Search Results (452)

Background: Balamuthia mandrillaris is a free-living amoebic parasite that primarily causes rare opportunistic infections in immunocompromised hosts. Balamuthia amoebic encephalitis (BAE) is a rare yet severe parasitic infection affecting the central nervous system. It has an extremely low incidence in China but can have a mortality rate as high as 98%. The clinical manifestations of amebic infections are similar to those of bacterial and tuberculous meningitis, lacking specificity, which makes accurate diagnosis challenging in the clinical setting. Case Presentation: A 61-year-old immunocompetent woman experienced worsening headache and a moderate fever over the course of five days, initially treated as a common cold. On 25 February 2025, she exhibited behavioral abnormalities, dysphagia, and a high fever of 40.2 °C, which progressed to a coma. On 26 February, her cranial CT scan revealed multifocal hemorrhagic lesions in the right frontotemporoparietal lobes. The MRI revealed similar lesions with slight enhancement and herniation. She underwent an emergency decompressive craniectomy, yet her condition continued to deteriorate following the surgery. On 27 February, serum targeted next-generation sequencing (tNGS) detected B. mandrillaris. Additionally, metagenomic NGS (mNGS) of the cerebrospinal fluid (CSF) sample confirmed the presence on 28 February. Finally, B. mandrillaris was identified through a brain tissue biopsy on 3 March. However, due to the delayed diagnosis and lack of effective drugs, her condition rapidly deteriorated and became irreversible. Her family ultimately chose to withdraw treatment. Conclusions: This study highlights the application of NGS for early diagnosis of patients with severe CNS infection. Both tNGS and mNGS can be considered for the rapid detection of rare or novel pathogens and for facilitating diagnosis. Full article

Didelphis aurita is a widely distributed neotropical marsupial frequently found in peri-urban environments and known to harbor various pathogens, including hemoparasites of the genus Hepatozoon. However, the systemic physiological responses of naturally infected individuals remain poorly understood. This study aimed to characterize the serum proteomic profile of Didelphis aurita naturally infected with Hepatozoon sp., providing insights into host–parasite interactions and potential biomarkers of infection. Serum samples were analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS), followed by functional annotation based on Gene Ontology and KEGG pathway enrichment. A total of 67 proteins were identified, 33 of which were exclusive to infected animals. The most abundant proteins included albumin, hemoglobin subunits, and venom metalloproteinase inhibitors (DM43 and DM64). Functional enrichment revealed significant involvement in complement and coagulation cascades, protease inhibition, antioxidant defense, and extracellular vesicle localization. Key proteins such as fibrinogen, plasminogen, antithrombin, SERPIN family members, vitronectin, and fibronectin suggest an integrated host response involving hemostasis, inflammation control, and tissue remodeling. This is the first report of the serum proteome of Didelphis aurita naturally infected with Hepatozoon sp. Despite the absence of protein validation, the findings provide novel insights into marsupial immunophysiology and offer a foundation for future biomarker research and ecoimmunological surveillance in synanthropic species. Full article

We aimed to assess the seroprevalence of anti-Neospora caninum and anti-Toxoplasma gondii antibodies in cattle intended for human consumption in Paraíba, Brazil, and the associated risk factors. A total of 110 serum samples from slaughtered cattle were analyzed using the Indirect Fluorescence Antibody Test (IFAT), with cut-off points of 1:200 for N. caninum and 1:64 for T. gondii. Seroprevalence was 8.2% (9/110) for N. caninum (titers 1:200–1:6400) and 18.2% (20/110) for T. gondii (titers 1:64–1:512). Risk factor analysis revealed that the variable female sex (cows) and the extensive farming system were statistically significantly associated with seroprevalence for N. caninum. Whereas for T. gondii, extensive farming, frequent animal purchase, and the lack of separation between calves and adult cattle were statistically significant. These findings demonstrate the circulation of these parasites in herds, with implications for animal and public health, indicating a potential risk of transmission to definitive hosts and humans through the consumption of raw or undercooked infected meat. 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

The actin cytoskeleton plays a crucial role in fundamental eukaryotic processes such as morphogenesis, motility, endocytosis, intracellular trafficking, and cell division. However, our understanding of actin and its associated proteins in trypanosomatid parasites like Leishmania remains limited. Over the past two decades, considerable progress has been made in elucidating the structure and functions of Leishmania actin and its core regulators. Notably, these findings are primarily derived from studies of the insect-stage promastigote form, while the roles of the actin machinery during the disease-causing amastigote stage within mammalian hosts remain largely unexplored. This review consolidates the current knowledge of actin and its interactors in Leishmania promastigotes, highlighting their potential roles in parasite development and stage-specific differentiation. Additionally, it explores the potential of targeting the cytoskeletal system as a strategy for novel therapeutic interventions against Leishmaniasis. The review concludes by identifying critical knowledge gaps and proposing future research directions to better understand actin-driven pathogenesis in this important human parasite. Full article

