R e vista da S o c ie d a d e B ra s ile ira d e M e d ic in a T r o p ic a l. 1 6 2 3 - 3 0 , J a rn - M a r , 1 9 8 3
C O U R S E O F I N F E C T I O N A N D H I S T O P A T H O L O G I C A L L E S I O N S I N
M I C E I N F E C T E D W I T H S E V E N T E E N
Trypanosoma cruzi
S T R A I N SI S O L A T E D F R O M C H R O N I C P A T I E N T S
1
B R S c h le m p e r J r 2 , C M Á v i l a 3 , J R C o u r a 4 , Z B r e n e r4
M ic e w e re in f e c te d w it h b lo o d fo r m s o f 17 T ry p a n o s o m a c ru z i s tr a in s r e c e n tly is o la t-e d f r o m c h r o n ic p a tit-e n ts , w h ic h w t-e rt-e d a s s ifit-e d as o f lo w , m t-e d iu m o r h ig h v iru lt-e n c t-e o n g ro u n d s o f th e p r e p a te n t p e r io d , p a ra s ite m ia a n d m o r t a lit y a t th e a c u te phase. A t o t a l o f
2 1 2 m ic e w e re s tu d ie d a f t e r 3 , 6 , 9 a n d 12 m o n th s o f in fe c tio n . In th e c h r o n ic phase, in t r a c e llu la r p a ra s ite s w e re d e te c te d in 1 1 .0 % ,2 7 .9 % a n d 54.0,% o f m ic e in o c u la te d ,
res-p e c tiv e ly , w it h th e lo w , m e d iu m a n d h ig h v ir u le n t strains ( r = 0 .9 8 , p < 0 .0 0 5 ) . H e a r t fib r o
-sis was a ls o r e la te d to v iru le n c e , a ffe c tin g 5 .7 % , 1 1 .6 % a n d 3 0 .8 % ( r = 0 .9 8 , p < 0 .0 0 1 ) o f th e m ic e in o c u la te d w it h th e a b o v e s tra in s ; a s im ila r r e la tio n s h ip w as o b s e rv e d b e tw e e n
in t e n s it y a n d fr e q u e n c y o f th e h e a rt in f la m m a t o r y r e a c tio n a n d th e s e v e r ity o f in f e c tio n a t it s e a r ly stage. N e c r o t iz in g a r t e r it is w as d e te c te d in 12.2% o f th e in o c u la te d a n im a is
a n d th is le s io n w as r e la te d to th e in f e c t io n d u r a t io n r a th e r th a n to s tr a in c h a ra c te ris tic s . I n f la m m a to r y le s io n s a n d tis su e p a ra s itis m w e re s ta b le w it h in th e p e r io d o f o b s e rv a tio n ,
w h e re a s fib r o s is w as Progressive. T he fin d in g s s uggest t h a t m ic e m a y re p ro d u c e h e a rt
le s io n s re s e m b lin g h u m a n p a t h o lo g y a n d t h a t o rg a n dam ag e a p p a r e n tly d e p e n d s o n th e p a ra s ite v iru le n c e .
( K e y w o r d s : T ry p a n o s o m a c ru z i. S tra in s . H is to p a th o lo g y . M o u s e ).
A n e x p e rim e n ta l c h ro n ic m o d e l o f Chagas' disease in w h ic h th e lesions resem ble th e p a th o lo g y pre sen t in T ry p a n o s o m a c r u z i in fe c te d hum ans w o u ld be h ig h ly d es ira b le fo r im m u n o - p a th o lo g ic a l and re la te d studie s. Dogs c h ro n i- c a lly in fe c te d w ith T. c r u z i m a y d is p la y m ild fo c a l c h ro n ic m y o c a rd itis w ith scarce fib ro s is , w h ic h is c h a ra c te ris tic o f th e in d e te rm in a te fo rm o f Chagas' disease. H o w e ve r, th e d evelo p- m e n t o f th e ty p ic a l m y o c a rd io p a th y is o fte n u n p re d ic ta b le a nd m a y o c c u r in o n ly a fe w a n i m ais. R a b b its have been d escribe d as a su ita b le c h ro n ic m o d e l b y T e ix e ira e t a l.18 b u t th e re- su lts are s till c o n tro v e rs ia l d e sp ite re ce n t fin d ings c o n firm in g th e o ccu rre n ce o f ty p ic a l h e a rt lesions in th is h o s t13.
