O iginal
a icle
P e alence o HTLV in ec ion in p egnan women
in Spain
Ana Machuca, Concepción Tuse , Vincen So iano, Es ella Caballe o, An onio Aguile a,
Raul O iz de Leja azu, and he HTLV Spanish S udy G oup
Objec i e: To es ima e he p e alence o HTLV in ec ion among p egnan women in Spain.
Me hods: A comme cial ELISA inco po a ing HTLV-I and HTLV-II an igens was used o
HTLV an ibody sc eening. Repea edly eac i e samples we e u he examined by wes e n blo .
Mo eo e , con i ma ion wi h PCR was pe o med when cells we e a ailable.
Resul s: 20 366 p egnan women in 12 diVe en Spanish ci ies we e es ed ina3yea pe iod
(July 1996 o Augus 1999). 32 samples we e epea edly eac i e by ELISA, and 10 o hem we e
con i med as posi i e by wes e n blo (eigh o HTLV-II and wo o HTLV-I). In addi ion,
h ee o 13 women who had an inde e mina e wes e n blo pa e n yielded posi i e esul s o
HTLV-II by PCR. All 11 HTLV-II in ec ed women had been bo n in Spain, and all bu one we e
o me d ug use s. Se en o hem we e coin ec ed wi h HIV-1. One HTLV-I in ec ed woman
was om Pe u, whe e HTLV is endemic and whe e she mos p obably was in ec ed du ing
sexual in e cou se.
Conclusion: The o e all p e alence o HTLV in ec ion among p egnan women in Spain is
0.064% (13/20 366), and HTLV-II ins ead o HTLV-I is he mos commonly ound a ian . A
s ong ela ion was ound among HTLV-II in ec ion and speci ic epidemiological ea u es, such
as Spanish na ionali y and injec ing d ug use. Al hough HTLV-II can be e ically ansmi ed,
mainly h ough b eas eeding, bo h he low p e alence o in ec ion and i s lack o pa hogenici y
would no suppo he in oduc ion o HTLV an ena al sc eening in Spain.
(Sex T ansm In 2000;76:366–370)
Keywo ds: HTLV; p egnan women; adul T cell leukaemia/lymphoma; opical spas ic pa apa esis;
epidemiology
In oduc ion
Human T lympho opic i us ypes I and II
(HTLV-I and HTLV-II) a e wo old human
e o i uses wi h a close gene ic sequence.
HTLV-I, he i s human e o i us iden i ied,
is endemic in Japan, wes A ica, he Ca ib-
bean, some a eas o Sou h Ame ica, and
Melanesia.12In con as , HTLV-II in ec ion is
common among se e al Ame indian ibes o
No h, Cen al, and Sou h Ame ica,34 pyg-
mies in Cen al A ica,5and among injec ing
d ug use s (IDUs) in No h Ame ica and
Eu ope.6–8 In Spain, HTLV-I/II in ec ion is
a e. Up o Decembe 1999, 240 indi iduals
wi h HTLV-II in ec ion and 40 wi h HTLV-I
had been iden i ied.8–10 Mos HTLV-I in ec ed
people we e immig an s om endemic a eas,
o na i es who had a elled o had had sexual
pa ne s om hose a eas, whe eas HTLV-II
in ec ion was mainly ound in Spanish IDUs,
o en coin ec ed wi h HIV-1.8–10
HTLV-I/II in ec ion is ansmi ed du ing
sexual in e cou se (mo e eYcien ly om male
o emale),11 blood ans usion,12 sha ing o
con amina ed needles,13 and om mo he o
child, mainly h ough b eas eeding,14 al-
hough ansplacen al ansmission can also
occu .15 In endemic a eas, HTLV is mainly
ansmi ed he e osexually and om mo he o
child. Up o 25% o babies bo n o HTLV-I
in ec ed mo he s become in ec ed i hey a e
b eas ed, and his a e declines o 5% i hey
a e bo le ed.16 17
HTLV-I in ec ed indi iduals a e p one o
de elop lymphop oli e a i e and neu ological
diso de s as adul s, classically adul T cell