Toxoplasma gondii is a widely distributed intracellular parasite that disrupts host immune and metabolic homeostasis. Although accumulating evidence highlights the role of gut microbiota in parasitic infections, the effects of acute T. gondii infection on host gut microbial ecology remain poorly understood. In this study, metagenomic sequencing technology was used to systematically analyze the composition and functional alterations of the ileal microbiota in BALB/c mice on day 10 post-infection. Compared to uninfected controls, T. gondii infected mice exhibited a significant reduction in microbial diversity and a pronounced shift in community structure. Notably, there was an expansion of Proteobacteria, particularly the Enterobacteriaceae family, alongside a marked decline in beneficial taxa such as Actinobacteria and Bacillota. Functional annotation using the KEGG and CAZy databases revealed enrichment of metabolic pathways related to glycolysis/gluconeogenesis, O-antigen nucleotide sugar biosynthesis, bacterial secretion systems, and biofilm formation-Escherichia coli in the infected microbiota. These findings provide novel insights into the dysbiosis of gut microbiota and host-microbe interactions during acute T. gondii infection. Full article

The zoonotic disease fasciolosis poses a significant global threat to both humans and livestock. The causative agent of fasciolosis is Fasciola hepatica, which is commonly referred to as liver fluke. The emergence of drug resistance has underscored the urgent need for new therapeutic treatments against F. hepatica. The tegument surface of F. hepatica is characterized by a dynamic syncytial layer surrounded by a glycocalyx, which serves as a crucial interface in host–parasite interactions, facilitating functions such as nutrient absorption, sensory input, and defense against the host immune response. Despite its pivotal role, only recently have we delved deeper into understanding glycans at the host–parasite interface and the glycosylation of hidden antigens. These glycan antigens have shown promise for vaccine development or as targets for drug manipulation across various pathogenic species. This review aims to consolidate current knowledge on the glycosylation of F. hepatica, exploring glycan motifs identified through generic lectin probing and mass spectrometry. Additionally, it examines the interaction of glycoconjugates with lectins from the innate immune systems of both ruminant and human host species. An enhanced understanding of glycans’ role in F. hepatica biology and their critical involvement in host–parasite interactions will be instrumental in developing novel strategies to combat these parasites effectively. In the future, a more comprehensive approach may be adopted in selecting and designing potential vaccine targets, integrating insights from glycosylation studies to improve efficacy. Full article

Background/Objectives: Leishmania spp. are protozoan parasites transmitted by female sandflies (Phlebotomus or Lutzomyia). Clinical manifestations depend on species and host immunity. While cutaneous and visceral forms prevail, mucocutaneous involvement—particularly isolated nasal septum leishmaniasis—is rare and frequently misdiagnosed as an inflammatory, infectious, or neoplastic condition. Risk factors associated with mucocutaneous leishmaniasis include systemic or local immunodeficiency, prior renal transplantation, treatment with chronic inhaled steroids, residence in endemic areas or travel to such regions, and previous Leishmania infections. Immunosuppressed patients are at higher risk for atypical presentations and delayed diagnosis, which can result in extensive tissue destruction. Early clinical suspicion, histopathological confirmation, and prompt therapy are essential to prevent permanent mucosal damage. Therefore, a multidisciplinary approach is needed for adequate evaluation and effective treatment. Methods: A 67-year-old man with rheumatoid arthritis on methotrexate reported a two-year history of right-sided nasal obstruction and ulceration that failed to respond to antibiotics. He did not present systemic symptoms. Results: Facial CT revealed a septal deviation; the patient underwent septoplasty, and biopsy confirmed Leishmania amastigotes. Serology (rK39 immunochromatographic test) was positive. He was treated with liposomal amphotericin B at 4 mg/kg/day for five days, followed by miltefosine at 100 mg/day orally for 14 days. At an eight-week follow-up, the nasal mucosa was fully healed, obstruction was resolved, and there was no evidence of recurrence. Conclusions: Although nasal septum leishmaniasis is uncommon, it should be considered in the differential diagnosis of chronic nasal lesions, especially in immunocompromised patients or those from endemic regions. Definitive diagnosis requires biopsy with histological or molecular confirmation. Combined liposomal amphotericin B and miltefosine therapy yields high cure rates and prevents mucosal destruction. Early recognition is critical to avoid diagnostic delays and long-term sequelae. Full article

