Search Results (183)

Information on Culicoides transmitted parasites, especially trypanosomatids, infecting animals and insects, is scarce. Our goal was to clarify the seasonal patterns of both Culicoides and trypanosomatids detected in these insects and the relationships between Culicoides abundance and meteorological parameters. UV light traps were used to collect biting midges in four study sites in 2022–2023; collected Culicoides females were dissected and analyzed using microscopy and PCR-based methods. Out of 1631 parous Culicoides females belonging to 14 different species, 6.5% were found to be infected with trypanosomatids (5.0% with at least three Trypanosoma species and 1.5% with monoxenous parasites). The highest Culicoides abundance was detected in June. The prevalence of trypanosomatids in biting midges increased during the summer (5.3% in June, 8.8% in July, and 11.2% in August). Temperature was recorded to be a presiding environmental gradient structuring Culicoides species composition, while wind speed and precipitation explained little of the variation. Our results indicate that both avian and mammalian trypanosomes can be found in these insects, although further research is needed to better understand the development of these parasites in biting midges and Culicoides vectorial capacity. Full article

The Apolipoprotein L1 (APOL1) innate immunity gene product represents the sole member of the APOL gene family in humans capable of secretion into circulation, thereby mediating the trypanolysis of T. brucei brucei. Gain-of-function variants of the APOL1 gene originated and spread among human population groups to extend APOL1’s protective capacity to include also serum-resistant subspecies, such as T. brucei gambiense (S342G known as APOL1-G1) and T. brucei rhodesiense (N388_Y389del known as APOL1-G2). The biochemical pathways underlying the lytic activity of these evolutionary favored mutations against bloodstream trypanosomes have been elucidated with remarkable precision. However, the intricate molecular mechanisms by which such variants confer an increased susceptibility to renal cellular injury and consequent kidney disease remain incompletely defined. In the absence of a consistent mechanistic explanation for differential kidney injury, we propose pursuing three interrelated avenues of investigation informed by prior epidemiological and mechanistic evidence linking them to APOL1’s cytotoxicity: (1) Molecular evolution of APOL1 haplotypes in human populations, (2) APOL1 splicing and consequent splice isoforms, (3) Interaction of APOL1 with other APOL gene family members, prioritizing APOL3. In the current study, we use reanalysis of population genetics datasets to resolve the haplotype contexts of all protein-altering APOL1 variants, uncovering previously unrecognized variant–haplotype couplings. We further characterize distinct cellular physiological properties among APOL1 splice isoforms, stressing the importance of isoform vB and what can be learned from isoform vC. Finally, a native interaction, and its interface, between APOL1 and APOL3 is reported, and shown to be differentially modulated by G1 and G2. We contend that continuing studies integrating these three interrelated domains will substantially advance mechanistic insights into APOL1 variant-driven renal injury, and leverage the findings to provide a more cohesive framework to guide future research. Full article

APOL1 is the most recent member of the APOL gene family and is expressed exclusively in humans and a few higher primates. More than twenty years ago, it was discovered that APOL1 protects humans from infections by trypanosome subspecies that cause African sleeping sickness. Interestingly, by a co-evolutionary process between parasite and host, two APOL1 variants emerged, which, in addition to their trypanotoxic effects, are simultaneously associated with a significantly increased risk for various different kidney diseases, which are now summarized as APOL1-mediated kidney diseases (AMKDs). The aim of this review is to highlight and formulate key aspects of APOL1’s cell biologic features, including questions and unaddressed aspects. This perspective may contribute to a deeper understanding of APOL1-associated cytotoxicity as well as AMKDs. Full article

Bovine trypanosomiasis, caused by Trypanosoma vivax, affects livestock productivity and is increasingly being reported in South America. This study aimed to detect and characterize Trypanosoma spp. infections, with a focus on T. vivax, in cattle from two distinct agroecological regions of central Argentina: a dairy-producing plain, located in the Espinal ecoregion, and a riparian zone, dedicated to beef production, located in the Delta and Islands of Paraná ecoregion. A total of 220 blood samples were collected from nine cattle farms and analyzed using real-time PCR, melting curve analysis, and the sequencing of 18S rRNA gene fragments. Trypanosoma vivax was detected at low prevalence (2.73%), exclusively in dairy cattle. In contrast, the prevalence of Trypanosoma theileri was much higher (10.91%), and it was found mainly in beef cattle from the riparian region. Phylogenetic analyses confirmed the species identity in all sequenced samples. No trypanosomes were observed by microscopy, and none of the animals showed clinical signs. The results indicate a differential distribution of T. vivax and T. theileri between regions and production systems. Although the study initially focused on T. vivax, the detection of T. theileri highlights the need to consider multiple Trypanosoma species in epidemiological surveys. This study contributes new data on the occurrence of bovine trypanosomes in central Argentina under extensive and semi-intensive management systems. Full article

