Association between chronic stress and immune response to influenza vaccine in healthcare workers
Abstract
A B S T R A C T - Introduction: Chronic stress can influence immune response to vaccines. Healthcare workersare exposed to stressors and biological hazards, the health effects of which may be preventedthrough vaccination.Objectives: This study aims to evaluate the association between stress in nurses and: (1)insufficient response to influenza vaccine, assessed one month after vaccination (T1); (2)the drop in haemagglutination-inhibition (HAI) antibodies (ab) six months after vaccination(T6).Methods: A nested case–control study was carried out with 136 healthy hospital nurses.Individual interviews, the General Health Questionnaire (GHQ12) and Maslach Burnout Inventory(MBI-HSS) were applied in order to determine the presence of stress, using the triangulationmethod at the beginning of the study (T0). Influenza vaccine was administered and titresof HAI above each strain composing influenza vaccine before vaccination (T0), at T1and T6were assessed.Results: There was no statistically relevant (5%) relationship between stress and the insuffi-cient immune response to the vaccine at T1. Nevertheless, there was an association betweenstress and the drop in HAI ab AH1at T6, when we assessed stress by the triangulation methodusing an interview (p = 0.006), GHQ12(p = 0.045) and combination of criteria (p = 0.001), evenafter multivariate analysis (respectively, p = 0.01, p < 0.05 and p = 0.002). The odds ratios were,respectively, 3.64, 2.73 and 5.22.Conclusions: The association we found, between chronic stress and the drop in HAI ab atT6, corroborates the hypothesis that stress can negatively influence immune response.Therefore, it seems reasonable to consider this issue when we implement vaccinationprogrammes for healthcare workers.
Full text
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www.else ie .p / psp
O iginal
A icle
Associa ion
be ween
ch onic
s ess
and
immune
esponse
o
influenza
accine
in
heal hca e
wo ke s
Ema
Sacadu a-Lei ea,b,c,∗,
An ónio
Sousa-U ab,c,
Helena
Rebelo-de-And aded,e,
Sancha
Fe ei aa,
Regina
Rochaa
aOccupa ional
Heal h
Depa men
o
Hospi al
de
San a
Ma ia/CHLN,
Lisbon,
Po ugal
bNa ional
School
o
Public
Heal h/New
Uni e si y
o
Lisbon,
Lisbon,
Po ugal
cCMDT
–
Cen o
de
In es igac¸ão
da
Malá ia
e
Doenc¸as
T opicais
–
Public
Heal h,
Lisbon,
Po ugal
dNa ional
Ins i u e
o
Heal h,
INSA,
Lisbon,
Po ugal
eFacul y
o
Pha macy,
Uni e si y
o
Lisbon,
Lisbon,
Po ugal
a
i
c
l
e
i
n
o
A icle
his o y:
Recei ed
15
Ap il
2013
Accep ed
27
Sep embe
2013
A ailable
online
19
Decembe
2013
Keywo ds:
An ibody
esponse
Heal hca e
wo ke s
Influenza
accine
Psychological
s ess
a
b
s
a
c
In oduc ion:
Ch onic
s ess
can
influence
immune
esponse
o
accines.
Heal hca e
wo ke s
a e
exposed
o
s esso s
and
biological
haza ds,
he
heal h
e ec s
o
which
may
be
p e en ed
h ough
accina ion.
Objec i es:
This
s udy
aims
o
e alua e
he
associa ion
be ween
s ess
in
nu ses
and:
(1)
insu ficien
esponse
o
influenza
accine,
assessed
one
mon h
a e
accina ion
(T1);
(2)
he
d op
in
haemagglu ina ion-inhibi ion
(HAI)
an ibodies
(ab)
six
mon hs
a e
accina ion
(T6).
Me hods:
A
nes ed
case–con ol
s udy
was
ca ied
ou
wi h
136
heal hy
hospi al
nu ses.
Indi idual
in e iews,
he
Gene al
Heal h
Ques ionnai e
(GHQ12)
and
Maslach
Bu nou
In en o y
(MBI-HSS)
we e
applied
in
o de
o
de e mine
he
p esence
o
s ess,
using
he
iangula ion
me hod
a
he
beginning
o
he
s udy
(T0).
Influenza
accine
was
adminis e ed
and
i es
o
HAI
abo e
each
s ain
composing
influenza
accine
be o e
accina ion
(T0),
a
T1and
T6
we e
assessed.
Resul s:
The e
was
no
s a is ically
ele an
(5%)
ela ionship
be ween
s ess
and
he
insu fi-
cien
immune
esponse
o
he
accine
a
T1.
Ne e heless,
he e
was
an
associa ion
be ween
s ess
and
he
d op
in
HAI
ab
AH1a
T6,
when
we
assessed
s ess
by
he
iangula ion
me hod
using
an
in e iew
(p
=
0.006),
GHQ12 (p
=
0.045)
and
combina ion
o
c i e ia
(p
=
0.001),
e en
a e
mul i a ia e
analysis
( espec i ely,
p
=
0.01,
p
<
0.05
and
p
=
0.002).
The
odds
a ios
we e,
espec i ely,
3.64,
2.73
and
5.22.
Conclusions:
The
associa ion
we
ound,
be ween
ch onic
s ess
and
he
d op
in
HAI
ab
a
T6,
co obo a es
he
hypo hesis
ha
s ess
can
nega i ely
influence
immune
esponse.
The e o e,
i
seems
easonable
o
conside
his
issue
when
we
implemen
accina ion
p og ammes
o
heal hca e
wo ke s.
©
2013
Escola
Nacional
de
Saúde
Pública.
Published
by
Else ie
España,
S.L.
All
igh s
ese ed.
∗Co esponding
au ho .
E-mail
add ess:
[email p o ec ed].p
(E.
Sacadu a-Lei e).
0870-9025/$
–
see
on
ma e
©
2013
Escola
Nacional
de
Saúde
Pública.
Published
by
Else ie
España,
S.L.
All
igh s
ese ed.
h p://dx.doi.o g/10.1016/j. psp.2013.09.002
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19
S esse
c ónico
e
a
imunidade
à
acina
con a
a
g ipe
em
p ofissionais
de
saúde
Pala as-cha e:
An ico pos
P ofissionais
de
saúde
Vacina
con a
a
g ipe
S esse
e
s
u
m
o
In oduc¸ão:
O
s esse
c ónico
pode
influencia
a
espos a
imuni á ia
à
acinac¸ão.
Os
p ofis-
sionais
de
saúde
es ão
expos os
a
s esso es
de
na u eza
p ofissional
e
ainda
a
agen es
biológicos
cujos
e ei os
pode ão
se
p e enidos
pela
acinac¸ão.
