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1Heuvelings CC, et al. BMJ Open 2018;8:e019642. doi:10.1136/bmjopen-2017-019642
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Effectiveness of service models and organisational structures supporting tuberculosis identification and management in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review
Charlotte C Heuvelings,1 Patrick F Greve,1 Sophia G de Vries,1 Benjamin Jelle Visser,1 Sabine Bélard,1 Saskia Janssen,1 Anne L Cremers,1 René Spijker,2 Elizabeth Shaw,3 Ruaraidh A Hill,4 Alimuddin Zumla,5 Andreas Sandgren,6 Marieke J van der Werf,6 Martin Peter Grobusch1
To cite: Heuvelings CC, Greve PF, de Vries SG, et al. Effectiveness of service models and organisational structures supporting tuberculosis identification and management in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review. BMJ Open 2018;8:e019642. doi:10.1136/bmjopen-2017-019642
► Prepublication history and additional material for this paper are available online. To view these files, please visit the journal online (http:// dx. doi. org/ 10. 1136/ bmjopen- 2017- 019642).
Received 15 September 2017Revised 14 March 2018Accepted 18 April 2018
For numbered affiliations see end of article.
Correspondence toDr Marieke J van der Werf; marieke. vanderwerf@ ecdc. europa. eu
Research
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
AbstrACtObjective To determine which service models and organisational structures are effective and cost-effective for delivering tuberculosis (TB) services to hard-to-reach populations.Design Embase and MEDLINE (1990–2017) were searched in order to update and extend the 2011 systematic review commissioned by National Institute for Health and Care Excellence (NICE), discussing interventions targeting service models and organisational structures for the identification and management of TB in hard-to-reach populations. The NICE and Cochrane Collaboration standards were followed.setting European Union, European Economic Area, European Union candidate countries and Organisation for Economic Co-operation and Development countries.Participants Hard-to-reach populations, including migrants, homeless people, drug users, prisoners, sex workers, people living with HIV and children within vulnerable and hard-to-reach populations.Primary and secondary outcome measures Effectiveness and cost-effectiveness of the interventions.results From the 19 720 citations found, five new studies were identified, in addition to the six discussed in the NICE review. Community health workers from the same migrant community, street teams and peers improved TB screening uptake by providing health education, promoting TB screening and organising contact tracing. Mobile TB clinics, specialised TB clinics and improved cooperation between healthcare services can be effective at identifying and treating active TB cases and are likely to be cost-effective. No difference in treatment outcome was detected when directly observed therapy was delivered at a health clinic or at a convenient location in the community.
Conclusions Although evidence is limited due to the lack of high-quality studies, interventions using peers and community health workers, mobile TB services, specialised TB clinics and improved cooperation between health services can be effective to control TB in hard-to-reach populations. Future studies should evaluate the (cost-)effectiveness of interventions on TB identification and management in hard-to-reach populations and countries should be urged to publish the outcomes of their TB control systems.PrOsPErO registration number CRD42015017865.
IntrODuCtIOn Prevention and control of tuberculosis (TB) is based on early detection and diagnosis of
strengths and limitations of this study
► Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration reporting guidelines for systematic reviews were followed.
► The search was highly sensitive, but we might have missed important information as many European countries do not publish their tuberculosis identifi-cation and management data in journals; our search focused on Embase and MEDLINE.
► We identified five studies and discuss the results to-gether with the six studies identified by the National Institute for Health and Care Excellence review to give the complete body of evidence.
► None of the included studies was of high quality, and there was high heterogeneity across the studies prohibiting a meta-analysis. on N
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TB followed by effective treatment. In 2015, there were an estimated 10.4 million incident TB cases worldwide, an estimated 4.3 million cases were either not diagnosed or diagnosed but not reported to national TB programmes.1 Trends for TB treatment are encouraging, with most noti-fied TB cases completing their treatment successfully, although treatment success rates in some regions, such as the European region, were considerably below the WHO World Health Assembly target of 85%.1
In many countries with a low TB incidence (less than 10 TB cases per 100 000 population),2 TB prevails in the big cities where vulnerable and hard-to-reach (underserved) populations are concentrated.3 These populations, such as people who are homeless (or have insecure accom-modation), misuse drugs or are migrants, are at higher risk of contracting TB and are more likely unable or unwilling to seek medical care and comply with the long-term TB treatment. Managing TB in those populations is therefore challenging, due to barriers caused by stigma, cultural barriers, poor access to healthcare services and low levels of accurate TB knowledge.4–7 This therefore requires special efforts. Healthcare services need to be organised effectively to identify and diagnose TB cases and to provide adequate treatment and support. This can be organised in different ways, for example, mainly as hospital based8 or health centre based,9 including the public sector, private sector,10 or civil society and other partners.11 Sometimes, organisation of the services has proven ineffective in managing TB.12
The review question of this systematic review with a scoping component was: ‘Which service models and organisational structures, including different types of healthcare workers and settings, are effective and cost-ef-fective for delivering TB services to hard-to-reach popula-tions in low- and medium-incidence countries?’.
Findings of this review and the previously published review series4 13 formed the base for the guidance docu-ment by the European Centre for Disease Prevention and Control (ECDC) on controlling TB in hard-to-reach and vulnerable populations.14
MEthODsIn 2011, the Matrix Knowledge Group published a review, commissioned by the National Institute for Health and Clinical Excellence (NICE), on effectiveness and cost-ef-fectiveness of service models or structures, focusing on the type of healthcare worker and setting, to identify and manage TB in hard-to-reach populations. We updated and extended the NICE review15 using the same meth-odology but adjusting the focus by excluding latent TB infection and including additional hard-to-reach popu-lations. The review was conducted following standards described by the Cochrane Collaboration16 and NICE methods guidelines.17 Results are reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.18 The review protocol was registered in advance in the database of
prospectively registered systematic reviews in health and social care, PROSPERO (CRD42015017865).
selection of studies and data managementThe same search strategy as for the previous NICE review15 and the previous published review by Heuvelings et al13 was used, searching Embase and MEDLINE through the Ovid platform. The search was expanded by including all European Union (EU)/European Economic Area and EU candidate countries to the Organisation for Economic Co-operation and Development countries (see box 1).15 Two hard-to-reach populations (people living with HIV and children within vulnerable and hard-to-reach popula-tions) were added in addition to the hard-to-reach popu-lations included by the NICE review (migrants including refugees, asylum seekers and the Roma population, home-less people including rough sleepers and shelter users, drug users, prisoners and sex workers).15 The update of the search conducted for the NICE review15 covered the period 1 January 2010 (overlapping the end of the search period of the NICE review15 with a few months) to 24
box 1 Inclusion/exclusion criteria for this review
Inclusion criteria ► Discussing service models and organisational structures, different types of healthcare workers and settings for delivering TB services to hard-to-reach populations.
► Having been conducted in any of the EU/EEA countries (only updat-ed review), the candidate countries* (only updated review) and the other OECD countries.†
► Having been published in 2010 or later for the OECD countries.† ► Having been published in 1990 or later for the EU/EEA countries and the EU candidate countries* not being one of the OECD countries (only updated review).
