Relationship between trabecular bone score, bone mineral density and vertebral fractures in patients with axial spondyloarthritis.

BACKGROUND: In patients with axial spondyloarthritis, vertebral fracture risk is elevated and not always correlated with bone mineral density (BMD). Trabecular bone score (TBS) may offer some advantages in the assessment of vertebral fracture risk in these patients. The primary objective of this study was to compare TBS and BMD between axial spondyloarthritis patients depending on their vertebral fracture status. Secondary objectives were to estimate the prevalence of morphometric vertebral fractures, and to explore factors associated with fracture, as well as the interference of syndesmophytes on BMD and TBS. METHODS: A cross-sectional study was conducted. Data were collected on demographic and clinical characteristics, lab results, imaging findings and treatment. Statistical analysis was performed using SPSS v.13 statistical software. RESULTS: Eighty-four patients (60 men and 24 women; mean age of 59 years) were included. Nearly half (47.6%) of them had lumbar syndesmophytes. The rate of morphometric fracture was 11.9%. TBS showed a higher area under the curve (0.89) than total hip, femoral neck and lumbar BMD (0.80, 0.78, and 0.70 respectively) for classifying patients regarding their fracture status. Nonetheless, the differences did not reach statistical significance. Syndesmophytes affected lumbar spine BMD (p < 0.001), but not hip BMD or TBS. Fractures were associated with TBS, total hip BMD, erythrocyte sedimentation rate and C-reactive protein levels. CONCLUSIONS: We identified decreased TBS and total hip BMD, as well as increased erythrocyte sedimentation rate and C-reactive protein levels as factors associated with morphometric vertebral fractures. Unlike lumbar spine BMD, TBS is not affected by the presence of syndesmophytes.

Chronic pithomycotoxicosis associated with obstructive rhinopathy in sheep.

Pithomycotoxicosis (facial eczema) is a seasonal hepatogenous photosensitization of sheep caused by the ingestion of sporidesmin contained in the spores of the fungus Pithomyces chartarum. We describe 4 cases of obstructive rhinopathy associated with chronic pithomycotoxicosis naturally occurring in the north of Spain. Sheep were 5 to 7 years old and Latxa breed. A detailed clinical study was conducted together with computerized tomography examination and completed by necropsy and histopathology. All sheep developed a permanent narrowing of the nasal lumen close to the nostrils causing inspiratory dyspnea and snoring. Computerized tomography demonstrated a significant increase of soft tissue in the rostral nasal cavity. Elevated gamma-glutamyl transferase, alanine aminotransferase, and lipase were noted on serum biochemistry. At necropsy, liver atrophy and fibrosis associated with chronic pithomycotoxicosis was identified in 3 of the sheep. All sheep had whitish elevations and rough surfaces on the alar folds and areas adjacent to the nasal surfaces. Histopathologic assessments, which included histochemical and immunohistochemical techniques, of the nasal lesions identified moderate to severe arteriosclerosis in 21.5% to 61.9% of the small arteries evaluated with surrounding fibrosis and edema. No changes associated with hypersensitivity reactions were found. These lesions were similar to the ones described in blood vessels of the liver in chronic pithomycotoxicosis and in our cases. The results of this study suggest a direct action of the sporidesmin on the rostral nasal cavity. Further studies are needed to analyze the impact of the sporidesmin on the sheep nasal mucosa.

Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg).

BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

Canine Leishmaniasis Control in the Context of One Health.

Dogs are the main reservoir of Leishmania infantum and in some countries have been regularly culled as part of government policy to control visceral leishmaniasis. At the 13th Symposium of the Companion Vector-Borne Diseases World Forum in Windsor, UK, March 19-22, 2018, we consolidated a consensus statement regarding the usefulness of dog culling as a means of controlling visceral leishmaniasis. The statement highlighted the futility of culling infected dogs, whether healthy or sick, as a measure to control the domestic reservoir of L. infantum and reduce the risk for visceral leishmaniasis.