Obje i os:
Es uda
a
associac¸ão
en e
a
p esenc¸a
de
s esse
e
(1)
a
“insuficien e”
espos a
imuni á ia
à
acina
con a
a
g ipe,
a aliada
um
mês
após
a
acinac¸ão
(T1);
(2)
a
educ¸ão
dos
í ulos
de
an ico pos
di igidos
às
hemaglu ininas
(HAI)
seis
meses
após
a
acinac¸ão
(T6).
Mé odos:
Realizou-se
um
es udo
caso-con olo
inco po ado
num
es udo
de
coo es
com
a
pa icipac¸ão
de
136
en e mei os
hospi ala es
saudá eis.
Realiza am-se
en e is as
indi idu-
ais
e
aplica am-se
os
ques ioná ios
The
Gene al
Heal h
Ques ionnai e
(GHQ12)
e
Maslach
Bu nou
In en o y
(MBI-HSS)
pa a
de e minac¸ão
da
p esenc¸a
de
s esse
c ónico
pelo
mé odo
da
iangulac¸ão,
no
início
do
es udo
(T0).
Foi
adminis ada
a
acina
con a
a
g ipe
e
de e minou-
se
os
í ulos
de
HAI
di igidos
a
cada
es i pe
componen es
da
acina
con a
a
g ipe,
an es
da
acinac¸ão(T0),
em
T1e
em
T6.
Resul ados:
Não
se
encon ou
associac¸ão
significa i a
(5%)
en e
a
p esenc¸a
de
s ess
e
a
“insuficien e”
espos a
à
acina
con a
a
g ipe
em
T1.
Con udo,
encon ou-se
uma
associac¸ão
en e
a
p esenc¸a
de
s ess
e
a
diminuic¸ão
do
í ulo
de
HAI
di igidos
à
es i pe
A(H1N1)
em
T6
quando
se
a aliou
a
p esenc¸a
de
s esse
pelo
mé odo
da
iangulac¸ão
usando
a
en e is a
(p=0,006),
o
GHQ12 (p=0,045)
e
a
combinac¸ão
dos
ês
c i é ios
(p=0,001),
que
se
man e e
após
análise
mul i a iada
( espe i amen e
p=0,01,
p<0.05
e
p=0.002).
Os
odds
a io
ajus ados
o am
de
3,64,
de
2,73
e
de
5,22.
Conclusões:
A
associac¸ão
encon ada
en e
a
p esenc¸a
de
s esse
c ónico
e
a
educ¸ão
do
í ulo
de
HAI
em
T6 em
apoia
a
hipó ese
de
que
o
s esse
pode á
influencia
nega i a-
men e
a
manu enc¸ão
dos
í ulos
de
an ico pos,
mesmo
em
indi íduos
adul os
não
idosos.
Assim,
pa ece
azoá el
conside a
es e
aspe o
quando
se
p e ende
implemen a
p og amas
de
acinac¸ão
di igidos
a
p ofissionais
de
saúde.
©
2013
Escola
Nacional
de
Saúde
Pública.
Publicado
po
Else ie
España,
S.L.
Todos
os
di ei os
ese ados.
In oduc ion
Heal hca e
wo ke s
a e
exposed
o
many
s esso s,
some
o
hem
ela ed
wi h
o ganisa ional
wo k
condi ions
and
o he s,
mo e
specific
o
his
p o ession,
ela ed
wi h
hei
ac i i y
o
ca ing
o
he
ill.1–3
Ch onic
s ess
and
bu nou
seem
o
be
e y
common
in
nu ses.4–6 Fo
example,
López-Cas illo
and
colleagues
ound
high
le els
o
emo ional
dis u bance
de e mined
by
he
Gen-
e al
Heal h
Ques ionnai e
(GHQ28)
in
39%
o
hospi al
nu ses.7
Amongs
he
consequences
o
ch onic
dis ess,
whe he
hey
a e
ela ed
o
no
wi h
wo k,
a e
he
possible
e ec s
on
he
immune
sys em,
including
e ec s
on
he
immune
esponse
o
accina ion.
Heal hca e
wo ke s
a e
s ongly
ad ised
o
be
accina ed
agains
influenza
in
o de
o
p o ec
hemsel es
agains
he
disease,
educe
s a
absen eeism
and
minimise
he
isk
o
nosocomial
ansmission
o
he
pa ien s
hey
ake
ca e
o .
Vaccina ion
is
a
possible
model
o
immune
esponse,
es -
ing
mos ly
he
humo al
immune
esponse.
Vaccina ed
people
de elop
an ibodies
(ab)
ha
bind
and
neu alise
he
i us,
in
mos
cases
ab
agains
he
su ace
glycop o ein
hemagglu-
inin.
Those
ab
can
be
used
as
ma ke s
o
p o ec ion
agains
he
disease,8caused
by
s ains
ha
a e
simila
o
he
accine
composi ion.
Acco ding
o
me a-analysis
by
Sege s om
and
Mille ,
ch onic
exposu e
o
s esso s
such
as
aking
ca e
o
spouses
wi h
demen ia,
unemploymen
and
su e ing
om
physi-
cal
disabili y
is
associa ed
wi h
a
smalle
ab
esponse
o
influenza
accine.9Some
e iews
also
sugges
ha
ch onic
s ess
is
associa ed
wi h
a
smalle
ab
esponse
o
influenza
accine.10–12
Gene ally
speaking,
s udies
e alua ing
he
associa ion
be ween
ch onic
s ess
and
immune
esponse
o
influenza
accine
showed
ela i ely
consis en
esul s
in
old
people.
In
hose
people,
ch onic
exposu e
o
s esso s
was
associ-
a ed
wi h
ch onic
anxie y
and
symp oms
o
dep ession
and
a
lowe
esponse
o
influenza
accine,
in
compa ison
o
a
con-
ol
g oup.13–17
The
use
o
a
s anda dized
dose
o
an igen
which
p omo es
a
good
immune
esponse
in
mos
adul s,
could
make
i
di -
ficul
he
de ec ion
o
he
influence
o
ch onic
s ess
in
he
immune
esponse
o
accina ion
in
younge
adul s,
wi h
a
obus
immune
sys em.
Olde
people
ha e
a
weake
immune
sys em,
ela ed
wi h
age,
so
his
could
be
an
explana ion
o
he
g ea e
con-
sis ency
o
esul s
showing
a
nega i e
associa ion
be ween
ch onic
s ess
and
immune
esponse
o
accines
in
hem.
Vedha a
and
colleagues
did
no
find
any
associa ion
be ween
aking
ca e
o
spouses
wi h
mul iple
scle osis
and
ab
esponse
o
influenza
accine
in
adul s
unde
he
age
o
55.18
20
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(1):18–26
Howe e ,
hose
adul s
showed
simila
s ess
le els
as
he
con-
ol
g oup.
In
younge
adul s,
such
as
uni e si y
s uden s,
some
s udies19–22 ound
an
associa ion
be ween
s ess,
cha ac-
e ised
in
di e en
ways,
and
he
immune
esponse
o
influenza
accine
(assessed
by
ab
i es
o
by
esponse
a e)
one
mon h
a e
accina ion.
