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Toxoplasmosis is a disease of worldwide distribution, causing high morbidity and mortality in humans, as well as heavily impacting animal health and the economy. Toxoplasma gondii, the causative agent, is an intracellular parasite with a complex life cycle whose completion entails asexual, pre-sexual, and sexual stage conversions. Pre-sexual and sexual differentiation take place only within the intestinal epithelium of felines. Recently, several transcriptional factors and epigenetic components crucial to trigger parasite stage transitions within the cat have been identified, allowing, through precise genetic manipulation, obtaining pre-sexual stages known as merozoites in vitro. Through conditional depletion of two pre-sexual stage-specific gene silencing transcription factors, AP2XII-1 and AP2XII-2, we have characterized the interplay between cell division and the sequence of events leading up to differentiation of tachyzoites into merozoites. We explored genome duplication, assembly of daughter cells, karyokinesis, and cytokinesis, characterizing the differential cell division modes and kinetics undergone by critical structures along the differentiation axis. Building onto the pre-existing body of knowledge, primarily describing the underpinnings of these forms of division by transmission electron microscopy, our work contributes previously unexplored temporal and spatial resolution to the transitions between endodyogeny and endopolygeny, providing a conceptual framework for understanding and exploring T. gondii’s route of sexual differentiation.IMPORTANCESexual development in Toxoplasma gondii is essential for transmission, but remains poorly understood, largely because pre-sexual stages are restricted to the feline intestine and have only recently become experimentally accessible. Here, we leverage an in vitro differentiation system to resolve how parasites transition toward merozoite formation at the cellular level. By combining expansion microscopy, stage-specific markers, and quantitative analyses, we define the temporal sequence of nuclear division and daughter cell assembly during merogony, addressing longstanding ambiguity regarding division modes in these stages. Our findings reveal that parasites can adopt alternative division strategies emerging from a polyploid intermediate, highlighting an unexpected degree of flexibility in how cell division is executed during differentiation. Beyond refining this developmental framework, this work establishes a foundation for future mechanistic studies of pre-sexual biology and provides broader insight into the diversity of eukaryotic cell division strategies.

The lytic cycle of Toxoplasma gondii is critical for parasite dissemination and disease progression in the host. Calcium signaling plays a crucial role in driving these processes; however, the molecules that control calcium storage and release remain poorly understood. The endoplasmic reticulum, likely the largest calcium reservoir in T. gondii , has been understudied in the context of calcium signaling. Here, we uncover a direct link between ER redox regulation and calcium homeostasis, showing that ER redox activity can influence calcium signaling events that govern microneme protein maturation and secretion, parasite invasion, and replication. Our findings indicate that redox-dependent calcium regulation in the ER contributes to control of the parasite lytic cycle and reveals a previously unrecognized mechanism that may influence parasite virulence.

Toxoplasma gondii is an obligate parasite whose infection can be detrimental when combined with pregnancy or immunodeficiency. Studies on T. gondii virulence have revealed various secretory proteins that inhibit the host interferon-gamma (IFN-γ) immune response. However, much of the broader virulence landscape remains unclear. To explore the unknown molecular pathways of T. gondii virulence in mice, we searched for immunosuppressive functions in genes encoding non-secretory proteins, associated with fundamental cellular processes of the virulent type I strain. Here, we found that TgJosephin, a highly conserved deubiquitinase, was important for virulence in wild-type mice but not mice lacking the IFN-γ receptor (IFNγR). In addition, TgJosephin expression was dependent on TgRad23, and loss of TgJosephin led to increased ubiquitination of a microtubule protein SPM1. Our results suggest a novel anti-IFN-γ pathway of T. gondii mediated by TgJosephin and SPM1 deubiquitination.

Onchocerca lupi , a zoonotic parasite, causes ocular onchocerciasis in both domestic and wild carnivores, as well as humans. Despite recent scientific advances, gaps remain in both the biology and genetic structure of this parasite. To date, two genotypes have been described (genotype 1 distributed in Europe, Asia, and the United States, and genotype 2 circulating in the Iberian Peninsula) based on mitochondrial gene analysis. This study provided three distinct genomes (nuclear, mitochondrial, and Wolbachia endosymbiont) of O. lupi isolated from a dog living in Portugal. Overall, the data presented here corroborate the divergence between the two genotypes and provide new insights into the identification of genes that could serve as novel therapeutic targets for this filarial disease.

Human sparganosis is a rare but important food borne zoonosis and could be attributed to increased consumption of raw meat of fish, frogs, snakes etc. Sparganosis may involve varied organ systems but subcutaneous sparganosis remains the one of the commonly reported clinical condition. Rarity of this problem reinforces the necessity of sensitising the treating physicians of the differential possibility of this infection in patients with history of practice of consuming raw meat. Expansion of health communication and provision of safe food and water by the civic agencies can be a part of powerful preventive strategies.

Vector‐borne diseases represent about 17% of all infectious diseases worldwide and they greatly impact on human and animal health. The impact of vector‐borne diseases is largely influenced by the worldwide distribution of blood‐feeding arthropod vectors which transmit pathogens via typical anthro‐ponotic (from human to human) or zoonotic (from animals to humans, and vice versa) cycles. This chapter discusses current knowledge on Vector‐Borne Parasitic Zoonotic Infections (VBPZs) (protozoa and helminths transmitted by arthropod vectors from animals to humans), their epidemiology, and impact on human health. Although VBPZs represent a relatively small number of diseases if compared to those caused by viral and bacterial agents, their distribution is increasing in many parts of the world. Proteomic and genomic projects have refined methods for pathogen detection, control, and prevention by improving the sensitivity and specificity of current diagnostic tools and by expediting the treatment in remote areas.

