Predictors of Bluetongue development in Sardinia (Italy) identification, using multilevel logistic mixed model

Objectives: The Bluetongue Virus is one of the most studied ruminant diseases, affecting particularly sheep and goats. This study aims to identify, for the first time, the specific risk factors influencing the disease development in Sardinia, using multilevel logistic regression model, in order to give a contribution to the sanitary programs and favour the early detection.   Methods: The data of the present retrospective study, collected from informatics systems of Istituto Zooprofilattico della Sardegna, are referred to all 15,780 Sardinian sheep farms observed for 3 years (2012-2014). The outcome of interest was dichotomous and defined the development of Bluetongue outbreak, after serological test or clinical signs. The effect of several region-specific prognostic factors on disease spread was investigated. Results: The final model indicated that Bluetongue development was significantly associated with an increase in number of animals (P < 0.0001), number of cattle around farm (P  < 0.0001), water surface area (P =0.002), and amount of rainfall in the previous days (P < 0.0001). Furthermore, the altitude over 450 MASL (P < 0.0001), the vaccination prophylaxis (P < 0.0001) and the previous outbreak event (P < 0.0001) had a protective effect against the outcome. Conclusion: The results of this study indicated that number of animals and the amount of rainfall were the most important risk factors that affected the Bluetongue development, while the vaccination prophylaxis was found to be an effective measure in decelerating the disease spread.&nbsp

Characterization of the interaction of African swine fever virus with monocytes and derived macrophage subsets.

Abstract African swine fever (ASF) is a devastating disease for which there is no vaccine available. The ASF virus (ASFV) primarily infects cells of the myeloid lineage and this tropism is thought to be crucial for disease pathogenesis. A detailed in vitro characterization of the interactions of a virulent Sardinian isolate (22653/14) and a tissue culture adapted avirulent strain (BA71V) of ASFV with porcine monocytes, un-activated (moMΦ), classically (moM1) and alternatively (moM2) activated monocyte-derived macrophages was conducted in an attempt to better understand this relationship. Using a multiplicity-of-infection (MOI) of 1, both viruses were able to infect monocytes and macrophage subsets, but BA71V presented a reduced ability to infect moM1 compared to 22653/14, with higher expression of early compared to late proteins. Using an MOI of 0.01, only 22653/14 was able to replicate in all the macrophage subsets, with initially lowest in moM1 and moM2. No differences were observed in the expression of CD163 between ASFV infected and uninfected bystander cells. ASFV down-regulated CD16 expression but did not modulate MHC class II levels in monocytes and macrophage subsets. BA71V-infected but not 22653/14-infected moMΦ and moM2 presented with a reduced expression of MHC class I compared to the mock-infected controls. Higher levels of IL-18, IL1-β and IL-1α were released from moM1 after infection with BA71V compared to 22653/14 or mock-infected control. These results revealed differences between these ASFV strains, suggesting that virulent isolates have evolved mechanisms to counteract activated macrophages responses, promoting their survival, dissemination in the host and so ASF pathogenesis

Evidence-based African swine fever policies : do we address virus and host adequately?

African swine fever (ASF) is one of the most threatening diseases for the pig farming sector worldwide. Prevention, control and eradication remain a challenge, especially in the absence of an effective vaccine or cure and despite the relatively low contagiousness of this pathogen in contrast to Classical Swine Fever or Foot and Mouth disease, for example. Usually lethal in pigs and wild boar, this viral transboundary animal disease has the potential to significantly disrupt global trade and threaten food security. This paper outlines the importance of a disease-specific legal framework, based on the latest scientific evidence in order to improve ASF control. It compares the legal basis for ASF control in a number of pig-producing regions globally, considering diverse production systems, taking into account current scientific evidence in relation to ASF spread and control. We argue that blanket policies that do not take into account disease-relevant characteristics of a biological agent, nor the specifics under which the host species are kept, can hamper disease control efforts and may prove disproportionate.https://www.frontiersin.org/journals/veterinary-science#am2022Veterinary Tropical Disease

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Editorial: African Swine Fever

2 Pág. Centro de Investigación en Sanidad Animal (CISA)Our gratitude also to the the European Union’s Horizon 2020 research and innovation programme under the grant agreement no. 862874, where all three editors are involved in.Peer reviewe