Howe e ,
o he
s udies
did
no
find
ha
associa ion.23–25
Some
o
he
s udies
ound
an
associa ion
be ween
s ess
and
a
d op
in
ab
i es
assessed
4–6
mon hs
a e
accina ion,19–23,25 e en
in
he
younges
adul s.
The
d op
in
he
ab
i es
associa ed
wi h
s ess
was
only
obse ed
agains
one
s ain
o
accine
componen s,
sugges ing
ha
di e en
exposu es
o
di e en
pas
accina ions
can
be
esponsible
o
hose
esul s.
In
an
occupa ional
con ex
o
heal hca e
se ings,
whe e
heal hca e
wo ke s
a e
in
he
labou
ma ke
(and
a e
he e-
o e
no
e y
old),
bu
a e
simul aneously
exposed
o
ch onic
s esso s
and
biological
isk
haza ds,
i
seems
impo an
o
s udy
he
influence
o
s ess
on
immune
esponse
o
influenza
accine.
The e o e,
his
s udy
analyses
he
associa ion
be ween
s ess
in
nu ses
and:
(1)
insu ficien
esponse
o
influenza
ac-
cine,
assessed
one
mon h
a e
accina ion
(T1);
(2)
he
d op
in
influenza
aemagglu ina ion-inhibi ion
(HAI)
ab
i es
six
mon hs
a e
accina ion
(T6),
as
compa ed
o
one
mon h
pos
accina ion
HAI
ab
i es.
Ma e ials
and
me hods
S udy
design
and
pa icipan s
The
s udy
was
a
nes ed
case–con ol
s udy,
conduc ed
o e
six
mon hs
in
a
uni e si y
hospi al
du ing
he
2007/2008
influenza
season.
Subjec s
we e
hospi al
nu ses
who
we e
no
aking
any
egula
medica ion,
including
d ugs
ha
could
a ec
immu-
ni y
(such
as
cance
he apy
d ugs
o
co icos e oids).
They
did
no
ha e
any
medical
condi ion
ha
could
a ec
he
immune
esponse
and
hey
also
had
no
majo
su ge y
in
he
p eceding
h ee
mon hs.
They
did
no
ha e
a
his o y
o
d ug
consump-
ion
o
alcohol
consump ion
g ea e
han
10
uni s
pe
week,
no
did
hey
handle
ci o oxic
d ugs
o
wo k
egula ly
wi h
ionising
adia ion
(n
=
136).
The
hospi al’s
E hics
Commi ee
app o ed
he
s udy
and
all
he
pa icipan s
signed
hei
ag ee-
men
o
pa icipa ing
in
i .
One-mon h
and
six-mon h
d op-ou
c i e ia:
•
clinical
diagnosis
o
medical
condi ion
ha
may
a ec
immune
esponse
a e
he
beginning
o
he
s udy
o
aking
any
egula
medica ion
ha
can
a ec
immuni y
(assessed
by
in e iew,
a
T1and
T6);
•
wo kplace
changes
wi h
egula
exposu e
o
ionising
adia-
ions
o
ci o oxic
d ugs
handling;
•
clinical
influenza
symp oms
wi h
i us
iden ifica ion
in
nasal
o
o opha yngeal
swab,
du ing
he
six
mon hs
o
he
s udy;
•
a
ise
in
HAI
Ab
i e
o
A(H1N1),
A(H3N2)
o
B
s ains
six
mon hs
a e
accina ion,
as
compa ed
wi h
he
i es
mea-
su ed
one
mon h
a e
accina ion.
Such
a
ise
in
HAI
Ab
i e
sugges s
an
exposu e
o
influenza
s ains
du ing
T1and
T6ins ead
o
a
delayed
esponse
o
he
accine.
S ess
assessmen
S uc u ed
indi idual
in e iews
we e
conduc ed
a
he
begin-
ning
o
he
s udy
(T0)
in
o de
o:
•
iden i y
socio-demog aphic
cha ac e is ics
and
possible
con oundable
a iables
ela ed
wi h
immuni y
(physical
exe cise,
nu i ional
pa ame e s,
nu i ional
supplemen s,
hou s
o
sleep
pe
day,
smoking
habi s,
shi
wo k)
and
influenza
accina ion
his o y;
•
iden i y
wo k- ela ed
and
non-wo k- ela ed
s esso s,
using
a
Like
scale
om
1
o
5;
•
assess
pe cei ed
s ess,
using
a
Like
scale
om
1
o
5;
•
iden i y
s ess- ela ed
beha iou al
changes
o
psychoso-
ma ic
symp oms.
We
also
applied
he
Po uguese
e sions
o
he
Gene al
Heal h
Ques ionnai e
(GHQ12)
and
Maslach
Bu nou
In en o y
(MBI-HSS
o
MBI)
exhaus ion
scale
a
he
beginning
o
he
s udy
(T0).
Al a
C onbach
o
hose
scales
was
0.855
and
0.874
espec i ely.
In
o de
o
assess
he
p esence
o
ch onic
s ess,
we
applied
he
iangula ion
me hod
a
T0,
as
sugges ed
by
Cox
and
colleagues,26 in
ou
di e en
ways:
•
h ough
in e iews:
we
accep ed
he
p esence
o
ch onic
s ess
using
in e iews
i
he e
we e
iden ified
s esso s
classified
as
4
o
5,
plus
pe cei ed
s ess
classified
as
4
o
5,
plus
a
leas
one
beha iou al
change
o
one
psychosoma ic
symp om
s ess- ela ed;
•
h ough
GHQ12:
we
accep ed
he
p esence
o
ch onic
s ess
using
GHQ12 i
he e
we e
iden ified
s esso s
classified
as
4
o
5,
plus
GHQ12 highe
han
2,
plus
a
leas
one
beha iou al
change
o
one
psychosoma ic
symp om
s ess- ela ed;
•
h ough
MBI:
we
accep ed
he
p esence
o
ch onic
s ess
using
MBI
i
he e
we e
iden ified
s esso s
classified
as
4
o
5,
plus
MBI
exhaus ion
scale
highe
han
24,
plus
a
leas
one
beha iou al
change
o
one
psychosoma ic
symp om
s ess-
ela ed;
•
combina ion
o
c i e ia:
we
accep ed
he
p esence
o
s ess
using
combina ion
o
c i e ia
i
he e
was
s ess
using
in e -
iew
and
s ess
using
GHQ12 o
i
he e
was
s ess
using
in e iew
and
s ess
using
MBI
exhaus ion
scale.
Vaccina ion
and
labo a o y
p ocedu es
Venous
blood
was
d awn
a
h ee
s ages
be ween
Oc obe
2007
and
Ap il
2008:
(i)
immedia ely
be o e
influenza
acci-
na ion
(T0);
(ii)
one
mon h
ollowing
immunisa ion
(T1);
and
(iii)
six
mon hs
a e
T0(T6).
