Abstract
African (sleeping sickness) and American (Chagas' disease) trypanosomiasis, caused by protozoa of the family Trypanosomatidae, are diseases that are endemic in parts of Africa and Latin America, respectively. Physicians in developed countries may occasionally see cases because of extensive travel and immigration from endemic countries. Although neurological involvement is common in both, its incidence and clinical presentation differ considerably. African trypanosomiasis, caused by subspecies of Trypanosoma brucei (T b rhodesiense, T b gambiense), is transmitted by the tsetse fly and causes meningoencephalitis, in which somnolence is a prominent feature. Parasites may reach the brain parenchyma through the choroid plexus or the Virchow Robin spaces. American trypanosomiasis, caused by Trypanosoma cruzi is transmitted by reduviid bugs. While lesions in the central nervous system are not prominent, except in the reactivated forms which occur in immunodeficient patients, the peripheral nerve, mainly the autonomic nervous system, is frequently involved, leading to the cardiomegaly and the digestive megaviscera. Congenital infections may also occur.
In this paper we give an account of the epidemiology, clinical presentation and pathological features of these two protozoal infections based on human and experimental studies of both the central and peripheral nervous system.
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References
- 1. Adams JH, Halier L., Boa FY, Doua F., Dago A., Konian K. (1986) Human African trypanosomiasis (T b gambiense). A study of 16 fatal cases of sleeping sickness with some observations on acute arsenical encephalopathy. Neuropathol Appl Neurobiol 12: 81–94. [DOI] [PubMed] [Google Scholar]
- 2. Alafiatayo RA, Crawley B., Oppenheim BA, Pentreath VW (1993) Endotoxins and the pathogenesis of Trypanosoma brucei brucei infection in mice. Parasitology 107: 49–53. [DOI] [PubMed] [Google Scholar]
- 3. Alencar A. (1964) Atrofia cortical na cardiopatia chagásica crônica. O Hospital 66: 131–137. [PubMed] [Google Scholar]
- 4. Almeida HO, Brandāo MC, Reis MA, Gobbi H., Teixeira VPA (1987) Denervaçäo e cardiopatia no chagásico crônico. Arq Bras Cardiol 48: 43–47. [PubMed] [Google Scholar]
- 5. Almeida HO, Teixeira VPA, Mahler‐Araújo MB (1988) Estudo comparativo das lesōes dos gânglios e nervos atrials em chagásicos crônicos. Arq Bras Cardiol 50: 159–162. [PubMed] [Google Scholar]
- 6. Amaral CFS, Tafuri WL, Brenner Z. (1975) Freqüência do parasitismo encefálico em camundongos experimentalmente inoculados com diferentes cepas de T cruzi. Rev Soc Bras Med Trop 9: 243–246. [Google Scholar]
- 7. Andrade ZA (1991) Pathogenesis of Chagas' disease. Res Immunol 146: 126–129. [DOI] [PubMed] [Google Scholar]
- 8. Andrade ZA, Lopes ER, Prata SP (1987) Alteraçōes do sistema de conduçāo do coraçāo em chagásicos acometidos de morte repentina. Arq Bras Cardiol 48: 5–9. [PubMed] [Google Scholar]
- 9. Anthoons JAMS, Van Marck EAE, Gigase PLJ, Stevens WJ (1989) Immunohistochemical characterisation of the mononuclear cells in the brain of the rat with an experimental chronic Trypanosoma brucei gambiense infection. Parasitol Res 75: 251–256. [DOI] [PubMed] [Google Scholar]
- 10. Bakhiet A‐MO (1993) Immunopathogenesis of experimental African trypanosomiasis. Interactions between Trypanosoma brucei brucei, CD8+ cells and interferon gamma. PhD Thesis, Karolinska Institute, Stockholm.
