 86% globally

Global WHO Regions

8584

86 86

83

80

75

80

85

90

2003 2004 2005 2006 2007 2008

Tre

atm

ent

succ

ess

rate

(%

)

Progress in most regions, but Europe lagging behind

65

70

75

80

85

90

95

2003 2004 2005 2006 2007 2008

W. Pacific

SE Asia

EMR

Africa

93

88

80

Americas77

66Europe

HIV testing for TB patients expanding

44

38

45

53

22

114

2622

20

129

30

10

20

30

40

50

60

2003 2004 2005 2006 2007 2008 2009

Pe

rce

nta

ge

Africa

World

Although more needed to reach 100% targets in Global Plan

Several countries show very high testing rates are achievable

Rwanda: 97%Kenya: 88%Tanzania: 88%Malawi: 86%Mozambique: 84%P

erce

nta

ge

of

TB

pat

ien

ts

CPT and ART for HIV-positive TB patients also expanding

83

70

75

37

0

20

40

60

80

100

2003 2004 2005 2006 2007 2008 2009

Per

cen

tag

e

Although more needed to reach 100% targets in Global Plan

Several countries show higher rates of enrolment are possibleCPT 86%–97% in 2009Kenya, Malawi, Mozambique, Rwanda, Tanzania, Uganda

ART close to 50% in 2009Rwanda, Malawi

CPT

ART

Perc

en

tag

e o

f H

IV+

TB

p

ati

en

ts

A. Establish NTP-NACP collaborative mechanisms Coordinating bodies Surveillance of HIV prevalence among TB cases TB/HIV planning Monitor and evaluate collaborative TB/HIV activities

B. Decrease burden of TB among PLHIV (the "3 Is") Intensified TB case finding INH preventive therapy Infection control in health care and congregate settings

C. Decrease burden of HIV among TB patients IV testing and counselling HIV prevention methods Co-trimoxazole preventive therapy IV/AIDS care and support ARVs

Policy on collaborative TB/HIV activities WHO recommendations

Increasing notifications via PPM (public-private mix)

Source: 2010 WHO global TB control report, Table 7, page 16

36

25

1917

15 14 13

36

29 28

21

0

5

10

15

20

25

30

35

40C

hin

a

Ira

n

Ta

nza

nia

Ca

mb

od

ia

Gh

an

a

Pa

kis

tan

Ind

on

es

ia

Ind

ia

Me

xic

o

Ph

ilip

pin

es

My

an

ma

r

National gap Parts of country

Per

cen

tag

e o

f to

tal n

oti

fica

tio

ns

NATIONAL PARTS OF COUNTRY

0

20

40

60

80

100

120

140

160

99q1

99q3

00q1

00q3

01q1

01q3

02q1

02q3

03q1

03q3

04q1

04q3

05q1

05q3

Quarter

Annualis

ed r

ate

of

ss+

cases d

iagnosed p

er

100,0

00

NGO

Private

Corporate

Medical college

Other Government

Health Department

• Public and private medical colleges (yellow) diagnose a huge number of cases, but many of them are from outside the city and need to be refereed for treatment elsewhere.

• The increase in diagnosed cases represents increased notification after medical colleges and other providers started to report to NTP in a standardised way

Case recovery into the NTP by different care providers, Bangalore, 1999-2005

Increasing case notifications is good,But…it is not yet early case detection

Proportion of TB patients tested for MDR-TB remains low

29%

11%

2% 2% 1% 0%7%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

% o

f p

ati

en

ts

New

Global plan target for 2015 =20%

36%

16%9% 7% 6%

2%7%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

% o

f p

atie

nts

Previously treated

Global plan target for 2015 =100%

• Action plans in 26 countries• In 23, funding increased from $ 0.1b in

2009 to 0.5b in 2011 (need is $ 0.9b)• Most countries still rely on external

resources

• 16 countries have a culture lab per 5m people and a DST lab per 10m people

• 11 countries are introducing GenXpert• 10% of 250,000 estimated cases on treatment • 13 countries reported cure rates (25-82% for 2007

cohort)• 19 countries did not report stock-out of 2nd-line drugs• 14 countries have national plans for infection control

Response to M/XDR-TB in 27 HBCs: 2011 Progress Report

1

10

100

1000

10000

2000 2010 2020 2030 2040 2050

Year

Inc

ide

nce

/mill

ion

/yr

Elimination 16%/yr

Global Plan 6%/yr

Current trajectory 1%/yr

Full implementation of Global Plan: 2015 MDGtarget reached but TB not eliminated by 2050

Elimination target: 1 / million / year by 2050

TB incidence 10x lower than today, but >100x higher than elimination target in 2050

Current rate of decline

Overview of this presentation

• Burden of TB, TB/HIV, MDR-TB

• Progress towards international targets

• Challenges in 2011

• Actions needed

3131

Innovative Actions Needed in 4 Areas

Early & increased case detection: new toolsScale-up TB/HIV and MDR-TB interventionsM&E and impact measurementEngage all care providersActive screening among at-risk populations

