R e v is t a d a S o c i e d a d e B r as ile ir a d e M e d ic in a T r o p ic al 2 9 ( 5 ) : 4 4 1 - 4 4 5 , se t - o u t , 1 9 9 6 .
AN TIBODY RESPONSE TO SALM O NELLA TY P H LW
H UMAN SCHISTOSOMIASIS MANSONI
M aria Imaculada M uniz-Junqueira, José Tavares-Neto,
Aluizio Prata and Carlos Eduardo Tosta
A n tibody respon se to Salmonella typhi O an d H an tig en s w as ev alu at ed in 2 4 in div idu als w ith either hepatoin testin al or hepatosplen ic schistosom iasis m an son i befo re an d aft er ty phoid v accin ation , an d c o m p ar e d with that o f n o n - in fec ted controls. B efo re v accin ation , Schistosom a- in fected patien ts sho w ed a hig her fr e qu e n c y o f positiv e an tibo dy to O an tig en an d the sam e fr e qu e n c y to H an tig en w hen c o m p ared w ith that o f healthy in div idu als. H owever, those with hepatosplen ic schistosom iasis sho w ed hig her titres o f an tibo dy to H an tig en than those with hepatoin testin al disease o r healthy in div idu als. In fec t ed subjects, p artic u larly those with hepatoin testin al disease, sho w ed a de c r e as e d respon se aft er ty phoid v accin e. Tins dim in ished ability to m ou n t an im m u n e respon se tow ards ty phoid an tig en s din in g schistosom iasis m ay in terfere ivith the c le ar an c e o f the bac teria fr o m blo o d stream an d, therefore, p lay a role in the p ro lo n g ed su rv iv al o f salm o n ella as o bsew ed in so m e p atien ts w ith c hro n ic salm on ellosis asso c iat ed with schistosom iasis.
K ey -w ords: Schistosom iasis m an son i. Salmonella typhi. O an d H antig ens. C hron ic salm on ellosis asso c iat ed with schistosomiasis.
A ctiv atio n o f the im m u ne sy stem has b e e n d em o nstrated d u ring acu te schisto so m iasis2 3 27 and , altho u gh m o d ulatio n o f b o th the cellular15” and hu m o ral1819 im m u ne resp o n ses o c c u r later d uring the c h ro n ic p h ase o f the d isease, hig h lev els o f an ti-S c h is t o s o m a m an s o n i antibo d ies are still d etec tab le. H o w ev er, the ab ility o f in fec ted ind iv id uals to m o u nt an im m une resp o n se to u nrelated antig ens has no t y et b e e n clearly estab lished .
It has b e e n sh o w n that so m e S c his t o s o m a-in fe c t e d ind iv id uals co -infected w ith salm o nella p ro d u c e le s s a n tib o d ie s to b o th O an d H antig ens o f this b ac te ria20 23, and antib o d ies p resen t in their sera sh o w an im p aired ability to inhib it in v itro salm o nella gro w th1'. H o w ev er, seru m fro m S c h is t o s o m a- in fe c t e d ham sters can inhib it b acterial g ro w th13. O n the o th er hand , so m e h u m an stu d ies hav e in d ic ated that
D epartam ento de Patologia da Faculdade de Ciências da S aúd e d a U n iv e rs id ad e d e B ras ília, B ras ília, D F, D epartam ento de Clínica M édica da Faculdade de M edicina da U niversid ade Federal da Bahia, Salvador, BA e D epartam ento de Clínica M édica da Faculdade de M edicina do Triângulo M ineiro, U beraba, MG.
A ddress to: Dr* M aria Imaculada M uniz-Junqueira. Laboratório de Im unologia C elular/D epto de Patologia/FCS/U nB, 70910-9 0 0 Brasília, DF, Brasil. Fax: (0 6 1 ) 233 0 2 70910-9 6
Receb ido para p ub licação em 0 5 / 1 0 / 9 5 .
schisto so m iasis im p airs the im m u ne resp o n se to anti-salm o nella v ac c in e5, w h ile o thers d o no t se em to su p p o rt this c o n c lu sio n 26.
A n altered ab ility o f S c h is t o s o m a- in fe c t e d ind iv id uals to p ro d u c e an tib o d ies to u nrelated a n tig e n s m ay re s u lt in a c o n s tra in t to th e elim inatio n o f so m e p atho g ens. Fo r in stan c e, it has b e e n sho w n that an tib o d ies help the c le aran c e o f salm o n e lla fro m th e b lo o d stream 11. Th erefo re, a d efic ien t p ro d u ctio n o f antib o d ies to salm o nella in schisto so m iasis m ay facilitate the d ev elo p m en t o f the aty p ic fo rm o f s a lm o n e llo s is w h ic h o c c u rs in
Sch is t o s o m a-infected ind iv id u als.