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 105 (G1), 104 (G2), 103 (G3), or 102 (G4) tachyzoites or subcutaneously with 104 (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6). Comparing challenge doses, G1 was the only group that had 100% abortion. Likewise, IFNγ levels in G1 increased earlier than those in other intravenously infected groups, and IgG levels on day 21 post-infection (pi) were higher in G1 than those in other intravenously infected groups. Concerning vertical transmission, G1 shows a higher parasite burden in the foetal brain than did G2 and G3. Comparing routes of administration, no differences in foetal survival rate or parasite load in the foetal brain were found. Although G2 had higher IFNγ levels than G5 on day 10 pi, no differences were found in humoral immune responses. Because the outcome after intravenous infection with 105 tachyzoites was similar to that observed after intravenous infection with 106 tachyzoites used in a previous work (100% abortion and vertical transmission), we conclude that it may be reasonable to use 105 tachyzoites administered by the intravenous route in further experiments when assessing drugs or vaccine candidates.

In silico identification and three-dimensional modelling of the missense mutation in ADAMTS2 in a sheep flock with dermatosparaxis.

BACKGROUND: Dermatosparaxis (Ehlers-Danlos syndrome in humans) is characterized by extreme fragility of the skin. It is due to the lack of mature collagen caused by a failure in the enzymatic processing of procollagen I. We investigated the condition in a commercial sheep flock. HYPOTHESIS/OBJECTIVES: Mutations in the ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2) locus, are involved in the development of dermatosparaxis in humans, cattle and the dorper sheep breed; consequently, this locus was investigated in the flock. ANIMALS: A single affected lamb, its dam, the dam of a second affected lamb and the rams in the flock were studied. METHODS: DNA was purified from blood, PCR primers were used to detect parts of the ADAMS2 gene and nucleotide sequencing was performed using Sanger's procedure. Skin samples were examined using standard histology procedures. RESULTS: A missense mutation was identified in the catalytic domain of ADAMTS2. The mutation is predicted to cause the substitution in the mature ADAMTS2 of a valine molecule by a methionine molecule (V15M) affecting the catalytic domain of the enzyme. Both the 'sorting intolerant from tolerant' (SIFT) and the PolyPhen-2 methodologies predicted a damaging effect for the mutation. Three-dimensional modelling suggested that this mutation may alter the stability of the protein folding or distort the structure, causing the protein to malfunction. CONCLUSIONS AND CLINICAL IMPORTANCE: Detection of the mutation responsible for the pathology allowed us to remove the heterozygote ram, thus preventing additional cases in the flock.

Wonderings to research questions: Engaging patients in long COVID research prioritization within a learning health system.

Background: An integral component of research within a learning health system is patient engagement at all stages of the research process. While there are well-defined best practices for engaging with patients on predetermined research questions, there is little specific methodology for engaging patients at the stage of research question formation and prioritization. Further, with an emerging disease such as Long COVID, population-specific strategies for meaningful engagement have not been characterized. Methods: The COVID-19 Focused Virtual Patient Engagement Studio (CoVIP studio) was a virtual panel created to facilitate patient-centered studies surrounding the effects of long-term COVID ("Long COVID") also known as post-acute SARS-CoV-2 syndrome (PASC). A diverse group of panelists was recruited and trained in several different areas of knowledge, competencies, and abilities regarding research and Long COVID. A three-step approach was developed that consisted of recording panelists' broad wonderings to generate patient-specific research questions. Results: The "wonderings" discussed in panelists' training sessions were analyzed to identify specific populations, interventions, comparators, outcomes, and timeframes (PICOT) elements, which were then used to create a survey to identify the elements of greatest importance to the panel. Based on the findings, 10 research questions were formulated using the PICOT format. The panelists then ranked the questions on perceived order of importance and distributed one million fictional grant dollars between the five chosen questions in the second survey. Through this stepwise prioritization process, the project team successfully translated panelists' research wonderings into investigable research questions. Conclusion: This methodology has implications for the advancement of patient-engaged prioritization both within the scope of Long COVID research and in research on other rare or emerging diseases.

