Schistosoma mansoni co-infection modulates Chagas disease development but does not impair the effect of benznidazole-based chemotherapy.

The adequate management of parasite co-infections represents a challenge that has not yet been overcome, especially considering that the pathological outcomes and responses to treatment are poorly understood. Thus, this study aimed to evaluate the impact of Schistosoma mansoni infection on the efficacy of benznidazole (BZN)-based chemotherapy in Trypanosoma cruzi co-infected mice. BALB/c mice were maintained uninfected or co-infected with S. mansoni and T. cruzi, and were untreated or treated with BZN. Body weight, mortality, parasitemia, cardiac parasitism, circulating cytokines (Th1/Th2/Th17); as well as heart, liver and intestine microstructure were analyzed. The parasitemia peak was five times higher and myocarditis was more severe in co-infected than T. cruzi-infected mice. After reaching peak, parasitemia was effectively controlled in co-infected animals. BZN successfully controlled parasitemia in both co-infected and T. cruzi-infected mice and improved body mass, cardiac parasitism, myocarditis and survival in co-infected mice. Co-infection dampened the typical cytokine response to either parasite, and BZN reduced anti-inflammatory cytokines in co-infected mice. Despite BZN normalizing splenomegaly and liver cellular infiltration, it exacerbated hepatomegaly in co-infected mice. Co-infection or BZN exerted no effect on hepatic granulomas, but increased pulmonary and intestinal granulomas. Marked granulomatous inflammation was identified in the small intestine of all schistosomiasis groups. Taken together, our findings indicate that BZN retains its therapeutic efficacy against T. cruzi infection even in the presence of S. mansoni co-infection, but with organ-specific repercussions, especially in the liver.

Oxidative stress, cardiomyocytes premature senescence and contractile dysfunction in in vitro and in vivo experimental models of Chagas disease.

AIMS: The relationship between redox imbalance and cardiovascular senescence in infectious myocarditis is unknown. Thus, the aim of this study was to investigate whether cardiomyocytes parasitism, oxidative stress and contractile dysfunction can be correlated to senescence-associated ß-galactosidase (SA-ß-Gal) activity in Trypanosoma cruzi-infection in vitro and in vivo. METHODS: Uninfected, T. cruzi-infected untreated and benznidazole (BZN)-treated H9c2 cardiomyocytes and rats were investigated. Parasitological, prooxidant, antioxidant, microstructural, and senescence-associated markers were quantified in vitro and in vivo. RESULTS: T. cruzi infection triggered intense cardiomyocytes parasitism in vitro and in vivo, which was accompanied by reactive oxygen species (ROS) upregulation, lipids, proteins and DNA oxidation in cardiomyocytes and cardiac tissue. Oxidative stress was parallel to microstructural cell damage (e.g., increased cardiac toponin I levels) and contractile dysfunction in cardiomyocytes in vitro and in vivo, whose severity accompanied a premature cellular senescence-like phenotype revealed by increased senescence-associated ß-galactosidase (SA-ß-Gal) activity and DNA oxidation (8-OHdG). Cellular parasitism (e.g., infection rate and parasite load), myocarditis and T. cruzi-induced prooxidant responses were attenuated by early BZN administration to interrupt the progression of T. cruzi infection, protecting against SA-ß-gal-based premature cellular senescence, microstructural damage and contractile deterioration in cardiomyocytes from T. cruzi-infected animals. CONCLUSION: Our findings indicated that cell parasitism, redox imbalance and contractile dysfunction were correlated to SA-ß-Gal-based cardiomyocytes premature senescence in acute T. cruzi infection. Therefore, in addition to controlling parasitism, inflammation and oxidative stress; inhibiting cardiomyocytes premature senescence should be further investigated as an additional target of specific Chagas disease therapeutics.

Insights into CX3CL1/Fractalkine during experimental Trypanosoma cruzi infection.

