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Revista da Sociedade Brasileira de Medicina Tropical

2 7(3):163-169, jul-set, 1994.

THE HAMSTER (MESOCRICETUS AURATUS) AS


EXPERIMENTAL MODEL IN CHAGAS DISEASE:
PARASITOLOGICAL AND HISTOPATHOLOGICAL STUDIES
IN ACUTE AND CHRONIC PHASES OF TRYPANOSOMA CRUZI
INFECTION

Luis Eduardo Ramirez, Eliane Lages-Silva, Jos Maria Soares Junior and
Edmundo Chapadeiro

This research characterizes the acute and chronic phases o f Chagas ' disease in hamster
through parasitological and histopathological studies. The acute phase was achieved with 44
young hamsters injected intraperitoneally with 100.000 blood trypomastigotes o f Benedito and
Y strains ofT. cruzi. The chronic phase was induced in 46 hamsters injected intraperitoneally
with 35.000 trypomastigotes ofVicentina, Benedito and Y strains. Animals were sacrificed at
regular intervals o f 24 hours o f acute phase and from the 3r<^ to the lCf^1 month o f infection
ofchronic phase. In the acute phase, parasites were easily recoveredfrom all animals and there
was an inflammatory reaction characterized by mononuclear and polymorphous leukocyte
infiltration o f variable degree in the majority o f tissues and organs, specially in the connective
loose andfatty tissues, smooth muscle myocardium and skeletal muscle. In the chronic phase
the lesions occurred in the same tissues and organs, but the inflammatory response was less
severe and characterized by mononuclear infiltration mainly withfocal or zonalfibrosis in the
myocardiun. In 50% of infected animalsparasites werefound inmyocardiun and recoveredfrom
pericardic, peritoneal and asciticfluids in some animals. Signs o f heartfailure, sudden death
and enlargement o f bowel were observed regularly. We concluded that the hamster is an useful
model fo r Chagas 'disease studies.

Key words: Chagas disease. Experimental model. Hamster.

Many species of animals have been used as the macrophagic system. They also observed high
models to study the infection of T. cruzi, being the mortality rates of the infected animals. Osimani and
mouse, rat, guinea pig, rabbit, dog and the monkey Gurri25 made compared between the infection of
the most frequently employed9. Although the many different Uruguayan strains of T. cruzi and
susceptibility of hamster to T. cruzi is well known, observed a higher susceptibility of mice (100%) in
this animal has been not used yet as an experimental relation to hamster (65%). Schoemaker and
model for Chagasdisease. Only a few papers Hoffman32 infected mice, rats, hamsters and guinea
describe the infection in the acute phase (AP) and no pigs with trypomastigotes of Tulahuen strain of T.
one in the chronic phase (CP). cruzi and observed that mice were more severely
Cariola et al10 infected hamsters with the infected than the other three species and that fat
Tulahuen strain of T. cruzi and observed nests of tissue and the adrenal cortex were not infected.
parasites in all organs, great inflammatory reaction, In view of the few papers about the infection by
degenerative phenomena and a high hyperplasia of T. cruzi in hamster and in order to search for anew
experimental model for Chagasdisease, as
Disciplina de Parasitologia, Departamento de Cincias Biolgicas recommended by WHO38, we decided to study this
da Faculdade de Medicina do Tringulo Mineiro, Uberaba,
animal both in the AP and in the CP o f the infection,
MG.
Supported by FMTM-FUNEPU, FAPEMIG and CNPq, analysing the parasitologic and the histopathologic
Address to: Dr. Luis Eduardo Ramrez. Praa Manoel Terra, s/ aspects, which preliminary results were related in
n, 38025-050 Uberaba, MG.
previous communications29 30.
Recebido para publicao em 21/03/94.

163
Ramirez LE, Lages-Silva E, Soares Junior JM, Chapadeiro E. The hamster Mesocricetus auratus as experimental
model in Chagas' disease: parasitologicaland histopathological studies in acute and chronic phases o/Trypanosoma
cruzi infection. Revista da Sociedade Brasileira de Medicina Tropical 27:163-169, jul-set, 1994.