Influence of reinforcement and its omission on trial-by-trial changes of response bias in perceptual decision making.

Discrimination performance in perceptual choice tasks is known to reflect both sensory discriminability and nonsensory response bias. In the framework of signal detection theory, these aspects of discrimination performance are quantified through separate measures, sensitivity (d') for sensory discriminability and decision criterion (c) for response bias. However, it is unknown how response bias (i.e., criterion) changes at the single-trial level as a consequence of reinforcement history. We subjected rats to a two-stimulus two-response conditional discrimination task with auditory stimuli and induced response bias through unequal reinforcement probabilities for the two responses. We compared three signal-detection-theory-based criterion learning models with respect to their ability to fit experimentally observed fluctuations of response bias on a trial-by-trial level. These models shift the criterion by a fixed step (1) after each reinforced response or (2) after each nonreinforced response or (3) after both. We find that all three models fail to capture essential aspects of the data. Prompted by the observation that steady-state criterion values conformed well to a behavioral model of signal detection based on the generalized matching law, we constructed a trial-based version of this model and find that it provides a superior account of response bias fluctuations under changing reinforcement contingencies.

Ischiofemoral impingement syndrome: A five-case series report.

Gluteal pain is a frequent cause of medical attention in the daily clinical practice. It can be caused by multiple pathologies, being ischiofemoral impingement syndrome among those included in its differential diagnosis. Encompassed within the deep gluteal syndromes, this entity occurs as a consequence of the entrapment of the neuromuscular structures between the lesser femoral trochanter and the ischial tuberosity, causing pain in the root of the lower limb, with irradiation towards the thigh or the gluteal region and poor tolerance to deambulation and sedestation. The magnetic resonance imaging of the hip is fundamental for its diagnosis, and its management consists on medical treatment at onset. Despite not being a frequent diagnosis in the clinical practice in Rheumatology, keeping it in mind helps improving its prognosis by establishing an early and adequate treatment.

Jaagsiekte sheep retrovirus found in milk macrophages but not in milk lymphocytes or mammary gland epithelia of naturally infected sheep.

Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma. JSRV can be transmitted via infected colostrum or milk, which contain somatic cells (SCs) harboring JSRV provirus. Nevertheless, the cell types involved in this form of transmission and the involvement of the mammary gland remain unknown. We separated adherent cells (macrophages and monocytes) by plastic adherence, and lymphocytes (CD4+ and CD8+ T cells, and B cells) by flow cytometry, from SCs in milk samples from 12 naturally infected, PCR blood test JSRV-positive, subclinical ewes. These cell populations were tested by PCR to detect JSRV provirus. The ewes were euthanized, and mammary gland samples were analyzed immunohistochemically to detect JSRV surface protein. We did not detect JSRV provirus in any milk lymphocyte population, but milk adherent cells were positive in 3 of 12 sheep, suggesting a potential major role of this population in the lactogenic transmission of JSRV. Immunohistochemistry did not reveal positive results in mammary epithelial cells, pointing to a lack of participation of the mammary gland in the biological cycle of JSRV and reducing the probability of excretion of free viral particles in colostrum or milk.

Anaemia in Ruminants Caused by Plant Consumption.

Plant toxicology has affected animals throughout evolution. Plants have adapted themselves to the environment. This adaptation has led to the development of defensive strategies to avoid being consumed. Plants have several chemical compounds, which can cause deleterious effects on people or animals that consume them, causing a wide variety of clinical signs. Plants from various latitudes, both cultivated for human and animal feeding or decorative purpose and even wild growth plants are able to generate anaemia in ruminants. Coumarins or ptaquiloside predispose bleeding and haemorrhages, causing a haemorrhagic disease in affected animals. In this group, some important fodder plants, such sweet clover (Genus Melilotus spp.), or other weeds distributed worldwide, such as bracken fern (Pteridium aquilinum) of giant fennel (Ferula communis), are included. On the other hand, sulfur-containing chemicals (e.g., n-propyl disulfate and S-propyl cysteine sulfoxides (SMCOs)) may cause severe direct damage to the erythrocyte and their membrane, leading to their destruction and causing haemolytic anaemia in the animal. This review presents the most frequent intoxication by plants causing anaemia in ruminants. Toxic compounds, clinical signs, diagnosis and possible treatments are also presented.