► Including data from any hard-to-reach population: – Homeless people. – People who abuse drugs or alcohol. – Sex workers. – Prisoners or people with a history of imprisonment. – Migrants, including vulnerable migrant populations such as asy-
lum seekers, refugees and the Roma population. – Children within vulnerable and hard-to-reach populations (only
updated review). – People living with HIV (only updated review).
► Present quantitative empirical data. ► Being a (cost)-effectiveness study or any other type of quantitative primary research, discussing (cost-)effectiveness.
Exclusion criteria ► Latent TB infection (only updated review). ► Systematic review (only used for reference searching).
*EU candidate countries: Albania, Montenegro, Serbia, the former Yugoslav Republic of Macedonia and Turkey.†OECD countries: Australia, Austria, Belgium, Canada, Chile, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Japan, Korea, Luxembourg, Mexico, the Netherlands, New Zealand, Norway, Poland, Portugal, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Turkey, UK and USA.EU, European Union; EEA, European Economic Area; OECD, Organisation for Economic Co-operation and Development; TB, tuberculosis.
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February 2017. The search for the expanded geograph-ical area and newly included hard-to-reach populations covered a time period from 1 January 1990 (beginning of the search period used in the NICE review15) to 24 February 2017.
Reference lists of relevant systematic reviews were scanned. No language restrictions were applied.
Studies focusing on the effectiveness and/or cost-effec-tiveness of interventions for service models and organ-isational structures supporting TB identification and management of hard-to-reach populations (see box 1) were included.
Predefined interventions were using more convenient locations (like specialised TB centres, shelters for home-less people or drug users, needle exchange/methadone programme locations, port of arrival, schools or mobile clinics) and peers or healthcare workers with the same ethnic or cultural background; however, other interven-tions could also be included if they supported TB iden-tification or management in hard-to-reach populations. TB identification tools, TB diagnostics, incentives, social support, directly observed therapy and treatment of comorbidities are discussed in another review.13 In this review, we aim to identify the effectiveness of the type of health worker and setting to identify and manage TB in hard-to-reach and vulnerable populations.
The comparator was defined during the review process; interventions were compared with a relevant comparator, for example, usual care or no intervention, another inter-vention or historical comparison.
Outcomes were defined as any measure of TB identifi-cation and management (eg, number of people screened, screening coverage, proportion receiving treatment and treatment completion rate). Effectiveness was defined as an improvement in any measure of TB identification and/or management. Randomised and non-randomised studies were eligible for inclusion.
See online supplementary material I for the PROS-PERO study protocol, online supplementary material II for Population-Intervention-Comparator-Outcome-Study design) questions and online supplementary material III for the complete search strategy and search results.
Data extraction, data items and synthesisIdentified citations were entered into an EndNote data-base, and duplicates were removed (EndNote X7.1, Thomson Reuters 2014). The inclusion criteria were piloted and refined using the first 25 citations. Double screening was conducted by one reviewer screening 100% of the citations (CCH), while another two reviewers screened 50% of the citations each (PFG and SGdV) for inclusion on title and abstract. Disagreement was resolved by discussion. Full-text files of included citations were retrieved; irretrievable articles (not available after attempts online, from the university library or through contacting authors) were excluded. Two reviewers assessed full-text records for inclusion (CCH and PFG). Disagreement was resolved by discussion. Agreement
after screening on title and abstract was 99.6% with an inter-rater reliability (Cohen’s kappa) of κ=0.985.
Data extraction forms from the NICE review15 were used to extract information on participant characteristics, settings, types of services/organisational structures, types of healthcare workers delivering the service, outcome measures, methods of analysis and results. For one study, data extraction was conducted by two reviewers (CCH and PFG) independently. For the remaining studies, data extraction was conducted by one reviewer (CCH) and checked by a second (PFG); disagreement was resolved by discussion. In one case, the study author was contacted to verify data and obtain additional data.19
To facilitate comparability, data synthesis was structured in a similar way to that of the NICE review.15 Studies were divided into those examining service models and organi-sational structures for TB identification (screening) and those examining service models and organisational struc-tures for TB management (treatment and support) in hard-to-reach populations. Data were analysed narratively, and appropriateness of meta-analysis was considered. Findings were reported as stated by the study authors.
risk of bias in individual studies and overall strength of evidenceThe modified NICE Quality Assessment Tools17 (based on the Graphical Appraisal Tool for Epidemiological studies) were used to assess quality and risk of bias of included studies. This included an assessment of selection of study sample, minimisation of selection bias and contami-nation, controlling confounding, outcome measure-ments, analytical methods and risk of bias. Two reviewers (CCH and PFG) assessed one study independently; the remaining studies were assessed by one reviewer (CCH) and checked by a second reviewer (PFG). Any disagree-ment was resolved by discussion. Studies were given a quality rating based on the quality assessment: high quality [++], medium quality [+] or low quality [−]. The strength of the evidence was assessed and reported as described in the previous NICE review15 (online supple-mentary material IV).
Patient and public involvement statementPatient and public were not involved in the design of this systematic review.
rEsultsOf the 19 720 citations identified by the literature search five studies were included in this review (figure 1).11 19–22 These five studies are in addition to the six studies23–28 included in the NICE review.15 The results section in this paper focuses on the evidence of the five studies identified in our updated review. The evidence state-ments (presented in online supplementary material IV) summarise evidence identified in terms of consistency, quality and applicability, combining evidence from the NICE review15 and this update.
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All five studies were conducted in the EU; two in the UK,19 22 one in Germany,20 one in Portugal11 and one in Spain.21 Two studies focused on homeless people,19 20 one on homeless people and drug users,22 one on drug users alone11 and one on migrants.21 Four studies5 19–21 addressed the influence of the type of healthcare worker on TB identification and TB management and one study focused on the influence of different settings on TB iden-tification.22 A variety of study designs were included: one study was a prospective cluster randomised controlled trial (RCT),19 one was an economic evaluation using a compartmental model of treated and untreated active TB cases22 and three studies were retrospective compar-ison studies.11 20 21 Study characteristics of included
studies are described in table 1. The data extraction forms by study are presented in online supplementary material V.
None of the included studies in this review had a low risk of bias, three studies19 21 22 had a medium risk of bias and the other two studies5 20 were assessed as having a high risk of bias (online supplementary material VI).
We did not perform a meta-analysis due to study hetero-geneity. Results were synthesised narratively.29
Main outcomes for services structures and organisa-tional models for TB identification among hard-to-reach populations, combined with the findings of the NICE review,15 are summarised in table 2. For full evidence statements, see online supplementary material IV.
Figure 1 Study selection process.
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Tab
le 1
C
hara
cter
istic
s of
stu
die
s ap
ply
ing
diff
eren
t se
rvic
e m
odel
s an
d o
rgan
isat
iona
l str
uctu
res
to im
pro
ve T
B id
entifi
catio
n an
d T
B m
anag
emen
t
Firs
t au
tho
r (y
ear)
, co
untr
yP
op
ulat
ion
Aim
sIn
terv
enti
on
Co
mp
arat
or
Stu
dy
des
ign
Out
com
e m
easu
reQ
ualit
y sc
ore
TB id
entifi
catio
n (s
tud
ies
iden
tified
by
this
rev
iew
)
Ji
t22 (2
011)
,
UK
Hom
eles
s p
eop
le a
nd d
rug
user
s.
