Some components of the cardiac β-adrenergic system are altered in the chronic indeterminate form of experimental Trypanosoma cruzi infection

The chronic indeterminate form of Trypanosoma cruzi infection could be the key to knowing which patients will develop chagasic myocardiopathy. Infected mice present a period in which cardiac functional and structural alterations are different from those described for acute or chronic phases. We studied some components of the cardiac β-adrenergic system in mouse hearts infected with T. cruzi Tulahuen strain or SGO-Z12 isolate during the chronic indeterminate phase of infection. We determined: (i) the primary messenger (epinephrine and norepinephrine) levels in plasma by reverse-phase-HPLC; (ii) the cardiac β-adrenergic receptors’ (β-AR) density and affinity by binding with tritiated dihidroalprenolol and by immunofluorescence; (iii) the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the phosphorylation of the proteins involved in cardiac contraction; (iv) the cardiac contractility and functional studies of the β-ARs as a response to the ligand binding to the receptor; and (v) the left ventricular ejection fraction as a measure of in vivo cardiac function. Plasma catecholamines levels remained similar to those found in uninfected controls. The β-ARs’ affinity decreased in both infected groups compared with the uninfected group (P < 0.05) while the receptors’ density increased only in the SGO-Z12 group (P < 0.01). Cyclic AMP levels were higher in both infected groups (P < 0.01) relative to controls, and were higher in SGO-Z12-infected mice compared with those infected with the Tulahuen strain. However, the basal contractile force remained unchanged and the response to catecholamines only increased in the Tulahuen group (P < 0.05). The left ventricular ejection fraction, on the other hand, was diminished in SGO-Z12-infected mice. Heterogeneity between T. cruzi strains determine, in the chronic indeterminate form, alterations in the signaling pathways of the β-adrenergic system at different levels: (i) between catecholamines and the β₁-receptors; (ii) between the receptors’ activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.     

Studies of membrane fluidity and heart contractile force in Trypanosoma cruzi infected mice

In Chagas disease serious cardiac dysfunction can appear. We specifically studied the cardiac function by evaluating: ventricle contractile force and norepinephrine response, affinity and density of beta-adrenergic receptors, dynamic properties of myocardial membranes, and electrocardiography. Albino swiss mice (n = 250) were infected with 55 trypomastigotes, Tulahuen strain and studied at 35, 75, and 180 days post-infection, that correspond to the acute, indeterminate, and chronic phase respectively. Cardiac beta-adrenergic receptors' affinity, myocardial contractility, and norepinephrine response progressively decreased from the acute to the chronic phase of the disease (p < 0.01). The density (expressed as fmol/mg.prot) of the receptors was similar to non-infected mice (71.96 +/- 0.36) in both the acute (78.24 +/- 1.67) and indeterminate phases (77.28 +/- 0.91), but lower in the chronic disease (53.32 +/- 0.71). Electrocardiographic abnormalities began in the acute phase and were found in 65% of the infected-mice during the indeterminate and chronic phases. Membrane contents of triglycerides, cholesterol, and anisotropy were similar in all groups. A quadratic correlation between the affinity to beta-adrenergic receptors and cardiac contractile force was obtained. In conclusion the changes in cardiac beta-adrenergic receptors suggests a correlation between the modified beta-adrenergic receptors affinity and the cardiac contractile force.     

Action of Trypanosoma rangeli in infections with virulent Trypanosoma cruzi populations

In experimental murine infections with Trypanosoma rangeli it has been observed development immune response to Trypanosoma cruzi. The aim of the present work was to analyze the result of antigenic stimuli and the protective effect with T. rangeli in T. cruzi infections. Mice groups immunized with metacyclic trypomastigotes of T. rangeli (Choach -2V strain), derived from haemolymph and salivary gland and reinfected with T. cruzi virulent populations (Tulahuen strain, SA strain and Dm28c clone) from infected in vitro cells, showed decrease severity of disease outcomes, low parasitemia levels and 100% survival of all mice immunized, in comparison with groups infected only with T. cruzi populations, which demonstrated tissue affection, high parasitemia levels and the death of all animals. The above mentioned data contribute to understand the biological behaviour of T. cruzi and T. rangeli and their interaction with vertebrate host.     

