Antiparasitic Chemotherapy Research Articles

CARDIAC HYDATID CYST: A RARE CASE REPORT

Introduction: Hydatidosis, an anthropozoonosis prevalent in many sheep-farming countries, continues to pose a significant health concern. Cardiac localization represents a rare and distinctive manifestation, accounting for less than 2% of total cases. This report details a case where surgical intervention, coupled with antiparasitic chemotherapy, was used for effective treatment. Patients and Methods: A 36-years-old female, residing in a rural area renowned for agricultural and livestock activities, was under cardiology supervision due to rheumatic polyvalvulopathy. Having undergone hepatic hydatid cyst surgery one year earlier, The reason for her consultation in cardiology was exertional dyspnea, left thoracic pain, palpitations, afebrility, and asthenia. The disease diagnosis relied on imaging findings.Treatment involved the urgent surgical excision of the cyst, followed by the oral administration of albendazole at 400mg x 2 per day, initiated 48 hours postoperatively. With no contraindications, the patient underwent continuous biological monitoring during hospitalization, reporting no adverse effects. The antiparasitic regimen persisted for 4 months. Conclusion: Albendazole, whether used as a standalone therapy or in combination, remains a highly effective treatment. It can either substitute for or complement surgical approaches, offering the flexibility of extended treatment durations. Vigilant monitoring of hepatic function is imperative in these instances to identify potential adverse effects. Two-dimensional transthoracic echocardiography plays a pivotal role in tracking patient progress and evaluating treatment efficacy.Prevention stands out as the most effective strategy against hydatid cysts, emphasizing collective awareness and proactive patient management to avert cyst dissemination.

Dietary glycemic and energy load differentially modulates Schistosoma mansoni-induced granulomatous inflammation and response to antiparasitic chemotherapy

The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of sucrose-rich diet and intermittent fasting on Schistosoma mansoni infection and praziquantel (PZQ)-based chemotherapy response in mice. BALB/c mice were infected with S. mansoni and followed for 15 weeks. The animals were randomized into nine groups receiving high glycemic load (high-sucrose diet - HSD), low caloric load (standard chow alternate-day fasting - ADF), and standard chow ad libitum (AL). Eight weeks after S. mansoni infection, these groups remained untreated or were treated with PZQ (300 mg/kg/day) for 3 days. Our results indicated that parasite load (S. mansoni eggs and parasite DNA levels), granulomatous inflammation (granulomas number and size), and liver microstructural damage (reduction in hepatocytes number, increase in nucleus-cytoplasm ratio, connective stroma expansion and fibrosis) were increased in ADF-treated animals. These animals also showed decreased eggs retention, granulomatous inflammation and collagen accumulation in the small intestine. Conversely, HSD diet and PZQ treatment attenuated all these parameters and stimulated hepatic regenerative response. PZQ also stimulated fibrosis resolution in HSD-treated mice, effect that was limited ADF-exposed mice. Our findings indicate that dietary glycemic and energy load can modulate schistosomiasis progression and the severity of hepatic and intestinal granulomatous inflammation in untreated and PZQ-treated mice. Thus, lower intestinal eggs retention may potentially be linked to worsening liver disease in ADF, while attenuation of hepatic and intestinal granulomatous inflammation is consistent with reduced parasite load in HSD- and PZQ-treated animals.

