IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
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IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
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Designed to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
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After a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
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Our innovative Book Series format brings you:
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Topic Focused Publications - Each topic showcases high impact subject areas
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Renowned Editorial Expertise - Series Editors, Topic Editors, and a team of international Board Members that permanently support each Book Series
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Fast Publishing - quick turnaround which is unique for book publishing
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The benefit of ISSN and ISBN for increased citation and indexing possibilities
\n
\n\n\n\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\n
IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
We invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
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Note: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6348",leadTitle:null,fullTitle:"Advanced Electronic Circuits - Principles, Architectures and Applications on Emerging Technologies",title:"Advanced Electronic Circuits",subtitle:"Principles, Architectures and Applications on Emerging Technologies",reviewType:"peer-reviewed",abstract:"This research book volume offers an important learning opportunity with insights into a variety of emerging electronic circuit aspects, such as new materials, energy harvesting architectures, and compressive sensing technique. Advanced circuit technologies are extremely powerful and developed rapidly. They change industry. They change lives. And we know they can change the world. The exhibition on these new and exciting topics will benefit readers in related fields.",isbn:"978-1-78923-207-3",printIsbn:"978-1-78923-206-6",pdfIsbn:"978-1-83881-420-5",doi:"10.5772/intechopen.69787",price:119,priceEur:129,priceUsd:155,slug:"advanced-electronic-circuits-principles-architectures-and-applications-on-emerging-technologies",numberOfPages:194,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c5a1bb3da69158c572f9983972ae97d0",bookSignature:"Mingbo Niu",publishedDate:"June 13th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6348.jpg",numberOfDownloads:13034,numberOfWosCitations:8,numberOfCrossrefCitations:12,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:17,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:37,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 22nd 2017",dateEndSecondStepPublish:"June 12th 2017",dateEndThirdStepPublish:"September 8th 2017",dateEndFourthStepPublish:"December 7th 2017",dateEndFifthStepPublish:"February 5th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"141595",title:"Dr.",name:"Mingbo",middleName:null,surname:"Niu",slug:"mingbo-niu",fullName:"Mingbo Niu",profilePictureURL:"https://mts.intechopen.com/storage/users/141595/images/system/141595.jpg",biography:"Mingbo Niu received a B. Eng. degree in Electronic Engineering from Northwestern Polytechnical University in China, and an M. Sc. (Eng.) degree (first-class) major in Communication and Information Systems from the same university. Prior to his Ph.D., he worked at a National Key Laboratory on Information and Signal Processing. He received his Ph.D. degree in Electrical and Computer Engineering from the University of British Columbia, Canada in 2013. From 2008 to 2012, he was a Research Assistant at Optical Wireless Communications Laboratory and Integrated Optics Laboratory where he contributed to the development of ultra-high speed optical data transmission links. Dr. Niu held a postdoctoral fellowship at Queen’s University from 2013 to 2015. He also worked for Defence Research and Development Canada (DRDC) at Calian Tech. Ltd where he contributed to statistical evaluation models of MIMO compressive sensing projects. He is now a Professor of Electrical Engineering at Okanagan College, Canada. Dr. Niu has co-authored more than 20 IEEE and OSA papers and supervised a number of students’ projects. Currently, he serves as a Lead Guest Editor for the journal Wireless Communications and Mobile Computing (IF: 1.899) and an Editor for InTech book projects on \\Advanced Analog/Digital Circuits\\. Dr. Niu was the recipient of numerous scholarships during his undergraduate and graduate studies, which included a Chinese Government Award, two University of British Columbia University Graduate Fellowships (UGFs), and a HuaWei Tech. Ltd Special Fellowship. His current research and teaching interests include digital communications, microcontrollers, MIMO, DSP, energy harvesting, electronic circuit theory, and ICs for data communication networks. Dr. Niu is a licensed Professional Engineer in British Columbia.",institutionString:"Chang'an University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Chang'an University",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"739",title:"Electronic Circuits",slug:"electrical-and-electronic-engineering-electronic-circuits"}],chapters:[{id:"58662",title:"Self-Oscillatory DC-DC Converter Circuits for Energy Harvesting in Extreme Environments",doi:"10.5772/intechopen.72718",slug:"self-oscillatory-dc-dc-converter-circuits-for-energy-harvesting-in-extreme-environments",totalDownloads:1207,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A novel self-starting converter circuit technology is described for energy harvesting and powering wireless sensor nodes, constructed from silicon carbide devices and proprietary high temperature passives for deployment in hostile environments. After a brief review of the advantages using Silicon Carbide (SiC) over other semiconductors in extreme environments, the chapter will describe the advantages and principles when designing circuitry and architectures using SiC for power electronics. The practical results from a novel self-starting DC-DC converter are reported, which is designed to supply power to a WSN for deployment in high temperature environments. The converter operates in the boundary between continuous and discontinuous mode of operation and has a Voltage Conversion Ratio (VCR) of 3 at 300°C. This topology is able to self-start and so requires no external control circuitry, making it ideal for energy harvesting applications, where the energy supply may be intermittent. Experimental results for the self-starting converter operating from room temperature up to 300°C are presented. The converter output voltage, switching frequency, total power loss and efficiency were presented at temperatures up to 300°C.",signatures:"Ming-Hung Weng, Daniel Brennan, Nick Wright and Alton Horsfall",downloadPdfUrl:"/chapter/pdf-download/58662",previewPdfUrl:"/chapter/pdf-preview/58662",authors:[{id:"175070",title:"Dr.",name:"Ming-Hung",surname:"Weng",slug:"ming-hung-weng",fullName:"Ming-Hung Weng"},{id:"215269",title:"Prof.",name:"Nick",surname:"Wright",slug:"nick-wright",fullName:"Nick Wright"},{id:"215271",title:"Dr.",name:"Alton",surname:"Horsfall",slug:"alton-horsfall",fullName:"Alton Horsfall"},{id:"222660",title:"Dr.",name:"Daniel",surname:"Brennan",slug:"daniel-brennan",fullName:"Daniel Brennan"}],corrections:null},{id:"58795",title:"New Energy Harvesting Systems Based on New Materials",doi:"10.5772/intechopen.72613",slug:"new-energy-harvesting-systems-based-on-new-materials",totalDownloads:1122,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This study starts with the ZnO nanostructured materials used for improve the efficiency of polycrystalline solar cells operation under low solar radiation conditions. The ZnO nanowires were prepared using the hydrothermal method of deposition on the seed layer by a new and complex process, with controllable morphological and optical properties. The analysis of the XRD patterns, scanning electron microscopy images (SEM) of the ZnO nanowires and a lot of tests made Pasan Meyer Burger HighLight 3 solar simulator, confirm the advantages of using the ZnO nanowires in solar cells applications for antireflection coatings. Then, piezoelectric structures based on new modified PZT zirconate titanate designed for energy harvesting applications is presented. Based on their piezoelectric characteristics, modified PZT zirconate titanate ceramics made of Pb(Zr0.53Ti0.47)0.99Nb0.01O3 ceramic have efficient applications in energy harvesting devices. A piezoelectric transducer, consisting of a thin plate of this piezoceramic material, with dimensions (34 mm × 14 mm × 1 mm), is illustrated. A multiphysics numerical simulation further illustrates such piezoelectric transducer operation. Finally, the miniature planar transformer with circular spiral winding and hybrid core—ferrite and magnetic nanofluid, designed for new energy harvesting systems is presented. We purpose now that the magnetic nanofluid be used both as a coolant and as part of the hybrid magnetic core.",signatures:"Lucian Pîslaru-Dănescu and Lipan Laurențiu Constantin",downloadPdfUrl:"/chapter/pdf-download/58795",previewPdfUrl:"/chapter/pdf-preview/58795",authors:[{id:"187612",title:"Dr.",name:"Lucian",surname:"Pîslaru-Dănescu",slug:"lucian-pislaru-danescu",fullName:"Lucian Pîslaru-Dănescu"},{id:"196151",title:"Dr.",name:"Laurentiu Constantin",surname:"Lipan",slug:"laurentiu-constantin-lipan",fullName:"Laurentiu Constantin Lipan"}],corrections:null},{id:"58619",title:"Nanoarchitecture of Quantum-Dot Cellular Automata (QCA) Using Small Area for Digital Circuits",doi:"10.5772/intechopen.72691",slug:"nanoarchitecture-of-quantum-dot-cellular-automata-qca-using-small-area-for-digital-circuits",totalDownloads:1634,totalCrossrefCites:6,totalDimensionsCites:10,hasAltmetrics:1,abstract:"Novel digital technologies always lead to high density and very low power consumption. One of these concepts—quantum-dot cellular automata (QCA), which is one of the new emerging nanotechnologies, is based on Coulomb repulsion. This chapter presents a novel design of 2-input Exclusive-NOR (XNOR)/Exclusive-OR (XOR) gates with 3-input Exclusive-NOR (XNOR) gates which are composed of 10 cells on 0.006 μm2 of area. A novel architecture of 3-input Exclusive-OR (XOR) gate is defined by 12 cells on 0.008 μm2 of area. The proposed design of 2-input XOR/XNOR gate structures provide less area and low complexity than the best reported design. The simulation results of proposed designs have been achieved using QCA Designer tool version 2.0.3.",signatures:"Radhouane Laajimi",downloadPdfUrl:"/chapter/pdf-download/58619",previewPdfUrl:"/chapter/pdf-preview/58619",authors:[{id:"218855",title:"Dr.",name:"Radhouane",surname:"Laajimi",slug:"radhouane-laajimi",fullName:"Radhouane Laajimi"}],corrections:null},{id:"58442",title:"Millimeter-Wave Multi-Port Front-End Receivers: Design Considerations and Implementation",doi:"10.5772/intechopen.72715",slug:"millimeter-wave-multi-port-front-end-receivers-design-considerations-and-implementation",totalDownloads:1526,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"This chapter covers recent achievements on the integrated 60 GHz millimeter-wave front-end receiver based on the multi-port (six-port) concept. For this purpose, the design procedure of a fully integrated 60 GHz multi-port (six-port) front-end receiver implemented on a thin ceramic substrate (εr = 9.9, h = 127 μm) using an miniature hybrid microwave integrated circuit (MHMIC) fabrication process is presented in detail. All components constituting the proposed front-end receiver including an 8 × 2 antenna array, a low-noise amplifier (LNA), a six-port circuit, and the RF power detectors are presented and characterized separately before they are integrated into the final front-end receiver prototype. The performance of the latter has been experimentally evaluated in terms of various M-PSK/M-QAM demodulations. The obtained demodulation results are very satisfactory (the constellation points for all considered M-PSK/M-QAM schemes are very close to the ideal locations), demonstrating and confirming the high ability of the proposed 60 GHz millimeter-wave six-port front-end receiver to operate as a high-performance quadrature demodulator, without any calibration, for modulation schemes up to 32 symbols.",signatures:"Chaouki Hannachi and Serioja Ovidiu Tatu",downloadPdfUrl:"/chapter/pdf-download/58442",previewPdfUrl:"/chapter/pdf-preview/58442",authors:[{id:"34160",title:"Prof.",name:"Serioja O.",surname:"Tatu",slug:"serioja-o.