Natural Clerodendrum-derived tick repellent: learning from Nepali culture.

Ticks attaching to ear canals of humans and animals are the cause of otoacariasis, common in rural areas of Nepal. The plant Clerodendrum viscosum is used in multiple indigenous systems of medicine by ethnic communities in the Indo-Nepali-Malaysian region. Visiting the Chitwan National Park, we learned that in indigenous medicine, flower extract of C. viscosum is utilized to treat digestive disorders and extracts from leaves as tick repellent to prevent ticks from invading or to remove them from the ear canal. The objective of our study was to provide support to indigenous medicine by characterizing the in vivo effect of leave extracts on ticks under laboratory conditions and its phytochemical composition. We collected plant parts of C. viscosum (leaves and flowers) and mango (Mangifera indica) leaves at the Chitwan National Park, previously associated with repellent activity to characterize their effect on Ixodes ricinus ticks by in vivo bioassays. A Q-ToF high-resolution analysis (HPLC-ESI-QToF) was conducted to elucidate phenolic compounds with potential repellent activity. Clerodendrum viscosum and M. indica leaf extracts had the highest tick repellent efficacy (%E = 80-100%) with significant differences when compared to C. viscosum flowers extracts (%E = 20-60%) and phosphate-buffered saline. Phytochemicals with tick repellent function as caffeic acid, fumaric acid and p-coumaric acid glucoside were identified in C. viscosum leaf extracts by HPLC-ESI-QToF, but not in non-repellent flower extracts. These results support the Nepali indigenous medicine application of C. viscosum leaf extracts to repel ticks. Additional research is needed for the development of natural and green repellent formulations to reduce the risks associated with ticks resistant to acaricides.

One Health Approach to Identify Research Needs on Rhipicephalus microplus Ticks in the Americas.

We aim to provide a harmonized view of the factors that affect the survival and promote the spread of R. microplus in the Neotropics, approaching its different facets of biology, ecology, distribution, and control. We review the interactions among environmental niche, landscape fragmentation, vegetal coverage (abiotic traits), and the biotic aspects of its ecology (abundance of domesticated or wild competent hosts), proposing emerging areas of research. We emphasize a holistic view integrating an economically and ecologically sustainable control of infestations and transmitted pathogens by R. microplus in the Neotropics. Examples of research link the trends of climate, the composition of the community of hosts, the landscape features, and a tailored management based on ecological grounds. Our view is that factors driving the spread of R. microplus are complex and deeply interrelated, something that has been seldom considered in control strategies. The effects of climate may affect the dynamics of wildlife or the landscape composition, promoting new patterns of seasonal activity of the tick, or its spread into currently free areas. In this paper we encourage a One Health approach highlighting the main aspects governing the components of the tick's life cycle and its interactions with livestock and wild animals.

Structure-based in silico design and in vitro acaricidal activity assessment of Acacia nilotica and Psidium guajava extracts against Sarcoptes scabiei var. cuniculi.

Infestation by Sarcoptes scabiei var. cuniculi mite causes scabies in humans and mange in animals. Alternative methods for developing environmentally friendly and effective plant-based acaricides are now a priority. The purpose of this research was the in silico design and in vitro evaluation of the efficacy of ethanol extracts of Acacia nilotica and Psidium guajava plant leaves against S. scabiei. Chem-Draw ultra-software (v. 12.0.2.1076.2010) was used to draw 36 distinct compounds from these plants that were employed as ligands in docking tests against S. scabiei Aspartic protease (SsAP). With docking scores of - 6.50993 and - 6.16359, respectively, clionasterol (PubChem CID 457801) and mangiferin (PubChem CID 5281647) from A. nilotica inhibited the targeted protein SsAP, while only beta-sitosterol (PubChem CID 222284) from P. guajava interacted with the SsAP active site with a docking score of - 6.20532. Mortality in contact bioassay at concentrations of 0.25, 0.5, 1.0, and 2.0 g/ml was determined to calculate median lethal time (LT50) and median lethal concentration (LC50) values. Acacia nilotica extract had an LC50 value of 0.218 g/ml compared to P. guajava extract, which had an LC50 value of 0.829 g/ml at 6 h. These results suggest that A. nilotica extract is more effective in killing mites, and these plants may have novel acaricidal properties against S. scabiei. Further research should focus on A. nilotica as a potential substitute for clinically available acaricides against resistant mites.

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines.

Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T- and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens.

Red deer in Iberia: Molecular ecological studies in a southern refugium and inferences on European postglacial colonization history.