We report a case of severe conjunctivitis in a traveler infected with a Philophthalmus lacrymosus eye fluke, probably acquired on the Galápagos Islands in Ecuador. This zoonotic parasite is endemic in Brazil and Venezuela, where it has been reported in birds and capybaras.

Background Parasitic infections, particularly those caused by protozoa, represent a considerable public health problem in developing countries. Blastocystis , Giardia duodenalis , Cryptosporidium spp. and the Entamoeba complex ( Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii) are the most common etiological causes of intestinal parasitic infections. Methods We carried out a descriptive cross-sectional study in school-age children attending a daycare institution in commune eight of Popayán, Cauca (Southwest Colombia). A total of 266 fecal samples were collected (258 from children and eight from pets). Blastocystis , G. duodenalis , Cryptosporidium spp. and the Entamoeba complex were identified by microscopy, quantitative real-time PCR (qPCR) and conventional PCR. The concordance of qPCR and microscopy was assessed using the Kappa index. Molecular characterization was conducted to identify Blastocystis subtypes (18S), G. duodenalis assemblages ( tpi and gdh ) and Cryptosporidium species/subtypes (18S and GP60). Potential associations between intestinal parasitism and sociodemographic factors were examined using bivariate analyses. Results A total of 258 fecal samples from children were analyzed by microscopy and 255 samples were analyzed by qPCR. The prevalence of Blastocystis was between 25.19% (microscopy) and 39.22% (qPCR), that of G. duodenalis was between 8.14% (microscopy) and 10.59% (qPCR), that of Cryptosporidium spp. was estimated at 9.8% (qPCR), and that of the Entamoeba complex was between 0.39% (conventional PCR) and 0.78% (microscopy). The concordance between microscopy and qPCR was very low. Blastocystis ST1 (alleles 4, 8, and 80), ST2 (alleles 11, 12, and 15), ST3 (alleles 31, 34, 36, 38,57, and 151), and ST4 (alleles 42 and 91), G. duodenalis assemblages AII, BIII, BIV and D, C. parvum subtype IIa and C. hominis subtype IbA9G3R2 were identified. The only identified member of the Entamoeba complex corresponded to E. histolytica . No statistically significant association was identified between parasitic infection and any sociodemographic variable. Conclusion This study revealed the usefulness of molecular methods to depict the transmission dynamics of parasitic protozoa in southwest Colombia. The presence of some of these protozoa in domestic animals may be involved in their transmission.

Intracellular bacteria and protists rely on the host cell to supply many metabolites, but the mechanisms through which pathogens manipulate host metabolism to their benefit are not understood. Here, we demonstrate that when the obligate intracellular parasite secretes its rhoptry organelle contents into the host cytoplasm before invasion-a process called \"kiss and spit\"-host cell metabolite abundance is altered in nucleotide synthesis, the pentose phosphate pathway, glycolysis, and amino acid synthesis. U-13C6-labeling metabolomics confirmed that kiss and spit increased the flow of carbon through the pentose phosphate pathway and nucleotide synthesis. An increase in 2,3-bisphosphoglycerate abundance led us to investigate the activation of host cytosolic nucleosidase II (cN-II) to provide purines for the parasite. We found that manipulates the host cN-II enzyme to dephosphorylate GMP and IMP that it needs for replication. Furthermore, we found that the approved anti-cancer drug fludarabine, which inhibits cN-II, also inhibits replication. These results reveal host cell manipulation and highlight potential therapies for toxoplasmosis.IMPORTANCEA fundamental challenge in parasitology is understanding how intracellular parasites rapidly reprogram host metabolism to support replication. This study reveals that initiates profound metabolic reprogramming through a \"kiss-and-spit\" mechanism, secreting effector molecules without invasion. We demonstrate that specifically hijacks host cytosolic 5'-nucleotidase II (cN-II) by elevating 2,3-bisphosphoglycerate levels, which allosterically activates this enzyme to generate purines essential for parasite survival. Genetic deletion of host cN-II significantly impairs parasite replication, establishing cN-II as a critical host dependency factor. These findings have important implications for antiparasitic drug development while advancing our understanding of purine metabolism in apicomplexan parasites. More broadly, elucidating the molecular mechanism linking parasite effector secretion to specific host enzyme activation provides a framework for understanding metabolic manipulation across other intracellular pathogens.

Young dogs are particularly susceptible to infections with endoparasites. The occurrence of endoparasites was investigated in young dogs from Central Germany between July 2020 and July 2022. In total, 386 fecal samples originating from 171 dogs were examined for the prevalence of endoparasites using a combined flotation- and sedimentation technique and conventional PCR. Overall, in 41.2% (159/386) of the examined samples, endoparasites were detected. The most frequently occurring endoparasites were Giardia duodenalis (29%), Cryptosporidium spp. (9.1%), Cystoisospora spp. (7.3%), and Toxocara canis (6%). Sequencing of G. duodenalis positive samples showed that most infections belonged to the host-specific assemblages C (38.4% (43/112)) and D (35.7% (40/112)). The zoonotic assemblage A was identified in 8% (9/112) of the samples. Moreover, mixed infections were observed as follows: C/D in 5 (4.5%), D/A in 4 (3.6%), and C/A in 3 (2.7%) samples. All assemblage A infections were assigned to the potentially zoonotic subassemblage AI. Co-infections of G. duodenalis and Cryptosporidium spp. were observed in 3.1% (12/386) of the samples. Analyzing several host factors for their potential association with endoparasitic infection, the origin of dogs, as well as the living environment were identified as the main risk factors for infection with endoparasites. Overall, this study shows a high infection rate with endoparasites, especially G. duodenalis , in young dogs from Germany. The results of this study contribute to further insight into the distribution and potential risk factors associated with endoparasitic infections, as well as the zoonotic potential these parasites may present.