More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
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Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
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“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
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Additionally, each book published by IntechOpen contains original content and research findings.
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We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
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Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
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IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
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Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
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\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:"10891",leadTitle:null,fullTitle:"Leishmaniasis - General Aspects of a Stigmatized Disease",title:"Leishmaniasis",subtitle:"General Aspects of a Stigmatized Disease",reviewType:"peer-reviewed",abstract:"Leishmaniasis is a major global health challenge, affecting approximately 12 million of the poorest people in 100 countries. It is a deforming and fatal disease in the visceral form. Therapies for leishmaniasis are numerically restricted, basically consisting of the administration of miltefosine, pentavalent antimonials, amphotericin B, or pentamidine. This is an important vulnerability against therapy efficiency that must be overcome by the scientific community. This book discusses important aspects of the disease, such as treatment, epidemiology, and molecular and cell biology. The information contained herein is important for young researchers as they seek to develop safe and effective treatments for this neglected tropical disease.",isbn:"978-1-83968-082-3",printIsbn:"978-1-83968-081-6",pdfIsbn:"978-1-83968-092-2",doi:"10.5772/intechopen.95200",price:119,priceEur:129,priceUsd:155,slug:"leishmaniasis-general-aspects-of-a-stigmatized-disease",numberOfPages:256,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"e2123440fdf88dfa14b4713a1a8ba58a",bookSignature:"Leonardo de Azevedo Calderonon",publishedDate:"April 13th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10891.jpg",numberOfDownloads:1085,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 5th 2021",dateEndSecondStepPublish:"June 2nd 2021",dateEndThirdStepPublish:"August 1st 2021",dateEndFourthStepPublish:"October 20th 2021",dateEndFifthStepPublish:"December 19th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"177382",title:"Dr.",name:"Leonardo de Azevedo",middleName:null,surname:"Calderon",slug:"leonardo-de-azevedo-calderon",fullName:"Leonardo de Azevedo Calderon",profilePictureURL:"https://mts.intechopen.com/storage/users/177382/images/system/177382.jpg",biography:"Leonardo de Azevedo Calderon obtained a bachelor\\'s degree and a doctorate in Biological Sciences from the University of Brasília (UnB), Brazil, in 2000 and 2004, respectively. He is a researcher in public health at the Oswaldo Cruz Foundation, lecturer in the Medicine Department, Federal University of Rondônia, Brazil, and head of the Center for the Study of Biomolecules Applied to Health. He has experience in the fields of biochemistry, molecular biophysics, and bioinformatics, working mainly in the prospection and development of new chemical entities with potentially useful activities in future therapies for leishmaniasis and malaria.",institutionString:"Oswaldo Cruz Foundation",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Oswaldo Cruz Foundation",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1046",title:"Infectious Diseases",slug:"infectious-diseases"}],chapters:[{id:"80467",title:"Leishmaniasis: Molecular Aspects of Parasite Dimorphic Forms Life Cycle",doi:"10.5772/intechopen.102370",slug:"leishmaniasis-molecular-aspects-of-parasite-dimorphic-forms-life-cycle",totalDownloads:60,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"According to WHO, Leishmaniasis is a complex neglected disease caused by a protozoa parasite from over 20 Leishmania species transmitted by more than 90 sandfly species, showing three main forms: visceral, cutaneous, and mucocutaneous. The efficient prevention and control of leishmaniasis are very difficult to achieve, depending on the combination of different intervention strategies, usually resulting in failure. Additionally, the correct diagnostics require the combination of clinical signs with laboratory tests, and only a few therapeutical options are available for patients. To improve this scenario, greater efforts in research for control and treatment are needed. For this purpose, the study and understanding of the life cycle of Leishmania are mandatory for all researchers who intend to dedicate their careers to the different aspects of this important disease. In order to support beginning researchers in the study of leishmaniasis, we propose in this review an update in the current knowledge about the major molecular aspects involved in the development of dimorphic forms of Leishmania parasites that replicate in the gut of sandflies (promastigotes) and in mammalian cells (amastigotes) and the relationship with host’s immune system.",signatures:"Natanael Endrew Souto Maior Torres Bonfim, Ana Lígia Barbour Scott and Leonardo de Azevedo Calderon",downloadPdfUrl:"/chapter/pdf-download/80467",previewPdfUrl:"/chapter/pdf-preview/80467",authors:[{id:"177382",title:"Dr.",name:"Leonardo de Azevedo",surname:"Calderon",slug:"leonardo-de-azevedo-calderon",fullName:"Leonardo de Azevedo Calderon"},{id:"465571",title:"Dr.",name:"Natanael",surname:"Endrew Souto Maior Torres Bonfim",slug:"natanael-endrew-souto-maior-torres-bonfim",fullName:"Natanael Endrew Souto Maior Torres Bonfim"},{id:"465572",title:"Dr.",name:"Ana",surname:"Lígia Barbour Scott",slug:"ana-ligia-barbour-scott",fullName:"Ana Lígia Barbour Scott"}],corrections:null},{id:"79372",title:"Protective and Pathogenic Immune Responses to Cutaneous Leishmaniasis",doi:"10.5772/intechopen.101160",slug:"protective-and-pathogenic-immune-responses-to-cutaneous-leishmaniasis",totalDownloads:75,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Leishmania (Kinetoplastida: Trypanosomatidae) parasites are known to cause a broad spectrum of clinical diseases in humans, collectively known as the leishmaniases. Cutaneous leishmaniasis is the most common clinical presentation with varying degrees of severity largely driven by host immune responses, specifically the interplay between innate and adaptive immune response. The establishment of a T lymphocyte driven cell-mediated immune response, leading to activated phagocytic cells, leading to Leishmania parasite killing and control of infection. Alternatively, the Leishmania parasite manipulates the host immune system, enabling parasite proliferation and clinical disease. Here we review how the cumulative interactions of different aspects of the host immune response determines disease outcome, severity, and immunity to re-infection.",signatures:"Elina Panahi, Danielle I. Stanisic, Christopher S. Peacock and Lara J. Herrero",downloadPdfUrl:"/chapter/pdf-download/79372",previewPdfUrl:"/chapter/pdf-preview/79372",authors:[{id:"80655",title:"Dr.",name:"Lara J.",surname:"Herrero",slug:"lara-j.-herrero",fullName:"Lara J. Herrero"},{id:"436057",title:"Ms.",name:"Elina",surname:"Panahi",slug:"elina-panahi",fullName:"Elina Panahi"},{id:"436058",title:"Dr.",name:"Christopher S.",surname:"Peacock",slug:"christopher-s.-peacock",fullName:"Christopher S. Peacock"},{id:"436059",title:"Dr.",name:"Danielle I.",surname:"Stanisic",slug:"danielle-i.