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1.
Parasite Epidemiol Control ; 26: e00364, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39021811

RESUMEN

Trypanosoma cruzi, the causative agent of Chagas disease, is primarily transmitted to humans by hematophagous bugs of the Triatominae subfamily. In the Colombian Caribbean region, particularly on Margarita Island, T. cruzi transmission is highly endemic and associated with vectors such as Triatoma maculata and Rhodnius pallescens. Additionally, T. cruzi-infected Didelphis marsupialis are commonly found in close proximity to human dwellings. Given the complex transmission dynamics involving various domestic and non-domestic hosts, this study aimed to analyze 145 T. cruzi clones from twelve strains isolated from T. maculata, R. pallescens, and D. marsupialis using spliced leader intergenic region (SL-IR) sequences and nine polymorphic microsatellite loci. The results indicate the presence of a single polymorphic T. cruzi population, suggesting sustained local transmission dynamics between triatomines adapted to A. butyracea forests and peridomestic areas inhabited by synanthropic mammal reservoir such as D. marsupialis. Notably, this population appears to lack substructure, highlighting the importance of adopting an alternative eco-health approach to complement traditional chemical vector control methods for more effective and sustainable interruption of transmission.

2.
Insects ; 15(7)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39057204

RESUMEN

Trypanosoma cruzi, the causative agent of Chagas disease (American trypanosomiasis), is a highly complex zoonosis that is present throughout South America, Central America, and Mexico. The transmission of this disease is influenced by various factors, including human activities like deforestation and land use changes, which may have altered the natural transmission cycles and their connection to the environment. In this study conducted in the Argentine Chaco region, we examined the transmission dynamics of T. cruzi by collecting blood samples from wild and domestic animals, as well as triatomine bugs from human dwellings, across five sites of varying anthropic intervention. Samples were analyzed for T. cruzi infection via qPCR, and we additionally examined triatomines for bloodmeal analysis via NGS amplicon sequencing. Our analysis revealed a 15.3% infection rate among 20 wild species (n = 123) and no T. cruzi presence in 9 species of domestic animals (n = 1359) or collected triatomines via qPCR. Additionally, we found chicken (34.28%), human (21.59%), and goat (19.36%) as the predominant bloodmeal sources across all sites. These findings suggest that anthropic intervention and other variables analyzed may have directly impacted the spillover dynamics of T. cruzi's sylvatic cycle and potentially reduced its prevalence in human habitats.

3.
Front Physiol ; 15: 1360255, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38983720

RESUMEN

Introduction: Triatomines are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Currently, there is no vaccine against this disease. Thus, control of the insect vector population is the main strategy available to reduce the number of cases. Triatomines are considered obligate hematophagous, but different alternative feeding behaviors were described, such as haemolymphagy or plant feeding. Methods: To determine the preference for sugar feeding in nymphs and adults of Rhodnius prolixus, the insects were exposed a piece of cotton containing bromophenol blue plus sucrose. In addition, we offered several sugars for different species of triatomines, and tested sugar meals as a route of delivery of insecticides in first-instar nymphs of R. prolixus. The effect of sugar feeding on the physiology of these different species of triatomines was recorded. Results: First instar nymphs ingested sucrose more strongly than other stages, and showed high mortality rates. In different species of triatomines, sucrose induced an ingestion, but engorgement varied according to the species. R. prolixus nymphs showed an indiscriminate intake of various sugars, with very different physiological effects. Furthermore, ingesting different combinations of insecticides + sugar significantly reduced insect survival. Discussion: In summary, we described for the first-time sugar feeding as a widespread behavior in several species of triatomines, and the possibility of the use of toxic sugar baits for the control of these vectors. The knowledge of feeding behavior in these insects can be fundamental for the development of new strategies to control Chagas disease.