M ice c o u ld be v e ry usefu l m od els fo r c h ro n ic C hagas' disease because o f th e ir a v a ila b ility , lo w m a in te n a n ce costs, h a n d lin g fa c ility and th e p o s s ib ility o f w o rk in g w ith anim a is o f k n o w n g e n e tic b a c k g ro u n d . In filtra te s o f m o n o n u c le a r ce lls, fib ro s is and n e u ro n a l d e s tru c tio n have been re p o rte d in c h ro n ic a lly in fe c te d m ice 2 . R e c e n tly , h is to p a th o lo g ic a l lesions and e le ctro - c a rd io g ra p h ic changes resem b ling th ose fo u n d in th e h um an c a rd io p a th y w ere described in
T. c r u z i in fe c te d m ic e 11. Nevertheless, a
m o re precise s ta n d a rd is a tio n o f th is m o d e l is s till needed, c h ie fly in aspects rela te d to th e in flu e n c e o f parasite strain s and th e course o f in fe c tio n . In th is pap er w e stu d ie d th e Progres sive aspects o f th e c h ro n ic lesions ind uc e d in
I 1 ) S u p p o rte d b y th e N a tio n a l R e se arch C o u n c il, B ra s il.
( 2 ) U n iv e rs id a d e F e d e ra l d e S a n ta C a ta rin a , (3 ) U n iv e rs id a d e F e d e ra l d o R io d e J a n e iro , (4 ) F u n d a ç ã o O s w a ld o C ru z , B ra s il.
R e c e b id o p a ra p u b lic a ç ã o e m 2 9 / 1 2 / 8 2
Schlemper Jr BR, Ávila CM, Coura JR, Brener Z. Course o f infection and histopathological lesions in mice infected with seventeenTr y p an o so m a cr u zi strains isoleted from chronic patients. Revista da Sociedade Brasileira de Medicina Tropical
16:23-30, 1983
m ice b y 17 T. c r u z i strain s iso la te d fr o m c h ro n ic p atie nts, as w e ll as th e role p la ye d b y th e parasite v iru le n ce in th e pathogenesis o f th e disease.
M A T E R IA L A N D M E T H O D S
T. c r u z i " s tra in s " . T h e parasite strain s w ere isola ted b y xe no dia gn osis p e rfo rm e d in p a tie n ts using 4 0 n ym p h s o f T ria to m a infe s ta n s . M eta- c y c lic try p o m a s tig o te s w ere c o lle c te d fro m th e faeces and u rin e o f p o s itiv e ins e cts19 and ino- cu la te d in to n o rm a l and X -irra d ia te d (5 0 0 r) m ice b y th e in tra p e rito n e a l ro u te . F u rth e r serial b lo o d passages w ere ca rried o u t, a cco rd in g to th e ch a ra cte ristics o f th e e stab lishe d in fe c tio n s , in variab le p eriod s o f tim e b etw een 15 and 30 days, using n o rm a l m ice. T h e n u m b e r o f passa ges o f th e strain s in m ice b e fo re u tiliz a tio n in th e e x p e rim e n ts ranged fro m 1 to 10 b u t, in m o st instances, th e parasites w ere used a fte r 7 to 9 serial passages. O f th e seventeen strain s used, eleven (V L -1 to V L -1 1 ) w ere isola ted fro m p a tie n ts liv in g in V irg e m da Lapa and six (lg-1 to lg-6) in Ig uatam a, b o th e n d e m ic areas in th e S tate o f M inas G erais, B ra sil. T he strain s had been isola te d fro m p a tie n ts w ith d iffe re n t c h ro n ic c lin ic a i fo rm s o f Chagas' disease, name- ly, 9 o f in d e te rm in a te , 2 o f ca rdiac, 3 o f diges- tive and 2 o f ca rd ia c plus dig estive fo rm s . T he isoenzym e p a tte rn s d e te rm in e d in 10 strain s fro m V irg e m da Lapa and 3 fro m Ig u a ta m a 15 show ed th a t ali o f th e m w ere e q u iv a le n t to zym od em e a1 o f M iles et a l.12, 14. M ale a lb in o o u tb re d m ice w e ig h in g 15 — 18g w ere used. In some e x p e rim e n ts C 3H m ale m ice o f th e same w e ig h t w ere also used.