VISCERAL MIGRATING LARVA. CLINICAL CASES. UKRAINIAN BURDEN

Introduction. The work highlights the problematic issues of diagnosis and treatment of toxocariasis infection in people in Ukraine, which become even more acute and urgent due to the migration of the population and animals, and the destruction of the country's infrastructure as a result of the war unleashed by Russia.
 The aim of the study. Improvement of aspects of clinical, laboratory and instrumental diagnostics, as well as treatment of VML in humans
 Materials and methods. A literature research of the state of the problem of primary and differential diagnosis of the migrating larva in Ukraine and the world has been conducted. 2 clinical cases of diagnosis and treatment of migrating larva in are described.
 Results. The article describes two clinical cases of visceral migrating larva. The differences of these cases, in addition to the migrating formations in the lungs, were the asymptomatic course, the absence of eosinophilia, and the simultaneous determination of blood class G antibodies by ELISA to Toxocar and human roundworm (A. lumbricoide), which persisted even after treatment. Patients at the stage of diagnosis were examined in an oncology hospital, were consulted by thoracic surgeons and oncologists to exclude lung cancer. Both women were immunocompetent, one patient had a history of cervical cancer. From the epidemiological anamnesis, both women kept cats, and one of them, during chemotherapy for the treatment of a tumor, had a propensity for carnivorous raw-eating. Before prescribing systemic antiparasitic chemotherapy, the patients were examined by an ophthalmologist to exclude parasitic chorioretinitis. The patients were prescribed a 20-day course of albendazal 800 mg/day in two doses. Support therapy consisted of a 5-day course of prednisolone at a dose of 30 mg/day orally in two doses, which started one day before the appointment of albendazole. A control CT scan of the lungs after therapy did not reveal any formations, fibrosis, or calcifications.
 Discussion. This case proves that tocoscarosis in humans is a multidisciplinary medical and social problem. Conclusions were made on the need to restore the national registration of the disease, adopt national consensuses on treatment and diagnosis, and implement into clinical practice modern methods of verification of specific antibodies to nematodes based on immunoblotting.
 Conclusions. The registration of cases of VML and T. in the system of control and prevention of infectious diseases in Ukraine should be resumed. It is expedient to introduce specific studies on nematodes in clinical laboratory practice.

Isolated Renal Hydatid Cysts in Children: A Systematic Review of Case Reports

Background: Echinococcosis is a zoonotic tapeworm infection caused by Echinococcus granulosus, occasionally affecting humans. The larval infection most commonly affects the liver and lungs and very rarely the kidneys. Objective: The present systematic review compiles data regarding clinical presentations, diagnostic modalities, management strategies and recurrences in children with isolated renal hydatid cysts. Methods: A comprehensive search was done in major databases PubMed and Google Scholar using defined search terms encompassing case reports or case series on isolated renal hydatid cysts in children. The identified reports underwent screening by three different authors for inclusion and exclusion criteria. Results: The median (range) age at presentation of isolated renal hydatid disease was 10 (6) years with female preponderance (52.7%). Most common presenting symptom and sign were abdominal pain (64.8%) and palpable abdominal mass (56.7%), respectively. Ultrasonography (94.5%) was most common diagnostic method. Patients were primarily managed with surgical interventions (95.5%) and only 2/37 were managed solely by medical management for a median duration of 3.5 weeks. Laparoscopic cystectomy was the most commonly used surgical procedure (45.9%). Recurrence was observed to be rare, seen in only 3 cases. Conclusion: Hydatid cysts need to be considered in the differential diagnosis of renal cysts. Radiological evaluation with pathological confirmation enables diagnosis. Surgery combined with adjuvant anti-parasitic chemotherapy is used to treat the condition.

Palliative Treatment for the Management of Advanced Pelvic Hydatid Bone Disease.

Hydatid bone disease is a zoonotic parasitic infection that is caused primarily by the tapeworm Echinococcus granulosus, and it continues to be a major public health concern in pastoral regions. The reconstruction of limb function after limb salvage surgery remains a challenge for clinicians. The purpose of this study was to determine the clinical efficacy of palliative treatment of the management of advanced pelvic hydatid bone disease. From March 2005 to December 2018, medical records and images of patients with advanced pelvic hydatid bone disease treated with surgery combined with antiparasitic chemotherapy were evaluated retrospectively. The Enneking classification was applied to determine the location of the lesion, and the Musculoskeletal Tumor Society score system was used for outcome evaluation. Fifteen patients who met the criteria were included in this study, with a mean follow-up of 4.40 ± 1.76 years. All patients received treatment with surgery combined with antiparasitic chemotherapy. The mean number of surgical interventions per patient for pelvic cystic echinococcosis was 5.3 (range, 2-9 interventions per patient). Recurrence of pelvic hydatid bone disease occurred in 5 patients and was managed successfully through repeated debridement procedures. Palliative treatment with limb salvage surgery was an effective and practical approach to the management of advanced pelvic hydatid bone disease. Standard antiparasitic chemotherapy, which included albendazole at a dose of 10 mg/kg/day administered in two daily doses for 3 to 6 months, was also considered an essential part of the overall treatment strategy.

