Features of the medically important sandfly‐borne viruses.
\r\n\tIn this field modern trends are oriented toward the employment of new control, protection and monitoring systems that move away from the older centralized paradigm to system distributed in the field with an increasing pervasion of intelligence devices. The large scale deployment of these solutions could lead to a more effective integration of renewable power generators into existing electrical grids and to a sensible improvement of the distribution network flexibility.
\r\n\r\n\tThis book aims to be focused on the enabling technologies and methodologies for Smart Grids. This area addresses many relevant topics ranging from methods for balancing resources to various control and security aspects. This book not only focuses on technological breakthroughs and roadmaps in implementing the technology, but also presents the much needed sharing of best practices.
",isbn:"978-1-78923-892-1",printIsbn:"978-1-78923-891-4",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"ca836c407ba574b88af44b497d45d42b",bookSignature:"Dr. Alfredo Vaccaro, Dr. Ahmed Faheem F Zobaa, Prof. Prabhakar Karthikeyan Shanmugam and Dr. Kannaiah Sathish Kumar",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/7613.jpg",keywords:"Demand Side Management, Plug-in Vehicles, Flexible Loads, Energy Storage, Optimal Location, Ancillary Services, Renewable Power Generators, Distributed Optimization, Robust Control, Grid Optimization, Proactive Control, State Estimation, Energy Price, Renewable Power, Multicarrier Energy Networks",numberOfDownloads:1414,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 4th 2018",dateEndSecondStepPublish:"September 25th 2018",dateEndThirdStepPublish:"November 24th 2018",dateEndFourthStepPublish:"February 12th 2019",dateEndFifthStepPublish:"April 13th 2019",remainingDaysToSecondStep:"a year",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,editors:[{id:"24725",title:"Dr.",name:"Alfredo",middleName:null,surname:"Vaccaro",slug:"alfredo-vaccaro",fullName:"Alfredo Vaccaro",profilePictureURL:"https://mts.intechopen.com/storage/users/24725/images/system/24725.jpeg",biography:"Alfredo Vaccaro got the MSc. degree cum laude and commendation in Electronic Engineering from the University of Salerno and the PhD in Electrical and Computer Engineering from University of Waterloo, Ontario, Canada.\nFrom March 2002 to October 2014 he has been Assistant Professor of Electric Power Systems at the Department of Engineering, Faculty of Engineering of University of Sannio.\nFrom February 2011 to December 2013 he was the Scientific Director of the bureau of the Research Centre on Pure and Applied Mathematic at the Department of Engineering, University of Sannio.\nOn October 2014 he obtained the National Scientific Qualification of Full Professor in Electrical Energy Engineering.\nSince November 2014 he is Associate Professor of Electric Power Systems at the Department of Engineering, Faculty of Engineering of University of Sannio.\nHe is the Editor in Chief of the International Journal of Renewable Energy Technology, Deputy Chair of the IEEE PES Award Committee, and Chair of the PES-IEEE Task Force on Enabling Paradigms for High-performance Computing in Wide Area Monitoring Protective and Control systems.",institutionString:"University of Sannio, Benevento",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Sannio",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:{id:"39249",title:"Dr.",name:"Ahmed Faheem",middleName:"F",surname:"Zobaa",slug:"ahmed-faheem-zobaa",fullName:"Ahmed Faheem Zobaa",profilePictureURL:"https://mts.intechopen.com/storage/users/39249/images/system/39249.jpg",biography:"Ahmed Faheem Zobaa received the B.Sc.(Hons), M.Sc., and Ph.D. degrees in electrical power and machines from Cairo University, Egypt, in 1992, 1997, and 2002, respectively. From 2007 to 2010, he was a Senior Lecturer in renewable energy at University of Exeter, U.K. He was also an Instructor from 1992 to 1997, a Teaching Assistant from 1997 to 2002, an Assistant Professor from 2003 to 2008, an Associate Professor from 2008 to 2013 at Cairo University where he has also been a Professor (on leave) since December 2013. Currently, he is a Senior Lecturer in power systems, an MSc Course Director and a Full Member of the Institute of Energy Futures at Brunel University London, U.K. His main areas of expertise are power quality, (marine) renewable energy, smart grids, energy efficiency, and lighting applications.\n\n Dr. Zobaa is an Editor-in-Chief for the International Journal of Renewable Energy Technology and Technology and Economics of Smart Grids and Sustainable Energy. He is also an Editorial Board member, Editor, Associate Editor, and Editorial Advisory Board member for many international journals. He is a registered Chartered Engineer, Chartered Energy Engineer, European Engineer, and International Professional Engineer. He is also a registered member of the Engineering Council U.K., Egypt Syndicate of Engineers, and the Egyptian Society of Engineers. He is a Senior Fellow of the Higher Education Academy of U.K. He is a Fellow of the Institution of Engineering and Technology, the Energy Institute of U.K., the Chartered Institution of Building Services Engineers, the Institution of Mechanical Engineers, the Royal Society of Arts, the African Academy of Science, and the Chartered Institute of Educational Assessors. He is a senior member of the Institute of Electrical and Electronics Engineers. Also, He is a member of the International Solar Energy Society, the European Power Electronics and Drives Association, and the IEEE Standards Association.",institutionString:"Brunel University London",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Brunel University London",institutionURL:null,country:{name:"United Kingdom"}}},coeditorTwo:{id:"30630",title:"Prof.",name:"Prabhakar",middleName:null,surname:"Karthikeyan Shanmugam",slug:"prabhakar-karthikeyan-shanmugam",fullName:"Prabhakar Karthikeyan Shanmugam",profilePictureURL:"https://mts.intechopen.com/storage/users/30630/images/system/30630.jpg",biography:"S. Prabhakar Karthikeyan has completed his B.E (EEE) from University of Madras, Tamil Nadu (1997), M.E (Electrical Power Engineering) from The M.S. University of Baroda, Vadodara, Gujarat (1999), PhD from VIT University, Tamil Nadu, India (2013) under the guidance of Prof. D. P. Kothari. He has also completed his Post-Doctoral Fellowship from Central Power Research Institute, Bengaluru, Karnataka, India. He is presently with the VIT University as an Associate Professor. He is a Senior Member-IEEE with 31 published articles in peer reviewed journals and 77 works in national and international conferences. His area of interest includes deregulation and restructured power systems under smart grid environment, electric vehicles and issues related to distribution system studies.",institutionString:"Vellore Institute of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Vellore Institute of Technology University",institutionURL:null,country:{name:"India"}}},coeditorThree:{id:"291294",title:"Dr.",name:"Kannaiah Sathish",middleName:null,surname:"Kumar",slug:"kannaiah-sathish-kumar",fullName:"Kannaiah Sathish Kumar",profilePictureURL:"https://mts.intechopen.com/storage/users/291294/images/system/291294.jpg",biography:"Dr. K. Sathish Kumar received a Ph.D from VIT University, Vellore, India. He has 17 years of total teaching experience and in 12 years of his research experience he has worked in various research teams to develop new applications of evolutionary computing algorithms for solving various power system problems like unit commitment, economic dispatch, emission reduction, smart grid, power system reconfiguration and restoration. His current area of interest is studying interconnection problems in linkages of HVDC and HVAC (765 kV) transmission lines with existing 230 kV high voltage lines, Nano additives for high voltage XLPE cables, Optimization of smart grids and Multi level inverters. He is a member of IEEE, IEEE-PES and SSI. He has published 75 research papers in different journals and conferences of international repute and authored a book on power quality. At present he is working for School of Electrical Engineering as an Associate Professor. He is the reviewer for various SCI journals like \\'Electrical power and energy systems\\', ISA Transactions, AAI, etc.",institutionString:"Vellore Institute of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorFour:null,coeditorFive:null,topics:[{id:"770",title:"Renewable Energy",slug:"engineering-energy-engineering-renewable-energy"}],chapters:[{id:"67026",title:"A Reliable Communication Model Based on IEEE802.15.4 for WSANs in Smart Grids",slug:"a-reliable-communication-model-based-on-ieee802-15-4-for-wsans-in-smart-grids",totalDownloads:108,totalCrossrefCites:0,authors:[null]},{id:"69616",title:"Hybrid Modeling Procedure of Li-Ion Battery Modules for Reproducing Wide Frequency Applications in Electric Systems",slug:"hybrid-modeling-procedure-of-li-ion-battery-modules-for-reproducing-wide-frequency-applications-in-e",totalDownloads:37,totalCrossrefCites:0,authors:[null]},{id:"66100",title:"Voltage Regulation in Smart Grids",slug:"voltage-regulation-in-smart-grids",totalDownloads:179,totalCrossrefCites:0,authors:[null]},{id:"65420",title:"A Distributed Optimization Method for Optimal Energy Management in Smart Grid",slug:"a-distributed-optimization-method-for-optimal-energy-management-in-smart-grid",totalDownloads:489,totalCrossrefCites:0,authors:[null]},{id:"65607",title:"Connected Autonomous Electric Vehicles as Enablers for Low-Carbon Future",slug:"connected-autonomous-electric-vehicles-as-enablers-for-low-carbon-future",totalDownloads:233,totalCrossrefCites:0,authors:[null]},{id:"69786",title:"Microgrid",slug:"microgrid",totalDownloads:56,totalCrossrefCites:0,authors:[null]},{id:"65727",title:"Solid-State Transformer for Energy Efficiency Enhancement",slug:"solid-state-transformer-for-energy-efficiency-enhancement",totalDownloads:317,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270941",firstName:"Sandra",lastName:"Maljavac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270941/images/7824_n.jpg",email:"sandra.m@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"3633",title:"Solar