Socio-economic factors: living conditions, food insecurity, awareness, risk behaviour, access to care

MDR-TB, Multi drug resistant TBM&E, Monitoring and evaluation

Innovative action needed in 4 spheres

Population attributable fraction – Selected Risk Factors & Determinants

Relative risk for active TB disease

Weighted prevalence (22 HBCs)

Population Attributable Fraction in

Adults

HIV infection 20.6/26.7* 1.1% 19%Malnutrition 3.2** 16.5% 27%Diabetes 3.1 3.4% 6%Alcohol use (>40g / d)

2.9 7.9% 13%

Active smoking

2.6 18.2% 23%

Indoor Air Pollution

1.5 71.1% 26%

1

1 1

P RRPAF

P RR

Sources: Lönnroth K, Raviglione M. Global Epidemiology of Tuberculosis: Prospects for Control. Semin Respir Crit Care Med 2008; 29: 481-491. *Updated data in GTR 2009. RR=26.7 used for countries with HIV <1%. **Updated data from Lönnroth et al. A consistent log-linear relationship between tuberculosis incidence and body-mass index.

Limitations of today’s Diagnostics, Drugs and Vaccine – But…something moving!

Diagnostics - More than 100 years old • Detects only half of the cases in patients tested• Less ffective for diagnosing TB in PLHIV• But…rapid tests for MDR strains (not yet PoC) finally available

Drugs – Last drug 40 years old • Four drugs, taken for at least 6 months• Not compatible with some ARVs• MDR-TB treatment lengthy, low cure rates, expensive, toxic• But…new drugs possibly being introduced starting in 2012/13

Vaccine – Nearly 90 years old• Unreliable protection against pulmonary TB• No apparent impact on the TB epidemic• But…a dozen candidates in clinical trial

Potential impact of new TB vaccines, diagnostics and drugs in SE Asia

Sou

rce:

L. A

bu R

adda

d et

al,

PN

AS

200

9

Add. Effects = effects also on latency and infectiousness of cases in vaccinated

• Led & NAAT at microscopy lab level• Dipstick at point of care

• Regimen 1 = 4-month, no effect on DR• Regimen 2 = 2-month, 90% effective in M/XDR• Regimen 3 = 10-day, 90% effective in M/XDR

3535

Going beyond smear & liquid cultureIntroducing GeneXpert

1. Xpert MTB/RIF should be used as the initial diagnostic test in individuals suspected of having MDR-TB or HIV-associated TB (strong recommendation)

2. Xpert MTB/RIF may be used as a follow-on test to microscopy where MDR and/or HIV is of lesser concern, especially in smear-negative specimens (conditional recommendation, major resource implications)

WHO endorsement 2010

Phased implementation & evaluation 2011

Scale up 2012

Current TB Therapy and Unmet Needs

* Rifampin (R), Isoniazid (H), Pyrazinamide (Z), Ethambutol (E)

Patient Population Current Therapy Unmet Needs

Drug-SusceptibleDS-TB

4 drugs; 6 month therapy (2RHZE + 4RH) Shorter, simpler therapy

Drug-ResistantM(X)DR-TB

At least 4 drugs (including injectable); ≥18 months;poorly tolerated

Fully oral, shorter and safer therapy

TB/HIVco-Infection

Drug-drug interactions (DDI) with ARVs

No or low DDI, co-administration with ARVs

Latent TBInfection 6-9 months H Shorter, safer therapy

► For all indications and treatment, issues in delivery and access► Need shorter and simpler therapies against both DS and DR-TB

Adapted from TB Alliance

Lead Identification Lead Optimization Preclinical Development Phase I Phase II Phase III

• Gatifloxacin• Moxifloxacin• Rifapentine

• TMC-207• OPC-67683• PA-824• SQ-109• PNU -100480• LL3858

• Rifapentine• Linezolid

• AZD5847• CPZEN-45• SQ641• SQ609• DC-159a• BTZ-043

Preclinical DevelopmentDiscovery Clinical Development

• Nitroimidazoles• Mycobacterial

Gyrase Inhibitors• Riminophenazines• Diarylquinoline• Translocase-1

Inhibitor• MGyrX1 inhibitor• InhA Inhibitor• GyrB inhibitor• LeuRS Inhibitor

• Summit PLC compounds

Global TB Drug Pipeline, June 2011

1.The world is on track to achieve the (un-ambitious) target of incidence reduction and the 50% mortality decrease in 2015

2. Universal access to quality TB care requires strengthening of lab services, further progress in implementation of PPM and TB/HIV interventions, massive scale-up of care for MDR-TB

3.Bold health policies, new tools rapidly transferred to endemic countries, and alleviation of socio-economic barriers are necessary to achieve acceleration of decline and elimination

Conclusions