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West Nile virus (WNV) is a mosquito-borne pathogen that can lead to encephalitis and death in susceptible hosts. Cytokines play a critical role in inflammation and immunity in response to WNV infection. Murine models provide evidence that some cytokines offer protection against acute WNV infection and assist with viral clearance, while others play a multifaceted role WNV neuropathogenesis and immune-mediated tissue damage. This article aims to provide an up-to-date review of cytokine expression patterns in human and experimental animal models of WNV infections. Here, we outline the interleukins, chemokines, and tumor necrosis factor superfamily ligands associated with WNV infection and pathogenesis and describe the complex roles they play in mediating both protection and pathology of the central nervous system during or after virus clearance. By understanding of the role of these cytokines during WNV neuroinvasive infection, we can develop treatment options aimed at modulating these immune molecules in order to reduce neuroinflammation and improve patient outcomes.

While fatal infections caused by the Usutu virus appeared to concern only passerines (especially the blackbird) and Strigiformes (especially the great gray owl), we report herein that the virus also naturally causes a fatal disease in an anseriforme species, the common scoter (Melanitta nigra).

Usutu virus (USUV), a mosquito-borne zoonotic flavivirus discovered in South Africa in 1959, has spread to many European countries over the last 20 years. The virus is currently a major concern for animal health due to its expanding host range and the growing number of avian mass mortality events. Although human infections with USUV are often asymptomatic, they are occasionally accompanied by neurological complications reminiscent of those due to West Nile virus (another flavivirus closely related to USUV). Whilst USUV actually appears less threatening than some other emergent arboviruses, the lessons learned from Chikungunya, Dengue, and Zika viruses during the past few years should not be ignored. Further, it would not be surprising if, with time, USUV disperses further eastwards towards Asia and possibly westwards to the Americas, which may result in more pathogenic USUV strains to humans and/or animals. These observations, inviting the scientific community to be more vigilant about the spread and genetic evolution of USUV, have prompted the use of experimental systems to understand USUV pathogenesis and to boost the development of vaccines and antivirals. This review is the first to provide comprehensive coverage of existing in vitro and in vivo models for USUV infection and to discuss their contribution in advancing data concerning this neurotropic virus. We believe that this paper is a helpful tool for scientists to identify gaps in the knowledge about USUV and to design their future experiments to study the virus.

Usutu virus (USUV) is a mosquito-borne flavivirus that shares many similarities with the closely related West Nile virus (WNV) in terms of ecology and clinical manifestations. Initially distributed in Africa, USUV emerged in Italy in 1996 and managed to co-circulate with WNV in many European countries in a similar mosquito−bird life cycle. The rapid geographic spread of USUV, the seasonal mass mortalities it causes in the European avifauna, and the increasing number of infections with neurological disease both in healthy and immunocompromised humans has stimulated interest in infection studies to delineate USUV pathogenesis. Here, we assessed the pathogenicity of two USUV isolates from a recent Belgian outbreak in immunocompetent mice. The intradermal injection of USUV gave rise to disorientation and paraplegia and was associated with neuronal death in the brain and spinal cord in a single mouse. Intranasal inoculation of USUV could also establish the infection; viral RNA was detected in the brain 15 days post-infection. Overall, this pilot study probes the suitability of this murine model for the study of USUV neuroinvasiveness and the possibility of direct transmission in mammals.

During late summer 2016, in a northwest European region extending over Belgium, the Netherlands and the eastern border of the German state of North Rhine Westphalia, an outbreak of wild bird deaths occurred similar to those reported on the continent since 1996. Dead birds were necropsied and examined by complementary methods. Pathologic and immunohistological investigations strongly suggested an infection by Usutu virus. Subsequently, genomic segments of the said virus were detected, the virus was isolated and its complete genome was sequenced. The strain, designated Usutu-LIEGE, is a close phylogenetic relative of those isolated in Germany which form a distinct group within the USUV phylogeny, the so-called Europe_3 lineage. Should this outbreak recapitulate the characteristics of those in southwest Germany in 2011 and in/around Vienna (Austria) in 2001, it is expected that specific avian populations in the affected area will face a significant reduction in size for a few years.

Usutu virus (USUV) is a neurotropic flavivirus closely related to West Nile virus (WNV). Its enzootic cycle mainly involves mosquitoes and birds. Human infection can occur with occasional, but sometimes severe, neurological complications. Since its emergence and spread in Europe over the last two decades, USUV has been linked to significant avian outbreaks, especially among Passeriformes, including European blackbirds (Turdus merula). Strikingly, no in vivo avian model exists so far to study this arbovirus. The domestic canary (Serinus canaria) is a passerine, which is considered as a highly susceptible model of infection by WNV. Here, we experimentally challenged domestic canaries with two different doses of USUV. All inoculated birds presented detectable amounts of viral RNA in the blood and RNA shedding via feathers and droppings during the early stages of the infection, as determined by RT-qPCR. Mortality occurred in both infected groups (1/5 and 2/5, respectively) and was not necessarily correlated to a pure neurological disease. Subsequent analyses of samples from dead birds showed histopathological changes and virus tropism mimicking those reported in naturally infected birds. A robust seroconversion followed the infection in almost all the surviving canaries. Altogether, these results demonstrate that domestic canaries constitute an interesting experimental model for the study of USUV pathogenesis and transmission.

