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.

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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.

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j.com/

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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

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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/.

rEFErEnCEs 1. World Health Organization (WHO). Global Tuberculosis report 2016.

Geneva: WHO, 2016. WHO/HTM/TB/2016.13. 2. World Health Organization (WHO) and European Respiratory Society.

Towards TB elimination: an action framework for low-incidence countries. Geneva: WHO, 2014. WHO/HTM/TB/2014.13.

3. de Vries G, Aldridge RW, Cayla JA, et al. Epidemiology of tuberculosis in big cities of the European Union and European Economic Area countries. Euro Surveill 2014;19.

4. de Vries SG, Cremers AL, Heuvelings CC, et al. Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature. Lancet Infect Dis 2017;17:e128–43.

5. Kamholz SL. Resurgence of tuberculosis: the perspective a dozen years later. J Assoc Acad Minor Phys 1996;7:83–6.

6. de Vries G, van Hest RA, Richardus JH. Impact of mobile radiographic screening on tuberculosis among drug users and homeless persons. Am J Respir Crit Care Med 2007;176:201–7.

7. van Hest NA, Aldridge RW, de Vries G, et al. Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement. Euro Surveill 2014;19.

8. Belling R, McLaren S, Boudioni M, et al. Pan-London tuberculosis services: a service evaluation. BMC Health Serv Res 2012;12:203.

9. Ohkado A, Williams G, Ishikawa N, et al. The management for tuberculosis control in Greater London in comparison with that in Osaka City: lessons for improvement of TB control management in Osaka City urban setting. Health Policy 2005;73:104–23.

10. Lei X, Liu Q, Escobar E, et al. Public-private mix for tuberculosis care and control: a systematic review. Int J Infect Dis 2015;34:20–32.

11. Duarte R, Santos A, Mota M, et al. Involving community partners in the management of tuberculosis among drug users. Public Health 2011;125:60–2.

12. Frieden TR, Fujiwara PI, Washko RM, et al. Tuberculosis in New York City--turning the tide. N Engl J Med 1995;333:229–33.

13. Heuvelings CC, de Vries SG, Greve PF, et al. Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review. Lancet Infect Dis 2017;17:e144–58.

14. European Centre for Disease Prevention and Control (ECDC). Guidance on tuberculosis control in vulnerable and hard-to-reach populations. Stockholm: ECDC, 2016.

15. Rizzo M, Martin A, Jamal F, et al. Evidence review on the effectiveness and cost-effectiveness of service models or structures to manage tuberculosis in hard-to-reach groups. London: Matrix evidence: NICE – National Institute for Health and Clinical Excellence, 2011.

16. Higgins J, Green S, eds. Cochrane handbook for systematic reviews of interventions version 5.1.0. London: The Cochrane Collaboration, 2011.

17. National Institute for Health and Clinical Excellence. Methods for the development of NICE public health guidance. 2nd edn. London: National Institute for Health and Clinical Excellence, 2009.

18. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.

19. Aldridge RW, Hayward AC, Hemming S, et al. Effectiveness of peer educators on the uptake of mobile X-ray tuberculosis screening at homeless hostels: a cluster randomised controlled trial. BMJ Open 2015;5:e008050.

20. Goetsch U, Bellinger OK, Buettel KL, et al. Tuberculosis among drug users and homeless persons: impact of voluntary X-ray investigation on active case finding. Infection 2012;40:389–95.

21. Ospina JE, Orcau A, Millet JP, et al. Community health workers improve contact tracing among immigrants with tuberculosis in Barcelona. BMC Public Health 2012;12:158.

22. Jit M, Stagg HR, Aldridge RW, et al. Dedicated outreach service for hard to reach patients with tuberculosis in London: observational study and economic evaluation. BMJ 2011;343:d5376.

23. Ricks PM. Tuberculosis control among substance users: the indigenous leadership outreach model vs. standard care. Chicago, IL: University of Illinois, 2008.

24. El-Hamad I, Casalini C, Matteelli A, et al. Screening for tuberculosis and latent tuberculosis infection among undocumented immigrants at an unspecialised health service unit. Int J Tuberc Lung Dis 2001;5:712–6.

25. Bothamley GH, Rowan JP, Griffiths CJ, et al. Screening for tuberculosis: the port of arrival scheme compared with screening in general practice and the homeless. Thorax 2002;57:45–9.

26. Miller TL, Hilsenrath P, Lykens K, et al. Using cost and health impacts to prioritize the targeted testing of tuberculosis in the United States. Ann Epidemiol 2006;16:305–12.

27. Mor Z, Lerman Y, Leventhal A. Pre-immigration screening process and pulmonary tuberculosis among Ethiopian migrants in Israel. Eur Respir J 2008;32:413–8.

28. Dèruaz J, Zellweger JP. Directly observed therapy for tuberculosis in a low prevalence region: first experience at the Tuberculosis Dispensary in Lausanne. Swiss Med Wkly 2004;134:552–8.

29. Popay J, Roberts H, Sowden A, et al. Guidance on the conduct of narrative synthesis in systematic reviews. A product from the ESRC methods programme. Lancaster, 2006.

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