leukaemia/lymphoma (ATL),1and opical
spas ic pa apa esis o HTLV-I associa ed
myelopa hy (TSP/HAM),18 al hough o he
in lamma o y condi ions ha e also been linked
o HTLV-I in ec ion. O e all, HTLV-I ca iage
is associa ed wi h a 2–5% li e ime isk o de el-
oping disease.19 HTLV-II has no ye been
de ini i ely associa ed wi h any disease, al-
hough se e al epo s o neu ological diseases
mimicking TSP/HAM ha e appea ed in he
li e a u e.20 21
HTLV-I in ec ion in Eu ope is hough o be
unusual excep among immig an s om e-
gions whe e HTLV is endemic. The sc eening
o blood dono s, which is cu en ly manda o y
in some Eu opean coun ies, has e ealed a
e y low p e alence o in ec ion ac oss
Eu ope.22 Howe e , ecen se osu eillance
s udies ha e poin ed ou ha he a e o in ec-
ion in p egnan women can be 50–100- old
highe han in blood dono s.23–25 O no e,
HTLV-I a he han HTLV-II is he i us
implica ed in mos ins ances. These da a migh
suppo he cos eVec i eness o he an ena al
HTLV sc eening.
The aim o ou s udy was o es ima e he
p e alence o HTLV-I/II in ec ion among
p egnan women in Spain in he pas 3 yea s,
and he e o e o p o ide in o ma ion o
conside ing whe he HTLV an ena al sc een-
ing should be ecommended.
Sex T ansm In 2000;76:366–370366
Se ice o In ec ious
Diseases, Hospi al
Ca los III, Ins i u o de
Salud Ca los III,
Mad id, Spain
A Machuca
V So iano
Hospi al Gene al
Uni e si a io, Valencia
C Tuse
Hospi al Vall
d’Heb on, Ba celona
E Caballe o
Hospi al Xe al,
San iago
A Aguile a
Hospi al Clínico
Uni e si a io,
Valladolid
R O iz de Leja azu
Co espondence o:
D Vincen So iano,
C/ Ra ael Cal o 7, 2º A
28010-Mad id, Spain
[email p o ec ed]
Accep ed o publica ion
15 May 2000
www.sex ansin .com
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Ma e ial and me hods
STUDY POPULATION
The p e alence o an ibodies o HTLV in
p egnan women was examined using se a col-
lec ed in 12 diVe en hospi als, dis ibu ed
h oughou Spain. Women had been e e ed
o ou ine ubella and oxoplasma an ibody
es ing. HTLV sc eening was pe o med by
anonymous es ing. In some ins i u ions, he
echnicians we e able o analyse hose se a
which we e eac i e o HTLV an ibodies. In
hese cases, and a e pa ien ’s signed consen ,
new blood was d awn, and pe iphe al blood
mononuclea cells (PBMCs) we e a ailable o
u he polyme ase chain eac ion (PCR)
analyses.
Be ween July 1996 and Augus 1999, a o al
o 20 366 samples we e analysed. Thei o igin
was Valencia (n=7523), Ba celona (n=3725),
San iago (n=3238), Valladolid (n=2686), Ma-
d id (n=1786), Cadiz (n=754), Se ille
(n=479), and O ense (n=128).
SEROLOGY
An ibodies o HTLV-I/II we e sc eened in
pools o i e se a, using a comme cial enzyme
linked immunoso ben assay (ELISA), which
inco po a es bo h HTLV-I and HTLV-II an i-
gens (Mu ex HTLV-I+II; Da o d, Ken ).
Each eac i e pool was u he analysed by
es ing he i e co esponding se a sepa a ely.
Repea edly eac i e ELISA samples we e
con i med by wes e n blo (WB HTLV plus;
Genelabs, Singapo e), which inco po a es on a
single ni ocellulose s ip HTLV-I and
HTLV-II an igens. The HTLV Eu opean
Resea ch Ne wo k (HERN) c i e ia we e used
o in e p e ing wes e n blo pa e ns.22 Figu e
1 summa ises he diagnos ic algo i hm p o-
posed by he HERN o HTLV and o he
ela ed in ec ions.
