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

The Global Burden of TB -2009

024 2549 5099 100299 300 and higher No estimate available

Estimated number of cases

Estimated number of deaths

All forms of TB HIV-associated TB Multidrug-resistant TB (MDR-TB)

9.4 million
(range: 8.99.9 million)

1.7 million
(range: 1.52.0 million)

1.1 million (12%)

(range: 1.01.2 million)

380,000
(range: 320,000450,000)

440,000
(range: 390,000510,000)

about 150,000

TB Incidence Rates - 2009

024 024 2549 2549 5099 5099 100299 100299 300 and higher >300 No estimate available No estimate

West Pacific 20%

Africa 30% Americas 3%

SE Asia 35%

East Mediterranean 7% Europe 4%

Per 100 000 population

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

Impact of HIV on TB in Africa

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
AFR South Africa SEA India Nigeria Zimbabwe Uganda Kenya Mozambique Ethiopia WPR Zambia AMR United Republic of Tanzania Malawi Cte d'Ivoire EUR Myanmar China Democratic Republic of the Congo Brazil Thailand Cameroon EMR 1% 5% 10% 20% 50% 90%

Notified cases per 100,000 pop. 1980-2008

700 Botswana Cte d'Ivoire DR Congo Gabon Guinea Kenya Malawi Mozambique South Africa UR Tanzania Zimbabwe

600

500

400

300

200

100

0 1980 1984 1988 1992 1996 2000 2004 2008

Percentage of global estimated HIV-positive TB cases

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

0-<3 3-<6 6-<12 12-<18 >=18 No data available Subnational data only
Australia, Democratic Republic of the Congo, Fiji, Guam, New Caledonia, Solomon Islands and Qatar reported data on combined new and previously treated cases.

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

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

Minsk, Belarus (2010)
Murmansk Oblast, Russian Federation (2008) Pskov Oblast, Russian Federation (2008) Arkhangelsk Oblast, Russian Federation (2008) Baku city, Azerbaijan (2007) Ivanovo Oblast, Russian Federation (2008) Republic of Moldova (2006) Kaliningrad Oblast, Russian Federation (2008) Belgorod Oblast, Russian Federation (2008) Dushanbe city and Rudaki district, Tajikistan (2009) Mary El Republic, Russian Federation (2008) Donetsk Oblast, Ukraine (2006) Estonia (2008) Tashkent, Uzbekistan (2005)

Preliminary results

35.3
28.3 27.3 23.8 22.3 20.0 19.4 19.3 19.2 16.5 16.1 16.0 15.4 14.8 0 5 10 15 20 25 30

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

____ TB ____ MDR-TB

100 -6.7% per year

100

____ TB

____ MDR-TB

2.4% per year

10

10
-2.4% per year

-5.1% per year 1

1998 2000 2002 2004 2006 2008
1
1999 2001 2003 2005

2007

2009

Estonia
1000

Tomsk Oblast, Russia

____ TB ____ MDR-TB

100

0.3% per year

10

Botswana

19.4% per year 1 1996 1998 2000 2002 2004 2006 2008

Countries that had reported at least one XDR-TB case by end March 2011

Argentina Armenia Australia Austria Azerbaijan Bangladesh Belgium Botswana Brazil Burkina Faso

Bhutan Cambodia Canada Chile China Colombia Czech Republic Ecuador Egypt Estonia

France Georgia Germany Greece India Indonesia Iran (Islamic Rep. of) Ireland Israel Italy

Japan Kazakhstan Kenya Kyrgyzstan Latvia Lesotho Lithuania Mexico Mozambique Myanmar

Namibia Nepal Netherlands Norway Pakistan Peru Philippines Poland Portugal Qatar

Republic of Korea Republic of Moldova Romania Russian Federation Slovenia South Africa Spain Swaziland Sweden Tajikistan

Thailand Togo Tunisia Ukraine United Arab Emirates United Kingdom United States of America Uzbekistan Viet Nam

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

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

1. Pursue high-quality DOTS expansion Address TB-HIV, MDRTB, and needs of the poor and vulnerable Contribute to health system strengthening To save lives, prevent suffering, protect the vulnerable, & promote human rights

2.

3.

4.
5. 6.

Engage all care providers

Empower people with TB and communities Enable and promote research

The Global TB Control Targets

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 2015 2050: elimination (<1 case per million population)

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

Prevalence
300 35

Mortality

200

25

15 100

target
0 1990 2015 1990

target

2015

shaded area = uncertainty band

Incidence rates falling globally after peak in 2004, but only at <1%/year
Incidence (all forms, incl. PLHIV)
Notification gap

shaded area = uncertainty band

Peak in 2004

TB Notifications

Incidence TB in PLHIV

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, 201115
36.9 22.6 7.1 2.8 4.0 0.4 9.8

% total
10000 9000

DOTS MDR-TB TB/HIV Lab strengthening Technical assistance R&D

48% 15% 6% 8% 1% 21%

US$ millions (nominal)

IMPLEMENTATION

79%

8000 7000 6000 5000 4000 3000 2000 1000 0 2010 2011 2012 2013 2014 2015 Funding needed Funding available

TOTAL

46.7

100%

Treatment success 86% globally

Global
90

WHO Regions
95
86 86
93 W. Pacific 88 SE Asia EMR 80 Africa Americas

Treatment success rate (%)

