Search Results (937)

The mitochondrial DNA of trypanosomatid parasites consists of thousands of catenated minicircles and dozens of maxicircles that form a complex network structure, the kinetoplast (kDNA). Although kDNA replication and segregation during mitotic division are well studied, its inheritance during genetic exchange events remains unclear. In Trypanosoma brucei, hybrids inherit minicircles biparentally but retain maxicircles from a single parent. Although biparental inheritance of minicircles has been described in natural Trypanosoma cruzi hybrids, this process has not been explored in laboratory-generated hybrids of this parasite. In the present study, we analyzed kDNA inheritance in T. cruzi experimental hybrids using a comprehensive minicircle hypervariable region (mHVR) database and genome sequencing data. Our findings revealed biparental inheritance of minicircles, with hybrid lines retaining mHVRs from both parents for over 800 generations. In contrast, maxicircles were exclusively inherited from one parent. Unexpectedly, we observed an increase in kDNA content in hybrids, affecting both minicircles and maxicircles, and exhibiting instability over time. To explain these findings, we propose a Replicative Mixing (REMIX) model, where the hybrid inherits one kinetoplast from each parent and they are replicated allowing minicircle mixing. Instead maxicircle networks remain physically separated, leading to uniparental fixation after segregation in the first cell division of the hybrid. This model challenges previous assumptions regarding kDNA inheritance and provides a new framework for understanding kinetoplast dynamics in hybrid trypanosomes. Full article

African trypanosomiasis is a protozoan disease that affects both humans and animals. Human African Trypanosomiasis (HAT) is a Neglected Tropical Disease targeted for elimination in 2030. Although WHO has not reported HAT from Nigeria in the last decade, there are published studies reporting seroprevalence, parasite detection/isolation, and animal reservoirs potentially involved in HAT transmission in Nigeria. Interestingly, the burden of Animal African Trypanosomiasis (AAT) continues to increase. In this study, we synthesized published reports on the prevalence of HAT and AAT in Nigeria from 1993–2021, the trypanosome species involved, the spread of animal reservoirs, and the variability in diagnostic methodologies employed. A scoping review was performed following the methodological framework outlined in PRISMA-ScR checklist. Sixteen eligible studies published between 1993 and 2021 were reviewed: 13 for AAT and 3 for HAT. Varying prevalence rates were recorded depending on the diagnostic methods employed. The average prevalence reported from these studies was 3.3% (HAT), and 27.3% (AAT). Diagnostic methods employed include microscopy, PCR and Card Agglutination Test for Trypanosomiasis (CATT). Cattle, pigs, and dogs were identified as carriers of human-infective trypanosomes. This study highlights the scarcity of HAT epidemiological studies/data from Nigeria, the high prevalence, complex epidemiology, limited attention and surveillance of African Trypanosomiasis in Nigeria. Remarkably, WHO records do not reflect the published data showing evidence of HAT prevalence/cases in Nigeria. Unfortunately, diagnostics challenges and unrealistic disease reporting protocols seem to limit HAT reporting from Nigeria. Therefore, adequately coordinated epidemiological surveys and targeted intervention policies are imperative to ascertain the true epidemiological status of HAT in Nigeria and prevent disease re-emergence towards achieving WHO’s elimination targets. The presence of animal carriers of human-infective trypanosomes underscores the importance of a one-health approach to combat African trypanosomiasis effectively. Full article

Pachysandra terminalis (P. terminalis), a plant belonging to the Buxaceae family, is known as a great source of aminosteroid alkaloids. In a previous communication, we reported on the isolation of a variety of aminosteroids from P. terminalis, which presented interesting activity against the protozoan pathogens, Trypanosoma brucei rhodesiense and Plasmodium falciparum. In the present study, variations in the alkaloid profile of P. terminalis related to seasonal changes as well as differences between plant organs (leaves and twigs) and between plant populations were investigated to prioritize candidates for targeted isolation in further studies. For this purpose, sample material of P. terminalis was collected from the two nearby populations in monthly intervals over one year. The ethanolic (75%) extracts were analyzed using UHPLC/+ESI-QqTOF-MS/MS, and the resulting data converted to variables encoding the intensity of MS signals in particular m/z and retention time (t_R) intervals over the chromatographic runs. The very large and complex data matrix of these <t_R:m/z> variables was evaluated using multivariate data analysis, especially principal component analysis (PCA) and volcano plot analysis of t-test data. The results of these analyses, for the first time, allowed a holistic analysis of variation in the alkaloid profiles in P. terminalis organs over the vegetation period. The evaluation of the PCA scores and loadings plots of principal components 1 through 3, as well as of volcano plots, highlighted 25 different compounds, mostly identified as aminosteroid alkaloids, that were most relevant for the differences between leaves and twigs and between the two populations and mainly determined the changes in their chemical profiles over the vegetation period. Full article