-tatu",fullName:"Serioja O. Tatu"},{id:"212045",title:"Ph.D.",name:"Chaouki",surname:"Hannachi",slug:"chaouki-hannachi",fullName:"Chaouki Hannachi"}],corrections:null},{id:"59972",title:"Applications of Compressive Sampling Technique to Radar and Localization",doi:"10.5772/intechopen.75072",slug:"applications-of-compressive-sampling-technique-to-radar-and-localization",totalDownloads:1076,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"During the last decade, the emerging technique of compressive sampling (CS) has become a popular subject in signal processing and sensor systems. In particular, CS breaks through the limits imposed by the Nyquist sampling theory and is able to substantially reduce the huge amount of data generated by different sources. The technique of CS has been successfully applied in signal acquisition, image compression, and data reduction. Although the theory of CS has been investigated for some radar and localization problems, several important questions have not been answered yet. For example, the performance of CS radar in a cluttered environment has not been comprehensively studied. Applying CS to passive radars and electronic warfare receivers is another concern that needs more attention. Also, it is well known that applying this strategy leads to extra computational costs which might be prohibitive in large-sized localization networks. In this chapter, we first discuss the practical issues in the process of implementing CS radars and localization systems. Then, we present some promising and efficient solutions to overcome the arising problems.",signatures:"Soheil Salari, Francois Chan and Yiu-Tong Chan",downloadPdfUrl:"/chapter/pdf-download/59972",previewPdfUrl:"/chapter/pdf-preview/59972",authors:[{id:"214787",title:"Dr.",name:"Francois",surname:"Chan",slug:"francois-chan",fullName:"Francois Chan"},{id:"214788",title:"Dr.",name:"Soheil",surname:"Salari",slug:"soheil-salari",fullName:"Soheil Salari"},{id:"214789",title:"Dr.",name:"Yiu-Tong",surname:"Chan",slug:"yiu-tong-chan",fullName:"Yiu-Tong Chan"}],corrections:null},{id:"60655",title:"High-Speed Electronic Memories and Memory Subsystems",doi:"10.5772/intechopen.76257",slug:"high-speed-electronic-memories-and-memory-subsystems",totalDownloads:871,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Memories have played a vital role in embedded system architectures over the years. A need for high-speed memory to be embedded with state-of-the-art embedded system to improve its performance is essential. This chapter focuses on the development of high-speed memories. The traditional static random access memory (SRAM) is first analyzed with its different variant in terms of static noise margin (SNM); these cells occupy a larger area as compared to dynamic random access memory (DRAM) cell, and hence, a comprehensive analysis of DRAM cell is then carried out in terms of power consumption, read and write access time, and retention time. A faster new design of P-3T1D DRAM cell is proposed which has about 50% faster reading time as compared to the traditional three-transistor DRAM cell. A complete layout of the structure is drawn along with its implementation in a practical 16-bit memory subsystem.",signatures:"Prateek Asthana and Loveneet Mishra",downloadPdfUrl:"/chapter/pdf-download/60655",previewPdfUrl:"/chapter/pdf-preview/60655",authors:[{id:"218477",title:"Mr.",name:"Prateek",surname:"Asthana",slug:"prateek-asthana",fullName:"Prateek Asthana"},{id:"221356",title:"Mr.",name:"Loveneet",surname:"Mishra",slug:"loveneet-mishra",fullName:"Loveneet Mishra"}],corrections:null},{id:"58744",title:"High Voltage Energy Harvesters",doi:"10.5772/intechopen.72959",slug:"high-voltage-energy-harvesters",totalDownloads:4659,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Green energy helps in reducing carbon emission from fossil fuel, harvesting energy from natural resources like wind to power consumer appliances. To date, many researches have been focusing on designing circuits that harvest energy from electromagnetic signals wirelessly. While it could be designed to be efficient, the generated power however is insufficient to drive large loads. Wind energy is highly available environmentally but development of small-scale energy harvesting apparatus aiming to extract significant power from miniature brushless fan has received limited attention. The aim of this chapter is to give audience an insight of different voltage multipliers used in energy harvester and knowledge on various circuit techniques to configure voltage multipliers for use in different high voltage applications. These include AC-DC converter, AC-AC converter and variable AC-DC converter.",signatures:"Xi Sung Loo, Kiat Seng Yeo, Joel Yang, Chee Huei Lee, Rong Zhao\nand Moe Z. Win",downloadPdfUrl:"/chapter/pdf-download/58744",previewPdfUrl:"/chapter/pdf-preview/58744",authors:[{id:"189098",title:"Dr.",name:"Xi Sung",surname:"Loo",slug:"xi-sung-loo",fullName:"Xi Sung Loo"},{id:"189214",title:"Prof.",name:"Kiat Seng",surname:"Yeo",slug:"kiat-seng-yeo",fullName:"Kiat Seng Yeo"},{id:"215816",title:"Prof.",name:"Joel",surname:"Yang",slug:"joel-yang",fullName:"Joel Yang"},{id:"215817",title:"Dr.",name:"Chee Huei",surname:"Lee",slug:"chee-huei-lee",fullName:"Chee Huei Lee"},{id:"215818",title:"Prof.",name:"Moe Z.",surname:"Win",slug:"moe-z.-win",fullName:"Moe Z. Win"},{id:"221473",title:"Prof.",name:"Rong",surname:"Zhao",slug:"rong-zhao",fullName:"Rong Zhao"}],corrections:null},{id:"60585",title:"Experimental Studies of the Electrical Nonlinear Bimodal Transmission Line",doi:"10.5772/intechopen.76204",slug:"experimental-studies-of-the-electrical-nonlinear-bimodal-transmission-line",totalDownloads:940,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"After a few years of calm, the investigations on the dynamic, especially nonlinear, systems returned to the front of the research in non-linear physics. We propose, in this chapter, a study of an electrical nonlinear transmission line, realized in a previous work, to use the latter to highlight certain properties (modulation instability—MI, Fermi-Pasta-Ulam (FPU) recurrence, fragmentation of solitons in wave trains, multiplication(increase) and division of frequencies, etc.), which are observed in several domains in applied physics: hydraulic, artificial neuronal, network physical appearance (physics) of the plasma, and the circulation.",signatures:"Abdou Karim Farota, Mouhamadou Mansour Faye, Bouya Diop,\nDiène Ndiaye and Mary Teuw Niane",downloadPdfUrl:"/chapter/pdf-download/60585",previewPdfUrl:"/chapter/pdf-preview/60585",authors:[{id:"107261",title:"Dr.",name:"Diene",surname:"Ndiaye",slug:"diene-ndiaye",fullName:"Diene Ndiaye"},{id:"214425",title:"Dr.",name:"Abdou Karim",surname:"Farota",slug:"abdou-karim-farota",fullName:"Abdou Karim Farota"},{id:"214426",title:"Prof.",name:"Bouya",surname:"Diop",slug:"bouya-diop",fullName:"Bouya Diop"},{id:"214427",title:"Prof.",name:"Mouhamadou Mansour",surname:"Faye",slug:"mouhamadou-mansour-faye",fullName:"Mouhamadou Mansour Faye"},{id:"214429",title:"Prof.",name:"Mary Teuw",surname:"Niane",slug:"mary-teuw-niane",fullName:"Mary Teuw Niane"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:[{id:"65",label:"highly cited contributor"}]},relatedBooks:[{type:"book",id:"3563",title:"Advanced Microwave Circuits and Systems",subtitle:null,isOpenForSubmission:!1,hash:"2d0a7e4bb67e54ab0bbe098ebb9537d4",slug:"advanced-microwave-circuits-and-systems",bookSignature:"Vitaliy Zhurbenko",coverURL:"https://cdn.intechopen.com/books/images_new/3563.jpg",editedByType:"Edited by",editors:[{id:"3721",title:"Prof.",name:"Vitaliy",surname:"Zhurbenko",slug:"vitaliy-zhurbenko",fullName:"Vitaliy Zhurbenko"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3576",title:"Solid State Circuits Technologies",subtitle:null,isOpenForSubmission:!1,hash:"a14e0865ac126e0234df9b53a5943ebf",slug:"solid-state-circuits-technologies",bookSignature:"Jacobus W. 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1. Introduction
Crohn’s disease (CD) is an idiopathic inflammatory disorder with genetic, immunologic and environmental influences [1]. It is characterized by a transmural inflammation that may involve any portion of the luminal gastrointestinal tract, from the oral cavity to the perianal area. The diagnosis is based on the combination of clinical, biochemical, radiological, endoscopic and histological findings. CD is a chronic and progressive disease, marked by frequent relapses which usually require repeated investigations.
The most common symptoms of CD are diarrhea, abdominal pain and fatigue. However, clinical manifestations can be very heterogeneous, depending on the disease location and phenotype. Patients with CD often show laboratory evidence of inflammatory activity and anemia. In addition, fecal calprotectin and serum C-reactive protein are useful markers to detect and monitor inflammation. The endoscopic hallmark of CD is the patchy distribution of inflammation and mucosal biopsies usually show focal inflammation (rather than diffuse), crypt distortion and/or granulomas. Finally, cross-sectional imaging techniques provide information about the bowel wall and extra-enteric soft tissues and, therefore, can better classify disease phenotype and behavior.
Endoscopy has major implications not only for the diagnosis of CD but also for treatment and follow-up. Indeed, ileocolonoscopy and upper gastrointestinal endoscopy have well-established roles in assessing disease activity and therapeutic intervention. However, the small bowel is one of the most common areas affected in patients with CD, which is often inaccessible to conventional endoscopy. In addition, at the time of diagnosis, up to 30% of patients have only small bowel involvement, especially in the young ones [2, 3]. The advent of video capsule endoscopy and both balloon-assisted and spiral enteroscopy is revolutionizing the management of small bowel CD [4]. In fact, these techniques allowed direct visualization of the entire small bowel which can assist in the diagnosis of CD. Moreover, device-assisted enteroscopy enables direct tissue sampling and allows therapeutic interventions. In this chapter, we aim to review the role of small bowel endoscopy in the management of patients with CD.
2. Diagnosis
2.1 Ileocolonoscopy
Colonoscopy with intubation of the terminal ileum and multiple biopsies is recommended as part of the initial evaluation of patients with suspected CD [5]. It has been reported a successful ileal intubation rate as high as % when the cecum is reached [6]. A minimum of two biopsies from five different sites, including the rectum and the ileum, should be obtained for a reliable diagnosis of CD. Samples are preferably obtained both from areas which are involved by the disease and from uninvolved areas. Mucosal changes suggestive of CD include discontinuous segments of edema, friability, ulcerations, fistulous orifices and stenosis (Figure 1). With respect to the histological exam, macroscopic and microscopic features include discontinuous chronic inflammation, with lymphocytes and plasma cells, focal crypt distortion and granulomas. Although the presence of granulomatous inflammation is helpful, it is not required for diagnosis and is seen in only 33% of patients with CD [7].
Figure 1.
Endoscopic appearance of Crohn’s disease - discontinuous segments of edema, friability, ulcerations (A) and stenosis (B and C).
Ileocolonoscopy is also helpful for the detection of stenosis, allowing tissue sampling for pathological diagnosis of dysplasia and cancer. Complementary radiological techniques to rule out additional stenotic lesions are necessary when the lesion is impassable with the endoscope.
Attempts to quantify the distribution and severity of mucosal involvement of the colon and the ileum in patients with CD have led to the development of multiple endoscopic scoring systems. Endoscopic scores that have been validated for ileocolonoscopy include both the Crohn’s Disease Endoscopic Index of Severity (CDEIS) [8] and the Simple Endoscopic Score for Crohn’s Disease (SES-CD) [9]. The CDEIS includes six endoscopic variables (presence of deep ulcers, superficial ulcers, nonulcerated stenosis, ulcerated stenosis, proportion of ulcerated surface and proportion of surface affected by disease), assessed in five bowel segments (terminal ileum, right colon, transverse, left colon and sigmoid, rectum) (Table 1). The CDEIS is complicated to use and requires training and experience. Therefore, it is used mainly in clinical trials. On the other hand, the SES-CD has been helpful to translate endoscopic activity into clinically meaningful and is easier to use and understand. The SES-CD includes four variables, each considered in five bowel segments (ulcer size, extent of ulcerated surface, extent of affected surface and stenosis) (Table 2).
Ileum
Right colon
Transverse colon
Left colon
Rectum
Sum
Deep ulceration (0 for none, 12 points if present)
Total 1
Superficial ulceration (0 for none, 6 points if present)
Total 2
Surface involved by disease (cm)
Total 3
Surface involved by ulceration (cm)
Total 4
Total 1 + 2 + 3 + 4
Total A
Number of segments totally or partially explored
n
Total A divided by n
Total B
Quote 3 if ulcerated stenosis anywhere
C
Quote 3 if nonulcerated stenosis anywhere
D
Total B + C + D
CDEIS
Table 1.
Crohn’s disease endoscopic index of severity (CDEIS). CDEIS includes deep ulceration (no = 0, yes = 12), superficial ulceration (no = 0, yes = 6), surface involved by disease (0–10), ulcerated surface (0–10), and ulcerated or non-ulcerated stenosis (no = 0, yes = 3), each considered in five ileocolonic segments. Severe disease: CDEIS ≥12, moderate disease: CDEIS = 9–12, mild disease: CDEIS = 3–9, remission: CDEIS <3.
Variable
0
1
2
3
Size of ulcers
None
Aphthous ulcers (0.2–0.5 cm)
Large ulcers (0.5-2 cm)
Very large ulcers (>2 cm)
Ulcerated surface
None
<10%
10–30%
>30%
Affected surface
None
<50%
50–75%
>75%
Presence of narrowing
None
Single, can be passed
Multiple, can be passed
Impassible
Table 2.
Simple endoscopic score for Crohn’s disease (SES-CD). SES-CD = sum of all variables of each explored segment (ileum, right colon, transverse colon, left colon and rectum). Severe disease: SES-CD ≥16, moderate disease: SES-CD = 7–15, mild disease: SES-CD = 3–6, inactive disease: SES-CD <3.
It is important to note that up to 25% of patients have isolated proximal small bowel disease beyond the reach of even complete ileocolonoscopy [10]. Therefore, radiological imaging should be performed in all patients with suspected CD to complement ileocolonoscopy.
2.2 Upper gastrointestinal endoscopy
The presence of CD of the upper gastrointestinal tract, including the duodenum, is uncommon in adults, with most studies showing a prevalence range of 0.3–5% [11]. Moreover, the majority of patients are asymptomatic at the time of evaluation [12]. However, it is important to note that CD in the proximal gastrointestinal tract is associated with a worse prognosis and there is usually a low threshold to initiate therapy with anti-tumor necrosis factor (TNF).
CD involving the upper gastrointestinal tract is almost invariably accompanied by small or large bowel involvement [13]. Esophagogastroduodenoscopy is recommended in patients with upper gastrointestinal signs and symptoms, being still debated whether asymptomatic adult CD patients should routinely undergo upper endoscopy [6]. In fact, esophagogastroduodenoscopy may support the diagnosis when it is difficult to obtain a histological diagnosis of CD. In addition, a more recent prospective registry reported a higher prevalence of upper gastrointestinal involvement in asymptomatic patients than initially expected, suggesting a place for a standard gastroscopy to correctly evaluate disease extent at diagnosis [12].
Endoscopic features suggestive of upper gastrointestinal involvement include mucosal nodularity, aphthous ulcers, superficial erosions, antral thickening and duodenal strictures [1]. Histologic changes consistent with CD are granulomatous inflammation, focally enhanced gastritis and focal cryptitis of the duodenum.
In the presence of upper tract stenosis, balloon dilatation is recommended as first-line therapy, followed by proton pump inhibitors as second-line and steroids/thiopurines/surgery as third-line [14]. Currently, there is no credible evidence to support the best modality to assess response to treatment of upper gastrointestinal CD, therefore it must be primarily monitored by the reference standard endoscopy.