-stanisic",fullName:"Danielle I. Stanisic"}],corrections:null},{id:"79300",title:"Extracellular Vesicles Released by Leishmania: Impact on Disease Development and Immune System Cells",doi:"10.5772/intechopen.101151",slug:"extracellular-vesicles-released-by-em-leishmania-em-impact-on-disease-development-and-immune-system-",totalDownloads:125,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Leishmania spp. release extracellular vesicles (EVs) containing parasite molecules, including several antigens and virulence factors. These EVs can interact with the host cells, such as immune cells, contributing to the parasite–host relationship. Studies have demonstrated that Leishmania-EVs can promote infection in experimental models and modulate the immune response. Although the immunomodulatory effect has been demonstrated, Leishmania-EVs can deliver parasite antigens and therefore have the potential for use as a new diagnostic tool and development of new therapeutic and vaccine approaches. This review aims to bring significant advances in the field of extracellular vesicles and Leishmania, focusing on their role in the cells of the immune system.",signatures:"Rogéria Cristina Zauli, Andrey Sladkevicius Vidal, Talita Vieira Dupin, Aline Correia Costa de Morais, Wagner Luiz Batista and Patricia Xander",downloadPdfUrl:"/chapter/pdf-download/79300",previewPdfUrl:"/chapter/pdf-preview/79300",authors:[{id:"421426",title:"Prof.",name:"Patricia",surname:"Xander",slug:"patricia-xander",fullName:"Patricia Xander"},{id:"421431",title:"Ms.",name:"Andrey",surname:"Sladkevicius Vidal",slug:"andrey-sladkevicius-vidal",fullName:"Andrey Sladkevicius Vidal"},{id:"421432",title:"Ms.",name:"Talita",surname:"Vieira Dupin",slug:"talita-vieira-dupin",fullName:"Talita Vieira Dupin"},{id:"421433",title:"Ms.",name:"Aline",surname:"Correia Costa de Morais",slug:"aline-correia-costa-de-morais",fullName:"Aline Correia Costa de Morais"},{id:"421434",title:"MSc.",name:"Rogéria Cristina",surname:"Zauli",slug:"rogeria-cristina-zauli",fullName:"Rogéria Cristina Zauli"},{id:"421435",title:"Prof.",name:"Wagner",surname:"Luiz Batista",slug:"wagner-luiz-batista",fullName:"Wagner Luiz Batista"}],corrections:null},{id:"79348",title:"Treatment of Leishmaniasis",doi:"10.5772/intechopen.101145",slug:"treatment-of-leishmaniasis",totalDownloads:47,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Treatment of Leishmaniasis is always not satisfactory despite advancement all these years. This chapter will discuss the standard treatment options like Amphotericin, oral miltefosine, topical paromycin, add more details about newer emerging drugs and alternative therapies, surgical treatment modalities for resistant cases. Will discuss few information regarding vaccines. Special precautions to be taken while travelling to endemic areas will be discussed. Management protocol for mucocutaneous and visceral type will be highlighted. Side-effects of drugs used in the treatment of Leishmaniasis will be discussed in short and measures to monitor these side effects will be discussed. Long term monitoring of relapse will also be discussed.",signatures:"R. Sivayogana, Aishwarya Krishnakumar, S. Kumaravel, Rajesh Rajagopal and P. Ravikanth",downloadPdfUrl:"/chapter/pdf-download/79348",previewPdfUrl:"/chapter/pdf-preview/79348",authors:[{id:"419522",title:"Assistant Prof.",name:"R.",surname:"Sivayogana",slug:"r.-sivayogana",fullName:"R. Sivayogana"},{id:"429065",title:"Dr.",name:"Aishwarya",surname:"Krishnakumar",slug:"aishwarya-krishnakumar",fullName:"Aishwarya Krishnakumar"},{id:"440470",title:"Dr.",name:"S.",surname:"Kumaravel",slug:"s.-kumaravel",fullName:"S. Kumaravel"},{id:"455626",title:"Associate Prof.",name:"Rajesh",surname:"Rajagopal",slug:"rajesh-rajagopal",fullName:"Rajesh Rajagopal"},{id:"455627",title:"Dr.",name:"P.",surname:"Ravikanth",slug:"p.-ravikanth",fullName:"P. Ravikanth"}],corrections:null},{id:"79223",title:"Visceral Leishmaniasis: Asymptomatic Facts",doi:"10.5772/intechopen.101109",slug:"visceral-leishmaniasis-asymptomatic-facts",totalDownloads:119,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Visceral Leishmaniasis (VL) caused by protozoan parasite Leishmania is a vector borne disease and infection is limited not to human but also to animals worldwide. For infection identification and prevalence in both Leishmania endemic and nonendemic regions, several serological and genetic techniques are used. Although diagnostic techniques and clinical symptoms can establish illness status, it is extremely difficult to diagnose infection in the absence of symptoms. Asymptomatic are healthy people who have an infection but are unaware of it. The epidemiology of asymptomatic Leishmaniasis is critical for its eradication. Only a small percentage of infected people are clinically suspected of having VL, as the majority of them may not show any symptoms and remain asymptomatic. Some asymptomatic infections may go away after a while, or they may linger for years, or they may develop to illness with clinical signs. Asymptomatic infection varies per endemic location, but almost all of them point to this hidden category of parasite infection. It is now critical to understand many factors such as diagnostic markers, genetic markers, and immunological markers along with different risk factors. All of these criteria, as well as some innovative techniques to diagnosing and controlling asymptomatic leishmaniasis, will be covered in this chapter. The main focus will be on asymptomatic condition of Indian Visceral Leishmaniasis, which is caused by Leishmania donovani and spreads via female sand fly P. argentipes biting. The numerous criteria that play a role in asymptomatic to symptomatic conversion in a specific time period will also be discussed in this chapter.",signatures:"Medhavi Sudarshan and Sumit Sharan",downloadPdfUrl:"/chapter/pdf-download/79223",previewPdfUrl:"/chapter/pdf-preview/79223",authors:[{id:"335269",title:"Assistant Prof.",name:"Medhavi",surname:"Sudarshan",slug:"medhavi-sudarshan",fullName:"Medhavi Sudarshan"},{id:"440228",title:"Dr.",name:"Sumit",surname:"Sharan",slug:"sumit-sharan",fullName:"Sumit Sharan"}],corrections:null},{id:"80815",title:"Geographical Distribution of Cutaneous Leishmaniasis and Pathogenesis",doi:"10.5772/intechopen.101841",slug:"geographical-distribution-of-cutaneous-leishmaniasis-and-pathogenesis",totalDownloads:61,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Leishmaniasis is still considered to be a global health problem, which spreads in most countries in the world. Leishmania is an intracellular obligate protistan parasite that causes different clinical symptoms in infected humans and other animals. There are clinically different types of the disease including: visceral, cutaneous or muco-cutaneous leishmaniasis. Approximately, two million new infections occurring annually; 0.7 to 1.2 million cases are recorded with cutaneous leishmaniasis and 200,000–400,000 cases return for visceral leishmaniasis. However, Cutaneous leishmaniasis considers one of uncontrolled wobbling endemic diseases, especially in Iraq, which occurs at the skin to cause a dermal lesion. Usually, the lesion is spontaneously healed to leave a colorless depressed scar and permanent immunity.",signatures:"Mohammed Hassan Flaih",downloadPdfUrl:"/chapter/pdf-download/80815",previewPdfUrl:"/chapter/pdf-preview/80815",authors:[{id:"419546",title:"Dr.",name:"Mohammed",surname:"Hassan Flaih",slug:"mohammed-hassan-flaih",fullName:"Mohammed Hassan Flaih"}],corrections:null},{id:"79230",title:"Geopolitical and Geospatial Conflicts Affecting Cutaneous Leishmaniasis: Iraqi Cases, 2014-2015",doi:"10.5772/intechopen.101147",slug:"geopolitical-and-geospatial-conflicts-affecting-cutaneous-leishmaniasis-iraqi-cases-2014-2015",totalDownloads:40,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In Iraq, increment of cutaneous leishmaniasis (CL) was reported, a zoonotic type caused by Leishmania major and an anthroponotic type caused by Leishmania tropica. This is attributed to environmental changes, irregular construction, increased waste, and stray dogs in the cities. Internal displacement, poverty, and malnutrition play a role in the occurrence of disease. Iraq has been exposed to wars, civil war, widespread violence, and terrorism, Internal displacement of population, unlawful housing, shortage of municipal services, and accumulation of garbage have been increasing in the cities since 2003. Reports from Iraqi MOH documented an increase in the rate of CL. Eventually, case investigation, vector, and reservoir controls were suspended. Geopolitical conflicts and geospatial health deterioration contributed to an increase in various dominant reservoir species in these areas, particularly for ZCL, and the activity of the sand flies. A sudden sharp increase in CL cases was observed during 2003–2015. In conclusion, ongoing crises exposed Iraq to deterioration, collapse, and destruction of health system infrastructure and uncontrolled urbanization, all of which can act as risk factors for Leishmaniasis.",signatures:"Karim Abdulkadim Muftin Al Zadawi",downloadPdfUrl:"/chapter/pdf-download/79230",previewPdfUrl:"/chapter/pdf-preview/79230",authors:[{id:"419629",title:"Dr.",name:"Karim",surname:"Abdulkadim Muftin Al Zadawi",slug:"karim-abdulkadim-muftin-al-zadawi",fullName:"Karim Abdulkadim Muftin Al Zadawi"}],corrections:null},{id:"79857",title:"Use of Cell Biology to Identify Cellular Targets in Drug Development Process against Leishmania Sp.",doi:"10.5772/intechopen.101662",slug:"use-of-cell-biology-to-identify-cellular-targets-in-drug-development-process-against-em-leishmania-e",totalDownloads:129,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Leishmaniasis is one of the most important neglected tropical diseases. The chemotherapy for its treatment uses very toxic compounds with a low efficacy rate. Thus, there is an urgent need to develop new chemotherapeutic agents to help countries control this devasting disease. In drug development, different approaches can be used to identify potential