MATERIAL AND METHODS parasitemia was on the 8 ^ day w ith 64


trypomastigotes/5/iil of blood. The parasitemia of
In the AP forty-four young non isogenic Syrian these animals was low and no death was observed
hamsters (Mesocricetus auratus), 34 males and 10 during the AP.
females, were infected intraperitoneally with In animals chronically infected (after three
100.000 trypomastigotes from Y and Benedito months) the parasitmie curves were very similar
strains of T. cruzi (Benedito strain was isolated to those observed when 100.000 blood
through xenodiagnosis from a patient with the trypomastigotes were injected. Nevertheless the
indeterminate form).Fifteen animals, nine males parasitemia was lower with the Vicentina strain,
and six females, were used as controls. with a maximum of 16.2 trypomatigotes/5fti of
The parasitologic study was performed through blood during the AP. In this experiment, two
the direct method7 at intervals of 24 hours until the animals infected with Y strain died, but no death
15thday post-infection. Three infected animals and was noticed in animals infected with the other
one control were randomly sacrificed after ether strains. The parasitemia detected at each 30 days
anesthesia at the same intervals . through microhematocrit and hemoculture methods
In the CP forty-six hamsters, 22 males and 24 was sometimes positive and sometimes negative.
females, in the same conditions as AP group were In the AP of both experiments no important
infected with 35.000 trypomastigotes forms from clinical signs were noticed. At necropsy infected
Y, Benedito and Vicentina strains (Vicentina strain animals showed enlargement and congestion of
was isolated through xenodiagnosis from a patient heart, spleen and liver. Microscopic lesions were
with chronic cardiac form) and twelve hamsters, common and progressive since the first 24 horns in
six males and six females, were used as controls. the majority of tissues and organs, being more
The parasitologic studies were performed at severe in the loose connective and fatty tissues
each 30 days through the methods o f (cellulitis) and the smooth muscle. The heart (Figure
microhematocrit concentration and hemoculture 1) presented carditis (peri, myo and endocarditis)
(LIT mediun). At each 30 days, three to four early in atria and later in ventricles with mononuclear
infected animals and one control were randomly and polymorphous leucocytes infiltration of the
sacrificed until the 10^ month post-infection. three layers including the specific conduction tissue.
Fragments of the same tissues and organs of the AP The autonomic atrial ganglia, as well as the nervous
were obtained and also from animals that died twigs (ganglionitis and neuritis), were also infiltrated
spontaneously or from those sacrificed in general by the same cells with degenerative changes and
bad state. nerve cells necrosis.
The tissue specimens obtained at the necropsy
in both experiments were fixed in 10% formalin
solution and embedded in paraffin; 5-7/un sections
were stained by hematoxylin-eosin (H.E) and
Gomori trichromic for routine histopathologic
analysis. The peroxidase - antiperoxidase
immunohistochemistry test was used for tissular
parasitism search.

RESULTS

During the AP all infected animals showed


patent parasitemia. Those infected with the Y strain
had a pre-patent period of 5 days and a maximum
peak of parasitemia on 6th, 9th, 13th and 15th days Figure 1 - Heart of infected animal sacrificed in the AP
with a maximum number of4.500 trypomastigotes/ showing severe mononuclear infiltration o f the
5/xl o f blood. In Benedito strain the pre-patent loose connective andfat tissues (cellulitis) of the
period was three days and the maximum peak of epicardium and ganglia (arrow). HE 40X.
164
Ramirez LE, Lages-Silva E, Soares Junior JM, Chapadeiro E. The hamster Mesocricetus auratus as experimental
mvdel in Chagas' disease: parasito logical and histopathological studies in acute and chronic phases o fT T yp u n o so m a .
cruzi infection. Revista da Sociedade Brasileira de Medicina Tropical 27:163-169, jul-set, 1994.

