Cross-country migration linked to people who inject drugs challenges the long-term impact of national HCV elimination programmes
Abstract
To the Editor: As of 2018, the majority of Western European countries – including Spain – have lifted restrictions to therapy based on disease severity in the context of HCV infections.1 Long overdue, most national elimination programmes now also include access to care for people who inject drugs (PWID), 2 who are at the core of ongoing HCV transmission.3 Macías et al.4 have recently shown in this Journal that high viral cure rates can be achieved in this group, hereby providing evidence that targeting PWID in treatment programmes is worthwhile. However, the extent to which such national efforts can reduce the HCV burden not only depends on the uptake into care and treatment success rates, it is also determined by the relative importance of within-country transmission and virus importation from elsewhere. As the chronic nature of most HCV infections hampers reliably reconstructing contact networks from patient interviews, virus genetic data can be a valuable alternative source of information for elucidating the geographic history of virus lineages (e.g. [5], [6]). Using such data, we have recently shown that for the most prevalent subtype among PWID in Spain (40%, 7), HCV1a, infections often link to infections abroad – in recent years >50% link to Western European countries, mostly European Union (EU) member states – as opposed to other infections ... Vrancken, B.; Cuypers, L.; Pérez, A.B.; Chueca, N.; Anton-Basantas, J.; de la Iglesia, A.; Fuentes, J.; Pineda, J.A.; Téllez, F.; Bernal, E.; Rincón, P.; Von Wichman, M.A.; Fuentes, A.; Vera, F.; Rivero-Juárez, A.; Jiménez, M.; Vandamme, A.M.; García, F.
Full text
C oss-coun y mig a ion linked o people who injec d ugs challenges
he long- e m impac o na ional HCV elimina ion p og ammes
To he Edi o :
As o 2018, he majo i y o Wes e n Eu opean coun ies –
including Spain – ha e li ed es ic ions o he apy based on
disease se e i y in he con ex o HCV in ec ions.
1
Long o e due,
mos na ional elimina ion p og ammes now also include access
o ca e o people who injec d ugs (PWID),
2
who a e a he co e
o ongoing HCV ansmission.
3
Macías e al.
4
ha e ecen ly
shown in his Jou nal ha high i al cu e a es can be achie ed
in his g oup, he eby p o iding e idence ha a ge ing PWID in
ea men p og ammes is wo hwhile. Howe e , he ex en o
which such na ional e o s can educe he HCV bu den no only
depends on he up ake in o ca e and ea men success a es, i
is also de e mined by he ela i e impo ance o wi hin-coun y
ansmission and i us impo a ion om elsewhe e.
As he ch onic na u e o mos HCV in ec ions hampe s eli-
ably econs uc ing con ac ne wo ks om pa ien in e iews,
i us gene ic da a can be a aluable al e na i e sou ce o in o -
ma ion o elucida ing he geog aphic his o y o i us lineages
(e.g. 5,6). Using such da a, we ha e ecen ly shown ha o
he mos p e alen sub ype among PWID in Spain (40%,
7
),
HCV1a, in ec ions o en link o in ec ions ab oad – in ecen
yea s >50% link o Wes e n Eu opean coun ies, mos ly Eu o-
pean Union (EU) membe s a es – as opposed o o he in ec ions
wi hin Spain.
8
Hence, educing HCV1a p e alence and sp ead
ac oss Eu ope will help o consolida e he impac o Spanish
e o s o educe he HCV bu den.
To in es iga e whe he his is a gene al pa e n ha also
holds o he second mos p e alen sub ype among PWID in
Spain (26.5%,
7
), HCV3a, we analysed newly gene a ed HCV3a
genome da a co e ing pa s o he NS5A and/o NS5B genes
om 196 HCV3a-in ec ed pa ien s sampled be ween Ap il
2014 and Ap il 2017 ac oss Spain (GenBank: accession numbe s
MN227780 - MN228016). O he 60% o whom in o ma ion on
he p obable ou e o ansmission was a ailable, 81.8%
epo ed injec ing d ug use. These sequences we e comple-
men ed wi h a backg ound da ase o publicly a ailable da a
om GenBank ( o alling 2752 axa), and analysed as p e iously
desc ibed.
5,8
The E hics Commi ee o he San Cecilio Hospi al,
G anada, app o ed he s udy, and no in o med consen was
equi ed as pa ien in o ma ion was anonymised and de-iden i-
ied p io o analysis.