Background: Chagas disease and leishmaniasis remain public health concerns. Despite the existence of approved medications for the treatment of these diseases, most patients discontinue treatment due to long drug regimens and/or the severe side effects of these drugs. This leads to treatment failure and potential future drug resistance. Therefore, the search for new molecules with trypanocidal activity, low cytotoxicity, and high selectivity is essential to address this challenge. Methods: In this work, three series (a, b, and c) of pyridine-2,5-dicarboxylate esters were synthesized using different β-keto-esters bearing naturally occurring fragments and 1,2,3-triazine-1-oxides via the inverse electron demand Diels–Alder (IEDDA) reaction. The structural elucidation of the compounds was performed using NMR (¹H and ¹³C) and HRMS, and the crystal structure of compound 6a was also obtained. Furthermore, a biological assay was performed for all synthesized and characterized compounds to determine their cytotoxicity against Trypanosoma cruzi, Leishmania mexicana, and the J774.2 macrophage cell line. Finally, the in silico determination of their pharmacokinetic and toxicological properties was performed using the SwissADME and ProTox 3.0 platforms. Results: Compounds 3a, 4a, 5a, 4b, and 8c had the highest anti-Trypanosoma cruzi activity against both strains (IC₅₀ ≤ 56.68 µM). Compounds 8b, 10a, 9b, and 12b had considerable leishmanicidal activity against Leishmania mexicana against both strains (IC₅₀ ≤ 161.53 µM). Furthermore, in silico prediction of ADMET properties suggest that these pyridine compounds possess good pharmacokinetic profile. The results are also consistent with low in vitro cytotoxicity and high selectivity. Conclusions: The synthesized pyridine-2,5-dicarboxylate esters have promising activity against Trypanosoma cruzi and Leishmania mexicana, with low cytotoxicity and good drug-like properties, suggesting that these compounds are potential candidates for further evaluation as new treatments for Chagas disease and leishmaniasis. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a major health concern in Latin America, particularly affecting low-income and rural communities. Among the many vaccine strategies explored, live attenuated parasites have shown the strongest ability to trigger protective immune responses. In this study, we investigated whether adding saponin-based adjuvants—Immunostimulant Particle Adjuvant (ISPA) and Quil-A—could improve the effectiveness and safety of a live parasite attenuated T. cruzi vaccine. Mice were vaccinated with a T. cruzi attenuated strain (TCC) alone or in combination with each adjuvant, and immunoglobulin G (IgG) subtypes in the serum of vaccinated mice, and interferon gamma (IFN-γ) and interleukin-10 (IL-10) in the supernatants of stimulated cells were measured at two weeks and twelve months post-vaccination. While protection levels were similar across all groups, the adjuvants assist in modulating the immune response over time: ISPA and Quil-A initially shifted antibody production toward IgG1 but later favored a balanced T_H1/T_H2 profile. ISPA also promoted long-term regulation through increased IL-10. Both adjuvants reduced tissue inflammation and enhanced clearance of vaccine-derived parasites. These findings suggest that while adjuvants may not boost protection directly, they significantly improve vaccine safety and immune quality, reinforcing their value in developing better vaccines for Chagas disease. Full article