In the digestive tract it was also observed acute noticed anywhere. It should be emphasized that the
inflamation with the same inflamatory cells mainly acute inflammatory response was present in variable
in the muscular layer (myositis) and myoenteric degree in the absence of parasites since the first 24
ganglia (ganglionitis) with signs of ganglion cells hours post-infection for both strains.
degeneration and necrosis (Figure 2). In the CP, some animals presented a bad
general state characterized by apathy, loss of weight,
ulcerative gingivitis, pallescense, dyspnea and
generalized edema; seven anim als died
spontaneously.
In seven animals it was observed edema in the
subcutaneous fat tissue and a clear and transparent
abdominal, pleural and pericardial liquid effusion.
In some of these animals it was found trypomastigotes
in the pleural, pericardic and ascitic fluid through
microhematocrit concentration and hemoculture
methods.
The heart of the majority of animals was
enlarged and congested with dilatation of the cavities
specially of the apex of the left ventricle with mural
trombosis (Figure 3). The liver was also enlarged
Figure 2 - Large intestine o f hamster infected in the AP and congested; mild to moderate splenomegaly was
exhibiting severe mononuclear infiltration o f noticed. In some animals, the intestinal tract,
the muscle layer (myositis) and myoenteric
specially the bowel, presented variable degree of
plexus (ganglionitis). HE 100X.
dilatation of the lumen (Figure 4). Atrophy of

Genital internal lesions were early and generaly


severe in the smooth muscle layer, intheinterstitium
of the testis (orchitis) and the adnexa (epididymitis,
vesiculitis, prostatitis and funiculitis), and also in
the ovary and uterus (oophoritis and metritis).
The spleen, thymus, lymph nodes and the bone
marrow presented, since the beginning, a reactive
state of variable intensity with phagocytosis of
parasites. Figure 3 - Control hamster heart (right) and chronic
Lesions in other organs as skeletal muscle chagasic heart (left) with dilatation o f cavities
(myositis), lungs and bronchia were less severe and (cardiomegaty).
appeared later. Adrenal glands showed nodules of
mononuclear and polymorphous leucocytes in
sinusoids with phagocytized parasites. Nothing
was noticed in other organs of the endocrine system.
In general, the tissue parasitism in the AP was
early and more severe in the loose connective and
fat tissues, particularly surrounding the internal
genitals, peritoneum and smooth muscle fibres of
internal genitals, from the 3rd day after-infection
for both strains. In other tissues and organs the
parasitism was delayed (seven to nine days after
infection). No correlation between the grade of
inflammatory reaction and tissue parasitism was Figure 4 - Control hamster bowel (left) and dilated
bowel o f chronic chagasic animal (right)
165
Ramirez LE, L ages-Silva E, Soares Junior JM, Chapadeiro E. The ham ster Mesocricetus auratus as experim ental
m odel in Chagas disease: parasito logicaland histopatholvgical studies in acute and chronic ph ases ofTrypanosoma
cruzi infection. Revista da Sociedade Brasileira de Medxina Tropical 27:163-169, ju l-set, 1994.

internal genitals mainly of testis, ovary and uterus


was frequent.
The microscopic lesions were relatively scanty
and found in the heart, digestive tract and adnexa
and internal genitals. All cardiac layers were
infiltrated only by round mononuclear cells,
nevertheless the myocardic lesions were more severe
with focal or zonal endomisial infiltration and
fibers destruction sometimes accompanied by
variable extension of fibrosis (Figure 5). The
myocardic specific tissue showed the same lesions.
In the myocardium were found amastigote nests in
50% o f infected animals. The epicardiun showed
also focal or patchy areas of mononuclear infiltration Figure 6 - Large intestine from, the same animal
as well as the autonomic cardiac ganglia and nerve exhibiting discreet mononuclear infiltration
twigs associated to degenerative changes and in the muscular layer (myositis) and in the
reduction of nerve cells (Unpublished data). m yoenteric p le x u s (ganglionitis) with
destruction o f nerve cells. HE 400X.