Extensive hydatid cysts involving the lumbosacral vertebrae and pelvis.

•A patient with typical hydatid cysts involving both lumbosacral vertebrae and pelvis is presented in this paper.•Conservative treatment with antiparasitic medication may improve symptoms.•Surgical treatment followed by antiparasitic chemotherapy may reduce the relapse rate of bone hydatid cysts.

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy.

The potentially lethal zoonosis alveolar echinococcosis (AE) is caused by the metacestode larval stage of the tapeworm Echinococcus multilocularis. Current AE treatment options are limited and rely on surgery as well as on chemotherapy involving benzimidazoles (BZ). BZ treatment, however, is mostly parasitostatic only, must be given for prolonged time periods, and is associated with adverse side effects. Novel treatment options are thus urgently needed. By applying a broad range of kinase inhibitors to E. multilocularis stem cell cultures we identified the proto-oncogene PIM kinase as a promising target for anti-AE chemotherapy. The gene encoding the respective E. multilocularis ortholog, EmPim, was characterized and in situ hybridization assays indicated its expression in parasite stem cells. By yeast two-hybrid assays we demonstrate interaction of EmPim with E. multilocularis CDC25, indicating an involvement of EmPim in parasite cell cycle regulation. Small molecule compounds SGI-1776 and CX-6258, originally found to effectively inhibit human PIM kinases, exhibited detrimental effects on in vitro cultured parasite metacestode vesicles and prevented the formation of mature vesicles from parasite stem cell cultures. To improve compound specificity for EmPim, we applied a high throughput in silico modelling approach, leading to the identification of compound Z196138710. When applied to in vitro cultured metacestode vesicles and parasite cell cultures, Z196138710 proved equally detrimental as SGI-1776 and CX-6258 but displayed significantly reduced toxicity towards human HEK293T and HepG2 cells. Repurposing of kinase inhibitors initially designed to affect mammalian kinases for helminth disease treatment is often hampered by adverse side effects of respective compounds on human cells. Here we demonstrate the utility of high throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. We propose EmPim as a promising target for respective approaches towards AE treatment.

A novel multi-epitope recombinant protein elicits an antigen-specific CD8+ T cells response in Trypanosoma cruzi-infected mice

About 6.5 million people worldwide are afflicted by Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi. The development of a therapeutic vaccine to prevent the progression of Chagasic cardiomyopathy has been proposed as an alternative for antiparasitic chemotherapy. Bioinformatics tools can predict MHC class I CD8 + epitopes for inclusion in a single recombinant protein with the goal to develop a multivalent vaccine. We expressed a novel recombinant protein Tc24-C4.10E harboring ten nonameric CD8 + epitopes and using Tc24-C4 protein as scaffold to evaluate the therapeutic effect in acute T. cruzi infection. T. cruzi-infected mice were immunized with Tc24-C4.10E or Tc24-C4 in a 50-day model of acute infection. Tc24-C4.10E-treated mice showed a decreased parasitemia compared to the Tc24-C4 (non-adjuvant) immunized mice or control group. Moreover, Tc24-C4.10E induced a higher stimulation index of CD8 + T cells producing IFNγ and IL-4 cytokines. These results suggest that the addition of the MHC Class I epitopes to Tc24-C4 can synergize the antigen-specific cellular immune responses, providing proof-of-concept that this approach could lead to the development of a promising vaccine candidate for Chagas disease.