Wildlife surveillance allowed the monitoring of the zoonotic mosquito-borne Usutu virus (USUV) in birds and bats (Pipistrellus pipistrellus) in southern Belgium in 2017 and 2018. USUV-RNA was detected in 69 birds (of 253) from 15 species, among which 7 species had not previously been reported to be susceptible to the infection. Similarly, 2 bats (of 10) were detected positive by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). USUV-associated lesions were mainly found in Eurasian Blackbirds (Turdus merula), in which USUV antigens were demonstrated by immunohistochemistry in the brain, heart, liver, kidney, intestine, and lung. Partial nonstructural protein 5 gene-based phylogenetic analysis showed several identical or closely related strains from 2016, 2017, and 2018 clustering together within Europe 3 or Africa 3 lineages. Further, one USUV strain detected in a common chaffinch (Fringilla coelebs) manifested a close genetic relationship with the European 1 strains circulating in Hungary and Austria. Our data provide evidence of USUV endemization in southern Belgium in local birds and bats, extension of the host range of the virus and ongoing virus introduction from abroad, likely by migratory birds. Our results highlight the need for vigilance in the forthcoming years toward new virus-associated outbreaks in birds and possible human infections in Belgium.

While fatal infections caused by the Usutu virus appeared to concern only passerines (especially the blackbird) and Strigiformes (especially the great gray owl), we report herein that the virus also naturally causes a fatal disease in an anseriforme species, the common scoter (

The family Parvoviridae contains diverse viruses that are capable of infecting a wide range of hosts. In this study, metagenomic sequencing of Ixodes ricinus ticks harvested in 2016 on red deer (Cervus elaphus) and European roe deer (Capreolus capreolus) in Belgium detected a new 6296-bp parvoviral genome. Phylogenetic and sequence analyses showed the new virus belongs to a new species within the Copiparvovirus genus. PCR screening of 4 pools of 10 serum samples from both deer species identified the new copiparvovirus DNA only in roe deer sera. Together, these results are the first evidence of a copiparvovirus in a deer species. Besides its potential pathogenicity to roe deers, the detection of this new virus in ticks raises questions about the possible transmission of parvoviruses by ticks. This report further increases the current knowledge on the evolution and diversity of copiparvoviruses.

West Nile Virus, Usutu virus, Bagaza virus, Israel turkey encephalitis virus and Tembusu virus currently constitute the five flaviviruses transmitted by mosquito bites with a marked pathogenicity for birds. They have been identified as the causative agents of severe neurological symptoms, drop in egg production and/or mortalities among avian hosts. They have also recently shown an expansion of their geographic distribution and/or a rise in cases of human infection. This paper is the first up-to-date review of the pathology of these flaviviruses in birds, with a special emphasis on the difference in susceptibility among avian species, in order to understand the specificity of the host spectrum of each of these viruses. Furthermore, given the lack of a clear prophylactic approach against these viruses in birds, a meta-analysis of vaccination trials conducted to date on these animals is given to constitute a solid platform from which designing future studies.

In this paper, we focus on a specific operations management related issue faced by home health care (HHC) services, namely the districting problem. Our contribution consists of formulating the HHC districting problem as a mixed-integer programming model by considering criteria such as the indivisibility of the basic units (i.e. locations where patients live), compactness, workload balance between human resources and compatibility. The formulations developed are based either on balancing the personnel care workload or minimizing the travel distance to reach the patients. Computational results obtained from the models show that they enable to improve the service quality towards HHC patients as well as caregivers by optimizing the compactness and workload balance criteria.

PurposeThe purpose of this paper is to assess the potential factors that may generate complexity in managing operations in home care (HC) organizations. Hence, a framework which might assist decision making regarding complexity‐driven issues in HC organizations is developed.Design/methodology/approachBased on a systems thinking view, a framework was developed identifying complexity factors in HC organizations. The paper is based on field research to explore the practical challenges of managing operations in HC structures. The authors additionally give a state of the art in many scientific domains; definition of complexity and its implications; complexity in health care; description of home care operations and their management. The literature review enlightens the lack of consensus on HC complexity and thus provides a broad view and a critical analysis of the underlying concepts.FindingsProposal of a HC operations complexity model (and validation due to a practical application).Practical implicationsThe framework developed by the authors permits one to identify rapidly the existing complexity factors which may create potential damages regarding value creation and cost improvement in HC. Two kinds of HC complexity are identified: HC organization complexity and HC individual patients' therapeutical projects complexity. Complexity factors are grouped into five categories: factors related to size; factors related to variety; interdependence factors; factors related to uncertainties; and factors related to context. By identifying the factors, decision support systems and response plans may be more adapted to the potential existing short comings of operations.Originality/valueBased on authors' extensive knowledge of HC practices, as well as an international systematic review of literature, this paper contributes to a better characterization of factors inducing complexity in the HC context. To the best of the authors' knowledge, operations management literature lacks a general framework enabling a better identification and understanding of what makes HC operations specific. The paper presents an innovative way to analyze HC complexity using a systems thinking‐based approach. In this sense, its contribution is very complementary to traditional operations management models.