To a
sses
s th
e ef
fect
iven
ess
and
cos
t-ef
fect
iven
ess
of t
he F
ind
an
d T
reat
ser
vice
for
dia
gnos
ing
and
man
agin
g ha
rd-t
o-re
ach
ind
ivid
uals
w
ith a
ctiv
e TB
in L
ond
on.
Per
iod
200
7–20
10: F
ind
an
d T
reat
ser
vice
:
►S
cree
ning
by
MX
U.
►
Pee
rs r
aisi
ng
awar
enes
s.
►Tr
eatm
ent
sup
por
t.
Pas
sive
cas
e d
etec
tion
and
st
and
ard
tre
atm
ent
at a
Lo
ndon
TB
clin
ic.
Ob
serv
atio
nal a
nd
cost
-effe
ctiv
enes
s st
udy.
Iden
tified
TB
ca
ses,
tre
atm
ent
com
ple
tion,
lost
to
follo
w-u
p a
nd
incr
emen
tal
cost
s fr
om
heal
thca
re
taxp
ayer
p
ersp
ectiv
e.
+
D
uart
e11 (2
011)
,
Por
tuga
lD
rug
user
s.To
eva
luat
e th
e ef
fect
of
an in
terv
entio
n w
ith k
ey
par
tner
s (T
B c
linic
, dru
g us
ers
sup
por
t ce
ntre
s,
shel
ters
, str
eet
team
s,
pub
lic h
ealth
dep
artm
ent
and
hos
pita
l) d
eliv
erin
g p
rom
otio
n of
hea
lth-
seek
ing
beh
avio
ur,
elim
inat
ing
pot
entia
l b
arrie
rs fo
r TB
scr
eeni
ng
at a
che
st c
linic
and
D
OT
on id
entif
ying
TB
ca
ses
and
tre
atm
ent
com
plia
nce.
Imp
rove
d c
oop
erat
ion
of
key
par
tner
s (2
005–
2007
):
►H
ealth
ed
ucat
ion
and
sc
reen
ing
pro
mot
ion.
►
Imp
rove
d s
cree
ning
p
roce
dur
es.
►
Imp
lem
enta
tion
of D
OT.
►
Free
TB
car
e an
d
tran
spor
t.
►P
rovi
din
g m
edic
al a
nd
dru
g ab
use
trea
tmen
t.
►A
ctiv
e fo
llow
-up
of n
on-
com
plia
nt p
atie
nts,
the
ke
y p
artn
ers
wor
ked
to
geth
er t
o re
ach
the
pat
ient
, id
entif
y th
e ca
use
and
org
anis
e su
itab
le t
reat
men
t st
rate
gies
.
Per
iod
bef
ore
the
inte
rven
tion
(200
1–20
03):
►
No
activ
e sc
reen
ing
pol
icy.
►
Ref
erra
l to
ches
t cl
inic
af
ter
dis
char
ge fr
om
hosp
ital.
►
Trea
tmen
t no
t co
mp
ulso
ry.
►
Info
rmat
ion
abou
t d
isea
se
and
tre
atm
ent
give
n to
im
pro
ve c
omp
lianc
e.
►P
sych
osoc
ial s
upp
ort.
►
Free
TB
tre
atm
ent,
tr
ansp
ort
and
bre
akfa
st.
Bef
ore–
afte
r st
udy.
Iden
tified
TB
ca
ses
and
tr
eatm
ent
com
plia
nce.
−
G
oets
ch20
(201
2),
G
erm
any
Hom
eles
s p
eop
le a
nd d
rug
user
s.
To e
stim
ate
the
cove
rage
of
a lo
w-t
hres
hold
CX
R
scre
enin
g p
rogr
amm
e fo
r p
ulm
onar
y TB
am
ong
illic
it d
rug
user
s an
d
hom
eles
s p
erso
ns.
CH
Ws
pro
vid
ing
TB
educ
atio
n an
d p
rom
otin
g vo
lunt
ary
CX
R s
cree
ning
1–
2×/y
ear.
Com
par
ing
the
beg
inni
ng o
f th
e 5-
year
inte
rven
tion
per
iod
w
ith t
he e
nd (2
002–
2007
).
Ret
rosp
ectiv
e ef
fect
iven
ess
stud
y.S
cree
ning
co
vera
ge.
−
O
spin
a21 (2
012)
,
Sp
ain
Mig
rant
s.To
eva
luat
e th
e ef
fect
iven
ess
of a
n in
terv
entio
n w
ith C
HW
s to
imp
rove
con
tact
tr
acin
g am
ong
mig
rant
s.
CH
Ws
activ
e fo
llow
-up
of
cas
es a
nd c
onta
cts,
in
clud
ing
visi
ts o
f the
cas
es
at h
ome,
acc
omp
anyi
ng a
t ou
tpat
ient
ap
poi
ntm
ents
, p
rovi
din
g co
unse
lling
and
in
form
atio
n on
tre
atm
ents
(2
003–
2005
).
Pre
inte
rven
tion
per
iod
(200
0–20
02).
Bef
ore–
afte
r st
udy.
Num
ber
of
mig
rant
s w
ho
wer
e in
clud
ed in
co
ntac
t tr
acin
g.
+
Con
tinue
d
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Firs
t au
tho
r (y
ear)
, co
untr
yP
op
ulat
ion
Aim
sIn
terv
enti
on
Co
mp
arat
or
Stu
dy
des
ign
Out
com
e m
easu
reQ
ualit
y sc
ore
A
ldrid
ge19
(201
5),
U
KH
omel
ess
peo
ple
.To
com
par
e TB
scr
eeni
ng
upta
ke b
etw
een
curr
ent
pra
ctic
e of
en
cour
agin
g ho
mel
ess
peo
ple
by
shel
ter
staf
f an
d e
ncou
rage
men
t b
y sh
elte
r st
aff p
lus
volu
ntee
r p
eer
educ
ator
s.
Enc
oura
gem
ent
of T
B
scre
enin
g b
y p
eers
in
add
ition
to
shel
ter
staf
f.
Enc
oura
gem
ent
of T
B
scre
enin
g b
y sh
elte
r st
aff
only
.
Clu
ster
RC
T.S
cree
ning
up
take
.+
TB id
entifi
catio
n (s
tud
ies
iden
tified
by
the
pre
viou
s N
ICE
rev
iew
15)
E
l-H
amad
24 (2
001)
,
Italy
Mig
rant
sTo
com
par
e th
e co
mp
letio
n ra
tes
of
scre
enin
g p
roce
dur
es
for
TB in
fect
ion
amon
g un
doc
umen
ted
mig
rant
s at
sp
ecia
lised
TB
uni
ts
and
non
-sp
ecia
lised
he
alth
clin
ics.
TB s
cree
ning
at
spec
ialis
ed
TB c
linic
.TB
scr
eeni
ng a
t a
gene
ral
heal
th s
ervi
ce fo
r m
igra
nts.
Pro
spec
tive
coho
rt.
Scr
eeni
ng
com
ple
tion.
+
B
otha
mle
y25 (2
002)
,
UK
Mig
rant
s an
d
hom
eles
s p
eop
le.
To c
omp
are
the
yiel
d a
nd
cost
s of
TB
scr
eeni
ng
in t
hree
set
tings
: a n
ew
entr
ants
’ clin
ic w
ithin
th
e P
OA
sch
eme;
a la
rge
gene
ral p
ract
ice;
and
ce
ntre
s fo
r th
e ho
mel
ess.