cellular targets that allow us to understand better the cell biology of eukaryotic cells. Several groups are dedicated to studying new molecules, searching for promising candidates against Leishmania. Different techniques have been used to characterize the cell biology, biochemistry, and molecular biology alterations induced by the treatments, trying to understand the mechanisms of action. The main goal of this chapter is to describe an overview of the literature exploring the several studies published about the chemotherapy of anti-Leishmania concerning the mechanisms of action of different classes of molecules or therapeutic alternatives.",signatures:"Gabrielle dos Santos da Silva e Miranda, Joseane Lima Prado Godinho, Sara Teixeira de Macedo-Silva, Brunno Renato Farias Verçoza, Alisson Amaral da Rocha, Milena Barenco Pires de Abreu Sodré, Victor Feliciano dos Santos Ramos and Juliany Cola Fernandes Rodrigues",downloadPdfUrl:"/chapter/pdf-download/79857",previewPdfUrl:"/chapter/pdf-preview/79857",authors:[{id:"420224",title:"Associate Prof.",name:"Juliany",surname:"Cola Fernandes Rodrigues",slug:"juliany-cola-fernandes-rodrigues",fullName:"Juliany Cola Fernandes Rodrigues"},{id:"420943",title:"Ms.",name:"Gabrielle",surname:"dos Santos da Silva e Miranda",slug:"gabrielle-dos-santos-da-silva-e-miranda",fullName:"Gabrielle dos Santos da Silva e Miranda"},{id:"420944",title:"Dr.",name:"Brunno Renato",surname:"Farias Verçoza",slug:"brunno-renato-farias-vercoza",fullName:"Brunno Renato Farias Verçoza"},{id:"420945",title:"Mr.",name:"Alisson",surname:"Amaral Da Rocha",slug:"alisson-amaral-da-rocha",fullName:"Alisson Amaral Da Rocha"},{id:"421145",title:"Dr.",name:"Joseane",surname:"Lima Prado Godinho",slug:"joseane-lima-prado-godinho",fullName:"Joseane Lima Prado Godinho"},{id:"421148",title:"Dr.",name:"Sara",surname:"Teixeira de Macedo-Silva",slug:"sara-teixeira-de-macedo-silva",fullName:"Sara Teixeira de Macedo-Silva"},{id:"421152",title:"Ms.",name:"Milena",surname:"Barenco Pires De Abreu Sodré",slug:"milena-barenco-pires-de-abreu-sodre",fullName:"Milena Barenco Pires De Abreu Sodré"},{id:"421153",title:"Mr.",name:"Victor",surname:"Feliciano Dos Santos Ramos",slug:"victor-feliciano-dos-santos-ramos",fullName:"Victor Feliciano Dos Santos Ramos"}],corrections:null},{id:"79559",title:"Toward New Antileishmanial Compounds: Molecular Targets for Leishmaniasis Treatment",doi:"10.5772/intechopen.101132",slug:"toward-new-antileishmanial-compounds-molecular-targets-for-leishmaniasis-treatment",totalDownloads:105,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The leishmaniases are a group of diseases caused by protozoan parasites—Leishmania sp. Leishmaniasis is classified among the 20 neglected diseases by WHO. Although the disease has been known for more than 120 years, the number of drugs used for the treatment is still limited to 5–6. The first-line drugs against leishmaniasis are pentavalent antimonials, which were introduced to the treatment 70 years ago—despite all their side effects. Molecular targets are becoming increasingly important for efficacy and selectivity in postgenomic drug research studies. In this chapter, we have discussed potential therapeutic targets of antileishmanial drug discovery such as pteridine reductase (PTR1), trypanothione reductase (TR), N-myristoyltransferase (NMT), trypanothione synthetase (TryS), IU-nucleoside hydrolase, and topoisomerases, enzymes and their inhibitors reported in the literature.",signatures:"Huseyin Istanbullu and Gulsah Bayraktar",downloadPdfUrl:"/chapter/pdf-download/79559",previewPdfUrl:"/chapter/pdf-preview/79559",authors:[{id:"419167",title:"Assistant Prof.",name:"Huseyin",surname:"Istanbullu",slug:"huseyin-istanbullu",fullName:"Huseyin Istanbullu"},{id:"435370",title:"Dr.",name:"Gulsah",surname:"Bayraktar",slug:"gulsah-bayraktar",fullName:"Gulsah Bayraktar"}],corrections:null},{id:"79649",title:"microRNAs: Are They Important in the Development of Resistance in Leishmaniasis?",doi:"10.5772/intechopen.101514",slug:"micrornas-are-they-important-in-the-development-of-resistance-in-leishmaniasis-",totalDownloads:172,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Leishmaniasis is an infectious and parasitic disease of great importance in public health. Numerous studies indicate that biochemical and molecular mechanisms are factors that contribute to the emergence of antileishmanial drug resistance. Currently, miRNAs have been identified as targets for the invasion of pathogens to control the immune response and imply resistance to treatments. Considering the alarming growth in drug resistance, new possibilities for controlling leishmaniasis have been emerging. Natural compounds originating from medicinal plants are being increasingly explored as promising antileishmanial alternatives. The chapter aims to provide a brief review on mechanisms of action associated with traditional agents used to treat leishmaniasis, focusing mainly on molecular bases associated with the resistance of Leishmania spp. to current drugs and identifying the possible miRNAs involved in this process. In addition, we seek to describe some of the promising plant molecules that can be used as potential antileishmanial agents and their possible mechanisms of action.",signatures:"Sandra Alves de Araújo, Tatiane Aranha da Penha-Silva, Jaqueline Diniz Pinho, Marcelo de Souza Andrade and Ana Lucia Abreu-Silva",downloadPdfUrl:"/chapter/pdf-download/79649",previewPdfUrl:"/chapter/pdf-preview/79649",authors:[{id:"223173",title:"Dr.",name:"Ana Lucia",surname:"Abreu-Silva",slug:"ana-lucia-abreu-silva",fullName:"Ana Lucia Abreu-Silva"},{id:"233684",title:"Dr.",name:"Tatiane",surname:"Aranha da Penha-Silva",slug:"tatiane-aranha-da-penha-silva",fullName:"Tatiane Aranha da Penha-Silva"},{id:"421473",title:"MSc.",name:"Sandra",surname:"Alves de Araújo",slug:"sandra-alves-de-araujo",fullName:"Sandra Alves de Araújo"},{id:"428524",title:"Dr.",name:"Jaqueline",surname:"Diniz Pinho",slug:"jaqueline-diniz-pinho",fullName:"Jaqueline Diniz Pinho"},{id:"428526",title:"Dr.",name:"Marcelo",surname:"de Souza Andrade",slug:"marcelo-de-souza-andrade",fullName:"Marcelo de Souza Andrade"}],corrections:null},{id:"79718",title:"Molecular Informatics of Trypanothione Reductase of Leishmania major Reveals Novel Chromen-2-One Analogues as Potential Leishmanicides",doi:"10.5772/intechopen.100594",slug:"molecular-informatics-of-trypanothione-reductase-of-em-leishmania-major-em-reveals-novel-chromen-2-o",totalDownloads:129,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Trypanothione reductase (TR), a flavoprotein oxidoreductase is an important therapeutic target for leishmaniasis. Ligand-based pharmacophore modelling and molecular docking were used to predict selective inhibitors against TR. Homology modelling was employed to generate a three-dimensional structure of Leishmania major trypanothione reductase (LmTR). A pharmacophore model used to screen a natural compound library generated 42 hits, which were docked against the LmTR protein. Compounds with lower binding energies were evaluated via in silico pharmacological profiling and bioactivity. Four compounds emerged as potential leads comprising Karatavicinol (7-[(2E,6E,10S)-10,11-dihydroxy-3,7,11-trimethyldodeca-2,6-dienoxy]chromen-2-one), Marmin (7-[(E,6R)-6,7-dihydroxy-3,7-dimethyloct-2-enoxy]chromen-2-one), Colladonin (7-[[(4aS)-6-hydroxy-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]methoxy]chromen-2-one), and Pectachol (7-[(6-hydroxy-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl)methoxy]-6,8-dimethoxychromen-2-one) with good binding energies of −9.4, −9.3, 8.8, and −8.5 kcal/mol, respectively. These compounds bound effectively to the FAD domain of the protein with some critical residues including Asp35, Thr51, Lys61, Tyr198, and Asp327. Furthermore, molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) computations corroborated their strong binding. The compounds were also predicted to possess anti-leishmanial activity. The molecules serves as templates for the design of potential drug candidates and can be evaluated in vitro with optimistic results in producing plausible attenuating infectivity in macrophages.",signatures:"Samuel K. Kwofie, Gabriel B. Kwarko, Emmanuel Broni, Michael B. Adinortey and Michael D. Wilson",downloadPdfUrl:"/chapter/pdf-download/79718",previewPdfUrl:"/chapter/pdf-preview/79718",authors:[{id:"419961",title:"Dr.",name:"Samuel K.",surname:"Kwofie",slug:"samuel-k.-kwofie",fullName:"Samuel K. Kwofie"},{id:"429019",title:"Mr.",name:"Gabriel B.",surname:"Kwarko",slug:"gabriel-b.-kwarko",fullName:"Gabriel B. Kwarko"},{id:"429020",title:"Dr.",name:"Emmanuel",surname:"Broni",slug:"emmanuel-broni",fullName:"Emmanuel Broni"},{id:"429021",title:"Prof.",name:"Michael B.",surname:"Adinortey",slug:"michael-b.-adinortey",fullName:"Michael B. Adinortey"},{id:"429022",title:"Prof.",name:"Michael D.",surname:"Wilson",slug:"michael-d.