The p esence o HIV an ibodies was exam-
ined in specimens showing eac i i y agains
HTLV. A comme cial ELISA (Axsym HIV
1+2, Abbo , Chicago, IL, USA), and wes e n
blo (HIV blo , Sano i-Pas eu , Pa is, F ance)
we e used o sc eening and con i ma o y pu -
poses, espec i ely. All assays we e pe o med
acco ding o he manu ac u e ’s ins uc ions.
HTLV POLYMERASE CHAIN REACTION
F ozen PBMCs we e s o ed om a ew HTLV
se o eac i e subjec s, om whom new blood
could be d awn, in o de o pe o m gene ic
analysis by PCR (Amplico HTLV-I/II PCR
ki , Roche, Swi ze land).26
Resul s
Thi y wo (0.16%) o he 20 366 es ed se a
we e epea edly eac i e using he sc eening
ELISA HTLV-I+II. Howe e , only 10 samples
we e con i med as posi i e by wes e n blo
(eigh HTLV-II and wo HTLV-I), he emain-
ing samples we e ei he inde e mina e (13 se a)
o nega i e (nine se a).
HTLV-I/II PCR analysis could be pe o med
in specimens belonging o 11 women, six o
whom had inde e mina e wes e n blo pa -
e ns, ou a posi i e wes e n blo o HTLV-II,
and one o HTLV-I. Th ee women wi h
HTLV inde e mina e wes e n blo we e con-
i med as HTLV-II posi i e by PCR. All o
hem showed a cha ac e is ic pa e n on
wes e n blo , wi h eac i i y agains he
HTLV-II ecombinan p o ein gp46-II along
wi h any o he isola ed band (see Fig 2, cases 1,
4, and 8). O no e, all h ee we e coin ec ed
wi h HIV-1.
PCR esul s ob ained in he ou women
wi h posi i e HTLV-II wes e n blo and
ano he posi i e o HTLV-I wes e n blo
yielded conco dan esul s, espec i ely.
In summa y, o 20 366 p egnan women
es ed in Spain since 1997, 11 (0.054%) we e
ound o be in ec ed wi h HTLV-II and wo
(0.01%) wi h HTLV-I. All 11 HTLV-II ca ie s
we e Spanish, and all bu one had been IDUs.
Ano he was he sex pa ne o a male IDU.
Se en o he 11 we e coin ec ed wi h HIV-1.
One woman who was posi i e o HTLV-I
was an immig an om Pe u, and was HIV-1
nega i e. She denied d ug addic ion p ac ices
o blood ans usions, bu admi ed mul iple
he e osexual con ac s in he coun y o o igin.
The o he HTLV-I in ec ed woman was HIV-1
nega i e, and no epidemiological da a we e
a ailable o he . Table 1 summa ises he main
ea u es o all HTLV in ec ed women iden i ied
in his s udy.
Figu e 1 Algo i hm o he diagnosis o HTLV in ec ion.
HTLV-I
posi i e
HTLV-II
posi i e STLV/PTLV
IFI
RIPA
RIBA
LIA
Gene ic PCR
Se a Cells
O he ela ed
in ec ions
Posi i e Nega i e
speci ic PCR Nega i e
HTLV-I HTLV-II Inde e mina e
P19 + p24
gp21
gp46-I
Wes e n blo
Posi i e
Sc eening assay
Objec i e
Nega i e
Nega i e Nega i e o HTLV-I/II
Based in i al
lysa e
Based in ecombinan
pep ides
(1) De ec ion o HTLV/STLV (2) De ec ion o HTLV-I/-II
Ano he
bands pa e n
Absence o
bands
P24
pg21
pg46-II
I pos e io sample is a ailable
HTLV in p egnan Spanish women 367
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Discussion
HTLV-I in ec ion has been associa ed wi h
neu ological disease o lymphop oli e a i e
diso de s in adul s. The i us can be ansmi -
ed by sexual con ac ,11 pa en e al
exposu e,12 13 o om mo he o child.14 15
Recen s udies ha e sugges ed ha b eas
eeding accoun s o mos cases o e ical
ansmission o HTLV-I in ec ion,16 17 hus
p o iding an oppo uni y o a oid mos in ec-
ions in child en bo n o se oposi i e mo he s.