Energy",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"solar-energy",bookSignature:"Radu D Rugescu",coverURL:"https://cdn.intechopen.com/books/images_new/3633.jpg",editedByType:"Edited by",editors:[{id:"8615",title:"Prof.",name:"Radu",surname:"Rugescu",slug:"radu-rugescu",fullName:"Radu Rugescu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3118",title:"Solar Cells",subtitle:"Research and Application Perspectives",isOpenForSubmission:!1,hash:"5502d7fd7559d60419f2615615ae4cf5",slug:"solar-cells-research-and-application-perspectives",bookSignature:"Arturo Morales-Acevedo",coverURL:"https://cdn.intechopen.com/books/images_new/3118.jpg",editedByType:"Edited by",editors:[{id:"90486",title:"Prof.",name:"Arturo",surname:"Morales-Acevedo",slug:"arturo-morales-acevedo",fullName:"Arturo Morales-Acevedo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"877",title:"Third Generation Photovoltaics",subtitle:null,isOpenForSubmission:!1,hash:"c3bdfaebac38dab83a69c488bcda219d",slug:"third-generation-photovoltaics",bookSignature:"Vasilis Fthenakis",coverURL:"https://cdn.intechopen.com/books/images_new/877.jpg",editedByType:"Edited by",editors:[{id:"68723",title:"Dr.",name:"Vasilis",surname:"Fthenakis",slug:"vasilis-fthenakis",fullName:"Vasilis Fthenakis"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1288",title:"Solar Cells",subtitle:"Dye-Sensitized Devices",isOpenForSubmission:!1,hash:"05a255471069664ecf5fbf8778b92076",slug:"solar-cells-dye-sensitized-devices",bookSignature:"Leonid A. 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Kosyachenko",coverURL:"https://cdn.intechopen.com/books/images_new/1289.jpg",editedByType:"Edited by",editors:[{id:"6262",title:"Prof.",name:"Leonid A.",surname:"Kosyachenko",slug:"leonid-a.-kosyachenko",fullName:"Leonid A. Kosyachenko"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1679",title:"Solar Radiation",subtitle:null,isOpenForSubmission:!1,hash:"b0b9fb90b15500b61d5a45e26648ff57",slug:"solar-radiation",bookSignature:"Elisha B. Babatunde",coverURL:"https://cdn.intechopen.com/books/images_new/1679.jpg",editedByType:"Edited by",editors:[{id:"103748",title:"Prof.",name:"Elisha B.",surname:"Babatunde",slug:"elisha-b.-babatunde",fullName:"Elisha B. Babatunde"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1328",title:"Hydropower",subtitle:"Practice and Application",isOpenForSubmission:!1,hash:"08b3b6e6e1b5339cad8f69c9d483a594",slug:"hydropower-practice-and-application",bookSignature:"Hossein Samadi-Boroujeni",coverURL:"https://cdn.intechopen.com/books/images_new/1328.jpg",editedByType:"Edited by",editors:[{id:"94088",title:"Dr.",name:"Hossein",surname:"Samadi-Boroujeni",slug:"hossein-samadi-boroujeni",fullName:"Hossein Samadi-Boroujeni"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"64267",title:"Alternative Approaches to Combat Medicinally Important Biofilm-Forming Pathogens",doi:"10.5772/intechopen.80341",slug:"alternative-approaches-to-combat-medicinally-important-biofilm-forming-pathogens",body:'Biofilm formation is structured accumulation of fastidious microorganisms attached on inanimate objects or compact surfaces that extensively have been examined in the past decades because they particularly cause infections and more often responsible for chronic infections [1, 2, 3]. They are predominantly problematic due to their antimicrobial resistant properties and their ability to evade host defense mechanisms, which substantially hinders disease treatment in the hospital [1, 2, 3, 4]. Bacterial biofilms are ubiquitous in nature and harbor phenotypic adaptations in the environment with respect to broader perspective [1]. The nature of single cell organisms enables them to adhere to each other and form a “complex structure,” which assists to survive under adverse environmental condition. The biofilm formation occurs from planktonic bacteria due to environmental changes and involves in conjugation gene transfer “multiple regulatory network” from one bacterium to another in response to environmental stress [5, 6, 7, 8, 9]. This type of cell-to-cell adhesion and gene transformation changes the expression of surface molecules, virulence factors, and nutrient utilization that enables their survival under unfavorable environmental condition [8, 10, 11, 12, 13, 14, 15, 16, 17].
Bacteria are cocooned within the biofilm and form extracellular matrix, which represents 90% of the biomass [18]. The matrix as a stabilizing scaffold for the three-dimensional structure is composed of extracellular polymeric substance (EPS) along with extracellular DNS and carbohydrate binding protein [19, 20, 21]. Nutrients are trapped by the resident bacteria in the matrix and water is retained efficiently via H-bond interaction with hydrophilic polysaccharides [18, 22]. The composition of extracellular polymeric substance (EPS) is modified in response to alterations in nutrient availability [23, 24] by certain enzyme secretion of bacteria, thus tailoring biofilm formation to the more specific environment [23, 25]. Therefore, the skeletal components of the extracellular matrix are highly hydrated and provide high tensile strength that enables bacteria to exchange their DNA by conjugation and promote cell-to-cell interaction while defending the biomass from predation, radiation, desiccation, oxidizing molecules, and other dangerous agents [18, 26, 27, 28].
The multifaceted nature of biofilms that allow the bacteria to form a community, i.e., division of labor and express their virulence factors in response to local oxygen and nutrient availability, makes them resistant against different antimicrobial agents [29, 30]. Some studies have shown that there are presence of nondividing metabolically inactive recalcitrant bacteria within the biomass [29, 31], which play very crucial role to cause tolerance against broad-spectrum antimicrobial drugs. The matrix protein inside the host cell protects bacterial biofilm against innate immune defenses, i.e., phagocytosis and opsonization [32]. The spread of other virulence factors inside the host cell and drug resistance marker is due to the cell-to-cell interaction [15]. Thus, biofilm-forming pathogens retained and adhere to the infected surface and cause recalcitrant and chronic infection, i.e., upper respiratory tract infection (particularly, Pseudomonas aeruginosa) [33, 34], dental decay (mixed culture of Streptococcus mutans, and other pathogens) [35], ventilated-induced and other device-associated infections (Escherichia coli, Klebsiella spp., Enterococcus faecalis, Staphylococcus aureus, etc.) [36, 37], urinary tract infections [Proteus spp., uropathogenic E. coli (UPEC)] [38]. In particular, immunocompromised patients are the most common target to all these biofilm-forming pathogens, causing a devastating impact on patients, and in many cases, leading to death. Here, we analyze the formation of intracellular and extracellular biofilm which is the underlying factor for various medically important microorganisms. Given the recalcitrance and prevalence of infections caused by biofilm-forming pathogens, we discuss knowledge about the most current progresses in the advancement of novel strategies of biofilm.
Bacterial biofilm growth, subsequent maturation, and aggregation consist of irreversible and reversible stages, which involve various conserved and species-specific aspects. At the first stage, the bacteria are introduced on the surface; a process of at least a part of stochastic that is driven by gravitational forces and Brownian motion, and usually influenced by nearby hydrodynamic forces [39, 40]. Microorganisms encounter with repelling or attractive forces—within the niche that alter depending on ionic strength, pH, nutrient levels, and temperature. Bacterial cell wall composition, along with medium properties, affects direction and velocity toward or away by the contact surface of pathogens [39]. Motile bacteria utilize flagella in order to overcome repulsive and hydrodynamic forces, by having a competitive advantage. The main function of flagella is to provide motility and initial cell attachment to the surface for various pathogens, including Listeria monocytogenes, E. coli, Vibrio cholerae, and P. aeruginosa [41, 42, 43, 44, 45]. In some species of bacteria, chemotaxis plays very important role in direct attachment to nutrient composition, for instance, mutations arise in CheR1 methyltransferase, which have been observed to vary the response of amino acid of P. aeruginosa and impair maturation of bacterial biofilm and attachment [46]. Some earlier studies have been shown that chemotaxis in E. coli is dispensable [5]; moreover, current observations revealed that the disruption occurs in the chemotaxis methyl accepting protein II and informs biofilm defects particularly in uropathogenic E. coli cells [47]. With respect to intercepting surface, bacterial attachment is facilitated by additional secreted molecules such as adhesin protein and extracellular adhesive appendages.
Initially, the attachment is reversible and dynamic during which pathogens can separate and rejoin planktonic biomass if agitated through repulsive forces [48], hydrodynamic forces—detach bacteria off from the surface. Some bacteria attained irreversible attachment in order to maintain a firm grip on the cell surface. Serotypes of other E. coli and uropathogenic E. coli depend intensely on the type 1 pili [5, 40, 49, 50, 51]. Uropathogenic E. coli harbors several pili systems (means CUP system), which mediate adhering to a specific niche [38]. Attachment on the bacterial surface is facilitated by the adhesion protein (FimH), which identifies mannosylated moieties [50, 51, 52]. The adhesive protein (FimH) plays a critical role in the pathogenesis of uropathogenic E. coli because it facilitates adherence and causes invasion to epithelial cells of bladder in human, adheres to the human uroplakin and is also critical in preclinical murine cystitis model, which causes human disease [51, 53, 54]. FimH is much more consistent to play a critical role in the virulence of human disease under positive selection [52, 53, 54, 55, 56].