-wilson",fullName:"Michael D. Wilson"}],corrections:null},{id:"80026",title:"Plant-Based Alternative Treatment for Leishmaniasis: A Neglected Tropical Disease",doi:"10.5772/intechopen.101958",slug:"plant-based-alternative-treatment-for-leishmaniasis-a-neglected-tropical-disease",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Leishmaniasis is a third most important vector born disease caused by intracellular parasite belongs to genus Leishmania. The leishmaniasis is prevalent in 102 countries/areas worldwide. Approximately, it effected 350 million people worldwide. Leishmaniasis effects developing and undeveloped countries globally. Antileishmanial drugs (pentavalent antimonials, stibogluconate, miltefosine, paramycin, and amphotericin) are most vital tool for curing leishmaniasis. However, none of these drugs is free from side effect including cost, toxicity, drug resistance, administration route, and prolong time, these disadvantages are main obstacle in the Leishmania infection eradication. Considering the increasing cases of leishmaniasis and drug resistance there is an urgent need for an effective and novel approach against leishmaniasis. Therefore, many researchers have tried to develop new medicines for the treatment of Leishmania infection. In the course of new therapies identification, plant based compounds were found to be an alternative that can be either used directly or with structural modifications. Several plants have been known for ages to be the source of phytochemicals with high values of medicines. These phytochemicals have been extracted by various techniques and have shown efficacy for the curing of several diseases. This chapter study explain various applications based on green approaches drugs for the treatment of leishmaniasis.",signatures:"Nargis Shaheen, Chaitenya Verma and Naveeda Akhter Qureshi",downloadPdfUrl:"/chapter/pdf-download/80026",previewPdfUrl:"/chapter/pdf-preview/80026",authors:[{id:"224439",title:"Dr.",name:"Naveeda",surname:"Akhter Qureshi",slug:"naveeda-akhter-qureshi",fullName:"Naveeda Akhter Qureshi"},{id:"420059",title:"Dr.",name:"Nargis",surname:"Shaheen",slug:"nargis-shaheen",fullName:"Nargis Shaheen"},{id:"420980",title:"Dr.",name:"Chaitenya",surname:"Verma",slug:"chaitenya-verma",fullName:"Chaitenya Verma"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"2327",title:"Chromatography",subtitle:"The Most Versatile Method of Chemical Analysis",isOpenForSubmission:!1,hash:"730549acc4ff27929bb106ba63661172",slug:"chromatography-the-most-versatile-method-of-chemical-analysis",bookSignature:"Leonardo de Azevedo Calderon",coverURL:"https://cdn.intechopen.com/books/images_new/2327.jpg",editedByType:"Edited by",editors:[{id:"177382",title:"Dr.",name:"Leonardo de Azevedo",surname:"Calderon",slug:"leonardo-de-azevedo-calderon",fullName:"Leonardo de Azevedo Calderon"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"825",title:"Current Topics in Tropical Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ef65e8eb7a2ada65f2bc939aa73009e3",slug:"current-topics-in-tropical-medicine",bookSignature:"Alfonso J. 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\r\n\tThe book covers one of the most actual and prospective areas of Artificial Intelligence (AI) – Multi-Agent Technologies (MATs) – and their nexus with Machine Learning (ML). MATs and Multi-Agent Systems (MASs) arise as an extremely powerful tool for the solution of various complicated problems regarding the planning of operation of distributed robotics and inter-robot communications, assessment and predictive modeling of situations, smart homes and cities supervising and control, financial, economic, ecological, biological and demographic modeling and simulation, etc. From the other side, ML joins a broad set of theoretical and technological approaches aimed to minimize the difficulty and time necessary for the development and maintenance of knowledge bases of MASs-based socio-technological smart systems. ML is conceptually and practically closely interconnected with artificial neural networks. So joint consideration of these two modern paradigms may produce a non-trivial synergetic effect in both directions: multi-agent implementation of ML logics and procedures, as well as ML-based algorithms of correcting MASs behaviour by changing their knowledge bases according to a volatile environment. The most interesting topic would be combined and deeply integrated MASs with neuro-based ML elements embedded in MAT inference and meta-inference engines.
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He has finished his education at the Academy by Peter The Great, department of electronics and computer science (1977), and at the Russian Presidential Academy, department of state financial policy (2006). \nHe is a corresponding member of the Russian Academy of Sciences (RAS), a professor, a deputy director for science of Russian foundation for basic research (RFBR), a deputy chair of RAS Systems analysis committee and of RAS Science board on robotics and mechatronics. Dr. Sheremet is also a Co-Chair of the Task Group 'Advanced Mathematical Tools for Data-Driven Applied Systems Analysis” of Committee on Data (CODATA) of International Council for Science (ICSU) and an active member of the Science Advisory Committee of International Institute for Applied Systems Analysis (IIASA).\nDuring 1977-1993 he has developed a theory and an implementational background of the Augmented Post Systems (APS), providing creation and maintenance of distributed intelligent middleware with very large knowledge and databases. During 1994-2014 Dr. Sheremet has developed and implemented a family of APS-based non-conventional computer architectures, providing deep integration of Multi-Agent Systems, Internet of Things and Big Data paradigms and efficient operation in highly volatile environments. Since 2005 he is successfully developing the theory of recursive multi-sets being a result of the convergence of classical optimization theory and modern knowledge engineering. Main areas of application of this theory are the future digital economy, data-driven applied systems analysis, large socio-technological systems, resource-driven games, as well as the assessment of large economical systems sustainability and vulnerability to various destructive impacts (poor decision making, natural hazards, terror, etc.). \nDr. Sheremet has also received several awards, including the L.Euler medal by European Academy of Natural Sciences (2011), Russian Federation Zhukov State Prize (2013), Gold medal and Diploma Di Merito for exceptional achievements by European Scientific-Industrial Chamber (2016), Russian Government Prize (2018).",institutionString:"Russian Foundation for Basic Research",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Russian Foundation for Basic Research",institutionURL:null,country:{name:"Russia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"9",title:"Computer and Information Science",slug:"computer-and-information-science"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"280415",firstName:"Josip",lastName:"Knapic",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/280415/images/8050_n.jpg",email:"josip@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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\n
1. Introduction
\n
Dengue is a dynamic systemic infectious disease and the most important arbovirus worldwide. Its occurrence has increased in past decades, and it is estimated that 390 million of infections occurs annually of which 67–136 million manifest clinically with any severity of disease. Another study shows that 3.9 billion people are at risk of infection with dengue virus (DENV) in 128 countries [1]. Diagnostic tests providing a proper identification of DENV infection by any of its four serotypes in symptomatic or asymptomatic cases in the population, and especially in areas that have more than one arbovirus or another micro-organism (virus, bacteria or parasite) producing similar signs and symptoms are the key aspect of any dengue research and surveillance programs [2]. Laboratory tests are based on the detection of the virus, part of its genome or structure, or specific result from an infected person or animal as immune response. In this chapter, the most used laboratory tests in an arbovirus study focused on diagnosis and research of dengue virus (DENV) will be assessed, some comparisons will be carried out with other laboratory tests, its features, advantages and disadvantages, and cautions need to be considered during the process.
\n
\n
\n
2. Laboratory test
\n
\n
2.1. Characteristics of diagnostic tests
\n
A diagnostic test intends to identify whether or not a patient has a disease that cannot be recognized by signs and symptoms. Ideally, such test must meet the following requirements:
To achieve high levels of sensitivity and specificity.