Howe e , da a om blood dono s unde line
ha HTLV in ec ions a e a e in Spain, like in
o he Eu opean coun ies, in he ange o
0.001%.10 22 An ena al sc eening is he e o e
no oVe ed o p egnan women. Howe e ,
ecen epo s ha e poin ed ou ha HTLV
p e alence in blood dono s migh be mislead-
ing, since a es o HTLV in ec ion 50–100-
old highe ha e been no iced in s udies
Figu e 2 Wes e n blo pa e n in 11 in ec ed p egnan Spanish women.
Case 1 PCR pos
Con ol + HTLV-I
gp46(II)
p53
p36
p24
p19
gp21
Case 2
Case 3
Case 4
Case 5
Case 6
Case 7
Case 8
Case 9
Case 10
Case 11
Case 12
Case 13
PCR pos
PCR pos
PCR pos
PCR pos
PCR pos
PCR pos
PCR pos
Con ol + HTLV-II
gp46(I)
p53
gp4
p36
p32
p28
p26
p24
p19
gp21
Table 1 Main ea u es o HTLV-I/II in ec ed p egnan women in Spain
No
Place o
diagnosis
Ye a o
diagnosis
Coun y o
bi h Risk p ac ice HIV-1 HTLV WB pa e n PCR
1 Valencia 1996 Spain IDU Posi i e gp46-II+ gp21 HTLV-II+
2 Valencia 1996 Spain IDU Posi i e gp46-II+ gp21+p24+p19 HTLV-II+
3 Valencia 1996 Spain IDU Nega i e gp46-II+ gp21+p24+p19 HTLV-II+
4 Valencia 1997 Spain IDU Posi i e gp46-II+ gp21 HTLV-II+
5 Ba celona 1997 Spain IDU Posi i e gp46-II+ gp21+p24+p19 ND
6 Cádiz 1998 Spain IDU Nega i e gp46-II+ gp21+p24+p19 HTLV-II+
7 Ba celona 1998 Spain IDU Posi i e Rgp46-II+ gp21+p24 ND
8 Valencia 1998 Spain IDU Posi i e gp46-II+ gp21 HTLV-II+
9 Valencia 1998 Spain IDU Nega i e Rgp46-II+ gp21+p24 HTLV-II+
10 Valencia 1998 Spain IDU pa ne Nega i e gp46-II+ gp21+p24+p19 ND
11 Mad id 1999 Spain IDU Posi i e gp46-II+ gp21+p24+p19 ND
12 Ba celona 1998 Pe u Sexual (?) Nega i e gp46-I+ gp21+p24+p19 HTLV-I+
13 Ba celona 1999 unknown unknown Nega i e gp46-I+ gp21+p24+p19 ND
ND = no done.
368 Machuca, Tuse , So iano, e al
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di ec ly a ge ing p egnan women in
Eu ope.23–25 In ou s udy he p e alence o
HTLV in ec ion in p egnan women om se -
e al Spanish ci ies was 0.064%, mo e han 50
imes highe han ha ound in Spanish blood
dono s.10 22 In some s udies ca ied ou in
England and F ance mos HTLV posi i e
p egnan women we e in ec ed wi h
HTLV-I.23–25 This could be explained mainly
by he ac ha hese s udies ha e ocused on
me opoli an a eas (London, Pa is, e c), which
ha e la ge A ican and/o A o-Ca ibbean
immig an communi ies. In con as , in Spain
HTLV-II ins ead o HTLV-I was he mos e-
quen a ian ound in p egnan women.
Mo eo e , only one o he wo women ound
o be HTLV-I in ec ed was an immig an om
an endemic egion (Pe u).