Figure 5 - Hamster heart in the CP showing focal


myocarditis extending to the epicardium and
ganglionitis (arrow). HE 100X. Figure 7 - Epidydimus fro m one animal in the CP
showing severe mononuclear infiltration o f
The gastro-intestinal tract presented the intersticium with tubular atrophy. HE
mononuclear cells infiltration of the muscle layer lOOx.
(myositis) and o f the nervous myoentericus ganglia
(ganglionitis Figure 6). In the liver, besides the showed the same chronic cell infiltration especially
congestion, there were intralobular nodules of in themuscle layer (cystitis, ureteritis and urethritis).
mononuclear infiltration, fatty degeneration of The thymus, lymph nodes and spleen presented
hepatocytes and deposits f Congo red stained discreet chronic reactional state.
material similar to amyloid. Chronic pancreatitis In the central nervous system there were the
with parenchimatous atrophy was also observed. same chronic focal cell infiltration (encephalitis and
Internal genitals exhibited chronic mononuclear meningitis). Focal neuritis and spinal ganglionitis
cells infiltration in the testis (orchitis), epididymus with characteristic infiltrate of mononuclear cells
(epididymitis, Figure 7), seminal vesicle (vesiculitis) were observed, too.
and prostate (protatitis) in males and ovary The skeletal muscles showed focal myositis
(oophoritis) and uterus (metritis) in females with with mononuclear cell infiltration and necrosis of
variable atrophy of these organs. The urinary tract fiber cells (Figure 8).

166
Ramirez LE, L ages-Silva E, Soares Junior JM, Chapadeiro E. The ham ster Mesocricetus auratus as experim ental
m odel in C h agas' disease: parasitological and histopathological studies in acute and chronic p h a ses o/Trypanosoma
cruzi infection. R evista da Sociedade B rasileira de M edicina Tropical 27:163-169, ju l-set, 1994.

invaded by the same inflammatory process as


described for mice17 and guinea pig15.
The mortality in the CP occurred occasionally
as consequence of the infection, heart failure or
even due to immunodepression. The urinary
incontinence was consequence of cystitis and
probably o f lesions in the hypogastric plexus
(ganglionitis).
The fluid effusion in the cavities and dyspnea
were probably due to the heart failure, in
consequence of the chronic myocarditis. It is
interesting to notice that these manifestations were
not discribed in mice and rats, although it has been
Figure 8 - Skeletal muscle with focal chronic necrotizing found in dogs19 and rabbits14 27 36.
myositis. HE 400x. The macroscopic and microscopic findings in
the majority of organs in the CP are similar to those
DISCUSSION foipd in other experimental models4 121419 2736 ancj
humans20. The chronic carditis is more discreet,
The parasitological behaviour of the T. cruzi sometimes focal as in the chronic indeterminate
infection in hamster (Mesocricetus auratus) during form, sometimes zonal as in the symptomatic chronic
the AP showed that Y strain is more virulent than cardiopathy. The left ventricle apex dilatation
Vicentina and Benedito strains. This fact is also suggests the human vorticilar lesion (apical
observed when Y strain is used in other experimental aneurism)3 23 31.
models1218 2S. Although the inocula utilized in AP The gastrointestinal tract enlargement specially
and CP were different from each other they of the bowel, found in some animals, may be a good
maintained their original characteristics curves. model to investigate the pathogenesis of chagasic
While the elevated number of trypomastigotes enteromegalies since this is questioned in other
o f Y strain in the AP killed the majority of mice4 8, models21 22 24. In this phase the liver lesion were
infected hamsters remained in a good general state similar to those observed in acute phase but no
and only two deaths ocurred. This is also observed parasites were seen in the intralobular infiltrates.
when infections are made with Y strain in other The pancreas atrophy was probably due to two
experimental models as rats12 rabbits28 and dogs11 factors: chronic inflammation and nutritional state
which demonstrate that the hamster has a more of animals in consequence o f the infection, since
efficient control of the infection than mice. controls did not show such lesions.
The parasitemia evaluated in CP through the Skeletal muscles and the nervous system were
hemoculture and microhematocrit concentration slightly damaged as in man26 and other experimental
methods, confirms that hamster does not abort the models1 2 16 34 35 37.
infection as does rats and other animal models9 and The urogenital organs were strongly affected in
probably the chagasic human39. The parasite isolation the hamster, as described in other experimental
from pericardic, pleural and ascitic fluids, in higher models13 17. Cystitis resulting from lesions of the
number than in blood through microhematocrit and muscular layer associated to the lesions of
hemoculture methods is a finding not yet related. hypogastric plexus were probably the main cause of
This fact needs further studies for explanation. bladder enlargement and urinary incontinence.
Our data shows that in the AP, macroscopic and Testes, ovaries and the uterus atrophy are probably
microscopic lesions in the heart and in other organs consequence of the severe chronic inflammatory
are similar to that found in man20 and in other process.
experimental models5 6 12 19 33. It should be In summary, our studies show for the first time
emphasized that the internal genitals and urinary that the hamster reproduces the main parasitological
tract of hamsters of both sexes are early and severely and histopathological characteristics of human