4.
Trop Med Int Health ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39031944

RESUMEN

OBJECTIVES: We aimed to evaluate the epidemiology of seven infections (Chagas disease, strongyloidiasis, schistosomiasis, human immunodeficiency virus, hepatitis B and C virus, and active tuberculosis) in migrant populations attended at primary care facilities in Catalonia, Spain. METHODS: This is a cross sectional study conducted from March to December 2018 at eight primary care centres in Catalonia, Spain where health professionals were recommended to systematically screen multiple infections in migrants considering the endemicity of the pathogens in their country of birth. Routine health data were retrospectively extracted from electronic health records of the primary care centres. The proportion of cases among individuals tested for each infection was estimated with its 95% confident interval (CI). Mixed-effects logistics regression models were conducted to assess any possible association between the exposure variables and the primary outcome. RESULTS: Out of the 15,780 migrants that attended primary care centres, 2410 individuals were tested for at least one infection. Of the 508 (21.1%) migrants diagnosed with at least one condition, a higher proportion originated from Sub-Saharan Africa (207, 40.7%), followed by South-East Europe (117, 23.0%) and Latin-America (88, 17.3%; p value <0.001). The proportion of migrants diagnosed with Chagas disease was 5/122 (4.1%, 95%CI 0.5-7.7), for strongyloidiasis 56/409 (13.7%, 95%CI 10.3-17.0) and for schistosomiasis 2/101 (2.0%, 95%CI 0.0-4.7) with very few cases tested. The estimated proportion for human immunodeficiency virus was 67/1176 (5.7%, 95%CI 4.4-7.0); 377/1478 (25.5%, 95%CI 23.3-27.7) for hepatitis B virus, with 108/1478 (7.3%, 95%CI 6.0-8.6) of them presenting an active infection, while 31/1433 (2.2%, 95%CI 1.4-2.9) were diagnosed with hepatitis C virus. One case of active tuberculosis was diagnosed after testing 172 migrant patients (0.6%, 95%CI 0.0-1.7). CONCLUSIONS: We estimated a high proportion of the studied infections in migrants from endemic areas. Country-specific estimations of the burden of infections in migrants are fundamental for the implementation of preventive interventions.

5.
Insect Biochem Mol Biol ; 172: 104154, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972513

RESUMEN

Chagas disease affects around 8 million people globally, with Latin America bearing approximately 10,000 deaths each year. Combatting the disease relies heavily on vector control methods, necessitating the identification of new targets. Within insect genomes, genes harboring small open reading frames (smORFs - < 100 amino acids) present numerous potential candidates. In our investigation, we elucidate the pivotal role of the archetypal smORF-containing gene, mille-pattes/polished-rice/tarsalless (mlpt/pri/tal), in the post-embryonic development of the kissing bug Rhodnius prolixus. Injection of double-stranded RNA targeting mlpt (dsmlpt) during nymphal stages yields a spectrum of phenotypes hindering post-embryonic growth. Notably, fourth or fifth stage nymphs subjected to dsmlpt do not undergo molting. These dsmlpt nymphs display heightened mRNA levels of JHAMT-like and EPOX-like, enzymes putatively involved in the juvenile hormone (JH) pathway, alongside increased expression of the transcription factor Kr-h1, indicating changes in the hormonal control. Histological examination reveals structural alterations in the hindgut and external cuticle of dsmlpt nymphs compared to control (dsGFP) counterparts. Furthermore, significant changes in the vector's digestive physiology were observed, with elevated hemozoin and glucose levels in the posterior midgut of dsmlpt nymphs. Importantly, dsmlpt nymphs exhibit impaired metacyclogenesis of Trypanosoma cruzi, the causative agent of Chagas disease, underscoring the crucial role of proper gut organization in parasite differentiation. Thus, our findings constitute the first evidence of a smORF-containing gene's regulatory influence on vector physiology, parasitic cycle, and disease transmission.

6.
Int J Mol Sci ; 25(13)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39000409

RESUMEN

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF-ß (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast Green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-ß inhibitor, IC50 114.3 µM), losmapimod (p38 inhibitor, IC50 17.6 µM) and SP600125 (c-Jun inhibitor, IC50 3.9 µM). This effect was independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the hearts of the patients.


Asunto(s)
Cardiomiopatía Chagásica , Fibrosis , Ratones Endogámicos C57BL , Piridonas , Animales , Piridonas/farmacología , Piridonas/uso terapéutico , Cardiomiopatía Chagásica/tratamiento farmacológico , Cardiomiopatía Chagásica/parasitología , Cardiomiopatía Chagásica/metabolismo , Cardiomiopatía Chagásica/patología , Ratones , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/parasitología , Miocardio/patología , Miocardio/metabolismo , Colágeno/metabolismo , Trypanosoma cruzi/efectos de los fármacos , Humanos , Enfermedad Crónica , Factor de Crecimiento Transformador beta/metabolismo , Modelos Animales de Enfermedad , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Masculino , Antracenos
7.
Artículo en Inglés | MEDLINE | ID: mdl-38972897