Accurate and precise results.
To deliver rapid results.
To be cost effective.
\n
Different studies can be carried out in the dengue research. For example, clinical diagnosis diseases, epidemiological studies, clinical assays, viral load tests, vaccines and anti-viral assessments, etc. Thus, it is necessary to know the testing capacity to detect the presence or absence of the disease (validation of diagnostic tests), so it is very useful to know the following diagnostic test indicators (Table 1).
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Result of the laboratory test
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Disease
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Positive
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Negative
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Total
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Positive
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a (True positive)
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b (False positive)
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a + b
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Negative
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c (False Negative)
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d (True negative)
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c + d
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Total
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a + c
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b + d
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a + b + c + d
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Table 1.
A double-entry table to obtain indicators of diagnostic tests from analyzing a sample showing all possible results.
Sensitivity: It is the probability that a sick person delivers a positive result in the diagnostic test (a/(a + c)).
Specificity: It is the probability that a person who is not sick delivers a negative results in the diagnostic test (d/(b + d)).
Positive predictive value: It is the probability that a person is sick and gets a positive result in the diagnostic test (a/(a + b)).
Negative predictive value: It is the probability that a healthy person gets a negative result in the diagnostic test (d/(c + d)).
Efficiency: It is the probability that a person is properly diagnosed using the diagnostic test ((a + d)/(a + b + c + d)).
Positive likelihood ratio (LR+): It is obtained when dividing sensitivity by the portion of false positives (1 − specificity), and it indicates the probability of being sick if the result is positive (Sensitivity/(1 − specificity)).
Negative likelihood ratio (LR−): It is obtained when dividing false negatives (1 − sensitivity) by specificity, and it indicates the probability of negative results obtained from a sick person ((1 − Sensitivity)/Specificity).
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The sensitivity and specificity have distinctive features of diagnostic tests, they are not compromised by the prevalence of the disease, and they are inversely proportional. If a study in which the majority of people are suffering from this disease is carried out, a high sensitivity test is needed in order to identify the highest number of true positive and the lowest number of false negative. However, it may increase the number of false positive. If you want to obtain a good disease diagnosis, a high specificity test must be used to detect the highest number of true negative. Here, the false positive will also be low. Moreover, positive and negative predictive values of the diagnostic tests are affected by the prevalence of the disease in the study population. The likelihood ratio (LR) that is independent of prevalence is used when the laboratory tests do not present dichotomous results but cut-off value. This is another way of assessing the accuracy. According to the results, the test can be classified into adequate (LR+ ≥ 10 to LR− ≤ 0.1), moderate (LR+ ≥ 5 < 10 to LR− > 0.1 ≤ 0.2), scarce (LR+ ≥ 2 < 5 to LR− > 0.2 ≤ 0.5) and insignificant (LR+ ≥ 1 < 2 to LR− > 0.5 < 1). Not only one but also many tests can be used to diagnose dengue in the epidemiological studies. It can be done sequentially or in parallel. For example, when performing a test with two sequential tests, all positive people need to be assessed with a second test upfront, and this will cause the reduction of net sensitivity and a net specificity enhancement obtained from both tests. It will be considered as positive if their tests are positive in all tests. Likewise, the negative ones will have negative results in the confirmatory test. On the other hand, if two simultaneous tests are used, a net sensitivity is gained, while a net specificity is reduced. This is different when tests are done independently. Negative is considered people whose negative results were in all tests and positive the ones whose positive results were in at least one of the tests [3, 4].
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2.2. Biological samples for dengue studies
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The type of sample taken in the right moment, storage and transport to the laboratory to be processed, and the appropriate documentation plays a key role to obtain results because if there is a change of sample quality, this can reduce antibody titers, viruses or genetic material resulting in lower titers or concentrations from the real ones in quantitative tests or false negative results in quantitative or qualitative tests.
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The most used samples to diagnose and to search about dengue are whole blood, serum, plasma, and human organs like spleen, liver, and heads of mosquitoes, pools of mosquitoes, brains of mice, serum samples saturated with filter paper, etc. The serum samples that will be processed for virus isolation and/or polymerase chain reaction tests and fluorescent focus assay to quantify the virus in serum are collected in tubes without anticoagulants. They must be taken within 1–5 days after the onset of symptoms, to detect the antigen (NS1 protein), within 1–6 days to detect IgM antibodies for enzyme-linked immunosorbent assay (ELISA) or a rapid test after day 5 of starting the symptoms, within 1–5 to detect IgG using matched serums to assess seroconversion for ELISA, neutralization test or hemagglutination inhibition used in acute serums, and convalescent serums after day 15. In the case of liver, spleen, kidney or nodes samples, a sample is immediately taken after the person’s death or the animal in experiment. The samples must be taken to the laboratory as soon as possible and preferably dealt with in dry ice or liquid nitrogen [5, 6].
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2.3. Primary and secondary dengue infections and dengue diagnostic
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Although most infections are asymptomatic or subclinical, a set of symptoms starts after a dengue infection elapses the 4–10-day incubation period. A four-fold increase of the IgG antibody titers in matched serums measured by ELISA IgG test or hemagglutination inhibition indicates recent flavivirus infection. When people are infected with the virus on the first time, dengue infections are known as a primary infection in which a viral load and the relevant antibody formation (IgM, IgG and IgA) are triggered. In a primary infection, the titer of IgM is generally much higher and more specific than in a secondary infection. Some studies consider that an infection is primary if the IgM/IgG relation is higher than 1.2 with diluted samples at 1:100 or 1.4 using diluted serum at 1:20. When people are previously exposed to any serotype or flavivirus, or even after a vaccine (i.e., yellow fever vaccine), dengue infections are secondary and the IgM/IgG relation is lower than 1.2 or 1.4. In secondary infections, the IgG is detected in the highest levels and even on the acute phase. It remains higher for 10 months and even lifelong in order to consider a person being infected with dengue virus (DENV), the following laboratory test interpretations need to be followed:
When a sample taken from the acute phase is positive for dengue due to the PCR test, viral isolation, and IgM serocoversion in matched serum samples, the IgG seroconversion in matched serum samples or the fourfold increase of IgG titer is considered confirmed cases.
When a positive IgM occurs in a single serum sample or a positive IgG in a single sample with hemagglutination inhibition titer is the same or higher than 1:1280, it is considered a suggestive case [5, 6, 7, 8].
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2.4. Laboratory test
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The laboratory tests can be interchangeably used in different researches, both basic and applied ones. We can classify them into direct methods that allow virus detection or part of its structure and indirect methods which identify a reaction produced by the presence of DENV in the organism.
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2.4.1. Direct detection methods
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2.4.1.1. Viral RNA extraction
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The genetic material extraction has a key role for PCR tests so that the quality of a product extracted can vary depending on the type of sample being used, and the extraction method applied will directly affect the test sensitivity. The dengue RNA can be recovered from serum, blood, urine, plasma samples and other organs. However, the viral load in blood is much higher (7.9 × 102–1.9 × 105 PFU/mL) in comparison with saliva and urine samples (1 × 101–5 × 101 PFU/mL). The RNA extraction can be done by guanidine thiocyanate and trizol methods and by the use of commercial kits like Qiagen kit (QIAamp® RNA Viral mini kit), etc. RNA extraction techniques in serum/plasma samples from patients using QIAamp® UltraSens Virus Kit (Qiagen Inc., Valencia, USA) were compared to the modified Chomczynski-Sacchi extraction technique in order to extract plasma RNA so that the original technique is used for cell or tissue samples being more cost effective than the kit commercial one. It was found that 34 samples out of 47 were positive by using the Chomczynski-Sacchi method, and the remaining 27 samples were positive by using the kit commercial method [8, 9, 10].
The RT-PCR techniques and their different variants are converted into one of the main tools for diagnosing DENV and other arbovirosis. Less time to process the results, being able to identify the circulating serotypes of the virus, presenting the highest sensitivity and specificity levels are among its advantages. This type of test has the benefit of obtaining rapid results while identifying circulating serotypes of dengue. The RT-PCR technique is the extraction of a RNA sample followed by a reverse transcription process, the actual PCR (nested or not), and the last screening in gel obtaining a qualitative result. The technique developed by Lanciotti and his collaborators or the variant developed by Harris and his collaborators, which have been used for many years, is recommended by the Pan American Health Organization (PAHO/OPS). The technique developed by Lanciotti starts with converting RNA into DNA by using a reverse transcriptase enzyme. Then, the PCR is carried out when primers are used to amplify prM genes and C virus areas to continue with a specific primer-nested PCR for each virus serotype. Harris and his collaborators developed a multiplex RT-PCR from Lanciotti and his collaborators’ method that uses five pairs of primers (four specific pairs for serotypes and one pair of the region of the capsid gene). There are many different variants in this technique having different sensitivity levels that are used in research laboratories. One of the main disadvantages is the possible existence of a false positive due to the contamination produced by amplicons during the reverse transcription of the genetic material, and it is necessary to consider that a negative result in these tests does not rule out DENV infection or other arboviruses, and the analysis must be complemented by serological findings (Figure 1) [9, 11].
