MDR-TB - Medico e Bambino

EPIDEMIOLOGIA GLOBALE DELLA TUBERCOLOSI
GIULIANO GARGIONI
Stop TB Department
WHO, Ginevra
I will…

Summarise the global epidemiology of TB

Review the achievements towards the 2015
Millennium Development Goals and the Stop TB
Partnership targets

Outline current challenges and Stop TB Strategy
Una strategia globale per battere la tubercolosi
deve tener conto:
• di tutti i nuovi casi, o della nuove ricadute
notificate
• dei casi di TB multi-resistente (alla idrazide e
alla rifampicina), MDR
• dei casi di TB estensivamente multi-resistente
(in genere anche agli aminoglicosidi), XDR-TB
• e infine dei casi di TB associata a HIV
Latest global TB Estimates - 2006
Estimated
number of
cases
All forms of TB
Greatest number of cases in Asia;
greatest rates per capita in Africa
Estimated
number of
deaths
9.15 million
1.65 million
(139 per 100,000)
(25 per 100,000)
Multidrug-resistant
TB (MDR-TB)
489,000
~130,000
Extensively drugresistant TB (XDR-TB)
~35,000
~20,000
HIV-associated TB
709,000 (8%)
231,000
Tuberculosis notification rates, 2006
(Total N = 5.4 million)
La notifica di nuovi casi nel 2006 è stata di 5,4 milioni, di cui la maggior
parte concentrata nell’Africa sub-sahariana, in India e nella Russia
asiatica
No report
0–24
25–49
50–99
100 or more
Notified TB cases (new and
relapse) per 100 000 population
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
L’impatto economico della TB è molto alto:
• a livello micro, personale, la spesa per le cure può
essere più alta del guadagno personale (vedi in
Malawi)
• a livello macro si calcola che siano necessari 5,5
miliardi di dollari all’anno
D’altronde, un aumento del 10% della TB riduce la
forza lavoro e produce un taglio alla crescita
economica che va dallo 0,2 allo 0,4% all’anno.
Il beneficio del controllo della TB ripaga di 10 volte
le spese di investimento.
Economic impact of TB
At Macro level:
At Micro level:
Provision of diagnostic and
treatment services:
US$ 5.5 billion per year on
average required, as
outlined in the Global Plan
Economic impact of TB at patient and household level
% annual
income
percapita
capita(year
(year 2001
2001 US$)
US$)
per
income
as %asannual
CostCost
180%
160%
TB Treatment based at
health facilities
149
140%
120%
100% annual income
100%
80%
70
56
60%
37
40%
19
20%
14
0%
Malaw i
Kenya
Tanzania
Uganda
South Africa
Pakistan
Sources: Croft et al, 1998; Needham et al, 1998; Wyss et al, 2001; Rajeshwari et al, 1999; Floyd et al, 2003; Nganda et al, 2003; Wandwalo
et al, 2005; Okello et al, 2003; Floyd et al, 1997; Khan et al, 2002
Macro-economic level:
recent study suggests 10%
increase in TB incidence
cuts economic growth by
0.2% - 0.4% per year
WB study shows that
benefits of TB control are
10 times the investments
foreseen in the Global Plan
Il Millennium Development Goal n°6 prevede un arresto
della crescita dei casi di TB e di AIDS per il 2015.
L’indicatore 23 per questo MDG si basa sulla
registrazione dei nuovi casi e dei casi di morte, e
l’indicatore 24 sulla proporzione dei casi diagnosticato e
seguito secondo il modello DOTS
Ma il successivo piano STOP TB si propone, per
quell’epoca, un dimezzamento dei nuovi casi e una
eliminazione della TB per il 2050
Global TB Control Targets
2015: Goal 6: Combat HIV/AIDS, malaria and other diseases
Target 8:
Indicator 23:
Indicator 24:
to have halted by 2015 and begun to reverse the
incidence…
incidence, prevalence and deaths associated with TB
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)
Case detection (smear+) increasing,
but at slower rate than 2002–2005
CDR, smear-positive cases (%)
80
70
Target 70%
60
61% in 2006
50
2.5 million
detected out
of 4.1 million
estimated
Global Plan:
65% in 2006
78% by 2010
il numero dei casi
40
correttamente
100
77 69
diagnosticati con
67
80
52 52 46
30 All new sm+
60
batterioscopia
40
secondo il modello
20
20
DOTS si avvicina
0
DOTS sm+
abbastanza
10
rapidamente al
numero totale
0
stimato dei casi, e
1990
1994
1998
2002
2006
2010
2014 al bersaglio del
70%
Africa 46%, Europe & Eastern Mediterranean: 52%
Treatment success target reached
(globally)
79
83
85
80
79
77
2005
2004
2003
2002
2001
2000
1998
1997
1996
1995
70
1999
244,662
78 77
74
82 82 82
84
2.34 million
81
82
1994
Percentage
86
Europe: 67%, Africa: 76%, Americas: 78%
Anche il
numero dei
successi
terapeutici
cresce di anno
in anno…
TB prevalence and mortality
Prevalence
Mortality
35
300
250
200
150
Target = 148
100
50
0
1990 1995 2000 2005 2010 2015
Deaths per 100,000 population
Cases per 100,000 population
350
30
25
20
15
Target = 14
10
5
Total deaths from TB
in 2006 = 1.65 million
0
1990 1995 2000 2005 2010 2015
… mentre si riducono i numeri di prevalenza e di mortalità,
anche se a un ritmo inferiore al desiderato
Cosa è emerso nel 2008? Che le cose vanno meno bene di
quello che dovrebbero, per un insieme di ragioni:
1. DOTS not yet fully expanded and of high quality everywhere
2. TB/HIV, especially in Africa; MDR-TB, especially in former USSR
and China; XDR-TB emerging everywhere but particularly in Africa
3. Weak health systems and services compromising TB care: need
by NTP to get engaged in HSS
4. Outside of NTP staff, not all practitioners, non-state and even
governmental, working at high standard
5. Communities un-aware, un-involved, not mobilised
6. Research delivering new tools too slowly, and operational
research often outside of the interest of TB "controllers"
A queste debolezze risponde la strategia del WHO,
STOP TB: perseguire nella campagna di espansione
e rinforzo del modello DOTS
•
•
•
•
•
Political commitment with increased and sustained financing
Case detection through quality-assured bacteriology
Standardized treatment, with supervision and patient support
An effective drug supply and management system
Monitoring and evaluation system, and impact measurement
TB/HIV Co-infection
Overlap of two populations
Il problema, sempre gravissimo, della associazione HIV-TB è,
