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    C:\Users\Lg\Documents\öZge\Tbc\Tb Net\Web\Barcelona 2009 Bk Ptbnet C:\Users\Lg\Documents\öZge\Tbc\Tb Net\Web\Barcelona 2009 Bk Ptbnet Presentation Transcript

    • Tuberculosis
in
children
in
Europe
 ‐
the
ptbnet
 Beate
Kampmann
FRCPCH
PhD
 A/Professor
in
Paediatric
Infection
&
Immunity
 Consultant
Paediatrician
 Imperial
College
London,
UK
 and

 Institute
of
Infectious
Diseases
and
Molecular
Medicine
 University
of
Cape
Town,
RSA
 XIII
Taller
Internacional
sobre
Tuberculosis
UITB‐2009,
Barcelona
1
de
Diciembre
2009

    • Presentation overview Acknowledgement & Thanks Childhood TB- special considerations Childhood TB- epidemiology Issues in Europe The rationale for the ptbnet Summary of European Practices Outlook
    • Paediatric TB: special & Thanks Acknowledgement considerations •  Significant
Morbidity
and
Mortality
 
 1.4
million
cases
annually
(95%
developing
countries)
 
 
450,000
Deaths
 
 estimated
10‐15%
of
global
burden
related
to
childhood
TB
 • 
Different
clinical
spectrum
of
disease
 
 5‐10%
<
2
yr
meningitis

 
 disseminated
disease
more
common
 • Remains
a
diagnostic
challenge
 
 paucibacillary,
rarely
culture
confirmed
:
 
 Sputum
smear
positive
in
10.3%
(10‐14yr),
1.8%
(5‐9)
and1.6%
(<5)
 
 Cultures
positive
21%
(10‐14),
5%
(5‐9)
and
4.2%
(<5),

 • 
Co
infection
with
HIV‐
clinically
very
difficult
to
distinguish

    • Tuberculosis
in
children
differs
from
adults
 Acknowledgement & Thanks • 

Immune
responses
are
 
 Age‐dependent:
Following
infection
40%
<
2
yr,
25%
2‐5
yr
and
 
 5‐15%
of
older
children
will
develop
disease
within
2
years
 • 
Majority
of
disease
results
from
progression
of
primary
 
 infection
rather
than
reactivation
 
 might
affect
detectable
immune
responses

 • 
More
likely
to
be
extrapulmonary
and
disseminated,
 
 
 particularly
in
infants
 Pulmonary TB 800 700 600 500 400 300 200 Extrapulmonary TB 100 0 10-14 25-29 40-44 55-59 70+ Age group (years) Newton,
Kampmann
The
Lancet
Infectious
Diseases,
August
2008;
Vol
8:
498‐510

    • Paediatric TB: Diagnostic challenges Thanks low bacillary load Acknowledgement & due to
    • Diagnostic approaches Acknowledgement & Thanks Microbiological
 Immunological
 Organism
 Host
response
 smear




culture





DNA
 skin
test









antigen‐specific

 

























production
of
IFNγ
    • Paediatric TB: Epidemiology Acknowledgement & Thanks • 
of
the
9
million
annual
TB
cases,
about
1
million
(11%)
occur
in
 children
(under
15
years
of
age).
 • 
reported
percentage
of
all
TB
cases
occurring
in
children
varies
 
 (from
3%
to
more
than
25%)
 • Children
can
present
with
TB
at
any
age,
but
the
most
common


 age
is
between
1
and
4
years
 • 
Most
children
will
have
a
known
household
contact
 • 
Chemopropphylaxis
is
a
recommended
intervention

    • Percentage of TB cases of foreign origin, 2006 Acknowledgement & Thanks Not
included
or
not
reporting
to
EuroTB
 0%
–
4%















 5%
–
19%







 20%
–
49%
 >
49%
 Andorra
 Malta
















 Monaco









 San
Marino


 Trends
in
incidence
of
TB
in
children
under
15
years

 by
ethnic
group
in
London,
2001‐2006

    • UK: Tuberculosis
rates
in
persons
born
abroad
by
age 180 1999 160 2000 140 2001 Rate (per 100,000) 120 2002 100 80 2003 Development
of
TB

 60 40 in
immigrant
children
 20 0 15 4 20 9 25 4 30 9 35 4 40 9 45 4 50 9 55 4 60 9 65 4 70 9 80 7 4 d 9 4 10 9 er -1 -1 -2 -2 -3 -3 -4 -4 -5 -5 -6 -6 -7 an 5-7 0- 5- ov Age group (years) Sources:
Enhanced
Tuberculosis
Surveillance,
Labour
Force
Survey
population
estimates,
Abubakar
et
al
Arch.
Dis.
Child.
2008;93;1017‐1021;

