Efficacy of immunization with a recombinant S. aureus vaccine formulated with liposomes and ODN-CpG against natural S. aureus intramammary infections in heifers and cows.

The aims of the present study were to evaluate the ability of a subunit vaccine composed of recombinant molecules of α-toxin, ß-toxin, FnBPA and ClfA, formulated with cationic liposomes and CpG-ODN, to confer protection against natural S. aureus intramammary infection (IMI) and to assess the antibody response against the vaccine components. A stringent criterion based on molecular identification of the isolates was used to define IMI. The proportion of animals that developed new S. aureus IMI was higher in the Control group compared with the Vaccine group (reduction of 60.7%), and time to new S. aureus IMI was higher for animals in the Vaccine group compared with animals in the Control group, although not statistically significant. Molecular identification of the isolates allowed the detection of S. aureus pulsotypes that appeared transiently in milk and others that were able to establish IMI, providing a new perspective to define parameters related to the definition of new IMI and cures. Specific IgG, IgG1 and IgG2 levels against the four recombinant proteins included in the vaccine were significantly increased in the vaccinated group and the recombinant α-toxin included in the vaccine generated antibodies that reduced significantly the haemolytic activity of native α-toxin. Data reported in the present study indicate a possible effect on both the proportion of animals developing new IMI and the time to new S. aureus IMI, but the incidence of disease within the study was too low to provide statistical confirmation.

Expression-based analysis of genes related to single nucleotide polymorphism hits associated with bovine leukemia virus proviral load in Argentinean dairy cattle.

In dairy cattle infected with bovine leukemia virus (BLV), the proviral load (PVL) level is directly related to the viral transmission from infected animals to their healthy herdmates. Two contrasting phenotypic groups can be identified when assessing PVL in peripheral blood of infected cows. A large number of reports point to bovine genetic variants (single nucleotide polymorphisms) as one of the key determinants underlying PVL level. However, biological mechanisms driving BLV PVL profiles and infection progression in cattle have not yet been elucidated. In this study, we evaluated whether a set of candidate genes affecting BLV PVL level according to whole genome association studies are differentially expressed in peripheral blood mononuclear cells derived from phenotypically contrasting groups of BLV-infected cows. During a 10-mo-long sampling scheme, 129 Holstein cows were phenotyped measuring anti-BLV antibody levels, PVL quantification, and white blood cell subpopulation counts. Finally, the expression of 8 genes (BOLA-DRB3, PRRC2A, ABT1, TNF, BAG6, BOLA-A, LY6G5B, and IER3) located within the bovine major histocompatibility complex region harboring whole genome association SNP hits was evaluated in 2 phenotypic groups: high PVL (n = 7) and low PVL (n = 8). The log2 initial fluorescence value (N0) transformed mean expression values for the ABT1 transcription factor were statistically different in high- and low-PVL groups, showing a higher expression of the ABT1 gene in low-PVL cows. The PRRC2A and IER3 genes had a significant positive (correlation coefficient = 0.61) and negative (correlation coefficient = -0.45) correlation with the lymphocyte counts, respectively. Additionally, the relationships between gene expression values and lymphocyte counts were modeled using linear regressions. Lymphocyte levels in infected cows were better explained (coefficient of determination = 0.56) when fitted a multiple linear regression model using both PRRC2A and IER3 expression values as independent variables. The present study showed evidence of differential gene expression between contrasting BLV infection phenotypes. These genes have not been previously related to BLV pathobiology. This valuable information represents a step forward in understanding the BLV biology and the immune response of naturally infected cows under a commercial milk production system. Efforts to elucidate biological mechanisms leading to BLV infection progression in cows are valuable for BLV control programs. Further studies integrating genotypic data, global transcriptome analysis, and BLV progression phenotypes are needed to better understand the BLV-host interaction.