Kinetoplastids are protozoa that possess a unique organelle called a kinetoplast. These include the parasites Trypanosoma cruzi, T. brucei and related African trypanosomes, and Leishmania spp. These parasites cause a variety of neglected tropical diseases in humans and livestock, with devastating consequences. In the absence of any vaccine, pharmaceutical interventions are the mainstay of control, but these have historically been underfunded, fragmented, and inadequately aligned with the complex zoonotic and ecological realities of the parasites’ transmission dynamics. In this review, the landscape of current and emerging drugs for treating leishmaniasis, Chagas disease, and African trypanosomiasis is critically evaluated across both veterinary and human contexts. It examines the challenges of legacy compounds, the pharmacological shortcomings in multi-host, multi-tropic and multi-stage disease systems, and the gaps in veterinary therapeutics, specifically for African animal trypanosomiasis and canine leishmaniasis but also the animal reservoir of T. cruzi. Emphasis is placed on pharmacokinetic divergence between species, the accompanying risks with the use of off-label human drugs in animals, and the ecological effects of environmental drug exposure. We propose a far-reaching One Health framework for pharmaceutical research and development, promoting dual-indication co-development, ecological pharmacology, regulatory harmonisation, and integrated delivery systems. In this context, we argue that the drug development pipeline must be rationalised as a transdisciplinary and ecologically embedded process, able to interrupt parasite transmission to human, animal, and vector interfaces. Our findings reveal that we can bridge age-old therapeutic gaps, advance towards sustainable control, and eventually eliminate the neglected diseases caused by kinetoplastid protozoan parasites by aligning pharmaceutical innovation with One Health principles. This article aims to promote future research and development of innovative drugs that are sustainable under the One Health framework. Full article

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), remains a significant public health challenge in Latin America. Traditional diagnostic methods relying on manual microscopy suffer from low sensitivity, subjective interpretation, and poor performance in suboptimal conditions. This study presents a novel computer vision framework integrating motion analysis with deep learning for automated T. cruzi detection in microscopic videos. Our motion-based detection pipeline leverages parasite motility as a key discriminative feature, employing frame differencing, morphological processing, and DBSCAN clustering across 23 microscopic videos. This approach effectively addresses limitations of static image analysis in challenging conditions including noisy backgrounds, uneven illumination, and low contrast. From motion-identified regions, $64\times 64$ patches were extracted for classification. MobileNetV2 achieved superior performance with 99.63% accuracy, 100% precision, 99.12% recall, and an AUC-ROC of 1.0. Additionally, YOLOv5 and YOLOv8 models (Nano, Small, Medium variants) were trained on 43 annotated videos, with YOLOv5-Nano and YOLOv8-Nano demonstrating excellent detection capability on unseen test data. This dual-stage framework offers a practical, computationally efficient solution for automated Chagas diagnosis, particularly valuable for resource-constrained laboratories with poor imaging quality. Full article

Rodents are among the most widespread mammals globally and serve as critical reservoirs for a wide array of zoonotic parasites that significantly impact human health. This review explores the growing public health concern of rodent-borne parasitic diseases, encompassing protozoa, helminths, and ectoparasites. Key protozoan parasites include Toxoplasma gondii, Trypanosoma cruzi, Leishmania spp., Giardia intestinalis, and Cryptosporidium spp., all of which are capable of causing severe diseases in humans and are found in rodent populations. Zoonotic helminths such as Hymenolepis spp., Trichinella spiralis, Angiostrongylus cantonensis, Capillaria hepatica, and Baylisascaris procyonis also demonstrate substantial zoonotic potential. Moreover, ectoparasites like Xenopsylla cheopis, Ornithonyssus bacoti, and Ixodes spp. play key roles in the transmission of vector-borne diseases, including plague, murine typhus, and Lyme disease. Anthropogenic factors, including urbanization, poor sanitation, habitat destruction, and climate change, exacerbate the emergence and spread of these infections. These drivers not only disrupt rodent ecology but also increase the frequency of human–rodent interactions, facilitating zoonotic transmission. Despite the severity of these threats, rodent-borne parasitic diseases remain underrecognized, particularly in low-resource settings where surveillance and control efforts are often limited. This review highlights the pressing need for integrated One Health strategies that encompass rodent population control, environmental hygiene, vector management, and public education. Strengthening global surveillance systems and investing in interdisciplinary research are critical for early detection, risk assessment, and prevention of future outbreaks. Tackling the ecological and environmental drivers of rodent-borne parasitic diseases is essential to safeguard both human and animal health in an increasingly interconnected world. Full article

