Transcriptomics of -Infected Fibroblasts Reveals Hallmarks of Early Fibrosis and Cancer Progression.

Endothelial injury, inflammatory infiltrate and fibrosis are the predominant lesions in the testis of bulls with besnoitiosis that may result in sterility. Moreover, fibroblasts, which are key players in fibrosis, are parasite target cells in a chronic infection. This study aimed to decipher the molecular basis that underlies a drift toward fibrosis during the disease progression.

A questionnaire-based survey in Spain provides relevant information to improve the control of ovine coccidiosis.

Ovine coccidiosis is a widespread intestinal parasitic disease caused by spp. Lambs are infected by the ingestion of sporulated oocysts, experiencing diarrhea and low growth rates. Control should be based on measures to reduce infection pressure and stress on the animals as well as on appropriate diagnosis and strategic treatment.

Transcriptional changes associated with apoptosis and type I IFN underlie the early interaction between Besnoitia besnoiti tachyzoites and monocyte-derived macrophages.

Besnoitia besnoiti-infected bulls may develop severe systemic clinical signs and orchitis that may ultimately cause sterility during the acute infection. Macrophages might play a relevant role in pathogenesis of the disease and the immune response raised against B. besnoiti infection.

Archetypal type II and III oocysts induce different immune responses and clinical outcomes in experimentally infected piglets.

Livestock animals, such as swine, are an important source of in the human population. Currently, there is limited knowledge regarding the potential influence that the genotype might exert on establishing infection in swine. Herein, we investigated the role of 2 isolates, type II and III, representative of the genotypes circulating in Europe, in the immune responses and infection dynamics in piglets.

Assessment of the Activity of Decoquinate and Its Quinoline--Carbamate Derivatives against In Vitro and in Pregnant Mice Infected with Oocysts.

The quinolone decoquinate (DCQ) is widely used in veterinary practice for the treatment of bacterial and parasitic infections, most notably, coccidiosis in poultry and in ruminants. We have investigated the effects of treatment of in infected human foreskin fibroblasts (HFF) with DCQ. This induced distinct alterations in the parasite mitochondrion within 24 h, which persisted even after long-term (500 nM, 52 days) treatment, although there was no parasiticidal effect.

A short-term treatment with BKI-1294 does not protect foetuses from sheep experimentally infected with Neospora caninum tachyzoites during pregnancy.

The Neospora caninum Calcium-dependent protein kinase 1 (NcCDPK1) inhibitor BKI-1294 had demonstrated excellent efficacy in a pregnant mouse model of neosporosis, and was also highly efficacious in a pregnant sheep model of toxoplasmosis. In this work, we present the efficacy of BKI-1294 treatment (dosed 5 times orally every 48 h) starting 48 h after intravenous infection of sheep with 10 Nc-Spain7 tachyzoites at mid-pregnancy. In the dams, BKI-1294 plasma concentrations were above the IC for N.

Changes in serum biomarkers of inflammation in bovine besnoitiosis.

Background: Acute and chronic besnoitiosis in extensive natural-service herds can have relevant effects in the health of bulls and negative consequences in their productive performance. Recent progress has been made in order to elucidate the pathogenesis of this disease. In this context, the study of biomarkers of inflammation in serum would contribute to gaining knowledge about the physiopathology of bovine besnoitiosis.

Identification of molecular biomarkers associated with disease progression in the testis of bulls infected with Besnoitia besnoiti.

Breeding bulls infected with Besnoitia besnoiti may develop sterility during either acute or chronic infection. The aim of this study was to investigate the molecular pathogenesis of B. besnoiti infection with prognosis value in bull sterility.

One health therapeutics: Target-Based drug development for cryptosporidiosis and other apicomplexa diseases.

This is a review of the development of bumped-kinase inhibitors (BKIs) for the therapy of One Health parasitic apicomplexan diseases. Many apicomplexan infections are shared between humans and livestock, such as cryptosporidiosis and toxoplasmosis, as well as livestock only diseases such as neosporosis. We have demonstrated proof-of-concept for BKI therapy in livestock models of cryptosporidiosis (newborn calves infected with Cryptosporidium parvum), toxoplasmosis (pregnant sheep infected with Toxoplasma gondii), and neosporosis (pregnant sheep infected with Neospora caninum).

Characterization of Fetal Brain Damage in Early Abortions of Ovine Toxoplasmosis.

There is an unacknowledged clinical presentation of ovine toxoplasmosis characterized by early abortions and lesions of fetal leukoencephalomalacia. To investigate the pathogenesis of this condition, the extent and distribution of leukomalacia and the variations in the cell populations associated with it were characterized in 32 fetal brains from 2 previously published experimental studies of infection in pregnant sheep. Immunohistochemical labeling of βAPP allowed for the detection of leukomalacia in 100/110 (91%) studied samples.

Vascular wall injury and inflammation are key pathogenic mechanisms responsible for early testicular degeneration during acute besnoitiosis in bulls.