- 11. Barreira AA, Said G., Krettli AU (1981) Multifocal demyelinative lesion of peripheral nerves in experimental chronic Chagas'disease (letter). Trans R Soc Trop Med Hyg 75: 751. [DOI] [PubMed] [Google Scholar]
- 12. Bittencourt AL (1976) Congenital Chagas' disease. Am J Dis Child 130: 97–103. [DOI] [PubMed] [Google Scholar]
- 13. Brandāo SH, Zulian R. (1966) Nerve cell depopulation in chronic Chagas' Disease. A qualitative study in the cerebellum. Rev Inst Med Trop Sāo Paulo 6: 281–286. [PubMed] [Google Scholar]
- 14. Brito Costa R., Gallina RA (1971) Hipotálamo anterior na Moléstia de Chagas humana. Rev Inst Med Trop Sāo Paulo 13: 92–98. [PubMed] [Google Scholar]
- 15. Chagas C. (1909) Nova tripanosomiase humana. Mem Inst Oswaldo Cruz 1: 159–218. [Google Scholar]
- 16. Chagas C. (1911) Nova entidade mórbida do homem. Resumo geral e estudos etiológicos e clínicos. Mem Inst Oswaldo Cruz 3: 219–275. [Google Scholar]
- 17. Chagas C. (1913) Les formes nerveuses d'une nouvelle trypanosomiase. Trypanosoma cruzi inoculé par Triatoma magista (Maladie de Chagas). Nouv Iconogr Salpêt 26: 1–9. [Google Scholar]
- 18. Chagas C. (1916) Tripanosomiase amencana. Forma aguda da moléstia. Mem Inst Oswaldo Cruz 8: 37–59. [Google Scholar]
- 19. Chimelli L., Schieber MB (1994) The penpneral nerve in Chagas' Disease. Morphological findings in the surai nerve of 45 autopsied cases (abs). XIIth International Corgress of Neuropathology ‐ Toronto, 1994. Brain Pathol 4: 560. [Google Scholar]
- 20. Collomb H. (1959) Encéphalite de la trypanosomiase humaine africaine. Gaz Méd France 64: 1069–1079. [PubMed] [Google Scholar]
- 21. Couceiro A. (1943) Lesōes do Ciático na infecçāo experimental de cāes pelo Schizotrypanum cruzi . Mem Inst Oswaldo Cruz 39: 435–439. [Google Scholar]
- 22. De Faria CR, Melo‐Scuza SE, Rassi A. (1977) Evidèncias eletromiográficas de desnervaçāo motora em pacientes na fase crônica da doença de Chagas. Rev Goiana Med 23: 125–127. [Google Scholar]
- 23. De Faria CR, Rezende JM, Rassi A. (1988) Desnervaçāo periférica nas diferentes formas clínicas da doença de Chagas. Arq Neuropsiquiatr 46: 225–237. [DOI] [PubMed] [Google Scholar]
- 24. Del‐Castillo M., Mendoza G., Oviedo J., Perez‐Bianco RP, Anselmo AE, Silva M. (1990) AIDS and Chagas' disease with central nervous system tumor‐like lesion. Am J Med 88: 693–694. [DOI] [PubMed] [Google Scholar]
- 25. De Raadt P. (1985) Trypanosomoses et leishmanioses congénitales. Arch Fr Pediatr 42: 925–927. [PubMed] [Google Scholar]
- 26. Di‐Lorenzo GA, Pagano MA, Taratuto AL, Garau ML, Meli FJ, Pomsztein MD (1996) Chagasic granulomatous encephalitis in immunosuppressed patients. Computed tomography and magnetic resonance imaging findings. J Neuroimaging 6: 94–97. [DOI] [PubMed] [Google Scholar]
- 27. Duggan AJ, Hutchison MP (1966) Sleeping sickness in Europeans: a review of 109 cases. J Trop Med Hyg 69: 124–131. [PubMed] [Google Scholar]
- 28. Dumas M., Boa FY (1988) Human African trypanosomiasis. In: Handbook of Clinical Neurology, Vinken PJ, Bruyn GW, Klawens HL (eds.), vol 8 pp. 339–344, Elsevier: Amsterdam . [Google Scholar]
- 29. Eddleston E., Mucke L. (1993) Molecular profile of reactive astrocytes‐implications for their role in neurologic disease. Neuroscience 54: 15–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Erro MG, Genovese J., Correale J., Sica REP (1989) Neuromuscular transmission studies in human chronic Chagas' disease. Arq Neuropsiquiatr 47: 279–282. [DOI] [PubMed] [Google Scholar]