Delayed hepatothorax: An unusual presentation case report.

INTRODUCTION AND IMPORTANCE: We are reporting a case of a delayed hepatothorax due to a right-sided diaphragmatic rupture 13 years after a blunt trauma due to a motor vehicle accident, who presented as isolated gastritis without any type of respiratory symptomatology. CASE PRESENTATION: Patient refers that his symptoms remained refractory to medical treatment and had gotten worse over time. Chest wall inspection showed asymmetric thoracic expansion and a decreased movement of right hemithorax when compared to the left. Cardiorespiratory auscultation was significant for growling sounds on the right second intercostal space and reduction of breath sounds on the right lower lobe region of the lung when compared to the left side. CLINICAL DISCUSSION: Thoracotomy was indicated since patient presented late. Meanwhile, laparotomy would have been appropriate if the patient had presented immediately after trauma. After the procedure, the patient presented in great condition and all the gastrointestinal symptoms associated with the traumatic diaphragmatic hernia had resolved. We propose that the absence of respiratory symptoms in our patient could be due to the progressive adaptation of small, cumulative changes in decreasing breathing capacity through time. CONCLUSION: A case like ours has not been reported in the literature and clinicians should take this case report into consideration when suspecting a possible diagnosis of a delayed traumatic diaphragmatic hernia that may be complicated by a hepatothorax. We recommend maintaining a high index of clinical suspicion for hepatothorax due to delayed traumatic diaphragmatic hernia for all patients with a history of trauma.

Comparative Study of the Use of Doxycycline and Oxytetracycline to Treat Anaplasmosis in Fattening Lambs.

Lamb icteric carcasses condemnation due to Anaplasma ovis is causing relevant economic losses. A comparative study was developed on the effects of different antibiotics to treat ovine anaplasmosis in fattening lambs. A total of 100 A. ovis naturally infected lambs were selected and randomly divided into four groups of 25 lambs: Group ID, treated with injectable doxycycline; Group OD, oral doxycycline; Group O, injectable oxytetracycline; and Group C, untreated animals for the control group. Clinical, haematological, and molecular analyses were performed before the treatment and 12 and 45 days after the beginning of the treatments, and carcass condemnation was followed after slaughter. The A. ovis bacterial load was high before the treatments in the four groups and decreased significantly 45 days after treatment in the ID and O Groups (p < 0.001). The parameters that were related to haemolysis showed similar results. At the abattoir, 15 out of the 47 examined carcasses were condemned; 7 of C Group, 6 of OD Group, 2 of O Group, and 0 of ID Group. It can be concluded that injectable doxycycline and oxytetracycline significantly reduce A. ovis bacterial load in blood and carcass condemnation at the abattoir. Further studies are needed in order to confirm these encouraging findings.

Tuning HAuCl4/Sodium Citrate Stoichiometry to Fabricate Chitosan-Au Nanocomposites.

Nanocomposite engineering of biosensors, biomaterials, and flexible electronics demand a highly tunable synthesis of precursor materials to achieve enhanced or desired properties. However, this process remains limited due to the need for proper synthesis-property strategies. Herein, we report on the ability to synthesize chitosan-gold nanocomposite thin films (CS/AuNP) with tunable properties by chemically reducing HAuCl4 in chitosan solutions and different HAuCl4/sodium citrate molar relationships. The structure, electrical, and relaxation properties of nanocomposites have been investigated as a function of HAuCl4/sodium citrate molar relation. It was shown that gold particle size, conductivity, Vogel temperature (glass transition), and water content strongly depend upon HAuCl4/sodium citrate relationships. Two relaxation processes have been observed in nanocomposites; the α-relaxation process, related to a glass transition in wet CS/AuNP films, and the σ-relaxation related to the local diffusion process of ions in a disordered system. The ability to fine-tune both α- and σ-relaxations may be exploited in the proper design of functional materials for biosensors, biomaterials, and flexible electronics applications.