C ours e o f th e a c u te in f e c t io n . G ro u p s o f 7 to 9 m ice w ere in o c u la te d b y th e in tra p e rito neal ro u te w ith 5 x 10 3 b lo o d s tre a m fo rm s o f th e d iffe re n t strains. Th e pa ra site m ia was d e te r m in ed a cco rd in g to B re n e r5 . Th e p re p a te n t p e rio d and th e curves o f parasite m ia w ere d e te r m in ed b y d a ily b lo o d e x a m in a tio n p e rfo rm e d d u rin g th e fir s t days o f in fe c tio n and, a fte r- w ards, b y c o u n tin g parasites every 3 to 4 days u n til th e 5 0 th da y o f in fe c tio n . M o r ta lity rates were reco rd ed d a ily .
S tu d ie s o f th e c h r o n ic p ha se. G ro u p s o f 20 — 25 m ice w ere in o c u la te d b y th e in tra p e ri to ne al ro u te w ith b lo o d s tre a m fo rm s o f ali 17 strains. In 12 g ro ups th e anim ais received ino- cula o f 5 x 10 3 parasites; in 4 gro up s, 1 x 104 parasites and, fin a lly , in one g ro u p , 2 x 104
b lo o d fo rm s . G rou ps o f u n in fe c te d m ice o f th e same age and sex w ere used as C o n t r o l s . T he
a nim a is w ere k ille d u s u a lly 9 0 and 1 80 days a fte r in fe c tio n ; in some e x p e rim e n ts , in fe c te d and c o n tro l a nim ais w ere k e p t in th e la b o ra to ry f o r 2 7 0 and 3 6 5 days, and th e n k ille d . Frag- m ents o f th e fo llo w in g organs and tissues w ere c o lle c te d and fix e d in 10% fo rm a ld e h y d e : h e a rt ( in t o t u m ) , esophagus, sm all in te s tin e , co lo n , liv e r, spleen and sk e le ta l m uscle (tric e p s ). F ro m each fra g m e n t and fr o m th e w h o le h e a rt th re e h is to lo g ic a l sections o f 5 /um separated b y 2 0 jum in te rva ls w ere o b ta in e d . T h e se ction s w ere sta in e d b y h e m a to x y lin -e o s in as w e ll as b y th e m e th o d o f Masson fo r th e s p e c ific s tu d y o f fib ro s is . T h e h is to lo g ic a l p re p a ra tio n s w ere c o d e d and th e n e xa m in e d fo r p aras itism and lesions.
S ta tis tic a l a n a /y s is . L in e a r regression was used to establish c o rre la tio n s whereas th e C hi- squared ( X 2 ) te st was used to e stim a te sig n ifi- cance.
