Search Results (519)

Chagas disease, caused by Trypanosoma cruzi, remains a significant public health challenge, particularly in Latin America, where it is one of the most neglected diseases and is primarily transmitted by triatomine insects. The disease exhibits complexity due to its diverse transmission routes, including vectorial and non-vectorial mechanisms such as blood transfusions and congenital transmission. Effective monitoring and control strategies are critical to mitigating its impact. This review focuses on current monitoring and control efforts, emphasizing the importance of enhanced surveillance systems, improved risk assessments, and integrated vector control programs. Surveillance plays a pivotal role in early detection and timely intervention, particularly in endemic regions, while vector control remains central to reducing transmission. Moreover, the development of novel diagnostic tools, treatments, and vaccines is a crucial step in advancing control efforts. This review also highlights the involvement of local governments, international organizations, and civil society in executing these strategies, stressing the need for sustained political commitment to ensure the success of public health programs. By addressing key challenges in monitoring, control, and prevention, this review aims to provide insights and recommendations to further global efforts in reducing the burden of Chagas disease. Full article

Chagas disease remains a significant public health concern, with limited treatment options and an urgent need for novel preventive strategies. Extracellular vesicles (EVs) from Trypanosoma cruzi have been shown to modulate host immune responses, often favoring parasite persistence. In this study, we characterized EVs derived from the non-pathogenic trypanosomatids Trypanosoma rangeli and Phytomonas serpens and evaluated their potential as immunogens capable of inducing cross-protection against T. cruzi infection. Isolated EVs were characterized by Nanoparticle Tracking Analysis (NTA) and electron microscopy. A comparative proteomic analysis of EVs was performed using Mass Spectrometry-Based Proteomic Analysis (LC-MS/MS). The effects of EVs on immunomodulation and T. cruzi infection were assessed through in vitro and in vivo assays, using peripheral blood mononuclear cells (PBMCs) and BALB/c mice. The proteomic analysis identified shared proteins between the EVs of T. rangeli, P. serpens, and T. cruzi, including immunogenic candidates such as calpain-like cysteine peptidase and elongation factor 2. In vitro, pre-stimulation with the T. rangeli EVs reduced infection rates of the host cells by T. cruzi. In vivo, immunization with the EVs from T. rangeli and P. serpens led to a significant reduction in parasitemia in the BALB/c mice challenged with T. cruzi, though this did not translate into improved survival compared to controls. Interestingly, the EVs from T. cruzi also reduced parasitemia but did not confer protection against mortality. These findings suggest that while non-pathogenic trypanosomatid EVs exhibit potential immunogenic properties and can reduce parasitic load, their efficacy in preventing disease progression remains limited. Further research is needed to explore the mechanisms underlying these effects and to optimize EV-based strategies for protective immunity against Chagas disease. Full article

Triatoma sordida is a native South American species and the most frequently captured triatomine in artificial environments in Brazil. Although considered a secondary vector of Trypanosoma cruzi, it is typically associated with low infection rates. To investigate its role in an endemic area for Chagas disease in northern Minas Gerais, Brazil, we employed a multidimensional approach that combined triatomine capture data with quantitative and qualitative analyses of T. cruzi. A total of 1861 T. sordida specimens were captured, of which 1455 were examined and 210 (14.4%) were found to be infected with T. cruzi. The most prevalent discrete typing unit (DTU) was TcI (80%), followed by TcII (8%), TcV (5%), and TcIII (3%). Molecular techniques provided new insights into the ecology of T. sordida, revealing a higher infection rate than previously reported and a parasitic load lower than that observed in other quantified species. Chickens were confirmed as the primary food source, playing an epidemiological role in maintaining infected insects with four T. cruzi DTUs. The observed diversity of T. cruzi DTUs suggests a lack of environmental segregation, likely due to the extensive movement of various host species between wild and domestic habitats, resulting in overlapping transmission cycles. Full article