[Cocaine-induced ischemic colitis in a high-risk patient treated conservatively]. / Colitis isquémica inducida por cocaína en un paciente de riesgo, tratada de forma conservadora.

Drug consumption is among the non-occlusive causes of ischemic colitis. We report a case of cocaine-induced ischemic colitis in a 34-year-old man who had undergone sigmoid resection and loop colostomy due to abdominal-pelvic injury 3 months previously. The patient presented with abdominal pain associated with diarrhea and slight transient fever of doubtful etiology and reported intranasal cocaine consumption. He was hemodynamically stable and showed no peritoneal irritation. Traces of blood were found in the colostomy bag. Colonoscopy showed ulcers and necrosis proximal to the stoma. Computed tomography angiography scan showed no abnormalities except filiform inferior mesenteric artery. The symptoms were self-limiting and the patient was discharged 3 days after admission. Subsequently the colostomy was closed without complications. A high degree of suspicion is required in young patients with abdominal pain not identified by conventional methods and a recent history of drug consumption.

Squamous cell carcinoma of the vagina and cervix in sheep - case report.

This report describes the clinical and histopathological characteristics of a squamous cell carcinoma infiltrating the cervix and the vaginal wall, producing reproductive symptoms and subnormal fertility in an adult ewe. Necropsy showed a large (15-cm-long) neoplastic mass infiltrating the vaginal wall and the cervix. Histopathological examination revealed atypical squamous epithelial cords invading the basal membrane and dermis, round anaplastic cells, focal areas of necrosis, keratinisation of isolated cells, and pronounced infiltration by mononuclear cells around the cords. No squamous cell carcinoma of such localisation has been reported from sheep before. In humans, this tumour is the most common gynaecological malignancy in the world.

Detection of aluminium hydroxide-induced granulomas in sheep by computed tomography: A feasible approach for small ruminant lentiviruses diagnosis and research.

Aluminium (Al) hydroxide use as adjuvant induces local formation of long-lasting subcutaneous granulomas in sheep. Macrophages within these granulomas have been identified as a new small ruminant lentivirus (SRLV) replication site in naturally infected animals. Diagnosis of Al hydroxide-induced granulomas in sheep is mostly based on postmortem observations but little information is available on in vivo detection. Computed tomography (CT) is used for studying these reactions in other animal species. To determine if CT could be a tool for in vivo diagnosis and research of subcutaneous Al hydroxide-induced granulomas in sheep. A retrospective survey on thoracic CT scans was performed on 46 adult sheep. Analysis included absence or presence, number and location of subcutaneous nodules. Thoracic CT scans and pathological studies were prescribed to two further sheep. Single or multiple subcutaneous nodules were detected in 26 (56.52%) sheep. One or two nodules per animal were most often observed (36.95%). Size ranged between 1.5 and 4.5 cm. Pre-contrast two-dimensional (2D) CT images showed focal or multifocal increases in subcutaneous tissue thickness. Post-contrast 2D CT images revealed hypointense areas in the centre. Histopathology indicated the presence of granulomas composed by a large number of activated macrophages, surrounding a central core of necrosis. Large intracytoplasmic Al-positive aggregates were demonstrated by lumogallion staining. CT is a useful tool to detect subcutaneous Al hydroxide-induced granulomas in vivo in sheep. CT provides a diagnostic and research tool that can be very useful in future works in Al hydroxide-induced pathology, SRLV infection, or both.

Effect of a Topical Formulation on Infective Viral Load in Lambs Naturally Infected with Orf Virus.