2.3 Video capsule endoscopy
Video capsule endoscopy is a method of endoluminal examination of the small bowel using a wireless capsule-shaped tool which is swallowed and then propelled through the gastrointestinal tract by gut motility [15]. Preparations for a video capsule endoscopy study usually include 8–12 hours’ fasting and some method of bowel cleansing (e.g. polyethylene glycol preparation). During the battery life of the capsule, images of the small bowel are recorded and reformatted into a continuous video file. After 8–10 hours, the antenna and storage unit are removed and the images transferred to a computer with specially adapted software. Images are then downloaded, processed and examined by a trained gastroenterologist (Figure 2).
Figure 2.
Video capsule endoscopy images showing mucosal inflammation and ulcerations consistent with a diagnosis of Crohn’s disease.
In addition to the small-bowel capsule, there are currently two more: the esophageal and the colon capsules [16]. The esophageal capsule is the same size as the small bowel capsule, but has lenses on both ends of the ‘pill.’ The capsule battery life is only 20 minutes (vs. 8–12 hours for small-bowel capsules), cameras are located on both ends of the capsule and take 18 frames per second (vs. 2–3 frames per second for small-bowel capsules). On the other hand, the second-generation colon capsule endoscope is equipped with two high-resolution cameras providing a viewing angle of 172° in front and back, senses the moving speed of the capsule endoscope and captures 4 to 35 images per second [17]. This capsule was primarily utilized in screening for colonic neoplasia, particularly in situations such as incomplete colonoscopy. However, it can play a key role in the diagnosis and evaluation of CD extent, severity and prognosis, with treatment modifications based on data from capsule examination.
Video capsule endoscopy is a useful adjunct in the diagnosis of patients with small bowel CD since it allows for direct visualization of the mucosa of the entire small intestine. It is able to identify mucosal lesions compatible with CD in patients in whom conventional endoscopic and small bowel radiographic imaging modalities have been nondiagnostic, especially in the proximal small bowel [18]. Several meta-analyses have examined the diagnostic yield of video capsule endoscopy in the evaluation of patients with suspected CD and showed that it is superior to small bowel barium studies, computed tomography enterography and ileocolonoscopy, with an incremental yield of diagnosis of 32%, 47% and 22%, respectively [19]. Moreover, video capsule endoscopy has a negative predictive value of 96%, essentially ruling out small bowel CD [20]. On the other hand, a study examining the sensitivity and specificity of different endoscopic and radiologic exams showed that the specificity of video capsule endoscopy was significantly lower than the other tests [21]. In fact, detected lesions are nonspecific and cannot be distinguished from those seen in patients treated by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, video capsule endoscopy should be reserved for cases in which ileocolonoscopy plus small bowel radiography is not diagnostic, but there is a high rate of CD suspicion.
Although there are no validated diagnostic criteria for the diagnosis of CD, the presence of more than three small bowel ulcerations, in the absence of NSAIDs ingestion for at least 1 month before the exam, constitutes the most commonly used diagnostic criterion in practice [22]. In addition, there are currently two validated indexes available, the Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI) [23] and the Lewis Score [24], which assess the disease location and activity of small bowel involvement. The CECDAI was validated in a multicenter prospective study of patients with isolated small bowel CD and evaluates the following three endoscopic parameters: inflammation, extent of disease and strictures for both the proximal and the distal segments of the small bowel, based on the transit time of the capsule (Table 3). The Lewis score is another scoring system based on the evaluation of three endoscopic parameters: villous appearance, ulcers and strictures (Table 4). The small bowel is divided into three equal parts and, for each tertile, a subscore is determined. The Lewis Score is the sum of the worst affected tertile plus the stenosis score. Both the scoring systems are incorporated into the software platform of the capsules and assists in the quantification of small bowel inflammatory burden and diagnosis of CD.
Parameter
Score and descriptor
A - Inflammation
0 - None 1 – Mild to moderate (edema, hyperemia or denudation) 2 – Severe (edema, hyperemia or denudation) 3 – Bleeding, exudate, erosion aphthae, ulcers <0.5 cm 4 – Pseudopolyp, ulcers 0.5-2 cm 5 – Ulcers >2 cm
Capsule endoscopy Crohn’s disease activity index (CECDAI). CECDAI = proximal segment (A x B + C) + distal segment (A x B+C). Clinical or endoscopic remission: CEDAI <4.
Lewis score. Score total = worst-affected tertile villous appearance and ulcers plus stenosis score. Clinically insignificant inflammation: Lewis score <135, mild inflammation: Lewis score = 135–790, moderate to severe inflammation: Lewis score >790.
Video capsule endoscopy may also identify a site for directed visualization with other endoscopic techniques. In fact, it can be complementary to device-assisted endoscopy since findings may help direct the most effective route of intubation (oral versus anal), in order to obtain a histopathological diagnosis or therapeutic intervention.
In addition, video capsule endoscopy allows detection of subtle small bowel lesions, which may affect the therapeutic management. Because of the high sensitivity of video capsule endoscopy, it has a potential role in the assessment of mucosal healing after drug therapy and can be used in the follow-up of treated patients. In fact, video capsule endoscopy has a significant impact on disease management and is associated with earlier escalation of therapy. In the largest retrospective series of patients with established CD that were evaluated with video capsule endoscopy, a change in management was suggested in 40–52% of individuals [25, 26].
The main advantage of video capsule endoscopy is the ability to visualize all of the small bowel with minimal discomfort for the patient. However, it lacks therapeutic capabilities and there is some risk of impaction due to possible strictures. The capsule retention rate in patients with suspected CD is 1.5–5.4% but can reach 13% in those with established CD, particularly if there are known intestinal stenosis [27, 28]. Therefore, those with obstructive symptoms or established CD of the small bowel should always have small bowel imaging and/or patency capsule evaluation before video capsule endoscopy to decrease the risk of capsule retention. Video capsule endoscopy is considered safe if the patency capsule is excreted before 30 hours, an intact capsule is excreted after 30 hours or passage to the colon of an intact patency capsule has been radiologically confirmed. Another disadvantage of video capsule endoscopy is that the quality of images is not comparable to the view achieved at conventional endoscopy with gas insufflation. In addition, it has been reported that the caecum is not reached in 8–40% of video capsule endoscopy studies [22, 29]. Finally, the most serious complication reported with video capsule endoscopy is perforation, which has been exceedingly rare [30].
2.4 Device-assisted endoscopy
Device-assisted endoscopy is a generic term for any endoscopic technique that includes assisted progression (i.e. balloons and overtubes) and comprises double-balloon enteroscopy, single-balloon enteroscopy and spiral enteroscopy [31]. Device-assisted endoscopy allows direct mucosal visualization of the entire small bowel as well as tissue sampling and therapeutic intervention (Figure 3). However, it is technically challenging and may require a bi-directional approach, deep sedation or general anesthesia.
Figure 3.
Device-assisted endoscopy images showing mucosal inflammation and ulcerations consistent with a diagnosis of Crohn’s disease.
Double-balloon enteroscopy was introduced in 2001 as the first method for device-assisted enteroscopy [32]. It allows deep intubation of the small bowel by pleating the bowel onto a long and flexible endoscope fitted with an overtube. The endoscope and the accompanying overtube have balloons at their distal end. By intermittent inflation and deflation of these two balloons, combined with instrument insertion and retraction, large portions of the small bowel can be visualized directly. Oral and anal routes are used to achieve a complete small bowel examination.
Single-balloon enteroscopy is able to achieve a complete examination of the small bowel using principles similar to double-balloon enteroscopy. However, in contrast to double-balloon enteroscopy, this exam has only one balloon at the distal end of the overtube, which simplifies the preparation of the scope before starting the procedure. Single-balloon enteroscopy uses scope tip angulation and suction instead of balloon inflation to maintain a stable position while advancing the overtube.
Spiral enteroscopy is based on a completely different concept, by pleating of the bowel on the instrumentation shaft by active rotation instead of applying pushing force. The distal end of the overtube harbors a flexible spiral thread for pleating the small intestine over the overtube. By manually rotating the overtube, the spiral engages the small bowel which is thus pleated onto or unpleated from the overtube, respectively, depending on the direction of the spiral rotation. Spiral assisted endoscopy has been approved for both anterograde and retrograde enteroscopy.
The Motorized Spiral Enteroscope is a new technology with an incorporated user-controlled motor contained in the handle of the endoscope [33]. This would offer the possibility to accelerate the procedure, facilitate insertion and simplify the technique with a single operator. Recently, Beyna et al. demonstrated that the Motorized Spiral Enteroscope is effective for diagnostic and therapeutic antegrade enteroscopy and may compare favorably with traditional methods of deep enteroscopy in ease of use and procedural duration [34].
Device-assisted endoscopy is not part of routine diagnostic testing in patients with suspected CD and should not be the first-line procedure in the evaluation of small bowel [1]. However, it may provide additional information when it is required biopsy of small bowel tissue to histological corroboration. Indeed, compared with video capsule endoscopy and small bowel imaging techniques, the advantages of device-assisted endoscopy include the evaluation of atypical lesions, the ability to obtain biopsies for histopathology and the potential for therapeutic intervention.
Device-assisted endoscopy studies in individuals with suspected CD have not included large numbers of patients but report a diagnostic yield as high as 80% [35]. In fact, device-assisted endoscopy is more sensitive in detecting lesions in patients with suspected CD than multiple radiographic imaging techniques. Nevertheless, because of the invasive and potentially time-consuming nature of the exam, it should be reserved for patients with high clinical suspicion of CD despite negative conventional studies (including ileocolonoscopy, video capsule endoscopy and radiographic imaging), particularly if endoscopic and histologic finding would alter disease management or potential therapeutic intervention is required [36]. In a prospective trial, positive findings at device-assisted enteroscopy led to a step-up of medical therapy in 74% of patients, leading to clinical remission in 88% [37]. In addition, device-assisted endoscopy may be preferable to video capsule endoscopy if there is a clinical suspicion of obstruction because it may allow therapeutic intervention and be safer, simply by avoiding capsule retention.
In patients with established CD, device-assisted endoscopy is indicated when endoscopic visualization and biopsies are necessary from areas of the small bowel inaccessible to conventional endoscopy [1]. Usually, previous video capsule endoscopy provides information on the optimal route of approach (oral or rectal) and lesion location. Adhesions may limit examination by device-assisted endoscopy and, in these circumstances, double-balloon enteroscopy may be preferred to single-balloon enteroscopy. In addition, device-assisted endoscopy has the capacity for endoscopic therapy, including dilation of small bowel strictures, removal of impacted capsules and treatment of bleeding lesions (vide infra).
Overall, diagnostic device-assisted endoscopy is safe, with few reports of complications (<1%) [38]. However, there appears to be an increased risk of complications in the case of active CD or previous intestinal surgery. The risk of perforation is 0.12% without therapeutic intervention and 1.74% with therapeutic intervention, the majority of which occurred after stricture dilatation [39]. Bleeding occurs in approximately 2.5%. In addition, device-assisted endoscopy involves risks related to sedation, in contrast to video capsule endoscopy where no sedation is required.
3. Treatment
3.1 Treatment of intestinal strictures
Strictures in CD develop during the course of the disease or as the presenting feature and are believed to result from partial healing and localized fibrosis. In addition, almost one-third of CD patients develop an anastomotic stricture after ileocecal resection/right hemicolectomy [40]. As a progressive disease, anastomotic strictures will be more likely over time.
Immunomodulators and biologic agents have been widely used for the treatment of CD, however endoscopic dilatation is a preferred technique for the management of symptomatic and mild to moderate stenosing disease [41]. Indeed, medical therapy for stricture management is limited due to fibrotic nature. Endoscopic dilatation may prevent or delay the need for surgical resection or strictureplasty. Moreover, endoscopic balloon dilation should be performed to access the mucosa proximal to strictures and evaluate disease activity, that otherwise may be missed if we only relied on symptoms or biochemical markers [42]. Thus, it can provide adequate endoscopic therapy and adjust or optimize medical therapy.
Endoscopic balloon dilation may be used in Crohn’s strictures of the gastric outlet, duodenum, colon, ileocolonic anastomosis and of the small bowel, if accessible [43]. It is performed using a through-the-scope balloon catheter, which is a simple and safe procedure (Figure 4). The dilation procedure is performed with monitoring of the pressure of the inflated balloon using a dilator with or without X-ray guidance. When performing endoscopic balloon dilation, forcible dilation to achieve a larger dilation diameter or pressure is not recommended, as it could lead to intestinal perforation. The length of the balloons for inflation is about 5 cm; therefore, stenoses longer than 5 cm are considered unsuitable for endoscopic balloon dilation. Moreover, intestinal strictures with deep ulcers and fistulous complications are contraindications for endoscopic dilatation. In case of long or inflammatory strictures, balloon dilation may significantly increase the risk of perforation [44]. Hence, inflammatory and ulcerative strictures should be primarily treated with medical therapy.
Figure 4.
A segment of short stenosis is delineated using injection of contrast via a catheter (A). A guide wire is inserted through the stenosis and a balloon is then advanced over the wire and carefully inflated (B).
Over the last years, there is increasing evidence for endoscopic balloon dilation as a safe and minimally invasive effective method for the treatment of stricturing disease. In a retrospective single tertiary center study, Lopes et al. evaluated the long-term efficacy and safety of endoscopic balloon dilation in ileocolonic strictures. The authors reported a technical success rate of 97.7% to anastomotic strictures and similar to non-anastomotic strictures (100%) without major adverse events (major bleeding and perforation) [40]. Endoscopic dilatation using balloon-assisted enteroscopy for small bowel strictures is almost the same as for ileocolonic strictures in terms of procedure and technique. However, there are some technical difficulties. In fact, it is not easy to stabilize the tip of the scope and to maintain a good visual field because of the limited space available, severe angulation, motility and adhesion in the small intestine. Nevertheless, the reported technical success rate is over 85% with a perforation rate of 1% [45, 46].