Trypanosoma cruzi: methoprene is a potent agent to sterilize blood infected with trypomastigotes

The effects of methoprene, a juvenile hormone analogue (JHA), on Trypanosoma cruzi bloodstream trypomastigotes (Tulahuen strain, Tul 2 stock) were studied. It was observed that 150microM of methoprene in in vitro experiments cause cellular death of T. cruzi.In contrast, methoprene was not able to clear bloodstream trypomastigotes in in vivo experiments, but it was observed a decrease of parasitemia levels of infected mice treated with 200microg of methoprene/mouse/day during 5 days. According to these results and the low toxicity of methoprene, we suggest that this compound will serve as an effective agent to sterilize blood for transfusions.     

Trypanosoma cruzi reinfections in mice determine the severity of cardiac damage

In two murine models we studied Trypanosoma cruzi reinfection in the acute and chronic phase of experimental Chagas' disease in order to elucidate the relevance of reinfections in determining the variability of cardiac symptoms and the irreversible cardiac damage. They were followed for 120 and 600 days post infection (p.i.) for the acute and chronic model, respectively. Reinfected mice reached higher parasitaemia levels than infected mice. The survival was 33 and 21% in the chronic phase for mice reinfected in the acute phase and 13% for mice reinfected in the chronic stage at the end of the experiments. Sixty-six percent of the infected group presented electrocardiographic abnormalities (heart frequency, prolonged PQ segment or QRS complex) in the chronic stage whereas 100% of the reinfected animals exhibited electric cardiac dysfunction since 90 and 390 days p.i. for the acute and chronic reinfected model, respectively (P<0.01). Heart histopathological studies showed fibrosis and necrosis areas and mononuclear infiltrates supporting the view that parasite persistence is a major factor in continuing the tissue inflammation. This work shows that T. cruzi reinfections could be related to the variability and severity of the clinical course of Chagas' disease and that parasite persistence is involved in exacerbation of the disease.     

Trypanosoma cruzi: Cardiac mitochondrial alterations produced by different strains in the acute phase of the infection

The parasite Trypanosoma cruzi is the causative agent of Chagas disease. T. cruzi invasion and replication in cardiomyocytes induce cellular injuries and cytotoxic reactions, with the production of inflammatory cytokines and nitric oxide, both source of reactive oxygen species. The myocyte response to oxidative stress involves the progression of cellular changes primarily targeting mitochondria. We studied the cardiac mitochondrial structure and the enzymatic activity of citrate synthase and respiratory chain CI–CIV complexes, in Albino Swiss mice infected with T. cruzi, Tulahuen strain and SGO Z12 isolate, in two periods of the acute infection. Changes in the mitochondrial structure were detected in both infected groups, reaching values of 71% for Tulahuen and 88% for SGO Z12 infected mice, 30 days post infection. The citrate synthase activity was different according to the evolution of the infection and the parasite strain, but the respiratory chain alterations were similar with either strain.     

Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E)

Trypanosoma cruzi causes a suppression of the immune system leading to persistence in host cells. The trans -sialidase expressed by T. cruzi is a major virulence factor and transfers sialic acid from host glycoconjugates to mucin-like molecules on the parasite. Here we demonstrate that these sialylated structures play a role in the immunosuppression. We used two T. cruzi strains, whose TS activity correlated with their pathogenicity. The Tulahuen strain, characterized by a high TS activity efficiently infected mice, whereas the Tehuantepec strain showing a reduced TS activity could not establish a patent parasitemia. In vitro analysis revealed that these two strains invaded phagocytic and non-phagocytic host cells at a comparable rate, but they exhibited different potentials to modulate dendritic cell function. In contrast to Tehuantepec, the Tulahuen strain suppressed the production of the proinflammatory cytokine IL-12 and subsequent T-cell activation. This inhibitory effect was absent upon desialylation of the parasite. Therefore, we analysed whether sialylated structures of T. cruzi interact with the inhibitory sialic acid-binding protein Siglec-E on DC. Indeed, Siglec-E interacted with the pathogenic Tulahuen strain, but showed a diminished binding to the Tehuantepec strain. Ligation of Siglec-E on DC using antibodies confirmed this inhibitory effect on DC function.     