Trypanosoma cruzi triggers a progressive myocarditis in mammalians through activation and recruitment of leukocytes and release of inflammatory mediators. The chemokine CX3CL1 has been highlighted for its potential role in the parasite controlling in end-pathological status of infected hosts. This study investigated the systemic and cardiac release of CX3CL1 in experimental T. cruzi infection and how this chemokine correlates with endothelin-1 and TNF. Male Fisher rats (n = 20) were infected, or not, by the Y strain of T. cruzi and parasitemia was daily evaluated and immunoassays performed in the cardiac tissue macerated supernatant and in serum to evaluate CX3CL1, endothelin, and TNF production on days 5 and 15 of infection. T. cruzi infection induced a higher serum and cardiac production of these mediators on days 5 and 15 of infection. In both periods of infection, respectively, CX3CL1 showed a positive correlation with TNF (r = 0.833, p < 0.001 and r = 0.723, p < 0.001) and endothelin-1 (r = 0.801, p < 0.05 and r = 0.857, p < 0.001), which reinforce its participation in the T. cruzi-induced myocarditis development.

Chronic rapamycin pretreatment modulates arginase/inducible nitric oxide synthase balance attenuating aging-dependent susceptibility to Trypanosoma cruzi infection and acute myocarditis.

Considering the efficacy of rapamycin in increasing lifespan and healthspan, attenuating the aging-dependent immunological decline, we compared the evolution of Trypanosoma cruzi infection and acute myocarditis in young and elderly mice untreated and chronically treated with this drug. Five groups were investigated: young uninfected and infected, elderly uninfected and infected with Trypanosoma cruzi untreated and treated with rapamycin (4 mg/kg every 3 days) from the 8th to the 96th week of age. Seven days after the last treatment, elderly mice were inoculated with T. cruzi. Young animals were infected at 8-weeks-old. Untreated elderly mice exhibited increase parasitemia, parasite load and myocarditis, which were associated to down-regulation in IL-2, IL-6, IFN-γ, TNF, anti-T. cruzi immunoglobulin G (IgG) total, IgG1 and IgG2a plasma levels, inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) cardiac production, as well as upregulation in Arginase-1 gene expression and arginase activity compared to young animals. These parameters were improved in rapamycin-pretreated elderly mice, which exhibited a better parasitological control, reduced heart inflammation and microstructural damage. These responses were associated with a better balance between Th1 and Th2 effectors similar to that observed in young animals, including an improved activation of Th1 cytokines and the iNOS pathway that positively regulates NO biosynthesis, contradicting the predominant activation of the arginase pathway in untreated elderly animals. Thus, our findings suggest that chronic pretreatment with rapamycin can attenuate immunosenescence in mice, contributing to prolong parasite resistance and attenuate acute myocarditis in elderly host challenged by T. cruzi.

Fat tissue regulates the pathogenesis and severity of cardiomyopathy in murine chagas disease.

Chronic Chagas cardiomyopathy (CCC) caused by a parasite Trypanosoma cruzi is a life-threatening disease in Latin America, for which there is no effective drug or vaccine. The pathogenesis of CCC is complex and multifactorial. Previously, we demonstrated T. cruzi infected mice lose a significant amount of fat tissue which correlates with progression of CCC. Based on this an investigation was undertaken during both acute and chronic T. cruzi infection utilizing the FAT-ATTAC murine model (that allows modulation of fat mass) to understand the consequences of the loss of adipocytes in the regulation of cardiac parasite load, parasite persistence, inflammation, mitochondrial stress, ER stress, survival, CCC progression and CCC severity. Mice were infected intraperitoneally with 5x104 and 103 trypomastigotes to generate acute and chronic Chagas models, respectively. Ablation of adipocytes was carried out in uninfected and infected mice by treatment with AP21087 for 10 days starting at 15DPI (acute infection) and at 65DPI (indeterminate infection). During acute infection, cardiac ultrasound imaging, histological, and biochemical analyses demonstrated that fat ablation increased cardiac parasite load, cardiac pathology and right ventricular dilation and decreased survival. During chronic indeterminate infection ablation of fat cells increased cardiac pathology and caused bi-ventricular dilation. These data demonstrate that dysfunctional adipose tissue not only affects cardiac metabolism but also the inflammatory status, morphology and physiology of the myocardium and increases the risk of progression and severity of CCC in murine Chagas disease.