A key concern of endoscopic dilatation is the long-term outcome. Indeed, a recent study showed that 63% of patients with anastomotic strictures and 41% of those with non-anastomotic strictures required additional dilation over a 4.4-year period [40]. However, Sunada et al. reported that the surgery-free rate in 321 patients with CD who underwent endoscopic dilatation for small intestinal strictures was 87% and 78% at 1 and 3 years, respectively [47]. Similarly, a systematic review assessed the role of device-assisted enteroscopy in 581 small bowel dilatations, showing an 80% long-term success rate without the need for surgery during follow-up (2.5 years per patient) [48].
In conclusion, endoscopic balloon dilation is a feasible, simple, effective and safe procedure and an appropriate option for either delaying or preventing surgery, with the possibility of being repeated as needed.
To have a persistent effect over time and avoid the high risk of recurrence, a self-expanding metallic stent has been proposed [49]. Stenting appeared to be an effective technique in treating symptomatic CD intestinal strictures, however the procedure was associated with a high rate of spontaneous migrations and complications. More recently, an anti-migration, removable and shaped self-expandable metal stent is available. Attar et al. performed a real-life study to describe short-and long-term results of the removable anti-migration stent [50]. The authors showed that it was safe and effective in about half of patients and had an extremely low migration rate, with no perforation reported. In addition, the high success rate was close to that obtained with endoscopic balloon dilation, but without complications. Taking this into account, the placement of a transient metallic stent is a new minimally invasive alternative to the management of refractory anastomotic stricture of less than 5 cm, before considering a new surgery. The use of biodegradable instead of metal stents was recently evaluated in intestinal and colonic CD strictures. Although it was technically feasible, premature stent failure occurred in all of the patients, as well as side effects such as mucosal overgrowth and stent collapse [51].
3.2 Removal of impacted capsules
One problem of video capsule endoscopy in patients with suspected or known CD is the risk of impaction due to previously undiagnosed stenoses. One effort to overcome this difficulty was the development of the patency capsule. However, the successful passage of the patency capsule does not absolutely guarantee that intestinal obstruction will not occur during the passage of the video capsule. Similarly, some stenoses may not be detected by prior radiographic methods. Therefore, capsule impaction can occur.
A retained capsule, in general, does not cause obstruction. In fact, the capsule can remain in the small bowel for several months without causing symptoms. Thus, unless malignancy is strongly suspected, conservative or pharmaceutical intervention, namely with corticosteroids, are justified therapeutic options in the majority of cases [52].
When patients develop obstructive symptoms, they may have to undergo device-assisted enteroscopy or surgery. Push-and-pull enteroscopy using the double-balloon technique has proven to be extremely effective (90–100% of cases) and is considered the method of choice [53]. Surgery is an alternative procedure for removing impacted capsules, especially in those cases in which investigations unequivocally suggest the presence of neoplastic disease. The surgical intervention allows the removal of both the capsule and the pathology that caused capsule retention. In addition, intra-operative enteroscopy can be a useful tool to establish intra-luminal pathology like ulceration as a cause of retained endoscopic capsule.
Besides some cases of acute intestinal obstruction, there are only a few more complications reported in the literature due to a retained capsule. In fact, bowel perforation and capsule disintegration have already been reported, but only in case reports [54, 55].
3.3 Treatment of bleeding lesions
CD may be associated with mild gastrointestinal bleeding while major hemorrhage is a rare complication. In addition, a definitive bleeding site is not identified in most patients. In fact, hemorrhage is frequently attributed to diffuse areas of active inflammation [56]. The majority of bleeds originate from the ileum and colon and only a small number of episodes have been attributed to a jejunal or upper gastrointestinal source.
Initial management of major hemorrhage should always include primary resuscitation, as in any individual with a significant gastrointestinal bleed [57]. Once a patient is stabilized, diagnostic maneuvers are of primary importance. The site of bleeding can be identified by endoscopy, angiography or labeled red blood cell scans. However, clinicians should be aware that identifying a precise source of bleeding is difficult and salvage surgery may be necessary.
In the context of CD, urgent device-assisted enteroscopy for large-volume bleeding should be performed via the retrograde route, given the propensity of these conditions to involve the distal small bowel [52]. When it is identified, the source of bleeding is more commonly described as a deep ulcer eroding into a blood vessel and therapy may be attempted [56]. Endoscopy therapy includes thermocoagulation alone or a combination of epinephrine injection and bipolar coagulation [58]. Application of hemoclips may be compromised in the presence of inflamed and friable mucosa. On rare occasions, a large pseudopolyp in the ileum or colon has been identified as the source of bleeding; polypectomy should be performed in these cases. Although endoscopic therapy can stop acute bleeding, it does not promote mucosal healing and therefore cannot prevent rebleeding. In fact, the risk of rebleeding associated with endoscopic hemostasis is about 50% [56]. Thus, therapies that can induce and maintain mucosal healing are necessary to prevent rebleeding, such as anti-TNF agents.
Intraoperative enteroscopy may be the most reliable method to achieve a complete small bowel evaluation. It involves evaluation of the small bowel at laparotomy and may be performed orally, rectally or via an enterotomy. Upper endoscopes, colonoscopes, push enteroscopes and balloon-assisted scopes have all been used. Although it is highly invasive and associated with major complications, it may help in the identification of the bleeding source and in planning the optimal therapeutic intervention [59].
When CD is complicated by obscure bleeding, video capsule endoscopy and device-assisted endoscopy may identify and treat the bleeding source beyond the reach of standard endoscopes [1]. In fact, video capsule endoscopy has a fundamental role in diagnosing obscure gastrointestinal bleeding in patients with CD. It has been found to be superior to push enteroscopy and small bowel radiography. Video capsule endoscopy should be performed immediately after a negative upper and lower endoscopy as a screening method. The results of video capsule endoscopy should guide the use of device-assisted endoscopy, which aims at both the confirmation and treatment of the detected lesions.
3.4 Intralesional injection
Although local injection of immunomodulatory drugs like corticosteroids and infliximab CD stricture may look like an attractive therapeutic strategy [60], the available evidence is inconsistent. Some studies have shown benefit of intralesional injection of triamcinolone [61] and infliximab [62] at the time of balloon dilatation of CD. On the other hand, East et al. compared local quadrantic injection of triamcinolone after endoscopic balloon dilatation of Crohn’s ileocolonic anastomotic strictures vs. saline placebo and showed that a single treatment of intrastricture triamcinolone injection did not reduce the time to redilatation [63]. Moreover, there was a trend toward a worse outcome. Similarly, Atreja et al. reported that intralesional steroid or biologics injection did not decrease the need for re-intervention or surgery for either primary or anastomotic strictures [64]. Until now, there is no strong evidence supporting the injection of drugs at the site of strictures and larger series are needed to evaluate the real effectiveness of these techniques in the treatment of patients with obstructive strictures.
4. Postoperative recurrence
In the natural history of CD, intestinal resection is unavoidable in a significant proportion of patients. The majority of individuals will develop disease recurrence at or above the anastomosis, which usually occurs within a few weeks to months after ileocolonic resection [65].
Diagnosis of postoperative recurrence is based on clinical symptoms, serum and fecal markers, radiological and endoscopic findings. Nevertheless, ileocolonoscopy remains the gold standard, by defining the presence and severity of morphological recurrence [41]. It is recommended within the first 6 to 12 months after surgery, when treatment decisions may be affected. In fact, endoscopic recurrence usually precedes clinical recurrence and severe endoscopic recurrence predicts a poor prognosis. Rutgeerts et al. developed an endoscopic scoring system to assess postoperative recurrence in patients having ileocolonic resection [66]. The patients were stratified into five groups according to the endoscopic severity (Table 5). An endoscopic score of i0 or i1 correlated with a low risk of endoscopic progression and had clinical recurrence rates of less than 10% over 10 years. An endoscopic score of i2 or above suggests mucosal inflammation and should prompt considered treatment escalation [14]. However, it is important to note that the i2 category, including aphthous lesions in the terminal ileum as well as ileocolonic anastomosis lesions, had a heterogeneous recurrence risk. Therefore, a modified Rutgeerts’ score has recently emerged in which i2 is subdivided into i2a for lesions confined to the ileocolonic anastomosis, including anastomotic stenosis, and i2b for more than 5 aphthous ulcers or larger lesions, with normal mucosa in between, in the neoterminal ileum, with or without anastomotic lesions [67]. With this modified score, stenosis and/or ulceration of the anastomosis, which might simply be related to ischemia or staples, do not define recurrent disease and have no prognostic or therapeutic implications [68]. Thus, possible confounding factors for recurrent disease are overcome with this score.
Rutgeerts´ score
Endoscopic description of findings
i0
No lesions
i1
≤5 aphthous ulcers
i2
>5 aphthous ulcers with normal intervening mucosa, skip areas of larger lesions or lesions confined to ileocolonic anastomosis
i3
Diffuse aphthous ileitis with diffusely inflamed mucosa
i4
Diffuse inflammation with large ulcers, nodules and/or narrowing
Video capsule endoscopy can also be used to assess postoperative recurrence of CD and should be considered if ileocolonoscopy is contraindicated or unsuccessful. Video capsule endoscopy may identify lesions in the small bowel that have not been detected by ileocolonoscopy after ileocolic resection. An important advantage of capsule endoscopy is the ability to detect proximal small bowel recurrence. However, patency capsule evaluation is recommended before capsule endoscopy to minimize the risk of retention.
5. Small bowel malignancy
Patients with CD are at an increased risk of developing malignancy, which is more frequent in the CD-affected colon. However, those with small bowel involvement may also develop cancer, which can be difficult to diagnose. In fact, compared with an age-matched population, patients with CD have an 18-fold increased incidence of small bowel malignancy and only a minority are detected at an early stage [69]. Adenocarcinoma is the most common form of all small bowel cancer. Prognosis of small bowel adenocarcinoma is poor and the mortality at 1 and 2 years ranges from 30–60% dependent on the stage of cancer [70].
Early detection of small bowel carcinoma remains a problem. Radiological imaging and video capsule endoscopy could potentially detect malignancies at an early stage. However, differentiation between inflammatory stenosis and cancer is difficult. In these cases, device-assisted enteroscopy should be performed to direct visualization and tissue sampling. Furthermore, these procedures are not routinely used for screening asymptomatic individuals. Therefore, every patient who has a change of symptoms should perform further exams as this might be an indicator of malignancy [69]. Moreover, most of the small bowel carcinoma in CD is located in strictures, so the endoscopist should have a low threshold for taking biopsies before endoscopic balloon dilatation [71].
6. Conclusions
Endoscopy has major implications for diagnosis, classification, therapeutic decision and prognosis of CD. Ileocolonoscopy with biopsy is the first-line exam for suspected CD. However, the small bowel is one of the most affected areas by inflammation, which may skip the terminal ileum and not be detected by ileoscopy. In fact, small intestine involvement is more difficult to assess by conventional endoscopy. In addition, radiological examinations, including both magnetic resonance imaging and computed tomography, may not detect disease of the small bowel, especially in mild lesions.