Mos HTLV-II in ec ions desc ibed so a in
Spain ha e been epo ed in IDUs, 90% o
hem coin ec ed wi h HIV-1.8In ou s udy, a
s ong ela ion was also ound be ween
HTLV-II in ec ion and p e ious d ug addic-
ion p ac ices. All he p egnan women
in ec ed wi h HTLV-II we e Spanish, and
se en o he 11 we e coin ec ed wi h HIV-1.
A oiding b eas eeding would educe he isk
o bo h HIV-1 and/o HTLV-II in ec ion in
newbo ns.
Se e al epo s ha e shown ha eac i i y o
HTLV-II can be diminished in HIV-1 coin-
ec ed people suVe ing a p o ound immune
impai men , leading o a cha ac e is ic inde e -
mina e pa e n on wes e n blo s ips ( eac i -
i y o gp46-I o gp46-II plus any o he
isola ed band).27 28 We ound h ee HTLV-II
in ec ed women who had an inde e mina e
pa e n on wes e n blo . All h ee we e Spanish
na i es, IDUs, and coin ec ed wi h HIV-1.
In conclusion, ou esul s show ha he
p e alence o HTLV in ec ion among p egnan
women in Spain is low, HTLV-II being (wi h
no p o ed clea pa hogenici y) mo e common
han HTLV-I. Mo eo e , mos HTLV-II posi-
i e p egnan women we e coin ec ed wi h
HIV-1. Since s opping b eas eeding is al eady
ad ised in all HIV posi i e women, addi ional
measu es o p o ec hei newbo ns om
HTLV-II does no seem o be equi ed. The
low p e alence o HTLV-I in ec ion and he
lack o pa hogenici y o he p edominan
HTLV-II would no suppo he in oduc ion
o HTLV an ena al sc eening in Spain. Selec-
i e an ena al sc eening should o be consid-
e ed in o me IDUs o immig an s om
endemic egions. Fu he cos -bene i s udies
a e needed o de e mine whe he HTLV an e-
na al sc eening should be ecommended in
Spain.
Appendix
Membe s o The HTLV Spanish S udy G oup.
C Tuse , G Ma caida, and R Gisbe , Hospi al Gene al
Uni e si a io, Valencia; E Caballe o, Hospi al Vall
d’Heb ón, Ba celona; JM Ei ós and R O iz de
Leja azu, Hospi al Clínico Uni e si a io, Valladolid; J
Ga cía, Hospi al C is al-Piño , O ense; A Aguile a, A
Cid, A Ja o, and B Reguei o, Hospi al Xe al, San iago;
G Cilla and E Pé ez-T alle o, Hospi al Nues a Seño a
de A ánzazu, San Sebas ián; F Me ino and B Espa za,
Uni e sidad del País Vasco, Bilbao; R Ma ínez-Zapico,
Hospi al La Paz, Mad id; E Calde ón, FJ Med ano and
M Leal, Hospi al Vi gen del Rocío, Se illa; J Capo e,
Hospi al Pue a del Ma , Cádiz; F D onda, Hospi al
Ramón y Cajal, Mad id; R Beni o, Hospi al Clínico,
Za agoza; MA Rod íguez-Iglesias, Hospi al Uni e si-
a io de Pue o Real, Cádiz; J del Rome o and C
Rod íguez, Cen o Sani a io Sando al, Mad id; AM
Ma ín and O E o a, Hospi al Insula , Las Palmas de
G an Cana ia; A Machuca, V So iano, M Gu ié ez,
and J González-Lahoz, Hospi al Ca los III, Ins i u o de
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This wo k was pa ially unded by an EC Conce ed Ac ion
HTLV Eu opean Resea ch Ne wo k (HERN) An ena al Se o-
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Con ibu o s: AM, VS, CT, EC, AA, and ROL ec ui ed
women, ook samples, and pe o med es ing. O he membe s o
he HTLV Spanish s udy g oup p o ided specimens, and
pa icipa ed ac i ely in he inal discussion o esul s, and he
conclusions o he manusc ip .
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