TB s
cree
ning
at
a G
P.TB
scr
eeni
ng a
t P
OA
and
at
hom
eles
s ce
ntre
s.C
ost
anal
ysis
.C
ost
per
per
son
scre
ened
per
ca
se o
f TB
p
reve
nted
.
−
D
erua
z28 (2
004)
,
Sw
itzer
land
Mig
rant
s, a
lcoh
ol
or d
rug
user
s,
hom
eles
s p
eop
le
and
pris
oner
s.
Eva
luat
ion
of fi
rst
exp
erie
nce
of t
he D
OT
pro
gram
me
for
TB
intr
oduc
ed in
the
Can
ton
of V
aud
in 1
997.
1. F
ull D
OT.
2. D
OT
del
iver
ed a
t TB
cl
inic
.
1. P
artia
l DO
T (D
OT
only
firs
t 2
mon
ths
of t
reat
men
t).2.
DO
T d
eliv
ered
at
soci
al
outr
each
site
.
Bef
ore–
afte
r st
udy.
Ad
here
nce
to
trea
tmen
t an
d
outc
ome.
−
M
iller
26 (2
006)
,
US
AH
omel
ess
peo
ple
and
p
rison
ers.
To e
valu
ate
and
com
par
e th
e ef
ficie
ncy
of a
non
-st
ate-
law
-man
dat
ed T
B
scre
enin
g p
rogr
amm
e fo
r ho
mel
ess
per
sons
with
a
stat
e-la
w-m
and
ated
TB
sc
reen
ing
pro
gram
me
for
pris
oner
s.
Non
-sta
te-l
aw-m
and
ated
TB
scr
eeni
ng p
rogr
amm
e fo
r ho
mel
ess
per
sons
.
Sta
te-l
aw-m
and
ated
TB
sc
reen
ing
pro
gram
me
for
pris
oner
s.
Ret
rosp
ectiv
e co
mp
aris
on o
f the
co
st a
nd h
ealth
im
pac
ts.
TB c
ases
av
erte
d a
nd
cost
.
+
R
icks
23 (2
008)
,
US
AD
rug
user
s.To
com
par
e th
e ef
fect
iven
ess
of u
sing
p
eers
ver
sus
‘sta
ndar
d’
pub
lic h
ealth
wor
kers
to
coor
din
ate
TB t
reat
men
t.
Enh
ance
d c
ase
man
agem
ent
by
pee
rs.
Lim
ited
cas
e m
anag
emen
t b
y he
alth
care
pro
fess
iona
ls.
RC
T.A
dhe
renc
e to
tr
eatm
ent.
++
Tab
le 1
C
ontin
ued
Con
tinue
d
on Novem
ber 2, 2020 by guest. Protected by copyright.
http://bmjopen.bm
j.com/
BM
J Open: first published as 10.1136/bm
jopen-2017-019642 on 8 Septem
ber 2018. Dow
nloaded from
7Heuvelings CC, et al. BMJ Open 2018;8:e019642. doi:10.1136/bmjopen-2017-019642
Open access
Three studies19–21 compared the effect of the type of healthcare worker on TB identification.
In the UK, a cluster randomised trial found that peer educators working together with shelter staff to encourage homeless people to participate in a TB screening programme using mobile X-ray units did not improve screening uptake compared with encourage-ment by shelter staff only (respectively 40%, IQR 25–61 vs 45%, IQR 33–55; adjusted risk ratio 0.98, 95% CI 0.80 to 1.20).19 Control sites were not ‘naïve’ for peer inter-vention, which could have caused contamination of the control sites and contributed to the negative finding.
In Germany, introduction of TB education and promo-tion of voluntary chest X-ray screening at least once every 2 years by community health workers (CHWs) improved screening uptake in homeless people and drug users. Annual screening coverage increased from 10.0% at the beginning of the study period (2002–2004) to 15.0% during the middle part of the study period (2004–2006); the last part of the study period had a 13.4% annual screening coverage (2005–2007). Screening once every 2 years increased screening coverage from 18.0% (2002–2004) to 26.4% (2004–2006). Coverage was 23.4% at the third and final study period (spanning 2005–2007).20 The authors did not test for statistical significance, and denominator data (the number of homeless people and drug users in the study area) were estimated.
In Barcelona, Spain, contact tracing organised by CHWs coming from the same migrant community as the person diagnosed with TB improved contact tracing among migrants to 66.2% (2003–2005) compared with 55.4% (2000–2002) in the period before the implementa-tion of the intervention using CHWs (adjusted OR of an index case having their contacts screened before and after the intervention was 1.8, 95% CI 1.3 to 2.5, p<0.001).21 Identification and tracing of at least one contact was taken as appropriate contact tracing, where all contacts at risk should be traced to detect and treat TB transmis-sion early. The population characteristics varied, and the age and country of origin were different between both periods. The importance of contact tracing is to identify cases early to reduce transmission; the authors did not report if any of the contacts traced had active TB.
Two studies11 22 evaluated the effect of the type of healthcare worker and the setting on TB identification and TB management.
In Portugal, improved cooperation of ‘key partners’ (street teams, TB clinics, drug user support centres, local public health department and local hospital) for TB iden-tification and management in drug users was evaluated in a before-and-after study. Representatives of all ‘key partners’ (authors’ term) worked on improving policies, clinic screening procedures and cooperation. Key part-ners were trained in identifying drug users in their popu-lation, and offering health promotion, notification cards, free transport to the TB clinic, free medical and substance abuse care, directly observed therapy (DOT) for active TB cases, identification of non-compliant patients and Fi
rst
auth
or
(yea
r),
coun
try
Po
pul
atio
nA
ims
Inte
rven
tio
nC
om
par
ato
rS
tud
y d
esig
nO
utco
me
mea
sure
Qua
lity
sco
re
M
or27
(200
8),
Is
rael
Mig
rant
s.To
exa
min
e th
e ef
fect
iven
ess
and
co
st-e
ffect
iven
ess
of
pre
mig
ratio
n sc
reen
ing
and
pos
tmig
ratio
n sc
reen
ing
at P
OA
.
Pre
mig
ratio
n sc
reen
ing.
Pos
tmig
ratio
n sc
reen
ing.
Ret
rosp
ectiv
e co
hort
an
alys
is.
Act
ive
TB c
ases
, tim
e b
etw
een
mig
ratio
n an
d
dia
gnos
is, a
nd
cost
-sav
ings
.
−
Stu
dy
qua
lity:
hig
h q
ualit
y [+
+],
med
ium
qua
lity
[+] o
r lo
w q
ualit
y [−
].C
HW
s, c
omm
unity
hea
lth w
orke
rs; C
XR
, che
st X
-ray
; DO
T, d
irect
ob
serv
ed t
reat
men
t; G
P, g
ener
al p
ract
ice;
MX
U, m
obile
X-r
ay u
nit;
n, n
umb
er o
f par
ticip
ants
; PO
A, p
ort o
f arr
ival
; R
CT,
ran
dom
ised
con
trol
led
tria
l; TB
, tub
ercu
losi
s.