R E S U L T S
C ou rs e o f th e a c u te p h a s e. T h e analysis o f th e course o f in fe c tio n in th e va rio u s group s o f m ice in o c u la te d w ith th e d iffe r e n t strain s p e rm itte d to d iffe re n tia te th e m in to : G ro u p I, in c lu d in g strain s V L -1 , V L -5 , V L -6 , V L -8 , lg-1, lg-2, lg-3, lg-4 and lg-5. T h e viru le n c e o f these strain s was lo w and th e y in d uc e d in fe c tio n s in m ice w ith a long p re p a te n t pe rio d (11 to 30 d a ys ), th e highe st p a ra site m ia o c c u rrin g b etw een 21 and 4 0 days o f in fe c tio n w ith a m a x im u m o f 10® p aras ite s/m l. A li anim ais survived th e acute phase, w ith th e e x c e p tio n o f the g ro u p in o c u la te d w ith th e V L -6 stra in w h ic h k ille d 12% o f th e m ice. G ro u p II, in c lu d in g strain s o f in te rm e d ia te v iru lence (V L -2 , V L -3 , V L -4 , V L -7 , V L -9 and V L - 1 1). T he p re p a te n t p e rio d was s h o rte r (8 to 18 days), th e peaks o f parasite m ia w ere d e te ct- ed b etw e en 23 and 29 days o f in fe c tio n , and th e n u m b e r o f b lo o d parasites a t th is tim e reached 6 x 1 0 s /m l. Th e an im a is also survived th e acute phase b u t, co nv e rse ly to w h a t was observed w ith th e strain s o f g ro u p I, m o r ta lity c o u ld be in d u ce d b y increasing th e n u m b e r o f b lo o d fo rm s in th e in o c u la . G ro u p III, w ith tw o h igh v iru le n t strain s (V L -1 0 and lg-6). T h e p re p a te n t p e rio d was ra th e r s h o rt (6 to 12 days),
Schlemper Jr BR, Ávila CM, Coura JR, Brener Z. Course o f infection and histopathological lesions in mice infected with seventeen Tr y p a n o so m a cr u zi strains isoleted from chronic patients. Revista da Sociedade Brasileira de Medicina Tropical
16:23-30, 1983
D a y s a f t e r i n o c u l a t i o n
Fig . 1 — C u rv e s o f p a ra s ite m ia in g ro u p s o f m ic e in o c u la te d w it h 5 .0 0 0 b lo o d s tre a m try p o m a s tig o te s o f T . c r u z i s tra in s o f lo w ( lg -3 , lg -3 I r r . ) , in te rm e d ia te ( V L - 3 ) a n d h ig h v ir u le n c e (Ig , 6 , V L - 1 0 ). In th e e x p e rim e n t p e r fo r m e d w it h lg -3 ( I r r . ) th e p a ra s ite s w a s in o c u la te d in t o im rn u n o s ijp p re s s e d X - ir ra d ia te d m ic e .
Schlemper Jr BR, Ávila CM, Coura JR, Brener Z. Course o f infection and histopathological lesions in mice infected with seventeen Tr y p an o so m a cr u zi strains isoleted from chronic patients. Revista da Sociedade Brasileira de Medicina Tropical
16:23-30, 1983
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Schlemper Jr BR, Ávila CM, Coura JR, Brener Z. Course o f infection and histopathological lesions in mice infected with seventeen Tr y p a n o so m a cr u zi strains isoleted from chronic patients. Revista da Sociedade Brasileira de Medicina Tropical
16:23-30, 1983
rr-v <r-v
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"r-F ig . 3 — A : S tr a in V L - 7 , c h ro n ic p ha se, 1 8 0 d a y s o f in fe c tio n . C h r o n ic m y o c a r d itis w it h m o n o c u c le a r in f ilt r a t e a n d m ild fib r o s is ( 2 0 0 X ) ; B : S tr a in V L - 6 , c h r o n ic p ha se, 2 7 0 d a y s o f in fe c tio n . M o n o n u c le a r in fla m m a to r y ce lls a n d fib ro s is ( 2 0 0 X ) ; C : S tr a in V L - 2 , c h ro n ic p h a se , 2 7 0 d a y s o f in fe c tio n . C h r o n ic m y o c a r d itis . D e s tru c tio n o f h e a rt m u s c le c e lls a n d fib r o s is ( 3 2 0 X ) ; D : S tr a in V L - 1 , c h r o n ic p h ase, 9 0 d a y s o f in fe c tio n . S k e le ta l m u s c le c e lls . N e c r o tiz in g a r te r itis ( 2 0 0 X ) .