Production and characterization of clones of the Brazil strain of Trypanosoma cruzi

Six clones and 4 subclones were isolated from the Brazil strain of Trypanosoma cruzi and were passaged in C3H(He) mice. Parasitemia levels and survival times of mice infected with 8 of the isolates were equivalent to the Brazil strain in virulence. Two clones, designated WFTc-5.1 and WFTc-6.1 (WFTc = Wake Forest Trypanosoma cruzi) were of lower virulence in C3H mice than the other isolates and the Brazil strain. C57BL/6 mice infected with WFTc-5.1 had significantly lower parasitemias and higher survival rates than C57BL/6 mice infected with the Brazil strain or a clone designated WFTc-3.2. Levels of anti-T. cruzi IgM and IgG antibodies were the same in mice infected with higher virulence or lower virulence isolates. Based on these results the Brazil strain of T. cruzi is composed of distinct subpopulations which are heterogeneous with respect to virulence.     

Passive protection of mice against infection with Trypanosoma cruzi with plasma: the use of blood- and vector bug-derived trypomastigote challenge

A study was made of the protective effects of plasma (CMP) from mice convalescent from infection with Trypanosoma cruzi. A single dose of CMP was injected into mice infected with blood trypomastigotes of 1 of each of 5 strains of T. cruzi. Protection was greatest with strains BG, M1 and Y, and least with strain Peru. Strain Tulahuen was of intermediate susceptibility. The protective effect of CMP was found to be similar in mice infected by metacyclic trypomastigotes harvested from vector bugs and mice infected by blood trypomastigotes. Plasma (IMP) from mice hyperimmunized with 6 doses of a killed T. cruzi epimastigote vaccine with saponin as an adjuvant gave no protection against challenge with strain Y, although a group of mice hyperimmunized in parallel with those from which IMP was taken were strongly resistant to challenge.     

Evaluation of immune responses raised against Tc13 antigens of Trypanosoma cruzi in the outcome of murine experimental infection

We have previously reported that genetic immunization with Tc13Tul antigen of Trypanosoma cruzi, the aetiological agent of Chagas' disease, triggers harmful effects and non-protective immune responses. In order to confirm the role of Tc13 antigens during T. cruzi infection, herein we studied the humoral and cellular immune responses to the Tc13Tul molecule and its EPKSA C-terminal portion in BALB/c T. cruzi-infected mice or mice immunized with recombinant Tc13Tul. Analysis of the antibody response showed that B-cell epitopes that stimulate a sustained IgM production along the infection and high levels of IgG in the acute phase are mainly located at the Tc13 N- and C-terminal domains, respectively. DTH assays showed that T-cell epitopes are mainly at the Tc13 N-terminal segment and that they do not elicit an efficient memory response. Recombinant Tc13Tul did not induce IFN-gamma secretion in either infected or immunized mice. However, a putative CD8+Tc13Tul-derived peptide was found to elicit IFN-gamma production in chronically infected animals. Immunization with recombinant Tc13Tul did not induce pathology in tissues and neither did it protect against the infection. Our results show that in the outcome of T. cruzi infection the Tc13 family protein mainly triggers non-protective immune responses.     

Influence of Trypanosoma cruzi strain on the pathogenesis of chronic myocardiopathy in mice

The murine model of chronic Chaga's myocardiopathy was developed in 201 inbred and outbred mice. The experimental groups consisted of 1st: 73 inbred AKR and A/J mice inoculated with one of the following Trypanosoma cruzi strains: Peruvian (Type I), 12 SF (Type II) or Colombian (Type III); 2nd: 128 outbred Swiss mice, chronically infected either with Type II or Type III strains isolated from human patients from different geographical areas. All T. cruzi strains were previously characterized by their morphobiological behaviour in mice and by isoenzymatic patterns. For the 1st group the inoculum was 5 x 10(4) for the Peruvian strain and 1 x 10(5) for the 12 SF and Colombian strains. In the 2nd group-Swiss mice the inoculum size varied from 2 x 10(4) to 2 x 10(5). The inbred animals were killed at a 3 time-point scale (90, 180 and 240 days) post-infection. The Swiss mice were killed from 180 to 660 days after infection. The evaluation of parasitemia and serology (xenodiagnosis and indirect immunofluorescent test) was performed. The incidence of macroscopic alterations of the heart and cardiac index were evaluated. Histopathological lesions of the myocardium were graded. The influence of T. cruzi strain on the intensity of cardiac lesions was evaluated by the Chi-square test; the incidence of inflammatory lesions and its relationship to the parasite strain was evaluated by the Fisher test. The influence of the duration of infection was evaluated by using the Gamma Coefficient of Kruskal and Goodman and its measure of significance. Slight to severe microscopic alterations occurred in 85% of the chronically infected mice. There were a clear predominance on the incidence and intensity of inflammatory and fibrotic alterations for the mice infected with Type III strains. Statistical analysis has shown significant differences among the infected groups, in the inflammatory and fibrotic lesions. Macroscopic alterations (right cavities dilatation and apex aneurism of left ventricle), differed in incidence according to mice strains; in Swiss and AKR mice, significant differences were seen in mice infected with different T. cruzi strains, but the A/J mice failed to show significant differences correlated with different parasite strains. The duration of infection, from 90 to 240 days, could not be correlated with the degree of lesions in the several groups.     