Protective immunity triggered by ectonucleoside triphosphate diphosphohydrolase-based biopharmaceuticals attenuates cardiac parasitism and prevents mortality in Trypanosoma cruzi infection

Chagas disease is a potentially fatal infection in 21 endemic Latin America countries for which the effectiveness of reference antiparasitic chemotherapy is limited. Thus, we developed three biopharmaceuticals and evaluated the effectiveness of different immunization strategies (recombinant protein NTPDase-1 [rNTPDase-1], DNA plasmid encoding Trypanosoma cruzi NTPDase-1 [TcNTPDase-1] and DNA-NTPDase-1 prime/rNTPDase-1 boost [Prime-boost]) based on the surface ecto-nucleoside triphosphate diphosphohydrolase (ecto-NTPDase) enzyme of T. cruzi in animals challenged with a virulent strain (Y) of this parasite. BALB/c mice were immunized three times at 30 days intervals, challenged with T. cruzi 15 days after the last immunization, and euthanized 30 days after T. cruzi challenge. Our results showed limited polarization of specific anti-ecto-NTPDase immunoglobulins in mice receiving both immunization protocols. Conversely, the Prime-boost strategy stimulated the Th1 protective phenotype, upregulating TNF-α and downregulating IL-10 production while increasing the activation/distribution of CD3+/CD8+, CD4+/CD44hi and CD8+/CD44hi/CD62L cells in immunized and infected mice. Furthermore, IL-6 and IL10 levels were reduced, while the distribution of CD4+/CD44hi and CD3+/CD8+ cells was increased from rNTPDase-1 and DNA-NTPDase1-based immunization strategies. Animals receiving DNA-NTPDase1 and Prime-boost protocols before T. cruzi challenged exhibited an enhanced immunological response associated with IL-17 upregulation and remarkable downregulation of heart parasitism (T. cruzi DNA) and mortality. These findings indicated that NTPDase-1 with Prime-boost strategy induced a protective and sustained Th17 response, enhancing host resistance against T. cruzi. Thus, ecto-NTPDase is a potentially relevant and applicable in the development of biopharmaceuticals with greater immunoprophylactic potential for Chagas disease.

Electrochemical Characterization of Auranofin in Aqueous Media

Detection of antibiotic compounds in various media is necessary in solving the public health crisis of antibiotic resistance[1]. Auranofin (AF) is a repurposed antibiotic first used as an antirheumatic in the 1950s. It is useful against various bacteria, fungi, virus infections and cancers either by itself or synergistically with other antibiotics[2–5]. AF is composed of aurothioglucose and phosphine moieties, and therefore, has lipophilic and hydrophilic properties, making its characterization in aqueous media particularly difficult. In the presented study, electrochemistry was employed to characterize and detect AF in aqueous solutions using modified glassy carbon electrodes (GCEs), coated with Carbon Black (CB). CB coating was optimized, oxidation and reduction potentials were identified, and pH dependence, as well as Limits of Detection (LOD) and Quantification (LOQ) were determined. Interferences with ions and other antibiotics was studies and are important factors for the detection of AF in the environment. This study reports on the sensitivity, stability, and selectivity of the CB-GCE sensors, proving useful for future field detection and/or bioelectrochemical investigations.CITATIONS[1] M.R. Islam, S. Kuss, F. Schweizer, Characterization of Antibiotic Compounds By Electrochemistry, ECS Meeting s. MA2020-01 (2020). https://doi.org/10.1149/ma2020-01442531mtgabs.[2] R. Díez-Martínez, E. García-Fernández, M. Manzano, Á. Martínez, M. Domenech, M. Vallet-Regí, P. García, Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections, Scientific Reports. 6 (2016). https://doi.org/10.1038/srep19525.[3] K.J. Habermann, L. Grünewald, S. van Wijk, S. Fulda, Targeting redox homeostasis in rhabdomyosarcoma cells: GSH-depleting agents enhance auranofin-induced cell death, Cell Death & Disease. 8 (2017). https://doi.org/10.1038/cddis.2017.412.[4] E. v. Capparelli, R. Bricker-Ford, M.J. Rogers, J.H. McKerrow, S.L. Reed, Phase I clinical trial results of auranofin, a novel antiparasitic agent, Antimicrobial Agents and Chemotherapy. 61 (2017). https://doi.org/10.1128/AAC.01947-16.[5] T. Onodera, I. Momose, M. Kawada, Potential anticancer activity of auranofin, Chemical and Pharmaceutical Bulletin. 67 (2019). https://doi.org/10.1248/cpb.c18-00767.