RESUMEN

Metal-Organic Frameworks (MOFs) have been shown to enhance the activity of encapsulated compounds by facilitating their passage across cell membranes, thereby enabling controlled and selective release. This study investigates the efficacy of BNZ@Zn-MOFs against the acute phase of Trypanosoma cruzi infection in a mouse model. The particles were synthesized by electroelution (EL), doped with BZN via mechanochemistry, and characterized using scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and X-ray diffraction (XRD). BNZ@Zn-MOFs released 80% of the encapsulated BZN within 3 h, demonstrating no cytotoxicity in NIH-3T3 and HeLa cells. Furthermore, in a model of acute experimental T. cruzi-infection in BALB/c mice, the delivery system exhibited antiparasitic activity at a significantly lower BZN concentration compared to free BZN treatment. PCR analysis of treated mice revealed no parasite DNA in their tissues, and hematoxylin-eosin staining showed no apparent damage to tissue architecture. Additionally, serum levels of liver function enzymes remained unchanged, indicating no adverse effects on liver function. This delivery system, utilizing suboptimal BZN doses, enables the preservation of drug activity while potentially facilitating a substantial decrease in side effects associated with Chagas disease treatment.

8.
J Med Entomol ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970363

RESUMEN

Population genetic structure of arthropod disease vectors provides important information on vector movement and climate or other environmental variables that influence their distribution. This information is critical for data-driven vector control. In the first comprehensive study of the genetic structure of T. dimidiata s.l. (Latreille, 1811) we focus on an area of active transmission designated as a top priority for control. We examined a high number of specimens across a broad geographic area along the border of Guatemala and El Salvador including multiple spatial scales using a high number of genome-wide markers. Measuring admixture, pairwise genetic differentiation, and relatedness, we estimated the specimens represented three genetic clusters. We found evidence of movement (migration/gene flow) across all spatial scales with more admixture among locations in El Salvador than in Guatemala. Although there was significant isolation by distance, the 2 close villages in Guatemala showed either the most or least genetic variation indicating an additional role of environmental variables. Further, we found that social factors may be influencing the genetic structure. We demonstrated the power of genomic studies with a large number of specimens across a broad geographic area. The results suggest that for effective vector control movement must be considered on multiple spatial scales along with its contributing factors.

9.
Int J Pharm ; 662: 124476, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39029635

RESUMEN

3D printing technology is revolutionizing pharmaceuticals, offering tailored solutions for solid dosage forms. This innovation is particularly significant for conditions like Chagas disease, which require weight-dependent treatments. In this work, a formulation of benznidazole (BNZ), the primary treatment for this infection, was developed to be utilized with the Melting Solidification Printing Process (MESO-PP) 3D printing technique. Considering the limited aqueous solubility of BNZ, an interpolyelectrolyte complex (IPEC), composed of chitosan and pectin, was integrated to improve its dissolution profile. The formulations, also called inks in this context, with and without IPEC were integrally characterized and compared. The printing process was studied, the release of BNZ from 3D-prints (3DP) was exhaustively analyzed and a physiologically based pharmacokinetic model (PKPB) was developed to forecast their pharmacokinetic performance. 3DP were successfully achieved loading 25, 50 and 100 mg of BNZ. The presence of the IPEC in the ink caused a decrease in the crystalline domain of BNZ and facilitated the printing process, reaching a print success rate of 83.3 %. Interestingly, 3DP-IPEC showed accelerated release dissolution profiles, releasing over 85 % of BNZ in 90 min, while 3DP took up to 48 h for doses above 25 mg. The PBPK model demonstrated that 3DP-IPEC tablets would present high bioavailability (0.92), higher than 3DP (0.36) and similar to the commercial product. This breakthrough holds immense potential for improving treatment outcomes for neglected diseases.

10.
J Migr Health ; 10: 100239, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39036036

RESUMEN

This qualitative study of the situation of Latin American migrants with Chagas Disease in Geneva analyses how precarious migration-related socioeconomic conditions determine health priorities and disease perception. The study was conducted between 2016 and 2019 and is based on survey data collected in three Chagas-related community events, as well as on open-ended interviews with Bolivian migrants. This research contributes to more appropriate development of public health policies for migrants, as well as to a more nuanced and culturally sensitive understanding of how precarity affects the delivery of, and access to, healthcare in Western Europe. The significance of this research is to highlight how perceptions of Chagas Disease provide a lens to better understand the links between precarity and health among Bolivian migrants.