In Brazil, Trypanosoma vivax was identified between 1970 and 1984 in buffalo, cattle, and sheep in northern Brazil. In the 1990s, the disease was diagnosed in the Pantanal of Mato Grosso. Currently, the disease is considered in enzootic stability in both regions. From 2006 to 2018, outbreaks of the disease associated with the presence of horseflies (Tabanidae) and stable flies (Stomoxys calcitrans) or transmitted by needle and syringe reuse were diagnosed in sheep, goats, and cattle during the rainy season in the semiarid region of Northeast Brazil, a region considered to have enzootic instability. Since 2013, numerous outbreaks have been diagnosed associated with oxytocin inoculation to induce milk letdown in dairy cows. Most outbreaks occur in cattle transported from areas of enzootic instability to areas of stability, or vice versa. Serological, parasitological, and molecular techniques have identified T. vivax in asymptomatic animals in all Brazilian regions. For disease prophylaxis, it is important not to reuse syringes and needles when administering medication and to avoid transporting animals during periods of insect abundance. It is also necessary to avoid the use of oxytocin or adopt safe injection practices, using disposable or disinfected needles and syringes only for cows with ineffective milk ejection. Full article

Background/Objectives: Temporizin-1, a hybrid antimicrobial peptide derived from the combination of Temporin A, Gramicidin peptide, and a poly-leu sequence, has strong trypanocide activity against Trypanosoma cruzi and moderate cytotoxicity towards mammalian cells. In this study, we investigated the mode of action of the peptide upon interaction with protozoan and eukaryotic membranes. Methods: To this end, we conducted a series of biophysical assays using liposomes as biomimetic models, along with fluorescence-based experiments such as lipid mixing, membrane leakage, and assays involving Thioflavin and Laurdan. Results: Temporizin-1 displayed potent membranolytic activity on protozoan and eukaryotic membranes, causing significant membrane fusion and leakage with consequent pore formation. In addition, we also performed structural studies on liposome interaction, where we observed a helical structure that is conserved during membrane interaction. The NMR study confirms all the data obtained, providing both the structure of free Temporizin-1 in solution and the way it interacts with micelles. Moreover, Temporizin-1 demonstrated high selectivity against intracellular forms of T. cruzi and exhibited an additive effect when combined with benznidazole, highlighting its promising therapeutic activity. Conclusions: In conclusion, elucidating the mechanism of action of Temporizin-1 is essential for optimizing its structure and improving target selectivity, and driving the rational design of next-generation antimicrobial peptides by applying chemical strategies and delivery system’s conjugation. Full article

Chagas disease, caused by Trypanosoma cruzi, presents a variety of clinical outcomes ranging from mild symptoms to Chagas cardiomyopathy, the most severe and life-threatening manifestation of the disease. The degree of virulence is influenced by both parasite and host factors. In this study, we characterized a murine infection model using the T. cruzi Dm28c strain in BALB/c mice to assess disease progression. Infected mice showed a peak of parasitemia at 14 dpi, followed by a progressive decrease. Spleen weight increased up to sixfold compared to uninfected controls at 14 and 21 dpi, correlating with parasitemia levels. Histological analysis revealed focal inflammatory infiltrates in the heart starting at 7 dpi, with maximal intensity at 14 and 21 dpi. The expression of inflammatory cytokines (IFN-γ, IL-1β, TNF-α) and anti-inflammatory cytokines (IL-10, TGF-β) in the spleen showed a dynamic profile, with an early increase during the acute phase. Dm28c infection of BALB/c mice can be considered as a non-lethal Chagas disease experimental model, with detectable parasitemia during the acute phase and a controlled inflammatory response. Full article