The
samples
es ed
1
h
a
ambien
empe a u e
ollow-
ing
cen i uga ion
a
3500
pm
o
10
min.
Se a
we e
s o ed
a
−20 ◦C
un il
used.
All
he
samples
d awn
a
T0,
T1and
T6we e
p ocessed
a
he
same
ime
and
unde
he
same
condi ions.
A
comme cially
a ailable
2007/2008
i alen
influenza
ac-
cine,
wi h
he
ecommended
composi ion
o
ha
season
in
No h
Hemisphe e,
was
adminis e ed
in amuscula ly,
in
he
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(1):18–26
21
del oid
muscle,
du ing
Oc obe .
All
he
accines
belonged
o
he
same
g oup
(AFLUA290AD).
Haemagglu ina ion
inhibi ion
eac ion
was
used
o
assess
specific
HAI
ab
i e
agains
influenza
A(H1N1),
A(H3N2)
and
B
s ains
included
in
he
influenza
accine,
in
acco dance
wi h
he
Wo ld
Heal h
O ganisa ion’s
manual.27 Immedia ely
be o e
he
labo a o ial
p ocedu es,
he
se a
we e
ea ed
by
a
Recep o -Des oying
Enzyme
(RDE)
in
o de
o
emo e
unspecific
agglu inins
and
inhibi o s.
The
e e ence
an igens
we e
dilu ed
o
ob ain
4
uni s
agains
haemmaglu inin
pe
25
l
and
incuba ed
wi h
he
ea ed
se a
samples.
E y h ocy es
we e
hen
added
o
he
fluid.
HAI
Ab
i e
co esponded
o
he
in e se
o
he
las
dilu ion
o
se um
ha
comple ely
inhibi ed
haemagglu ina ion.
We
used
p og essi e
dilu ions,
s a ing
wi h
1:10
up
o
1:20.480.
The
se ological
pa ame e s
ob ained
we e:
•
HAI
Ab
i e
agains
influenza
A(H1N1),
A(H3N2)
and
B
s ains
included
in
influenza
accine,
be o e
(T0)
and
a e
accina ion
(T1and
T6);
•
ise
in
HAI
Ab
i e
agains
influenza
A(H1N1),
A(H3N2)
and
B
s ains
included
in
influenza
accine,
assessed
one
mon h
a e
accina ion
(compa ed
o
HAI
Ab
i e
immedia ely
be o e
accina ion);
•
d op
in
HAI
Ab
i e
agains
influenza
A(H1N1),
A(H3N2)
and
B
s ains
included
in
influenza
accine,
be ween
T1and
T6.
Defini ions
Fo
analysis
a
T1and
a
T6,
we
defined
he
ollowing
g oups:
esponde s
a
T1(one
mon h
a e
accina ion):
pa icipan s
ha
showed,
a
T1,
a
leas
a
ou old
ise
in
HAI
ab
i e
compa ed
o
he
i e
be o e
accina ion;
non- esponde s
a
T1(one
mon h
a e
accina ion):
pa ic-
ipan s
ha
did
no
show,
a
T1,
a
ou old
ise
in
HAI
ab
i e
compa ed
o
he
i e
be o e
accina ion;
HAI
ab
i e
d op
g oup
a
T6(six
mon hs
a e
accina ion):
pa icipan s
wi h
a
leas
a
ou old
ise
in
HAI
ab
i e
a
T1,
bu
who
showed
a
d op
in
HAI
ab
i e
a
T6,
as
compa ed
o
HAI
ab
i e
a
T1;
no
change
in
HAI
ab
i e
g oup
a
T6(six
mon hs
a e
ac-
cina ion):
pa icipan s
wi h
a
leas
a
ou old
ise
in
HAI
ab
i e
a
T1,
bu
wi h
no
change
in
HAI
ab
i e
a
T6,
as
compa ed
o
HAI
ab
i e
a
T1.
S a is ical
analyses
Fo
dicho omous
a iables,
we
used
he
Qui-squa e
and
Fishe
exac
es s
and
de e mined
he
odds
a io.
Fo
nume ical
a iables,
we
used
he
Kolmogo o –Smi no
and
Shapi o–Wilk
es s
o
assess
no mal
dis ibu ion
in
non-
esponde s
and
esponde s
(T1)
and
in
he
HAI
Ab
i e
d op
g oup
and
no
change
in
HAI
Ab
i e
g oup
(T6).
Fo
no mal
dis ibu ions,
he
T
S uden
es
was
used
o
compa e
means,
and
he
Le ene
es
o
assess
a iance
homogenei y.
Fo
no
no mal
dis ibu ions,
we
applied
he
Mann–Whi ney
es
o
compa e
medians.
We
also
used
he
mul i a ia e
analysis
and
de e mined
he
adjus ed
odds
a io
o
he
con ounding
a iables.
We
conside ed
a
s a is ical
significance
o
5%.
All
es s
we e
un
in
he
S a is ical
Package
o
Social
Sciences
–
SPSS®so wa e,
e sion
14.0
o
Windows.
Resul s
We
s udied
136
nu ses,
mos
o
whom
we e
emale
(83.8%),
Caucasian
(96.3%)
and
did
no
smoke
(77.9%).
Thei
a e age
age
was
33
and
he
median
age
was
29
(22–63
yea s
old).
Only
one
pa icipan
was
mo e
han
six y
yea s
o
age.
Mo e
han
one
hal
o
he
pa icipan s
had
been
gi en
an
influenza
accine
sho
a
leas
one
o
he
ou
seasons
p io
o
he
beginning
o
he
s udy
(52.9%),
mos ly
in
he
yea
imme-
dia ely
be o e
(44.1%).
Nu ses
included
in
he
s udy
wo ked
mos ly
on
a
shi
wo k
basis
(70.6%),
had
a
co po al
index
mass
(kg/m2)
be ween
18.5
and
24.9
(72.1%)
and
slep
a
leas
7
h
pe
day
(66.2%).
The
majo i y
did
no
ake
i amin
supplemen s
(86.8%)
o
fish
oil
(98.5%).
Only
54.4%
did
egula
physical
exe -
cise
and
46.3%
a e
yogu
daily.
Associa ion
be ween
ch onic
s ess
and
non- esponde s
a
T1
One
mon h
a e
accina ion
(T1),
we
did
no
find
any
associ-
a ion
o
s a is ical
significance
be ween
non- esponde s
o
A(H1N1)
i us
s ain
included
in
he
influenza
accine
and
he
p esence
o
ch onic
s ess
a
T0,
assessed
in
ou
di e -
en
ways.
Simila ly,
he e
was
also
no
associa ion
be ween
non- esponde s
o
A(H3N2)
o
non- esponde s
o
B
s ains
included
in
he
influenza
accine
and
ch onic
s ess
a
T0.