naturalmente, maggiore in Africa che in Europa
Infection
Infection with
with HIV
M. tuberculosis
Rich European Country
World Health Organization
TB/HIV Co-infection
Overlap of two populations
Sub-Saharan African country
Infection
Infection
with HIV
with
M.
tuberculosis
World Health Organization
Incidence of TB among TB-infected persons
HIV (+) vs HIV(-)
l’associazione alla infezione TB dell’HIV produce una malattia clinica nel 5-10%
ogni anno (contro un 5% nei primi 2 anni nelle infezioni TB pure) e una riduzione
del 30% dell’attesa di vita (contro una riduzione di <105 nella TB pura)
TB Infection
HIV (-)
HIV (+)
5-10%
every year
>30%
lifetime
5%
first 2 years
<10%
lifetime
World Health Organization
Impact of HIV on TB in Africa
Notified cases per 100,000
700
600
500
400
300
Botswana
Côte d'Ivoire
DR Congo
Gabon
Guinea
Kenya
Malawi
Mozambique
South Africa
UR Tanzania
Zimbabwe
Il preoccupante aumento dei casi di
associazione HIV-TB in Africa è
documentato dalle curve
200
100
0
1980
1984
1988
1992
1996
2000
2004
L’altro problema è quello delle resistenze
(resistenza primaria o resistenza acquisita).
La TB multi-resistente (MDR-TB) è resistente agli
antitubercolari maggiori, Idrazide e Rifampicina.
Il problema è mondiale; in Africa la prevalenza
non è apparentemente troppo alta, ma solo per
un difetto di riconoscimento e quindi di
segnalazione
Drug-resistant TB: Definitions
• Drug resistance among new cases (or “primary drug
resistance”) is the presence of resistant strains of
M.tuberculosis in a newly diagnosed patient who has never
received TB drugs or has received them for less than one
month of treatment
• Drug resistance among previously treated cases (or
“acquired drug resistance”) is that found in a patient
who has previously received at least one month of TB
therapy
• Multidrug-resistant TB (MDR-TB) is a form of TB
caused by bacilli that are resistant to, at least, isoniazid and
rifampicin.
MDR-TB among new cases 1994-2007
* Sub-national coverage in India,
China, Russia, Indonesia.
< 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
MDR-TB is harder to cure
La MDR-TB è naturalmente più difficile da curare
L’istogrammma mostra le percentuali di guarigione nei vari paesi, confrontate con
quelle generali della TB (per lo più non resistente)
Cure rate (%)
100
all TB
MDR-TB
80
56
60
54
59
35
40
26
20
6
0
Russia
Dominican
Rep
Italy
Korea
Peru
(Espinal, Raviglione et al. JAMA 2000)
Hong Kong
La resistenza estensiva XDR-TB
comporta una resistenza ai fuorochinoloni
e agli aminoglicosidi.
È dovuta in larga misura all’associazione
HIV-TB, specie in Africa
XDR-TB – Extensive Drug Resistance
The new threat – 24 March 2006
XDR = Resistance to at least INH
and RIF (MDR) PLUS resistance to
any fluoroquinolones, AND any one
of the second-line injectable drugs
(amikacin, kanamycin, capreomycin)
Of 17,690 isolates from 49 countries
during 2000-2004 20% were MDR
and 2% were XDR
XDR found in:
USA: 4% of MDR
Latvia: 19% of MDR
S Korea: 15% of MDR
XDR found in Southern
Africa associated with
HIV
Countries with XDR-TB confirmed
Cases as of February 2008
Italy
Armenia
Japan
Azerbaijan
Latvia
Australia
Lithuania
Bangladesh
Botswana
Brazil
Canada
Chile
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 WHO 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 2005. All rights reserved
Argentina
Mexico
Moldova
Mozambique
Netherlands
Nepal
China, Hong Kong SAR
Czech Rep.
Ecuador
Estonia
France
Georgia
Germany
Ireland
India
Norway
Peru
Philippines
Poland
Spain
Portugal
Sweden
Rep of Korea
Romania
Thailand
UK
Russian Fed.
Islamic Rep. of Iran
Israel
South Africa
Slovenia
Ukraine
USA
Vietnam
I casi confermati sono rari, e si riscontrano nei Paesi
sviluppati piuttosto che nei Paesi sottosviluppati,
essenzialmente
le provided
difficoltà
tecniche
della
diagnosi
Based onper
information
to WHO Stop
TB Department
- February
2008
Il trattamento delle TB resistenti richiede uno
sforzo particolare di politica sanitaria e
naturalmente è meno efficace dove le strutture
sanitarie sono più deboli
Global Policy: MDR-TB and XDR-TB
• Strengthen basic TB and HIV/AIDS control, to
avoid creation of MDR-TB and XDR-TB
• Scale-up programmatic management of MDRTB and XDR-TB
• Strengthen laboratory services for adequate
and timely diagnosis of MDR-TB and XDR-TB
• Expand MDR-TB and XDR-TB surveillance
• Introduce infection control, especially in high
HIV prevalence settings
• Strengthen advocacy, communication and
social mobilization (e.g., Response Plan)
• Pursue resource mobilization at global, regional
and country levels
• Promote research and development into new
diagnostics, drugs and vaccines
» WHO's XDR-TB Task Force
Weak health system & services
Good TB care and control more difficult
Il fatto che la TB sia trattata anche dalla medicina privata comporta
spese e indebolisce l’azione di governo e di controllo
1.
Little active participation in country-led & global efforts
to improve human resources, management; financing;
infrastructure and supply systems; information systems;
non-state and community involvement
2.
Slow scaling-up and adaptation of TB control
innovations to benefit the system as a whole (eg, PAL,
PPM etc)
3.
Not yet the mentality to adapt and apply innovations
from other fields (eg, financing frameworks from
immunization, social mobilization from HIV/AIDS etc.)
Private care providers and TB control:
 PPs are growing everywhere in the world
 Manage large proportions of TB suspects and cases
 For-profit, impose large financial burden on patients
 No mandatory continuing medical education
 No regulation or monitoring
 No licensing or re-certification
International Standards for TB Care:
available but not yet widely adopted
The International Standards for TB
Care describe a widely accepted level
of care that all practitioners should
seek to achieve in managing patients
who have or are suspected of having
tuberculosis
Community information, education
and participation is too often ignored