Furthermore, antigen 43, curli fibers, and type 1 pili have been observed to facilitate attachment and cell-to-cell interaction on inanimate surfaces [57]. Curli fiber also mediates attachment to the extracellular matrix components in eukaryotes such as plasminogen, fibronectin, and laminin [58]. Pseudomonas aeruginosa, for instance, uses various additional organelles, which assist in adherence to the surface, irreversibly. Contrary to UPEC and P. aeruginosa, Gram-positive bacteria (Enterococci) are lactose producing, nonmotile, and recently identified to contain nonadhesive (pili) that mediate attachment to the extracellular matrix components in eukaryotes. Examples of these include Ace (E. faecalis) and SagA (E. faecium), which attach to the collagen protein [59] and surface protein (Esp). This has been observed to stimulate abiotic formation of biofilm on the contact surface specifically in E. faecalis [60]. Current studies showed the existent of biofilm-associated pili (Ebp) and also confirmed their contribution toward urinary tract infections, endocarditis, and biofilm formation and attachment [61].
Cell-to-cell interaction triggers specific intrinsic responses that cause changes in the gene expression, upregulating factors favorable to sessility especially for those involved in extracellular matrix protein formation [40]. However, relatively very little information is obtained about the matrix constituents with respect to E. coli pathogen. Initially, cellulose was recognized as essential components in E. coli pellicle biofilms and later on expressed with curli fibers in gastrointestinal E. coli strains [62]. Curli fiber plays a critical role in pellicles, for instance, curli fiber (amyloid) that leads to the pellicle biofilm formation. It also acts as a curlicide to prevent pellicle formation, and some of them have deficient to form pellicles (known as curli mutants) [63]. Further studies revealed that colonic acid and polyglucosamine (PGA) take part in biofilm architecture [64], while the PGA being predominant among the clinical strains, particularly in UPEC isolates. Thus, more detailed investigations are required for further characterization of extracellular matrix protein in E. coli. The composition of extracellular matrix protein has been extensively analyzed in P. aeruginosa and varies depending on external environmental conditions [65]. The primary components of EPS are Psl and Pel [25]. Psl enhances the attachment of P. aeruginosa to epithelial cells [66] and mucin, while the expression of Pel increased in small colony variants (SCV) isolated from the cystic fibrosis patients associated with Pseudomonas persistence in the airways of lung [67]. Moreover, intercellular interactions and biofilm stabilizations in P. aeruginosa are critical in response to environmental DNA (eDNA) [68].
Mature P. aeruginosa biofilm formations are more resistant to treatment with DNase as compared to young biofilms, demonstrating that eDNA remains stable because the components of EPS are not abundant during the initial stage of biofilm when the bacterial cells come to attach each other. In contrast, the concentration of eDNA increases during biofilm maturation stage due to the occurrence of bacterial cell lysis in response to quorum sensing mechanism of Pseudomonas quinolone signal (Pqs) [69]. In Pseudomonas, type IV pili play an essential role in the migrating pathogens to form aggregation in the area of high eDNA binding attraction [70]. The amount of eDNA to form biofilm structure has already been observed in E. faecalis. Some reports identified that biofilm formation in this organism is influenced by the affected autolysis of cells and intracellular release of DNA [71, 72]. Initial study reported that the mutant reduced the biofilm formation by 30% due to the lack of autolysin gene, Atn [59]. In another study investigated, it showed that specific stage of bacterial biofilm formation required temporal regulation by Atn for the release of DNA [73].
Bacterial mature biofilm provides a suitable living environment to the resident microorganisms for making compact surface adherence community, so as to share products and actively exchange their genetic materials by conjugation. Moreover, as biofilms mature, dispersal becomes a choice. In addition to passive dispersal caused by shear stress, the pathogen develops different ways to recognize environmental changes, which make it to stay within the biofilm. Bacterial biofilm dispersal occurs as a result of various clues such as oxygen fluctuations, modifications in nutrient availability, and increases in toxic products [74]. Biofilm dispersal is induced by the increase of extracellular iron in uropathogenic E. coli [75], while in Pseudomonas spp., it is due to the increased quantities of various nitrogen and carbon source [76]. The amounts of small molecules such as alterations in environment and changes in gene expression are monitored by various sensory systems [77]. Among various other signals, for instance, universal cyclic-di-GMP has been used in P. aeruginosa and E. coli causing implication in a shift between motility and sessility. Typically, an increase in the level of cyclic-di-GMP is favorable to sessility, while a reduction in cyclic-di-GMP induces upregulation of motility [78].
Recently, some results reported the factors responsible for such changes such as downregulation of extracellular polymeric substance, reduction of cyclic-di-GMP in bacterial biofilm communities, and upregulation of swarming and swimming motility [25]. Certain type of enzymes (such as alginate lyase) also participates in pathogen detachment from surface especially in P. aeruginosa [79], whereas in E. coli, the enzyme (CsrA) is responsible to repress the synthesis of PGA [80]. Along with that downregulation of EPS, certain molecules of surfactant are produced causing a reduction in cell-to-cell interaction. Moreover, studies identified that flagellated populations within the biofilms of P. aeruginosa migrate to other void surface in order to make colonies [65]. Initially, these colonies loosely attach to compact surface, but after maturation process, they make a hard shell in the surrounding and use the infected surface as a source of nutrient. Sometimes, live cells use dead cells as a source of carbon. When bacteria become dead, then live cells accumulate on it, bind to each other by sharing their genetic materials and form a compact layer that is usually very hard to break. Dead cells are also responsible for creating cavity within the bacterial biomass. The bacteria within the biofilm can be scattered by applying dispersal mechanism.
Due to dispersing nature of bacteria, they may have the ability to restart the biofilm formation process after encountering a favorable environmental condition [81]. This is another sophisticated mechanism of dispersal revealed by using B. subtilis, which could be prevalent among the bacterial species. Researchers reported that the pathogen (B. subtilis) lost its cellular integrity within 5–8 days and also found that disassembly of biofilm is associated with a mixture of different amino acids (D-tyrosine, D-methionine, etc.) that are formed during bacterial stationary growth phase [82]. These D-types of amino acids interfere with bacterial attachment to cell surface and perturbation to fiber dissociation, without influencing matrix component expression or bacterial growth [83]. In B. subtilis, the performance of biofilm is disrupted by the addition of D-type amino acid mixture [83]. Further studies showed that another factor such as norspermidine, which is produced by B. subtilis, works together with D-type amino acid leading to biofilm disassembly [84]. So, this type of association—norspermidine/D-type amino acid—is essential for the eradication of bacterial biofilm and makes them vulnerable to antimicrobial agents used in the hospital.
Gathering evidence have showed that numerous bacterial pathogenic species formerly considered as extracellular can retain within the host cell by adapting intracellular bacterial lifestyle that includes the bacterial communities having biofilm-like properties. First, a murine model of infection was used to assess the bacterial communities for UPEC [85]. Type 1 pili in uropathogenic E. coli bind to the receptor on superficial bladder cells [86], triggering to induce bacterial internalization. Toll-like receptor-4 (TLR-4)-dependent process used to expel out from inside the UPEC [87], but certain bacteria elude exocytic procedure and leave out from the cytoplasm of host cell, where they duplicate into intracellular bacterial communities (IBCs) [85]. Several developmental stages lead to the process of IBCs that indicate distinct morphological features [85]. After passing first 6 h ensuing bladder inoculation, UPEC rapidly divides (replication time 30–35 min) causing small clusters associated with loosely attached rods (during early IBCs), having a coccoid shape and an average bacterial length of about 0.7 mm. The bacterial exponential growth rate dramatically drops between 6 and 8 h, exceeding replication time to 60 min. This is the second stage where bacteria accumulate and are tightly packed within the biofilm and organized a compact sphere-shaped structure (mature-stage IBCs) (Figure 1).
Schematic diagram of the development of IBC cascade in uropathogenic E. coli (UPEC), taken by scanning electron microscope (SEM) images indicating different structural changes from attachment to dispersion and fluxing.
The amount of IBCs is found between 3 and 700 in an infected patient’s bladder—IBCs are composed of 104–105 bacterial cells [88]. There are numerous fibers surrounded on IBC bacteria that originate from the surface of pathogen and enclose pathogens in individualized sections. One of the main components present on the surface of IBCs called polysaccharide (sialic acid) that provides protection from the attack of immune system and environmental stress. The heterogeneous nature of IBCs, such as extracellular bacterial biofilm, composed of different subpopulation having distinct gene expression systems [89]. As IBCs expand, they induce the bacterial biofilm to cause interruption against cell membrane of host, producing a pod-like structure on the infected cell surface. Ultimately, UPEC detaches as filament or single rod at the IBC boundary and the infected cells are flux out into the lumen of bladder where can invade epithelial cells and restart the process through binding [85]. The inhibitor (SuIA) of cell division has been observed to be crucial for dispersal and filamentation of UPEC from the bacterial biofilm. The patients suffered from urinary tract infections (UTIs) are more likely observed with the UPEC filaments in their urine, but not in comparison with healthy controls [90].