Triatomines are vectors of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae), the agent of Chagas disease. Stercorarian transmission occurs when infectious parasites are passed in insect feces to vertebrates through the biting wound or mucosa. Defecating on hosts during or shortly after blood feeding is, therefore, critical for transmission, and delayed triatomine defecation behavior has been posited to contribute to a low incidence of human Chagas disease in the U.S. We allowed nymphal T. cruzi-infected and uninfected Triatoma gerstaeckeri (Stål, 1859) and Triatoma sanguisuga (LeConte, 1855) to interact with restrained guinea pigs and measured insect feeding and defecation events; South American Rhodnius prolixus (Stål, 1859; Latin America) served as a comparison group. In 148 trials, 40.0% of insects fed, of which 71.2% defecated. Compared to R. prolixus, T. gerstaeckeri had >9 times higher odds of feeding, and T. sanguisuga fed longer. Observations of defecation while feeding occurred across all three species. The post-feeding defecation interval (PFDI) of R. prolixus was significantly shorter (4.54 ± 2.46 min) than that of T. gerstaeckeri (9.75 ± 2.52 min) and T. sanguisuga (20.69 ± 8.98 min). Furthermore, the PFDI was shorter for TcI-infected insects compared to uninfected insects. Triatoma gerstaeckeri and T. sanguisuga are capable of stercorarian transmission, although the calculated metrics suggest they are less efficient vectors than R. prolixus. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a neglected tropical disease with limited and often suboptimal chemotherapeutic treatment options. The WHO recommends nifurtimox (NFX) for treating Chagas disease, which, although it is effective in the early stages of infection, has variable efficacy in the chronic phase and induces adverse effects that frequently compromise the continuity of the treatment. This study focused on the development and characterization of innovative lipid-based self-emulsifying drug delivery systems (SEDDSs) and poly(ε-caprolactone) implants containing NFX. The SEDDS formulations modified the NFX release extent and rate. The implant characterization included thermal analysis, X-ray diffraction, thermo-optical analysis, and scanning electron microscopy, confirming the low interaction between NFX and the polymer. In vitro assays demonstrated the enhanced anti-T. cruzi activity of the NFX-SEDDS, with minimal cytotoxicity in mammalian cells. In vivo studies using T. cruzi-infected mice revealed that both formulations effectively suppressed parasitemia, achieving cure rates comparable to those of the standard oral NFX treatment. Additionally, the implants showed improved tolerability and sustained efficacy, delivering a prolonged effect equivalent to 40 oral doses. These findings highlight the potential of these innovative NFX formulations as promising alternatives for treating Chagas disease, particularly in the chronic phase, offering improved adherence and comparable efficacy to the existing therapies. Full article

Chagas disease (ChD) is a neglected tropical disease caused by Trypanosoma cruzi, endemic in 21 countries across the Americas, with increasing cases globally. In São Paulo, Brazil, vector control has focused on Triatoma infestans, but secondary triatomine species continue to pose transmission risks. This study aimed to investigate the prevalence of T. cruzi in triatomine feces and characterize its genetic diversity using molecular techniques. Fecal samples were collected from 570 triatomines across 25 municipalities in São Paulo, followed by DNA extraction and PCR amplification targeting the mitochondrial cytochrome b gene and the V7V8 region of the 18S rRNA gene. The results revealed a low overall infection rate (3.2%). However, excluding the triatomines collected in palm trees, all of which were negative, we found mainly Panstrongylus megistus in residences and peridomiciles, showing the highest infection rate (65%) for T. cruzi, followed by Triatoma sordida and Rhodnius neglectus. Phylogenetic analysis confirmed that DTU TcI was the most prevalent genotype, consistent with previous findings in the region. This study highlights the importance of continued vector surveillance, as these secondary species are capable of maintaining T. cruzi transmission in both urban and rural environments, underscoring the ongoing risk of ChD resurgence in São Paulo. Full article

Neglected Tropical Diseases are a group of 25 conditions caused by diverse agents. They mostly affect people with poorer health outcomes, particularly preventable diseases. The social determinants of health influence the development and progression of these poverty diseases, with inadequate sanitation presenting chronicity, high morbidity, and economic impacts. Chagas disease, a prominent Neglected Tropical Disease caused by the intracellular pathogen Trypanosoma cruzi, is endemic in Latin America but is increasing as a global concern due to population migration. It is transmitted through insect vectors, congenitally, orally via contaminated food and beverage, via transfusions and organ donation, and due to laboratory accidents, among other minor relevant routes. As a silent illness, with many infected individuals remaining asymptomatic, it contributes to underdiagnosis, and delayed treatment that involves nitro derivatives is often discontinued due to side effects. Chagas disease spreads in non-endemic areas like the United States of America and Europe. Blood screening practices vary, with endemic regions implementing universal testing, while non-endemic areas rely on selective methods. Recent innovations, such as riboflavin–ultraviolet light treatment and arylimidamide compounds, represent promising alternatives to reduce transfusion transmission. This review presents an analysis of Trypanosoma cruzi transmission through blood and derivatives, addressing the main routes, globally implemented control strategies, and recent advancements in blood bank safety. Full article