Tab
le 1
C
ontin
ued
on Novem
ber 2, 2020 by guest. Protected by copyright.
http://bmjopen.bm
j.com/
BM
J Open: first published as 10.1136/bm
jopen-2017-019642 on 8 Septem
ber 2018. Dow
nloaded from
8 Heuvelings CC, et al. BMJ Open 2018;8:e019642. doi:10.1136/bmjopen-2017-019642
Open access
Tab
le 2
E
ffect
iven
ess
of s
ervi
ce m
odel
s an
d o
rgan
isat
iona
l str
uctu
res
inte
rven
tions
to
imp
rove
TB
iden
tifica
tion
and
TB
man
agem
ent
Po
pul
atio
nIn
terv
enti
on
(I)C
om
par
ato
r (C
)
Stu
die
s (fi
rst
auth
or,
year
, co
untr
y)
No
. of
par
tici
pan
ts
Co
mp
aris
on
Out
com
eR
isk
of
bia
sI
C
Hom
eles
s p
eop
leH
ealth
/TB
ed
ucat
ion
an
d p
rom
otio
n of
scr
eeni
ng
by
stre
et t
eam
s,
dru
g us
ers
sup
por
t ce
ntre
s,
shel
ters
and
C
HW
s.
Beg
inni
ng o
f the
in
terv
entio
n w
hen
CH
Ws
wer
e ju
st
intr
oduc
ed.
Goe
tsch
,20 2
012,
G
erm
any.
465
125
Ret
rosp
ectiv
e co
mp
aris
on
over
in
terv
entio
n p
erio
d.
Imp
rove
d a
nnua
l TB
scr
eeni
ng u
pta
ke a
mon
g ho
mel
ess
peo
ple
and
dru
g us
ers
(from
10.
0%
to 1
5.0%
at
the
pea
k).20
The
per
cent
age
of a
ll d
rug
user
s w
ith a
ctiv
e TB
iden
tified
by
scre
enin
g in
crea
sed
from
13.
4% t
o 61
.0%
(OR
10.
1 (9
5%C
I 4.
44 t
o 23
.0)).
11
Hig
h*
Dru
g us
ers
No
activ
e sc
reen
ing
pol
icy.
D
uart
e,11
201
1,
Por
tuga
l. R
etro
spec
tive
bef
ore–
afte
r co
mp
aris
on.
Hig
h†
Hom
eles
s p
eop
leTB
ed
ucat
ion
and
pro
mot
ion
of s
cree
ning
b
y p
eers
and
sh
elte
r st
aff.
TB e
duc
atio
n an
d p
rom
otio
n of
sc
reen
ing
by
shel
ter
staf
f onl
y.
Ald
ridge
,19
2015
, UK
.11
5011
92C
omp
arin
g ra
ndom
ised
in
terv
entio
n cl
uste
r
with
co
mp
arat
or
clus
ter.
No
diff
eren
ce in
scr
eeni
ng u
pta
ke (I
=40
% (I
QR
25–
61) v
ersu
s C
=45
% (I
QR
33–
55),
aRR
=0.
98 (9
5% C
I 0.
80 t
o 1.
20)).
Med
ium
‡
Mig
rant
sP
rem
igra
tion
scre
enin
gP
ostm
igra
tion
scre
enin
g at
PO
A.
Mor
,27 2
008,
cite
d
in t
he N
ICE
rev
iew
, Is
rael
.
162
105
Ret
rosp
ectiv
e In
terv
entio
n ve
rsus
co
mp
arat
or
com
par
ison
.
Red
uced
the
ris
k of
dev
elop
ing
TB in
the
new
co
untr
y an
d w
as c
ost-
effe
ctiv
e (0
.28%
of t
he
pre
mig
ratio
n ve
rsus
0.3
2% o
f the
pos
tmig
ratio
n sc
reen
ing
mig
rant
s d
evel
oped
TB
; RR
0.8
2,
p<
0.01
). Th
e d
etec
tion
per
iod
was
sho
rter
as
wel
l (19
3 d
ays
vs 4
87 d
ays
bet
wee
n en
try
an
d d
iagn
osis
; OR
=0.
72 (9
5% C
I 0.5
9 to
0.8
9)
p=
0.00
2).
Hig
h§
Pris
oner
s an
d
hom
eles
s p
eop
le
TB s
cree
ning
in
a p
rison
.TB
scr
eeni
ng a
t a
hom
eles
s ce
ntre
.M
iller
,26 2
006,
cite
d
in t
he N
ICE
rev
iew
, U
SA
.
22 9
2082
2R
etro
spec
tive
com
par
ison
of
tw
o co
hort
s.
No
diff
eren
ce in
scr
eeni
ng u
pta
ke (9
4.7%
in p
rison
vs
95%
in h
omel
ess
cent
re p
=0.
179)
but
hig
her
pro
por
tion
of a
ctiv
e TB
cas
es w
ere
iden
tified
at
the
hom
eles
s ce
ntre
(1.2
% v
s 0.
03%
at
a p
rison
set
ting,
p
<0.
001)
.
Med
ium
¶
Hom
eles
s p
eop
le a
nd
mig
rant
s
Act
ive
case
fin
din
g b
y sy
mp
tom
-bas
ed
que
stio
nnai
re
at h
omel
ess
cent
res.
Act
ive
case
find
ing
by
sym
pto
m-b
ased
q
uest
ionn
aire
at
PO
A.
Bot
ham
ley,
25 2
002,
ci
ted
in t
he N
ICE
re
view
, UK
.
262
199
Cos
t ana
lysi
s.A
ctiv
e ca
se fi
ndin
g at
PO
A w
as m
ost
cost
-effe
ctiv
e (c
osts
per
per
son
scre
ened
for
ever
y ca
se p
reve
nted
at
PO
A £
10.0
0, a
t ho
mel
ess
cent
re £
23.0
0).
Hig
h**
Con
tinue
d
on Novem
ber 2, 2020 by guest. Protected by copyright.
http://bmjopen.bm
j.com/
BM
J Open: first published as 10.1136/bm
jopen-2017-019642 on 8 Septem
ber 2018. Dow
nloaded from
9Heuvelings CC, et al. BMJ Open 2018;8:e019642. doi:10.1136/bmjopen-2017-019642
Open access
Po
pul
atio
nIn
terv
enti
on
(I)C
om
par
ato
r (C
)
Stu
die
s (fi
rst
auth
or,
year
, co
untr
y)
No
. of
par
tici
pan
ts
Co
mp
aris
on
Out
com
eR
isk
of
bia
sI
C
Mig
rant
sA
ctiv
e ca
se
find
ing
at a
sp
ecia
lised
TB
cl
inic
usi
ng t
wo
visi
ts.
Act
ive
case
find
ing
at
a g
ener
al
prim
ary
care
clin
ic,
with
ref
erra
l for
CX
R,
usin
g th
ree
vi
sits
.
El-
Ham
ad,24
200
1,
cite
d in
the
NIC
E
revi
ew, I
taly
.
749
483
Pro
spec
tive
inte
rven
tion
vers
us
com
par
ator
co
mp
aris
on.
Imp
rove
d s
cree
ning
com
ple
tion
amon
g m
igra
nts
(85.
6% in
TB
clin
ic v
s 71
.4%
at
prim
ary
care
clin
ic,
p=
not r
epor
ted
; OR
=2.
57 (9
5% C
I 1.9
2 to
3.4
2)).
