Can sexual transmission support the enzootic cycle of Trypanosoma cruzi?

BACKGROUND Trypanosoma cruzi circulates in sylvatic habitats, mainly through blood-feeding triatomines, although other routes also contribute to its dispersion. Sexual transmission of T. cruzi is an understudied topic, especially among wild mammals. Because of the difficulties inherent to field work, experimentally infected mice are frequently used to evaluate the transmission of T. cruzi. OBJECTIVE This study aimed to evaluate the sexual transmission of T. cruzi in acutely infected mice. METHODS Male and female mice in the acute phase of Chagas disease were mated with naïve partners. Then, parasitological tests, immunohistochemistry, serological assays, and polymerase chain reaction (PCR) assays were used to detect infection. FINDINGS Parasitological analysis showed trypomastigotes in the blood of 20% of the naïve mice after mating with infected partners. Serological assays detected anti-T. cruzi antibodies in all naïve females mated with infected males and in 60% of naïve males mated with infected females. PCR showed T. cruzi nDNA bands for all naïve mice mated with infected partners. The possibility of sexual transmission was also confirmed by visualisation of amastigotes in the testes. MAIN CONCLUSIONS Our results demonstrate that sexual transmission of T. cruzi is an ordinary event that may contribute to maintenance of the parasite's enzootic cycle

Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism

Background: The administration of anti-trypanosome nitroderivatives curtails Trypanosoma cruzi infection in Chagas disease patients, but does not prevent destructive lesions in the heart. This observation suggests that an effective treatment for the disease requires understanding its pathogenesis. Methodology/Principal Findings: To understand the origin of clinical manifestations of the heart disease we used a chicken model system in which infection can be initiated in the egg, but parasite persistence is precluded. T. cruzi inoculation into the air chamber of embryonated chicken eggs generated chicks that retained only the parasite mitochondrial kinetoplast DNA minicircle in their genome after eight days of gestation. Crossbreeding showed that minicircles were transferred vertically via the germ line to chicken progeny. Minicircle integration in coding regions was shown by targeted-primer thermal asymmetric interlaced PCR, and detected by direct genomic analysis. The kDNA-mutated chickens died with arrhythmias, shortness of breath, cyanosis and heart failure. These chickens with cardiomyopathy had rupture of the dystrophin and other genes that regulate cell growth and differentiation. Tissue pathology revealed inflammatory dilated cardiomegaly whereby immune system mononuclear cells lyse parasite-free target heart fibers. The heart cell destruction implicated a thymus-dependent, autoimmune; self-tissue rejection carried out by CD45+, CD8cd+, and CD8a lymphocytes. Conclusions/Significance: These results suggest that genetic alterations resulting from kDNA integration in the host genome lead to autoimmune-mediated destruction of heart tissue in the absence of T. cruzi parasites

Sexual transmission of American trypanosomiasis in humans : a new potential pandemic route for Chagas parasites

Background: the Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease. Objectives: a short-term longitudinal study was conducted to evaluate this hypothesis. Methods: the study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing. Results: three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109) of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109) of the study samples. Moreover, the semen from 82.6% (19/23) of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube. Main conclusions: T. cruzi infections can be transmitted from females or males to naïve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to develop drugs to eradicate the infections. Additionally, the importance of a vigorous education, information, and communication program to prevent sexually transmitted Chagas disease in humans cannot be underemphasised

Can sexual transmission support the enzootic cycle of Trypanosoma cruzi?

BACKGROUND Trypanosoma cruzi circulates in sylvatic habitats, mainly through blood-feeding triatomines, although other routes also contribute to its dispersion. Sexual transmission of T. cruzi is an understudied topic, especially among wild mammals. Because of the difficulties inherent to field work, experimentally infected mice are frequently used to evaluate the transmission of T. cruzi. OBJECTIVE This study aimed to evaluate the sexual transmission of T. cruzi in acutely infected mice. METHODS Male and female mice in the acute phase of Chagas disease were mated with naïve partners. Then, parasitological tests, immunohistochemistry, serological assays, and polymerase chain reaction (PCR) assays were used to detect infection. FINDINGS Parasitological analysis showed trypomastigotes in the blood of 20% of the naïve mice after mating with infected partners. Serological assays detected anti-T. cruzi antibodies in all naïve females mated with infected males and in 60% of naïve males mated with infected females. PCR showed T. cruzi nDNA bands for all naïve mice mated with infected partners. The possibility of sexual transmission was also confirmed by visualisation of amastigotes in the testes. MAIN CONCLUSIONS Our results demonstrate that sexual transmission of T. cruzi is an ordinary event that may contribute to maintenance of the parasite's enzootic cycle