The formation of IBC is prevented by intense molecular blockages and during acute infection—development of chronic cystitis—the IBC numbers are higher, representing the significance of intracellular pathways in the pathogenesis of UTIs [88]. The cycle of IBC is dependent on FimH, causing interruption in the expression of type-1 pili after invasion to host cell, and disrupts normal development of IBC due to attenuation of UPEC [54]. The two-component system (QseBC) is a key factor influencing curli expression, formation of IBC and type-1 pili. Some studies indicated that the intracellular pathway of UPEC is necessary for the TCA cycle completion [47]. The techniques such as qPCR and DNA microarray analyses interpreting the UPEC expression patterns within IBC pathogen exposed that acquisition of iron in bacteria is upregulated, representing the significance of system biomass formation [91]. While in clinical isolates of UPEC, the iron acquisition patterns are prevalent [92]. Moreover, the pathogen Klebsiella pneumoniae is more commonly seen in community- and hospital-acquired infection. About up to 5% forms intracellular communities and is more predominant in hospitalized diabetic patients [93]. Likewise to UPEC, the Klebsiella pneumoniae invasion is mediated by type-1 pili and formation of IBC, although the differences occur in the expression kinetic of pili and filaments [90]. The ability to occupy an intracellular niche and persist within the host cell through transitioning from single microbial cell to the multicellular community is not confined to uropathogens. Researchers showed that by using different animal models and cell line of acute lung infection, the cluster formation occurs inside the lung airways due to P. aeruginosa, morphology similar to Klebsiella and UPEC (IBCs) [94]. The biofilm formation ability could be evolutionary adaptation of pathogens that enable the bacteria to persist within the host cell. All these findings represent the formation of IBC, a process that enables the bacteria to rapidly expand inside the host cell and take part in bacterial persistence.
Broad-spectrum antibiotics are the drug of choice for the treatment of bacterial infections. Conventional antibiotics act as either killing the bacterial cell (bactericidal) or inhibiting the cell division (bacteriostatic). Numerous evidence shows that the use of antibiotics extensively causes damage to the host microbiota, producing a condition where invading bacteria can prevail and enhance the selective pressure against drug resistance [95]. Furthermore, surgery proceeded by administering antibiotics is highly successful in order to minimize the infection prophylactically. In certain cases, the perfect treatment of choice for foreign material associated with biofilm infections is the removal of infectious device. In some cases like pacemakers, cardiac implants and implantable prostheses, device removal is difficult [37]. Biofilm formation nature of bacteria that make them recalcitrant against different antimicrobial drugs is a result of prolonged treatment. There is a need for the irradiation or complete removal of these kinds of pathogens. Antibiotic resistance is not only due to increased resistance markers transmitted within the bacterial biofilm community, but also due to high metal ion concentration, low pH, and the presence of persistent cells that are metabolically inactive and inactivate the antibiotics [31]. All these characteristics make bacterial biofilm more tolerant/resistant to antimicrobial drugs up to 1000-fold more when compared to planktonic bacterial cells [96]. Therefore, an alternative strategy must be investigated to combat the antibiotic resistant strains and make them vulnerable to antimicrobial drugs. Here below, we have mentioned some of the recent developments in strategies that are considered to prevent formation of biofilm by bactericidal mechanism or targeting distinct developmental stages of biofilm (Figure 2).
Schematic diagram about the different stages in the development of biofilm and indicating the strategies to preventing and damaging the bacterial biofilm production at particular stages.
There are studies that have reported that the presence of any foreign body (indwelling medical devices such as implants or prostheses or catheters) in low inoculums of Staphylococcus aureus (102 CFU/ml) in animal tissues was sufficient to form abscesses in the patients (95%) despite significant existence of leukocytes. In fact, this could be associated with the existence of any foreign material considerably intracellular bactericidal effects of body immune cells (leukocytes) and downregulated the mechanism of phagocytosis [97]. The polymorphonuclear leukocytes cannot perform well in the presence of any foreign body because it provides a surface ideal for the bacterial attachment. Therefore, the existence of any foreign material considerably increases the chances of bacterial biofilm formation. This leads to the pathogen becoming more persistent and resistant against conventional antibiotics. Thus, potential therapeutic strategy is required for the elimination of such type of bacterial biofilm formations. Certain precautionary measures could be employed, for instance, to replace the infected devices used for medical purposes in the patients with a new one. Otherwise, it would be hard to overcome the problem regardless of applying various effective antimicrobial drugs in response to fastidious pathogens. Changing dialysis catheter if it is infected by the pathogens is another measure that could be taken. When pathogen forms biomass on the catheter, it could be the source of bacterial colonization leading to bacteremia which may be caused by a deadly bacterial strain. For the cure of catheter-associated infections caused by bacterial biofilm formation, it is important to change the catheter infected with pathogens along with administration of antibiotic intravenously during a short time in order to eradicate the pathogen before it invades into the bloodstream. However, in some cases, it is hard to change the catheter temporarily; therefore, antimicrobial drugs and other alternative therapy may be the best option for the minimal release of pathogens from the infected site.
An alternative approach to antibiotic treatment is phage therapy [98]. Phages are present in a wide range in the environment. It can be isolated easily and ubiquitous in nature. Their host ranges from specific to narrow, they are able to self-replicate, and therefore, a small dosage may be sufficient to disturb the host microorganisms. Furthermore, high mutation rate of phage facilitates adaptation as conforming bacterial host aggregate mutations to fix in a specific environment. Phage therapy has various advantages during lytic cycle phage that does not enter prophage cycle and rarely transfers or contains a virulence gene, thus causing destruction of bacterial cell rapidly. Many phages are associated with EPS degrading protein [99] or spread during stationary growth phase; these features allow to persist inside the bacterial biofilm [100].
This is another alternative approach used for the improvement of new type of antimicrobial drug, usually produced by innate immune response mechanism [101]. Contrary to that, their mechanism of action and antimicrobial spectrum activity must be defined more accurately before applying as a therapeutic strategy. Cathelicidin, for instance, possesses most essential type of antibacterial peptides. The biofilm formation of multidrug-resistant Pseudomonas strains, isolated from cystic fibrosis (CF) patients, is reduced considerably by BMAP-28, BMAP-27, and BMAP-29 [102]. According to a recent study by Pompilio et al. [102], antimicrobial activity of tobramycin against multidrug-resistant strains is less than cathelicidin peptides. This study indicates that the multidrug-resistant strains are vulnerable to cathelicidins due to antibiofilm agents. Another important group that can be used to assess the inhibitory effects is called lytic peptides. These peptides assist in attachment of lipopolysaccharides (LPS) to the cell membrane of pathogen and cause cell membrane disruption. The study on Staphylococcus aureus indicated that in vitro formation of biofilm is prohibited by the lytic peptide (PTP-7) and easily penetrates the bacterial biofilm causing death of the bacteria at a rate of 99.9%. This peptide has the capacity to bear extreme acidic environment and inhibit the biofilm formation of Staphylococcus aureus [103].
Many researchers have done research on the antimicrobial property of silver nanoparticles. Fey [37] found that the silver nanoparticles are the best alternative strategy to combat the bacterial biofilms. For example, antimicrobial agents (silver nanoparticles) have been incorporated with medical devices and have showed to inhibit the device-associated bacterial biofilms. Silver was frequently used as an antimicrobial agent for different pathogens over a 100 years; for instance, during World War 1, it was extensively used to sterilize the wound infections [104]. The antimicrobial activity of silver nanoparticles depends on the positively charged ions of metal and electrostatic interactions between negatively charged cell membrane of bacteria [105]. The thiol group in silver is the main cause of death in bacteria that play an important role in the inactivation of enzyme [106]. This is the reason why silver nanoparticles are increasingly used in response to various bacterial infections. The antimicrobial agents contain different properties such as high aspect ratios, nonimmunogenic, biocompatible, nonbiodegradable, ultralight weight, and easy cell membrane penetration. Due to such remarkable properties, we can apply silver nanoparticles in various applications such as infection therapy, gene therapy, and as antioxidants. The size of silver nanoparticles is typically smaller than 100 nm. The mechanism of action of silver nanoparticle is to interrupt the cell membrane of bacteria, generate the reactive oxygen species (ROS), interrupt the metabolic pathway, prevent the replication of DNA, disrupt the bacterial electron transport chain (ETC) [106], and release the toxic ions outside the bacterial cells that lead to the death of bacteria. There are large numbers of studies conducted regarding toxicity mechanism of silver nanoparticles in rabbits. There is a study that showed that silver nanoparticles inhibited bacterial biofilm formation against Staphylococcus aureus, without accumulating inside the host tissue [106, 107].
Bacterial cell-to-cell interaction mediated by the exopolysaccharides is a serious threat to the formation of biofilm and stabilization. Mutants incapable to export or synthesize such exopolysaccharides are usually deficient in the formation of biofilm and adherence and hence are extremely sensitive to killing through host immune defenses and antimicrobial drugs [108]. Recent studies showed that certain bacterial exopolysaccharides destabilize or prevent biofilm formation by some pathogenic species. For instance, the existence of Pseudomonas aeruginosa prevented biofilm formation of S. epidermidis in in vitro experiments [109]. Polysaccharides along with nonbactericidal antibiofilm characteristics have been separated from acellular biofilm (or biomass) extracts of various species [108]. The antibiofilm properties of Pseudomonas aeruginosa have the ability to act as signaling molecules that effect the expression of genes in susceptible pathogens, change the physical features of isolated bacterial cells, and prevent the protein-carbohydrate interactions. Most polysaccharides with antibiofilm properties allow a broad-spectrum inhibition of biofilm, while some are proficient of scattering preformed biofilms. So far, there are evidence suggests that polysaccharide with antibiofilm features acts as a surfactant molecule that alters the physical properties of abiotic surfaces and bacterial cells. Some results also show that polysaccharides might modulate the expression of genes of the recipient pathogenic bacteria by acting as signaling molecules [110]. Another potential mode of action of polysaccharide is to prevent competitively the multivalent protein-carbohydrate interactions [66]. As a result, polysaccharides with antibiofilm properties might block tip adhesins of pili and fimbriae, or block sugar or lectin-binding proteins that are present on the outer surface of pathogens. In pathogen P. aeruginosa, for instance, lectin-dependent adhesion to human cell is proficiently repressed by galactomannans [111]. This kind of polysaccharides that inhibit the biofilm could be a prominent strategy appropriate for the prevention of bacterial infections. Some scientist showed that antibiofilm polysaccharides can be used as an adjuvant because of enhancing antibiotic drug functions [108].