The red deer (Cervus elaphus) is a widespread wild ungulate in Europe that has suffered strong anthropogenic impacts over their distribution during the last centuries, but also at the present time, due its economic importance as a game species. Here we focus on the evolutionary history of the red deer in Iberia, one of the three main southern refugial areas for temperate species in Europe, and addressed the hypothesis of a cryptic refugia at higher latitudes during the Last Glacial Maximum (LGM). A total of 911 individuals were sampled, genotyped for 34 microsatellites specifically developed for red deer and sequenced for a fragment of 670 bp of the mitochondrial (mtDNA) D-loop. The results were combined with published mtDNA sequences, and integrated with species distribution models and historical European paleo-distribution data, in order to further examine the alternative glacial refugial models and the influence of cryptic refugia on European postglacial colonization history. Clear genetic differentiation between Iberian and European contemporary populations was observed at nuclear and mtDNA levels, despite the mtDNA haplotypes central to the phylogenetic network are present across western Europe (including Iberia) suggesting a panmictic population in the past. Species distribution models, fossil records and genetic data support a timing of divergence between Iberian and European populations that overlap with the LGM. A notable population structure was also found within the Iberian Peninsula, although several populations displayed high levels of admixture as a consequence of recent red deer translocations. Five D-loop sub-lineages were found in Iberia that belong to the Western European mtDNA lineage, while there were four main clusters based on analysis of nuclear markers. Regarding glacial refugial models, our findings provide detailed support for the hypothesis that red deer may have persisted in cryptic northern refugia in western Europe during the LGM, most likely in southern France, southern Ireland, or in a region between them (continental shelf), and these regions were the source of individuals during the European re-colonization. This evidence heightens the importance of conserving the high mitochondrial and nuclear diversity currently observed in Iberian populations.

Artificial feeding of Rhipicephalus microplus female ticks with anti calreticulin serum do not influence tick and Babesia bigemina acquisition.

Ticks are obligate haematophagous ectoparasites considered the principal vectors of disease among animals. Rhipicephalus microplus and R. annulatus ticks are the most important vectors for Babesia bigemina and B. bovis, two of the most important intraerythrocytic protozoan parasites species in cattle, responsible for babesiosis which together with anaplasmosis account for substantial economic losses in the livestock industry worldwide. Anti-tick vaccines are a proved alternative to traditional tick and tick borne diseases control methods but are still limited primarily due to the lack of effective antigens. Subsequently to the identification of antigens the validation is a laborious work often expensive. Tick artificial feeding, is a low cost alternative to test antigens allowing achieving critical data. Herein, R. microplus females were successfully artificially fed using capillary tubes. Calreticulin (CRT) protein, which in a previous study has been identified as being involved in B. bigemina infection in R. annulatus ticks, was expressed as recombinant protein (rCRT) in an E. coli expression system and antibodies raised against rCRT. Anti-rCRT serum was supplemented to a blood meal, offered to partially engorged R. microplus females and their effect in feeding process as well as infection by B. bigemina was analyzed. No significant reductions in tick and egg weight were observed when ticks fed with anti-rCRT serum. Furthermore, B. bigemina infection levels did not show a statistically significant decrease when ticks fed with anti-rCRT antibodies. Results suggest that CRT is not a suitable candidate for cattle vaccination trials.

Consenso de uso de rituximab en artritis reumatoide. Un documento con recomendaciones basadas en la evidencia / Consensus on the use of Rituximab in Rheumatoid Arthritis. A document with evidence based recommendations

Introducción. El rituximab se ha empleado con éxito en el tratamiento de la artritis reumatoide (AR). Sin embargo, su particular mecanismo de acción, así como la ausencia de pautas concretas en su manejo, hace que se hayan generado dudas sobre su utilización. Objetivo. Establecer recomendaciones que faciliten el empleo de rituximab en la práctica clínica habitual. Métodos. En una primera ronda Delphi, se reunieron nueve reumatólogos expertos que desarrollaron preguntas sobre los temas con mayor duda sobre eficacia y seguridad del fármaco. Estas se adecuaron para hacer una revisión sistemática de la evidencia, que se presentó en una segunda reunión. Se formaron grupos nominales para dar respuesta a cada pregunta y emitir la recomendación. Estas recomendaciones fueron presentadas en una segunda ronda Delphi a un grupo ampliado de reumatólogos expertos. De nuevo se discutieron, se modificaron y se votaron las recomendaciones. Una vez aprobada cada recomendación, se votó el grado de acuerdo. Resultados. Se establecieron 17 recomendaciones: diez de eficacia y siete de seguridad. Todas las recomendaciones de eficacia, excepto tres, presentaron un nivel de evidencia bueno o moderado. Entre las recomendaciones de seguridad, tres presentaron un nivel de evidencia bueno o moderado, mientras que para el resto la evidencia fue indirecta, escasa o nula y son producto de las recomendaciones de los expertos. El grado de acuerdo entre expertos fue elevado para la mayoría de las recomendaciones. Conclusiones. Estas recomendaciones pretenden aclarar dudas sobre el uso de rituximab y establecer pautas de empleo en la práctica clínica. Las recomendaciones de eficacia tienen un nivel de evidencia alto y permiten guiar al médico en decisiones terapéuticas. Las recomendaciones de seguridad tienen un nivel de evidencia menor (AU)