Prevalence of Cardiovascular Complications in Malaria: A Systematic Review and Meta-Analysis.

Recent studies have suggested that malaria may affect the cardiovascular system. The aim of this systematic review and meta-analysis was to determine the prevalence of cardiovascular complications in symptomatic malaria patients. We searched databases such as Pubmed, Embase, Cochrane, and Web of Science (January 1950-April 2020) for studies reporting on cardiovascular complications in adults and children with malaria. Cardiovascular complications were defined as abnormalities in electrocardiogram (ECG), cardiac biomarkers, and echocardiography on admission or during outpatient examination. Studies of patients with known heart disease or cardiovascular evaluation performed after the start of intravenous antimalarial medication were excluded. The study was registered in International Prospective Register of Systematic Reviews (PROSPERO) (No.: CRD42020167672). The literature search yielded 1,243 studies, and a total of 43 studies with symptomatic malaria patients were included. Clinical studies (n = 12 adults; n = 5 children) comprised 3,117 patients, of which a majority had Plasmodium falciparum (n = 15) and were diagnosed with severe malaria (n = 13). In random-effects models of adults, the pooled prevalence estimate for any cardiovascular complication was 7% (95% CI: 5-9). No meta-analysis was conducted in children, but the range of abnormal ECG was 0-8%, cardiac biomarkers 0-57%, and echocardiography 4-9%. We analyzed 33 cases (n = 10 postmortem), in which the most common cardiovascular pathologies were myocarditis and acute coronary syndrome. All histopathological studies found evidence of parasitized red blood cells in the myocardium. Cardiovascular complications are not uncommon in symptomatic adults and children with malaria. Additional studies investigating malaria and cardiovascular disease are encouraged.

Toxoplasmosis and the Heart.

Toxoplasmosis is a common disease caused by Toxoplasma gondii, a parasite with high prevalence in tropical regions. Most infections show minimal symptoms, but immunocompromised patients tend to have a poor prognosis. Cardiovascular manifestations in toxoplasmosis are rare and reported in a limited number of patients. As part of the "Neglected Tropical Diseases and Other Infectious Diseases Affecting the Heart" (NET-Heart) project, this paper aims to systematically review all available information regarding the cardiovascular implications of toxoplasmosis. Relevant studies were identified in the MEDLINE and/or PubMed database, and 48 articles were ultimately included. This was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Cardiac compromise in toxoplasmosis mainly involves myocarditis, and complications vary widely in severity. Toxoplasmic myocarditis is challenging to diagnose, as endomyocardial biopsy is usually required. This article provides a summary of cardiac toxoplasmosis, including an original algorithm facilitating diagnosis and treatment.

Myocarditis Associated With Enteric Amebiasis in an Adolescent.

Parasitic diseases may occasionally affect the cardiovascular system while it is rarely seen in childhood. Parasites may directly or indirectly affect the heart in the form of myocarditis, pericarditis, pancarditis, or pulmonary hypertension. Therefore, it should be kept in mind that parasites may be responsible for myocardial and pericardial disease anywhere around the globe. Herein, we report an adolescent boy with myocarditis associated with enteric amebiasis.

The first case of combined heart-liver transplantation in a patient with alveolar echinococcosis.

We report a rare case of liver alveolar echinococcosis with an invasion of the hepaticocaval confluence, inferior vena cava, pericardium, right atrium, atrial septum, and superior vena cava, and its successful treatment by combined heart-liver transplantation.

Impact of diminazene aceturate on renin-angiotensin system, infectious myocarditis and skeletal myositis in mice: An in vitro and in vivo study.