Parasitic infections, such as those caused by the myxozoans Myxobolus cerebralis and Tetracapsuloides bryosalmonae, pose major threats to wild and farmed salmonids due to severe tissue damage and impairment of the host immune system. While individual infections have been studied, limited information is available on the host response during co-infection. This study investigated the transcriptomic immune response of rainbow trout (Oncorhynchus mykiss) during single and sequential co-infections with M. cerebralis and T. bryosalmonae using RNA-seq. Trout were exposed to single infections (Mc or Tb) followed by co-infections (Mc⁺ or Tb⁺). Fish were sampled at 31 days post-single infection (1 day post-co-infection). RNA from gill and caudal fin (portal of parasite entry) was sequenced, followed by differentially expressed genes (DEGs) identification and GO and KEGG enrichment. In the caudal fin, Mc⁺ (1 day after co-infection with T. bryosalomne) fish showed mild immune activation with C4B upregulation, while Tb⁺ fish exhibited a stronger response involving IFI44, ISG15, RSAD2, and TLR7 signaling. In gills, Mc⁺ fish showed moderate cytokine-related gene upregulation, while Tb⁺ (1 day after co-infection with M. cerebralis) fish displayed increased expression of humoral response genes (C3, immunoglobulin pathways) but suppression of genes involved in B cell development. These results indicate that the order of infection shapes the outcome of the host immune response, offering candidate targets at the host–pathogen interface. Full article

Tuberculosis and parasitic infections, including Toxocara, frequently coexist in many regions worldwide, yet their interaction remains poorly understood. Tuberculosis triggers a type 1 immune response characterized by IL-12, IFN-γ, and TNF-α production, while toxocariasis elicits a type 2 response, mediated by cytokines such as IL-4, IL-5, IL-13, and IL-33. The coexistence of these divergent immune pathways can disrupt immune regulation and impair the host’s ability to control both infections, potentially leading to persistent hypereosinophilia. We illustrate this complex interplay through a real-world case involving a heavy smoker in whom Toxocara infection likely reactivated latent tuberculosis, resulting in severe, unexplained hypereosinophilia and late-onset asthma with recurrent exacerbations. After excluding other causes and completing full antituberculosis therapy along with three courses of antiparasitic treatment and systemic corticosteroids, hypereosinophilia persisted. The introduction of benralizumab, a biologic therapy targeting IL-5Rα, led to a rapid reduction in eosinophils to normal ranges and significant clinical improvement. This case underscores the diagnostic and therapeutic challenges posed by the intersection of common infections and highlights that even a neglected parasitic infection such as toxocariasis can underlie severe respiratory complications with eosinophilia, where paradoxically biologic therapy may ultimately provide a very effective intervention. Full article

Toxoplasma gondii is responsible for the disease toxoplasmosis and has the broadest host range among apicomplexan parasites, as it infects virtually all warm-blooded vertebrates. Toxoplasmosis is a zoonotic and emerging public health concern with considerable morbidity and mortality, especially in the developing world, affecting approximately one-third of the world’s human population. Clinical presentation varies among species, and the infection establishes lifelong chronicity in hosts. Most of the host species (including healthy humans) are asymptomatic on the one hand, it is fatal to marsupials, neotropical primates and some marine mammals on the other hand. In immunocompetent humans, infection is typically asymptomatic, whereas immunocompromised individuals may develop disseminated disease affecting virtually any organ system—most commonly reproductive, cerebral, and ocular systems. Toxoplasmosis spreads by ingestion of food or water contaminated with T. gondii oocysts, consumption of undercooked/raw meat containing tissue cysts, transplacental transmission from mother to fetus, or by receiving infected organ/blood from the infected individual. Toxoplasmosis is mainly diagnosed by serologic tests and polymerase chain reaction (PCR). It is treated with pyrimethamine combined with sulfadiazine or clindamycin, often supplemented with leucovorin, atovaquone, and dexamethasone. Despite having many potent anti-T. gondii antigenic candidates, there is no commercially available vaccine for humans due to many factors, including the complex life cycle of the parasite and its evasion strategies. To date, the only commercially available anti-T. gondii vaccine is for sheep, licensed for veterinary use to prevent ovine abortions. In this review, we have summarized the current understanding of toxoplasmosis. Full article