As o HCV1a,
8
we ound ha he ansmission ne wo k size
s uc u e is no domina ed by a ew la ge exclusi ely Spanish
ansmission ne wo ks, meaning ha HCV3a ansmission ho
spo s in Spain mo e o en b idge o ne wo ks ab oad a he han
being connec ed domes ically. Whe eas we p e iously ound an
inc easing impo ance o Eu opean lineages in seeding he
HCV1a epidemic in Spain,
8
ou cu en econs uc ions showed
ha HCV3a i us mo emen s om wi hin he EU accoun o
~85% o all mig a ions owa ds Spain, wi h li le luc ua ion o e
ime. The numbe o impo ed HCV3a in ec ions pe yea om
o he EU membe s a es – which is a lowe bound es ima e –
has inc eased on a e age by 1 o 4 pe yea , o alling 125
(95% c edible in e al: 92–158) in oduc ions (Fig. 1). The end
and magni ude a e simila o hose o HCV1a, o which he
numbe o lineage in oduc ions o als 114 (95% c edible in e -
al: 72–156) (Fig. 1).
The Spanish na ional s a egy agains HCV is based on a com-
bina ion o ac o s, including a ocus on inc eased sc eening and
diagnosis, enhancing he ea men in as uc u e, he a ailabil-
i y o imp o ed he apeu ic egimens and a ge ing he g oups
a highes isk o ansmi ing HCV, including PWID.
9–11
Despi e
exis ing challenges and policy di e ences be ween egions, his
mul i ac o ial app oach has led o Spain being one o he ew
coun ies in Eu ope ha a e epo ed o be on ack o mee
he Wo ld Heal h O ganiza ion HCV elimina ion a ge s by
2030.
12
As mo e ecen sub ype 1a and 3a in ec ions a e associ-
a ed wi h illici (injec ing) d ug use (e.g. 3), a ge ing his g oup
ha d i es onwa ds sp ead, and o which Macías e al.
4
ha e
demons a ed ha ea men can be highly e ec i e, is mos
desi able in many coun ies. Howe e , ac oss Eu ope, mos
coun ies ha e ye o emb ace he uni e sal ea men pa a-
digm, and e en mo e a e ye o de elop and implemen a
na ional s a egy owa ds he elimina ion o HCV.
1
Ou cu en
and p e ious esul s
8
illus a e ha in he absence o he la e ,
HCV will apidly be e-seeded in he Spanish PWID popula ion,
challenging he long- e m impac o he cu en Spanish in e -
en ion e o s. This demons a es ha he e a e bene icial
scale-e ec s o implemen ing concu en na ional e o s in
he EU and elsewhe e, wi hou which he ul ima e goal, namely
elimina ing HCV, will likely emain elusi e.
Con lic o in e es
All au ho s ha e no hing o disclose, excep o Fede ico Ga cia,
Joaquin An on-Basan as and Miguel Angel Von Wichmann who
epo g an s and pe sonal ees om Vii Heal hca e, pe sonal
ees om Gilead, pe sonal ees om Abb ie and/o pe sonal ees
om MSD and/o pe sonal ees om Janssen, ou side he sub-
mi ed wo k; and Anne-Mieke Vandamme who epo s g an s
om he Resea ch Founda ion Flande s (FWO), du ing he con-
duc o he s udy (as decla ed in he acknowledgmen s sec ion).
Please e e o he accompanying ICMJE disclosu e o ms o
u he de ails.
Au ho s’ con ibu ions
B am V ancken and Lize Cuype s designed and de eloped he
phylogene ic analysis pipeline, pe o med he phylogeog aphic
analyses and w o e subsequen d a s o he manusc ip . Na alia
Chueca and Ana Belen Pé ez we e esponsible o pe o ming all
Jou nal o Hepa ology 2019 ol. xxx jxxx–xxx
Keywo ds: HCV; PWID; Elimina ion; Na ional s a egy; Spain; Eu opean Union.
JOURNAL
OF HEPATOLOGY
Le e o he Edi o
HCV sequencing expe imen s, and bo h assis ed in w i ing he
manusc ip . Joaquin An on-Basan as, Albe o de la Iglesia, Ja ie
Fuen es, Juan An onio Pineda, F ancisco Téllez, En ique Be nal,
Pila Rincón, Miguel Angel Von Wichman, Ana Fuen es, F an-
cisco Ve a, An onio Ri e o-Juá ez, Miguel Jiménez p o ided
samples om hei clinical cen e o be analysed wi hin his
s udy, and assis ed in w i ing he manusc ip . Anne-Mieke Van-
damme p o ided subs an ial suppo o he phylogene ic com-
pu a ions and assis ed ex ensi ely in w i ing he manusc ip .
Fede ico Ga cia supe ised he design o he analyses, he
sequencing expe imen s and assis ed ex ensi ely in w i ing
he manusc ip .
