Recrudescence induced by cyclophosphamide of chronic Trypanosoma cruzi infection in mice is influenced by the parasite strain

Reactivation of chronic chagasic patients may occur upon use of immunosuppressive drugs related to kidney or heart transplantation or when they are affected by concomitant HIV infection. This recrudescence, however, does not occur in all chagasic patients exposed to immunosuppressive agents. We therefore investigated the influence of Trypanosoma cruzi strains in the recrudescence of the parasitism in mice at the chronic phase treated with cyclophosphamide, an immunosuppressor that blocks lymphocytes DNA synthesis and therefore controls B cells response. A large variation was detected in the percentages of newly established acute phases in the groups of mice inoculated with the different strains. We suggest that reactivation of chronic T. cruzi infections is influenced by the parasite intrinsic characteristics, a phenomenon that might occur in the human disease.

Trypanosoma cruzi infection in offspring born to chagasic C3H/He mice

This study reports the effects of Trypanosoma cruzi infection induced in C3H/He male and female mice born to chagasic mice. An experimental model was established infecting female C3H/He mice with a low virulent T. cruzi clone. In this model, mating, fertilization, pregnancy evolution and delivery was carried out successfully. The offspring was infected at four, six and eigth weeks of age. The results showed that the offspring born to chagasic mothers present decreased resistance to acquired T. cruzi infection. This decreased resistance was expressed by higher levels of parasitaemia and higher mortality rates in offspring born to chagasic mothers than in controls. Age and sex were shown to be important factors of this phenomenon. The results suggest that maternal immune system products can modulate the immune response of the offspring.

Trypanosoma cruzi strains and autonomic nervous system pathology in experimental chagas disease

Lesions involving the sympathetic (para-vertebral ganglia) and para-sympathetic ganglia of intestines (Auerbach plexus) and heart (right atrial ganglia) were comparatively analyzed in mice infected with either of three different strain types of Trypanosoma cruzi, during acute and chronic infection, in an attempt to understand the influence of parasite strain in causing autonomic nervous system pathology. Ganglionar involvement with neuronal destruction appeared related to inflammation, which most of the times extended from neighboring adipose and cardiac, smooth and striated muscular tissues. Intraganglionic parasitism was exceptional. Inflammation involving peripheral nervous tissue exhibited a focal character and its variability in the several groups examined appeared unpredictable. Although lesions were generally more severe with the Y strain, comparative qualitative study did not allow the conclusion, under the present experimental conditions, that one strain was more pathogenic to the autonomic nervous system than others. No special tropism of the parasites from any strain toward autonomic ganglia was disclosed.

Biological comparison between three clones of Trypanosoma cruzi and the strain of origin (Bolivia) with reference to clonal evolution studies

After isolating three clones of Trypanasoma cruzi (Bolivia), we first characterized them according to parasitaemia, pleomorphism and virulence, and then histopathologically. The study's interest lies on the hypothesis that clonal evolution of T. cruzi has a major impact on biologically relevant properties of this parasite. Data obtained from the studies of parasitaemia, pleomorphism and virulence showed no differences between the groups studied. As a final point, the histopathological study shows us a muscular tissue tropism both in clones and in their mother strain (Bolivia). In this paper, we conclude that Bolivia strain and clones isolated from it, pertaining to the same major clone share similar biological properties.

Trypanosoma cruzi in the anal glands of urban opossums: I- isolation and experimental infections

Opossums (Didelphis marsupialis) captured in intensely urbanized areas of the city of Caracas, Venezuela, were found infected with Trypanosoma cruzi. The developmental cycle of trypomastigote-epimastigote-metacyclic infective trypomastigote, usually occurring in the intestine of the triatomine vector, was taking place in the anal odoriferous glands of the opossums. Material from the glands, inoculated in young, healthy opossums and white mice by different routes, subcutaneously, intraperitoneally, orally, and into the eye, induced T. cruzi infections in all animals. Parasitemia, invasion of cardiac and skeletal muscle, and intracellular multiplication of amastigotes were observed. Inoculation of metacyclics from anal glands, cultured in LIT medium, gave equivalent results. All opossums survived; all mice died. Excreta of opossums may thus transmit Chagas' disease by contamination, even in urban areas where insect vectors are not present.

Histopathological study of experimental and natural infections by Trypanosoma cruzi in Didelphis marsupialis

Didelphis marsupialis, the most important sylvatic reservoir of Trypanosoma cruzi, can also maintain in their anal scent glands the multiplicative forms only described in the intestinal tract of triatomine bugs. A study of 21 experimentally and 10 naturally infected opossums with T. cruzi was undertaken in order to establish the histopathological pattern under different conditions. Our results showed that the inflammation was predominantly lymphomacrophagic and more severe in the naturally infected animals but never as intense as those described in Chagas' disease or in other animal models. The parasitism in both groups was always mild with very scarce amastigote nests in the tissues. In the experimentally infected animals, the inflammation was directly related to the presence of amastigotes nests. Four 24 days-old animals, still in embryonic stage, showed multiple amastigotes nests and moderate inflammatory reactions, but even so they survived longer and presented less severe lesions than experimentally infected adult mice. Parasites were found in smooth, cardiac and/or predominantly striated muscles, as well as in nerve cells. Differing from the experimentally infected opossums parasitism in the naturally infected animals predominated in the heart, esophagus and stomach. Parasitism of the scent glands did not affect the histopathological pattern observed in extraglandular tissues.