Community resources, complementary to NTP, to
contribute to local TB care and control not harnessed

Concepts of subsidiarity and solidarity are key to
community engagement, yet not widely disseminated

An opportunity to increase rapid case detection and
support patients until cure not exploited by health care staff

New Patients Charter not yet widely adopted and
disseminated
Research not yet delivering new tools
And not the interest of "controllers"

Currently TB R&D emphasises new diagnostics, drugs and
vaccines, through global working groups and partnerships

New diagnostics are emerging and re-tooling has begun, but we
are far from new drug regimens and vaccines

Without basic science, research in immunology, pathogenesis,
genomics etc, scarcity of products to get into pipeline for
development

Most TB control staff have little interest in advocating for
intensified and well financed operational research

Scarcity of funds (1/20 of HIV R&D devoted to TB at NIH) and
scarcity of coordination and debate world-wide
Per finire, ecco le raccomandazioni che
derivano dalla strategia STOP-TB, le
nuove sfide, e la sintesi della relazione
WHO recommended Stop TB Strategy
to reach the 2015 MDGs
A new vision…
New challenges require the
new Stop TB Strategy
The Global Plan 2006-2015 clearly outlines
what needs to be done and the costs
2006-2015:
56 billion US$
necessary to
control TB in
endemic
countries
11 billion US$
necessary to
develop new
tools
In summary…
 Evident progress 1994-2006: 32 million patients treated under DOTS. Latest
cure rate 84.6%.
 Latest case detection rate 61%, with deceleration in 2006. 69% of the
progress in case detection globally depends on Africa, India and China.
 TB incidence decreasing or stabilising in all regions, but TB/HIV and M/XDRTB are grave threats. Still nearly 4500 deaths a day caused by TB!
 Urgent need to strengthen programmes, with adequate primary care services,
human resources and labs to reach MDGs in 2015.
 New tools necessary to speed up control and seriously target elimination.
 Other socio-economic factors contribute to TB incidence trends. Addressing
those will be key to target elimination.