Schlemper Jr BR, Ávila CM, Coura JR, Brener Z. Course o f infection and histopathological lesions in mice infected with seventeen Tr y p an o so m a cr u zi strains isoleted from chronic patients. Revista da Sociedade Brasileira de Medicina Tropical
16:23-30, 1983
and m o st anim ais d ie d b etw een 2 0 to 3 0 days a fte r in fe c tio n w ith parasitem ias as h ig h as 2 — 3 x 106 p aras ite s/m l.
T y p ic a l curves o f parasite m ia are illu s tra te d in Fig u re 1.
TIS S U E P A R A S IT IS E M A N D P A T H O L O G Y A T T H E C H R O N IC S T A G E
Tissue p a ra s ite s . F ro m th e to ta l o f 2 1 2 e xam in e d anim ais, in tra c e llu la r parasites w ere d e te cte d in 4 2 (19 .8 % ), d is trib u te d am ong 13 o f th e 17 g ro ups o f a nim a is in o c u la te d w ith th e variou s strains. T h e presence o f tissue parasites in th e c h ro n ic phase was d ir e c tly re la te d to th e v iru le n ce e x h ib ite d b y th e strain s in th e acute stage o f in fe c tio n : 11.4% (1 4 /1 2 2 ), 27 .2 % (2 1 /7 7 ) and 53.8 % (7 /1 3 ) o f th e m ice in fe c te d re sp ec tiv e ly w ith th e strain s o f lo w , in te rm e d ia - te and h igh v iru le n c e d isp la ye d in tra c e llu la r pa rasites, a fin d in g o f h igh sig n ific a n ce (r = 0 .9 9 , p < 0 .0 0 1 ). A n e x c e p tio n was rep resented b y strain V L -6 w h ic h , a lth o u g h o f lo w viru le n ce , ind uce d tissue p a ra sitis m in 46 % o f th e anim ais. The percentage o f anim a is sh o w in g tissue para sites in th e c h ro n ic phase was ra th e r stable , as fo llo w s : 3 m o n th s , 22.8 % ; 6 m o n th s , 15.0% ; 9 m o n th s, 20.0 % and 12 m o n th s , 30.8% .
In fla m m a to r y le sio n s. In filtra te s o f in fla - m m a to ry cells, p re d o m in a n tly m o n o n u c le a r cells
were th e m o s t fre q u e n t lesions in th e h e a rt and skeletal m uscle. P ra c tic a lly ali in fe c te d anim ais d isplayed variab le degrees o f in fla m m a to ry lesions in th e he a rt, fro m sm all fo c i to d iffu s e c o n flu e n t cell in filtr a tio n (Figs. 2 e 3 ). In gene ral th e lesions w ere m ore severe in th e atria than in th e ve n tric le s. T h e fre q u e n c y and in te n - s ity o f th e in fla m m a to ry lesions w ere d ir e c tly related to th e v iru le n ce o f th e s tra in in th e acute phase, w ith th e e x c e p tio n o f stra in V L -6 w h ic h was o f lo w v iru le n ce b u t in d u ce d a severe c h ro n ic m y o c a rd io p a th y .
A c e rta in s ta b ility o f th e lesions o ccu rre d w ith in th e p e rio d o f 3 to 12 m o n th s o f obser- v a tio n and no te n d e n c y to d e clin e o r enhance- m e n t o f th e in fla m m a to ry process c o u ld be observed. C ell in filtr a tio n o f th e in tra c a rd ia c gangliae o f th e a u to n o m ic nervous system was
also o fte n present.