In vivo administration of recombinant IFN-gamma induces macrophage activation, and prevents acute disease, immune suppression, and death in experimental Trypanosoma cruzi infections

Recombinant murine IFN-gamma (rMu-IFN-gamma) was demonstrated to be a potent in vivo activator of mouse peritoneal macrophages to kill Trypanosoma cruzi in vitro and to be capable of conferring protection against death from acute T. cruzi infection. Following i.p. injections of rMu-IFN-gamma, resident peritoneal macrophages were cultured and infected with T. cruzi in vitro. Numbers of intracellular parasites were determined at different times thereafter. Ten or 100 micrograms (1 microgram = 6.5 X 10(5) U) of Mu-IFN-gamma, injected both 24 and 4 h before macrophage harvest, induced up to 99% inhibition of T. cruzi. One microgram of rMu-IFN-gamma was not effective under these conditions. In vitro inhibition of T. cruzi by peritoneal macrophages occurred by 24 h after infection and continued until at least 120 h after infection. There were no significant differences in initial parasite uptake by macrophages from IFN-gamma-treated or control mice, indicating that the rMu-IFN-gamma induced parasite killing. One i.p. dose of 10 micrograms was as effective as two doses if the single injection was given 24 h before macrophage harvest. In subsequent experiments, mice were given multiple injections of 10 micrograms rMu-IFN-gamma beginning 24 h before or 2 h after infection with virulent T. cruzi. Mice treated with rMu-IFN-gamma had significantly lower parasitemias and decreased morbidity compared with control mice. Proliferative responses to Con A and antibody responses to SRBC were not significantly lowered in IFN-gamma-treated mice, in contrast to untreated infected controls. All of the IFN-gamma-treated mice survived acute T. cruzi infection, whereas 100% of saline-treated infected mice died. It was demonstrated in this study that rMu-IFN-gamma activated mouse macrophages in vivo to kill T. cruzi and that rMu-IFN-gamma significantly reduced morbidity and immune suppression, and eliminated mortality resulting from acute infection with this parasite.     

Immune dysfunction in caveolin-1 null mice following infection with Trypanosoma cruzi (Tulahuen strain)

In recent years, host cell caveolae/caveolins have emerged as potentially important targets for pathogenic microorganisms; therefore, we investigated the role of caveolin-1 (Cav-1) in T. cruzi infection using Cav-1 null mice. Cav-1 null and wild type mice were infected with the virulent Tulahuen strain. The mortality was 100% in both groups, but death was slightly delayed in wild type mice. The parasitemia in the Cav-1 null mice was significantly reduced compared with wild type littermates. Histopathologic examination of the heart revealed numerous pseudocysts, myonecrosis, and marked inflammation, which was similar in both mouse groups. Real-time PCR confirmed these observations. Infection of cultured cardiac fibroblasts obtained from Cav-1 null and wild type mice revealed no differences in infectivity. Determination of serum levels of several inflammatory mediators revealed a striking reduction in IFN-gamma, TNF-alpha and components of the nitric oxide pathway in infected Cav-1 null mice. Infection of wild type mice resulted in the expected enhancement of inflammatory mediators. The defective production of chemokines and cytokines observed in vivo is in part attributed to Cav-1 null macrophages. Despite these marked differences in the response to infection by inflammatory mediators between the two mouse strains, the final outcome was similar. These results suggest that Cav-1 may play an important role in the normal development of immune responses.     