Until a decade ago, mucosal visualization of the small intestine was limited to the reach of the push enteroscope. The advent of video capsule endoscopy and device-assisted endoscopy is revolutionizing small bowel CD diagnosis and treatment. In fact, these techniques allowed direct visualization of the entire small intestine, which would alter patient management, especially in those with inconclusive results from conventional studies. Device-assisted endoscopy has also the ability to obtain biopsies for histopathology and the potential for therapeutic intervention. Finally, video capsule endoscopy and device-assisted endoscopy play an important role in assessing response to therapy.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"Inflammatory bowel disease, Crohn’s disease, endoscopy, small bowel",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/75242.pdf",chapterXML:"https://mts.intechopen.com/source/xml/75242.xml",downloadPdfUrl:"/chapter/pdf-download/75242",previewPdfUrl:"/chapter/pdf-preview/75242",totalDownloads:309,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:36,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"September 28th 2020",dateReviewed:"January 9th 2021",datePrePublished:"March 8th 2021",datePublished:"March 24th 2021",dateFinished:"February 13th 2021",readingETA:"0",abstract:"Crohn’s disease (CD) is a complex disorder with variable age of onset, disease location and behavior. It is characterized by a transmural inflammation that may involve any portion of the gastrointestinal tract. Ileocolonoscopy with biopsy is established as the first-line investigation for suspected CD. However, small bowel involvement is more difficult to assess by conventional endoscopy. Therefore, radiological imaging should also be performed to complement ileocolonoscopy in all patients with suspected CD. Recently, video capsule endoscopy and device-assisted enteroscopy have revolutionized the management of small bowel CD. In fact, video capsule endoscopy is a non-invasive test that provides the visualization of the entire small bowel mucosa, which can assist in the diagnosis of CD and assess the therapeutic response. On the other hand, device-assisted enteroscopy enables direct tissue sampling for histopathology confirmation when traditional endoscopy, video capsule endoscopy and cross-sectional imaging are inconclusive. Moreover, it allows therapeutic interventions such as balloon stricture dilation. In this chapter, we review the role of endoscopy in the diagnosis and management of patients with small bowel CD.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/75242",risUrl:"/chapter/ris/75242",book:{id:"10309",slug:"endoscopy-in-small-bowel-diseases"},signatures:"Isabel Garrido, Susana Lopes and Guilherme Macedo",authors:[{id:"307882",title:"Prof.",name:"Guilherme",middleName:null,surname:"Macedo",fullName:"Guilherme Macedo",slug:"guilherme-macedo",email:"guilhermemacedo59@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"333240",title:"Prof.",name:"Susana",middleName:null,surname:"Lopes",fullName:"Susana Lopes",slug:"susana-lopes",email:"su.isa.lopes@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"338772",title:"Dr.",name:"Isabel",middleName:null,surname:"Garrido",fullName:"Isabel Garrido",slug:"isabel-garrido",email:"isabelmng@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Diagnosis",level:"1"},{id:"sec_2_2",title:"2.1 Ileocolonoscopy",level:"2"},{id:"sec_3_2",title:"2.2 Upper gastrointestinal endoscopy",level:"2"},{id:"sec_4_2",title:"2.3 Video capsule endoscopy",level:"2"},{id:"sec_5_2",title:"2.4 Device-assisted endoscopy",level:"2"},{id:"sec_7",title:"3. Treatment",level:"1"},{id:"sec_7_2",title:"3.1 Treatment of intestinal strictures",level:"2"},{id:"sec_8_2",title:"3.2 Removal of impacted capsules",level:"2"},{id:"sec_9_2",title:"3.3 Treatment of bleeding lesions",level:"2"},{id:"sec_10_2",title:"3.4 Intralesional injection",level:"2"},{id:"sec_12",title:"4. Postoperative recurrence",level:"1"},{id:"sec_13",title:"5. Small bowel malignancy",level:"1"},{id:"sec_14",title:"6. Conclusions",level:"1"},{id:"sec_18",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG Clinical Guideline: Ulcerative Colitis in Adults. 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Long-term Outcomes in Patients with Small Intestinal Strictures Secondary to Crohn\'s Disease After Double-balloon Endoscopy-assisted Balloon Dilation. Inflamm Bowel Dis. 2016;22(2):380-386'},{id:"B48",body:'Baars JE, Theyventhiran R, Aepli P, Saxena P, Kaffes AJ. Double-balloon enteroscopy-assisted dilatation avoids surgery for small bowel strictures: a systematic review. World J Gastroenterol. 2017;23(December (45)):8073-81'},{id:"B49",body:'Attar A, Maunoury V, Vahedi K, Vernier-Massouille G, Vida S, Bulois P, et al. Safety and efficacy of extractible self-expandable metal stents in the treatment of Crohn’s disease intestinal strictures: A prospective pilot study. Inflamm Bowel Dis. 2012;18(10):1849-1854'},{id:"B50",body:'Attar A, Branche J, Coron E, Privat J, Caillo L, Chevaux JB, et al. An Anti-Migration Self-Expandable and Removable Metal Stent for Crohn\'s Disease Strictures: A Nationwide Study From the Getaid and the Sfed. J Crohns Colitis. 2020:jjaa208'},{id:"B51",body:'Karstensen JG, Christensen KR, Brynskov J, Rønholt C, Vilmann P, Hendel J. Biodegradable stents for the treatment of bowel strictures in Crohn\'s disease: technical results and challenges. Endosc Int Open. 2016.;4(3):E296–E300'},{id:"B52",body:'Rondonotti E, Spada C, Adler S, May A, Despott EJ, Koulaouzidis A, et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy. 2018;50(4):423-446'},{id:"B53",body:'Mitsui K, Fujimori S, Tanaka S, Ehara A, Omori J, Akimoto N, et al. Retrieval of retained capsule endoscopy at small bowel stricture by double-balloon endoscopy significantly decreases surgical treatment. J Clin Gastroenterol. 2016;50:141-146'},{id:"B54",body:'Gonzalez Carro P, Picazo Yuste J, Fernández Díez S, Pérez Roldán F, Roncero García-Escribano O. Intestinal perforation due to retained wireless capsule endoscope. Endoscopy. 2005;37:684'},{id:"B55",body:'Fry LC, De Petris G, Swain JM, Fleischer DE. Impaction and fracture of a video capsule in the small bowel requiring laparotomy for removal of the capsule fragments. Endoscopy. 2005;37:674-676'},{id:"B56",body:'Podugu A, Tandon K, Castro FJ. Crohn\'s disease presenting as acute gastrointestinal hemorrhage. World J Gastroenterol. 2016;22(16):4073-4078'},{id:"B57",body:'Korzenik JR. Massive Lower Gastrointestinal Hemorrhage in Crohn\'s Disease. Curr Treat Options Gastroenterol. 2000 Jun;3(3):211-216'},{id:"B58",body:'Belaiche J, Louis E, D\'Haens G, Cabooter M, Naegels S, De Vos M, et al. Acute lower gastrointestinal bleeding in Crohn\'s disease: characteristics of a unique series of 34 patients. Belgian IBD Research Group. Am J Gastroenterol. 1999;94:2177-2181'},{id:"B59",body:'Daperno M, Sostegni R, Rocca R. Lower gastrointestinal bleeding in Crohn’s disease: how (un-)common is it and how to tackle it? Dig Liver Dis. 2012;44:721-722'},{id:"B60",body:'Kochhar R, Poornachandra KS. Intralesional steroid injection therapy in the management of resistant gastrointestinal strictures. World J Gastrointest Endosc. 2010;2:61-68'},{id:"B61",body:'Brooker JC, Beckett CG, Saunders BP, Benson MJ. Long-acting steroid injection after endoscopic dilation of anastomotic Crohn’s strictures may improve the outcome: a retrospective case series. Endoscopy. 2003;35:333-337'},{id:"B62",body:'Hendel J, Karstensen JG, Vilmann P. Serial intralesional injections of infliximab in small bowel Crohn\'s strictures are feasible and might lower inflammation. United European Gastroenterol J. 2014;2(5):406-412'},{id:"B63",body:'East JE, Brooker JC, Rutter MD, Saunders BP. A pilot study of intrastricture steroid versus placebo injection after balloon dilatation of Crohn’s strictures. 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Correlation Between Calprotectin and Modified Rutgeerts Score. Inflamm Bowel Dis. 2016;22(9):2173-2181'},{id:"B69",body:'Laukoetter MG, Mennigen R, Hannig CM, Osada N, Rijcken E, Vowinkel T, et al. Intestinal cancer risk in Crohn\'s disease: a meta-analysis. J Gastrointest Surg. 2011;15(4):576-583'},{id:"B70",body:'Rieder F, Latella G, Magro F, Yuksel ES, Higgins PD, Di Sabatino A, et al. European Crohn’s and Colitis Organisation topical review on prediction, diagnosis and management of fibrostenosing Crohn’s disease. J Crohns Colitis. 2016;10:873-885'},{id:"B71",body:'Maaser C, Sturm A, Vavricka SR, Kucharzik T, Fiorino G, Annese V, et al. European Crohn’s and Colitis Organisation [ECCO] and the European Society of Gastrointestinal and Abdominal Radiology [ESGAR]. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019;13(2):144-164'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Isabel Garrido",address:"isabelmng@hotmail.com",affiliation:'
Gastroenterology and Hepatology Department, Centro Hospitalar Universitário de São João, Portugal
World Gastroenterology Organization (WGO) Porto Training Center, Portugal
Gastroenterology and Hepatology Department, Centro Hospitalar Universitário de São João, Portugal
World Gastroenterology Organization (WGO) Porto Training Center, Portugal
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1. Introduction: veterinary pharmaceuticals and antimicrobials
Veterinary pharmaceuticals include drugs, medications, and other substances in use to treat or prevent animal diseases for health, growth promotion, and productivity [1]. These drugs can be broadly divided into categories according to the different pathogens or targeted infections. They include antiparasitic drugs, antiinflammatory, reproductive medication, surgical medications, anesthetics, nutritional drugs, and feed additives sometimes used as growth promoters (Table 1). Among commonly used drug in veterinary medicine are antibiotics. These drugs and medicaments can be administered in form of injectable, tablet, bolus, drench, and bath/wash or added to feed and drinking water. There are documented evidence of earlier norms and practices of animal husbandry regarding how shepherd and nomads provide medication for livestock. Some were written document by priests in monasteries, such as the use of garlic (Allium sativum L.) and ointment made from honey and grease [2]. This is similar to what has now been recognized in modern veterinary medicine as ethno-veterinary or alternative medicine in human and according to the World Health Organization (WHO); 75% of the world’s population are using herbs for basic healthcare [3]. Such practices predate modern day pharmacopeia, which has, however, refined and synthesized the delivery of veterinary and human medicines. Some global industrial leaders in modern veterinary pharmaceuticals include Zoetis (formerly Pfizer Animal Health), Merck, Bayer, Elanco Animal Health, Boehringer Ingelheim Animal Health (Merial), Norvatis Animal Health, and many others. These companies and their subsidiaries are engaged in the multibillion dollars profitable business of drug distribution in developing countries (and also from Asia to Africa) in millions of doses some of which may be overused and contributing to drug resistance [4, 5].
Antibiotics
Antiparasitic
Antiinflammatory
Anesthetics
Growth promoters
Terramycin
Banminth
Ibuprofen
Phenobarbital
Feed grade antibiotics
Penicillin
Ivermectin
Meloxicam
Thiamylal
Probiotics
Streptomycin
Diminazene aceturate
Dexamethasone
Xylazine hydrochloride
Dihydropyridine
Colistin
Amprolium
Prednisone
Chlorpromazine
Organic acids
Erythromycin
Piperazine
Prednisolone
Diazepam
Amino acids
Doxycycline
Albendazole
Aspirin
Thiopental sodium
Racto-amine
Enrofloxacin
Closantel
Phenylbutazone
Pentobarbital
Sodium-bicarbonate
Tylosin
Dermatocide
Dimethylsulfoxide
Chloral hydrate
Potassium chloride
Oxytetracycline
Diazinon
Flunixin
Methohexital
Fatty acids
Amoxycillin
Nitroxynil
Meglumine
Methoxyflurane
Zytomil
Gentamycin
Cypermethrin
Cortisone
Halothane
Renature-Z oral powder
Chloramphenicol
Pyrantel pamoate
Methimazole
Diethyl ether
Vita-Sel-E oral solution
Ciprofloxacin
Praziquantel
Celecoxib
Isoflurane
Eucament plus oral solution
Griseofulvin
Mectizan
Colchicine
Enflurane
Chicktonic
Norfloxacin
Nitroxyl
Cyclooxygenase
Nitrous oxide
Aminogrow WS
Rifampin
Diclazuril
Pylorus
Glyceryl quiacolate
Electromix WS
Novidium chloride
Mavacoxib
Succinyl choline
Introvit A+ WS
Isomethadone
Tepoxalin
Curare
Introvit-ES-200 WS
Furazolidone
Homidium chloride
Piroxicam
Lidocaine
Introvit-K-200 WS
Table 1.
Some veterinary pharmaceuticals distributed in Nigeria.
Source: survey of commonly use veterinary antimicrobials in Nigeria, courtesy of Dr. Jolly Amoche of National Veterinary Research Institute, Vom.
Globally, there are more livestock in the world than human, with livestock systems occupying about 30% of the planet’s ice-free terrestrial surface area [6]. Most of these animals are kept in free range husbandry systems in under-developed countries where the enterprise supports the livelihood of about 600 million small holders [7]. The livestock sector in developing countries is also evolving in response to rapidly increasing demand for livestock products with changes in the demand for livestock products being driven among other factors by human population growth, urbanization, and increasing income [8, 9].
A major limiting factor in profitable livestock production in developing country is the burden of infectious diseases. These livestock diseases cause great socioeconomic impact, and the burdens are most of the time exasperated by poor biosecurity in both intensive and open production systems. This has made the use of antimicrobials for treatment of diseases indispensable [10]. It is important to emphasize that the reduction in the burden of infectious livestock diseases has been possible due in part to the use of a wide range effective drugs and vaccines and improvements in diagnostic techniques and services [11].
Therapeutic treatments are targeted at animals that are diseased. In food animals, it is usually often more convenient to treat entire groups by administering medication through feed or water, though individual animals may also be treated. For animals like poultry and fish, mass medication is the most feasible means of treatment but with the possibility of drug dispersal into the environment via leaching and agricultural wastewater [12]. Furthermore, certain mass-medication procedures called metaphylaxis, aimed at treatment of sick animals while medicating others in the group that may not be sick but exposed, can also be counterproductive. Other prophylactic antimicrobial treatments are typically used during high-risk periods for infectious diseases even, while the animals may not be infected also described as nonspecific infection prevention [13]. These practices, however plausible, are currently considered as contributing to emergence of antimicrobial resistance due to subtherapeutic exposure to veterinary pharmaceuticals by both infected and noninfected animals, as well as the environment [14].
Antimicrobial resistance has been described as the ability of bacterial, parasites, viruses, and fungi to survive and spread despite treatment with specific and combination therapy that are normally used against them [15]. The World Health Organization also emphasized that resistance happens when microorganisms change when they are exposed to antimicrobial drugs (such as antibiotics, antifungals, antivirals, antimalarials, and antihelmintics). These microorganisms that develop antimicrobial resistance are sometimes referred to as “superbugs”. Antimicrobial resistance may be spontaneous and occur as a natural process, and resistance to antimicrobials dates back as far as when the first generations of antibiotics including penicillin were introduced in 1943/44 by Alexander Fleming [13]. In evolution, selection pressure is bound to cause subpopulation of microorganism with resistance genes to emerge [16]. This selective pressure has been ascribed to appropriate and inappropriate use of antimicrobials but aggravated by (1) intensity of usage, (2) persistence of usage, (3) under usage and subtherapeutic doses that animals are exposed to in prophylactic treatment, and (4) unintended human exposure through antimicrobials in food residues and the environment [10].