The parasites of the genus Trypanosoma have a great diversity of vertebrate hosts and can be transmitted by several groups of invertebrates. All rodent and marsupial species are potential hosts of different trypanosome species. Most species descriptions of trypanosomes have been based only on morphological characteristics. In this study, we conducted a survey on trypanosome infection in small mammals that were caught in an area of the Brazilian Pantanal (Wetlands) and Cerrado (Savanna) biomes in the state of Mato Grosso. The trypanosomes isolated were included in phylogenetic studies based on the SSUrDNA and gGAPDH genes, which were complemented through morphological studies based on scanning and transmission electron microscopy. The morphological and biological discontinuities, along with the phylogenetic position, made it possible to describe four new species of trypanosome hosted by marsupials and rodents, which we described and named as Trypanosoma daniloi sp. nov., Trypanosoma favoritoae sp. nov., Trypanosoma percequilloi sp. nov., and Trypanosoma trefauti sp. nov. Full article

Background: Human African trypanosomiasis (HAT), caused by Trypanosoma brucei, is a neglected tropical disease with limited treatments, highlighting the pressing need for new drugs. Cell division cycle-2-related kinase 12 (CRK12), a pivotal protein involved in the cell cycle regulation of T. brucei, has emerged as a promising therapeutic target for HAT, yet effective CRK12 inhibitors remain lacking. Methods: An integrated strategy combining computational modeling, virtual screening, molecular dynamics (MD) simulations, and experimental validation was adopted to discover potential inhibitors against CRK12. By using the predicted and refined 3D structure of CRK12 from AlphaFold2 and MD simulation, over 1.5 million compounds were screened based on multiple-scale molecular docking, and 26 compounds were selected for evaluation of biological activity based on anti-T. brucei bioassays. Dose–response curves were generated for the most potent inhibitors, and the interaction mechanism between the top four compounds and CRK12 was explored by MD simulations and MM/GBSA binding free energy analysis. Results: Of the 26 compounds, six compounds demonstrated sub-micromolar to low-micromolar IC₅₀ values (0.85–3.50 µM). The top four hits, F733-0072, F733-0407, L368-0556, and L439-0038, exhibited IC₅₀ values of 1.11, 1.97, 0.85, and 1.66 µM, respectively. Binding free energy and energy decomposition analyses identified ILE335, VAL343, PHE430, ALA433, and LEU482 as hotspot residues for compound binding. Hydrogen bonding analysis demonstrated that these compounds can form stable hydrogen bonds with the hinge residue ALA433, ensuring their stable binding within the active site. Conclusions: This study establishes a robust and cost-effective pipeline for CRK12 inhibitor discovery, identifying several novel inhibitors demonstrating promising anti-HAT activity. The newly discovered scaffolds exhibit structural diversity distinct from known CRK12 inhibitors, providing valuable lead compounds for anti-trypanosomal drug development. Full article

Passerine birds (n = 3335) of 19 species were caught and investigated for the presence of Trypanosomatidae and Onchocercidae parasites using the buffy coat method, microscopy and PCR in Ventės Ragas, Lithuania. Data on the spread patterns of these parasites are still lacking. The prevalences of Trypanosoma parasites in birds of different species varied from 2.2% to 36.1%, while the prevalences of Onchocercidae parasites varied from 0% to 17.3%. Statistically significant differences between spring and autumn in the prevalences of Trypanosomatidae were determined for Acrocephalus schoenobaenus, Hirundo rustica and Turdus philomelos. No significant differences between the prevalences of Onchocercidae in spring and autumn were determined. The prevalence of Trypanosoma was significantly higher for long-distance migrant birds compared with short-distance migrants, for omnivorous birds compared with insectivorous birds, and for open-nesting birds compared with birds nesting in nest boxes. The prevalences of Onchocercidae parasites did not differ for the same bird groups except for the prevalence in omnivorous birds, which was higher compared with insectivorous birds. Both groups of parasites were detected in juveniles, showing the presence of transmission in the study area. The diet, breeding behaviour and migration features of avian hosts can influence the prevalence of avian blood parasites. Full article