Reproductive biotechnologies, such as embryo transfer (ET) and fixed-time artificial insemination (FTAI), are increasingly adopted to enhance genetic progress in tropical cattle production systems. However, the high prevalence of reproductive infectious diseases in tropical regions may compromise reproductive outcomes. This study evaluated the impact of eight reproductive pathogens (Neospora caninum, Leptospira spp., Anaplasma spp., Babesia spp., Trypanosoma spp., BVDV, IBR, and BLV) on pregnancy success, embryonic loss, and abortion in 296 bovine females subjected to ET and FTAI in Huila, Colombia. Animals were classified into six genetic groups and monitored for pregnancy at 45 and 90 days post-treatment. Logistic regression models were used to evaluate associations between disease prevalence and reproductive outcomes. Neospora caninum emerged as the most detrimental pathogen, significantly reducing pregnancy rates (OR = 0.443; p = 0.034) and increasing both embryonic loss (OR = 7.35; p = 0.073) and abortion risk (ET: OR = 20.3; p = 0.0002; FTAI: OR = 3.95; p = 0.0436). Leptospira spp. and BLV were also associated with increased embryonic losses, whereas Babesia spp. and IBR were linked to a reduced risk of embryo resorption because of enhanced care, monitoring, or vaccination. Creole cattle showed lower disease susceptibility than crossbred or commercial breeds. These findings highlight the need for comprehensive disease control, targeted vaccination, and reproductive planning to improve biotechnology outcomes in tropical cattle systems. Full article

The neglected Chagas disease, a zoonosis caused by the Trypanosoma cruzi parasite, has limited treatment options like nifurtimox and benznidazole, known for their toxic effects and controversial efficacy. Natural products present opportunities for therapeutic alternatives, particularly in Chile, which has a rich variety of endemic flora. This study focused on the Chilean Buddleja globosa, evaluating the antioxidant activities and biological effects of its methanolic extract (MET) and BG500, an enriched iridoid fraction (6-O-methylcatalpol), against T. cruzi trypomastigotes. Although the trypanocidal activity of the extract was significantly lower than that of nifurtimox (280 ± 3.5 vs. 5.0 ± 0.5), its selectivity was comparable (selectivity index > 15). The MET and enriched fraction also induced hyperpolarization of mitochondrial membrane potential (ΔΨm). In silico docking studies suggested that T. cruzi’s Old Yellow (OYE) could be a potential target for 6-O-methylcatalpol. This work provides the first report on the potential trypanocidal activity of a B. globosa extract, highlighting the need for further studies to connect ΔΨm and OYE inhibition to the effects of 6-O-methylcatalpol. Full article

Trypanosoma cruzi is a hemoflagellate protozoan and the causative agent of Chagas disease, also known as American trypanosomiasis. Transmission occurs through the feces of triatomine insects, its biological vector. It is estimated that around 7 million people are infected across Mexico, Central America, and South America. This study aimed to identify and characterize T. cruzi isolates obtained from wild triatomine vectors collected in Aguascalientes, Mexico. Molecular identification was performed at different developmental stages—epimastigotes in culture media, metacyclic trypomastigotes in triatomine feces, and amastigotes in mouse cardiac tissue—using endpoint PCR targeting satDNA and mtCytB regions. In addition, next-generation sequencing was employed to analyze variable regions of kinetoplast DNA minicircles. The pathogenicity of the isolated and identified T. cruzi strain was assessed in a murine model, where trypomastigote stages were detected in peripheral blood and amastigote stages in muscle tissue. Molecular analyses confirmed the presence of T. cruzi across different developmental stages from wild vectors, demonstrating that the isolated wild strain possesses pathogenic potential when completing its life cycle in an experimental mammalian host, specifically BALB/c mice. Full article

Hemoparasites are blood-borne parasites transmitted by vectors and are commonly found in wild birds worldwide. The most frequently reported genera include Plasmodium, Haemoproteus, Leucocytozoon, and Trypanosoma, while filarial worms and other hemoparasites are less frequently reported. Despite their importance, knowledge of their effects on the health of wild birds remains limited. This systematic review summarizes all scientific findings on hemoparasites in wild birds, emphasizing their implications for host health. The literature reveals a high number of articles in this area in recent decades, reflecting a growing concern about hemoparasites in wildlife and their ecological impact. However, studies remain unevenly distributed across regions and bird taxa. Diagnostic limitations, particularly in fieldwork and wildlife rehabilitation, continue to present challenges for the accurate detection and monitoring of these parasites. Nevertheless, molecular tools have advanced our understanding of parasite diversity and host–parasite dynamics. Our work highlights key knowledge gaps and stresses the need for further research to improve the understanding of the role of hemoparasites in avian ecology, particularly concerning environmental change and emerging infectious diseases. Full article