Although renin-angiotensin system (RAS) imbalance is manifested in cardiomyopathies with different etiologies, the impact of RAS effectors on Chagas cardiomyopathy and skeletal myositis is poorly understood. Given that diminazene aceturate (DMZ) shares trypanocidal, angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) stimulatory effects, we investigated the impact of DMZ on cardiomyocytes infection in vitro, renin-angiotensin system, Chagas cardiomyopathy and skeletal myositis in vivo. Cardiomyocytes and T. cruzi were used to evaluate DMZ toxicity in vitro. The impact of 20-days DMZ treatment (1 mg/kg) was also investigated in uninfected and T. cruzi-infected mice as follows: control uninfected and untreated, uninfected treated with DMZ, infected untreated and infected treated with DMZ. DMZ had low toxicity on cardiomyocytes, induced dose-dependent antiparasitic activity on T. cruzi trypomastigotes, and reduced parasite load but not infection rates in cardiomyocytes. DMZ increased ACE2 activity and angiotensin-(1-7) plasma levels but exerted no interference on angiotensin-converting enzyme (ACE) activity, ACE, ACE2 and angiotensin II levels in uninfected and infected mice. DMZ treatment also reduced IFN-γ and IL-2 circulating levels but was ineffective in attenuating parasitemia, MCP-1, IL-10, anti-T. cruzi IgG, nitrite/nitrate and malondialdehyde production, myocarditis and skeletal myositis compared to infected untreated animals. As the antiparasitic effect of DMZ in vitro did not manifest in vivo, this drug exhibited limited relevance to the treatment of Chagas disease. Although DMZ is effective in upregulating angiotensin-(1-7) levels, this molecule does not act as a potent modulator of T. cruzi infection, which can establish heart and skeletal muscle parasitism, lipid oxidation and inflammatory damage, even in the presence of high concentrations of this RAS effector.

Could phenothiazine-benznidazole combined chemotherapy be effective in controlling heart parasitism and acute infectious myocarditis?

Phenothiazines inhibit major antioxidant defense mechanisms in trypanosomatids and exhibit potent cytotoxic effects in vitro. However, the relevance of these drugs in the treatment of Trypanosoma cruzi-induced acute myocarditis is poorly explored, especially in combination with reference trypanocidal drugs. Thus, we compared the antiparasitic and cardioprotective potential of thioridazine (TDZ) and benznidazole (Bz) administered in monotherapy and combined in a murine model of T. cruzi-induced acute myocarditis. Female mice were randomized into six groups: (i) uninfected untreated, (ii) infected untreated, or infected treated with (iii) Bz (100 mg/kg), (iv) TDZ (80 mg/kg), (v) Bz (100 mg/kg) + TDZ (80 mg/kg), or (vi) Bz (50 mg/kg) + TDZ (80 mg/kg). Infected animals were inoculated with 2000 T. cruzi trypomastigotes and treated by gavage for 20 days. Animals that received TDZ alone presented the highest levels of parasitemia, parasitic load and anti-T. cruzi immunoglobulin G titers; cardiac upregulation of N-acetyl-ß-D-glucosaminidase activity, nitric oxide, malondialdehyde and cytokines (IFN-γ, TNF-α, IL-10 and IL-17); as well as microstructural damage compared to the other groups (p < 0.05). These parameters were reduced in groups receiving Bz monotherapy compared to the other groups (p < 0.05). The combination of TDZ and Bz attenuated the response to treatment, worsening parasitological control, oxidative heart damage and myocarditis compared to the group treated with Bz alone (p < 0.05). Our results indicate that when administered alone, TDZ potentiated the pathological outcomes in animals infected with T. cruzi. Moreover, TDZ attenuated the antiparasitic effect of Bz when administered together, impairing parasitological control, potentiating inflammation, molecular oxidation and pathological microstructural remodeling of the heart. Thus, our findings indicate that TDZ acts as a pharmacological risk factor and Bz-based monotherapy remains a better cardioprotective drug against Trypanosoma cruzi-induced acute myocarditis.