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Figure 1.
Reverse transcriptase semi-nested reactions, using primers targeted to the C/PrM genomic region as described by Lanciotti et al. (a photo taken on April 24, 2018 in the molecular biology laboratory with the authorization of the U.S. Naval Medical Research Unit Six (NAMRU-6).
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2.4.1.3. RT-PCR multiplex to DENV and different microorganism identifications
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Chikungunya (CHIKV), Zika (ZIKV), Yellow Fever (YFV) and DENV are arboviruses with the highest prevalence in the American continent. They are transmitted by the same vector Aedes aegypti y Aedes albopictus facilitating its cocirculation in some areas of the region. Because of these arboviruses, the affected patients develop similar symptoms but its clinical management and its possible results as the aftermath of the disease, and mortality rates are different. They can even produce coinfection with other microorganisms making a proper identification necessary in an early stage of the disease (acute phase). There are commercial and standardized testing in a laboratory allowing qualitative identification of DENV, ZIKV, and CHIKV in serum, plasma, and even some urine samples [12]. Other commercial testing like FilmArray Global fever panel has the capacity of detecting genetic material in viruses, bacteria and protozoa (nine viruses like YFV, DENV, ZIKV, WNV, CHIKV, among others, six bacteria and four protozoa) in whole blood (EDTA), with automated equipment. A study to determine a detection limit for microorganisms using FilmArray Global fever panel found the following results for DENV like DENV-1 (Hawaii) 2.7 × 101, DENV-2 (New Guinea C) 3.6 × 101, DENV-3 (H87) 1.6 × 103 and DENV-4 (H241) 7.6 × 101. The main advantage of this test is time reduction to obtain results (about an hour), discriminating the amount of pathogens, and minimizing cross-contamination problems so that all reactions are carried out among a closed system. The cost of the product and a machine analyzing only a sample at a time is within its limiting [13].
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2.4.1.4. Real-time PCR
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It uses conventional RT-PCR principles, and it combines with fluorochromes like SYBR Green or TaqMan probes with fluorochromes capable of producing proportional fluorescence to the DNA copy samples. The strengths of this test are the same as the conventional RT-PCR, it also reduces time when releasing the results as well as the cross-contamination risk post PCR, the levels of sensitivity and specificity are higher than the conventional RT-PCR, and overall it allows quantifying the genetic material. There are different commercial kits in the market to diagnose DENV, and its sensitivity and specificity levels vary when they are compared among them [14, 15]. The CDC elaborated a real time RT-PCR in order to diagnose four serotypes in serum or human plasma samples using an ABI 7500 FAST DX thermo-cycler of Applied Biosystems and hydrolysis dual-marker TaqMan probes, and it is the first RT-PCR approved by Food and Drug Administration (FDA) to detect DENV [16].
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2.4.1.5. Viral isolation in cell lines
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Viral isolation in cell cultures or mosquitoes followed by the virus detection using indirect immunofluorescence is considered as gold standard [8, 17]. In order to carry out the DENV viral isolation and as a general rule to any virus, it is necessary to consider the following:
To know the isolated virus (virus characteristics, replication, transmission mechanism, etc.)
To know which biosafety level a virus can be performed. In the case of DENV, biosafety level 2 is needed [18].
To determine which cell line to use and to be able to isolate the virus, it is essential to identify the most sensitive cell line from mosquitoes and mammals, and its use for the isolation and DENV propagation, being the most sensitive cell lines of mosquitoes as follows:
C6/36: they are easy cell propagation, highly sensitive to DENV infection, and cultivated at 28°C that are obtained from salivary glands of Aedes albopictus.
C6/36 HT (hot temperature): they can be spread at 34°C and have a bigger sensitivity to detect DENV. This cell line maintains its high sensitivity only for some weeks due to its higher temperatures, so some researchers suggest adapting at 34°C, a C6/36 cell line growing at 28°C, and using an alternative method.
TRAS-284-SF cell has the main benefit of not requiring the use of fetal bovine serum (FBS) as a culture medium, and it presents a higher sensitivity to the DENV isolation [6, 9, 17].
Knowing the viral isolation technique that provides better results to isolation and virus propagation. The standard method is based on the virus propagation in a sensitive cell line for inoculating a previous diluted sample in a cell culture medium. After the infection process, the cultures are placed on incubation for the binding of the virus to the cell; subsequentially, it is placed on a means of maintenance with the essential nutrients to maintain the live cultures for a period of time that can be 13–15 days. Then, the infected cells are recovered, and the virus presence is determined by an immunofluorescence process, ELISA, molecular techniques, and others. Bottles, tubes, 6–96 well culture plates, and others are used in order to sustain the binding to cell cultures. A modified shell vial technique allows the recovery of a higher number of YFV, SLV, WNV, ILHV, GCV, OROV, MAYV and DENV isolations. This technique follows the same steps as a standard method, but after inoculating cells, the cultures are centrifuged to velocities between 1800 and 2200 rpm. This technique can also be used to isolate DENV coinfections. However, it seems not to have good results for VEE isolation [19, 20, 21, 22].
The sample type to be used. The sample type to be used and its proper preservation until the processing time are extremely important to isolate a virus. The most used dilutions to a viral isolation vary from 1:5 to 1:20. A very concentrated dilution of the sample could generate a toxic effect in the cells. On the other hand, a much diluted sample could cause the inability of isolating the virus because of having a low concentration virus in the inoculum [19, 21].
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2.4.1.6. Plaque assay
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It is the most used test to determine viral vaccine titers so that it quantifies the virus to infect cells. It is based on the infection of a cell monolayer with different virus dilutions to evaluate. After an incubation period, the viral infection results in lytic plaques. If they are colored, they are displayed as holes in the cell monolayer. Each plaque corresponds with an infectious virus. One of the main disadvantages of this technique is that it can only use viruses being able to produce a cytopathic effect. Another one is that all native strains of DENV are not always capable of producing well-defined plaques, and the viral titers can vary depending on the cell line used. For a dengue virus case, the most used cell lines are VERO and BHK-21 (Figure 2) [5, 6, 23].
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Figure 2.
Plaque assay titration for DENV-2 using VERO-76 cells and a semi-solid method (a photo taken on March 2017, in the Virology and Molecular Biology Laboratory of the Faculty of Biological Sciences at National University of San Marcos, Peru).
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2.4.1.7. Fluorescent focus assay
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It is a combination of plaque assay and immunofluorescence. Viruses are inoculated in different dilutions in the cell line, then a cell incubation period is fixed to plaques with any organic solvent, and an immunofluorescence is carried out. Positive cells are observed with fluorescent foci that can be counted. One of its advantages is to reduce the incubation period in order to obtain the results in comparison with plaque assay. It allows processing a bigger number of samples so that it can be adapted to use 96-well culture plates in comparison with the 24-well plates which are used in the plaque assay. Another advantage is to allow the use of C6/36 cells that are highly sensitive to detect dengue virus, and they cannot be used for the plaque assay as they do not form lytic plaques (Figure 3) [23].
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Figure 3.
Fluorescent focus assay for DENV-2 using the C6/36 (A) and VERO-76 cells (B). The indirect immunofluorescence performed to visualize the foci was carried out on the fifth day of incubation, using the fluorescein isothiocyanate (FITC) conjugate (a photo taken on March 15, 2016 in the Serology laboratory with the authorization of the U.S. Naval Medical Research Unit Six (NAMRU-6)).
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2.4.1.8. Viral isolation in nursing mice
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Suckling mice were greatly used because of their easy reproduction and handling to isolate virus as well as the antigen production. About 1–3 neonatal mice and an intracranial inoculation are carried out. Then, a 21-day daily checking to observe the occurrence of neuromotor symptoms is needed. This technique is starting to cease to use due to a great variety of cell cultures that allow good sensitivity levels in DENV detection. This is why the Institutional Animal Care Committee and IACUC Committee recommend reducing this activity. One of the most common practices to carry out euthanasia on suckling mice is using a CO2 camera. When using this technique, it is necessary to make sure such mice are dead as they are very resilient to lacking of oxygen so it is advisable to continue with other euthanasia techniques like cervical dislocation, decapitation, etc. [6, 9, 24].