To
simpli y
he
able,
we
named
esponde s
o
non- esponde s
o
A(H1N1)
and
o
A(H3N2)
as
esponde s
o
non- esponde s
AH1and
AH3 espec i ely
(Table
1).
Aemagglu ina ion-inhibi ion
an ibodies
i es
a
T0in
esponde s
and
non- esponde s
a
T1
Using
he
Kolmogo o –Smi no
and
Shapi o–Wilk
es s,
we
ound
ha
he e
is
no
no mal
dis ibu ion
in
non- esponde s
and
esponde s
a
T1 o
he
conside ed
con inuous
a iables
(p
<
0.001).
The e o e,
we
applied
he
Mann–Whi ney
es
o
compa e
medians
be ween
HAI
ab
i es
a
T0in
esponde s
and
non- esponde s
a
T1.
We
ound
ha
non- esponde s
AH1a
T1had
significan ly
highe
HAI
ab
AH1 i es
a
T0
han
esponde s
AH1a
T1.
The
same
happened
wi h
non-
esponde s
AH3a
T1and
non- esponde s
B
a
T1,
who
had
significan ly
highe
HAI
AH3 i es
a
T0and
HAI
B
i es
a
T0
han
he
co esponding
esponde s
(Table
2).
Associa ion
be ween
ch onic
s ess
and
d op
in
aemagglu ina ion-inhibi ion
ab
i es
a
T6
A
T6(six
mon hs
a e
accina ion),
he
p esence
o
s ess
in
he
HAI
ab
AH1 i e
d op
g oup
was
highe
han
in
he
no
change
in
HAI
ab
AH1 i e
g oup,
when
we
assessed
s ess
by
all
he
conside ed
di e en
ways,
being
s a is ically
signi-
fica i e
when
we
assessed
he
p esence
o
ch onic
s ess
by
22
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(1):18–26
Table
1
–
S ess
in
non- esponde s
and
in
esponde s
AH1,
AH3and
B
a
T1.
HAI
ab
g oups
a
T1Ch onic
s ess
assessmen
S ess
in
non- esponde s
a
T1
S ess
in
esponde s
a
T1
S a is ical
analysis
(Qui-squa e
es )
n
(%)
n
(%)
OR
(95%
CI)
p
AH1(n
=
135)
Non- esponde s:
45
Responde s:
90
S ess
(in e iew)
28
(62.2)
46
(51.1)
1.575
(0.759–3.272)
0.221
S ess
(GHQ12)a19
(42.2)
44
(48.9)
0.764
(0.371–1.572)
0.464
S ess
(MBI)b16
(35.6)
36
(40.0)
0.828
(0.394–1.738)
0.617
S ess
(combina ion
o
c i e ia)c20
(44.4)
41
(45.6)
0.956
(0.466–1.963)
0.903
AH3(n
=
136)
Non- esponde s:
50
Responde s:
86
S ess
(in e iew)
27
(54.0)
47
(54.7)
0.974
(0.484–1.961)
0.941
S ess
(GHQ12)a20
(40.0)
43
(50.0)
0.667
(0.329–1.351)
0.259
S ess
(MBI)b15
(30.0)
37
(43.0)
0.568
(0.271–1.190)
0.132
S ess
(combina ion
c i e ia)c20
(40.0) 41
(47.7) 0.732
(0.361–1.483) 0.386
B
(n
=
135)
Non- esponde s:
59
Responde s:
76
S ess
(in e iew)
31
(52.5)
43
(56.6)
0.850
(0.429–1.683)
0.640
S ess
(GHQ12)a24
(40.7)
39
(51.3)
0.651
(0.327–1.293)
0.219
S ess
(MBI)b22
(37.3)
30
(39.5)
0.912
(0.453–1.836)
0.796
S ess
(combina ion
o
c i e ia)c24
(40.7)
37
(48.7)
0.723
(0.364–1.437)
0.354
OR
–
odds
a io;
95%
CI
–
95%
confidence
in e al.
aGene al
Heal h
Ques ionnai e
(GHQ12).
bMaslach
Bu nou
In en o y
(MBI).
cS ess
(in e iew
and
GHQ12)
o
s ess
(in e iew
and
MBI).
iangula ion
me hod
a
T0using
in e iews,
GHQ12 and
he
combina ion
o
he
h ee
me hods.
On
he
con a y,
we
did
no
find
any
s a is ically
significan
associa ion
be ween
he
o h-
e s
HAI
ab
i e
d op
g oups
a
T6and
he
p esence
o
ch onic
s ess
(Table
3).
Associa ion
be ween
o he
possible
con ounding
a iables
and
aemagglu ina ion-inhibi ion
ab
AH1 i e
d op
g oup
a
T6
Some
condi ions
ha
can
a ec
immuni y
could
ha e
been
possible
con ounding
ac o s,
when
we
conside ed
he
asso-
cia ion
be ween
s ess
and
he
HAI
ab
AH1 i e
d op
g oup
a
T6.
Using
he
Kolmogo o –Smi no
and
Shapi o–Wilk
es s,
we
ound
ha
he e
is
no
no mal
dis ibu ion
in
HAI
ab
AH1 i e
d op
g oup
a
T6and
in
no
change
in
HAI
ab
AH1 i e
a
T6 o
he
conside ed
con inuous
a iables
(p
<
0.001).
The e o e,
we
applied
he
Mann–Whi ney
es
o
compa e
hei
medians.
The
s a is ical
analyses
did
no
find
any
significan
di e -
ence
be ween
g oups
a
T6 o
he
a iables
(con inuous
and
dicho omous)
aken
in o
conside a ion
(Table
4).
Mul i a ia e
analysis
and
adjus ed
odds
a ios
o
s ess,
age
and
aemagglu ina ion-inhibi ion
ab
AH1 i es
a
T0
and
T1conside ing
aemagglu ina ion-inhibi ion
ab
AH1
i e
d op
g oup
a
T6
S ess
–
assessed
by
in e iew,
GHQ12 o
using
he
combina ion
o
he
h ee
me hods
–
was
he
exclusi e
a iable
associa ed
wi h
HAI
ab
AH1 i e
d op
g oup
a
T6,
bu
we
also
ook
he
age
a iable
in o
conside a ion
in
he
mul i a ia e
analysis.
Tha
op ion
was
made
because
age
is
a
s ong
ac o
influencing
immuni y
and,
in
he
simple
analysis,
he
median
di e ence
be ween
g oups
would
be
di e en
i
we
conside ed
a
confi-
dence
le el
o
90%
(ins ead
o
95%).
Fu he mo e,
Beye
and
colleagues
showed
ha
basal
HAI
ab
AH1 i es
influence
HAI
ab
AH1 i es
one
mon h
a e
Table
2
–
HAI
an ibodies
AH1,
AH3and
B
i es
a
T0in
non- esponde s
and
in
esponde s
AH1,
AH3and
B
a
T1.