167
R amirez LE, L ages-Silva E, Soares Junior JM, Chapadeiro E. The ham ster Mesocricetus auratus as experim ental
m odelin C h agas' disease: parasitologicalan d h islopath olopcal studies in acute and chronic ph ases o fT rypanosoma
cruzi infection. R evista da Sociedade Brasileira de M edicina Tropical 27:163-169, ju l-set, 1994.

C hagasdisease infection. Although the 2. Alencar A. Histogenese do granulona chagsico do


eletrocardiografic study and radiological Sistema Nervoso Central do co. Segundo Congresso
examination o f the digestive tract are going on we Latino-Americano de Anatomia Patolgica So Paulo
51-52,1958.
can conclude that the hamster is an useful model for
3. Almeida HO. A leso vorticilar da cardiopatia
Chagasdisease research.
chagsica crnica. Tese de Doutorado, Universidade
Federal de Minas Gerais, Belo Horizonte, MG, 1976.
RESUMO 4. A ndrade SG. C ara cteriza o de cep as de
Trypanosoma cruzi isoladas no Recncavo Baiano.
Opresente trabalho tem comofinalidade caracterizar Revista de Patologia Tropical 3:65-121,1974.
as fases aguda e crnica da doena de Chagas em 5. Andrade V, Brodskyn C, Andrade SG. Correlation
ha m ster, atravs de estudos p arasitolgicos e between isoenzyme patterns andbiological behaviour
histopatolgicos. A fase aguda fo i induzida em 44 o f different strains of Trypanosom a cruzi.
hamsters jovens, inoculados intraperitonealmente, com Transactions o f the Royal Society of Tropical
100.000 tripomastigotas sanguneos das cepas Y e Medicine and Hygiene 77: 796- 799, 1983.
Benedito do T. cruzi. A fase crnicafo i produzida em 46 6. Anselmi A, Pifano FC, Suarez JA, Dominguez A,
hamsters, inoculados intraperitonealmente, com 35.000 V asq u e z A D , A nselm i G. E x p erim e n ta l
tripomastigotas sanguneos das cepas Y, Vicentina e Schizotrypanum cruzi myocarditis. American Heart
Benedito. Os animais foram sacrificados a intervalos Journal 70:638-656, 1965.
regulares de 24 horas na fa se aguda, durante 15 dias e 7. Brener Z. Therapeutic activity and criterion of cure
na fa se crnica, a partir do 3 ms at o 10 ms da on mice experimentally infected with Trypanosoma
infeco. Na fa se aguda, o parasita fo i facilmente cruzi. Revista do Instituto de Medicina Tropical de
recuperado de todos os animais, os quais apresentaram So Paulo 4: 389-396, 1962.
reao inflamatria, de intensidade varivel, de clulas 8. Brener Z. Comparative studies of different strains of
mononucleares e polimorfonucleares, na maioria dos Trypanosoma cruzi. Annals of Tropical Medicine
tecidos e rgos, principalmente nos tecidos conjuntivo and Parasitology 59: 19-26, 1965.
frouxo e adiposo, msculo liso, cardaco e esqueltico. 9. Brener Z, Ramirez LE. Modelos crnicos da doena
Na fa se crnica, as leses ocorreram nos mesmos tecidos de Chagas experimental. /n:Canado JR, ChusterM
e rgos, mas a resposta inflamatria com infiltrado (eds) Cardiopatia chagsica, Fundao Carlos
mononuclear fo i mais grave no miocrdio onde adquiriu Chagas, Belo Horizonte p. 29-32, 1985.
carter fibrosante. No miocrdio os parasitas foram 10. Cariola J, Prado R, Agosin M , Christen R.
encontrados em 50% dos casos. A partir do lquido Susceptibilidad dei hamster (Cricetus auratus) &
pericrdico, peritoneal e asctico desses animais foram Peromyscus (Peromyscus maniculatus gambeliX, a
recuperados parasitas atravs do microhematcrito e la infeccin experimental por Trypanosoma cm zi,
hemocultura. Regularmente, observaram-se sinais de cepa Tulahun. Boletin Informativo Parasitarias
insuficincia cardaca, com morte sbita e de dilatao Chilenas V: 44-45, 1950.
do intestino grosso e atrofia dos genitais internos. 11. Castro MA, Brener Z. Estudo parasitolgico e
Conclui-se que o hamster um modelo til para o estudo anatomo-patolgico da fase aguda da doena de
da doena de Chagas. Chagas em ces inoculados com duas diferentes
cepas de Trypanosoma cruzi. Revista da Sociedade
Palavras-chaves: Doena de Chagas. Modelo Brasileira de Medicina Tropical 18:223-229,1985.
experimental. Hamster. 12. Chapadeiro E, Beraldo PSS, Jesus PC, Oliveira Jr
WP, Junqueira Jr LF. Leses cardacas em ratos
ACKNOWLEDGMENTS W istar infectados com diferentes cepas do
Trypanosoma cruzi. Revista da Sociedade Brasileira
We thank Luzia Helena Gonalves dos Santos de Medicina Tropical 21:95-103, 1988.
and Valria Ramos for technical assistance and 13. Ciconelli AJ, Estudo quantitativo dos neurnios do
plexo hipogstrico inferior em ratos normais e em
Najara Vieira Galvo for help with the manuscript.
infectados experimentalmente pelo Trypanosoma
cruzi. Tese de Doutorado, Universidade de So
REFERENCES Paulo, Ribeiro Preto,SP, 1963.
14. Figueiredo F, Rossi MA, Ribeiro dos Santos R.
1. Alcntara FG. Desnervao dos gnglios cardacos Evoluo da cardiopatia experimentalmente induzida
intramurais e cervitorxicos na molstia de Chagas. em coelhos infectados com Trypanosoma cruzi-
Revista Goiana de Medicina 16:259-277,1970. Revista da Sociedade Brasileira de Medicina Tropical