F ib ro s is . F ib ro sis was d ete cte d in m ice
in fe cte d w ith 10 o u t o f th e 17 strain s inve sti- gated. T his lesion o c c u rre d in 5.7% o f th e 122 anim ais in o c u la te d w ith th e lo w v iru le n t strain s, 11.6% o f 77 in fe c te d w ith th e strain s o f in te r- m ed ia ry viru le n ce and 30.8 % o f 13 anim ais h arbo rin g th e high v iru le n t parasites (r = 0 .9 8 ,
p < 0 .0 1 ). T h e fib ro s is was P r o g r e s s i v e and has
been fo u n d in 0% (0 /7 9 ), 7.5% (6 /8 0 ), 2 5 .0 % (1 0 /4 0 ) a nd 30.8 % (4 /1 3 ) o f th e m ic e in fe c t ed fo r re s p e ctive ly 3, 6, 9 and 12 m o n th s
( r = 0 .9 8 , p < 0 .0 0 1 ).
N e c r o tiz in g a r t e r it is . T h is lesion w as cha- ra c te riz e d b y in f iltr a t io n o f in fla m m a to ry cells in th e w a ll o f arte rie s w ith necrosis p re d o m i n a n tly in th e in tim a and m edia (Fig . 3 ). S uch lesions w ere fo u n d m o s tly in ske le ta l m uscle b u t also in th e h e a rt and c o lo n ; th e y w ere d e te c te d in a nim ais in o c u la te d w ith 13 o f th e 17 strain s and fo u n d in 2 6 o u t o f 2 1 2 an im a is (1 2 .2 % ). T h e vascula r lesions w e re a p p a re n tly P rogressive since th e y w e re observed in 1.6% , 20.0 % , 2 7 .3 % a nd 4 5 .5 % o f th e a nim ais sacri- fic e d re s p e ctive ly a fte r 9 0 , 180, 2 7 0 and 3 6 5 d ays o f in fe c tio n (r = 0 .9 8 ). N o c o rre la tio n c o u ld be e stab lish ed b etw een th e prevalence o f n e c ro tiz in g a rte ritis and e ith e r in fla m m a to ry re a c tio n o r s tra in viru le n ce .
Th e describ ed lesions w e re n o t fo u n d in th e c o n tro l anim a is w ith in th e p e rio d o f observa- tio n . N o re la tio n s h ip c o u ld be e stab lishe d b e t w een th e p a th o g e n ic ity o f th e strain s and th e c lin ic a i fo rm s o f p a tie n ts fr o m w h o m th e y had been isola te d .
D IS C U S S IO N
S om e re q u ire m e n ts fo r th e id e n tific a tio n o f su ita b le c h ro n ic m ode ls fo r Chagas,disease have been a lre a d y established and o ne o f th e m is th a t th e a n im a l s h o u ld d e ve lo p lesions w h ic h w o u ld resem ble h u m a n p a th o lo g y 15. S om e o bs e rv a tio n s in th e lite ra tu re suggest th a t m ice m ig h t be su ita b le m o d els fo r th e c h ro n ic cha- gasic m y o c a rd io p a th y 11. H ow ever, a s tu d y o f th e in flu e n c e o f th e n a tu ra l course o f in fe c tio n o f d iffe r e n t T. c r u z i strain s in th e develop- m e n t o f h is to p a th o lo g ic a l lesions, m a in ly in th e h e a rt, has n o t y e t a p p a re n tly been re p o rte d . In th is paper w e stu d ie d th e ro le p la ye d b y n e w ly isola te d strain s fro m c h ro n ic p a tie n ts w ith d iffe r e n t c lin ic a i fo rm s , p re se n tin g va ria ble degrees o f v iru le n ce , o n th e p a th o lo g y o f in fe c t ed m ice.