Med
ium
††
Dru
g us
ers
Con
tact
tra
cing
b
y p
eers
or
CH
Ws
from
the
sa
me
mig
rant
co
mm
unity
.
Pee
rs v
ersu
s ot
her
heal
thca
re w
orke
rs.
Ric
ks,23
200
8,
cite
d in
the
NIC
E
revi
ew, U
SA
.48
46R
CT
Imp
rove
d c
onta
ct t
raci
ng a
mon
g d
rug
user
s
(75%
by
pee
rs v
s 47
% b
y he
alth
care
wor
kers
, p
=0.
03)23
and
mig
rant
s (fr
om 5
5.4%
with
out
CH
Ws
to 6
6.2%
with
CH
Ws;
aO
R 1
.8 (9
5% C
I 1.3
to
2.5)
p<
0.00
1).21
Low
Mig
rant
s N
orm
al p
ract
ice
bef
ore
intr
oduc
ing
CH
Ws.
Osp
ina,
21 2
012,
Sp
ain.
388
572
Bef
ore–
afte
r co
mp
aris
on.
Med
ium
‡‡
Dru
g us
ers
and
ho
mel
ess
peo
ple
Mob
ile T
B
scre
enin
g an
d t
reat
men
t se
rvic
e at
co
nven
ient
lo
catio
n in
the
co
mm
unity
.
Pas
sive
cas
e d
etec
tion
and
m
anag
emen
t at
a T
B
clin
ic.
Jit,
22 2
011,
UK
.48
252
Pro
spec
tive
inte
rven
tion
vers
us
com
par
ator
co
mp
aris
on
plu
s ec
onom
ic
eval
uatio
n.
Imp
rove
d T
B id
entifi
catio
n am
ong
hom
eles
s p
eop
le
and
dru
g us
ers;
par
ticul
arly
in a
sym
pto
mat
ic p
atie
nts
(35.
4% e
xtra
iden
tified
) and
tho
se w
ho d
elay
see
king
he
alth
care
(22.
2% e
xtra
iden
tified
). H
ighe
r tr
eatm
ent
com
ple
tion
rate
(67.
1% v
s 56
.8%
) and
low
er
lost
to
follo
w-u
p r
ate
(2.1
% v
s 17
.2%
). B
oth
par
ts o
f th
e se
rvic
e ar
e co
st-e
ffect
ive
(scr
eeni
ng=
£1
8 00
0/Q
ALY
gai
ned
, tre
atm
ent
is £
4100
/QA
LY
gain
ed).
Med
ium
§§
Dru
g us
ers
Enh
ance
d c
ase
man
agem
ent
by
pee
rs.
Lim
ited
cas
e m
anag
emen
t
by
regu
lar
he
alth
care
w
orke
rs.
Ric
ks,23
200
8,
cite
d in
the
NIC
E
revi
ew, U
SA
.
4846
RC
TIm
pro
ved
tre
atm
ent
com
ple
tion
in d
rug
user
s (8
5%
by
pee
rs v
s 61
% b
y he
alth
care
wor
kers
, RR
=2.
68
(95%
CI 1
.24
to 5
.82)
p=
0.01
).
Low
Dru
g us
ers
DO
T an
d a
ctiv
e fo
llow
-up
of
non-
com
plia
nt
pat
ient
s b
y ‘k
ey
par
tner
s’.
Non
-com
pul
sory
TB
tre
atm
ent
and
ed
ucat
ion
ab
out
TB d
isea
se
and
tre
atm
ent
to
imp
rove
co
mp
lianc
e.
Dua
rte,
11
2011
, Por
tuga
l.46
512
5R
etro
spec
tive
bef
ore–
afte
r co
mp
aris
on.
Red
uced
tre
atm
ent
def
ault
rate
s (fr
om 3
5.4%
to
10.2
%; O
R 0
.21
(95%
CI 0
.08
to 0
.54)
).H
igh*
*
Tab
le 2
C
ontin
ued
Con
tinue
d
on Novem
ber 2, 2020 by guest. Protected by copyright.
http://bmjopen.bm
j.com/
BM
J Open: first published as 10.1136/bm
jopen-2017-019642 on 8 Septem
ber 2018. Dow
nloaded from
10 Heuvelings CC, et al. BMJ Open 2018;8:e019642. doi:10.1136/bmjopen-2017-019642
Open access
Po
pul
atio
nIn
terv
enti
on
(I)C
om
par
ato
r (C
)
Stu
die
s (fi
rst
auth
or,
year
, co
untr
y)
No
. of
par
tici
pan
ts
Co
mp
aris
on
Out
com
eR
isk
of
bia
sI
C
Mig
rant
s,
dru
g us
ers,
ho
mel
ess
peo
ple
an
d
pris
oner
s
DO
T at
a
conv
enie
nt
loca
tion
in t
he
com
mun
ity.
DO
T at
a h
ealth
clin
ic.
Dèr
uaz,2
8 200
4,
cite
d in
the
NIC
E
revi
ew, S
witz
erla
nd.
3618
Ret
rosp
ectiv
e b
efor
e–af
ter
com
par
ison
.
No
sign
ifica
nt d
iffer
ence
in s
ucce
ssfu
l tre
atm
ent
outc
ome,
tre
atm
ent
com
ple
tion
and
cur
e ra
te (8
5.2%
at
con
veni
ent
loca
tion
vs 9
2.6%
at
heal
th c
linic
, p
=0.
67).
Hig
h¶¶
Foot
note
s ris
k of
bia
s:*N
ot a
dju
sted
for
imp
orta
nt c
onfo
und
ing
fact
ors
(inte
rven
tion
and
com
par
ator
gro
up w
ere
recr
uite
d o
ver
diff
eren
t tim
e p
erio
ds)
. Den
omin
ator
not
giv
en t
here
fore
una
ble
to
calc
ulat
e sc
reen
ing
cove
rage
.†R
isk
of s
elec
tion
bia
s as
par
ticip
atio
n w
as v
olun
tary
. Not
ad
just
ed fo
r im
por
tant
con
foun
din
g fa
ctor
s (in
terv
entio
n an
d c
omp
arat
or g
roup
wer
e re
crui
ted
ove
r d
iffer
ent
time
per
iod
s). N
o st
atis
tical
tes
t us
ed t
o sh
ow s
tatis
tical
sig
nific
ance
of t
he fi
ndin
gs; a
n es
timat
ed n
umb
er w
as u
sed
for
the
den
omin
ator
.‡M
ost
com
par
ator
site
s w
ere
not
naïv
e fo
r p
eer
inte
rven
tion,
no
ind
ivid
ual i
nfor
mat
ion
of t
he p
artic
ipan
ts w
as c
olle
cted
and
the
cha
ract
eris
tics
bet
wee
n th
e tw
o gr
oup
s m
ight
hav
e b
een
sign
ifica
ntly
diff
eren
t.§N
ot a
dju
sted
for
imp
orta
nt c
onfo
und
ing
fact
ors
(inte
rven
tion
and
com
par
ator
gro
up w
ere
recr
uite
d o
ver
diff
eren
t tim
e p
erio
ds)
, pre
mig
ratio
n gr
oup
had
a s
hort
er fo
llow
-up
per
iod
tha
n p
ostm
igra
tion
grou
p w
hat
may
hav
e in
fluen
ced
the
det
ectio
n of
num
ber
of T
B c
ases
in t
he p
rem
igra
tion
grou
p.