The burden of infectious diseases in developing countries and intensive use of antimicrobials to combat this has also been stressed in a study that suggested that up to a third of the global increase (67%) in antibiotic consumption will be in food animals, over the period 2010–2030 and attributable to low-middle income countries [17]. This challenge is in view of the high burden of foodborne infectious and zoonotic diseases especially also in developing countries [18]. Veterinary practices use drugs for mitigating these diseases in animals, including food animals that have to be maintained in health and productivity (meat, egg, and milk). To prevent these drugs from getting into the food chain and being consumed by humans, “withdrawal time,” which is the last time any drug may be administered before egg/milk and meat from such animals are collected and consumed is specified. The withdrawal time for antimicrobials is intended to prevent harmful drug residues in meat, milk, and eggs [19]. These waiting periods need to be observed from the time of treatment to when the animals are slaughtered for food. This is important because food products that contain antimicrobial residues not metabolized leaves residues beyond permissible limits at the end of the withdrawal period may be considered unwholesome for consumption and may contribute to antimicrobial resistance in humans [20].
Veterinary pharmaceuticals, therefore, contribute in many ways to the emergence of antimicrobial resistance either directly in suboptimal usage in animals or indirectly in human who consume subtherapeutic doses in animal products [13]. When resistant organism emerges, it has also been argued that human sources also seed these resistant bacteria to animals and the environment through sewage [21]. A recent study by Marcelino et al. [22] described high levels of antibiotic resistance gene expression among birds living in a wastewater treatment plants. The study observed that birds feeding at a wastewater treatment plant carried greatest resistance gene burden, suggesting that human waste, even after treatment, contributes to the spread of antibiotic resistance genes to the wild. Domestic and wild animals, including rodents, and birds, can acquire these environmental contaminants and pass them on via their excreta to grazing land or feed of food animals, which may in turn end up in human through the food chain [23]. While it is imperative to canvass AMR stewardship through rational and circumspect usage of antimicrobial in animals, it is important to bear in mind that human also present risk to animals. The USFD described the phenomenon of antimicrobial resistance as a very complex and nonvictimless phenomenon, affecting both human and animal health [13].
2. Livestock diseases and the application of veterinary pharmaceuticals
In the management of infectious and noninfectious diseases of livestock in developing countries, a number of veterinary pharmaceuticals are administered. The choice of drugs is often determined by efficacy, availability, and cost. These factors are explored by manufacturers mostly based in developed countries from where the drugs are exported to developing countries. This distribution chain is also largely driven by business interest such that drug companies sell volumes that are targeted at frequent, intensive usage that may have deleterious effect such as emergence of AMR.
Intensive use of veterinary chemotherapy on the other hand may be justifiable considering that many bacterial, viral, and parasitic diseases like mycoplasmosis, Newcastle disease, avian influenza, anthrax, coccidiosis, brucellosis, foot and mouth disease (FMD), rift valley fever, etc. threatens socioeconomics, instills fear that shock systems, either by suddenly and rapidly killing large number of animals or causes large-scale drop in demand through fear of zoonotic diseases [24, 25]. On the other hand, the growing concern that animals are major sources of human diseases and that around 60% of all animal diseases are zoonotic [26] make treatment of such diseases in animals an essential control measure before it is transmitted to human, and to reduce their capacity to cause epidemics and pandemics.
The livability and economic impacts of animal disease disaster is well documented, for instance, highly pathogenic avian influenza recently killed millions of poultry birds in Nigeria (including other countries in West Africa) and wiped out entire farms [27]. The costs of epidemic African swine fever in Cote d’Ivoire was estimated at $9.2 million; Nipah virus in Malaysia $114 million, while contagious bovine pleuropneumonia in Botswana costs about $300 million [25]. In the absence of preventive measures such as biosecurity and vaccination, the use of antimicrobial especially for nonviral infections is essential for profitable livestock production and to prevent infections that may be transmitted from animals to human as attested to by WHO [28].
3. Development of AMR in veterinary practice
The global antimicrobial resistance (AMR) crisis is predicted to kill roughly 10 million people annually by 2050 due to antibiotic-resistant infections, with Africa alone accounting for about 4.15 million [29]. This is estimated to cost the global economy about $100 trillion [30] with about 28.3 million people pushed into extreme poverty [31]. The alarming rate of AMR in developing countries can be attributed to gross misuse of antimicrobials in human and animals [32]. Although resistance can still develop even at an appropriate antimicrobial use, however the situation can be made worse whenever there is excessive and unnecessary usage [33]. The global revolution in livestock and aquaculture is an underlying factor for frequent antimicrobial use and subsequent development of AMR. This is also driven by population increase, urbanization, improving economic conditions, and globalization. Countries like Brazil, China, and India are currently the hotspots for livestock intensification, while Nigeria, Myanmar, Peru, and Vietnam are future spots (Van [17]). In developing countries, most nonhuman-medical use of antimicrobials is almost certainly in livestock and farmed fish production and it is likely that most veterinary use is in intensive production rather than pastoralist or small-holder systems [34]. In Nigeria and other developing countries in sub-Saharan Africa, Asia and Middle East, there is paucity of information on antimicrobial drug resistance in farm animals, although little information exists on residue level [35, 36, 37, 38]. However, there is information on antimicrobial drug resistant microbes isolated from human patients from different parts of Nigeria [39, 40]. Previous report by Adesokan et al. [41] on pattern of antimicrobial usage in livestock production in three states of South-Western Nigeria between the period of 2010 and 2012 showed an increased use of tetracyclines (33.6%) followed by fluoroquinolones (26.5%) and beta-lactams/aminoglycosides (20.4%). Similar trend was also reported in Africa for tetracycline & beta-lactams [42]. However, studies by Idowu et al. [35] showed level of tetracycline residues between the ranges of 0.1–1.0% in chicken eggs.
The process of AMR development is very complex, and all of the factors that contributed to the events are not fully understood. It is clear that genetic change or mutation in microbial DNA may often cause resistance to antimicrobial agents, and this change might also be passed to the offspring or transferred to other related or even unrelated microorganisms [43]. This is known as “selection pressure” where the use of antimicrobial drugs in health care, agriculture, or industrial settings favor the survival of resistant strains (or genes) over susceptible ones, thus leading to a relative increase in resistant bacteria within microbial communities [44]. This is because no matter how effective an antimicrobial is, it rarely kills 100% of the organisms, meaning some may still survive due to genetic change, which can be passed forward. Currently, science has not fully proved the causes of different types of AMR that are causing great public health risks. The widespread use of antimicrobials in food production system especially in food-producing animals is another cause of AMR [45]. The extensive use of antimicrobials in animal production as growth promoters widely exposes the microbes to the drugs, thus enhancing the development of microbial resistance causing health consequences in both animals and humans. However, the scientific evidence of how and to what extent such drug exposure affects human health still remains unclear. It is interesting to note that antimicrobial resistance would not develop in animals if antimicrobial drugs were never used in them [12].
There is danger to public health if resistant organism from animals can also cause disease in human exposed by a way of food consumption or direct contact with food-producing animals, companion animals, or through environmental spread [46]. The threat to public health also exists even if the organisms do not cause disease in human, because they may still be able to transfer the resistant genes from food-producing animals to unrelated human pathogenic bacteria as well as normal commensals [47]. It is then clear that the increase use of antimicrobials in animal production for variety of purposes such as for therapeutic and nontherapeutic use has contributed to increasing AMR in bacteria affecting man and animals [48]. In Africa and other developing countries, studies have suggested a strong correlation between the use of antimicrobials in veterinary practice and the development of AMR [49], because it is shown that a larger proportion of antimicrobial medications have been used in animals than humans mainly for food production purposes [50]. There is presence of high antimicrobial residue in meat and milk meant for human consumption correlating with the detection of multidrug resistance (MDR) bacteria in animals and their products [51] as well as in humans in contact with the animals [52, 53, 54]. This is also because a large proportion of the population in developing countries lives in close proximity with livestock, which enhance the chances of transfer of resistant microorganisms from animals to humans [55, 56]. Similarly, the increasing use of antimicrobials as prophylaxis in aquaculture in developing countries further contributed to the emergence of AMR causing problems in human, animal, and environmental health [57]. The risk to humans further exists especially when similar antimicrobial is used in both animals and humans, or there is presence of cross resistance between antimicrobial used in human and veterinary practice. Using antimicrobials that are also used in human medicine for growth promotion is especially conducive to AMR because exposure of many animals to low dosages makes resistance more likely to emerge [34].
For some antimicrobials, there is development of resistance by bacteria through plasmid-mediated transferable resistance [58]. The minimum inhibitory concentrations (MIC) for a target pathogen might be considerably different from those of commensals, and thus, the resistance gene in commensals may be selected and transferred to humans and then to human pathogens leading to development of AMR [59]. Despite the fact that the exchange of genetic materials and the short generation time of organism contributed to the development of AMR by many bacteria [60], some drugs such as penicillin still retains excellent activity on certain organism (e.g., Streptococcus agalactiae) after about 6 decades of usage [61].
AMR development can often be caused by inhibition of specific antimicrobial pathways such as cell wall synthesis, nucleic acid synthesis, ribosome function, protein synthesis, foliate metabolism, and cell membrane function by the organism [62, 63, 64]. The various steps involved in the production, distribution, prescription, dispensing, and finally consumption of the drug by human patient or its use in animal production often contributed to the emergence of AMR especially when there is imprudent or irresponsible practice along the supply chain [65]. Part of veterinary medical education is to understand how antimicrobials affect microorganisms, and how they can be used responsibly to protect human and animal health [66]. In food production systems, veterinarians are on the frontline when it comes to keeping nation’s food supply safe. Advances in animal health care and management have greatly improved food safety over the years and have reduced the need for antimicrobials in food production systems [67]. Nevertheless, antimicrobials are an important part of the veterinarian’s toolkit, and so veterinarians are aware that they should be used judiciously and in the best interest of animal and public health [66]. More importantly in the development of AMR is the quality of antimicrobials. Though difficult to implement, it has been suggested that incidence of microbial resistance can be reduced if the antimicrobials that are used in human health are not used in veterinary practice [68]. Moreover, the practices of mass treatment of all animals in a group when only one animal is sick (metaphylaxis) as well as the treatment of all animals when they are exposed to conditions that can make them likely to be ill (prophylaxis) will result in an increased antimicrobial use and as such would encourage the development of resistance [69].
Although the development of animal-related AMR is associated with the quality and quantity of antimicrobial usage in veterinary practice, there are other underlining factors that can influence AMR development:
Lack of awareness: in developing countries, there is little or no awareness or concern in the use of antimicrobials as compared to developed nations who recognize AMR as a global challenge. Omulo et al. [70] showed that only 24% of studies in Africa are related to AMR in animals or their products. In East Africa for example, despite the relevance of antibiotic procurement in health budgets, there was still a slow progress in research focusing on AMR of enteric pathogens. There is still lack of awareness among many veterinarians and other food producing personnel on the negative impact to human health as a result of extensive use of antimicrobials in animals [71].
Lack of information: the information is lacking in developing countries concerning the existence and prevalence of AMR in animals and animal products and the negative health consequence as well as the cost of AMR illness in people and animals.
Fake and substandard drugs: there is much concern over counterfeits and substandard drugs in animal health care, but there is insufficient data to understand its importance. Counterfeits and substandard products, which contain active ingredient at a lower level, will increase the chance of developing resistance. There is no comprehensive information on fake/substandard veterinary drugs.
Lack of adequate ‘One Health’ integration between animal and human healthcare: in developing countries, there is poor collaboration in healthcare sectors between human and veterinary practice especially on collection and sharing of data on antimicrobial usage. However, at international level, good collaboration exists in the area of AMR between human and animal world health bodies like WHO, OIE, and FAO.
Lack of substitution to the use of antimicrobials: alternative to the use of antimicrobials is lacking in developing countries unlike the developed nations that had successfully banned the use of antimicrobials as growth promoters and replaced with alternative growth promoters and good practice without having negative impact on the performance of their livestock industries. This could hardly be achieved in developing nations that have propensity to source antimicrobials from the black markets, which may be of poor quality, thus exacerbating the problem and creating a considerable increase in disease, with consequent mortality and morbidity losses [34].
4. Prevention of AMR in veterinary practice
In a bid to ensure measurable containment of AMR, there is a global formal declaration on AMR calling for the development of action plans on AMR by both international and national bodies. The Global Action Plan on Antimicrobial Resistance was approved in May 2015 by the World Health Assembly with the key strategies to increase global AMR awareness as well as developing policies that will attract more investment in the area of new medical interventions [72]. There is also a call to all Member States for establishing National Action Plans for AMR by 2017 of which about 57 countries have formalized such plans so far. The 2016 meeting of the UN General Assembly was another milestone focusing on multidisciplinary solution to the problems of AMR [73]. Moreover, the G20 called for the creation of a Global Research and Development (R&D) Collaboration Hub on AMR in July 2017 that could coordinate international funding efforts [74], and the search for the appropriate individuals to lead that hub began early this year. In line with the global agreement to develop National Action Plan on AMR, Nigeria (with some other developing nations) keyed into this agreement in 2017 through a ‘One Health’ approach [75] and then enrolled into a Global Antimicrobial Resistance Surveillance System (GLASS). The Action Plan addresses five strategic objectives:
improving awareness and understanding of AMR through effective communication, education, and training
strengthening the knowledge and evidence base through surveillance and research
reducing the incidence of infection through effective sanitation, hygiene, and preventive measures
optimizing the use of antibiotics in human and animal health
preparing the economic case for sustainable investment and increasing investment in new medicine, diagnostic tools, vaccines, and other interventions
Several challenges exist regarding AMR containment in developing country like Nigeria; however, the development of this action plan is an important positive step in the right direction as it aims to address the problem at all level of governance and society [75].