Schlemper Jr BR, Ávila CM, Coura JR, Brener Z. Course o f infection and histopathological lesions in mice infected with seventeen Tr y p a n o so m a cr u zi strains isoleted from chronic patients. Revista da Sociedade Brasileira de Medicina Tropical
16:23-30, 1983
in th e acute phase, an in d ic a tio n th a t th e increased m u ltip lic a tio n rate o f som e T. c r u z i strains is an in trin s ic c h a ra c te ris tic w h ic h is m a in ta in e d in b o th disease stages. Parasites in th e he a rt have been d e te c te d in a b o u t 50% o f m ice in o c u la te d b y F e d e rici et a l.9 and G onza- lez-Cappa e t a l.10 a nd m a in ta in e d fo r over 12 m o n th s. A n d ra d e & R a m a lh o 3 fo u n d parasites in 30% o f 126 hearts fro m c h ro n ic chagasic p a tie nts w h o d ie d fr o m co ngestive h e a rt fa ilu re . This h igh fig u re m ig h t suggest a re la tio n s h ip betw een tissue p aras itism (o r viru le n c e ) and se verity o f h e a rt lesions.
The tw o m a in fe a tu re s o f th e c h ro n ic cha gasic m y o c a rd io p a th y , n a m e ly, th e in fla m m a to ry process and th e fib ro s is w ere c le a rly asso- ciated to th e viru le n c e o f T. c r u z i strain s. O n th e o th e r ha nd, fib ro s is was rela te d to th e in te n s ity o f th e in fla m m a to ry re a c tio n , in accordance w ith th e fin d in g s re p o rte d b y Ta- f u r i17. H e a rt fib ro s is in c h ro n ic a lly in fe c te d m ice is a p p a re n tly a late p h e n o m e n o n a nd has been d e te c te d o n ly a fte r 6 m o n th s in fe c tio n b y Fed erici et a l.9 . A c c o rd in g to A n d ra d e 1, fib ro - b la stic p ro life r a tio n was observed in in fe c te d m ice b e tw e e n 9 0 — 1 2 0 days o f in fe c tio n , whereas fib ro s is was pre sen t o n ly a fte r 6 m o n ths. O u r d ata are in agree m e nt w ith th ose pre- vious o b se rv a tio n s and c o n firm th e Progressive c h a ra c te ris tic o f th e fib r o tic lesions in th e cha gasic m y o c a rd io p a th y 2 .
The p o s s ib ility th a t h um an c h ro n ic ca rd io - p a th y m ig h t in som e w a y be re la te d t o th e course o f in fe c tio n in th e acute phase was re c e n tly raised b y D ias8 . In a co m p re he ns ive analysis o f a p ro lo n g e d fo llo w -u p o f acute cases
o f Chagas' disease th e a u th o r re p o rte d th a t th e prevale nce o f th e c h ro n ic c a rd io p a th y in a g ro u p o f p a tie n ts w h o presented severe c lin ic a i m a n ife s ta tio n s in th e a cute phase was signi- fic a n tly h ig he r (66 .6 % ) th a n in th e g ro u p w ith m ild s y m p to m s (7.6% ).
T h e d e m o n s tra tio n th a t a h ig h percentage o f T. c r u z i strain s iso la te d fro m h um an p a tie nts are o f lo w v iru le n c e in e x p e rim e n ta l c o n d itio n s in d ic a te s th a t m o re a tte n tio n s h o u ld be p aid to th os e p o p u la tio n s , w h ic h are o fte n neglected beca use o f th e ir d if f ic u lt a d a p ta tio n to anim a l m odels. T he re are o th e r evidences th a t such stra in s are m o re re p re se n ta tiv e o f th e p o o l o f T. c r u z i p o p u la tio n s w h ic h c irc u la te in na tu re . A n d ra d e l iso la te d 15 strain s fro m hum ans in Bahia, B ra zil and re p o rte d th a t 7 w ere o f lo w v iru le n c e , 7 o f m ild viru le n c e and o n ly 1 was o f high viru le n ce . C a rn e iro e t a l.7 describea th a t am ong 11 strain s fro m c h ro n ic p a tie n ts in B a m b u f, B ra zil o n ly 1 was v iru le n t to m ice. I t s h o u ld be m e n tio n e d th a t th e lo w v iru le n t s tra in s te n d to keep th is c h a ra c te ris tic in th e la b o ra to ry regardless o f e x p e rim e n ta l m an ip u - la tio n s such as in o c u la tio n in to b a b y-m ice o r X -irra d ia te d an im a is w h ic h ind uce o n ly tran- s ie n t e n h a n ce m e n t o f p aras ite m ia and m o rta - l i t y 16.