Parasitic diseases pose a serious threat to the health of humans and the steady development of livestock husbandry. Although there are certain drug-based treatment methods, with the widespread application of drugs, various parasites are gradually developing drug resistance. Natural products are highly favored by researchers due to their characteristics such as low toxicity, multi-target effects, and low risk of drug resistance. The ocean, as the largest treasure trove of biological resources on Earth, has a special ecosystem (high pressure, high salt, and low oxygen). This enables marine organisms to develop a large number of unique structures during their survival competition. So far, a variety of compounds, such as terpenoids, have been isolated from the algae. As potential drugs, these compounds have certain curative effects on various diseases, including tumors, parasitic diseases, Alzheimer’s disease, and tuberculosis. This paper systematically reviews and analyzes the current advances in research on the antiparasite effects of seaweed extracts. The primary objective of this research is to formulate a conceptual foundation for marine pharmaceutical exploration, focusing on the creation of innovative marine-based medicinal compounds to overcome the emerging problem of parasite resistance to conventional treatments. Full article

Trypanosomes are parasitic protozoa that cause severe diseases in humans and animals. The most important species of Trypanosmes include Trypanosoma evansi and Trypanosoma brucei gambiense. The most well-known human diseases are sleeping sickness in Africa and Chagas disease in South America. The most identified animal diseases include Nagana in the African tsetse fly belt and Surra in South Asia, North Africa, and the Middle East. Surra is caused by Trypanosoma evansi. Diminazene resistance is an emerging threat caused by T. evansi infecting animals. The underlying mechanism of diminazene resistance is poorly understood. Trypanosoma brucei gambiense causes African sleeping sickness. The development of diminazene resistance in Trypanosoma brucei gambiense is associated with the alterations in the corresponding P2 adenosine transporter-1 (AT-1) gene. In the present study, by extrapolating the findings from Trypanosoma brucei gambiense, we analyzed genetic diversity in the P2 adenosine transporter-1 gene (AT-1) from T. evansi to explore a potential link between the presence of mutations in this locus and diminazene treatment in ruminants. We examined T. evansi-infected blood samples collected from goats, sheep, camels, buffalo, and cattle in seven known endemic regions of the Punjab province of Pakistan. Heterozygosity (H_e) indices indicated a high level of genetic diversity between seven T. evansi field isolates that had resistance-type mutations at codons 178E/S, 239Y/A/E, and 286S/H/I/D/T of the P2 adenosine transporter-1 (AT-1) locus. A low level of genetic diversity was observed in 19 T. evansi field isolates with susceptible-type mutations at codons A178, G181, D239, and N286 of the P2 adenosine transporter-1 (AT-1) locus. Our results on T. evansi warrant further functional studies to explore the relationship between diminazene resistance and the mutations in AT-1. 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

Bats and rodents serve as reservoirs for numerous zoonotic pathogens, including species of Trypanosoma and Leishmania. Domestic rats host the flea-transmitted Trypanosoma (Herpetosoma) lewisi, which can be associated with humans, particularly young or immunocompromised individuals. Using Fluorescent Fragment Length Barcoding (FFLB) and phylogenetic analyses based on SSU rRNA sequences, we identified two Herpetosoma species, T. lewisi-like and T. musculi-like species, in bats of different families inhabiting rooftops and peridomestic structures in Brazil (44%, 107 bats examined) and Venezuela (50%, 52 bats examined). These species are typically associated with Rattus spp. (domestic rats) and Mus musculus (house mice), respectively. Furthermore, bats were co-infected with up to five other species, including Trypanosoma dionisii, Trypanosoma cruzi marinkellei, and isolates from the Trypanosoma Neobat clade, all strongly associated with bats, and Trypanosoma cruzi and Trypanosoma rangeli, known to infect various mammals, including humans. Therefore, our findings expand the known host range of Herpetosoma to bats, marking the first report of potential spillover of Herpetosoma trypanosomes from rodents to bats and underscoring the potential for the cross-species transmission of flea-borne trypanosomes. These results highlight the need for a One Health approach to assess infection risks associated with trypanosome spillover from synanthropic rodents and bats to humans. Full article

Animal trypanosomiasis, such as nagana, surra, and dourine, represent a significant challenge to animal health and economic development, especially in tropical and subtropical regions where livestock production is an essential component of a country’s economy. Despite advances in the control of human trypanosomiasis, animal diseases caused by several species of trypanosomes remain neglected. The lack of funding for the development of new treatments and vaccines contributes to sustaining the severe economic impacts these diseases have on the farming industry, especially in low-income rural areas. Recent advances in the understanding of the immune processes involved during infection have been essential for the development of new approaches towards disease control including vaccines. These new approaches must be part of integrated control programs, which must also include vector management and the awareness of good veterinary practices. Addressing the challenges posed by the control of animal trypanosomiasis requires collaborative and continuous efforts shared among scientists, governments, and the farming industry, if significant progress is to be made to mitigate the impact of these diseases. In this literature review, we discuss the main challenges for the development of vaccines for animal trypanosomiasis and the research underway, including the prospects for employing new vaccine platforms, such as an mRNA vaccine, vector-based vaccine, and CRISPR-attenuated parasite vaccine. Full article