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2.4.1.9. Inoculation in mosquitoes
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The mosquitoes like Aedes genus can be used for dengue virus isolation when infection and disease transmission studies are carried out. The intracerebral and intrathoracic inoculations are used for mosquitoes which are immobilized at low temperatures. The mosquito infection technique is to feed them directly with the dengue-infected patient blood in the acute phase of the disease. The mosquitoes of the Toxorhynchites genus, which are not blood-feeding insects, can be used for the four-serotype dengue isolation, Japanese encephalitis and encephalitis of San Luis are more susceptible than cell culture isolation of dengue virus as well as the Drosophila melanogaster that can be inoculated by micro injection in the abdomen, and it could reach higher titers using less time in comparison with the Aedes aegypti inoculation [6, 25, 26].
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2.4.1.10. Automated equipment for virus counting
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There are redesigned flow cytometers to quantify a virus in solutions like The ViroCyt® Virus Counter (VC) 2100 (ViroCyt, Boulder, CO, USA) using a specific fluorescent dye for the envelope proteins and the other one for the nucleic acids that allows recognizing viral particles having both components in its structure. Then, it eliminates anything that represents one type of fluorescent [27].
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2.4.1.11. Enzyme-linked immunosorbent assay (ELISA) for NS1
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The NS1 nonstructural protein is produced during dengue infection and accumulated in higher concentrations in the human serum (up to 50 μg/ml) being detected during the acute phase (day 0–6) after the symptoms in primary and secondary infection start. Some studies have reported a correlation between elevated NS1 protein levels with hemorrhagic dengue cases, and even this technique seems to be effective to detect DENV in the vector. When evaluating three of these commercial tests from different manufacturers with human serum samples, it is found sensitivity between 85.5 and 95.9% and specificity between 95.0 and 100% using the viral isolation as a reference test [28].
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2.4.2. Indirect methods
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2.4.2.1. IgM ELISA
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IgM can be detected on 50% infected people within 3–5 days and after the symptoms onset, and it reaches approximately to 80% infected people on day 5 and to 99% infected people on day 10 reaching maximum levels in humans at the 2 weeks to falter until they are not detected on 2–3 months. An indirect capture ELISA is usually used for detecting IgM, and it allows increasing sensitivity of the test in detecting antibodies. However, IgM antibodies are not specific, and they could present a cross-reaction with other flavivirus like YFV, ZIKV, etc. Besides, some particular test characteristics could alter the result of the test as the rheumatoid factor depending on IgM ELISA type causes false positives [5, 7, 8, 9].
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2.4.2.2. IgG ELISA
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The IgG is detected with low titers when ending the first week of the onset symptoms in humans, and they could even be detected for a lifelong. The tests to detect an IgG using the virus bind to a plate in a smooth antigen way (protein cocktail) usually present a low specificity so that there is a cross-reaction with other viruses from the same genus due to the proteins found in the antigen, and this test cannot be used to determine the infectious dengue serotype but it can present a higher sensitivity than the hemagglutination inhibition test. The ELISA is also used for studying how different IgG sub-classes react in a dengue infection [5, 7, 8, 9].
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2.4.2.3. IgG inhibition ELISA tests
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It can be used to differentiate a primary infection and a secondary infection from dengue replacing an hemagglutination inhibition test using a percentage of inhibition higher or the same as 50% as a positivity criterion. In case of having only a serum sample, a primary infection is considered when the antibody IgG titer is ≤20, and a secondary infection is considered if the antibody titer is ≥1280. In both cases, the sample must be collected on 5–7 days. If there are paired samples, a primary infection is considered when the seroconversion in antibody titers from the acute and convalescent phase occurs, and a secondary infection is considered when the antibody titers increase four times or more between the acute and convalescent phase, or in both serums [6].
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2.4.2.4. IgA ELISA test
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It was used in some studies to identify the infected people in an early stage of dengue infection. Thus, it was found 100% of sensitivity in people with secondary dengue infection after symptom onset-day 1. However, the results were not very favorable for primary infections [29].
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2.4.3. Neutralization test
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2.4.3.1. Plaque reduction neutralization test (PRNT)
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This test is considered the gold standard to detect neutralizing IgG antibodies because they have high sensitivity but can have a cross-reaction among members of flavivirus group. It is based on the binding of antibodies present in the sample which contains a known virus load (working dilution). The mixture of both is incubated and inoculated in a cell line until forming lytic plaques that are observed when coloring the cell monolayer. All samples neutralizing and avoiding the forming of certain number of plaques (being the most commonly used for 50–90% reduction) are with the presence of neutralizing antibodies indicating exposure to dengue. Using 1 in 30 diluted serum samples allowed discriminating between DENV-1 and DENV-2 serotypes in collected serum in Cuba, before and after the 1981 epidemic caused by DENV-2. There are many different variants of a PRNT test that could produce a variation in the results when being compared with using different used reduction rates, different PRNT methods (solid or semi-solid), and different cell lines. The most used for dengue are VERO cells that are recommended by World Health Organization (WHO), and BHK-21 that are used by other laboratories like Pedro Kouri Institute of Cuba. The use of different genotypes can alter the antibody titer results. Kochel et al. [30] evaluated Peruvian samples infected with DENV-2 American genotype. Antibody titers were found in higher levels when using the same genotype rather than using the Asian genotype. PRNT can be used to differentiate dengue infection to yellow fever infection. It has been found that the lowest serum dilution capable of distinguishing between both infections is 1 in 5. In a dengue secondary infection, PRNT can have a cross-reaction with other serotypes. In infected populations with sequentially different serotypes of dengue, the highest antibody titer pertains to the first infection (the “original antigenic” sin phenomenon) (Figure 4) [5, 6, 7, 30, 31, 32].
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Figure 4.
Plaque reduction neutralization test for DENV-2 using BHK-21 clone 15 cells. Dilutions from 1:20 to 1: 160 were used. Sample A and C do not present antibodies against the DENV2, and sample B is positive up to a dilution greater than 1: 160 (a photo taken on March 23, 2012 in the PRNT laboratory with the authorization of the U.S. Naval Medical Research Unit Six (NAMRU-6)).
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2.4.3.2. Focus reduction neutralization test (FRNT)
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It combines the PRNT test with immunofluorescence or ELISA to count fluorescent foci or spots and calculate their reduction rate in the samples. Among its advantages, this allows reducing the days to obtain the results and undertaking studies with native strains so that some of them produce tenuous plates that are difficult to count but they make easier to detect fluorescent foci. Moreover, more sensitive lines can be used to detect dengue, not forming C6/36 plates, and they can be adapted to plates with a higher number of wells enabling to process a higher number of samples and saving materials. And, fluorescent foci can be counted with an ultraviolet light microscope or using computerized readers capable of reading fluorescent foci and reducing time to obtain results [33, 34].
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2.4.3.3. Microneutralization-ELISA
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It is a variable in the PRNT test and uses the same immunological basis with the advantage of being worked on 96-well plates different from the PRNT that generally uses 24-well plates. This allows saving materials and handling a higher number of samples. This technique is used to detect the presence of neutralizing antibodies in the sample which is mixing the patient’s sample that is previously inactivated in different dilutions with the dengue virus serotype to be evaluated, once the antigen-antibody binding is inoculated in the specified cell line as VERO-76 cells. If there were neutralizing antibodies in the sample, these ones would block the entry from the virus to the cell and would not produce the infection. The presence of the virus in the cell is revealed by an ELISA procedure. Samples exposing the color change in a substrate will be considered as negatives to an IgG antibody against the dengue serotype under study, and the samples that do not produce color change in the substrate will be positive for the presence of IgG antibodies (Figure 5). When this technique was evaluated with serum samples from patients with primary infection, the results were very similar to the ones in PRNT. However, the result correlation was very poor in comparison with this technique using samples from patients with secondary infections [35].
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Figure 5.
Enzyme-linked immunosorbent assay-format microneutralization test for DENV-2. The samples were inoculated in triplicate in VERO-76 cells using dilutions from 1:40 to 1: 320, and the ELISA test was performed on day 5 post inoculation (a photo taken on April 24, 2018 in the serology laboratory with the authorization of the U.S. Naval Medical Research Unit Six (NAMRU-6)).