INTRODUCTION: Orf is a highly contagious eruptive viral disease of the skin and mucosa of sheep and goats. Although vaccination with live or attenuated orf virus is the preferred option for disease control, the vaccine is unavailable in many countries. Treatment of orf lesions involves standard hygiene and in numerous cases, management of presumptive secondary infections with antibiotics, increasing risks of antimicrobial resistance (AMR). The wound dressing formulation Tri-Solfen® containing two local anaesthetics (lignocaine and bupivacaine), adrenaline and an antiseptic (cetrimide) in a gel formulation was developed for pain relief in sheep undergoing surgical husbandry procedures in Australia. Recently, TS therapy was found to reduce suffering and enhance recovery in cattle and buffalo with oral and skin lesions due to foot-and-mouth disease (FMD) virus infection. It was noted that TS has a low pH and is potentially viricidal, potentially aiding disease control. METHODS: One-month-old lambs (n=14), naturally infected with orf, were recruited from a farm during a natural outbreak of the disease. The animals were selected at the early stages of the infection and randomly divided into two cohorts: Group A (n=11) treated with the topical wound gel formulation (TS); and Group B (n=3) an untreated control group. Swabs were obtained before treatment (T0) and on days one (T1), 3 (T2) and 5 (T3) post-treatment, then submitted to direct DNA extraction with real-time PCR quantification, plus incubation with primary tissue cultures from ovine skin fibroblasts (OSF) and T-immortalized goat embryonic fibroblasts (TIGEF). RESULTS: Although no significant differences were found in the clinical progression of the lesions and PCR quantification (p=0.722) between these small cohorts, there was a significant difference (p<0.05) in reduction in infective viral load between the groups when assessed in OSF cell cultures between T0 and T3. CONCLUSION: These preliminary findings suggest that treatment of early stage lesions with this TS may reduce the infective viral load present in orf lesions.

Epidemiological Study Related to the First Outbreak of Ovine Anaplasmosis in Spain.

Ovine anaplasmosis is a vector-borne disease caused by Anaplasma ovis and mainly transmitted through tick bites. In Spain, the first outbreak of ovine anaplasmosis occurred in 2014. An epidemiological study in fifty-one farms was carried out associated with this outbreak in the affected geographical area. An epidemiological questionnaire was performed. In addition, whole blood samples were taken for molecular analysis in 47 of these farms to determine the prevalence of infection of Anaplasma ovis. A. ovis was present in 44 out of 47 PCR-analysed farms (93.6%). However, only 40.4% of the studied farms showed severe clinical signs. The clinical signs affected mainly young animals, which showed severe anaemia, weakness, anorexia, cachexia and epiphora. The early culling of young animals was more frequently reported by severely affected farms than the analysed farms without clinical signs (71.4% vs. 12.5%, p < 0.001). The geographical area where the farm is located seems to be relevant for the presence of clinical signs of the disease. Ovine anaplasmosis is an emerging disease in Europe that spreads rapidly through tick bites and is capable of causing significant economic losses when it spreads in a naive area and causes an epidemic.

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 105 Nc-Spain7 tachyzoites at mid-pregnancy. In the dams, BKI-1294 plasma concentrations were above the IC50 for N. caninum for 12-15 days. In treated sheep, when they were compared to untreated ones, we observed a minor increase in rectal temperature, higher IFNγ levels after blood stimulation in vitro, and a minor increase of IgG levels against N. caninum soluble antigens through day 28 post-infection. Additionally, the anti-NcSAG1 and anti-NcSAG4 IgGs were lower in treated dams on days 21 and 42 post-infection. However, BKI-1294 did not protect against abortion (87% foetal mortality in both infected groups, treated and untreated) and did not reduce transplacental transmission, parasite load or lesions in placentomes and foetal brain. The lack of foetal protection was likely caused by short systemic exposure in the dams and suboptimal foetal exposure to this parasitostatic drug, which was unable to reduce replication of the likely established N. caninum tachyzoites in the foetus at the moment of treatment. New BKIs with a very low plasma clearance and good ability to cross the blood-brain and placental barriers need to be developed.