HAI
an ibodies
a
T0Non- esponde s
a
T1Responde s
a
T1S a is ical
analysis
(Mann–Whi ney
es )
Md
(min–max)
Md
(min–max)
Md
di e ences
p
HAI
ab
AH1 i es
a
T0in
non- esponde s
AH1(n
=
45)
and
esponde s
AH1(n
=
90)
a
T1
640.0
(80–10,240)
20.0
(10–1280)
620.0
<0001
HAI
ab
AH3 i es
a
T0in
non- esponde s
AH3(n
=
50)
and
esponde s
AH3(n
=
86)
a
T1
160.0
(10–5120)
20.0
(10–1280)
140.0
<0001
HAI
ab
B
i es
a
T0in
non- esponde s
B
(n
=
59)
and
esponde s
B
(n
=
76)
a
T1
160.0
(20–10,240)
60.0
(10–640)
100.0
<0001
Md
-
median.
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(1):18–26
23
Table
3
–
S ess
in
HAI
an ibodies
i e
d op
g oup
and
in
no
change
in
HAI
Ab
i e
g oup
AH1,
AH3and
B
a
T6.
HAI
ab
g oups
a
T6Ch onic
s ess
assessmen
S ess
in
HAI
ab
i e
d op
g oup
a
T6
S ess
in
no
change
in
HAI
Ab
i e
g oup
a
T6
S a is ical
analysis
(Qui-squa e
es )
n
(%)
n
(%)
OR
(95%
CI)
p
AH1
(n
=
88)
HAI
ab
i e
d op
g oup:
57
No
change
in
HAI
ab
i e
g oup:
31
S ess
(in e iew) 36
(63.2) 10
(32.3)
3.600
(1.427–9.084)
0.006
S ess
(GHQ12)a33
(57.9)
11
(35.5)
2.500
(1.012–6.176)
0.045
S ess
(MBI)b25
(43.9)
10
(32.3)
1.641
(0.656–4.104)
0.288
S ess
(combina ion
o
c i e ia)c
34
(59.6)
7
(22.6)
5.068
(1.875–13.70)
0.001
AH3
(n
=
81)
HAI
ab
i e
d op
g oup:
48
No
change
in
HAI
ab
i e
g oup:
33
S ess
(in e iew)
25
(52.1)
21
(63.6)
0.621
(0.251–1.539)
0.302
S ess
(GHQ12)a26
(54.2)
(51.5)
1.112
(0.458–2.703)
0.814
S ess
(MBI)b20
(41.7)
16
(48.5)
0.759
(0.311–1.851)
0.544
S ess
(combina ion
o
c i e ia)c
23
(47.9)
18
(54.5)
0.767
(0.315–1.865)
0.558
B
(n
=
76)
HAI
ab
i e
d op
g oup:
51
No
change
in
HAI
ab
i e
g oup:
25
S ess
(in e iew)
26
(51.0)
17
(68.0)
0.489
(0.179–1.335)
0.160
S ess
(GHQ12)a27
(52.9)
12
(48.0)
1.219
(0.468–3.177)
0.686
S ess
(MBI)b17
(33.3)
13
(52.0)
0.462
(0.174–1.226)
0.118
S ess
(combina ion
o
c i e ia)c
22
(43.1)
15
(60.0)
0.506
(0.191–1.339)
0.167
OR
–
odds
a io;
95%
CI
–
95%
confidence
in e al.
aGene al
Heal h
Ques ionnai e
(GHQ12).
bMaslach
Bu nou
In en o y
(MBI).
cS ess
(in e iew
and
GHQ12)
o
s ess
(in e iew
and
MBI).
Table
4
–
Va iables
dis ibu ion
(s ess
no
included)
in
HAI
ab
AH1 i e
d op
g oup
a
T6and
in
no
change
in
HAI
ab
AH1
i e
g oup
AH1a
T6.
Va iables HAI
ab
AH1 i e
d op
g oup
a
T6(n
=
57)
No
change
in
HAI
ab
AH1 i e
g oup
a
T6
(n
=
31)
S a is ical
analysis
(Fishe
es
o
Qui-squa e
es
o
Mann–Whi ney
es )
n
(%)
n
(%)
OR
(95%
CI)
p
Male
gende
5
(8.8)
7
(22.6)
0.330
(0.095–1.145)
0.103a
Caucasian
53
(93.0)
31
(100)
0.631
(0.536–0.743)
0.293a
Shi
wo k
35
(61.4)
23
(74.2)
0.553
(0.211–1.453)
0.250a
Daily
sleep
hou s
<
7
20
(35.1)
8
(25.8)
0.643
(0.244–1.699)
0.372b
Smoke s
10
(17.5)
9
(29.0)
0.520
(0.185–1.461)
0.211b
Vi amin
supplemen s
10
(17.5)
4
(12.9)
1.436
(0.410–5.025)
0.762a
Fish
oil
consump ion
0
(0.0)
0
(0.0)
Daily
consump ion
o
yogu s
27
(47.4)
15
(48.4)
0.960
(0.400–2.304)
0.927b
No
egula
physical
ac i i y
29
(50.9)
11
(35.5)
1.883
(0.765–4.634)
0.166b
Pas
influenza
accine
17
(29.8)
12
(38.7)
0.673
(0.268–1.687)
0.397b
Influenza
accine
a
2006
14
(24.6)
11
(35.5)
0.592
(0.229–1.533)
0.278b
HAI
ab
AH1a
T0≥
40 25
(43.9)
17
(54.8)
0.643
(0.267–1.551)
0.325b
Va iables
HAI
ab
AH1 i e
d op
g oup
a
T6(n
=
57)
No
change
in
HAI
ab
AH1 i e
g oup
a
T6
(n
=
31)
S a is ical
analysis
(Fishe
es
o
Qui-squa e
es
o
Mann–Whi ney
es )
Md
(min–max)
Md
(min–max)
Md
di e ences
p
Age
31.0
(23.0–63.0)
26.0
(22.0–56.0)
5.0
0.072c
Body
index
mass
22.7
(17.7–37.8)
22.0
(18.0–37.5)
0.7
0.793c
HAI
ab
AH1 i es
a
T020.0
(10–640)
40.0
(10–1280)
−20.0
0.276c
HAI
ab
AH1
i es
a
T11280.0
(40–20,480)
1280.0
(160–20,480)
0.0
0.265c
Md
–
median.
aFishe
es .
bQui
Squa e
es .
cMann–Whi ney
es .
24
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(1):18–26
Table
5
–
Mul i a ied
analysis
(mul iple
logis ic
eg ession)
o
s ess
(assessed
by
iangula ion
me hod
using
GHQ12,
using
in e iew
and
using
he
combina ion
o
he
h ee
me hods)
in
HAI
ab
AH1 i e
d op
g oup
a
T6conside ing
age,
HAI
ab
AH1 i es
a
T0and
a
T1.