¶U
ncle
ar if
the
diff
eren
ces
in o
utco
me
was
cau
sed
by
the
sett
ing
or b
y th
e d
iffer
ent
met
hod
s or
to
diff
eren
ces
in T
B p
reva
lenc
e in
the
diff
eren
t p
opul
atio
ns.
**TB
pre
vale
nce
mig
ht b
e d
iffer
ent
in t
he d
iffer
ent
pop
ulat
ions
as
the
cost
s ar
e ca
lcul
ated
per
act
ive
case
det
ecte
d t
his
is a
maj
or is
sue,
the
re w
ere
only
thr
ee a
ctiv
e TB
cas
es d
etec
ted
, all
in
the
PO
A g
roup
. The
eco
nom
ic p
ersp
ectiv
e us
ed w
as n
ot r
epor
ted
, and
the
cos
ts o
f id
entifi
catio
n w
ere
not
dis
coun
ted
.††
Not
ad
just
ed fo
r d
iffer
ence
in b
asel
ine
char
acte
ristic
s.‡‡
Not
ad
just
ed fo
r im
por
tant
con
foun
din
g fa
ctor
s (in
terv
entio
n an
d c
omp
arat
or g
roup
wer
e re
crui
ted
ove
r d
iffer
ent
time
per
iod
s). C
onta
ct t
raci
ng o
f onl
y on
e co
ntac
t w
as e
noug
h to
be
calle
d
cont
act
trac
ing,
and
the
ulti
mat
e ai
m o
f con
tact
tra
cing
(inc
reas
e ca
sed
det
ectio
n an
d r
educ
e tr
ansm
issi
on) w
as n
ot a
naly
sed
in t
his
stud
y.§§
Stu
dy
was
des
igne
d t
o ev
alua
te t
he c
ost-
effe
ctiv
enes
s, n
o st
atis
tical
tes
t us
ed t
o ev
alua
te s
tatis
tical
sig
nific
ant
find
ings
. The
‘Fin
d a
nd T
reat
’ ser
vice
iden
tifies
ext
rem
ely
hard
-to-
reac
h p
opul
atio
ns t
hat
wou
ld n
ever
sel
f-p
rese
nt, a
nd t
he fi
ndin
gs w
ould
und
eres
timat
e th
e b
enefi
t of
the
ser
vice
. The
eco
nom
ical
eva
luat
ion
is b
ased
on
a co
mp
artm
enta
l mod
el t
hat
doe
s no
t ta
ke
seco
ndar
y tr
ansm
issi
on a
nd d
rug
resi
stan
ce in
to a
ccou
nt.
¶¶
Ris
k of
bia
s d
ue t
o d
iffer
ence
in c
olle
ctin
g tr
eatm
ent
adhe
renc
e ou
tcom
e at
the
hea
lth c
linic
a n
urse
rec
ord
ed t
reat
men
t ad
here
nce
at t
ime
of v
isit,
in t
he s
ocia
l out
reac
h gr
oup
a h
ealth
care
w
orke
r w
as in
terv
iew
ed u
p t
o 6
mon
ths
afte
r tr
eatm
ent
com
ple
tion
and
was
ask
ed a
bou
t th
e tr
eatm
ent
adhe
renc
e, r
isk
of r
ecal
l bia
s. N
ot r
ecor
ded
how
man
y p
eop
le p
er s
ettin
g re
ceiv
ed
6 m
onth
s of
DO
T (fu
ll D
OT)
and
how
man
y re
ceiv
ed 2
mon
ths
of D
OT
and
4 m
onth
s of
sel
f-tr
eatm
ent
(par
tial D
OT)
, wha
t w
as a
noth
er in
terv
entio
n in
thi
s st
udy.
Allo
catio
n to
set
ting
was
bas
ed
on n
eed
s of
par
ticip
ants
wha
t m
ight
hav
e ca
used
bia
s.aO
R, a
dju
sted
OR
s; a
RR
, ad
just
ed ri
sk r
atio
; CH
Ws,
com
mun
ity h
ealth
wor
kers
; CX
R, c
hest
X-r
ay; D
OT,
dire
ctly
ob
serv
ed t
reat
men
t; P
OA
, por
t of a
rriv
al; Q
ALY
s, q
ualit
y-ad
just
ed li
fe y
ears
; R
CT,
ran
dom
ised
con
trol
led
tria
l; TB
, tub
ercu
losi
s.
Tab
le 2
C
ontin
ued
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the cause of non-compliance and tailor-made strategies to improve compliance. This resulted in an increase of TB screening uptake, from 52 drug users being screened before the intervention (2001–2003 when there was no active screening policy) to 465 drug users screened thereafter (2005–2007). Of all people misusing drugs taking up screening, the proportion without TB symptoms increased from 41.6% to 93.5% (OR=21.76; 95% CI 13.03 to 36.33) indicating improved TB awareness and access to screening facilities for drug users. Of all drug users with active TB, the proportion identified by screening increased from 13.4% to 61.0% (OR 10·1; 95% CI 4.44 to 23.0). Treatment default rates decreased from 35.4% to 10.2% (OR 0.21, 95% CI 0.08 to 0.54), compared with the period before the intervention (2001–2003) when TB treatment was not compulsory and compliance was stimulated by TB education and providing information on the importance of treatment completion.11 Although the absolute number of drug users screened increased, information on the screening coverage was not available as denominator data were not provided. Another limita-tion is that the results were not adjusted for confounding factors, baseline characteristics might have been different as the two cohorts were recruited over different time periods and participation was voluntary which may have led to selection bias.
In the UK, the effectiveness and cost-effectiveness of the ‘Find and Treat’ service (raising awareness of TB screening and providing a mobile TB screening and treatment service) for homeless people and drug users was evaluated and compared with people (with a history of homelessness, imprisonment, drug abuse or mental health problems) self-presenting to a London TB clinic receiving standard TB care at the clinic.22 The authors estimated that 22.9% of the patients detected by the ‘Find and Treat’ service with the longest first symptom-to-detec-tion time would not have self-presented plus 35.4% were asymptomatic at time of detection and would not have self-presented, only part of the asymptomatic patients would self-present to a TB clinic at a later stage when symptoms would have developed. The ‘Find and Treat’ service had a higher treatment completion rate (67.1% vs 56.8%) and a lower lost to follow-up rate (2.1% vs 17.2%) compared with the control group receiving stan-dard TB care at a TB clinic. The authors concluded that the ‘Find and Treat’ service was cost-effective when using the threshold used by NICE of £20 000 to £30 000/QALY gained, with an incremental cost ratio of £18 000 per QALY gained for the TB screening service and £4100 per QALY gained for the TB management service. This study has a few limitations: first, it is a non-randomised study, second, the ‘Find and Treat’ service identifies extremely hard-to-reach populations of which some would never self-present, therefore the findings could be even better in less hard-to-reach populations, and third, the econom-ical evaluation is based on a compartmental model that does not take secondary transmission and drug resistance into account.