Introduction. Rituximab has been employed successfully for the treatment of Rheumatoid Arthritis (RA). However, its particular mechanism of action, as well as a lack of concrete guidelines for its management have generated doubts on its use. Objective. To establish recommendations that facilitates the use of rituximab in common clinical practice. Methods. In a first Delphi round, 9 expert rheumatologists got together to develop questions on those subjects generating most doubts on the efficacy and safety of the drug. These were adapted to perform a systematic review of the evidence, which was presented in a second meeting. Nominal groups were formed to respond to each question and give a recommendation. These recommendations were presented in a second Delphi round to a larger group of experts in rheumatology. Once again recommendations were discussed, modified and voted upon. Once approved, a vote on the degree of agreement for each recommendation was carried out. Results. 17 recommendations were established, 10 regarding efficacy and 7 safety. All of the efficacy recommendations except 3 presented a good or moderate degree of evidence. Among the safety recommendations, 3 had a good or moderate degree of evidence while in the rest it was indirect, scarce or non-existent and a product of expert recommendation. The degree of agreement between experts was elevated for most of the recommendations. Conclusions. These recommendations attempt to clear doubts on the use of rituximab and establish guidelines for its use in daily practice. Efficacy recommendations have a high degree of evidence, allowing the clinician to be guided in therapeutic decisions. Safety recommendations have a lower degree of evidence (AU)

Actualización del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide / Update of the Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in rheumatoid arthritis

Objetivo Servir de referencia para reumatólogos e implicados en el tratamiento de la artritis reumatoide que vayan a utilizar o consideren la utilización de terapias biológicas en su manejo. Métodos Las recomendaciones se emitieron siguiendo la metodología de grupos nominales y basadas en revisiones sistemáticas. El nivel de evidencia y el grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por técnica Delphi. Resultados Se realizan recomendaciones sobre el uso de los siete agentes biológicos disponibles para la artritis reumatoide en la actualidad en nuestro país. El objetivo del tratamiento es lograr la remisión de la enfermedad lo más precozmente posible. Se revisan las indicaciones y matizaciones del uso de terapias biológicas y cuál debe ser la evaluación previa y la vigilancia del paciente con estos fármacos. Conclusiones Se presentan las actualizaciones a las recomendaciones SER para el uso de terapias biológicas en pacientes con artritis reumatoide(AU)

Objective To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. Methods Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Results We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. Conclusions We present an update on the SER recommendations for the use of biologic therapy in patients with RA(AU)

First serological and molecular evidence on the endemicity of Anaplasma ovis and A. marginale in Hungary.

Recurring and spontaneously curing spring haemoglobinuria was recently reported in a small sheep flock in a selenium deficient area of northern Hungary. In blood smears of two animals showing clinical signs, Anaplasma-like inclusion bodies were seen in erythrocytes. To extend the scope of the study, 156 sheep from 5 flocks and 26 cattle from 9 farms in the region were examined serologically with a competitive ELISA to detect antibodies to Anaplasma marginale, A. centrale and A. ovis. The seropositivity in sheep was 99.4%, and in cattle 80.8%. A. ovis and A. marginale were identified by PCR and sequence analysis of the major surface protein (msp) 4 gene in sheep and cattle, respectively. Haemoglobinuria, an unusual clinical sign for anaplasmosis might have been a consequence of transient intravascular haemolysis facilitated by selenium deficiency in recently infected sheep, as indicated by the reduction of mean corpuscular haemoglobin concentration (MCHC). Membrane damage was also demonstrated for parenchymal cells, since their enzymes showed pronounced elevation in the plasma. Ticks collected from animals in the affected as well as in neighbouring flocks revealed the presence of Dermacentor marginatus, Ixodes ricinus and D. reticulatus, with the dominance of the first. The present data extend the northern latitude in the geographical occurrence of ovine anaplasmosis in Europe and reveal the endemicity of A. ovis and A. marginale in Hungary.

III Actualización del Consenso de la Sociedad Española de Reumatología sobre terapia biológica en la artritis reumatoide / No disponible

No disponible

Actividad biológica de Ricinus communis sobre mosca doméstica (Musca domestica)

Se evaluó el efecto insecticida de una lectina obtenida a partir de Ricinus communis (higuereta), sobre una población de mosca doméstica procedente de San José de las Lajas. Los ensayos se realizaron con adultos y larvas. Se observó mayor mortalidad a medida que aumentó el tiempo de exposición frente al extracto, la DL50 a las 72 h de exposición fue de 353,4 p.p.m.; además, se apreció una disminución altamente significativa en el desarrollo pupal en presencia del extracto lo que pone de manifiesto su actividad insecticida.

The insecticide effect of a lectin obtained from Riccinus communis (castor-oil plant) on a population of houseflies from San José de Las Lajas was evaluated. Assays were performed with adults and larvas. Mortality was higher as the time f exposure to the extract increased. DL50 was of 353.4 p.p.m. after 72 hours of exposure. It was observed a remarkedly significant reduction of the pupal development in the presence of the extract, which shows its insecticide activity.