Ch onic
s ess
assessmen
Conside ed
a iables
in
mul i a ied
analysis
S a is ical
analysis
(mul iple
logis ic
eg ession)
Adjus ed
OR
(95%
CI)
p
GHQ12 a
Age
1.038
(0.989–1.089)
0.134
S ess
2.733
(1.039–7.186)
0.042
HAI
ab
AH1a
T00.998
(0.995–1.000)
0.100
HAI
ab
AH1a
T11.000
(1.000–1.000)
0.793
In e iew
Age 1.043
(0.994–1.094) 0.083
S ess
3.643
(1.371–9.684)
0.010
HAI
ab
AH1a
T00.999
(0.996–1.001)
0.236
HAI
ab
AH1a
T11.000
(1.000–1.000)
0.987
Combina ion
o
c i e iab
Age
1.044
(0.994–1.096)
0.087
S ess
5.223
(1.828–14.924)
0.002
HAI
ab
AH1a
T00.999
(0.996–1.001)
0.255
HAI
ab
AH1a
T11.000
(1.000–1.000)
0.892
Adjus ed
OR
–
adjus ed
odds
a io;
95%
CI
–
95%
confidence
in e al.
aGene al
Heal h
Ques ionnai e
(GHQ12).
bS ess
(in e iew
and
GHQ12)
o
s ess
(in e iew
and
MBI).
accina ion.28 The e o e,
we
also
conside ed
HAI
ab
AH1 i es
a
T0and
T1in
he
mul i a ia e
analysis.
We
ound
ha
s ess,
assessed
by
iangula ion
me hod
using
GHQ12,
using
in e iew
and
using
he
combina ion
o
he
h ee
me hods,
main ained
he
associa ion
wi h
HAI
ab
AH1 i e
d op
g oup
a
T6.
The
associa ion
be ween
HAI
ab
AH1 i e
d op
g oup
a
T6and
he
o he s
a iables
did
no
e eal
any
s a is ical
significance
(Table
5).
When
we
assessed
s ess
by
iangula ion
me hod
using
GHQ12,
he
model
was
s a is ically
significan
(p
<
0.029)
and
sui able,
gi en
ha
null
hypo hesis
was
no
ejec ed
in
he
Hosme –Lemeshow
es
(p
<
0.106).
The
model
showed
a
alid-
i y
a e
o
65.9.
When
we
assessed
s ess
by
iangula ion
me hod
using
in e iew,
he
model
was
s a is ically
significan
(p
<
0.009)
and
sui able,
gi en
ha
null
hypo hesis
was
no
ejec ed
in
he
Hosme –Lemeshow
es
(p
<
0.761).
The
model
showed
a
alid-
i y
a e
o
71.6.
When
we
assessed
s ess
by
iangula ion
me hod
using
he
combina ion
o
he
h ee
me hods,
he
model
was
s a-
is ically
significan
(p
<
0.002)
and
sui able,
gi en
ha
null
hypo hesis
was
no
ejec ed
in
he
Hosme –Lemeshow
es
(p
<
0.679).
The
model
showed
a
alidi y
a e
o
73.9.
Discussion
and
conclusions
When
human
beings
a e
exposed
o
ch onic
s esso s,
hey
may
espond
o
hem
wi h
neu oendoc ine
changes
ha
include
he
elease
o
neu opep ides,
monoamines
and
ho -
mones.
Mos
o
hose
subs ances
a e
able
o
change
he
immune
cells
beha iou .29
Psychological
ch onic
s ess
can
change
an ibody
(ab)
p o-
duc ion
and
kine ics
a e
accina ion,
in
pa icula
a e
he
influenza
accine
is
gi en
o
elde ly
people
who
ake
ca e
o
spouses
wi h
demen ia.9–12
Va ious
s udies
o
elde ly
people
ha e
ound
an
asso-
cia ion
be ween
exposu e
o
a
long- e m
s esso
(such
as
demen ia
spouse
ca egi ing)
and
a
small
p opo ion
o
hem
who
eached
a
leas
ab
HAI
i es
ha
we e
ou old
wha
hey
had
be o e
flu
accina ion,
assessed
one
mon h
a e
accina ion.13–15 Be ea emen
and
ma iage
seem
o
be
asso-
cia ed
wi h
an ibody
esponse
o
influenza
accina ion
in
he
elde ly
as
well.17
In
ou
s udy,
as
in
some
o he
s udies
in ol ing
young
adul s,18,23–25 we
did
no
find
any
associa ion
be ween
he
p esence
o
ch onic
s ess
in
nu ses
and
he
p opo ion
o
hem
ha
each
a
leas
ou
imes
he
ab
HAI
i e
le els
hey
had
be o e
flu
accina ion.
On
he
con a y,
o he
s udies
ha e
ound
an
associa ion
among
pe cei ed
dis ess,19 li e
e en s,20
neu o icism21 and
loneliness22 and
he
immune
esponse
o
flu
accina ion,
assessed
one
mon h
o
fi e
weeks
a e .
I
is
possible
ha
me hodological
issues
can
explain
dis-
c epancies
in
esul s
e ified
in
s udies
wi h
younge
g oups,
such
as:
(1)
di e en
ways
o
cha ac e ising
independen
a i-
ables;
(2)
samples
wi h
di e ing
demog aphic
cha ac e is ics
and
dimensions;
(3)
di e ing
his o ies
o
flu
i us
exposu e.
Wi h
espec
o
he
la e
issue,
ou
s udy
ound
ha
non-
esponde s
had
significan ly
highe
ab
HAI
AH1N1,
AH3N2and
B
i es
a
T0 han
esponde
g oups.
The e o e,
as
pos ula ed
by
Beye
and
colleagues,28 ab
HAI
i es
a
T0,
showed
o
be
an
impo an
con ounding
a iable
when
s udying
he
ela ion-
ship
be ween
s ess
and
immune
esponse
o
flu
accine
one
mon h
a e
accina ion
and
mus
be
conside ed.
Ne e heless,
we
ound
an
associa ion
be ween
he
p es-
ence
o
ch onic
s ess
(measu ed
in
h ee
di e en
ways)
and
a
d op
in
ab
HAI
(AH1N1)
a
T6.
O he
s udies
also
ound
an
asso-
cia ion
be ween
dis ess,19,25 li e
e en s,20 li e
e en s
weighed
wi h
pe cei ed
s ess,23 neu o icism,21 o
loneliness22 and
a
d op
in
ab
HAI
ou
o
six
mon hs
a e
accina ion.
Those
associa ions
we e
ound
o
a
leas
one
s ain
composing
he
flu
accine.