Heritability of the non-Mendelian kDNA mutations in CB chicken families A, B, and C.

<p>Heritability of the non-Mendelian kDNA mutations in CB chicken families A, B, and C.</p

Immune tolerance and its disruption during the rejection of incompatible tissue grafts.

<p>A) The acceptance of compatible heart grafts from syngeneic chickens. Left, healed surgical skin incision and reporter heart acceptance (top) and skin ulcer and reporter heart rejection (bottom). The compatible healthy myocardium was cuffed by loose fibrous tissue (middle) at 17 days. The incompatible heart exhibited extensive necrosis (right) at 14 days. Inset, control heart prior to grafting. B) Fluorochrome-labeled immune cells in congenic Prague chickens. Top row, kDNA- normal BMC and spleen lymphoid follicle histology. Bottom row, kDNA+ BMC and splenic lymphoid follicles exhibiting hypercellularity. Right column, normal histology of one-day-old chick myocardium. Staining: H-E, PkH26, and PkH67. C) Rejection of incompatible heart grafts in congenic chickens. The donor CC graft was acutely rejected by the recipient CB immune cells within 11 days. Left, H-E; middle, red and green labels. Right, one-day-old heart graft displaying normal histology. Bars, 10 µm. Three independent experiments were performed.</p

Mapping and schematic representations of the <i>T. cruzi</i> kDNA mutations in the chicken genome.

<p>A) Distribution of somatic cell mutations in the chromosomes of parental and progeny CB chickens. B) Schematic representation of the <i>T. cruzi</i> minicircle CSB3 and CSB1 mediating kDNA integration into the <i>NADPME</i> locus (HG531657) on chromosome 1. C) Minicircle kDNA (HG531412 and HG 531409) integration into a Hitchcock element at chromosome 3. D) Minicircle kDNA (HG531589) insertion into a repetitive element containing a CR1B element at chromosome Z. E) Three kDNA minicircle sequences hitchhike from the dystrophin locus at chromosome 1 (HG531399) to a second chromosome at an undetermined locus.</p

Microscopic pathology in the heart and skeletal muscles of a dystrophin gene kDNA-mutated rooster, showing inflammatory infiltrates and lysis of striated muscle and of parasympathetic neurons.

<p>A) and B) Heart (left) and skeletal muscle (right) sections showing vacuolation of fibers and inflammatory infiltrates (arrows) in rooster 24 with mutation (HG531472) in the dystrophin gene. C) Inflammatory infiltrations and target striated muscle cell lysis in a chicken progeny. D and E) Inflammatory lymphocytes infiltrates (arrows) parasympathetic ganglia of the large bowel (middle) and of the heart (right), and neuronolysis. Bars, 10 µm.</p

Inhibition and transfer of heart pathology by bone marrow transplantation.

<p>A) Inhibition of heart lesions by the replacement of kDNA+ sick BMCs with healthy kDNA- BMCs in syngeneic chickens. Heart (10.6 g) from a kDNA+ chicken receiving BMCs from a kDNA- donor revealing normal histology. B) Transfer of the heart lesion by the transplantation of sick BMCs from kDNA+ to kDNA- chickens. The heart weighed 26.1 g, and the myocardium exhibited infiltration by effectors lymphocytes and lysis of target cells. C) The reporter heart graft pathology in a kDNA NC chicken receiving BMCs from kDNA+ chicken. The insets present one-day-old normal heart histology before grafting. Data are representative of three independent experiments. Bars: gross, 1 cm; micro, 10 µm.</p