Role of glutathione in the susceptibility of Trypanosoma cruzi to drugs

1. Glutathione (G-SH) concentration, gamma-glutamyltranspeptidase and glutathione S-transferase activities were studied in several strains of T. cruzi epimastigotes. GSH varied from 1.04 mM for the LQ strain to 0.61 mM for the Tulahuen strain. 2. Cultures of the LQ strain presented more resistance to drugs than those of the Tulahuen. It was necessary a concentration of nifurtimox 4 times higher and one of benznidazole 10 times higher in order to inhibit approximately to 50% the growth of LQ strain cultures when compared with the Tulahuen strain. 3. Buthionine sulfoximine decreased the concentration of glutathione to about 50% in the LQ and Tulahuen strains and potentiated the toxicity of nifurtimox and benznidazole in T. cruzi epimastigote cultures. These results suggest that glutathione is an important factor in the resistance of T. cruzi to nifurtimox and benznidazole.     

Ultrastructure of murine cardiac ganglia in experimental Chagas' disease.

Albino mice, infected with Trypanosoma cruzi (Tulahuen strain) were sacrificed on days 7, 9, 12, 14, 16, 18, 21, 32 and 39 following infection. Transmission electron microscopic examination of the cardiac ganglia revealed no ultrastructural change at day 7. At day 9 there was peri- and intraganglionic monocytic infiltration but parasites were absent. Between days 12 and 16 there was intense monocytic infiltration, with intra-ganglionic presence of parasites within fibroblasts, monocytes and macrophages. None were seen within capsular cells, endothelial cells, Schwann cells, satellite cells and ganglion cells. The Schwann cells and satellite cells, however, showed phagocytic activity. Satellite cells were also reactive with proliferative pseudopodia which encircled neuronal processes. By day 18, parasites were absent in the ganglia. But monocytes were still present up to day 39, some of them still engulfing satellite cell and neuronal processes. Satellite cells continued to be reactive and Schwann cells phagocytic. Ganglion cells remained normal throughout the experiment. The results suggest that infection of Schwann cells, satellite cells and ganglion cells may depend upon the tissue tropism of the strain of the parasite used and its concentration in the inoculum. The results are consistent with the view that any parasympathetic dysfunction in experimental Chaga's disease in the mouse may be of a transient nature.     

Significance of inducible nitric oxide synthase in acute myocarditis caused by Trypanosoma cruzi (Tulahuen strain)

Chagas' disease, caused by Trypanosoma cruzi, is associated with myocarditis and expression of myocardial cytokines and inducible nitric oxide synthase (NOS2). To assess the functional significance of NOS2 in murine Chagas' disease, we infected NOS2 knockout (NOS2(-/-)) and C57BL/6x129sv (wild type) mice with the Tulahuen strain of T. cruzi. Serial transthoracic echocardiography was performed to assess the progression of left and right ventricular dysfunction in infected mice. Uninfected wild type and NOS2(-/-) mice served as controls. At day 10 post-infection (p.i.), infected wild type mice had larger left ventricular end-diastolic diameter (2.52+/-0.14-vs-2.11+/-0.06 mm, P<0.02) and right ventricle (0.6+/-0.2-vs-0 visual grade, P<0.02) as compared with uninfected wild type mice. At day 19 p.i., compared with uninfected controls, infected wild type mice had larger left ventricular end-diastolic diameter (3.30+/-0.29-vs-2.11+/-0.07 mm), left ventricular end-systolic diameter (1.86+/-0.29-vs-0.88+/-0.05 mm), right ventricle (1.6+/-0.2-vs-0 visual grade), lower heart rate (413+/-27-vs-557+/-25 beats per min), left ventricular relative wall thickness (0.44+/-0.05-vs-0.64+/-0.03) and fractional shortening (45+/-4-vs-57+/-2%) [P<0.05 for all]. In contrast, no differences in left ventricular end-diastolic diameter or fractional shortening were noted among infected and uninfected NOS2(-/-) mice at day 19 p.i. Compared with uninfected controls, infected NOS2(-/-) mice had significantly lower heart rate (272+/-23-vs-512+/-31 beats per min, P<0.01) and larger right ventricle (0.6+/-0.2-vs-0, P<0.05 visual grade). The magnitude of right ventricular dilation in NOS2(-/-) mice was less than that observed in infected wild type mice. At necropsy, the heart weight was greater (129+/-16-vs-109+/-7 mg, P=0.02) and myocardial inflammation more severe in infected wild type compared with infected NOS2(-/-) mice. Myocardial interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha, and interferon-gamma were induced in all infected mice. These data indicate that nitric oxide derived from NOS2 plays an important role in the development and progression of ventricular dilation and systolic dysfunction in acute murine chagasic myocarditis caused by infection with the Tulahuen strain.     