Rapamycin Treatment Reduces Acute Myocarditis Induced by Trypanosoma cruzi Infection.

Chagas disease affects millions of people mainly in Latin America and is a protozoan illness caused by the parasite Trypanosoma cruzi. Chagasic cardiomyopathy is the leading cause of mortality of infected patients, due to compromised electrical and mechanical cardiac function induced by tissue remodeling, especially fibrosis, and lymphocytic infiltration. Some cellular biochemical pathways can be protective to the heart, and we tested if the in vivo activation of the autophagic machinery by rapamycin could reduce parasite-induced myocarditis. Regarding the expression of LC3, an autophagy marker, we observed its upregulation in the cardiac tissue of infected untreated mice. However, after rapamycin treatment, an autophagy inducer, infected mice showed reduced electrical cardiac dysfunctions, myocarditis, cardiac damage, and reduced production of pro-inflammatory cytokines by the heart. On the other hand, the parasite's life cycle was not affected, and we observed no modulations in cardiac tissue or blood parasitemia. Our data indicate that, at least partially, autophagy induction controls inflammation in the heart¸ illustrating the complexity of the pathways that concur to the development of the infection.

Sesquiterpene lactone potentiates the immunomodulatory, antiparasitic and cardioprotective effects on anti-Trypanosoma cruzi specific chemotherapy.

We investigated the immunomodulatory, antiparasitic and cardioprotective effects of a sesquiterpene lactone (SL) administered alone or combined with benznidazole (Bz), in a murine model of Chagas' disease by in vitro and in vivo assays. Antiparasitic and cytotoxic potential of tagitinin C (SL) and Bz were tested in vitro against T. cruzi epimastigotes and cardiomyocytes. Swiss mice challenged with T. cruzi were also treated for 20 days with tagitinin C (10 mg/kg) alone and combined with Bz (100 mg/kg). Tagitinin C exhibited a higher antiparasitic (IC50: 1.15 µM) and cytotoxic (CC50 at 6.54 µM) potential than Bz (IC50: 35.81 µM and CC50: 713.5 µM, respectively). When combined, these drugs presented an addictive interaction, determining complete suppression of parasitemia and parasitological cure in all infected mice (100%) compared to those receiving Bz alone (70%). Anti-T. cruzi immunoglobulin G, and pro-inflammatory cytokines IFN-γ and TNF-α levels were reduced in animals treated with tagitinin C combined with Bz, while IL-10 production was unaffected. Heart inflammation was undetectable in 90% of the animals receiving this combination, while only 50% of the animals receiving Bz alone showed no evidence of myocarditis. Together, our findings indicated that the combination of tagitinin C and Bz exerts potent antiparasitic, immunomodulatory and cardioprotective effects. Due to the remarkable suppression of parasitemia and high parasitological cure, this combination was superior to Bz monotherapy, indicating a high potential for the treatment of Chagas's disease.

CD43 sialoglycoprotein modulates cardiac inflammation and murine susceptibility to Trypanosoma cruzi infection.

CD43 (leukosialin) is a large sialoglycoprotein abundantly expressed on the surface of most cells from the hematopoietic lineage. CD43 is directly involved in the contact between cells participating in a series of events such as signaling, adherence and host parasite interactions. In this study we examined the role of CD43 in the immune response against Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, a potential life-threatening illness endemic in 21 Latin American countries according to the WHO. The acute stage of infection is marked by intense parasitemia and cardiac tissue parasitism, resulting in the recruitment of inflammatory cells and acute damage to the heart tissue. We show here that CD43-/- mice were more resistant to infection due to increased cytotoxicity of antigen specific CD8+ T cells and reduced inflammatory infiltration in the cardiac tissue, both contributing to lower cardiomyocyte damage. In addition, we demonstrate that the induction of acute myocarditis involves the engagement of CD43 cytoplasmic tripeptide sequence KRR to ezrin-radixin-moiesin cytoskeletal proteins. Together, our results show the participation of CD43 in different events involved in the pathogenesis of T. cruzi infection, contributing to a better overall understanding of the mechanisms underlying the pathogenesis of acute chagasic cardiomyopathy.