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects millions globally, with limited treatment options available. Current therapies, such as benznidazole and nifurtimox, present challenges, including their toxicity, side effects, and inefficacy in the chronic phase. This study explores the potential of drug repurposing as a strategy to identify new treatments for T. cruzi, focusing on compounds from the Medicines for Malaria Venture (MMV) COVID Box. An initial screening of 160 compounds identified eight with trypanocidal activity, with almitrine and bortezomib showing the highest efficacy. Both compounds demonstrated significant activity against the epimastigote and amastigote stages of the parasite and showed no cytotoxicity in murine macrophage cells. Key features of programmed cell death (PCD), such as chromatin condensation, mitochondrial membrane potential disruption, and reactive oxygen species accumulation, were observed in T. cruzi treated with these compounds. The potential to induce controlled cell death of these two compounds in T. cruzi suggests they are promising candidates for further research. This study reinforces drug repurposing as a viable approach to discovering novel treatments for neglected tropical diseases like Chagas disease. Full article

Chagas disease (CD) is a global health concern, with no existing therapies to prophylactically treat adults traveling to endemic countries or those who may already be infected with Trypanosoma cruzi. The economic burden of Chagas cardiomyopathy and heart failure, due to healthcare costs and lost productivity from premature deaths, provides a strong rationale for investment in the development of immune therapies against CD. Vaccine efficacy is proposed to depend heavily on the induction of a robust Th1 response for the clearance of intracellular pathogens like T. cruzi. In this review, updated information on the efforts for vaccine development against CD is provided. Full article

Chagas disease, caused by the protozoan Trypanosoma cruzi, represents a significant public health challenge, particularly in Latin America’s endemic regions. The limited efficacy and frequent adverse effects of current treatments underscore the need for novel therapeutic options. This research explores marine natural compounds as potential candidates for Chagas disease treatment using virtual screening and in silico evaluation methods. Techniques such as molecular docking, drug-likeness evaluation, and pharmacokinetic analysis were employed to identify promising anti-parasitic compounds. Among the candidates, chandrananimycin A, venezueline A, and dispacamide demonstrated high binding affinities to key targets in T. cruzi alongside favorable docking scores and compliance with essential drug-likeness criteria. Pharmacokinetic profiling further supported their therapeutic potential, revealing desirable properties like effective absorption and minimal toxicity. These findings underscore the promise of marine-derived compounds as a valuable source of new drugs, emphasizing the need for further in vitro and in vivo investigations to elucidate their molecular mechanisms and optimize their development as viable treatments for Chagas disease. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a significant global health challenge, particularly in the molecular diagnostics of low parasitemia during the chronic phase. This highlights the critical need for enhanced diagnostic methodologies. In response, this study evaluates the effectiveness of an automated magnetic beads-based DNA extraction method in improving the molecular diagnosis of Chagas disease compared to the traditional silica column-based extraction. Accordingly, this research seeks to enhance the DNA yield, purity, and sensitivity of real-time PCR (qPCR) assays for detecting T. cruzi satDNA. Blood samples spiked with guanidine–EDTA solution and varying concentrations of T. cruzi were used to compare the two extraction methods. The results indicated that the magnetic bead-based method outperformed the silica column in terms of DNA concentration, purity, and earlier detection of T. cruzi satDNA. Although both methods had similar limits of detection at a 95% confidence interval, the magnetic bead-based approach demonstrated higher sensitivity and reproducibility, particularly in low-parasitemia samples. The findings suggest that the magnetic beads-based DNA extraction method offers a more reliable, faster, and more sensitive alternative for diagnosing chronic Chagas disease, potentially improving clinical outcomes by enabling more accurate and earlier parasite detection. Full article