Many studies have been carried out on biofilm inhibition caused by interruption of the pathogen signaling cascades. This is possible provided that the two-component systems in bacteria establish a dominant means of translating and intercepting the environmental changes. Signal transduction inhibition system plays a critical role in response to antimicrobial therapy because of this type of signaling cascade interruption. Not only does it kill the pathogen, but it also interferes with the gene expression. Two-component system (QseBC) is the best alternative candidate for targeting the drugs, particularly in Gram-negative biofilm-forming pathogens [112]. QseC/QseB establishes a significant association between the bacterial environmental signaling and the host stress response. The pathogen (E. coli) responds to autoinducer-3 in the intestine that is formed by the human stress hormones (such as epinephrine and norepinephrine) and gut flora. The cascade of signaling transduction comprises chemotaxis by activation of QseC and by using the serine receptor Tsr. In the quest for novel antimicrobial drugs and therapeutic targets, two-component system (QseBC) can play an important role to inhibit biofilm formation by blocking the binding of epinephrine or norepinephrine to QseC, as a result to reduce QseB/QseC signaling and decrease virulence and motility [113]. Studies have also suggested that the removal of QseC in EHEC and UPEC causes an excessive activation of response regulator QseB, owing to particular QseC phosphatase activity required for deactivation of QseB. The optimal strategy behind targeting the phosphate activity is to interfere with common gene expression in QseC containing pathogens [47]. Some other studies focused on the FsrATC/FsrA inhibitors in E. faecalis. The expression of gelE-sprE and FsrBDC control by the FsrC/FsrA leads to increase in the production of serine protease and gelatinase, both are crucial for the proper eDNA production [71].
Apart from that, extracellular matrix with disrupting components is also very important to target the bacterial aggregates. Various observations exploited the inhibiting enzymes potentially involved in the modification or synthesis of cell wall-secreted or associated with EPS components. In these studies, use of engineered or naturally occurring enzyme and use of phage therapy as an enzyme delivery vehicle or to interrupt with matrix integrity by taking benefits from metal chelators have been recommended.
Metal cations such as iron, magnesium, and calcium have been associated with stabilizing the matrix integrity [114]. Chelating agents indicated to cause interruption in the bacterial cell membrane stability besides disrupting the bacterial biomass structure [39]. In vitro study showed that biofilm formation was inhibited in various Staphylococcus species by sodium citrate [115]. Furthermore, eradication of bacterial biofilms in in vitro experiments is also facilitated by tetrasodium EDTA, while disodium EDTA only reduced the bacterial biofilm formations in P. aeruginosa and Staphylococcus species [116]. Current reports suggested that the solution of minocycline-EDTA was used to inhibit indwelling catheter-associated infections especially in children. There were no adverse side effects observed in patients treated with the solution of minocycline-EDTA but only a limited number (21%) of untreated group (control) developed infections [117]. Moreover, in hemodialysis patients, catheter-associated bloodstream infections were observed after applying minocycline-EDTA [118].
The main mechanism of active dispersal of bacterial biofilm is through the formation of extracellular enzymes (proteins) that act on several structural components (such as exopolysaccharides, surface proteins, and extracellular DNA) of the extracellular polymeric substances. These enzymes play an important role in the cell separation from the bacterial biofilm colonies and facilitate their planktonic discharge into the environment [119]. Through purifying and isolating these enzymes, therapist can apparently add them to preformed bacterial biofilms exogenously at raised concentrations, in order to make biofilm-associated bacteria more susceptible to antimicrobials/antibiotics and to achieve interventional dispersal of biofilms. For this purpose, several classes of enzymes (specifically proteases, glycoside hydrolases, and deoxyribonucleases) have been explored for the eradication of bacterial biofilms [119]. The enzymes dispersin-B and DNase-I have gained greater attention as possible antibiofilm agents, especially in response to Gram-positive bacteria. The DNase effect depends on its capability to interrupt the eDNA that is established within the bacterial biomass structure [73]. The treatment of DNase prevents biofilm formation in Enterococcus and Staphylococcus and dispersed bacterial biofilm [73]. For the treatment of patients with cystic fibrosis (CF), a recombinant enzyme (pulmozyme) is used in some cases [37]. However, treatment with dispersin-B represented to be more effective in response to S. aureus and S. epidermidis [77]. In vitro studies indicated that engineered dispersin-B used bacteriophage machinery in order to replicate during the stationary phase of cell growth, hence causing disruption of complete E. coli biofilms [120].
Currently, the removal of bacterial biofilm is the most challenging task for the clinicians and microbiologists. Antibiotics are not the best choice for the treatment of infections caused by bacteria forming biofilm. Biofilm formation allows the pathogen to adhere to the host surface under extreme condition and is resistant against a wide range of antibiotics. The choice of drug depends on the characteristics of the biofilm such as composition, age, solidity, and type of pathogens. These are the major components influencing the microbial susceptibility. As the bacterial biofilm matures, it enhances the accumulation of exopolymeric substance (EPS), attaches with the oxygen and nutrient gradients that effect bacterial growth rates and metabolism of cells, becomes impermeable, and reduces the activity of antimicrobial agents. This leads to resistance to most antibiotic regime. Therefore, novel potential therapeutic strategies should be considered to curb bacterial biofilm formation at specific stage without harming the pathogen. Antiadhesion and antimatrix agents are exciting strategies that may be used pending further investigation. extracellular polymeric substance deoxyribonuclease carbohydrate-binding protein deoxyribonucleic acid chaperone-usher pathway uropathogenic E. coli polyglucosamine small colony variants environmental deoxyribonucleic acid Pseudomonas quinolone signal cyclic di-GMP alginate lyase Bacillus subtilis toll-like receptor-4 intracellular bacterial communities urinary tract infections scanning electron microscope tricarboxylic acid quantitative polymerase chain reaction hospital-acquired infections colony forming unit multidrug resistant lipopolysaccharides electron transport chain reactive oxygen species enterohemorrhagic E. coli ethylene-diamine-tetra-acetic acid cystic fibrosisList of abbreviations
Sandflies are present in tropical and subtropical, arid and semi-arid areas and temperate zones including southern Europe, Asia, Africa, Australia, Central and South America. Phlebotomine sandflies are tiny diptera insects grouped in the family Psychodidae, subfamily Phlebotominae. To date, over 800 species are estimated to exist in different regions of the world [1]. Two genera (Phlebotomus and Sergentomyia) of Phlebotominae are mostly recorded in the old world (OW) and the other genus Lutzomyia exists in the new world (NW) [2]. Only females are hematophagous and require a blood meal to develop their eggs. Sandflies take blood from a wide range of animals such as cold-blooded vertebrates, mammals and birds; trophic preferences vary depending on the sandfly species.
Of the 800 sandfly species, at least 98 are proven or suspected vectors of microorganisms capable to cause parasitic, viral or bacterial diseases in vertebrates [1]. This chapter will focus essentially on sandfly-borne viruses, which have been proven agents of diseases in humans.
The arthropod-borne diseases including sandfly-borne viral diseases affect urban, peri-urban, and rural population but mostly the communities with poor living conditions. Economic, social and ecological conditions have a huge impact on sandfly-borne viral diseases [3, 4]. The factors that described as associated with arthropod-borne diseases emergence or invasion are (i) competent vector and vertebrate host population repeatedly in contact within an appropriate environment, (ii) vertebrate or vector host species composition changes, (iii) environmental or niche changes and (iv) genetic changes [5].
Although sandflies can transmit a number of arthropod-borne viruses within the families Phenuiviridae, Reoviridae and Rhabdoviridae, they remain neglected vectors of viral diseases in contrast with a high interest for parasitic diseases such as leishmaniasis. The three virus families contain human/animal pathogens. In the Rhabdoviridae family, attention will be given to Chandipura virus; in the Reoviridae family, we will focus on Changuinola virus [2, 6, 7, 8]. In the Phenuiviridae family, we will focus on Sandfly fever Sicilian virus, Sandfly fever Naples virus, Toscana virus, Adria virus and Punta Toro virus (PTV).
Phleboviruses are enveloped viruses with single-stranded trisegmented RNA. They contain three genomics segments: L (Large) segment encodes the viral RNA polymerase (RdRp), M (medium) segment encodes envelope glycoproteins (Gn and Gc) and non-structural protein m (NSm) and S (small) segment encodes nucleocapsid protein (N) and non-structural protein s (NSs) [9].
Currently, 10 species within the genus Phlebovirus are recognized by the International Committee on Taxonomy of Viruses (ICTV): Sandfly fever Naples virus, Salehabad virus, Rift Valley fever virus, Uukuniemi virus, Bujaru virus, Candiru virus, Chilibre virus, Frijoles virus, Punta Toro virus, and Severe fever with thrombocytopenia syndrome virus. Of interest, almost 40 phleboviruses are still listed as tentative species for which the ICTV has not officially ruled; interestingly, Sandfly fever Sicilian virus still belongs to this pending group although discovered in 1943 [10].