This w o rk aim ed at ev alu ating the antib o d y resp o n se to S alm o n e lla t y p hi in S c his t o s o m a-in fe c t e d ind iv id uals b efo re and after ty p ho id v accine.
M A TERIA L A N D M ETH O D S
T h e ru le s p u t f o rw a rd b y th e H e ls in k i D eclaratio n fo r exp erim ents in hum an su bjects630 w e r e s t r i c t l y f o l l o w e d th r o u g h o u t th is inv estig atio n.
M u n iz - Ju n q u e ir ã M I, T av ar e s - N e t o J, P r at a A , T o sta CE. A n t ib o d y r e s p o n s e to Salm o nella typ hi in h u m a n s c h is t o s o m ias is m an s o n i. R ev is t a d a S o c i e d a d e B r as ile ir a d e M e d ic in a T r o p ic al 2 9 : 4 4 1 - 4 4 5 , se t- o u t, 1 9 9 6 .
co m p rised
16
individuals w ith d ie hepatointestinal,and 10 w ith the h ep ato sp len ic schisto so m iasis, ch arac teriz ed ac c o rd in g to the criteria d efined b y Prata21. Th eir c linic al an d nutritio nal status w ere satisfato ry . Egg s o f S c h is t o s o m a m an s o n i in fae c e s w ere q u antified by the Kato -Katz m etho d 8. Th e c o n tro l g ro u p co m p rised nine h ealth y ind iv id uals o f b o th se x e s, 20 to 50 y ears o ld (m e an ± SD = 29 ± 9), 70% b e in g C au casians.
T h e S alm o n e lla t y p hi v ac cin e, p rep ared
w ith 10s fo rm o l-treated b acteria strain Ty 2 b y the Institu to O sw ald o Cruz, w as intrad erm aliy ad m inistered in a sing le d o se, as ind ic ated b y the m anufacturer. Be fo re v ac c in atio n and 30 d ays after seru m an tib o d ies to O and H a n ti g e n s w e r e d e t e c te d u s i n g a W id a l ag g lu tinatio n test29 p ro v id ed b y Lab o rclin. Titres > 20 w e re c o n sid ered as p o sitiv e.
Th e results w ere statistically an alised b y the C hi-sq u are test and Fish e r’s e x ac t test, at a le v el o f 5% o f sig n ific an c e (p < 0.05).
RESULTS
A ntib o d ies to O antig en o f S alm o n e lla
t y p hi w e re d e te c te d in 3 o u t o f th e
2 6
Sc h is t o s ow a-in fec ted p atients (11.5% ) b efo re the ap p lic atio n o f ty p ho id v ac c in e an d in n o n e o f the no rm al c o n tro ls (Tab le 1). In the p o sitiv e ind iv id uals, the antib o d ies titres w ere 40, 80 and 160, and th ey p resen ted 96, 672 and 984 eg g s o f S c h is t o s o m a m an s o n i p e r g ram o f faec es, resp ectiv ely . Th e freq u en c y o f p re v ac c in atio n p o sitiv e titres to H antig en w as the sam e in in fec ted and h ealth y ind iv id u als (Tab le 1). H o w ev er, the hig hest titres o f an tib o d y to H antig en w ere fo u n d in the h ep ato sp len ic p atients and n o d ifferen ce w as d etec ted b e tw e e n the hep ato intestinal and c o ntro l g ro u p s (Tab le 2).
T able 1 - F r e q u e n c y o f p r e - v ac c in at io n p o sit iv it y o f an t ib o d y to
Salm o nella typhi O' a n d H an t ig e n s in he p at o in t e s t in al ( H I) a n d he p at o s p le n ic (H S) Schisto so m a m an s o m - in fe c t e d p at ie n t s a n d h e alt h y in div idu als.
A ntib o d ies to
Gro up O antig en H antig en
ns % ns %
N o rmal 0/ 9 0.0 4/ 9 44.4
HI 1/ 16 6.3 8/ 16 50.0
HS 2/ 10 20.0 5/ 10 50.0
p > 0.05 fo r b o th antig ens b y C hi-sq uare test ( 3 x 2 tab le) and Fisher's e x ac t test ( 2 x 2 tab le: H I x N o rm al. H S x N o rm al, H I x HS).