Trypanosomatids of the genera Trypanosoma and Leishmania are parasites of medical and veterinary importance that infect mammals, including humans and domestic and wild animals. Among mammals, rodents and marsupials play a crucial role in maintaining and spreading the zoonotic transmission cycle of these parasites. The present study aimed to detect the natural occurrence of Trypanosoma spp. and Leishmania spp. in rodents and marsupials in the state of Amapá, northern Brazil. In total, 137 samples were analyzed, of which 19 (6 marsupials and 13 rodents) were positive for trypanosomatid DNA. Partial sequences of the 18S rRNA gene of trypanosomatids were obtained from 10 out of 19 positive samples. Specifically, an undescribed Trypanosoma sp. was detected in Marmosa demerarae, Marmosa murina, Zygodontomys brevicauda, and Neacomys paracou. Trypanosoma cruzi was detected in a Philander opossum, whereas sequences close to Trypanosoma wauwau and Trypanosoma freitasi were obtained from Didelphis imperfecta and N. paracou, respectively. Finally, Leishmania (Viannia) sp. was detected in Mesomys hispidus, Hylaeamys megacephalus, and Z. brevicauda. The present study expands the knowledge about marsupials and rodents as hosts of trypanosomatids and emphasizes the need for further studies on the role of these animals as potential reservoirs of these parasites in the Amazon region. Full article

Chagas disease, caused by Trypanosoma cruzi, is a parasitic zoonosis with significant health impacts, particularly in Latin America. While traditionally associated with vector-borne transmission, increased migration has expanded its reach into urban and non-endemic regions. Congenital transmission has become a critical route of infection, involving intricate maternal–fetal immune interactions that challenge diagnosis and treatment. This review synthesizes findings from three RNA-seq studies that explore the molecular underpinnings of congenital Chagas disease, emphasizing differentially expressed genes (DEGs) implicated in host–pathogen interactions. The DAVID tool analysis highlighted the overexpression of genes associated with the innate immune response, including pro-inflammatory cytokines that drive chemotaxis and neutrophil activation. Additionally, calcium-dependent pathways critical for parasite invasion were modulated. T. cruzi exploits the maternal–fetal immune axis to establish a tolerogenic environment conducive to congenital transmission. Alterations in placental angiogenesis, cellular regeneration, and metabolic processes further demonstrate the parasite’s ability to manipulate host responses for its survival and persistence. These findings underscore the complex interplay between the host and pathogen that facilitates disease progression. Future research integrating transcriptomic, proteomic, and metabolomic approaches is essential to unravel the molecular mechanisms underlying congenital Chagas disease, with a particular focus on the contributions of genetic diversity and non-coding RNAs in immune evasion and disease pathogenesis. Full article

Kinetoplastids display a single, large mitochondrion per cell, with their mitochondrial DNA referred to as the kinetoplast. This kinetoplast is a network of concatenated circular molecules comprising a maxicircle (20–64 kb) and up to thousands of minicircles varying in size depending on the species (0.5–10 kb). In Trypanosoma cruzi, maxicircles contain typical mitochondrial genes found in other eukaryotes. They consist of coding and divergent/variable regions, complicating their assembly due to repetitive elements. However, next-generation sequencing (NGS) methods have resolved these issues, enabling the complete sequencing of maxicircles from different strains. Furthermore, several insertions and deletions in the maxicircle sequences have been identified among strains, affecting specific genes. Unique to kinetoplastids, minicircles play a crucial role in a particular U-insertion/deletion RNA editing system by encoding guide RNAs (gRNAs). These gRNAs are essential for editing and maturing maxicircle mRNAs. In Trypanosoma cruzi, although only a few studies have utilized NGS methods to date, the structure of these molecules suggests a classification into four main groups of minicircles. This classification is based on their size and the number of highly conserved regions (mHCRs) and hypervariable regions (mHVRs). Full article

Trypanosoma cruzi is the parasite responsible for Chagas disease, which has a significant amount of genetic diversification among the species complex. Many efforts are routinely made to characterize the genetic lineages of T. cruzi circulating in a particular geographic area. However, the genetic loci used to typify the genetic lineages of T. cruzi have not been consistent between studies. We report a quantitative analysis of the phylogenetic power that is acquired from the commonly used genetic loci that are employed for the typification of T. cruzi into its current taxonomic nomenclature. Based on three quantitative criteria (the number of phylogenetic informative characters, number of available reference sequences in public repositories, and accessibility to DNA sequences for their use as outgroup sequences), we examine and discuss the most appropriate genetic loci for the genetic typification of T. cruzi. Although the mini-exon gene is by far the locus that has been most widely used, it is not the most appropriate marker for the typification of T. cruzi based on the construction of a resolved phylogenetic tree. Overall, the mitochondrial COII-NDI locus stands out as the best molecular marker for this purpose, followed by the Cytochrome b and the Lathosterol oxidase genes. Full article