Acknowledgmen s
The au ho s wish o hank Aida Sel a, Jose de Juan Rami ez, Juan Ca -
los Alados, Ma Masiá, Ma ía José Rios, An onio Collado, Jesús San-
os, Miguel Ga cía del To o, Juan Manuel Pascasio, Jose Miguel
Rosales-Zabal, Magdalena La a, Te esa Aldamiz and Sil ia Ga cia-B
as hey p o ided samples om hei clinical cen e o be analysed
wi hin his s udy. The E hics Commi ee o he San Cecilio Hospi al
in G anada app o ed he s udy. This wo k was suppo ed by he Bij-
zonde Onde zoeks onds KU Leu en (BOF) No. OT/14/115, he Fonds
oo We enschappelijk Onde zoek Vlaande en (FWO) (p ojec s
G066215N and G0E8416N, and a pos doc o al manda e o B am
V ancken), and by g an s om Fondo de In es igacion Sani a ia
(www.isciii.es) (PI15/00713), Plan Nacional de I + D + I, Fondo Eu -
opeo de Desa ollo Regional-FEDER (www. edes/ edes/inicio)
(RD16/0025/0040) and GEHEP-SEIMC (GEHEP-004). Pa o he com-
pu a ional esou ces and se ices we e p o ided by he He cules
Founda ion and he Flemish Go e nmen – depa men EWI-FWO
K edie aan Na o se s (Theys, KAN2012 1.2.249.12). None o he
unding agencies we e in ol ed in he design o he s udy, no in
he collec ion, analysis and in e p e a ion o he da a, he w i ing
o he manusc ip and he decision o submi he manusc ip o
publica ion.
Supplemen a y da a
Supplemen a y da a o his a icle can be ound online a
h ps://doi.o g/10.1016/j.jhep.2019.08.010.
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Au ho names in bold designa e sha ed co- i s au ho ship
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1950 1960 1970 1980 1990 2000 2010 2020
Time (yea )
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
Cumula i e # o in oduc ions in o Spain ha o igina e om wi hin Eu ope
sub ype 1a
sub ype 3a
Fig. 1. F equen impo a ion o HCV sub ype 1a and 3a lineages in o Spain
mos ly om o he coun ies wi hin he Eu opean Union. The lines
co espond o he a e age cumula i e numbe o in oduc ion e en s o
hese sub ypes om o he coun ies wi hin he Eu opean Union in o Spain,
wi h he shaded a eas indica ing he unce ain y (95% c edible in e al). G ey
colo s pe ain o sub ype 1a, and blue colo s o sub ype 3a.
Le e o he Edi o
2Jou nal o Hepa ology 2019 ol. xxx jxxx–xxx
B am V ancken
1,#,
⇑
Lize Cuype s
1,#,
⇑
Ana Belen Pé ez
2
Na alia Chueca
2
Joaquin An on-Basan as
3
Albe o de la Iglesia
4
Ja ie Fuen es
5
Juan An onio Pineda
6
F ancisco Téllez
7
En ique Be nal
8
Pila Rincón
6
Miguel Angel Von Wichman
9
Ana Fuen es
2
F ancisco Ve a
10
An onio Ri e o-Juá ez
11
Miguel Jiménez
12
Anne-Mieke Vandamme
1,13
Fede ico Ga cía
2
1
KU Leu en, Depa men o Mic obiology, Immunology
and T ansplan a ion, Rega Ins i u e o Medical Resea ch,
Leu en, Belgium
2
Clinical Mic obiology, Uni e si y Hospi al San Cecilio, Resea ch
Ins i u e Ibs, G anada, Spain
3
Cen o Peni encia io, Albolo e, G anada, Spain
4
Clinical Mic obiology, Hospi al Juan Ramón Jimenez, Huel a, Spain
5
Hepa ology Uni , Hospi al Miguel Se e , Za agoza, Spain
6
In ec ious Diseases Uni , Uni e si y Hospi al o Valme, Se illa, Spain
7
In ec ious Diseases Uni , Uni e si y Hospi al o Pue o Real, Cádiz,
Spain
8
In ec ious Diseases, Uni e si y Hospi al Reina So ía, Mu cia, Spain
9
In ec ious Diseases Uni , Uni e si y Hospi al Donos ia, San Sebas ian,
Spain
10
In ec ious Disease Uni , Uni e si y Hospi al San a Lucía, Ca agena,
Mu cia, Spain
11
In ec ious Diseases Uni , Uni e si y Hospi al Reina So ía, Có doba,
Spain
12
Hepa ology Uni , Hospi al Ca los Haya, Málaga, Spain
13
Cen e o Global Heal h and T opical Medicine, Mic obiology Uni ,
Ins i u e o Hygiene and T opical Medicine, Uni e si y No a Lisbon,
Lisbon, Po ugal
⇑
Co esponding au ho s. Add ess: KU Leu en, Depa men o
Mic obiology, Immunology and T ansplan a ion, Rega Ins i u e o
Medical Resea ch, Leu en, Belgium. LC: Tel.: +32 16 32 11 76 o BV:
+32 16 37 44 00.
E-mail add esses:b am. ancken@kuleu en.be (B. V ancken),
[email p o ec ed] (L. Cuype s).
#
These i s au ho s con ibu ed equally o his a icle.
JOURNAL
OF HEPATOLOGY
Jou nal o Hepa ology 2019 ol. xxx jxxx–xxx 3