- 31. Ferreira MS, Nishioka SA, Rocha A., Silva AM, Ferreira RG, Olivier W., Tostes S. Jr. (1991) Acute fatal Trypanosoma cruzi meningoencephalitis in a human immunodeficiency virus‐positive hemophiliac patient. Am J Trop Med Hyg 45: 723–727. [DOI] [PubMed] [Google Scholar]
- 32. Genovese O., Ballario C., Storino R., Segura E., Sica REP (1996) Clinical manifestations of peripheral nervous system involvement in human chronic Chagas' disease. Arq Neuropsiquiatr 54: 190–196. [DOI] [PubMed] [Google Scholar]
- 33. Gluckstein D., Ciferri F., Ruskin J. (1992) Chagas' disease: another cause of cerebral mass in the Acquired Immunodeficiency Syndrome. Am J Med 92:429–432. [DOI] [PubMed] [Google Scholar]
- 34. Gonzales Cappa SM, Sanz OP, Mulier LA, Molina HA, Fernandez J., Rimoldi MT, Sica REP (1987) Peripheral Nervous System Damage in Experimental Chronic Chagas' Disease. Am J Trop Med Hyg 36: 41–45. [DOI] [PubMed] [Google Scholar]
- 35. Greenwood BM, Whittle HC (1980) The pathogenesis of sleeping sickness. Trans R Soc Trop Med Hyg 74: 716–725. [DOI] [PubMed] [Google Scholar]
- 36. Haller L., Adams H., Merouze F., Dago A. (1986) Clinical and pathological aspects of human African trypanosomiasis (T b gambiense) with particular reference to reactive arsenical encephalopathy. Am J Trop Med Hyg 35: 94–99. [DOI] [PubMed] [Google Scholar]
- 37. Hamon JF, Seri B., Doua F., Camara P., Aba L. (1990) Effects of mel B, arsobal and alpha‐difluoromethylornithine on the awakening electroencephalogram of humans with Gambiense trypanosomiasis disease: preliminary report. Pharmacol Biochem Behav 36: 831–835. [DOI] [PubMed] [Google Scholar]
- 38. Hamon JF, Camara P., Gauthier P., Arnaud C., Gottesmann C. (1993) Waking electroencephalograms in the blood‐lymph and encephalitic stages of Gambian trypanosomiasis. Ann Trop Med Parasitol 87: 149–155. [DOI] [PubMed] [Google Scholar]
- 39. Hoff R., Teixeira RS, Carvalho JS, Mott KE (1978) Trypanosoma cruzi in the cerebrospinal fluid during the acute stage pf Chagas' disease. N Engl J Med 298: 604–606. [DOI] [PubMed] [Google Scholar]
- 40. Hunter CA, Gow JW, Kennedy PGE, Jennings F. Murray M. (1991) Immunopathology of experimental African sleeping sickness: detection of cytokine mRNA in the brains of Trypanosoma brucei brucei‐infected mice. Infect Immun 59: 4636–4646. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. Hunter CA, Jennings FW, Adams JH, Murray M., Kennedy PGE (1992) Subcurative chemotherapy and fatal post‐treatment reactive encephalopathies in African trypanosomiasis. Lancet 339: 956–958. [DOI] [PubMed] [Google Scholar]
- 42. Hunter CA, Jennings FW, Kennedy PGE, Murray M. (1992) Astrocyte activation correlates with cytokine production in the central nervous system of Trypanosoma brucei brucei infected mice. Lab Invest 67: 635–642. [PubMed] [Google Scholar]
- 43. Hunter CA, Jennings FW, Tierney JF, Murray M., Kennedy PGE (1992) Correlation of autoantibody titres with central nervous system pathology in experimental African trypanosomiasis. J Neuroimmunol 41: 143–148. [DOI] [PubMed] [Google Scholar]
- 44. Hunter CA, Kennedy PGE (1992) Immunopathology in central nervous system Human African trypanosomiasis. J Neuroimmunol 36: 91–95. [DOI] [PubMed] [Google Scholar]
- 45. Hutt MSR, Wilks NE (1971) African trypanosomiasis (sleeping sickness). In: Pathology of Protozoal and Helmintic Diseases with Clinical Correlation, Marcial‐Rojas RA (ed.), pp 57–68, Williams & Wilkins: Baltimore . [Google Scholar]