Phleboviruses can be detected and isolated from blood-sucking female sandflies and from non-blood-sucking males in equal proportions [11, 12, 13, 14]. This suggests that alternative transmission pathways (other than blood-borne from vertebrate reservoir) such as transovarial transmission (female to offsprings) and/or venereal transmission play an important role in the natural cycle [2]. Experimental results done with colonized P. papatasi sandflies proved venereal virus transmission and transovarial virus transmission [15]. Viral maintenance during the diapausing period of Phlebotomus perniciosus larvae was proved and was not affected by transstadial transmission in laboratory [15]. These routes of virus transmission suggest that phleboviruses can be sustainably transmitted from one generation of sandflies to the next generation. It also raises the question of whether a vertebrate host acting as reservoir is required or not for virus perpetuation. To date, these experiments have been performed primarily with high passage colonies and should be taken with caution because laboratory reared sandflies may behave differently from wild populations. In addition, they have been performed with few species of phlebovirus and with P. papatasi and P. perfiliewi only. Elucidation of phlebovirus maintenance and transmission is crucial to understand better the natural history of these viruses and to develop adapted method to combat those which are human pathogens [15, 16, 17]. Although several sandfly-borne phlebovirus species were isolated from humans, bats and sandflies [18, 19, 20, 21, 22, 23], there is no undisputable evidence that vertebrates play an important role in the natural history of sandfly-borne phleboviruses other that as dead-end hosts.
With recently discovered novel viruses, the geographic distribution of phleboviruses has drastically increased in both the new and the old worlds. The current situation depicts a high viral diversity with taxonomic groups containing pathogenic and non-pathogenic viruses. This merits to provide insight to address the question of medical and veterinary public health impact of all these viruses, which are poorly studied.
In the old world (OW), the risk for the infection with sandfly-borne phleboviruses is high depending upon the presence and the density of vectors [24].
Historic and recent epidemics have been caused by sandfly-borne phleboviruses in the OW. In 1937, a massive outbreak occurred in, Athens, Greece [25, 26]. During World War II (WWII), outbreaks were described among out-comer soldiers in the Mediterranean basin and Middle East (the Austrian Commission in Balkan countries, British and German troops in the Mediterranean area) [17, 26, 27].
After WWII, sandfly fever epidemics were reported in Belgrade, Serbia, where thousands were sick [28], with subsequent spread into other regions of the Balkans [29, 30, 31, 32]. More recently, large epidemics were recorded in Cyprus, Iraq, Turkey and Ethiopia [33, 34, 35, 36].
In addition, during the last two decades, an impressive number of novel phleboviruses was either isolated or detected by molecular techniques in France, Italy, Portugal, Greece, Albania, Croatia, Bosnia Herzegovina, Turkey, Iran, Tunisia, Algeria and Morocco [11, 12, 13, 14, 23, 37, 38, 39, 40, 41, 42, 43]. Accordingly, the Mediterranean area witnesses a very high diversity of phleboviruses transmitted by sandflies [44]. This situation has raised the public health concerns in southern Europe, North Africa and in the Middle East [11, 13, 14, 39, 41, 45, 46].
OW sandfly-borne phleboviruses can be classified into three serological complexes, which are also regarded as taxonomic species, Salehabad species, Sandfly fever Naples species and Sandfly fever Sicilian tentative species.
Sandfly fever Sicilian and Sandfly fever Naples viruses cause fever, also known as “sandfly fever”, “Pappataci fever” or “three-day fever”. It is not possible to distinguish Sandfly fever Sicilian virus infection from Sandfly fever Naples virus infection based on clinical signs, which are virtually identical. They both cause abrupt illness with fever, headache, malaise, photophobia, myalgia and retro-orbital pain usually lasting 2–3 days after 3–5 day incubation [47].
Toscana virus, which belongs to the Sandfly fever Naples species, is so far the most pathogenic sandfly-borne phlebovirus due to its propensity to affect the central nervous system (CNS) and cause meningitis and meningoencephalitis [45]. Recently, Adria virus, identified in a case of meningitis, is the first virus belonging to the Salehabad species to display human pathogenesis [38].
Before WWII, the knowledge on sandfly fever was limited to clinical and epidemiological grounds. It was known that the fever caused by a filterable agent and transmitted by Phlebotomus papatasi sandflies [48, 49]. Early assumptions claimed that sandfly fever might be caused by distinct agents or viruses, despite it was impossible to distinguish them from the clinical symptoms [47, 50].
Between 1934 and 1939, human sera samples from sandfly fever virus-infected individuals (presumably containing the infectious agent) were inoculated into rhesus monkeys which presented with febrile illness [51]. Inoculation of infectious human serum (i) into chick embryos showed lesions on the chorioallantoic membrane, whereas (ii) no clinical sign were noticed after inoculation to guinea pigs, rabbits or dogs [47]. Three out of four human volunteers without a previous sandfly fever history developed the typical symptoms and fever after inoculation of 1 ml of the pool of acute sandfly fever serum [47]. Subsequently, Phlebotomus papatasi, Culex pipiens and Pulex irritans fed on sandfly fever acutely infected volunteers, only P. papatasi was able to transmit the disease to naïve volunteers [47]. In 1937, a massive outbreak occurred in Athens, Greece [26]. However, most of the outbreaks occurred in non-native persons having entered the endemic area for the first time recently such as soldiers [13]. During WWII, several outbreaks of sandfly fever knocked down battalions of soldiers in both the Allied and Axis troops which were stationed in the Middle East, the Mediterranean and North Africa [17, 52, 53]. The suspected variety of causing agents was shown through isolation of two different viruses names Naples and Sicilian virus from sick soldiers in southern Italy [47, 53]. The antigenic differences between Naples virus and Sicilian virus were confirmed by human cross-immunity test, neutralization and complement fixation test [54].
Sandfly fever Naples virus was first isolated from blood of a febrile soldier who became ill when stationed in Naples, Italy in 1944 [47]. Afterward, Naples virus was isolated again (i) from febrile patients in Egypt, Turkmenia, Pakistan, Italy, Cyprus and India [55, 56, 57, 58, 59, 60, 61] (ii) and from sandflies in Egypt (P. papatasi), in Italy (P. perniciosus) and Serbia (P. perfiliewi) [19, 59, 62]. This was the first clue that Naples virus could be transmitted by distinct vector species. A large and seminal neutralization-based seroprevalence study, performed by Tesh et al. in 1976, showed that Naples virus was likely to have a much wider distribution than initially believed from virus isolation reports [24]; indeed, neutralizing antibodies were detected in human populations from Bangladesh, Ethiopia, Greece, Iraq, Morocco, Saudi Arabia, Sudan, Djibouti, Turkey and former Yugoslavia [24]. Highest rates (55–62%) were observed in Egypt, former Yugoslavia (now Croatia), and Turkey. Another study reported neutralizing antibodies in populations living in Turkmenia, Tajikistan, Uzbekistan, and Moldavia [63]. Clearly, Naples virus circulation has drastically decreased after the 1980s, and the absence of virus isolation or PCR detection, despite an increasing number of studies conducted in previously endemic areas, question whether Naples virus has gone extinct or not [58].
Toscana virus (TOSV) was first isolated from P. perniciosus in central Italy in 1971 [17]. It has taken 12 years to recognize that TOSV was capable to infect humans and was able to cause not only sandfly fever, but also more severe infections characterized by central nervous system (CNS) manifestations such as meningitis and encephalitis. The first cases pointing out that Toscana virus causes CNS infections came from two travelers returning from Italy and Portugal to the United States and Sweden, respectively [64, 65]. This underlines the importance of travel-related medicine in the surveillance of infectious diseases, particularly vector-borne infectious diseases. Most of the Toscana virus case records are coming from important or autochthonous human cases from the Mediterranean basin countries [45, 70]. Autochthonous cases in humans have been reported in Italy [71], Greece [72], Cyprus [73], Croatia [74], Turkey [75, 76], Portugal [77] and France [78]. However, these cases account for a minimal proportion of literature-described cases. In most countries, where TOSV is endemic, it is not a notifiable disease; this together with the absence of pathognomonic clinical sign, and the very limited number of commercially available diagnostic assay may explain why autochthonous cases are drastically under detected, and that most of reported cases have affected travelers, the diagnosis of which is done when returning to their homeland. TOSV cases in travelers have been reported from Italy [66], France [67], Spain [68, 69] and Portugal [64], but also from the Mediterranean islands such as Cyprus [73], Elba [79, 80], Sicily [81] and Sardinia [82].
Seroepidemiological studies showed the presence of neutralizing antibodies against Toscana virus in several Mediterranean countries, however, the rates vary depending on the region Mediterranean basin considered as endemic region of Toscana virus [45, 71, 74, 78, 83, 84, 85, 86, 87, 88].
Special attention must also be brought to the technique used for serology, since results can greatly vary due to different levels of cross-reactivity depending on the assay; for instance, the most stringent technique is based on neutralization assays whereas ELISA or immunofluorescence techniques are more prone to cross-reactivity between phleboviruses within the same antigenic group, but also between antigenically distinct phleboviruses [88, 89, 90].
The geographic distribution of sandfly-borne phleboviruses can also be measured by surveillance of non-human vertebrates such as domestic animals: such studies have demonstrated that TOSV was actively circulating in Portugal, Greece, Cyprus and Algeria [83, 84, 85] from the study of dog sera, and in Kosovo from studying cow and sheep sera [86]. TOSV was also isolated and/or detected in different phlebotomine species such as P. perniciosus, P. perfiliewi, P. longicuspis, P. sergenti, P. neglectus and Sergentomyia minuta in Italy, France, Spain, Croatia, Morrocco, Tunisia, Algeria and Corsica [13, 18, 82, 87, 91, 92, 93, 94, 95, 96]. These results tend to suggest that TOSV can be transmitted by species other that P. perniciosus and P. perfiliewi. Such data are compatible with the fact that TOSV might be more widely dispersed than believed from the early studies. Of course, this merit to be further investigated through experimental studies addressing competence of these species for TOSV. TOSV belongs to the Sandfly fever Naples species.