Characterization of Trypanosoma cruzi Strains Isolated from Chronic Chagasic Patients, Triatomines and Opossums Naturally Infected from the State of Rio Grande do Sul, Brazil

Thirty-five Trypanosoma cruzi strains were isolated from chronic chagasic patients, triatomines and opossums from different municipalities of the State of Rio Grande do Sul. Parasites were characterized by means of mice infectivity, enzyme electrophoresis and randomly amplified polymorphic DNA (RAPD) analysis. Twenty-nine strains were isolated from chagasic patients, 4 from triatomines (2 from Triatoma infestans and 2 from Panstrongylus megistus) and 2 from opossums Didelphis albiventris. Thirty-three T. cruzi strains were of low and 2 strains of high virulence in mice. Both virulent strains were isolated from P. megistus. Isoenzyme analysis of the strains showed 3 different zymodemes. Eleven strains isolated from chagasic patients and 2 from D. albiventris were Z2. Eighteen strains from patients and 2 from T. infestans were ZB and 2 T. cruzi strains isolated from P. megistus were Z1. RAPD profiles obtained with 4 random primers showed a high genetic heterogeneity of the T. cruzi strains. Zymodeme 2 and ZB strains were the more polymorphic. A band sharing analysis of the RAPD profiles of Z2 and ZB strains using 3 primers, showed a very low percentage of shared bands, 20% among 13 ZB strains and 14% among 13 Z2 strains. According to the isoenzyme results, 3 T. cruzi populations were present in State of Rio Grande do Sul. Zymodeme 2 and ZB strains were found infecting man (domiciliar transmission cycle) whereas Z1 strains were found infecting the sylvatic vector P. megistus

Genetic Variability and Microdistribution of Triatoma infestans Genotypes and Trypanosoma cruzi Clones in Arequipa Region (Peru)

The genetic variability of Triatoma infestans and Trypanosoma cruzi populations was studied by isoenzyme analysis in two distinct areas of Arequipa province (Peru); one, Santa Rita de Siguas, being an endemic area for Chagas' disease, the second, Arequipa, recently infected. Analysis of T. infestans genetic variability indicates, (i) temporal stability of genotypes found in Santa Rita de Siguas, (ii) high genetic differences between Arequipa and Santa Rita de Siguas populations suggesting minor contact between them, (iii) multiple origin of the T. infestans population in Arequipa, and (iv) poor dispersal capacity of T. infestans: the panmictic unit could be reduce to a house. Parasite isoenzyme analysis was performed in 29 Peruvian stocks of T. cruzi, mainly isolated from bugs taken in a single locality, Santa Rita de Siguas. The results show, (i) a high genetic polymorphism, (ii) nine different multilocus genotypes were detected and clustered in two different clades, (iii) most of the parasite isolates pertained to one of the clade and were genetically similar to those analyzed 12 years before. This sample allowed the study of the mating system of T. cruzi in strict sympatic conditions and gave more strength to the hypothesis of the clonal structure of T. cruzi populations

Immune Response to Trypanosoma cruzi Shed Acute Phase Antigen in Children from an Endemic Area for Chagas' Disease in Bolivia

A field study of the immune response to the shed acute phase antigen (SAPA) of Trypanosoma cruzi was carried out in the locality of Mizque, Cochabamba department, Bolivia. Schoolchildren (266), with an average of 8.6 ± 3.6 years, were surveyed for parasitological and serological diagnosis, as well as antibodies directed against SAPA using the corresponding recombinant protein in ELISA. The antibodies against SAPA were shown in 82% of patients presenting positive serological diagnosis (IgG specific antibodies). The positive and negative predictive values were 0.88. Antibodies anti-SAPA were shown in 80.8% of the chagasic patients in the initial stage of the infection (positive IgM serology and/or positive buffy coat (BC) test) and in 81.4% of the patients in the indeterminate stage of the infection (positive IgG serology with negative BC and IgM tests). These results show that the anti-SAPA response is not only present during the initial stage of the infection (few months) but extends some years after infection

TcruziDB, an Integrated Database, and the WWW Information Server for the Trypanosoma cruzi Genome Project

Data analysis, presentation and distribution is of utmost importance to a genome project. A public domain software, ACeDB, has been chosen as the common basis for parasite genome databases, and a first release of TcruziDB, the Trypanosoma cruzi genome database, is available by ftp from ftp://iris.dbbm.fiocruz.br/pub/genomedb/TcruziDB as well as versions of the software for different operating systems (ftp://iris.dbbm.fiocruz.br/pub/unixsoft/). Moreover, data originated from the project are available from the WWW server at http://www.dbbm.fiocruz.br. It contains biological and parasitological data on CL Brener, its karyotype, all available T. cruzi sequences from Genbank, data on the EST-sequencing project and on available libraries, a T. cruzi codon table and a listing of activities and participating groups in the genome project, as well as meeting reports. T. cruzi discussion lists (tcruzi-l@iris.dbbm.fiocruz.br and tcgenics@iris.dbbm.fiocruz.br) are being maintained for communication and to promote collaboration in the genome project

The Trypanosoma cruzi Genome Project: Nuclear Karyotype and Gene Mapping of Clone CL Brener

By using improved pulsed field gel electrophoresis conditions, the molecular karyotype of the reference clone CL Brener selected for Trypanosoma cruzi genome project was established. A total of 20 uniform chromosomal bands ranging in size from 0.45 to 3.5 Megabase pairs (Mbp) were resolved in a single run. The weighted sum of the chromosomal bands was approximately 87 Mbp. Chromoblots were hybridized with 39 different homologous probes, 13 of which identified single chromosomes. Several markers showed linkage and four different linkage groups were identified, each comprising two markers. Densitometric analysis suggests that most of the chromosomal bands contain two or more chromosomes representing either homologous chromosomes and/or heterologous chromosomes with similar sizes