- 46. Janssen P., van Bogaert L., Haymaker W. (1956) Pathology of the peripheral nervous system in African Trypanosomiasis. A study of seven cases. J Neuropathol Exp Neurol 15: 269–287. [DOI] [PubMed] [Google Scholar]
- 47. Jardim E. (1967) Alteraçōes quantitativas das celulas de Purkinje na Moléstia de Chagas experimental no camundongo. Arq Neuropsiquiatr 25: 199–208. [Google Scholar]
- 48. Jardim E. (1971) Moléstia de Chagas aguda experimental: parasitismo do Hipotálamo. Arq Neuropsiquiatr 29: 190–197. [DOI] [PubMed] [Google Scholar]
- 49. Jennings FW, Hunter CA, Kennedy PGE, Murray M. (1993) Chemotherapy of Trypanosoma brucei infection of the central nervous system: the use of a rapid chemotherapeutic regimen and the development of post‐treatment encephalopathies. Trans R Soc Trop Med Hyg 87: 224–226. [DOI] [PubMed] [Google Scholar]
- 50. Jorg ME, Zalazar‐Rovira I. (1980) Formas clinicas encefalopáticas de enfermidad de Chagas crónica observadas en la Argentina. Pren Med Argent 67: 757–764. [Google Scholar]
- 51. Jorg ME, Zalazar‐Rovira I., Oliva R. (1980) Encefalitis aguda por Trypanosoma cruzi . Pren Med Argent 67: 5–14. [Google Scholar]
- 52. Jorg ME, Azader A., Brocheriou J., Bessola T. (1981) Encefalitis crónica por Trypanosoma cruzi. Participatión inmunopatogénica. Pren Med Argent 68: 85–93. [Google Scholar]
- 53. Junqueira LF Jr, Beraldo PS, Chapadeiro E., Jesus PC (1992) Cardiac autonomic dysfunction and neuroganglionites in a rat model of chronic Chagas' Disease. Cardiovas Res 26: 324–329. [DOI] [PubMed] [Google Scholar]
- 54. Köberle F. (1956) Patogênese dos megas. Rev Goiana Med 2: 101–110. [Google Scholar]
- 55. Köberle F. (1959) Cardiopathia parasympathicopriva. Münchm Med Wschr 101:1308–1310. [PubMed] [Google Scholar]
- 56. Köberle F. (1968) Chagas' disease and Chagas' syndromes: the pathology of American trypanosomiasis. Adv Parasitol 6: 63–116. [DOI] [PubMed] [Google Scholar]
- 57. Köberle F. (1970) The causation and importance of nervous lesions in American Trypanosomiasis. Bull WHO 42: 739–743. [PMC free article] [PubMed] [Google Scholar]
- 58. Köberle F., Schwartzburd H. (1959) Chagas myelopathie. Zschr Tropenmed u parasitol 10: 309–314. [PubMed] [Google Scholar]
- 59. Lambert PH, Berney M. and Kazyumba G. (1981) Immune complexes in serum and cerebrospinal fluid in African trypanosomiasis. Correlation with polyclonal B cell activation and with intracerebral immunooglobulin synthesis. J Clin Invest 67: 77–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60. Leiguarda R., Roncoroni A., Taratuto AL, Jost L., Berthier M., Nogués M., Freilij H. (1990) Acute CNS infection by Trypanosoma cruzi (Chagas'disease) in immunosuppressed patients. Neurology 40: 850–851. [DOI] [PubMed] [Google Scholar]
- 61. Lopes ER, Marques JO, da Costa Neto B., Menezes AA, Chapadeiro ME (1991) Association of encephalitic vascular accidents and Chagas disease. Rev Soc Bras Med Trop 24: 101–104. [DOI] [PubMed] [Google Scholar]
- 62. Lopes ER, Tafuri WL, Chapadeiro E. (1969) Estudo morfolólogico e quantitativa dos núcleos dorsal do vago e hipoglosso em cnagásicos crônicos com e sem megaesôfago. Rev Inst Med Trop Sāo Paulo 11: 123–129. [PubMed] [Google Scholar]
- 63. Lopes ER, Tafuri WL (1983) Involvement of the autonomic nervous system in Chagas heart disease. Rev Soc Bras Med Trop 16: 206–212. [Google Scholar]
- 64. Losavio A., Jones MC, Sanz OP, Mirkin G., Gonzalez Cappa SM, Muchnik S., Sica REP (1989) A secuential study of the peripheral nervous system involvement in experimental Chagas' disease. Am J Trop Med Hyg 41: 539–547. [DOI] [PubMed] [Google Scholar]