This study characterizes Phoradendron nervosum, a hemiparasitic mistletoe species prevalent in Ecuador, using morphological, molecular, and ecological modeling approaches. Morphological analysis revealed that P. nervosum possesses green-yellowish cylindrical stems, lanceolate leaves with entire margins, and berry-like fruits with mucilaginous pulp. DNA sequencing of the internal transcribed spacer (ITS) region confirmed a 99.43% identity with P. nervosum (GenBank: AH009776.2), supporting the taxonomic classification. A maximum entropy (MaxEnt version 3.4.4) model was developed using 36 occurrence points and 19 bioclimatic variables to assess potential distribution across the Tumbaco region in Ecuador. Key environmental factors influencing the species’ distribution were precipitation during the warmest quarter (BIO_18), temperature seasonality (BIO_4), and mean diurnal temperature range (BIO_2). The model showed good predictive performance (AUC = 0.736), identifying areas with high suitability for P. nervosum, particularly in habitats with adequate water availability and thermal stability. Findings suggest that this mistletoe parasitizes both native and exotic tree species, potentially impacting biodiversity and forest health. This research provides a baseline for monitoring mistletoe spread under climate change scenarios and emphasizes the need for management strategies in agroforestry systems where host trees are vulnerable. Full article

One of the most concerning ruminant infections is the parasite Ostertagia ostertagi. Known commonly as the brown stomach worm, it is ingested by grazing cattle where it then progresses its life stages, occupying the host abomasum and then the intestine, causing illness. This results in lower commercial production and at worst, death of young calves. Over time, anthelmintic treatment has become less efficacious against cattle nematodes. As a result, alternative control strategies are needed. Our study looked to elucidate mechanisms underlying attenuation of the host immune response by examining global immune expression in cattle during infection. To this end, four steers were infected with the third stage larvae (L3) of O. ostertagi, then peripheral blood mononuclear cells (PBMCs) were collected weekly for 26 days post-infection (dpi). After sequencing, gene expression was compared between each timepoint. The analyses indicated that the immune responses to Ostertagia are targeted to the parasite’s life stages and mimics anti-viral gene expression. Overall, the results showed that O. ostertagi led to host immune responses characterized by multiple gene ontology and pathway terms indicating that by 26 dpi the host immune system transitions from fighting the parasite to repairing the host intestine. Full article

Leishmaniases are neglected tropical diseases caused by protozoan parasites of the Leishmania genus, with a significant global health burden, particularly in low-income regions. The parasites rely on a unique thiol-based redox system centered on trypanothione, which is essential for survival under oxidative stress encountered during their life cycle in both insect vectors and mammalian hosts. Given the absence of mammalian analogs, the trypanothione system represents an attractive target for antileishmanial drug development. However, accurate quantification of the reduced and oxidized forms of trypanothione has been challenging due to its instability and structural similarity between redox states. Here, we developed and validated a rapid, sensitive liquid chromatography–mass spectrometry (LC-MS) method for assessing the trypanothione redox state in Leishmania infantum. By incorporating N-ethylmaleimide as a thiol-blocking agent during sample preparation, the native redox state was preserved, enabling precise measurement of the reduced-to-oxidized ratio. Our approach demonstrated high sensitivity (nanomolar range), a rapid analysis time (5 min/sample), and robustness across various conditions. Moreover, we validated the method’s relevance in detecting oxidative stress and response to the trypanothione reductase inhibitor auranofin. This LC-MS technique provides a valuable tool for exploring Leishmania redox biology and supports the discovery of redox-targeting therapies against leishmaniasis. Full article

Plasmodium parasites rely on host iron for survival and replication, making host iron availability a critical determinant of malaria pathogenesis. Central to iron homeostasis is the hepcidin–ferroportin regulatory axis, where hepcidin suppresses iron export by inducing ferroportin degradation, thus modulating systemic and cellular iron availability. In the Plasmodium infection model (P. yoelii), we observed a significant downregulation of hepatic hepcidin expression, accompanied by an increase in hepatic ferroportin expression. On the contrary, RBC-ferroportin protein level was notably suppressed upon P. yoelii infection. Given these findings, we aim to investigate the role of a ferroportin inhibitor in Plasmodium infection. In a P. yoelii mouse model, treatment with an oral ferroportin inhibitor, VIT-2763 (Vamifeport) increased parasitemia, accompanied by increased levels of pro-inflammatory cytokines, erythropoietin, and liver injury markers. In P. yoelii infected mice, VIT-2763 treatment suppressed hepcidin expression and increased ferroportin expression in hepatocytes, while reducing ferroportin protein levels in RBCs. VIT-2763 mediated exacerbation of P. yoelii infection reveals the tissue-specific regulation of ferroportin in hepatocytes and RBCs, underscoring the therapeutic potential of modulating the hepcidin–ferroportin axis as an intervention strategy in malaria. Full article