11.
Acta Trop ; 257: 107329, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033969

RESUMEN

In Triatoma infestans it was observed pyrethroid resistance attributed in part to an elevated oxidative metabolism mediated by cytochromes P450. The nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome P450 reductase (CPR) plays a crucial role in catalysing the electron transfer from NADPH to all cytochrome P450s. The daily variations in the expression of CPR gene and a P450 gene (CYP4EM7), both associated with insecticide resistance, suggested that their expressions would be under the endogenous clock control. To clarify the involvement of the clock in orchestration of the daily fluctuations in CPR and CYP4M7 genes expression, it was proposed to investigate the effect of silencing the clock gene period (per) by RNA interference (RNAi). The results obtained allowed to establish that the silencing of per gene was influenced by intake schemes used in the interference protocols. The silencing of per gene in T. infestans reduced its expression at all the time points analysed and abolished the characteristic rhythm in the transcriptional expression of per mRNA. The effect of the per gene silencing in the expression profiles at the transcriptional level of CPR and CYP4EM7 genes showed the loss of rhythmicity and demonstrated the biological clock involvement in the regulation of t heir expression.

12.
Cureus ; 16(6): e62398, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39006585

RESUMEN

Introduction Chagas disease is caused by the protozoan Trypanosoma cruzi. It is endemic in 21 countries in Central and South America. Spain is the only nonendemic country with the highest number of Chagas disease cases outside the Americas. The only transmission mechanism in Spain is vertical transmission. Materials and methods We reviewed the records of pregnant women from endemic countries who underwent prenatal care at the Hospital Universitario de Guadalajara, from January 1, 2009, to December 31, 2022, to determine the rate of Chagas disease screening and vertical transmission. Results Out of a total of 1,681 pregnant women from endemic countries, prenatal screening was conducted on 316 (18.7%) of them. According to our study, the prevalence of the disease in the population of pregnant women from endemic countries is 0.95% with a 95% confidence interval (ranging from 0.32% to 2.75%), with three out of the 316 screened women testing positive for the disease. All positive cases were among Bolivian women. Vertical transmission was not observed in any of the cases. However, because of the small sample size, this study cannot conclusively determine the vertical transmission rate in the province of Guadalajara. Conclusions Implementing regulated prenatal screening protocols for Chagas disease at regional or national levels is necessary to increase the rate of prenatal screening. Additionally, increasing awareness of this condition among healthcare professionals and at-risk populations could further improve prenatal screening rates and treatment adherence.

13.
Lancet Reg Health Am ; 36: 100821, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39006126

RESUMEN

Chagas disease, caused by Trypanosoma cruzi, affects millions worldwide. The 2030 WHO roadmap aims to eliminate it as a public health concern, emphasising the need for timely diagnosis to enhance treatment access. Current diagnostic algorithms, which rely on multiple tests, have prolonged turnaround times. This proves particularly problematic in resource-limited settings. Addressing this issue necessitates the validation and adoption of innovative tools. We explore recent developments in Chagas disease diagnosis, reviewing historical context and advancements. Despite progress, challenges persist. This article contributes to the understanding of current and future directions in this neglected healthcare area. Parasitological methods are simple but exhibit low sensitivity and require supplementary tests. Molecular methods, with automation potential, allow quantification and higher throughput. Serological tools show good performance but struggle with parasite antigenic diversity. Prioritising point-of-care tests is crucial for widespread accessibility and could offer a strategy to control disease impact. Ultimately, balancing achievements and ongoing obstacles is essential for comprehensive progress.