168
Ramirez LE, Lages-Silva E, Soares Junior JM, Chapadeiro E. The hamster Mesocricetus auratus as experimental
m odel in C hagas1disease: parasitologicalan d histopathological studies in acute and chronic ph ases o/Trypanosoma
cruzi infection. R evista da Sociedade Brasileira de Medicina Tropical 27:163-169, ju l-set, 1994.

18: 133-141, 1985. Doutorado, Universidade Federal de Minas Gerais,


15. Franco MF. Cardite experimental do cobaio pela ' Belo Horizonte-MG, 1984
cepa Y do Trypanosoma cruzi. Correlao entre a 28. Ramirez LE, Brener Z. Evaluation o f the rabbit as
histopatologia e a presena de antgenos parasitrios amodel for Chagasdisease. I. Parasitological studies.
identificados por imunofluorescncia indireta. Memrias do Instituto Oswaldo Cruz 82: 531- 536,
Revista da Sociedade Brasileira de Medicina Tropical 1987.
23: 187-189, 1990. 29. Ramirez LE, Lages-Silva E, Chapadeiro E. Infeco
16. Jardim E. Molstia de Chagas experimental no rato: do hamster pelo Trypanosoma cruzi. Revista da
parasitismo do ncleo do 111par craniano. Revista do Sociedade Brasileira de Medicina Tropical 24:119-
Instituto de Medicina Tropical de So Paulo 13:405- 120, 1991.
410, 1971. 30. Ramirez LE, Lages-Silva E, Soares Jr JM,
17. Lamano Carvalho TL, Ribeiro RD, Lopes RA. Chapadeiro E. Infeco experimental do hamster
Parasitism of the male reproductive organs by pelo Trypanosoma cruzi: fase crnica. Revista da
T rypanosom a cru zi (Bolivia strain). Memrias do Sociedade Brasileira de Medicina Tropical 26: 253-
Instituto Oswaldo Cruz 84(suppl.II):22, 1989. 254, 1993.
18. Lana M. O co como modelo experimental para o 31. Raso P, Chapadeiro E, Tafuri WL, Lopes ER,
estudo da doena de Chagas. Tese de Doutorado, Rocha A. Anatomia patolgica da cardiopatia
Universidade Federal de Minas Gerais, Belo crnica. In: CanadoJR, ChusterM(eds) Cardiopatia
Horizonte, MG, 1992. Chagsica. Fundao Carlos Chagas, Belo Horizonte
19. Lana M, Chiari E, Tafuri WL. Experimental p.41-53, 1985.
Chagasdisease in dogs, Memrias do Instituto 32. Schoemaker JP, Hoffman Jr RV. Possible stimulatory
Oswaldo Cruz 17:59-71,1 m, faeter(s) In brow n adipose tissue in mice.
20. Lopes ER, Chapadeiro E,Tafuri WL, Prata AR, Experimental Parasitology 35: 272-274, 1971,
Doena de Chagas. In: Lopes ER, Chapadeiro E, 33. Sousa MA, Alencar A A . On the tissular parasitism
Raso E, Tafuri WL (eds) Bogliolo Patologia, Rio de of Trypanosoma cruzi and strain in Swiss mice,
Janeiro, Guanabara, Koogan p. 1047-1065, 1987. Revista do Instituto de Medicina Tropical de SIo