    • 
 
 
 
 
Children
with
TB
at
Imperial
HCT 
 

 Ethnicity
and
country
of
birth:

 south asian Travel to TB endemic countries 29% yes no dk black african afro-caribbean dk black african caucasian 5% 47% SE asian mixed race arab no south asian arab 39% 5% no dk household visitor mixed race yes 4% 56% visitor SE asian 6% 6% afro-caribbean caucasian 2% no 7% Country of Birth 28% dk UK 4% 38% UK household non-UK 62% non-UK 62%
    • Issues
for
children
with
TB
in
Europe
 Acknowledgement & Thanks • 
Incidence
and
prevalence
vary
depending
on
countries
 • 
Data
on
childhood
TB
are
not
recorded
as
systematically‐

 
 ‐
no
age‐related
reporting
(0‐14)
 • 
Children
are
infected
from
adult
contacts,
but
the
contact
details
are
not
recorded
 • 
Clinical
practice
for
prevention
varies
from
country
to
country
 • 
Chemoprophylaxis
protocols
vary
 • 
Monitoring
varies
 • 
No
idea
about
MDR
prevalence
in
children
 • 
Treatment
/(MDR)
protocols
derived
from
adult
practice

    • ECDC‐
reported
variables Acknowledgement & Thanks Total
No
of
cases
and
Notification
rate/100
000
 Sex
ratio
 Median
age
group‐
nationals
and
non‐nationals
 New
(never
treated)
 Foreign
born
 Culture
positive
 pTB
 HIV
positive
TB
cases‐
not
stratified
for
children
 TB
deaths
 Drug
resistance
 Treatment
outcome

    • 2
Key
recommendations:
 A.
2
age
bands
to
be
reported:
0‐4,
5‐14
 “Enumerating
children
with
TB
is
a
key
 step
in
bringing
their
management
into
the
mainstream
of
the

 Stop
TB
Strategy
as
part
of
routine
NTP
activities.”
 B.

Dosage
adjustments
for
TB
therapy
 “revised
recommended
dose
of
Ethambutol
is
now
20
mg/kg
(range
 15–25
mg/kg)
daily.

    • what else can&we do? Acknowledgement Thanks to
improve
the
care
for
children
with
TB

 in
Europe
 
 
 
 
by
creating
a
network
of
pediatric
experts
in
TB
in
Europe

 ‐
to
more
accurately
describe
active
and
latent
TB
in
children
in
Europe
 ‐
to

identify
differences
in
practice
between
European
countries
 ‐
to
improve
clinical
management
and
research
in
childhood
TB
in
Europe
 ‐ 
to
develop
a
European
"expert
panel"
for
consultation
on
paediatric
TB

 

and
possibly
a
training
course

 
 
 
 
 
 
 
 
 
 
 






clinicians
 ‐
to
conduct
collaborative
research

 
 
 

 
 
 
 
 
 
 
 
epidemiologists
 
 
 
laboratory
scientists
 
 
 
 
 
 


    • • 
founded
in
April
2009

 • 
to
date:
25
members
from
15
European
 

countries,
incl
Eastern
Europe
 • 
includes
clinicians,
epidemiologists
and

 

laboratory
scientists

 

www.ptbnet.org
 Aims
 • 
enhance
the
understanding
of
the
pediatric
aspects
of
tuberculosis
 • 
facilitate
collaborative
research
studies

for
childhood
TB
in
Europe

 • 
provide
expert
opinion
through
excellence
in
science
and
teaching
 • 
establish
a
better
evidence
base
for
diagnosis
and
treatment
of
TB

 


in
children

    • April
09
 Agenda
 1.  Presentations
from
each
country:
 Theme
1:
Data
capture
for
TB
in
your
country
 Theme
2:
Practical
Care
for
children
in
your
 country/at
your
hospital

 2.
Data
collection:

 Discussion
of
shared
database
options
 3.
Discussion
of
multicentre
studies:
 Defining
research
priorities
and
possible
future
 studies
 4.
Conclusions
and
future
plans:
 What
do
we
want
to
be/do
 Possible
funding
streams‐
where
to
go

    • Acknowledgement & Thanks Summary
of
ptbnet‐data:
Epidemiology
 140
 120
 100
 80
 total
no
of
cases/100
000
 60
 percentage
of
ped.
cases
 40
 20
 0
 National
TB
guidelines
for
children
 Yes:
8/11
(72%)
 No:
2/11
(18%)
 Proposed:
1/11
(9%)