T able 2 - F r e q u e n c y o f hig h tit res o f an t ib o d y to s alm o n e lla H an t ig e n in h e p at o in t e s t in al (HT) a n d h e p at o s p le n ic fH S)
Schisto so m a m an s o n i- in fe c t e d p at ie n t s a n d h e alt h y in div idu als b e fo r e t y p ho id v ac c in e .
Gro up Titre > 80
ns %
N o rmal 1/ 4 25
HI 2/ 8 25
HS 4/ 5 80
p > 0.05 b y Fisher's exac t test ( 2 x 2 tab le: HI x N o rm al, HS x N o rm al, HI x HS).
Thirty d ays after v ac cin atio n , 20.8% o f S c h is t o s o m a- in fe c t e d p atients and 55.5% o f n o rm a l c o n tr o ls p r e s e n te d a n ti b o d ie s to salm o nella O antig en. W ithin the g ro u p o f i n f e c te d in d iv id u a ls a d i f f e r e n c e in th e freq u en c y o f p o sitiv ity w as fo u nd b e tw e e n the hep ato intestinal (12.5% ), hep ato sp len ic (37.5% ) and no rm al (55.5% ) su b jec ts (Tab le 3). A n antib o d y resp o n se to H antig en w as also less freq u ently fo u nd in the h ep ato intestinal (50% ) th an in h e p a to s p le n ic ( 7 5 % ) o r n o rm a l ind iv id uals (100% ) (p < 0.05) (T ab le 3).
T able 3 - F r e q u e n c y o f an t ib o d y r e s p o n s e to Salm o nella typhi O a n d H an t ig e n in he p at o in t e s t in al Th i) a n d h e p at o s p le n ic (H S) p at ie n t s a n d h e alt h y in div idu als aft e r t y p ho id v ac c in at io n .
Gro up A ntibo d y resp o nse to
O antigen H antig en
ns % n2 %
Normal 5/ 9 55.5 9/ 9 100
HI 2/ 16 12.5* 8/ 16 50**
HS 3/ 8 37.5 6/ 8 75
p - 0.07 fo r O antig en b y C hi-sq uare test ( 3 x 2 tab le) p = 0.03 fo r H an tig en by C hi-sq uare test ( 3 x 2 tab le)
* p = 0.058 fo r O antig en b y Fisher's exac t test ( 2 x 2 tab le: H I x N o rmal)
**p * 0.02 fo r H antig en b y Fisher's exac t test ( 2 x 2 tab le: HI x no rm al)
D ISCUSSIO N
Befo re v ac cin atio n , 11.5% o f S c his t o s o m a-in fec ted p atients sho w ed p o sitiv e antib o d y resp o n se to salm o nella O antig en as c o m p ared to n o resp o n se o f health y co ntro ls. H o w ev er, the b asal freq u en c y o f reactiv ity to salm o nella H an tig en in o u r in fec ted g ro u p w as sim ilar to that o f the c o ntro ls. This sam e freq u en c y o f antib o d ies to salm o nella w as p rev io u sly sho w n b y Shikanai-Yasu d a et a I25 in h ep ato sp len ic p atients an d b y M ilho m en an d Su assu na14 in healthy ind iv id uals.
M u n iz - Ju n q ue ir a M I, T av ar e s - N e t o J, P r at a A , T osta CE. A n t ib o d y r e s p o n s e t o Salm o nella typ hi in h u m a n s c h is t o s o m ias is r n an s o n i. R e v is t a d a S o c i e d a d e B r as ile ir a d e M e d ic in a T r o p ic al 2 9 :4 4 1 - 4 4 5 , s e t - o u t , 1 9 9 6 .
ind icates rec en t in fec tio n b y this b ac te ria1410. H o w e v e r, s in c e o u r p a tie n ts h ad n e ith e r a h isto ry n o r an y c lin ic a l e v id e n c e o f o v e rt s a l m o n e l l o s i s , it is p o s s i b l e th a t a n ti- O ag g lutinins w ere o rig inated fro m su b clinical s a l m o n e l l a b a c te r e m i a s . O u r f in d in g o f i n c r e a s e d l e v e l s o f a n ti- H a n ti b o d i e s in su b jec ts w ith h ep ato sp len ic schisto so m iasis su p p o rts this hy p o thesis. A no ther p o ssib ility w h ic h c an n o t b e ru led o u t is the o c c u rren c e o f c r o s s a n ti g e n s b e tw e e n s a l m o n e ll a a n d sc h isto so m e7.