Gas‐phase experimental and computational studies of human hypoxanthine‐guanine phosphoribosyltransferase substrates: Intrinsic properties and biological implications

AbstractThe gas‐phase acidity and proton affinity of nucleobases that are substrates for the enzyme human hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) have been examined using both theoretical and experimental methods. These thermochemical values have not heretofore been measured and provide experimental data to benchmark the computational results. HGPRT is important for human health and is also a key target for antiparasitic chemotherapy. We use our gas‐phase results to lend insight into the HGPRT mechanism and also propose kinetic isotope studies that could potentially differentiate between possible mechanisms.

Blood Characteristics in Dogs During Treatment of Babesiosis Using Transfusion of Cryopreserved Erythrocytes

Babesiosis is one of the most common protozoan diseases in dogs, which in the absence of the necessary veterinary care often leads to the animal death. The changes of hematological parameters in dogs during complex treatment of babesiosis and transfusion of cryopreserved erythrocytes were evaluated in the research. Erythrocytes were frozen using 20% DMSO by immersion into liquid nitrogen. Transfusion of cryopreserved erythrocytes together with antiparasitic chemotherapy has been shown to promote rapid recovery of hematological parameters of animal blood (hemoglobin, hematocrit and erythrocyte counts), as well as improves their well-being, promotes faster recovery. Cryopreserved with DMSO erythrocytes can be recommended for long-term storage of blood at cryobanks.

Multiple debridement of cavity lesions combined with antiparasitic chemotherapy in the treatment of mid or advanced spinal echinococcosis: a retrospective study of 33 patients

ObjectiveThe purpose of this study was to evaluate and document the complications and outcomes (bone and functional) of multiple debridement of cavity lesions combined with antiparasitic chemotherapy in the treatment of mid or advanced spinal echinococcosis. MethodsFrom January 2007 to February 2019, the medical records and imaging of all patients with mid or advanced spinal echinococcosis, who were treated by multiple debridement of cavity lesions, were evaluated retrospectively. The Braithwaite and Less classification system of spinal echinococcosis and the Frankel classification system were used to evaluate the results, both preoperatively and postoperatively. ResultsBetween January 2007 and February 2019, 33 patients met the criteria and were included in this study, with a mean postoperative follow-up time of 4.9 (1–10) years. They included 18 males (54.5%) and 15 females (45.4%), with a mean age of 41.5 years (range 23–70 years). A satisfactory recovery of lower-limb motor function was found in 32 patients, while 24 patients (72.7%) presented with recurrence of spinal echinococcosis. ConclusionsMultiple debridement and spinal cord decompression, combined with antiparasitic chemotherapy after surgery, are effective methods for delaying or preventing disease progression or recurrence. A recurrence of infection is common in most cases. CT and MRI are the preferred methods for diagnosing this disease.

Clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis induced by Leishmania infantum infection.