90 85 80 75 70

85 85 83 80 80

84

77 66 Europe

75 2003 2004 2005 2006 2007 2008

65 2003 2004 2005 2006 2007

2008

Progress in most regions, but Europe lagging behind

HIV testing for TB patients expanding

Although more needed to reach 100% targets in Global Plan

60

Percentage of TB patients Percentage

53

50 40 30
22 20 38

45

Africa

Several countries show very high testing rates are achievable

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

26 22

20
9 12 11 3

World

10
4

2003 2004 2005 2006 2007 2008 2009

CPT and ART for HIV-positive TB patients also expanding

Although more needed to reach 100% targets in Global Plan

of HIV+ PercentagePercentage TB patients

100

CPT
80
83 70 75

Several countries show higher rates of enrolment are possible

CPT 86%97% in 2009
Kenya, Malawi, Mozambique, Rwanda, Tanzania, Uganda

60

ART
40
37

20

ART close to 50% in 2009

Rwanda, Malawi
2003 2004 2005 2006 2007 2008 2009

Policy on collaborative TB/HIV activities WHO recommendations

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

Increasing notifications via PPM (public-private mix)

40

Percentage of total notifications

36

36 29 25

35 30 25 20 15 10 5 0 19 17 15 14 13 28 21

Cambodia

Indonesia

National NATIONAL

gap

Parts PARTSof country OF COUNTRY

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

Philippines

Myanmar

Ghana

China

India

Iran

Tanzania

Pakistan

Mexico

Increasing case notifications is good, Butit is not yet early case detection
Annualised rate of ss+ cases diagnosed per 100,000

160 140 120

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

NGO 100 80 60 40 20 0
99q1 99q3 00q1 00q3 01q1 01q3 02q1
Quarter

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

02q3

03q1

03q3

04q1

04q3

05q1

05q3

Proportion of TB patients tested for MDR-TB remains low

100% 90%

New
% of patients

100% 90% 80% 70% 60% 50% 40% 30% 20%

36%

Previously treated

80%

% of patients

70% 60% 50% 40% 30% 20% 10% 0%

Global plan target for 2015 =20%

Global plan target for 2015 =100%

29% 11% 2% 2% 1% 0%

16% 9% 7% 6% 7% 2%

7%

10% 0%

er ic as SE A si a W Pa ci fic

ic a

ro pe

LD

si a A W

A fr

O R

m er

Eu r

Eu

ac ifi

EM

fri ca

EM

A m

.P

SE

RL D

ic a

op e

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

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

Full implementation of Global Plan: 2015 MDG target reached but TB not eliminated by 2050
10000
Current rate of decline

Incidence/million/yr

1000
TB incidence 10x lower than today, but >100x higher than elimination target in 2050

100

10

Elimination 16%/yr Global Plan 6%/yr Current trajectory 1%/yr

Elimination target: 1 / million / year by 2050

1 2000

2010

2020 Year

2030

2040

2050

Overview of this presentation

Burden of TB, TB/HIV, MDR-TB

Progress towards international targets Challenges in 2011 Actions needed

Innovative actionActions Needed in 4 Areas Innovative needed in 4 spheres

TB care and control
Early & increased case detection: new tools Scale-up TB/HIV and MDR-TB interventions M&E and impact measurement Engage all care providers Active screening among at-risk populations

Health systems and policies

Free services, labs, quality drugs, regulated private care, better M&E

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

Research sensu lato

MDR-TB, Multi drug resistant TB M&E, Monitoring and evaluation 31

New tools Operational research Transfer of technology

Population attributable fraction PAF P RR 1 1 Selected Risk Factors & Determinants

Relative risk for active TB disease

P RR 1

Weighted prevalence (22 HBCs)

Population Attributable Fraction in Adults

HIV infection

20.6/26.7*

1.1%

Malnutrition
Diabetes Alcohol use (>40g / d) Active smoking Indoor Air Pollution

3.2**
3.1 2.9 2.6 1.5

16.5%
3.4% 7.9% 18.2% 71.1%

19% 27% 6% 13% 23% 26%

Sources: Lnnroth 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 Lnnroth et al. A consistent log-linear relationship between tuberculosis incidence and body-mass index.

Limitations of todays Diagnostics, Drugs and Vaccine Butsomething moving!

Diagnostics - More than 100 years old Detects only half of the cases in patients tested Less ffective for diagnosing TB in PLHIV Butrapid 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 Butnew 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 Buta dozen candidates in clinical trial

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

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

Source: L. Abu Raddad et al, PNAS 2009

Going beyond smear & liquid culture Introducing GeneXpert

WHO endorsement 2010

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) Phased implementation & evaluation 2011
Scale up 2012
35

Current TB Therapy and Unmet Needs

Patient Population
Drug-Susceptible DS-TB

Current Therapy
4 drugs; 6 month therapy (2RHZE + 4RH) At least 4 drugs (including injectable); 18 months; poorly tolerated Drug-drug interactions (DDI) with ARVs 6-9 months H

Unmet Needs
Shorter, simpler therapy

Drug-Resistant M(X)DR-TB
TB/HIV co-Infection Latent TB Infection

Fully oral, shorter and safer therapy

No or low DDI, coadministration with ARVs Shorter, safer therapy

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

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

Global TB Drug Pipeline, June 2011

Discovery

Preclinical Development

Clinical Development

Lead Identification Summit PLC compounds

Lead Optimization Nitroimidazoles Mycobacterial Gyrase Inhibitors Riminophenazines Diarylquinoline Translocase-1 Inhibitor MGyrX1 inhibitor InhA Inhibitor GyrB inhibitor LeuRS Inhibitor

Preclinical Development CPZEN-45 SQ641 SQ609 DC-159a BTZ-043

Phase I AZD5847

Phase II TMC-207 OPC-67683 PA-824 SQ-109 PNU -100480 LL3858 Rifapentine Linezolid

Phase III

Gatifloxacin Moxifloxacin Rifapentine

Conclusions
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 socioeconomic barriers are necessary to achieve acceleration of decline and elimination