Background: Bovine besnoitiosis, caused by the apicomplexan parasite Besnoitia besnoiti, is a chronic and debilitating cattle disease that notably impairs fertility. Acutely infected bulls may develop respiratory signs and orchitis, and sterility has been reported in chronic infections. However, the pathogenesis of acute disease and its impact on reproductive function remain unknown.

Added value of IgM detection and low avidity index as markers of acute bovine besnoitiosis.

Early in vivo diagnosis of bovine besnoitiosis is crucial for the success of control programmes. However, diagnosis in acutely infected animals is hindered by the low sensitivity of the available serological tools. In this study, a novel ELISA to detect specific anti-Besnoitia besnoiti IgM antibodies was developed.

Peripheral and placental immune responses in sheep after experimental infection with Toxoplasma gondii at the three terms of gestation.

Although it is known that gestation could influence the clinical course of ovine toxoplasmosis, the precise effect of the term of gestation when sheep are infected are yet mostly unknown. The aim of this study was to evaluate the peripheral and placental immune responses developed in pregnant sheep after experimental infection with Toxoplasma gondii at different times of gestation. Thirty-six pregnant sheep were allocated in different groups, orally inoculated with sporulated oocysts of T.

A model for chronic bovine besnoitiosis: Parasite stage and inoculation route are key factors.

In this work, an experimental model for chronic besnoitiosis in bovine was developed and characterized. Using a previously established calf model, two new variables (parasite stage and inoculation route) were combined and used. Twelve Holstein Friesian 3-month-old male calves were randomly divided into four groups of three animals each.

Treatment with Bumped Kinase Inhibitor 1294 Is Safe and Leads to Significant Protection against Abortion and Vertical Transmission in Sheep Experimentally Infected with Toxoplasma gondii during Pregnancy.

Previous studies on drug efficacy showed low protection against abortion and vertical transmission of in pregnant sheep. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites and in laboratory animal models. Here, we present the safety and efficacy of BKI-1294 treatment (dosed orally at 100 mg/kg of body weight 5 times every 48 h) initiated 48 h after oral infection of sheep at midpregnancy with 1,000 TgShSp1 oocysts.

Virulence in Mice of a Type II Isolate Does Not Correlate With the Outcome of Experimental Infection in Pregnant Sheep.

is an apicomplexan parasite that infects almost all warm-blooded animals. Little is known about how the parasite virulence in mice extrapolates to other relevant hosts. In the current study, phenotype and behavior in mice and sheep of a type II isolate (TgShSp1) were compared with the reference type II isolate (TgME49).

Treatment of Toxoplasmosis and Neosporosis in Farm Ruminants: State of Knowledge and Future Trends.

Toxoplasmosis and neosporosis are closely related protozoan diseases that lead to important economic impacts in farm ruminants. Toxoplasma gondii infection mainly causes reproductive failure in small ruminants and is a widespread zoonosis, whereas Neospora caninum infection is one of the most important causes of abortion in cattle worldwide. Vaccination has been considered the most economic measure for controlling these diseases.

Effect of parasite dose and host age on the infection with Besnoitia besnoiti tachyzoites in cattle.

Bovine besnoitiosis is continuing to spread in Europe. Therefore, the development of ruminant animal models of infection is urgently needed to evaluate therapeutic and prophylactic tools. Herein, we studied the effect of parasite dose and host age on the infection dynamics with Besnoitia besnoiti tachyzoites in cattle in two independent experimental infections.

Influence of dose and route of administration on the outcome of infection with the virulent Neospora caninum isolate Nc-Spain7 in pregnant sheep at mid-gestation.

Experimental infections in pregnant sheep have been focused on studying the effect of the time of challenge on the outcome of N. caninum infection, whereas the impact of the dose and route of challenge has not been studied in depth. Therefore, clinical outcome, immune responses, parasite detection and burden, and lesion severity in placental tissues and foetal brains were investigated in 90-day-pregnant sheep inoculated intravenously with 10 (G1), 10 (G2), 10 (G3), or 10 (G4) tachyzoites or subcutaneously with 10 (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6).

Seroprevalence of Toxoplasma gondii in Iberian pig sows.

The objective of the present study was to investigate the seroprevalence of Toxoplasma gondii infection in Iberian sows reared in extensive and intensive management conditions and to compare two serologic techniques used for diagnosis. In addition, some possible risk factors associated with the presence of serum antibodies to T. gondii were also studied.

Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites.

Neospora caninum is one of the main causes of abortion in cattle, and recent studies have highlighted its relevance as an abortifacient in small ruminants. Vaccines or drugs for the control of neosporosis are lacking. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models.

Advances in the diagnosis of bovine besnoitiosis: current options and applications for control.

Bovine besnoitiosis, which is caused by the tissue cyst-forming intracellular parasite Besnoitia besnoiti, is a chronic and debilitating disease that is responsible for severe economic losses in the cattle raised under extensive husbandry systems. The absence of vaccines, treatments or a health scheme at local, national and international levels has led to a rapid spread of bovine besnoitiosis from western Europe towards eastern countries and northwards. Moreover, this parasitic disease is widely present in many sub-Saharan countries.