BackgroundVisceral leishmaniasis (VL) could progress to secondary hemophagocytic lymphohistiocytosis (HLH), which is a rare but life-threatening condition with poor prognosis. So far, the clinical and laboratory characteristics of VL associated HLH have not been well elucidated.Method and findingsIn this study, we retrospectively analyzed the clinical and laboratory profiles between 17 patients with VL associated HLH and 27 patients with VL alone admitted at the Beijing Friendship Hospital, Capital Medical University from May 2016 to March 2021. In addition to the identification of Leishmania infection, hemophagocytosis was identified in bone marrow in the most cases of VL associated HLH (15/17). The patients with VL associated HLH had higher chances of bleeding, hepatomegaly, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, hypofibrinogenemia, elevated secretion of soluble IL-2 receptor or lower NK cell activity compared to patients with VL only. Furthermore, patients with VL associated HLH had higher inflammation status associated with higher levels of Th1 (TNF-α, IFN-γ, IL-1beta, IL-6, IL-8, IL-12p70), Th2 (IL-4) and Th17 cytokines (IL-17, IL-23) in the peripheral blood, and higher parasite load (qPCR and parasite culture). All 27 VL cases were totally recovered after being treated with Sodium Stibogluconate, five of the 17 patients with VL associated HLH died even after timely treatment with anti-parasite and immunosuppressive chemotherapy.ConclusionWithout appropriate treatment, visceral leishmaniosis could develop to secondary HLH. The parasite culturing and qPCR detection of bone marrow samples facilitates the diagnosis of VL associated HLH in addition to other findings of HLH. Prompt treatment with anti-Leishmania and immunosuppressive chemotherapy is critical to reduce the mortality of VL associated HLH.

Management of a hepatic hydatid cyst ruptured into the retroperitoneum and the abdominal wall muscles: A case report

Introduction. Hydatid disease is a zoonosis caused by the tapeworm Echinococcus granulosus. The liver is the most commonly involved organ, followed by lungs. The most common complications of hepatic hydatid cyst are rupture into the biliary tract and secondary bacterial infection. However, rupture into the retroperitoneum and the abdominal wall muscles is exceptional. Case presentation. We describe an unusual case of a 27-year-old female who was referred to our department for right flank pain for four months. Abdominal ultrasound and CT scan revealed a huge hydatid cyst in liver segment VI fistulizing to the retroperitoneum and the lateral and posterior abdominal wall muscles, causing anterior displacement of the right kidney, with two other cysts in segment II and VIII. Surgery was performed associated with perioperative antiparasitic chemotherapy. The cysts were unroofed and a resection of the protruding domes was performed. The hydatid material in the retroperitoneum and the muscles were completely evacuated by aspiration. Follow-up showed no recurrence. Discussion. Hepatic hydatid cyst rupture usually occurs into biliary tract, pleural cavity, bronchial tree and intraperitoneal cavity. Rupture into the retroperitoneum and the lateral and posterior abdominal wall muscles is exceptional. To our knowledge, this complication has never been documented before. The hydatid disease may involve insidiously for a long time to lead to such a complication. Surgery was inevitable in our case. It allowed to treat both the hydatid cyst and its complication. Conclusions. A rupture into the retroperitoneum and the abdominal wall muscles as a complication of a liver hydatid cyst is exceptional. In this presentation, we noticed that hydatid cysts can reach an extremely large size while remaining for a long time asymptomatic. We aim to highlight the significance of preventive measures and public health education to fight against the hydatid disease in endemic areas.

Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale.

Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. The mechanism of pathogenesis is poorly understood and the lack of a robust, predictive animal model has held back research. We screened a series of mouse models using gastrointestinal tracer assays and in vivo infection imaging systems to discover a subset exhibiting chronic digestive transit dysfunction and significant retention of faeces in both sated and fasted conditions. The colon was a specific site of both tissue parasite persistence, delayed transit and dramatic loss of myenteric neurons as revealed by whole-mount immunofluorescence analysis. DCD mice therefore recapitulated key clinical manifestations of human disease. We also exploited dual reporter transgenic parasites to home in on locations of rare chronic infection foci in the colon by ex vivo bioluminescence imaging and then used fluorescence imaging in tissue microdomains to reveal co-localisation of infection and enteric nervous system lesions. This indicates that long-term T. cruzi-host interactions in the colon drive DCD pathogenesis, suggesting that the efficacy of anti-parasitic chemotherapy against chronic disease progression warrants further pre-clinical investigation.