14.
Animals (Basel) ; 14(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38997996

RESUMEN

We aimed to characterize the echocardiographic alterations in dogs from an endemic region that were naturally infected with T. cruzi. Dogs (n = 130) seropositive for antibodies against T. cruzi and/or with acute parasitemia were enrolled in the study. Indicators of changes in the structure and systolic and diastolic functions of the left ventricle (LV) and blood flow patterns were evaluated by echocardiography. The frequency and extent of alterations in these indicators were associated with the severity of the disease. Briefly, 15 (11.54%) dogs were diagnosed with dilated cardiomyopathy (DCM), and 115 (88.46%) dogs were diagnosed as being without DCM. Infected dogs with DCM exhibited structural features of LV dysfunction, e.g., a significant (p < 0.05) increase in the LV internal diameter at systole and diastole (LVID-s, LVID-d) and a decline in the LV posterior wall (LVPW-d) thickness at diastole. Despite an increase in stroke volume and cardiac output indicating contraction force, DCM resulted in a decreased ejection fraction, affecting systolic function. Dogs that were diagnosed as DCM-negative but were positive for T. cruzi by PCR exhibited a high frequency of an increase in the thickness of the interventricular septum in systole (IVS-s) and the LV posterior wall in diastole (LVPW-d), a decline in the LV inner diameter (LVID-d, LVID-s), and fractional shortening (FS). The thinning of the LVPW at systole was the most defining feature observed in chronically infected dogs. In summary, this is the first study reporting the echocardiographic changes occurring in dogs naturally infected with T. cruzi and developing DCM. Our data suggest that changes in LVID are a major indicator of risk of cardiac involvement, and the observation of changes in the IVS, LVPW, and FS have predictive value in determining the risk of DCM development in infected dogs.

15.
J Med Entomol ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995691

RESUMEN

Triatomine bugs are vectors for the Trypanosoma cruzi Chagas parasites, the etiological agent for Chagas disease. This study evaluated 6 epidemiologically significant behaviors (development time, number of blood meals required for molting to the next instar, mortality rate, aggressiveness, feeding duration, and defecation delay) across 4 populations of Triatoma mexicana Herrich-Schaeffer (Heteroptera: Reduviidae), a major T. cruzi vector in Central Mexico. We collected triatomines from areas characterized by high (HP), medium (MP), medium-high (MHP), and low (LP) prevalence of human T. cruzi infection. The MHP population had the shortest development time, <290 days. Both the HP and MP populations required the most blood meals to molt to the next instar, with a median of 13. Mortality rates varied across all populations, ranging from 44% to 52%. All of the tested populations showed aggressive behavior during feeding. All populations shared similar feeding durations, with most exceeding 13 min and increasing with each instar. Quick defecation, during feeding, immediately after or less than 1 min after feeding, was observed in most nymphs (78%-90%) from the MP and MHP populations and adults (74%-92%) from HP, MP, and MHP populations. Though most parameters suggest a low potential for T. mexicana to transmit T. cruzi, unique feeding and defecation behaviors in 3 populations (excluding the LP group) could elevate their epidemiological importance. These population-specific differences may contribute to the varying prevalence rates of T. cruzi infection in areas where T. mexicana is found.

16.
Parasit Vectors ; 17(1): 305, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39010122

RESUMEN

BACKGROUND: Chagas disease (CD), a neglected parasitic disease caused by Trypanosoma cruzi, poses a significant health threat in Latin America and has emerged globally because of human migration. Trypanosoma cruzi infects humans and over 100 other mammalian species, including dogs, which are important sentinels for assessing the risk of human infection. Nonetheless, the serodiagnosis of T. cruzi in dogs is still impaired by the absence of commercial tests. In this study, we investigated the diagnostic accuracy of four chimeric recombinant T. cruzi IBMP antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) for detecting anti-T. cruzi antibodies in dogs, using latent class analysis (LCA). METHODS: We examined 663 canine serum samples, employing indirect ELISA with the chimeric antigens. LCA was utilized to establish a latent variable as a gold standard for T. cruzi infection, revealing distinct response patterns for each antigen. RESULTS: The IBMP (Portuguese acronym for the Molecular Biology Institute of Paraná) antigens achieved area under the ROC curve (AUC) values ranging from 90.9% to 97.3%. The highest sensitivity was attributed to IBMP-8.2 (89.8%), while IBMP-8.1, IBMP-8.3, and IBMP-8.4 achieved 73.5%, 79.6%, and 85.7%, respectively. The highest specificity was observed for IBMP-8.4 (98.6%), followed by IBMP-8.2, IBMP-8.3, and IBMP-8.1 with specificities of 98.3%, 94.4%, and 92.7%, respectively. Predictive values varied according to prevalence, indicating higher effectiveness in endemic settings. CONCLUSIONS: Our findings underscore the remarkable diagnostic performance of IBMP-8.2 and IBMP-8.4 for the serodiagnosis of Trypanosoma cruzi in dogs, representing a promising tool for the diagnosis of CD in dogs. These chimeric recombinant antigens may not only enhance CD surveillance strategies but also hold broader implications for public health, contributing to the global fight against this neglected tropical disease.