To date, three genetic groups of TOSV have been recognized, and they are called lineages A, B and C. Although only one lineage has been identified in a given country, the co-circulation of two lineages has been shown in France, in Turkey, and in Croatia. It is possible that different lineages are transmitted by the same sandfly species and that sympatry may be frequent [91, 93, 97]. Recent Toscana virus antibody characterization assay performed with 41 patients diagnosed with Toscana virus meningitis of meningoencephalitis found that specific IgM titers were high during acute infection up to day 30, the presence of IgM antibodies lasts up to 6 months after acute infection in 71% of cases, however IgG antibodies against Toscana virus persisted at least 2 years in the patients, which gets in line with the fact that TOSV infection is associated with long-term, maybe lifelong immunity [88]. There is accumulating evidence that TOSV is one important cause of meningitis and encephalitis during the warm season and that it should be included in the panel of microorganisms to be systematically tested in clinical microbiology laboratory for patients presenting with febrile illness, CNS and peripheral nervous system manifestations.
Sandfly fever Sicilian virus (SFSV) was first isolated, characterized and named Sicilian virus, from the serum of a US soldier, presenting with sandfly fever when he was stationed in Palerma (Sicily) after the landing of the Allied army forces in Italy, in 1943 during WWII [47]. Almost simultaneously, it was also described in sick US soldiers stationed in Egypt. Subsequent studies allowed isolation of SFSV in Egypt, India, Iran, Pakistan and Afghanistan [56, 98, 99, 100].
Accumulating direct (virus isolation or molecular detection) and indirect (seroprevalence studies) data allowed to list the following countries as areas where SFSV was circulating: Bangladesh, Greece, Cyprus, Iraq, Morocco, Saudi Arabia, Somalia, Ethiopia, Sudan, Tunisia, Turkey, Turkmenia, Tajikistan, Uzbekistan, Azerbaijan, Moldavia, Croatia, Kosovo, France and Portugal [24, 33, 34, 61, 63, 83, 86, 101, 102, 103]. Beside the outbreaks described in the Allied and Axis forces during WWII, more recent epidemics were reported in Cyprus, in Turkey and in Ethiopia caused by genetic variants [29, 30, 31, 32, 33, 34, 35, 36, 104]. Recent seroprevalence studies provided evidence that SFSV and its genetic variants were still actively circulating in Greece, Cyprus, Portugal and Kosovo [83, 84, 86]. Although Phlebotomus papatasi, Phlebotomus ariasi and P. major complex were indisputably identified as SFSV vectors, transmission might also be done by phlebotomies belonging to other species [20, 100].
Adria virus was first detected in 2005 from field-collected sandflies in Albania [39]. Genetic data consisting of partial sequence in the polymerase gene showed that Adria virus is much closely related with viruses belonging to the Salehabad species than with other phleboviruses belonging to the Sandfly fever Naples or to the Sandfly fever Sicilian species. In 2009, a 30-month-old patient was admitted to hospital in Greece for fever and seizure during summertime; his blood was tested positive for the presence of phlebovirus RNA, whose sequence was most closely related with Adria virus sequence [23]. Adria virus is the first, and so far the only member of the Salehabad species to be associated with human disease. Interestingly, the number of viruses identified in this species has drastically increased during the last decade. Thus efforts should now be deployed to investigate to what extent, Adria virus in particular but also other newly recognized Salehabad viruses have a medical impact.
The last decade has been marked by discovery of an unprecedented number of sandfly-borne phleboviruses in old world phlebotomies. Although most of the remains to be classified or listed by the ICTV, they each belong to one of the three species aforementioned: Sandfly fever Naples, Sandfly fever Sicilian or Salehabad. Accordingly, they have drastically increased the genetic diversity within each of these species. Since several of these viruses were discovered in sandflies trapped in countries where phleboviruses had never been described before, the geographic range of circulation of the phleboviruses transmitted by sandflies has dramatically expanded.
Sandfly fever Naples species shows an important genetic diversity which has motivated a proposed subdelineation into four groups [42]: subgroup I includes Tehran virus (Iran), Zerdali virus (Turkey) and Sandfly fever Naples virus strain YU 8–76 (Serbia); subgroup II contains the three genotypes of Toscana virus; subgroup III includes Sandfly fever Naples virus and subgroup IV comprises Massilia virus (France), Arrabiata virus (Portugal), Granada virus (Spain) and Punique virus (Tunisia) [11, 18, 37, 42, 46, 47, 105]. Whether viruses belonging to subgroup I and IV can infect humans and may cause disease is currently unknown.
Genetic and phylogenetic analyses show that viruses that can be grouped into the Sandfly fever Sicilian/Corfou virus group or tentative species can be subdivided into two clusters: (i) lineage I contains Sandfly fever Sicilian viruses together with the newly isolated Dashli virus [43] and (ii) lineage II includes Corfou virus together with Toros virus which were isolated from Greece and Turkey, respectively [42, 89].
During the last decade, the Salehabad virus species which contained initially only Salehabad and Arbia viruses has greatly increased by addition of newly discovered viruses such as Adana virus, Alcube virus and Medjerda Valley virus, respectively, isolated from sandflies collected in Turkey, Portugal and Tunisia [37, 38, 39, 40, 106]. Several other viruses were not isolated but discovered through sequencing a part of their genome such as Adria virus (Albania and Greece), Edirne virus (Turkey) and Olbia virus (France) [23, 39, 107, 108]. To date, Adria virus is the only virus belonging to the Salehabad species that was associated with a case of human disease.
Although a large number of these viruses have not been associated with cases of human or veterinarian diseases, it must be remembered that 12 years have passed between the discovery of Toscana virus and the first evidence that it was pathogenic for humans. It is, therefore, crucial to address the public health impacts of these newly described phleboviruses via seroprevalence studies and molecular virological investigations of clinical cases of fever of unknown origin and infections of the central nervous system during summer.
Medically speaking, it is the most important phlebovirus in the Americas. Punta Toro virus (PTV) was first identified in the blood of a febrile soldier who participated in military training in the jungle of the Panama Canal Zone, in 1966 [109]. PTV was isolated for the second time in the blood of an entomologist who was doing field collection of insects in the forested area of Darien Province in Panama [108]. Fever, headache, weakness, back, and retro-orbital pain were the common symptoms in both cases with 3–4 days duration. Several Punta Toro virus strains were isolated from sandflies and wild sentinel hamsters in Bayano district of Panama between 1975 and 1976 [109]. To date, PTV has been described only in Central America where several strains of the virus isolated from Lutzomyia (Nyssomyia) trapidoi and L. (Ny.) ylephiletor [16]. One strain was isolated from the blood of an apparently healthy wild-caught sloth in central Panama [110]. In 1974, a seroprevalence study showed that 5% of the children under the age of 20 and 27–40% of adults in Panama had specific antibodies [111]. In 2009, during the dengue surveillance programme in Panama, dengue virus-negative human samples were found to contain PTV RNA strains. Of the 201 tested sera from febrile patients, 27 (13.4%) were positive for PTV [112].
PTV has been used in several experimental studies [113, 114, 115]. Interestingly, when Syrian golden hamsters are inoculated with the Adames strain (PTV-A), they develop a fatal disease; in contrast, hamsters infected with the Baillet strain (PTV-B) do develop a disease but all survive the challenge [113].
A large number of phleboviruses have been isolated from sandflies in Brazil, Panama and Peru [116, 117]. Several viruses have been classified into one the five following groups or species: Punta Toro, Candiru, Bujaru, Tapara and Frijoles species. However, those which were not classified were included in the tentative species category.
Cocle virus (Punta Toro species) was isolated from the serum of a febrile patient in Cocle province, Panama in 2009 [109]. Although it appears that Cocle virus belongs to a species which contains viruses transmitted by sandflies, the absence of entomological data does not allow to conclude about the vector involved in the natural cycle.
Oriximina, Turuna, and Ariquemes viruses (Candiru species) were isolated from Lutzomyia sp. sandflies in Brazil and Nique virus was isolated from Lutzomyia panamensis in Madre de Dios, Peru [116]. Although several viruses belonging to the Candiru virus species were identified from febrile patients, there is limited knowledge about the nature of the insect species that transmit these viruses.
The Rhabdoviridae family includes 18 genera and 134 species with negative-sense, single-stranded RNA genomes [118]. In this family, members of the Vesiculovirus genus are able to infect at least 28 invertebrates and vertebrates including human [27, 119]. They cause vesicular stomatitis in human and domestic animals and they show a worldwide distribution both in the new and old worlds.
The disease manifests itself into two different forms in the United States; either as sporadic outbreaks with a 10-year intervals in the southwestern states (New Mexico, Arizona, Utah and Colorado) [120]. However, in some other states as Georgia, Alabama, North and South Carolina, the disease occurred yearly with clinical signs in cattle, pig and horses. Since 1970, viral activity has been focal and limited to isolated wildlife populations. [120]. In addition, the virus is considered as endemic in Colombia, Venezuela, Ecuador, Peru and Mexico, where outbreaks occur every year [121, 122].