- 65. Lucas R., Magez S., Songa B., Darji A., Hamers R. and de Baetseller P. (1993) A role for TNF during African, trypanosomiasis: Involvement in parasite control, immunosuppression and pathology. Res Immunol 144: 370–376. [DOI] [PubMed] [Google Scholar]
- 66. Manuelidis EE (1972) Trypanosomal encephalitides. In: Pathology of the Nervous System, Minckler J. (ed.), vol 3 pp 2545–2559, McGraw‐Hill Book Co: New York . [Google Scholar]
- 67. Mattosinho‐França LC, Fleury RN, Ramos HA Jr., Lemos S., Melaragno Filho R., Pasternak J. (1969) Moléstia de Chagas crônica associada a leucemia linfática: ocorrência de encefalite aguda como alteraçāo do estado imuritário. Arq Neuropsiquiatr 27: 59–66. [Google Scholar]
- 68. Mello de Oliveira JA, Oliveira JSM, Köberle F. (1972) Pathologic anatomy of the His‐Tawara system and electrocardiographic abnormalities in chronic Chagas' heart disease. Arq Bras Cardiol 25: 17–25. [PubMed] [Google Scholar]
- 69. Metze K., Maciel JA Jr. (1993) AIDS and Chagas' disease. Neurology 43: 447–448. [DOI] [PubMed] [Google Scholar]
- 70. Molina HA, Cardoni RL, Rimoldi MT (1987) The neuromuscular pathology of experimental Chagas' disease. J Neurol Sci 81: 287–300. [DOI] [PubMed] [Google Scholar]
- 71. Monteverde DA, Taratuto AL, Lucatelli N. (1976) Meningoencefalitis chagasica aguda en pacientes inmunosuprimidos. Rev Neurol Argent 2: 260–266. [Google Scholar]
- 72. Nascimento OJM, De Fredas MRG, Chimelli L. (1991) Polyneuropathie axonale dans la maladie de Chagas. Rev Neurol 147: 679–681. [PubMed] [Google Scholar]
- 73. O'Caliaghan JP, Seicler FJ (1992) 1, Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced astrogliosis does not require activation of ornithine decarboxylase. Neurosci Lett 148: 105–108. [DOI] [PubMed] [Google Scholar]
- 74. Oddó D., Casanova M., Acun̄a G., Ballesteros J., Morales B. (1992) Acute Chagas' disease (Trypanosomiasis ameri‐cana) in Acquired Immunodeficiency Syndrome: report of two cases. Hum Pathol 23: 41–44. [DOI] [PubMed] [Google Scholar]
- 75. Oka M., Ito V., Furuya M. and Osaki H. (1984) Trypanosoma gambiense: immunosuppression and polyclonal B‐celi activation in mice. Exp Parasitol 58: 209–214. [DOI] [PubMed] [Google Scholar]
- 76. Oliveira JSM, Araújo RRC, Navarro MA, Muccillo G. (1983) Cardiac thrombosis and thromboembolism in chronic Chagas' heart disease. Am J Cardiol 52: 147–151. [DOI] [PubMed] [Google Scholar]
- 77. Pan American Health Organization (1990) Health Conditions in, the Americas. Scientific Publication 524 Volume 1 Washington, DC, pp. 160. [Google Scholar]
- 78. Pentreath VW (1994) Endotoxins and their significance for murine trypanosomiasis. Parasitol Today 10: 226–229. [DOI] [PubMed] [Google Scholar]
- 79. Pentreath VW (1995) Trypanosomiasis and the nervous system. Pathology and immunology. Trans R Soc Trop Med Hyg 89: 9–15. [DOI] [PubMed] [Google Scholar]
- 80. Pentreath VW, Owolabi CA, Doua F., (1992) Survival of Trypanosoma brucei brucei n cerebrospinal fluid Ann Trop Med Parasitol 86: 29–34. [DOI] [PubMed] [Google Scholar]
- 81. Pépin J. and Milord F. (1991) African trypanosomiasis and drug induced encephalopathy: risk factors and pathogenesis. Trans R Soc Trop Med Hyg 85: 222–224. [DOI] [PubMed] [Google Scholar]
- 82. Pittella JEH (1985) Brain, involvement in the chronic cardiac form of Chagas'disease. J Trop Med Hyg 88: 313–317. [PubMed] [Google Scholar]