Fatal Sarcocystis cruzi-induced eosinophilic myocarditis in a heifer in Uruguay.

Sarcocystis spp. are causative agents of bovine eosinophilic myositis and/or myocarditis, which are chronic subclinical myopathies that are occasionally responsible for condemnation at slaughterhouses. Sarcocystis cruzi is a protozoan parasite of worldwide distribution transmitted by canids, most commonly associated with subclinical infection in cattle. Although S. cruzi infections can rarely lead to fatal systemic disease, fatal cardiac cases with confirmation of the etiologic diagnosis have not been reported, to our knowledge. We describe herein an unusual case of S. cruzi-induced fatal bovine eosinophilic myocarditis. A 22-mo-old, Holstein-Hereford heifer, in a group of 110 cattle on pasture, manifested growth retardation and died in February 2017. Autopsy revealed myriad yellow-green 1-3-mm coalescing foci, surrounded by fibrosis, affecting ~75% of the ventricular myocardium. Pulmonary edema, ascites, and hydrothorax were consistent with chronic congestive heart failure. Histology revealed severe eosinophilic, granulomatous, necrotizing myocarditis, with multinucleate giant cells, fibrosis, and mineralization. Numerous thin-walled protozoan cysts resembling Sarcocystis spp. were present in the necrotic foci and within the sarcoplasm of adjacent cardiomyocytes. PCR and sequencing of the 18S rRNA gene revealed 99.9-100% homology with S. cruzi. Sarcocystosis can be a rare cause of fatal myocarditis in cattle.

Purinergic Antagonist Suramin Aggravates Myocarditis and Increases Mortality by Enhancing Parasitism, Inflammation, and Reactive Tissue Damage in Trypanosoma cruzi-Infected Mice.

Suramin (Sur) acts as an ecto-NTPDase inhibitor in Trypanosoma cruzi and a P2-purinoceptor antagonist in mammalian cells. Although the potent antitrypanosomal effect of Sur has been shown in vitro, limited evidence in vivo suggests that this drug can be dangerous to T. cruzi-infected hosts. Therefore, we investigated the dose-dependent effect of Sur-based chemotherapy in a murine model of Chagas disease. Seventy uninfected and T. cruzi-infected male C57BL/6 mice were randomized into five groups: SAL = uninfected; INF = infected; SR5, SR10, and SR20 = infected treated with 5, 10, or 20 mg/kg Sur. In addition to its effect on blood and heart parasitism, the impact of Sur-based chemotherapy on leucocytes myocardial infiltration, cytokine levels, antioxidant defenses, reactive tissue damage, and mortality was analyzed. Our results indicated that animals treated with 10 and 20 mg/kg Sur were disproportionally susceptible to T. cruzi, exhibiting increased parasitemia and cardiac parasitism (amastigote nests and parasite load (T. cruzi DNA)), intense protein, lipid and DNA oxidation, marked myocarditis, and mortality. Animals treated with Sur also exhibited reduced levels of nonprotein antioxidants. However, the upregulation of catalase, superoxide dismutase, and glutathione-S-transferase was insufficient to counteract reactive tissue damage and pathological myocardial remodeling. It is still poorly understood whether Sur exerts a negative impact on the purinergic signaling of T. cruzi-infected host cells. However, our findings clearly demonstrated that through enhanced parasitism, inflammation, and reactive tissue damage, Sur-based chemotherapy contributes to aggravating myocarditis and increasing mortality rates in T. cruzi-infected mice, contradicting the supposed relevance attributed to this drug for the treatment of Chagas disease.

First case report of Toxoplasma gondii-induced abortions and stillbirths in sheep in Argentina.