Desperately Seeking Therapies for Cerebral Malaria.

Malaria is a deadly infectious disease caused by parasites of the Plasmodium spp. that takes an estimated 435,000 lives each year, primarily among young African children. For most children, malaria is a febrile illness that resolves with time, but in ∼1% of cases, for reasons we do not understand, malaria becomes severe and life threatening. Cerebral malaria (CM) is the most common form of severe malaria, accounting for the vast majority of childhood deaths from malaria despite highly effective antiparasite chemotherapy. Thus, CM is one of the most prevalent lethal brain diseases, and one for which we have no effective therapy. CM is, in part, an immune-mediated disease, and to fully understand CM, it is essential to appreciate the complex relationship between the malarial parasite and the human immune system. In this study, we provide a primer on malaria for immunologists and, in this context, review progress identifying targets for therapeutic intervention.

Could pre-infection exercise training improve the efficacy of specific antiparasitic chemotherapy for Chagas disease?

Considering a potential exercise-drug interaction, we investigated whether exercise training could improve the efficacy of specific antiparasitic chemotherapy in a rodent model of Chagas disease. Wistar rats were randomized into five groups: sedentary and uninfected (CT); sedentary and infected (SI); sedentary, infected and treated (SIT); trained and infected (TI); trained, infected and treated (TIT). After 9-weeks running training, the animals were infected with T. cruzi and followed up for 4 weeks, receiving 100 mg kg-1 day-1 benznidazole. No evidence of myocarditis was observed in CT animals. TI animals exhibited reduced parasitemia, myocarditis, and reactive tissue damage compared to SI animals, in addition to increased IFN-γ, IL-4, IL-10, heart non-protein antioxidant (NPA) levels and glutathione-s transferase activity (P < 0.05). The CT, SIT and TIT groups presented similar reductions in parasitemia, cytokines (IFN-γ, TNF-α, IL-4, IL-10, IL-17 and MCP-1), inflammatory infiltrate, oxidative heart damage and antioxidant enzymes activity compared to SI and TI animals, as well as reduced heart microstructural remodeling (P < 0.05). By modulating heart inflammation and redox metabolism, exercise training exerts a protective effect against T. cruzi infection in rats. However, the antiparasitic and cardioprotective effects of benznidazole chemotherapy are more pronounced, determining similar endpoints in sedentary and trained T. cruzi-infected rats.

Anti-Trypanosoma cruzi effect of the photodynamic antiparasitic chemotherapy using phenothiazine derivatives as photosensitizers.

Chagas disease is endemic in Latin America and increasingly found in non-endemic countries. Its treatment is limited due to the variable efficacy and several side effects of benznidazole. Photodynamic antimicrobial chemotherapy (PACT) may be an attractive approach for treating Chagas disease. Here, the trypanocidal activity of PACT was investigated in vitro using phenothiazine derivatives. The cytotoxicity of both, methylene blue (MB) and toluidine blue (TBO), was determined on macrophages cultures using AlamarBlue method. The trypanocidal activity of the two photosensitizers was initially evaluated by determining their IC50 values against trypomastigote forms. After this, the trypanocidal effect was evaluated in cultures of infected macrophages using an automatized image analysis protocol. All experiments were performed in the dark and in the clear phase (after a photodynamic exposure). The compounds showed no cytotoxicity in both phases at the tested concentrations. The IC50 values for the sole use of MB and TBO were 2.6 and 1.2μM, respectively. The photoactivation of the compounds using a fixed energy density (J/cm2) caused a reduction of the IC50 values to 1.0 and 0.9μM, respectively. It was found that, on infected macrophage, the use of TBO significantly reduced the number of infected cells and parasitic load, and this effect was increased in the presence of light. The results of the present study are indicative that PACT may be considered as both selective and effective therapeutic intervention for treating Chagas disease.

Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland.

BACKGROUNDChronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease.OBJECTIVESWe tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy.METHODSWe retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases.FINDINGSOf the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases.CONCLUSIONSOur results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.