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(1):18–26
25
Ou
s udy
ound
a
la ge
p opo ion
o
nu ses
wi h
ch onic
s ess
in
he
HAI
ab
AH1 i e
d op
g oup
a
T6,
as
compa ed
o
he
no
change
in
HAI
Ab
AH1 i e
g oup
a
T6,
when
we
measu ed
s ess
by
iangula ion
me hod,
using
in e iew
o
GHQ12 o
assess
pe cei ed
s ess,
and
using
he
combina ion
o
he
h ee
me hods
(as
desc ibed
in
he
me hods
sec ion).
We
did
no
find
any
s a is ically
significan
associa ion
when
we
assessed
he
p esence
o
s ess
by
he
iangula ion
me hod
bu
using
he
MBI
exhaus ion
scale
o
measu e
pe cei ed
s ess.
A
possible
explana ion
is
he
ac
ha
he
MBI
exhaus-
ion
scale
measu es
specifically
wo k- ela ed
s ess
and
he
possible
immunologic
epe cussions
o
ch onic
s ess
seem
o
be
independen
o
he
s ess
sou ce.
As
desc ibed
in
o he
s udies,19–23,25 he
associa ion
be ween
s ess
and
a
d op
in
ab
HAI
a
T6did
no
occu
o
all
he
accine
s ains
componen s.
S ain
no el y
can
be
an
impo an
ac o
in
ha
analy-
sis,
as
a gued
by
o he
au ho s.15,20 P essman
and
colleagues,
o
example,
only
ound
an
associa ion
be ween
s ess
and
a
d op
in
HAI
ab,
ou
mon hs
a e
accina ion,
o
a
s ain
ha
was
no
included
in
p e ious
accina ions
he
pa ici-
pan s
ecei ed.25 In
ou
s udy,
he
exclusi e
s ain
ha
was
no
included
in
flu
accines
in
he
h ee
p eceding
yea s
was
he
A(H1N1)
s ain.
In
Po ugal
he
p edominan
ci cula ing
s ains
wi h
high
flu
ac i i y
since
1990
ha e
been
A(H3N2)
and
B.
F om
1990
o
he
beginning
o
he
s udy,
he
A(H1N1)
s ain
was
only
p e-
dominan
in
2005,
simul aneously
wi h
s ain
B,
and
2005
was
a
yea
wi h
e y
low
flu
ac i i y.30 We
also
know
ha
A
s ains
unde go
mo e
d i
mu a ions
han
B
s ains,31 so
his
can
con-
ibu e
o
hei
being
a
ela i e
no el y
o
he
pa icipan s’
immune
sys em.
Finally,
in
ou
s udy,
he
A(H1N1)
influenza
s ain
p o ed
o
be
he
mos
immunogenic
one,
showing
a
ise
in
he
HAI
Ab
i e
geome ic
mean
o
11.1.
A
(H3N2)
and
B
s ains
showed
ises
o
6.2
and
4.6
imes,
espec i ely,
be ween
T0and
T1.
I
is
possible
ha
he
bes
immunogenici y
obse ed
o
he
A
(H1N1)
s ain
was
ela ed
wi h
he
ac
ha
some
pa ici-
pan s
had
had
a
p ima y
in ec ion
wi h
an
A
(H1N1)
s ain,
so
he
esponse
o
A
(H1N1)
an igens
ha e
been
mo e
obus
in
hem.32 Tha
could
be
a
ac o
ha
may
influence
he
de ec-
ion
o
he
associa ion
be ween
s ess
and
d ops
in
HAI
ab
a e
a
pe iod
o
ime.
Gi en
ha
ou
sample
was
no
a
andomised
sample
because
i
depended
on
nu ses
olun a ily
being
accina ed
and
pa icipa ing
in
he
s udy,
we
analysed
dis ibu ion
di -
e ences
o
some
a iables
in
he
HAI
ab
AH1 i e
d op
g oup
a
T6and
he
no
change
in
HAI
Ab
AH1 i e
g oup
a
T6 ha
a e
no
included
in
d op
ou
c i e ia.
As
he e
a e
a
lo
o
a iables
o
which
we
do
no
ye
know
i
hey
can
influence
immu-
ni y,
we
s udied
hose
ha
a e
mos
e e ed
o
in
he
ele an
li e a u e.33
We
did
no
find
any
di e ences
in
he
dis ibu ion
o
he
s udied
a iables
in
he
wo
g oups
a
T6.
Ne e heless,
we
decided
o
include
ab
AH1 i es
a
T0,
ab
AH1 i es
a
T1and
age
in
mul iple
logis ic
eg ession.
The
eason
o
including
he
fi s
wo
a iables
was
he
s ong
sugges ion
in
li e a u e
ha
hey
can
influence
ab
i es
a e
accina ion
(immune
esponse),28 e en
hough
we
ound
no
e e ences
o
he
influence
hey
ha e
on
a
d op
in
i es
six
mon hs
a e
flu
accina ion.
Age
is
s ongly
ela ed
wi h
immuni y33 bu
we
did
no
find
any
di e ence
in
e ms
o
age
be ween
he
wo
g oups
conside ed
a
T6a
he
significance
le el
we
con-
side ed
(5%).
I
we
conside ed
a
significance
le el
o
10%
he
esul
would
be
di e en .
Hence,
we
also
included
age
in
he
mul i a ia e
analysis.
A e
he
mul i a ia e
analysis,
we
s ill
ound
an
associ-
a ion
wi h
s a is ical
significance
be ween
he
p esence
o
ch onic
s ess
and
he
HAI
ab
AH1 i e
d op
g oup
a
T6,
when
we
assessed
s ess
in
h ee
di e en
ways,
all
o
hem
using
he
iangula ion
me hod,
as
sugges ed
by
Cox
and
colleagues,
as
a
good
way
o
measu ing
s ess.26 The e o e,
he
ela ion-
ship
ha
we
ound
be ween
ch onic
s ess
and
a
d op
in
HAI
ab
a
T6suppo s
he
hesis
ha
s ess
can
nega i ely
influence
HAI
ab
i es
some
mon hs
a e
flu
accina ion
e en
in
people
in
adul s
unde
he
age
o
60.
As
we
could
no ice,
his
is
he
fi s
s udy
assessing
he
associa ion
be ween
ch onic
s ess
and
immune
esponse
o
influenza
accine
in
heal hca e
wo ke s,
who
is
an
impo an
a ge
g oup
o
influenza
accine.
The e-
o e,
in
an
occupa ional
heal h
en i onmen ,
i
is
easonable
o
conside
he
possible
in e e ence
o
ch onic
s ess
wi h
ab
i es
when
we
implemen
accina ion
p og ammes
o
p e en
biological
occupa ional
isks.
Funding
Au o idade
pa a
as
Condic¸ões
de
T abalho
(ACT)
unded
he
labo a o ial
e alua ion
o
he
s udy.
Conflic s
o
in e es
The
au ho s
ha e
no
conflic s
o
in e es
o
decla e.
e
e
e
n
c
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o
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