Mathematical Approach to Estimating the Main Epidemiological Parameters of African Swine Fever in Wild Boar

African swine fever (ASF) severely threatens the swine industry worldwide, given its spread and the absence of an available licensed vaccine, and has caused severe economic losses. Its persistence in wild boar (WB), longer than in domestic pig farms, and the knowledge gaps in ASF epidemiology hinder ASF virus (ASFV) eradication. Even in areas where disease is effectively controlled and ASFV is no longer detected, declaring eradication is difficult as seropositive WBs may still be detected. The aim of this work was to estimate the main ASF epidemiological parameters specific for the north of Sardinia, Italy. The estimated basic (R0) and effective (Re) reproduction numbers demonstrate that the ASF epidemic is declining and under control with an R0 of 1.139 (95% confidence interval (CI) = 1.123&ndash;1.153) and Re of 0.802 (95% CI = 0.612&ndash;0.992). In the last phases of an epidemic, these estimates are crucial tools for identifying the intensity of interventions required to definitively eradicate the disease. This approach is useful to understand if and when the detection of residual seropositive WB is no longer associated with any further ASFV circulation

Socio-economic factors as indicators for various animal diseases in Sardinia.

The need to consider the role of social factors in the efficacy of farm management and, consequently, in the onset and persistence of diseases typical to animal farms is increasingly being realized increasingly worldwide. Many risk analysis studies have been conducted to assess the role of various factors in the development of animal diseases; however, very few have accounted for the role of social factors. The aim of this work was to bridge this gap, with the main hypothesis that different socio-economic factors could be valid indicators for the occurrence of different animal diseases. A socio-economic analysis was performed using demographic characteristics of the farmers and data from 44 social indicators released by the Italian Statistician National Institute of Statistics (ISTAT) database. African swine fever (ASF) in wild boars (WB) and domestic pigs and other endemic animal diseases and zoonoses in Sardinia were considered, such as cistic echinococcosis (CE), contagious agalactia (CA), trichinellosis, West Nile disease (WND), and bluetongue (BT). Seven different negative binomial regression models were fitted using the number of cases between 2011-2017. Three indicators-cultural demand, employment rate, and legality-showed a statistically significant association with risk for all the diseases considered, but with varying effects. Some indicators, such as the age and sex of the farmer, material deprivation index, number of farms and animals, micro-criminality index, and rate of reported thefts were common to ASF, CA, trichinellosis, and CE cases. Others such as the forest surface and the energy produced from renewable sources were common to BT, WND, and ASF in WB. Tourism in seasons other than summer was a valid predictor of ASF and trichinellosis, while out-of-region hospital use had a statistically significant role in CE risk identification. These results may help understand the social context in which these diseases may occur and thus guide the design and implementation of additional risk management measures that go beyond well-known veterinary measures

Correction: Socio-economic factors as indicators for various animal diseases in Sardinia.

[This corrects the article DOI: 10.1371/journal.pone.0217367.]

Approaches and Perspectives for Development of African Swine Fever Virus Vaccines

African swine fever (ASF) is a complex disease of swine, caused by a large DNA virus belonging to the family Asfarviridae. The disease shows variable clinical signs, with high case fatality rates, up to 100%, in the acute forms. ASF is currently present in Africa and Europe where it circulates in different scenarios causing a high socio-economic impact. In most affected regions, control has not been effective in part due to lack of a vaccine. The availability of an effective and safe ASFV vaccines would support and enforce control-eradication strategies. Therefore, work leading to the rational development of protective ASF vaccines is a high priority. Several factors have hindered vaccine development, including the complexity of the ASF virus particle and the large number of proteins encoded by its genome. Many of these virus proteins inhibit the host's immune system thus facilitating virus replication and persistence. We review previous work aimed at understanding ASFV-host interactions, including mechanisms of protective immunity, and approaches for vaccine development. These include live attenuated vaccines, and "subunit" vaccines, based on DNA, proteins, or virus vectors. In the shorter to medium term, live attenuated vaccines are the most promising and best positioned candidates. Gaps and future research directions are evaluated