In o u r stud y, sch isto so m e-infected p atients, p artic u larly th o s e w ith th e h e p a to in te s tin a l d is e a s e , sh o w e d an in a d e q u a te an tib o d y resp o n se to salm o n ella O and H antig ens after a sing le d o se o f ty p ho id v ac cin e. T h e im m u ne resp o n se o f h ep ato sp len ic su b jec ts ap p ears to b e less im p aired , as p rev io u sly sho w n after three d o ses o f the v ac c in e 26 in th o se w ith this fo rm o f the d isease. Th e find ing that su p resso r T ly m p h o c y te s (C D 8+) are in c re ase d in h ep ato intestinal p atients and d ec reased in th o se w ith h e p ato sp le n ic sc h isto so m iasis28, m ay h e lp u n d e rs ta n d in g th e s e re su lts. A lternativ ely , the b etter antib o d y resp o n se o f h e p a to s p le n ic in d iv id u als m ay b e d u e to p rev io u s c o n tac t w ith salm o nella, m ad e easier b y the p o rto -sy stem ic shu nts fo u nd in these p atients. T h e in c reased p re-v accinatio n lev els o f anti-salm o nella antib o d ies in this gro up fav o rs this p o ssib ility .
It has b e e n rec o g n iz ed that b o th the functio ns o f T lym p ho cy tes1517 and m acro p hag es16 are altered in S c h is t o s o m a- in fe c t e d p atients. O u r d ata d e m o n s tra te th at th e a b ility to p ro d u c e an tib o d ies to u nrelated antig ens is also im p aired in schisto so m iasis. Th e fac t that increasing the an tig en ic stim ulu s m ay ind u ce antib o d y p ro d u ctio n in in fec ted su b jec ts26 m ay b e in te rp re te d as an tig e n ic c o m p e titio n 12 b etw een schisto so m e27 and salm o nella9 antig ens p resent in the seru m o f th e se ind iv id uals.
T h e d e c re a s e d a b ility o f s c h is to s o m e - in fec ted ind iv id uals to m o u nt an ad eq u ate im m u ne resp o n se to salm o n ella m ay v ery w ell c o ntrib u te to the estab lishm ent and p ro lo ng ed surv iv al o f this b ac teria in su b jec ts su ffering fro m schisto so m iasis.
RESUM O
A resposta d e an ticorpos p a r a o s an tíg en os O e H d a Salmonella typhi f o i av aliada em 2 4 in div ídu os
com esquistossomose hepatointestinal ou hepatoesplênica an tes e apô s v ac in aç ão an titifoídica, e c o m p ar ada com a resposta de in div ídu os con troles n orm ais. A ntes d a v ac in aç ão , p ac ie n t e s esqu istossom óticos m ostraram u m a m aio r fr e q u ê n c ia d e an t ic o ip o s positiv os p ar a o an tíg en o O e a m esm a fr e q u ê n c ia d e an t ic o ip o s positiv os p ar a o an tíg en o H qu an do c o m p arada c o m aqu e la de in div ídu os con troles n o rm ais. P orém , aq u e le s c o m esqu istossom o se he p at o e s p lê n ic a m o st raram títulos m aio r e s de an t ic o ip o s p ar a o an tíg en o H do qu e aqu eles c o m a fo r m a hepatoin testin al d a do e n ç a ou os in div ídu os c on troles n orm ais. P ac ien t es esqu istossom ótic os, partic u larm en te aqu eles com a fo r m a hepatointestinal, m ostraram u m a m en o r resposta após a v ac in aç ão antitifoídica. Esta m en or c ap ac idade p ar a ap resen t ar u m a resposta im u n e p ar a an tíg en os d e salm o n ela p o d e in terferir c o m a retirada d a bac téria d a corren te san g u ín ea e, portan to, co n tribu ir c o m o um dos determ in an tes de su a p r o lo n g ada sobrev iv ên cia c o m o o bs e w ada em p ac ie n t e s com salm o n elo se septicêm ic a p ro lo n g ada asso c iada â esquistossomose.
P alav ras- c hav es: Esqu isto so m o se rn an son i.
Salmonella typhi, A n tíg en os O e H . Salm on elose septicêm ica p ro lo n g ada asso c iada à esquistossomose.
A CK N O W LED G EM EN TS
W e thanks Mr. Ro d o lfo G o m es d e O liv eira and Mr. Jo aq u im C ând id o d e Lim a b y their h elp in the field stu d ies.
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