Veterinarians play an important role in limiting and minimizing the spread of antimicrobial resistance (AMR). Because vets are often the first point of contact for livestock owners seeking animal medical attention, they can therefore play a part in addressing the problem of AMR [45]. One of the ways to reduce the risk of transfer of AMR from animals to humans is by minimizing the zoonotic transfer of bacteria [76]. This could be achieved by practicing stringent hygiene in the farms and any meat processing plants including the abattoirs and the markets. Thorough and effective cooking of meat product can also reduce the risk of AMR [77]. There is need to strengthen the information resources in developing countries to support health workers, patients, animal owners, and attendants as well as the general public to help in reducing the risk of AMR arising from the use of antimicrobials in animals. This will enable the society to better understand the importance and value of antimicrobials. The excessive and inappropriate use of antimicrobials in veterinary practice should be discouraged. Because antimicrobials are an extremely valuable resource in livestock production, their prudent use in animals will continue to provide benefits to society and will help ensure high standards of welfare for those animals in the care of veterinarians [78]. Since exposure of bacteria to subtherapeutic concentrations of antimicrobials is thought to increase the speed of the selection of resistance, this should always be avoided [14, 15, 79]. Appropriate pharmacokinetic and pharmacodynamic relations for antimicrobials used in animals should be developed [12]. Optimal dosage strategies for eliminating zoonotic organisms in animals will reduce the risk of transferring resistance to humans [80].
According to Delia [34], broad consensus on the management of AMR in human and animal healthcare will require to:
reduce antibiotic use in humans and animals through public health improvement such as hygiene and sanitation, immunization, infection control, as well as good housing and environment.
regulate the sale and use of antibiotics through prescription.
encourage research and development of new antimicrobials.
minimize the level of environmental contamination of antimicrobials emanating from manufacturing process as well as agricultural, hospital, and community use.
develop integrated global policies on the use of antibiotics.
ban the nontherapeutic use of antimicrobials as growth promoters in agriculture.
Currently, there is no adequate information on animal production losses due to disease burden and the extent at which it could be prevented through proper use of antibiotics or their alternatives.
Although in Europe and other developed nations, the use of alternatives to antimicrobials as growth promoters is a success; their applicability in developing countries is not fully understood.
Despite the huge investments in the control of diseases in developing countries through vaccination, vector control, and the use of resistant breeds, evaluation from the angle of reduction in the usage of veterinary drug is lacking. In developing countries, the incidence and composition of substandard and fake drugs as well as their effects on treatment failure and resistance development is not well known. Similarly, the level of resilience of livestock farmers in developing countries to ban or restrict access to antimicrobials is equally not well known. It should be noted that policy and regulation alone is unlikely to improve use of vet drugs and the options for improving the use of vet drugs in agriculture and their effectiveness, feasibility, and affordability are not well understood.
4.1 Rational drug use
There have been success factors in the improvement of drug use in human health through wide range of intervention studies. Similarly, the World Animal Health Organization (OIE) and other world veterinary bodies also developed frameworks on rational use of vet drugs to which there is a limit veterinarians can make profit from antimicrobial sale for food animal production [71]. This is not the case in developing countries where the sale and use of veterinary antimicrobials is facing challenges for improvement. It was found from series of intervention studies that training remains the most common strategy for improving drug use, but this gave little success unless when combined with other strategies like changing the market condition [1].
4.2 Governance of antimicrobial use
Antimicrobial use in human and veterinary practice requires holistic approach in order to improve drug governance. There is need to list the critical or essential drugs in human and veterinary practice with requirement for prescription and guidelines such as banning the use of medically important antibiotics in agricultural practice and off-label use of antimicrobials as well as monitoring antimicrobial use and resistance. Not much success has been recorded in this regard in developing countries especially in livestock production and aquaculture due to little investments. According to OIE, better governance of veterinary antimicrobials comes from empowering veterinarians and limiting prescription to them. Most of the private veterinary service providers in developing countries are not operating at a significant scale and as such are often employed directly by agriculture and agro-allied companies making them to be less independent. The few that are successful are not operating with the guidelines of current OIE policy [81]. The community animal health workers (CAHWs), that have proven to be effective, are very expensive to train and may not be politically acceptable [82]. This is because there is lack of resources to support them by public veterinary services, and the private veterinarians often see them as potential competitors. A study investigated rational drug use by farmers and found that farmers in West Africa were mainly responsible for buying and using antimicrobials, and providing simple information on correct drug use could lead to improved drug usage as well as reduced amount of underdosages, which is an important factor for the development of AMR [83].
4.3 Antimicrobial alternatives in veterinary practice
As previously mentioned, developed countries banned the use of medically important antibiotics as well as growth promoters in animal production, which has led to better farming practices as well as reduction in AMR of medically important microbes found in farm animals. With this natural experiment, it demonstrated that routine antimicrobial usage is not a precondition for healthy animals as long as there is better hygiene and sanitation with good housing condition, and the use of antibiotics is only limited to clinical condition. The benefit of antimicrobials as growth promoters may sound reasonable only under poor management and hygiene situations [71]. Although the type of intensive livestock production in developing countries makes them rely more on nontherapeutic use of antimicrobials, there are many other promising innovations that could support profitable and productive agriculture with less reliance on antimicrobials use such as:
The use of nonantibiotic growth promoters like enzymes in feed, competitive exclusion products as well as probiotics and prebiotics
The use of other animal health technologies such as vaccines, vector control, disinfectants, phyto-therapy, as well as phage-therapy, which are underutilized in developing countries. The phage products can readily be designed to thwart development of resistance. They have been used as antibacterial agents for nearly 100 years in the former Soviet Union, and they are now undergoing a renaissance in other countries due to the growing AMR problem [33, 84, 85, 86, 87].
The use of robust diagnostic techniques for improved drug selection and identification of AMR pathogens
The management and bio-security innovations like all-in-all-out systems, pathogen-free systems, stocking density reduction, and improved waste management systems.
The use of genetically disease resistant animals as well as avoidance of monocultures of genetically similar animals.
All these intervention strategies will improve animal welfare as well as reducing environmental externalities of animal agriculture. A more radical suggestion is to decrease the amount of consumption of animal source food or shift from intensive to organic animal production.
5. Veterinary antimicrobial stewardship in developing countries
The safeguarding of antimicrobial agents for future generations is of utmost priority as AMR threatens the very core of modern medicines and the sustainability of an effective, global public health response to the enduring threats from infectious diseases [72]. In many developing countries of the world, gaps exist among health care professionals on the current status of antibiotic resistance in their area due to lack of a systematic surveillance at country, provincial, and district level [88]. There is a paucity of clinical data on antibiotic resistance, and this is particularly the case in resource-poor settings. Tons of antibiotics are used annually in clinical and agricultural settings worldwide. The estimates of the total annual global consumption of antimicrobials in animal production vary considerably due to poor surveillance and data collection in many countries [89]. In 2013, food animals alone consumed over 130,000 tons of antibiotics [90]. It cannot be ignored that two-thirds of the estimated future growth of usage of antimicrobials is estimated to be within the animal production sector, with use in pig and poultry production predicted to double [89]. Nigeria, Pakistan, India, Bangladesh, China, and Egypt are the developing countries with massive consumption of antibiotics [88].
The implementation of rational and restricted use of antibiotics is lacking in most developing countries where you have the largest market of antimicrobial drugs and reports of the highest rate of antibiotic resistance [86, 87]. Due to these developments, antimicrobial stewardship programs have emerged as an essential means to attenuate the threat of a real possibility of the specter of a “postantibiotic era” [91, 92].
Antimicrobial stewardship is a harmonized program (the optimal selection, dosage, and drug regimen) that fosters the proper use of antimicrobials (including antibiotics) with the goal of optimizing clinical outcomes, reducing microbial resistance, and lessening the spread of infections produced by multidrug-resistant organisms. The main objectives of antimicrobial stewardship are to attain excellent patient outcomes associated with antimicrobial use while reducing toxicity and other unfavorable events, thereby curbing the discriminatory pressure on bacterial population that propels the emergence of multidrug-resistant strains [93, 94].
Antimicrobial stewardship programs (ASPs) are a cornerstone of the response to the AMR crisis in human medicine but are still largely underdeveloped in veterinary medicine [95]. Antimicrobial stewardship is important to both animal health and food safety. Just like humans, animals get infections that require treatment with antibiotics. The rise of antimicrobial resistance is a serious threat to public health [30]. It is imperative that antibiotic stewardship programs seeking to preserve the effectiveness of existing antibiotics in human health also consider strategies that reduce overuse of antibiotics in the agricultural sector as antimicrobials are used in terrestrial animal production practices to preserve animal and public health, but also as growth promoters at a subtherapeutic level [89]. Other aspects to be considered with regard to antimicrobial use include the distinction between therapeutic and nontherapeutic use, between the diverse existing production systems and between specifics related to the different animal species and their eco-geographical location [72, 89].
According to the WHO, FAO, and OIE global tripartite database for antimicrobial resistance country self-assessment in 2016–2017, 42% of the countries on question regarding antimicrobial stewardship and regulation in animals and crop production responded that no national policy or legislation regarding the quality and efficacy of antimicrobials and their use in animals, and crops was available [101]. Responses to other veterinary-related questions showed a huge gap in the preparedness for combating AMR and also the lack of policy making and implementation of a successful antimicrobial stewardship program.
Various strategies have been shown to improve appropriateness of antimicrobial use and cure rates, decrease failure rates, and reduce healthcare-related costs in human hospitals [96, 97, 98]. According to Guardabassi & Prescott [95], the following successful strategies used in human hospitals can be adopted with focus on their implementation in veterinary practice.
educational approaches
development and implementation of guidelines
preprescription approval
postprescription review
computer-based decision support
It should be noted that one strategy does not exclude the other and that multiple strategies can be successfully used in combination.
A good antimicrobial stewardship program (ASP) needs remarkable input in research and training by all stakeholders including national and international veterinary organizations, funding concerns, and animal health industries [95]. At governmental levels, the growth and execution of ASPs need coordination of the task of national public health and veterinary authorities, veterinary clinics, organizations, and private practitioners. The concept of antimicrobial stewardship and of its continuous improvement is in its relative infancy in various sectors of veterinary practice in developing countries, but every veterinary component of the agricultural sector has the responsibility and access to a wide range of resources to develop an ASP.
Stewardship of antimicrobial drugs in human healthcare and veterinary settings is essential to slow the emergence of resistance and extending the useful life of effective antimicrobials according to FDA Center for Veterinary Medicine [99]. All developing countries should be committed to advancing efforts to implement good antimicrobial stewardship practices in veterinary settings as part of their role to protect human and animal health. Each program must be region-specific and constantly under review given that resistance patterns change, requiring changes to local policy of, for example, empirical antibiotic choice [100].
Therefore, the goals in all countries should be to align antimicrobial drug product use with the principles of antimicrobial stewardship, foster antimicrobial stewardship in veterinary settings, and enhance monitoring of antimicrobial resistance and use in animals to further preserve antimicrobial drugs to ensure human and animal health [99].
6. Conclusion and recommendation
Resistance to antimicrobial agents arises in some instance through excessive use in animals as chemotherapeutics, and as subtherapeutic additives in feeds. Prolong exposure of microorganisms to sublethal doses of antimicrobials can result in spontaneous emergence of resistance gene and its subsequent transfer among animals, environment and animal products in food chain, and transfer of resistance to human. A pragmatic approach to slow down the development of antimicrobial resistance is to control abuse of antimicrobials through a number of measures. First, it is important to recognize that veterinary pharmaceuticals are important beyond animals and include human health and the environment, hence the need for “One Health” guidiance and regulation. Secondly, it is necessary to reduce drugs that are used as prophylaxis and should rather improve research and innovation for vaccine development, application and explore other alternatives to chemotherapies. The use of feed grade antibiotics and additives in feed as growth promoters also need to be discouraged in developing countries and instead promote organic, home grown livestock husbandry to complement intensive and factory farming. Alternatives to growth-promoting and prophylactic uses of antimicrobials in agriculture include improved management practices, wider use of vaccines, probiotics, and phage virus. Monitoring programs, prudent usage that are controlled, and educational campaigns are some of the approaches that can minimize further development of antimicrobial resistance in developing countries especially. These can be achieved through mutual and ‘One Health’ understanding of the challenges and informed solution through antibiotic stewardship by promoting collective action of all parties with interest including producers, consumers, and mediators.