DIsCussIOnTo tackle TB and disrupt transmission in high-income, low TB incidence settings, improvement of TB care in hard-to-reach populations is of vital importance. In this updated review, five studies,11 19–22 published between 1 January 2010 and 24 February 2017, evaluating effec-tiveness of services models and organisational structures supporting TB identification and management of hard-to-reach populations, were identified in addition to the six studies considering active TB23–28 identified by the NICE review.15 Only one study22 evaluated cost-effective-ness. Although the evidence from two reviews is limited, it highlights those interventions that are likely to be effec-tive and those that have no clear evidence of being effec-tive (table 2). For development of the ECDC guidance document,14 a scientific panel compiled by ECDC care-fully considered these findings. Their main suggestions for action were to involve CHWs or peers to improve TB screening uptake and TB treatment completion among homeless people20 and drug users5 20 23; to use outreach teams to improve TB screening uptake and TB treatment completion among vulnerable populations22; and to strengthen relationships and good collaboration between healthcare workers, peers, communities and patients to improve treatment outcome among vulnerable popu-lations.5 20 22 23 The updated systematic review provided evidence for all suggestions except for using peers to improve screening uptake. This is in contrast to an Amer-ican study23 included in the original NICE review,15 which showed that peers improved contact tracing and treat-ment adherence among drug users.
strengths and limitationsPRISMA and Cochrane Collaboration reporting guide-lines for systematic reviews were followed. Established screening protocols were used, including double screening, and the search was highly sensitive. The meth-odology from the previous NICE review15 was followed, in order to connect this update and, so, describe the full body of relevant evidence. High-quality evidence is lacking. Only one23 study from the NICE review15 was considered to be of high quality; all other studies had some risk of bias (five medium risk19 21 22 24 26 and five high risk11 20 25 27 28). Therefore, only limited conclusions can be drawn. Most studies lacked identification and adjustment for confounding factors and the use of appro-priate analytical methods. In addition, many studies were biased, particularly with regard to potential selection bias. A meta-analysis could not be performed because of heterogeneity across the studies. Gaps in evidence exist; no studies focusing on children within vulnerable and hard-to-reach populations or on people living with HIV or sex workers were identified. Only three studies provided economic data; one study identified by this review22 and two studies25 27 by the NICE review.15
Our search focused on publications in databases Embase and MEDLINE. Many European countries have strong organisational structures for TB identification and
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management, but these countries did not publish their data on these organisational structures in journals, which may have caused a publication bias. Comparing findings of the NICE review15 with this review comes with some limitations. For the NICE review, only 10% of the citations were double screened,15compared with 100% for this updated review; therefore, studies conducted between 1990 and 2010 might have been missed. The NICE review focused their recommendations on the population in the UK,15 and this review focused on populations in high-in-come, low TB incidence countries. Further methodology was identical.
The evidence identified by this review and the previous NICE review15 along with evidence presented in a review series covering the barriers and facilitators of seeking TB care,6 and the effectiveness of interventions for TB identi-fication and management in hard-to-reach populations,13 was used to develop the ECDC guidance on improving TB identification and management among hard-to-reach and vulnerable populations in Europe.14 ECDC recommended that implementation of the interven-tions is context specific; it depends on the setting, target population, resources available and healthcare systems in place. Interventions focusing on one specific hard-to-reach population might not work in another hard-to-reach population; therefore, the interventions have to be adapted and reassessed per target population.14 Given the scope of this review, considering settings across Europe, findings presented here are potentially relevant to any low incidence region and are relevant to other institu-tions/governmental organisations seeking to improve service structures for TB identification and management among hard-to-reach populations.
Characteristics of different hard-to-reach populations and their TB epidemiology vary per country and setting. Challenges in identification and management of TB should be identified and targeted, tailored to the specific setting and hard-to-reach population. These TB interven-tions could be integrated within broader programmes targeting specific populations. A follow-up systematic review should include information from national public health services about their organisational structures for TB identification and management. National public health services are urged to regularly analyse their organi-sational structures for TB identification and management and publish these data.
Efforts to improve quality of research on service models and organisational structures should be made, even though it is often challenging to perform ‘clean’, unbi-ased and unconfounded trials in hard-to-reach popula-tions, as attrition rates are often high, and confounding factors are plentiful. This includes conducting (cluster) RCTs and before-and-after studies where appropriate, recruiting an adequate number of participants, using relevant control groups and minimising selection bias. Standardised case definitions for hard-to-reach popu-lations should be created. Feasibility, effectiveness, cost-effectiveness and impact of interventions should be
evaluated. Mathematical economic models can be used to evaluate costs.14
COnClusIOnsIdentification and management of TB in hard-to-reach populations is suboptimal.2 Therefore, service models and organisational structures to identify and manage TB in hard-to-reach populations should be improved and evaluated regularly.
Our systematic review, in conjunction with the original NICE review,15 provides limited evidence, due to the lack of high-quality studies, that interventions such as using peers and CHWs, mobile TB services, specialised TB clinics, screening or active case finding in non-health-care settings, as well as improved cooperation between key services can help to improve TB identification and management.
Further research should be undertaken to evaluate other effective and cost-effective ways to identify and manage TB in hard-to-reach populations, and countries with good TB control systems are urged to evaluate their system and publish the data.
Author affiliations1Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, Center of Tropical Medicine and Travel Medicine, University of Amsterdam, Amsterdam, The Netherlands2Medical Library, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands3National Institute for Health and Care Excellence, Manchester, UK4Liverpool Reviews and Implementation Group, Health Services Research, University of Liverpool, Liverpool, UK5Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre at UCL Hospitals, London, UK6European Centre for Disease Prevention and Control, Stockholm, Sweden
Contributors CCH: created the protocol, performed study selection, collected the data, performed quality/risk of bias assessment, synthesised the data, interpreted the data and created the manuscript and supplementary files. PFG: performed the study selection, collected the data, performed quality/risk of bias assessment, synthesised the data, involved in interpretation of the data and contributed to and endorsed the final version of the manuscript. SGdV: created the protocol, performed study selection, involved in interpretation of the data and contributed to and endorsed the final version of the manuscript. BJV: created the protocol, involved in interpretation of the data and contributed to and endorsed the final version of the manuscript. SB, SJ, ALC and AS: involved in interpretation of the data and contributed to and endorsed the final version of the manuscript. RS: conducted the literature search, involved in interpretation of the data and contributed to and endorsed the final version of the manuscript. ES and RAH: expert input especially on the interpretation of the NICE findings, involved in interpretation of the data and contributed to and endorsed the final version of the manuscript. AZ: expert input, involved in interpretation of the data and contributed to and endorsed the final version of the manuscript. MJvdW: involved in the study design, data interpretation and contributed to and endorsed the final version of the manuscript. MPG: is the guarantor of this review, supervised every step in the process, commented and provided input at every stage of the review process, was involved in creating the protocol, interpretation of the data and contributed to and endorsed the final version of the manuscript.
Funding This study was funded by the European Centre for Disease Prevention and Control (contract reference OJ/02/05/2014-PROC/2014/014). None of the authors have received payment from a pharmaceutical company or other agency to write this article.
Disclaimer The funder of the study was involved in study design, data interpretation, and reporting. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication.
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Competing interests MPG reports grants from ECDC, for the conduct of part of the study. ES reports that NICE—her employing organisation—has published guidance in this area.
Patient consent Not required.
Ethics approval Ethics approval was not required for this systematic review.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data extraction forms and quality assessment forms are available from supplementary files V and VI.
Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/.
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