21. Marsden PD, AlvarengaNJ, Soares VA, Gama MP, Paulo 26: 316-321, 1984.
Attempts to produce megasyndrome in mice using 34. Tafuri WL, Brener Z. Leses do sistema nervoso
stocks o f Trypanosoma cruzi associated with autnomo do camundongo albino na Tripanosomase
megaoesophagus in man. Transactions Royal Society cruzi experimental na fase aguda. O Hospital 69:
Tropical Medicine and Hygiene, London 73: 651, 179-191, 1966.
1979. 35. Tafuri WL, Lima Pereira FE, Bogliolo L, Raso P.
22. Marsden PD, Seah SKK, Draper CC, Pettitt LE, Leses do sistema nervoso autnomo e do tecido
Miles MA, Voller A. Experimental Trypanosoma muscular estriado esqueltico na fase crnica da
cruzi infection in rhesus monkey. II The early Tripanosomose cruzi experimental. Estudos ao
chronic phase. Transaction of the Royal Society of microscpio ptico e eletrnico. Revista Goiana de
Tropical Medicine and Hygiene, London 70: Medicina 26: 61-67, 1979.
247:251, 1976 36. Teixeira ARL, Figueiredo F, Rezende Filho J,
23. Mignone C . Alguns aspectos da patologia da cardite M acedo V . C h a g a sd ise a se : a c lin ic a i,
chagsicacrnica. Tesededoutorado, Universidade parasitological, immunological and pathological study
So Paulo, So Paulo-SP, 1958. in rabbits. The American Journal of Tropical
24. Okumura M. Doena de Chagas experimental. In: Medicine and Hygiene 32: 258-272, 1983.
Raia AA (ed) Manifestaes digestivas da Molstia 37. Vichi FL. Estudo do parasitismo na medula espinal
de Chagas, So Paulo p. 35-59, 1983. de ratos na fase aguda da molstia de Chagas.
25. Osimani JJ, Gurri J. Infeccin experimental dei Revista do Instituto de Medicina Tropical de So
hamster dorado (Mesocrycetus auratus) co n algunax Paulo, 3: 37-42, 1961.
cepas uruguayas de Trypanosoma cruzi. Archivos 38. Word Health Organization. Report o f the Scientific
de la Sociedad de Biologia de Montevideo XVIII: Working Group on the Development and Evaluation
73-78, 1954. of Animal Models for Chagasdisease. Geneva,
26. Prata A, Porto G. Biopsia de msculo na doena de 1984.
Chagas. Revista do Instituto de Medicina Tropical 39. Zeledn R, Dias JCP, Salazar-Brilla A, Rezende
de So Paulo 8:19-196, 1966. JM, Vargas LG, Urbina A. Does a spontaneous cure
27. Ramirez LE . O coelho como modelo experimental for Chagas disease exist? Revista da Sociedade
no estudo da doena de Chagas crnica. Tese de Brasileira de Medicina Tropical 21: 15-20, 1988.

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