- 83. Pittella JEH, Meneguette C., Barbosa AJA, Bambirra EA (1990) Histopathological and Immunohistochemical study of the brain in the acute and chronic phases of experimental trypanosomiasis cruzi in dogs. Ann Trop Med Parasitol 84: 615–621. [DOI] [PubMed] [Google Scholar]
- 84. Pittella JEH (1991) Central Nervous System involvement in experimental Trypanosomiasis cruzi. Mem Inst Oswaldo Cruz 86: 141–145. [DOI] [PubMed] [Google Scholar]
- 85. Pittella JEH (1993) Central nervous system, involvement in Chagas' disease. An updating. Rev Inst Med Trop Sāo Paulo 35: 111–116. [DOI] [PubMed] [Google Scholar]
- 86. Pittella JEH, Meneguette C., Barbosa AJA (1993) Histopathological and immunohistochemica study of the brain and heart in tho chroric form of Chagas' disease. Arq Neuropsiquiatr 51: 8–15. [DOI] [PubMed] [Google Scholar]
- 87. Poitera AA (1980) Immunopathological and chemotherapeutc studies in experimental trypanosomiasis witn special reference to heart and brain. Trans R Soc Trop Med Hyg 74: 706–715. [DOI] [PubMed] [Google Scholar]
- 88. Poltera AA, Lambert PH and Mescher PA (1979) Immunopathology of cerebral trypanosomiasis in mice. In: Proceedings of the Menarini Symposium on Immunopathology of the Central and Peripheral nervous System, Miescher PA (ed.), pp 156–164, Schwave & Co: Basel . [Google Scholar]
- 89. Queiroz AC (1973) Tumour like lesion of the brain caused by Trypanosoma cruzi . Am J Trop Med Hyg 22: 473–476. [DOI] [PubMed] [Google Scholar]
- 90. Queiroz AC (1978) Estudo anatomopatológico do encéfalo na forma crônica da doença de Chagas. Rev Pat Trop 7: 135–145. [Google Scholar]
- 91. Ramos SG, Matturri L., Ross L., Rossi MA (1996) Lesions of mediastinal paraganglia in chronic chagasic cardiomyopathy: Cause of sudden death Am Heart J 131: 417–420. [DOI] [PubMed] [Google Scholar]
- 92. Reis MA, Costa RS, Ferraz AS (1995) Causes of death in renal transplant recipients: a study of 102 autopsies from 1968 to 1991. J R Soc Med 88: 24–27. [PMC free article] [PubMed] [Google Scholar]
- 93. Rocha A., Meneses ACO, Silva AM, Ferreira MS, Nishioka SA, Burgarelli MKN, Almeida E., Turcato G. Jr, Metze K., Lopes ER (1994) Pathology of patients with Chagas' disease and Acquired immunodeficiency Syndrome. Am J Trop Med Hyg 50: 261–268. [DOI] [PubMed] [Google Scholar]
- 94. Rosemberg S., Chaves CJ, Higuchi ML, Lopes MBS, Castro LHM, Machado LR (1992) Fatal meningoencephalitis caused by reactivation of Trypanosoma cruzi infection in a patient with AIDS. Neurology 42: 640–642. [DOI] [PubMed] [Google Scholar]
- 95. Rossi MA, Bestetti RB (1995) The Challenge of Chagasic Cardiomyopathy. The pathologic roles of autonomic abnormalities, autoimmune mechanisms and microvascular changes, and therapeutic implications. Cardiology 86:1–7. [DOI] [PubMed] [Google Scholar]
- 96. Said G., Joskowicz M., Barreira AA, Elsen H. (1985) Neuropathy associated with experiments Chagas'disease. Ann Neurol 18: 676–683. [DOI] [PubMed] [Google Scholar]
- 97. Scaravilli F. (1992) Parasitic and Fungal infections. In: Greenfield's Neuropathology, Adams JH & Duchen LW (eds), 5th ed. pp. 400–446, Edward Arnold: London . [Google Scholar]
- 98. Schultzberg M., Ambatsis M., Samuelsson E‐B, Kristensson K. and Van Meirvenne N. (1988) Spread of Trypanosoma brucei to the nervous system: early attack on the circumventricular organs and sensory ganglia. J Neurosci Res 21: 51–61. [DOI] [PubMed] [Google Scholar]
- 99. Sica REP, Filipini D., Panizza M., Fumo T., Basso S., Lazzari J., Molina H. (1986) Involvement of the peripheral sensory nervous system in human chronic Chagas' disease. Mediciana (Buenos Aires) 46: 662–668. [PubMed] [Google Scholar]