    • Summary
of
ptbnet‐data:


 Acknowledgement & Thanks MDR
‐
TB

 percentage
of
MDR
TB
 18
 16
 14
 12
 10
 8
 6
 percentage
of
MDR
TB
 4
 2
 0
 percentage
of
MDR
TB
 Austria
 Belgium
 Greece
 Holland
 Italy
 Lithuania
 No
data
in
children
 Romania
 Spain
 Turkey

    • Summary
of
ptbnet‐data:

 Prevention
and
Treatment
 • 
Routine
use
of
BCG:
7/11
 • 
Targeted
use
of
BCG:
2/11
 • 
No
BCG:
4/11
 • 
Chemoprophylaxis:
11/11,
but
ages
vary,
as
do
regimes
 • 
Treatment:
available
free
of
charge

    • Summary
of
ptbnet‐data:
 TB
and
HIV • 
Few
data
available
on
prevalence
of
HIV
in
children
with
active
TB
 • 
Only
2/11
countries
routinely
test
TB
cases
for
HIV
 • 
HIV
results
generally
not
recorded
in
reporting
systems

    • Summary
of
ptbnet‐data:

 Use
of
Interferon‐gamma
release
Assays
(IGRA)

 • 
IGRA
Recommended
in
8/11
countries
 • 
Widely
used
for
diagnosis
of
active
TB
 • 
Used
for
LTBI
screening
in
only
4
countries
 • 
QFG‐IT
preferred
test
(7/11
vs
3/11)
 • 
Data
in
different
age
groups
could
be
combined

 

to
comment
on
age‐related
performance

    • Future
plans
of
the
ptbnet
 1.
Designated
database
 Consensus
that
a
paediatric
database
is
highly
desirable
 ?
Use
existing
platforms
or
start
from
scratch
 ?
ECDC
information‐
too
limited,
disease
only
 ?
Should
be
able
to
combine
with
adult
data
(contacts)
 ?
What
to
include
 Needs
to
not
just
focus
on
TB
disease
but
include
exposure/infection/disease
 Designated
funding
needs
to
be
identified
to
move
this
project
forwards
substantially
 In
the
shorter
term,
we
will
investigate
existing
platforms
 and
compile
the
data
fields
that
we
would
like
to
include
 (potential
data
protection
issues
in
our
individual
countries)



    • Future
plans
of
the
ptbnet
 2.
Defining
research
priorities
 Immuno‐assays
in
children
 Longitudinal
studies,
age
related,
MDR
monitoring,
site‐specific,
in
immunocompromised
 Pharmacokinetics
 New
and
old
TB
drugs
 MDR
TB
 Risk
factors,
management
(exposed
and
cases)
 Members
with
existing
studies
will
liaise

 to
share
data
and
compare
experience
and
recommendations
as
well
as

 prepare
shared
data
for
joint
publications
 (f.ex.:
Bamford
et
al,
ptbnet
(UK),
Arch
Dis
Child
2009)
 Protocol
sharing
in
labs/training

    • Where
from
here
 Logo


 website 
 
 
 
 
www.ptbnet.org
 Database
negotiations
with
TBNET‐
in
process,
needs
to
be
intensified
 Funding
opportunities
?
within
EU‐
FP7
calls
 Descriptive
manuscript
of
childhood
TB
in
Europe
to
be
prepared
 ptbnet

members
contributing
to
TBNET
anti‐TNF
and
IGRA
consensus
statement

 Expansion
of
the
group
to
include
clinician,
laboratory
and
epidemiologist
in
each
place
 Close
collaborations
with
TBNET
(www.tb‐net.org)
 
 
 
 
Database
 
 
 




Website
space
 
 
 
 
MDR
study
 
 
Paediatric
aspects
of
other
studies

    • How
can
you
help?
 • 
Consider
TB
as
a
family
disease
and
set
up
your
clinics
in
this
way
 • 
Ensure
that
paediatric
information
is
collected
specifically/identifiable
 • 
Collect
information
on
contact
screening
 • 
Collect
information
on
chemoprophylaxis
and
outcome
 • 
Join
paediatric
research
studies
 



‐
Diagnostics
 



‐
TB/HIV
coinfection‐
test
the
cases
also
in
children
 



‐
be
aware
of
drug
formulations
for
children
 
Join
the

    • Muchas
graçias
de
su
atençión
 Hay
preguntas???
 
 
 
 
b.kampmann@imperial.ac.uk
 www1.imperial.ac.uk/medicine/people/b.kampmann