\n',keywords:"veterinary drugs, antimicrobial resistance, stewardship, developing countries",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/66512.pdf",chapterXML:"https://mts.intechopen.com/source/xml/66512.xml",downloadPdfUrl:"/chapter/pdf-download/66512",previewPdfUrl:"/chapter/pdf-preview/66512",totalDownloads:1569,totalViews:0,totalCrossrefCites:10,dateSubmitted:"August 23rd 2018",dateReviewed:"February 1st 2019",datePrePublished:"June 5th 2019",datePublished:"March 11th 2020",dateFinished:"April 2nd 2019",readingETA:"0",abstract:"Veterinary pharmaceuticals include a wide range of anti-infectives and additives in the use for animal health, nutrition, reproduction, and productivity. Antimicrobials are among the most extensively used drugs in developing countries largely due to large population of livestock and the burden of infectious diseases. The introduction of penicillin in 1943 and other antibiotics thereafter provided remedies for many infections in humans and animals, reducing mortality and productivity losses. Since then, a repertoire of antibiotics and antimicrobials has been introduced as chemotherapeutics and/or prophylaxis. This success notwithstanding, many pathogens of consequences are no longer susceptible owing to emergence of antimicrobial-resistant (AMR) microorganisms. This has made treatment of infectious diseases less effective. Beside spontaneous emergence of mutant microorganisms, scientists are wary of AMR caused by intensive use of antibiotics in humans and animals, sometimes in subtherapeutic doses as preventive medicine. In developing countries, environmental exposure and persistent use of antibiotics in food animals may leave residues in the food chain. The consequences include development of AMR. In this chapter, we reviewed antimicrobial use in veterinary medicine and sequela in the emergence of AMR and described the imperative of antimicrobial stewardship in veterinary practice to combat AMR in developing countries.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/66512",risUrl:"/chapter/ris/66512",signatures:"Meseko Clement, Makanju Olabisi, Ehizibolo David and Muraina Issa",book:{id:"8634",type:"book",title:"Veterinary Medicine and Pharmaceuticals",subtitle:null,fullTitle:"Veterinary Medicine and Pharmaceuticals",slug:"veterinary-medicine-and-pharmaceuticals",publishedDate:"March 11th 2020",bookSignature:"Samuel Oppong Bekoe, Mani Saravanan, Reimmel Kwame Adosraku and P K Ramkumar",coverURL:"https://cdn.intechopen.com/books/images_new/8634.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-440-4",printIsbn:"978-1-78985-439-8",pdfIsbn:"978-1-83880-062-8",isAvailableForWebshopOrdering:!0,editors:[{id:"186990",title:"Dr.",name:"Samuel Oppong",middleName:null,surname:"Bekoe",slug:"samuel-oppong-bekoe",fullName:"Samuel Oppong Bekoe"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",fullName:"Clement Meseko",slug:"clement-meseko",email:"cameseko@yahoo.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",institution:{name:"National Veterinary Research Institute",institutionURL:null,country:{name:"Nigeria"}}}],sections:[{id:"sec_1",title:"1. Introduction: veterinary pharmaceuticals and antimicrobials",level:"1"},{id:"sec_2",title:"2. Livestock diseases and the application of veterinary pharmaceuticals",level:"1"},{id:"sec_3",title:"3. Development of AMR in veterinary practice",level:"1"},{id:"sec_4",title:"4. Prevention of AMR in veterinary practice",level:"1"},{id:"sec_4_2",title:"4.1 Rational drug use",level:"2"},{id:"sec_5_2",title:"4.2 Governance of antimicrobial use",level:"2"},{id:"sec_6_2",title:"4.3 Antimicrobial alternatives in veterinary practice",level:"2"},{id:"sec_8",title:"5. Veterinary antimicrobial stewardship in developing countries",level:"1"},{id:"sec_9",title:"6. Conclusion and recommendation",level:"1"}],chapterReferences:[{id:"B1",body:'Shah NM et al. Can interventions improve health services from private providers in low and middle-income countries? A comprehensive review of the literature. Health Policy and Planning. 2011;26(4):275-287. 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Strategies to reduce the use of antibiotics in animals. The Pharmaceutical Journal. 2014;293(7836). DOI: 10.1211/PJ.2014.20067064. Available from: https://www.pharmaceutical-journal.com/news-and-analysis/features/strategies-to-reduce-the-use-of-antibiotics-in-animals/20067064.article?firstPass=false'},{id:"B77",body:'Brad S, Gail RH, Avinash K, Carmen DC, Lance BP, James RJ. Antibiotic Resistance in Humans and Animals. Discussion Paper of National Academy of Medicine. 2016. Available from: https://nam.edu/wp-content/uploads/2016/07/Antibiotic-Resistance-in-Humans-and-Animals.pdf'},{id:"B78",body:'Barza MD et al. The need to improve antimicrobial use in agriculture: Ecological and human health consequences. Barza M, Gorbach SL, editors. Clinical Infectious Diseases. 2002;34(Suppl 3):S76-S77. Arlington, VA: Infectious Diseases Society of America'},{id:"B79",body:'Lessar TS, Rotschafer JC, Strand LM, Solem LD, Zaske DF. Gentamicin dosing errors with four commonly used nomograms. Journal of the American Medical Association. 1982;248:11903'},{id:"B80",body:'McEwen SA, Fedorka-Cray PA. Antimicrobial use and resistance in animals. Clinical Infectious Diseases. 2002;34(Suppl 3):S93-S106'},{id:"B81",body:'Lewis S. The role of the agro-vet shop in animal health information delivery in Kenya [MSc dissertation]. University of Edinburgh; 2001'},{id:"B82",body:'Leyland T et al. Community-Based Animal Health Workers in the Horn of Africa: An Evaluation for the US Office for Foreign Disaster Assistance. UK, Great Holland: Feinstein International Center, Tufts University Africa Regional Office, Addis Ababa and Vetwork; 2014'},{id:"B83",body:'Grace D et al. Training farmers in rational drug-use improves their management of cattle trypanosomosis: A cluster-randomised trial in South Mali. Preventive Veterinary Medicine. 2008;83:83-97'},{id:"B84",body:'Abedon ST, Kuhl SJ, Blasdel BG, Kutter EM. Phage treatment of human infections. Bacteriophage. 2011;1:66-85'},{id:"B85",body:'Kutter E, De Vos D, Gvasalia G, Alavidze Z, Gogokhia L, Kuhl S, et al. Phage therapy in clinical practice: Treatment of human infections. Current Pharmaceutical Biotechnology. 2010;11:69-86'},{id:"B86",body:'Reardon S. Phage therapy gets revitalized. Nature. 2014;510:15-16'},{id:"B87",body:'Reardon S. Antibiotic resistance sweeping developing world. Nature. 2014;509:141-142'},{id:"B88",body:'Syed MA, Bana NF. Developing countries need action plans to combat the challenge of antimicrobial resistance. iMedPub Journals. 2016;7(2):12. Available from: http://www.acmicrob.com/'},{id:"B89",body:'FAO. Antimicrobial Resistance: Animal Production. 2018. Available from: www.fao.org/antimicrobial-resistance/key-sector/animal-production/en. [Accessed: 03 November 2018]'},{id:"B90",body:'Van Boeckel TP, Glennon EE, Chen D, Gilbert M, Robinson TP, Grenfell BT, et al. Reducing antimicrobial use in food animals. Science. 2017;357(6358):1350-1352'},{id:"B91",body:'Gallagher J. Antibiotic Resistance: World on Cusp of ‘Post-Antbiotic Era’. BBC News, Health; 2015. Available from: www.bbc.co.uk'},{id:"B92",body:'O’Brien DJ, Gould IM. Maximizing the impact of antimicrobial stewardship: The role of diagnostics, national and international efforts. Current Opinion in Infectious Diseases. 2013;26:352-358. DOI: 10.1097/QCO.0b013e3283631046'},{id:"B93",body:'Gerding DN. The search for good antimicrobial stewardship. Joint Commission Journal on Quality Improvement. 2001;27(8):403-404'},{id:"B94",body:'Neil F, Society for Healthcare Epidemiology of America, Infectious Diseases Society of America. Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infection Control and Hospital Epidemiology. 2012;33:322-327'},{id:"B95",body:'Guardabassi L, Prescott JF. Antimicrobial stewardship in small animal veterinary practice: From theory to practice. Veterinary Clinics: Small Animal Practice. 2015;45:361-376. DOI: 10.1016/j.cvsm.2014.11.005'},{id:"B96",body:'MacDougall C, Polk RE. Antimicrobial stewardship programs in health care systems. Clinical Microbiology Reviews. 2005;18:638-656'},{id:"B97",body:'Owens RC Jr. Antimicrobial stewardship: Concepts and strategies in the 21st century. Diagnostic Microbiology and Infectious Disease. 2008;61:110-128'},{id:"B98",body:'Tamma PD, Cosgrove SE. Antimicrobial stewardship. Infectious Disease Clinics of North America. 2011;25:245-260'},{id:"B99",body:'Food and Drug Administration-Centre for Veterinary Medicine (FDA-CVM). The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals; 2012. Available from: https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM216936.pdf'},{id:"B100",body:'Aryee A, Price N. Antimicrobial stewardship—Can we afford to do without it? British Journal of Clinical Pharmacology. 2014;79(2):173-181. DOI: 10.1111/bcp.12417'},{id:"B101",body:'WHO, FAO, OIE. Global Tripartite Database for Antimicrobial Resistance Country Self-Assessment. Export of Year One Data 2016-2017. 2017. Available from: https://amrcountryprogress.org/ [Accessed: 23 May 2017]'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Meseko Clement",address:"cameseko@yahoo.com",affiliation:'
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\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\t
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t
\r\n
\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
\r\n
\r\n\t
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
\r\n
\r\n\t
\r\n
\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
\r\n
\r\n\t
\r\n
\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
\r\n
\r\n\t
\r\n
\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
\r\n
\r\n\t
\r\n
\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
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\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
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His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. Prof. Navarro-Pedreño is also a director of the Ph.D. Program Environment and Sustainability (2012-present) and a member of several societies among which are the Spanish Society of Soil Science, International Union of Soil Sciences, European Society for Soil Conservation, DessertNet and the Spanish Royal Society of Chemistry.",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,series:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713"},editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",slug:"elke-jurandy-bran-nogueira-cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",slug:"sandra-ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},onlineFirstChapters:{paginationCount:14,paginationItems:[{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"80954",title:"Ion Channels and Neurodegenerative Disease Aging Related",doi:"10.5772/intechopen.103074",signatures:"Marika Cordaro, Salvatore Cuzzocrea and Rosanna Di Paola",slug:"ion-channels-and-neurodegenerative-disease-aging-related",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Ion Channels - From Basic Properties to Medical Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/10838.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"81647",title:"Diabetes and Epigenetics",doi:"10.5772/intechopen.104653",signatures:"Rasha A. 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\r\n\tIn general, the harsher the environmental conditions in an ecosystem, the lower the biodiversity. Changes in the environment caused by human activity accelerate the impoverishment of biodiversity.
\r\n
\r\n\tBiodiversity refers to “the variability of living organisms from any source, including terrestrial, marine and other aquatic ecosystems and the ecological complexes of which they are part; it includes diversity within each species, between species, and that of ecosystems”.
\r\n
\r\n\tBiodiversity provides food security and constitutes a gene pool for biotechnology, especially in the field of agriculture and medicine, and promotes the development of ecotourism.
\r\n
\r\n\tCurrently, biologists admit that we are witnessing the first phases of the seventh mass extinction caused by human intervention. It is estimated that the current rate of extinction is between a hundred and a thousand times faster than it was when man first appeared. The disappearance of species is caused not only by an accelerated rate of extinction, but also by a decrease in the rate of emergence of new species as human activities degrade the natural environment. The conservation of biological diversity is "a common concern of humanity" and an integral part of the development process. Its objectives are “the conservation of biological diversity, the sustainable use of its components, and the fair and equitable sharing of the benefits resulting from the use of genetic resources”.
\r\n
\r\n\tThe following are the main causes of biodiversity loss:
\r\n
\r\n\t• The destruction of natural habitats to expand urban and agricultural areas and to obtain timber, minerals and other natural resources.
\r\n
\r\n\t• The introduction of alien species into a habitat, whether intentionally or unintentionally which has an impact on the fauna and flora of the area, and as a result, they are reduced or become extinct.
\r\n
\r\n\t• Pollution from industrial and agricultural products, which devastate the fauna and flora, especially those in fresh water.
\r\n
\r\n\t• Global warming, which is seen as a threat to biological diversity, and will become increasingly important in the future.
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\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
\r\n\tWater is not only a crucial substance needed for biological life on Earth, but it is also a basic requirement for the existence and development of the human society. Owing to the importance of water to life on Earth, early researchers conducted numerous studies and analyses on the liquid form of water from the perspectives of chemistry, physics, earth science, and biology, and concluded that Earth is a "water polo". Water covers approximately 71% of Earth's surface. However, 97.2% of this water is seawater, 21.5% is icebergs and glaciers, and only 0.65% is freshwater that can be used directly by humans. As a result, the amount of water reserves available for human consumption is limited. The development, utilization, and protection of freshwater resources has become the focus of water science research for the continued improvement of human livelihoods and society.
\r\n
\r\n\tWater exists as solid, liquid, and gas within Earth’s atmosphere, lithosphere, and biosphere. Liquid water is used for a variety of purposes besides drinking, including power generation, ecology, landscaping, and shipping. Because water is involved in various environmental hydrological processes as well as numerous aspects of the economy and human society, the study of various phenomena in the hydrosphere, the laws governing their occurrence and development, the relationship between the hydrosphere and other spheres of Earth, and the relationship between water and social development, are all part of water science. Knowledge systems for water science are improving continuously. Water science has become a specialized field concerned with the identification of its physical, chemical, and biological properties. In addition, it reveals the laws of water distribution, movement, and circulation, and proposes methods and tools for water development, utilization, planning, management, and protection. Currently, the field of water science covers research related to topics such as hydrology, water resources and water environment. It also includes research on water related issues such as safety, engineering, economy, law, culture, information, and education.
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Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/233645",hash:"",query:{},params:{id:"233645"},fullPath:"/profiles/233645",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()