- 100. Sica REP, Genovese OM, Erro MG (1991) Peripheral motor nerve conduction studies in patients with chronic Chagas' disease. Arq Neuropsiquiatr 49: 405–408. [DOI] [PubMed] [Google Scholar]
- 101. Solari A., Saavedra H., Sepulveda C., Oddó D., Acuna G., Labarca J., Munoz S., Cuny G., Brengues C., Veas F., Bryan RT (1993) Successful treatment of Trypanosoma cruzi encephalitis in a patient with hemophilia and AIDS. Clin Infec Dis 16: 255–259. [DOI] [PubMed] [Google Scholar]
- 102. Spina‐França A., Yasuda N. (1974) Incidência do acidente cerebrovascular embólico na cardiopatia chagásica crônica. Arq Neuropsiquiatr 32: 195–198. [DOI] [PubMed] [Google Scholar]
- 103. Spina‐França A. (1988) Trypanosomiase américaine (Maladie de Chagas) et le système nerveux. Bull Soc Path Ex 81: 645–649. [PubMed] [Google Scholar]
- 104. Stevens RR and Moulton JE (1977) Experimental meningoencephalitis in Trypanosoma brucei infection of deer mice (Peromyscus maniculatus). A light, immunofluorescent and electron microscopic study. Acta Neuropathol 38: 173–180. [DOI] [PubMed] [Google Scholar]
- 105. Tafuri WL (1970) Pathogenesis of the autonomic nervous system of the mouse in experimental acute Chagas' disease. Am J Trop Med Hyg 19: 405–417. [DOI] [PubMed] [Google Scholar]
- 106. Taratuto A., Pagano MA, Fumo T., Sanz O., Sica REP (1978) Histological and histochemical changes of the skeletal muscle in human chronic Chagas' Disease. Arq Neuropsiquiatr 36: 328–330. [DOI] [PubMed] [Google Scholar]
- 107. Teixeira VPA, Araújo MB, Reis MA, Reis L., Silveira SA, Rodrigues MLR, Franquini J. Jr (1993) Possible role of an adrenal parasite reservoir in the pathogenesis of chronic Trypanosoma cruzi myocarditis. Trans R Soc Trop Med Hyg 87: 552–554. [DOI] [PubMed] [Google Scholar]
- 108. Traub N., Hira PR, Chintu C., Mhango G. (1978) Congenital trypanosomiasis: report of a case due to Trypanosoma brucei rhodesiense. East Afr Med J 55: 477. [PubMed] [Google Scholar]
- 109. Vichi FL (1964) Destruiçāo de neurônios motores na medula espinhal de ratos na fase aguda da Moléstia de Chagas. Rev Inst Med Trop Sāo Paulo 6: 150–154. [PubMed] [Google Scholar]
- 110. Villanueva MS (1993) Trypanosomiasis of the central nervous system. Semin Neurol 13: 209–218. [DOI] [PubMed] [Google Scholar]
- 111. Weffort JL (1995) Clinico‐neuroiogic, electroneuromyographic and pathologic aspects of the predominantly somato‐sensitive peripheral neuropathy associated to chronic Chagas' disease (abs) Arq Neuropsiquiatr 53: 855. [Google Scholar]
- 112. Woodhouse JIJA (1993) The prevalence of clinical peripheral neuropathies in human chronic Chagas' disease. J R Army Med Corps 139: 54–55. [DOI] [PubMed] [Google Scholar]
- 113. Younès‐Chennoufi AB, Joskowicz MH, Tricottet V., Einsen H., Reynes M. (1988) Persistence of Trypanosoma cruzi antigens in the inflammatory lesions of chronically infected mice. Trans R Soc Trop Med Hyg 82: 77–83. [DOI] [PubMed] [Google Scholar]
- 114. Zeledon R. (1974) Epidemiology, modes of transmission and reservoir hosts of Chagas'disease. In: Trypanosomiasis and Leishmaniasis with especial reference to Chagas' disease, Ciba Foundation Symposium, No. 20, pp 51–57, Elsevier: Amsterdam . [Google Scholar]
- 115. Zoli M., Zini I., Grimaldi R., Biagini G. and Agnati LF (1993) Effects of polyamine synthesis blockade on neuronal loss and astroglial reaction after transient forebrain ischemia. Int J Dev Neurosci 11: 175–187. [DOI] [PubMed] [Google Scholar]