In the old world, another vesiculovirus, Chandipura virus has recently emerged and caused severe encephalitis in human in different parts of India [6, 123]. The first isolation of Chandipura virus was from two patients with febrile illness in 1965 [6]. In 2003, the virus caused the first outbreak of acute encephalitis in children with high fatality rate (183 deaths out of 329 cases, 55.6%) in Andhra Pradesh, India [124]. The second outbreak has occurred in the eastern state of Gujarat with higher fatality rate in 2004 (>75%) [123]. Recently, an outbreak of acute encephalitis syndrome was recorded in Maharashtra, India with 43.6% fatality rate in children younger than 15-year-old [125].
Chandipura virus has been isolated from field-collected Phlebotomus spp. sandflies [7]. The virus was also detected in sandflies belonging to the genus Sergentomyia in India [126]. This virus has not only been detected in India but also in Senegal and Nigeria, respectively, from phlebotomine sandflies and hedgehog (Atelerix spiculus) [127]. This suggests that Chandipura virus is widely distributed and should be investigated in a more detailed manner.
Changuinola virus was first isolated from Lutzomyia sp. sandflies in 1960 in Panama [128]. Since then 12 isolates were described from phlebotomine flies [129]. Another, seven strains were isolated from 80 wild-trapped sloths (Bradypus variegatus and Choloepus hoffmanni) from Central Panamá [109]. Neutralizing antibody were detected in these two sloth species, despite they were virtually absent from other wild vertebrate species tested. Several strains were associated with prolonged or recrudescent viremias in slots [130]. Besides, one strain of Changuinola virus was identified from a febrile patient [8]. Changuinola virus can replicate in mosquito cell lines (C6/36 [Aedes albopictus cells]), Culicoides sonorensis KC and African green monkey kidney Vero cells [131].
Sandfly-borne viral pathogens are widespread in both old and new worlds particularly in tropical/subtropical areas, and temperate zones including southern Europe, Asia, Africa, Australia and Central and South America [24]. Due to vector sandfly species activity, the sandfly-borne viral diseases peaks during summer which affect both urban, peri-urban and rural population, but mostly the communities with poor living conditions [3, 4] (Figure 1, Table 1).
Schematic overview of the sandfly-brone viruses, according to geographical regions.
Group | Virus | Virus origin | Country |
---|---|---|---|
Sandfly-borne phleboviruses of demonstrated medical importance | |||
Old World Sandfly-borne phleboviruses of demonstrated medical importance | |||
Sandfly fever Naples Species | Sandfly fever Naples virus Sabin | Blood sample | Italy |
Sandfly fever Naples virus R-3 | Human sera | Cyprus | |
Sandfly fever Naples virus Namru | Phlebotomus papatasi | Egypt | |
Sandfly fever Naples virus | Human | Turkmenistan | |
Sandfly fever Naples virus | Human | Afghanistan | |
Sandfly fever Naples virus | Phlebotomus longicuspis | Algeria | |
Sandfly fever Naples virus | Phlebotomus spp. and humans | India | |
Sandfly fever Naples virus YU 8-76 | Phlebotomus perfiliewi | Serbia | |
Toscana virus | Phlebotomus perniciosus | Italy | |
Toscana virus | Human CSF | Italy | |
Toscana virus | Pipistrellus kuhli brain | Italy | |
Toscana virus | Phlebotomus spp. | Italy | |
Toscana virus | Phlebotomus perniciosus | France | |
Toscana virus | Sergentomyia minuta | France | |
Toscana virus | human CSF | Croatia | |
Toscana virus | Phlebotomus neglectus | Croatia | |
Toscana virus | Phlebotomus spp. | Cyprus | |
Toscana virus | Human sera, urine | Turkey | |
Toscana virus | Phoenicopterus roseus, Pelecanus onocrotalus, Ciconia nigra | Turkey | |
Toscana virus | Phlebotomus perniciosus | Morocco | |
Toscana virus | P. longicuspis, P. sergenti | Morocco | |
Toscana virus | Phlebotomus spp. | Algeria | |
Toscana virus | Phlebotomus spp. | Tunisia | |
Toscana virus | Human CSF | Greece | |
Sandfly Fever Sicillian Species | Sandfly fever Sicilian virus Sabin | Human sera | Italy |
Sandfly fever Sicilian virus | Phlebotomus spp. | Iran | |
Sandfly fever Sicilian virus | Human sera | Cyprus | |
Sandfly fever Sicilian virus | Phlebotomus papatasi | Pakistan | |
Sandfly fever Sicilian virus | Phlebotomus ariasi | Algeria | |
Sandfly fever Sicilian virus | Phlebotomus papatasi | Algeria | |
Sandfly fever Sicilian virus | Human | Afghanistan | |
Sandfly fever Sicilian virus | Phlebotomus spp. | India | |
Sandfly fever Sicilian virus | Human | Ethiopia | |
Sandfly fever Cyprus virus | Human sera | Cyprus | |
Sandfly fever Turkey virus | Human sera | Turkey | |
Sandfly fever Turkey virus | Phlebotomus major complex | Turkey | |
Dashli virus | Phlebotomus spp./Sergentomyia spp. | Iran | |
Salehabad Species | Adria virus | Human blood | Greece |
Adria virus | Phlebotomus spp. | Albania | |
New World Sandfly-borne phleboviruses of demonstrated medical importance | |||
Punta Toro Species | Punta Toro virus Adames | Human | Panama |
Punta Toro virus Balliet | Human | Panama | |
Punta Toro virus | Human | Panama | |
Punta Toro virus | Human | Panama | |
Punta Toro virus | Sentinel hamster | Panama | |
Punta Toro virus | Sentinel hamster | Panama | |
Punta Toro virus | Lutzomyia spp. | Panama | |
Punta Toro virus | Human | Panama | |
Punta Toro virus | Human | Panama | |
Punta Toro virus | Human | Panama | |
Punta Toro virus | Human | Panama | |
Sandfly-borne Rhabdoviruses | |||
Vesiculovirus Species | Vesiculovirus | Horse | South Africa |
Vesiculovirus | Bovine | Indiana, USA | |
Vesiculovirus | Bovine, equine | New Jersey | |
Vesiculovirus | Cattle, horse | Wisconsin, Minnesota, Dakota | |
Vesiculovirus | Cattle, horse | Argentine | |
Vesiculovirus | Cow, horse, pig | Venezuela | |
Vesiculovirus | Horse | Texas, Louisiana | |
Vesiculovirus | Horse | Kansas | |
Vesiculovirus | Horse | Colorado | |
Vesiculovirus | Swine | Colombia | |
Vesiculovirus | Swine | Venezuela | |
Vesiculovirus | Swine | Missouri | |
Vesiculovirus | Swine | Colorado | |
Vesiculovirus | Cattle | California | |
Vesiculovirus | Horse | Arizona | |
Vesiculovirus | Cattle | Mexico | |
Vesiculovirus | Horse | Alabama | |
Vesiculovirus | Horse | Mississippi, Georgia, Tennessee, Florida | |
Vesiculovirus | Bovine, porcine | Guatemala | |
Vesiculovirus | Equine | Belize | |
Vesiculovirus | Bovine | Honduras | |
Vesiculovirus | Bovine | El Salvador | |
Vesiculovirus | Bovine, porcine | Nicaragua | |
Vesiculovirus | Bovine | Costa Rica | |
Vesiculovirus | Bovine | Peru | |
Chandipura virus | Human | India | |
Chandipura virus | Sandfly | India | |
Chandipura virus | Sandfly | Senegal | |
Chandipura virus | Sandfly | Nigeria | |
Sandfly-borne Reoviruses | |||
Changuinola virus Species | Changuinola virus | Lutzomyia sp. | Panama |
Changuinola virus | Rice rat, armadillo, sloth | Panama | |
Changuinola virus | Human | Panama | |
Changuinola virus | Lutzomyia sp. | Colombia | |
Changuinola virus | Bradypus variegatus, Choloepus hoffmanni | Panama |
Features of the medically important sandfly‐borne viruses.
Both molecular characterization and seroepidemiological studies demonstrated broad distribution of sandfly-borne phleboviruses in the old world in the Mediterranean region, in the African continent, in the Indian subcontinent, in the Middle East and in Central Asia. However, the pathogen sandfly-borne phleboviruses were recorded in the limited geographical area (Panama) in the new world with sporadic human cases. This must be due to (i) limited investigations in the new world; (ii) vector competence of phlebovirus in the new world; (iii) small-sized human population and (iv) lack of case report.
This work was supported in part by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 653316. Nazli Ayhan is a Post-Doctoral fellow supported by a IRD grant.
Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.
",metaTitle:"IntechOpen Women in Science Program",metaDescription:"Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"At IntechOpen, we’re laying the foundations for the future by publishing the best research by women in STEM – Open Access and available to all. Our Women in Science program already includes six books in progress by award-winning women scientists on topics ranging from physics to robotics, medicine to environmental science. Our editors come from all over the globe and include L’Oreal–UNESCO For Women in Science award-winners and National Science Foundation and European Commission grant recipients.
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\n\n“My scientific path has given me the opportunity to work with colleagues all over Europe, including Germany, France, and Norway. Editing the book Graph Theory: Advanced Algorithms and Applications with IntechOpen emphasized for me the importance of providing valuable, Open Access literature to our scientific colleagues around the world. So I am highly enthusiastic about the Women in Science book collection, which will highlight the outstanding accomplishments of women scientists and encourage others to walk the challenging path to becoming a recognized scientist." Beril Sirmacek, TU Delft, The Netherlands
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I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. 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