the global burden of tb (dr. mario raviglione)
DESCRIPTION
The Global Burden of TB (Dr. Mario Raviglione)TRANSCRIPT
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
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
TB care and control
Development agenda
Research sensu lato
Health systemsand policies
Free services, labs, quality drugs, regulated private care, better M&E
New toolsOperational researchTransfer of technology
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
•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