Asunto(s)
Anticuerpos Antiprotozoarios , Antígenos de Protozoos , Enfermedad de Chagas , Enfermedades de los Perros , Ensayo de Inmunoadsorción Enzimática , Sensibilidad y Especificidad , Pruebas Serológicas , Trypanosoma cruzi , Animales , Perros , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/veterinaria , Enfermedad de Chagas/parasitología , Trypanosoma cruzi/inmunología , Trypanosoma cruzi/genética , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/parasitología , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/genética , Pruebas Serológicas/métodos , Pruebas Serológicas/veterinaria , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Anticuerpos Antiprotozoarios/sangre , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética
18.
Artículo en Inglés | MEDLINE | ID: mdl-39052317

RESUMEN

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. It bears a significant global health burden with limited treatment options, thus calling for the development of new and effective drugs. Certain trypanosomal metabolic enzymes have been suggested to be druggable and valid for subsequent inhibition. In this study, the crystal structure of glycerol kinase from T. cruzi, a key enzyme in glycerol metabolism in this parasite, is presented. Structural analysis allowed a detailed description of the glycerol binding pocket, while comparative assessment pinpointed a potential regulatory site which may serve as a target for selective inhibition. These findings advance the understanding of glycerol metabolism in eukaryotes and provide a solid basis for the future treatment of Chagas disease.

19.
Travel Med Infect Dis ; : 102745, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39048021

RESUMEN

BACKGROUND: Chagas Disease (CD) can cause Chagas cardiomyopathy. The new coronavirus disease (COVID-19) also affects the cardiovascular system and may worsen Chagas cardiomyopathy. However, the cardiac evolution of patients with CD infected by COVID-19 is not known. Thus, the objective of this study is to assess, within one year, whether there was cardiac progression after COVID-19 in CD. METHODS: Longitudinal study with CD patients. The outcome was cardiac progression, defined as the appearance of new major changes in the current ECG compared to the previous ECG considered from the comparison of electrocardiograms (ECGs) performed with an interval of one year. Positive Anti-SARS-CoV2 Serology was the independent variable of interest. For each analysis, a final multiple model was constructed, adjusted for sociodemographic, clinical, and pandemic-related characteristics. RESULTS: Of the 404 individuals included, 22.8 % had positive serology for COVID-19 and 10.9 % had cardiac progression. In the final model, positive serology for COVID-19 was the only factor associated with cardiac progression in the group as a whole (OR=2.65; 95 % CI= 1.27-5.53) and for new-onset cardiomyopathy in the group with normal previous ECG (OR=3.50; 95 % CI=1.21-10.13). CONCLUSION: Our study shows an association between COVID-19 and progression of Chagas cardiomyopathy, evaluated by repeated ECGs, suggesting that COVID-19 accelerated the natural history of CD.

20.
Transpl Infect Dis ; : e14336, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980983

RESUMEN

BACKGROUND: Chagas disease (ChD) is endemic in many parts of the world and can be transmitted through organ transplantation or reactivated by immunosuppression. Organs from infected donors are occasionally used for transplantation, and the best way of managing the recipients remains a subject of debate. METHODS: We present a single-center cohort study describing a 10-year experience of kidney transplantation in patients at risk of donor-derived ChD and or reactivation. Patients received prophylactic treatment with Benznidazole and were monitored for transmission or reactivation. Monitoring included assessing direct parasitemia, serology, and polymerase chain reaction (PCR). RESULTS: Fifty-seven kidney transplant recipients (KTRs) were enrolled in the study. Forty-four patients (77.2%) were at risk of primary ChD infection, nine patients (15.8%) were at risk of disease reactivation, and four patients (7.0%) were at risk of both. All patients received Benznidazole prophylaxis, starting on the first day after transplantation. Parasitemia was assessed in 51 patients (89.5%), serology also in 51 patients (89.5%), and PCR in 40 patients (70.2%). None of the patients exhibited clinically or laboratory-detectable signs of disease. A single patient experienced a significant side effect, a cutaneous rash with intense pruritus. At 1-year post-transplantation, the patient and graft survival rates were 96.5% and 93%, respectively. CONCLUSION: In this study, no donor-derived or reactivation of Trypanosoma cruzi infection occurred in KTRs receiving Benznidazole prophylaxis.

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