The hemoflagellate parasite Trypanosoma rangeli is transmitted by triatomine kissing bugs and may co-infect humans together with its Chagas disease-causing congener T. cruzi. Using real-time quantitative polymerase chain reaction (RT-qPCR) and antimicrobial assays, we studied (i) the temporal and spatial distribution of T. rangeli in common bed bugs, Cimex lectularius, following oral ingestion and hemocoelic injection of T. rangeli, and (ii) the immune responses of bed bugs induced by T. rangeli infections. Irrespective of infection mode, no live T. rangeli were present in the bed bugs’ hemolymph, salivary glands, or feces. On day 1 following infection, the bed bugs strongly upregulated the antimicrobial peptide CL-defensin. Following hemocoelic injection of T. rangeli, live parasites were absent in any bed bug tissues examined throughout the 10-day study period. The ingestion of T. rangeli-infected blood had no significant effect on bed bug survival. Our findings indicate that bed bugs disable the development of T. rangeli within their body, in stark contrast to triatomine kissing bugs, which allow the development and transmission of T. rangeli. Our findings help unravel the intricate relationships between bed bugs and trypanosomes, and they contribute to our understanding of vector biology. Full article

Salinomycin and its derivatives display promising anti-proliferating activity against bloodstream forms of Trypanosoma brucei. The mechanism of trypanocidal action of these compounds is due to their ionophoretic activity inducing an influx of sodium cations followed by osmotic water uptake, leading to massive swelling of bloodstream-form trypanosomes. Generally, higher trypanocidal activities of salinomycin derivatives are associated with higher cell swelling activities. Although ironomycin (C20-propargylamine derivative of salinomycin) and salinomycin showed identical cell swelling activities, ironomycin was 6 times more trypanocidal than salinomycin, and the 50% growth inhibition (GI₅₀) values were 0.034 μM and 0.20 μM, respectively. However, when bloodstream-form trypanosomes were incubated with ironomycin in the presence of vitamin E and ammonium ferric citrate, the trypanocidal activity of the compound was reduced to that of salinomycin (GI₅₀ = 0.21 μM vs. GI₅₀ = 0.20 μM). In addition, vitamin E was found to decrease the trypanocidal activity of ironomycin much more than ammonium ferric citrate (GI₅₀ = 0.18 μM vs. GI₅₀ = 0.042 μM). Moreover, ironomycin caused a reduction in the uptake of the iron-carrier protein transferrin mediated by a downregulation of the transferrin receptor and led to the accumulation and sequestering of iron(II) in the parasite’s lysosome, triggering an increase production of reactive oxygen species (ROS). These results suggest that the increased trypanocidal activity of ironomycin can be mainly attributed to an increased ROS production and, to a lesser extent, an impairment in iron uptake. Full article

Apolipoprotein-L1 (APOL1) is a membrane-interacting protein induced by inflammation, which confers human resistance to infection by African trypanosomes. APOL1 kills Trypanosoma brucei through induction of apoptotic-like parasite death, but two T. brucei clones acquired resistance to APOL1, allowing them to cause sleeping sickness. An APOL1 C-terminal sequence alteration, such as occurs in natural West African variants G1 and G2, restored human resistance to these clones. However, APOL1 unfolding induced by G1 or G2 mutations enhances protein hydrophobicity, resulting in kidney podocyte dysfunctions affecting renal filtration. The mechanism involved in these dysfunctions is debated. The ability of APOL1 to generate ion pores in trypanosome intracellular membranes or in synthetic membranes was provided as an explanation. However, transmembrane insertion of APOL1 strictly depends on acidic conditions, and podocyte cytopathology mainly results from secreted APOL1 activity on the plasma membrane, which occurs under non-acidic conditions. In this review, I argue that besides inactivation of APOL3 functions in membrane dynamics (fission and fusion), APOL1 variants induce inflammation-linked podocyte toxicity not through pore formation, but through plasma membrane disturbance resulting from increased interaction with cholesterol, which enhances cation channels activity. A natural mutation in the membrane-interacting domain (N264K) abrogates variant APOL1 toxicity at the expense of slightly increased sensitivity to trypanosomes, further illustrating the continuous mutual adaptation between host and parasite. Full article