The aim of this study is to report an episode of reproductive losses due to toxoplasmosis in a sheep flock in Argentina. A total of 15 abortions and 9 stillbirths were recorded in a flock of 190 Texel ewes. The affected ewes were more likely to be seropositive for Toxoplasma gondii (15/24) than ewes that delivered normal lambs (5/34, OR=9.6, 95%CI=2.7-34.0, p=0.0004). A pair of aborted twins was recovered for diagnostic investigation. One of these fetuses and its dam were seropositive for T. gondii. Histological examination of the two fetuses revealed non-suppurative myocarditis and epicarditis, portal hepatitis and multifocal necrotizing encephalitis with protozoal cysts in the brain. T. gondii was detected intralesionally by immunohistochemistry in one fetus and by PCR in both. Further investigations are necessary to evaluate the economic losses due to T. gondii in the Argentinean ovine industry.

Comparison of myocardial damage among dogs at different stages of clinical leishmaniasis and dogs with idiopathic chronic kidney disease.

Canine leishmaniasis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum. Myocarditis in CanL has been described previously in CanL by histopathological analysis of post-mortem specimens and by evaluation of cardiac troponin I (cTnI) levels. However, the degree of myocardial damage at different stages of CanL and the role that concurrent azotaemia plays in this myocardial injury are unknown. The aim of this study was to prospectively evaluate and compare the presence of myocardial injury in dogs at different stages of clinical CanL and in dogs with severe idiopathic chronic kidney disease (CKD) by measuring cTnI. Forty-eight dogs were included in the study, divided into four groups: (1) group A (10 healthy dogs); (2) group B (17 dogs with CanL without renal azotaemia, classified as mild to severe in the LeishVet scheme); (3) group C (11 dogs with CanL and renal azotaemia, classified as very severe in the LeishVet scheme); and (4) group D (10 dogs with idiopathic CKD). Dogs in group C had significantly higher cTnI than dogs in groups B and D, although cTnI was also elevated in these groups. Dogs in group A had normal cTnI values. Dogs in groups D and C had similar renal IRIS classification scorers. Severe lymphoplasmocytic myocarditis and a positive real time PCR of L. infantum DNA were observed in all dogs in group C. Dogs with very severe CanL exhibit more myocardial injury than dogs with milder CanL or dogs with idiopathic CKD.

S. mansoni-T. cruzi co-infection modulates arginase-1/iNOS expression, liver and heart disease in mice.

Although Schistosoma species and Trypanosoma cruzi share common endemic areas, co-infections by these parasites remains overlooked. By using a murine model of S. mansoni and T. cruzi co-infection, we investigated if and to what extent these infections might interact to change the pathological outcomes typically observed when the host is infected by a single parasite species. Swiss mice were randomized into four groups: uninfected (NI) and those infected by S. mansoni (SM), T. cruzi (TC) or co-infected (SM + TC). After 120 days of S. mansoni infection, T. cruzi was concurrently inoculated and the infection occurred for 30 days. Taken together, we identified that the overlap of Th2 (schistosomiasis) and Th1 (Chagas disease) immunological patterns changes the host resistance against both pathogens. Beyond impairing the control of granulomatous inflammation, T. cruzi parasitemia and parasitism in co-infected animals, the Th2 inflammatory response against S. mansoni elicits the activation of the arginase-1 pathway to the detriment of inducible oxide nitric synthase (iNOS) expression and nitric oxide (NO) production, contributing to the liver damage, with minor effects on heart pathology.

Molecular mechanisms of cardiac electromechanical remodeling during Chagas disease: Role of TNF and TGF-ß.

Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease. Evidence from the literature, mostly provided using experimental models, supports this view and argues in favor of new strategies for treating cardiac arrhythmias in Chagas disease by modulating cytokine production and/or action. But the complex nature of myocardial inflammation underlies the need to better understand the molecular mechanisms of the inflammatory response during Chagas disease. Here, particular attention has been paid to tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF-ß) although other cytokines may be involved in the chagasic cardiomyopathy.