T h e vascular lesions (n e c ro tiz in g a rte ritis ) fo u n d in o u r in fe c te d m ice w ere m ore related to th e d u ra tio n o f in fe c tio n ra th e r th a n w ith th e stra in viru le n ce . T h e pathogenesis o f th is va scula r dam age w h ic h has also been described in th e h u m a n disease6 is n o t clear and has been suggested to rep re se n t a p h e n o m e n o n o f h y p e rs e n s itiv ity .
R E S U M O
C a m u n d o n g o s fo ra m in o c u la d o s c o m fo rm a s s a ng ü ín ea s d e 17 cepas d e T . c ru z i re ce n te m e n te isolada s d e p a c ie n te s chagásicos c r ô n ic o s e q u e fo ra m c las s ific a d a s c o m o d e a lta ,
m é d ia e b a ix a v iru lê n c ia a tra vé s d a d e te rm in a ç ã o d o p e r ío d o p ré -p a te n te , p a ra s ite m ia e m o r ta lid a d e n a fase a g u d a d a in fe c ç ã o . C erca d e 2 1 2 a n im a is in o c u la d o s c o m as d ife re n te s cepas fo r a m e s tu d a d o s a p ó s 3 , 6 , 9 e 12 m eses d e in fecção. N a fase c rô n ic a d a in fe c ç ã o p a ra s i
tas in tra c e lu la re s fo r a m o b s e rv a d o s e m 11.0% , 2 7 .0 % e 5 4 .0 % d o s c a m u n d o n g o s in o c u la d o s re s p e c tiv a m e n te c o m as cepas d e b a ix a , m é d ia e a lta v iru lê n c ia ( r = 0 .9 9 , p < 0 .0 0 1 ). A fib ro s e c a rd ía c a ta m b é m esteve re la c io n a d a à v iru lê n c ia s e n d o e n c o n tr a d a e m 5.7% , 11.6% e 3 0 .8 % das m es m as cepas ( r = 0 .9 8 , p < u .0 0 5 ) ; rela çã o s im ila r f o i e n c o n tra d a e n tr e a in te n s id a d e e fr e q ü ê n c ia d o p ro c e s s o in f la m a tó r io n o c o ra ç ã o e a g ra v id a d e da
in fe c ç ã o aguda. A r t e r it e n e c r o tiz a n te f o i d e te c ta d a em 12.2% d o s a n im a is e esta lesão estava m a is re la c io n a d a c o m a d u ra ç ã o d a in fe c ç ã o q u e c o m as c a ra c te rís tic a s das c ep a s
Os in f ilt r a d o s in fla m a tó r io s e o p a ra s itis m o tis s u la r p e rm a n e c e ra m e stáveis d u r a n te o
c u rs o d a in fe c ç ã o e n q u a n to q u e a fib ro s e f o i p ro gres siva . Esses a c h a do s s ugerem q u e o
c a m u n d o n g o p o d e r e p r o d u z ir lesões c a rd ía c a s q u e se a s sem elham às d a c a rd io p a tia ch ag ásica h u m a n a e q u e as lesões d e p e n d e m d a ce pa d e T . c ru z i u tiliz a d a .
(P alavras-chav es: T ry p a n o s o m a c ru zi. Cepas. H is to p a to lo g ia . C a m u n d o n g o )
Schlemper Jr BR, Ávila CM, Coura JR, Brener Z. Course o f infection and histopathological lesions in mice infected with seventeen Tr y p an o so m a cr u zi strains isoleted from chronic patients. Revista da Sociedade Brasileira de Medicina Tropical
16:23-30, 1983
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