Eficacia del monepantel para el control de aislamientos de Haemonchus contortus y Trichostrongylus spp. con resistencia múltiple (ivermectina y febendazole) en caprinos

El monepantel es un nuevo antihelmíntico registrado en nuestro país exclusivamente para el control de los nematodes gastrointestinales de los ovinos y su uso ha sido direccionado mayormente hacia el control de parásitos resistentes a las clases de antihelmínticos disponibles actualmente. Estos mismos nematodes también parasitan a los caprinos, pero en estos rumiantes la patofisiología y la respuesta a los antihelmínticos es diferente, lo cual resulta en un mayor parasitismo y complejidad en el manejo de la resistencia. La presente comunicación informa sobre la eficacia del monepantel en dos hatos caprinos mantenidos bajo condiciones de campo y parasitados naturalmente por los géneros de nematodes gastrointestinales más comunes del área central de la Argentina (Haemonchus y Trichostrongylus) y portando alelos de resistencia múltiple (ivermectina y febendazole). El test de reducción en el conteo de huevos post tratamiento comparando diversas fórmulas, indicaron que en todos los hatos el monepantel por vía oral y a la dosis de 3,75 mg/kg de peso (1,5 veces mayor a la dosis ovina), resultó en eficacias del 99% al 100 %. Se realizan breves consideraciones sobre el uso potencial de esta droga en caprinos.

Monepantel is a new anthelmintic registered in Argentina exclusively for control of gastrointestinal nematodes of sheep and mostly directed toward controlling resistant parasites to current available classes of anthelmintics. The same nematodes also parasitize goats but pathophysiology and response are different in these hosts resulting in more severe parasitism and complexity in handling anthelmintic resistance. This report assess the efficacy of monepantel in goats maintained under field conditions and naturally parasitized by most common gastrointestinal nematodes from central Argentina (Haemonchus and Trichostrongylus) carrying alleles of multiple resistance (ivermectin and febendazole). According to the egg count reduction test, efficacies of 99% to 100% were observed after monepantel treatment at 3.75 mg/kg orally (1.5 ovine dose).

Monepantel y control de Haemonchus contortus en ovinos: Evaluación de la eficacia luego de cuatro años de uso en condiciones de refugio reducido

La resistencia de los nematodes ovinos a los antihelmínticos está generalizada en el centro-norte de la Argentina y la mayor preocupación actual es el aumento y dispersión de Haemonchus contortus portando alelos con resistencia múltiple. Actualmente los únicos antihelmínticos de amplio espectro sin documentación de resistencia en nuestro país son el monepantel y derquantel. Con la primera de estas drogas ya se han registrado casos de resistencia en Uruguay y Brasil por lo que es crítica la información actualizada sobre la actividad en el campo de estos antihelmínticos. Este estudio informa sobre la eficacia del monepantel luego de cuatro años de uso de esta droga sobre un aislamiento de H. contortus con resistencia múltiple (lactonas macrociclicas, closantel, levamisol y benzimidazoles) y bajo condiciones de refugio reducido. Se realizaron dos experiencias A y B (años 2014 y 2016 respectivamente) con corderos naturalmente parasitados y seleccionados en función del número de huevos por gramo de heces (≥ 250) los que fueron tratados con monepantel (2,5 mg/Kg oral). El test de reducción en el conteo de huevos post tratamiento comparando diversas fórmulas indicó que en ambas experiencias, la droga mantuvo una eficacia mayor al 97 % y que permanece activa para controlar este aislamiento de H. contortus luego de cuatro años de uso y bajo las particulares condiciones en las que se realizaron estos estudios.

Resistance to anthelmintics in sheep nematode is widespread in central-northern Argentina and current major concern is the rise and spread of Haemonchus contortus carrying multiple resistance alleles. Currently, monepantel and derquantel are the only broad-spectrum anthelmintics without documentation of resistance in our country. With the first of these drugs, have already been registered cases of resistance in Uruguay and Brazil so it is critical update on the activity in the field of these anthelmintics. This study aims to test the effectiveness of monepantel after four years of use of this drug on an isolation of H. contortus with multiple resistance (macrocyclic lactones, closantel, levamisole and benzimidazole) and under conditions of reduced refugia. Two experiences, A and B (2014 and 2016 respectively), were carried out with lambs naturally parasitized and selected by the number of eggs per gram of feces (≥ 250). In both experiences, the test of reduction in egg counts after treatment with monepantel (2.5 mgr/Kg orally) comparing various formulas indicated that the drug remained with efficacy greater than 97% after four years of use to control this isolation of H. contortus under the field conditions of these studies.