Follow-up of patent and subpatent parasitemias and development of muscular lesions in mice inoculated with very small numbers of Trypanosoma cruzi.

A sequential analysis of patent and subpatent parasitemias, mortality, and histopathology during acute Chagas' disease experimentally produced by inoculation of 10 or 100 bloodstream forms of Trypanosoma cruzi Y strain in susceptible mice was carried out. Parasites were searched for comparatively using three different methods: direct counting, Ficoll-MI density flotation, and hemoculture. Ficoll-MI density flotation promptly discriminated with high reproducibility subpatent parasitemic states not detected in the blood samples analyzed by direct counting. Despite the high proportion of supposedly uninfected animals and depending on the postinfection time, the majority of the mice had bloodstream parasites at the subpatent level detected by Ficoll-MI, and all of them had muscular lesions during the acute phase. All Ficoll-MI-negative blood samples from infected mice were also negative by hemoculture. Normal mouse blood purposely contaminated with parasite quantities ranging from 200 to 2000/ml was tested comparatively by density flotation and hemoculture and showed frequencies of reisolation varying from 25 to 100%. Overall, these data showed that inoculum as low as 10 infective forms of Y strain is able to induce acute Chagas' disease in susceptible mice and that a subpatent parasitemic state of 600-1000 forms/ml is a common finding. The use of Ficoll-MI to detect subpatent parasitemia is discussed.     

DNA damage and nitric oxide synthesis in experimentally infected Balb/c mice with Trypanosoma cruzi

This study aimed to evaluate whether experimental Chagas disease in acute phase under benznidazole therapy can cause DNA damage in peripheral blood, liver, heart, and spleen cells or induce nitric oxide synthesis in spleen cells. Twenty Balb/c mice were distributed into four groups: control (non-infected animals); Trypanosoma cruzi infected; T. cruzi infected and submitted to benznidazole therapy; and only treated with benznidazole. The results obtained with the single cell gel (comet) assay showed that T. cruzi was able induce DNA damage in heart cells of both benznidazole treated or untreated infected mice. Similarly, T. cruzi infected animals showed an increase of DNA lesions in spleen cells. Regarding nitric oxide synthesis, statistically significant differences (p<0.05) were observed in all experimental groups compared to negative control, the strongest effect observed in the T. cruzi infected group. Taken together, these results indicate that T. cruzi may increase the level of DNA damage in mice heart and spleen cells. Probably, nitric oxide plays an important role in DNA damaging whereas benznidazole was able to minimize induced T. cruzi genotoxic effects in spleen cells.     

Trypanosoma cruzi: explant organ cultures from mice with chronic Chagas' disease

Explants of 13 different organs obtained from C3H/HEN, Swiss-Webster, and C57Bl/6 mice chronically infected with Trypanosoma cruzi (Y strain) were cocultivated with mouse embryo fibroblasts to determine the organs that contain T. cruzi during the chronic infection. Explant cultures frequently yielded T. cruzi as late as 12 months after infection. Spleen and skeletal muscle were most frequently positive; heart cultures were rarely positive in any mouse strain. C3H/HEN mice had significantly more cultures positive than Swiss-Webster mice, as expected from relative susceptibility of C3H/HEN mice to acute infection. In contrast, C57Bl/6 mice, relatively resistant to acute infection, had significantly more cultures positive at 12 months of infection than Swiss-Webster mice. Also, C57Bl/6 mice had a significant increase in the number of positive cultures at 12 months of infection compared to 6 months of infection. These results show that organisms can be recovered routinely from some tissues during the chronic infection, that murine susceptibility to infection should differentiate between acute and chronic infection, and that C57Bl/6 mice may lose control of infection during the chronic infection.     

Creatine phosphokinase isoenzymes and Trypanosoma cruzi infections.

1. Substantial increases in total creatine phosphokinase (CPK) and in isoenzymes from heart (CPK-MB) and skeletal muscle (CPK-MM) were observed during acute infections with the House 510 and House 11 strains of Trypanosoma cruzi. 2. In infections with the reticulotropic Tulahuen strain total CPK levels were lower and the isoenzyme pattern was essentially normal. 3. Gamma-glutamyl transpeptidase was considerably increased in the Tulahuen but not in the House 510 and House 11 infections. 4. These findings are useful in assessing tissue damage during T. cruzi infections and they also demonstrate differences between myotropic and reticulotropic strains which may aid in their taxonomic classification.