Estudios sobre la anaplasmosis ovina en la comarca del Matarraña (Teruel)

Tras haber diagnosticado en el curso 2013-2014 un caso de anaplasmosis ovina, remitido al SCRUM (Servicio Clínico de Rumiantes del Hospital Clínico Veterinario de la Universidad de Zaragoza) se decide abordar una investigación más profunda sobre dicha enfermedad. Este trabajo se engloba dentro de un trabajo mayor, compuesto por tres Trabajos de Fin de Grado que buscan investigar y conocer la epidemiología, la patogenia y el tratamiento de la anaplasmosis ovina. En particular, este estudio comprende la infección experimental de tres animales libres de la enfermedad y su posterior monitorización. La infección se realiza mediante la inoculación de sangre de animales infectados, con una concentración bacteriana conocida, gracias al empleo de una PCR cuantitativa, en tres animales jóvenes, nacidos en la facultad y aislados de cualquier otro patógeno. Posteriormente, se procede a una monitorización de los animales que consta de una evaluación clínica diaria a lo largo de dos meses, siendo complementada con varios tipos de pruebas laboratoriales: extracción de sangre para valorar los parámetros hematológicos, realización de frotis sanguíneos teñidos con Giemsa para observar formas compatibles y análisis mediante PCR cuantitativa para valorar la evolución de la bacteria en el tiempo dentro del organismo. Los resultados obtenidos demuestran el desarrollo de la enfermedad y que ésta es transmitida por la sangre. Los animales desarrollan una anemia severa debido a la hemolisis inmunomediada de los eritrocitos y la qPCR ayuda a entender la dinámica y evolución de la bacteria en el organismo. Ésta revela una curva asociada al grado de anemia con un pico en torno al mes de la infección que va decayendo progresivamente, en paralelo a la recuperación de los valores hematológicos por parte de los animale

Long-lasting infection with Anaplasma ovis in sheep

Ovine anaplasmosis is an emerging vector-borne disease in Europe caused by Anaplasma ovis. The infection has spread quickly in recent years, causing moderate to severe outbreaks in sheep flocks, leading to relevant economic losses in sheep farming. This wider spread has been associated with global warming and climate change, favouring the maintenance and life cycle of their main vector, the ticks. However, another epidemiological aspect could favour this quick spread. Long persistence infection of Anaplasma ovis has been proposed as a hypothesis in several articles but never scientifically proven. The results of the present study demonstrate that eight adult sheep, both naturally or experimentally infected, maintain Anaplasma ovis load in blood during their whole productive life (4 to 6 years), being permanently infected. In addition, the results suggest that A. ovis bacterial load can be constant or suffer fluctuations, as has been demonstrated in other Anaplasma species. Both aspects can be determinants in the epidemiology and the transmission of the infection

MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations

The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML

<em>Salmonella enterica</em> subsp. <em>diarizonae</em> Serotype 61:k:1:5:(7) a Host Adapted to Sheep

Salmonella genus is widely distributed in nature and causes a spectrum of diseases in man and animals. Salmonella enterica subsp. diarizonae serotype 61: k: 1,5, (7) (SED) is a host adapted to sheep and its presence as saprophytic bacteria in sheep has been described in different countries. Several studies performed in abattoirs reported the presence of SED in healthy sheep in the intestinal content and also in the respiratory tract. In addition, this microorganism has also been isolated from nostril and faecal samples in healthy live animals. For this reason, this microorganism is considered well adapted to sheep, behaving normally these animals as asymptomatic carriers. However, SED has also been reported causing health disorders such as chronic proliferative rhinitis in adult sheep, abortions, testicular lesions in rams or alimentary tract disorders in young animals. The zoonotic potential of this microorganism is also discussed

NGS-Based Molecular Karyotyping of Multiple Myeloma: Results from the GEM12 Clinical Trial

Simple Summary Multiple Myeloma (MM) is considered an incurable chronic disease, which prognosis depends on the presence of different genomic alterations. To accomplish a complete molecular diagnosis in a single essay, we have designed and validated a capture-based NGS approach to reliably identify pathogenic mutations (SNVs and indels), genomic alterations (CNVs and chromosomic translocations), and IGH rearrangements. We have observed a good correlation of the results obtained using our capture panel with data obtained by both FISH and WES techniques. In this study, the molecular classification performed using our approach was significantly associated with the stratification and outcome of MM patients. Additionally, this panel has been proven to detect specific IGH rearrangements that could be used as biomarkers in patient follow-ups through minimal residual disease (MRD) assays. In conclusion, we think that MM patients could benefit from the use of this capture-based NGS approach with a more accurate, single-essay molecular diagnosis. Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients

Anaemia in Sheep Caused by <i>Babesia</i> and <i>Theileria</i> Haemoparasites

Piroplasmoses in sheep are caused by vector-borne apicomplexan protozoa, Babesia and Theileria. Different species are responsible for the disease; some species are more pathogenic than others and have a worldwide distribution. In this sense, these causative agents can cause anaemia in flocks. In general, these vector-borne diseases infect small ruminants and cause host-mediated pathology. In the case of Babesia species, a combination of different mechanisms is involved: red blood cell lysis due to intracellular parasite multiplication, activation of biogenic amines and the coagulation system with the possibility of disseminated intravascular coagulation. By contrast, less information is available on the different immunopathogenic mechanisms involved in the development of anaemia in sheep with theileriosis. However, the mechanisms of pathogenic action in theileriosis are similar to those studied in babesiosis. Diagnosis is based on compatible clinical signs, laboratory findings, specific diagnostic tests and the presence of the tick vector. Some of these tests detect the causative agent itself, such as direct identification by light microscopy and molecular analysis. In contrast, other tests detect the sheep’s immune response to the organism by serology. Both diseases pose a significant diagnostic challenge for veterinary practitioners around the world. This review presents the most frequent clinical signs, pathogenesis and clinicopathological findings, diagnosis