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2.4.3.4. Immunofluorescence test
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This test can be direct or indirect, and it is the most commonly used to identify the infected cells deriving from cell lines, salivary glands of mosquitoes, etc. It is based on the binding of the actual virus to a sample that can be infected cells with a dengue virus antibody joined to a fluorescent marker named conjugated (direct immunofluorescence). One of the most used fluorochromes for this technique is the fluorescein isothiocyanate (FITC). First, a specific antibody is to bind to a specific virus in the indirect immunofluorescence (the used antibody can be monoclonal or polyclonal, and it is bind to a conjugated). Observing the samples under ultraviolet light of the microscope, the fluorescent cells indicate the presence of the virus in the cell. This test is quite cost effective, and its sensibility and specificity can vary depending on the antibody quality used for virus identification. The polyclone antibodies are produced by sensitizing mice with the specific virus to detect. If an inactivated and structurally complete virus is used, the mice will produce antibodies against virus proteins resulting in a high cross-reaction within the virus of the same genome as it is the case of DENV, YFV, ZIKV, SLV, WNV, etc. Monoclonal antibodies produced in hybridomas can eliminate or reduce cross-reactions (cell lines are able to produce antibodies against one or various virus epitopes) with bigger specificity. There are antibodies produced in hybridomas capable of identifying and differentiating flavivirus group, a general dengue virus (dengue complex), and to each dengue virus serotype (Figure 6) [5, 6].
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Figure 6.
Indirect immunofluorescence test performed on C6/36 cells. In (A), uninfected red cells are observed and in (B), infected green cells are observed (a photo taken on April 24, 2018 in the serology laboratory with the authorization of the U.S. Naval Medical Research Unit Six authorization (NAMRU-6)).
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2.4.3.5. Rapid tests
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There are rapid tests based on lateral flow chromatographic immune assays produced by different laboratories. Proteins such as NS1, IgM, IgG in serum, blood or plasma samples can be detected through these tests, and they can simultaneously identify antibodies or proteins produced by ZIKV, DENV, and CHIKV. Assessing four rapid tests for NS1, its sensibility was in 71.9–79.1% range and its specificity in 95–100% antibodies compared to the viral isolation. These tests have the benefit of being cost effective, not requiring qualified personnel to be done nor using sophisticated equipment. Within its limitations, it is not possible to identify the circulating serotype in a virus, the band intensity is not related to the antibody titers nor the actual NS1 antigen in the sample, cross-reactions with other flavivirus are common, a negative result in these tests does not exclude that the patient has been exposed to the virus, and some samples present high titers of rheumatoid factor affecting the results. The positive samples for these results should be verified with other alternative methods [28].
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2.5. The animal models for dengue virus
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Studies to evaluate antivirals against dengue, vaccines, plant extracts, etc. mainly use the mouse model and nonhuman primates (NHPs). However, each of them presents a series of constraints that impair research developments. The infections of the mouse model are used for pre-clinical development of vaccines. In this model, a neurotropic disease can occur; however, this does not usually happen in humans. Some mice like C57BL/6, BALB/c and A/J enable viral replication, but A/J and BALB/c mice develop paralysis. Some studies show that C57BL/6 mice can have hemorrhages when being infected with a DENV2 strain 16681 using a virus with a titer of 3 × 109 PFU/mL. Moreover, an infection and endothelial cell damage as well as hemorrhages in tissues can occur without showing signs of disease. The DENV replication in mice is low, but suckling mice inoculated by an intracranial via at high DENV doses can induce neurological illnesses and paralysis that is used to measure the effectiveness of the vaccines. They can also be used to test a virus neurovirulence or an attenuation to produce vaccines. NHPs are used to research an immune reaction against DENV, an evaluation of candidates’ vaccines, a replication kinetic, etc. This model has a major constraint because it does not produce signs of clinical disease. Nonetheless, DENV can infect some cells in the body. An inoculation with 105 PFU DENV concentrations enables a lower viral replication in humans, and it is restricted to lymphoid-rich tissues producing lymphadenopathy, lymphocytosis, and leukopenia. Rhesus macaques can produce antibodies against DENV and a similar viral load to the humans. The inoculation of high titer DENV via intravenous in rhesus macaques can produce hemorrhage. The physiology of pigs is similar to the human one. Yucatan miniature swine models present an immunological and physiological result similar to the human ones. It is known that it is susceptible to a flavivirus such as the Japanese encephalitis, YFV, and Murray valley encephalitis. Studies about infected porcine models administered subcutaneously with DENV-1 (107 PFU) resulting to developed viremia, and IgM and IgG antibodies without symptoms are carried out. The secondary infection with the same serotype produced extensive macular and papular rashes similar to the ones affecting humans. When infecting the swine model with a DENV-1 intravenous line, a rash skin and dermal edemas appeared on the animal [36, 37].
\n
\n
\n
2.6. The future of laboratory tests and its connection with dengue studies
\n
Throughout a dengue research, the use of laboratory tests play a fundamental role in identifying the virus (serotype, genotype and lineage), its genetic material, viral proteins, the presence of antibodies against the virus or assessing the patient’s condition, and for instance, hematocrit, platelet count, white blood cell count, blood count, etc. together with patient’s signs and symptoms and some epidemiological criteria, it allows categorizing the disease for dengue with or without warning signs or severe dengue. This classification assists in deciding what therapy to choose and preventing from a severe dengue development. Besides the above mentioned techniques in this chapter, there are laboratory techniques which are not commonly used at present because they are expensive and/or they require sophisticated equipment but they could be used for DENV studies. Among them, there is the transmission electron microscopy (TEM) which is a gold standard technique for the absolute quantification of particles. However, it does not allow differentiating an infectious virus from a noninfectious one. The high performance liquid chromatography (HPLC) where the virus load is quantified through the UV analysis of fractions produced during HPLC. Flow cytometry (FC) can be used to quantify viral proteins being present on the surface of the infected cells. The next-generation whole genome sequencing is the most advanced sequencing technology which allows learning the complete and detailed genome sequence of an organism in a short period of time (days), though its cost is still quite higher to some researches [27, 38].
\n
Dengue researches in the future will try to respond to different problems, needs, and gaps in knowledge like:
\n
The production and improvement of the vaccine against DENV like Dengvaxia® (CYD-TDV), produced by Sanofi Pasteur, is a prophylactic, tetravalent, live attenuated recombinant viral vaccine which uses a 3-dose vaccination schedule, and it is recommended for people ranged from 9 to 45, or 9 to 60 year old (depending on the license) [39]. Nonetheless, it is necessary to continue with searches to develop a vaccine which can be used from the first year of life enabling to achieve the maximum immunity with a single dose and can be used in different endemic areas obtaining the same immunity level regardless the disease prevalence.
\n
Today, it is acknowledged that the immunity against dengue after a natural infection can be for a lifetime [5]; however, some studies indicate that a dengue reinfection may occur under certain conditions [40].
\n
The relation between chronic diseases and dengue has been studied as risk factors in order to determine the severity of dengue disease in individuals. In recent decades, the increase of chronic diseases and being one of the main causes of death in today’s world require to continue and deepen the study of these diseases as well as its association with the dengue disease [5].
\n
In endemic areas, dengue studies in blood banking are essential especially in epidemic outbreaks so that when there is a large amount of asymptomatic DENV, the virus may be transmitted through blood transfusions [41].
\n
Individuals with inapparent dengue virus infection are considered dead-end hosts for transmission because they do not present high enough levels of viremia to infect mosquitoes; nonetheless, some studies show that asymptomatic people for dengue can transmit the virus to mosquitoes when bitten, although having a lower average of viremia, increasing the risk of disease spread in different areas [42]. Therefore, it is important to carry out studies with individuals presenting inapparent dengue virus infections aimed at breaking the transmission cycle and avoiding disease spread.
\n
Wildlife mammals with genetic material and antibody against DENV like bats have been found, but their participation in the transmission cycle have not been approved yet [43].
\n
Because of not having found an animal model able to replicate the dengue disease, it is necessary to continue searching for different animal models which can support the study of this disease so that the use of humanized mice becomes an attractive area of research [36, 37].
\n
The development of new drugs and the vegetal compound assessment with antiviral activity against DENV are needed because there is no specific treatment for this disease yet.
\n
The use of mathematical models to predict the pace of dengue spread based on clinical data and laboratory results may support the prognosis of this disease.
\n
DENV has a type of RNA genome, with a dependent RNA polymerase without a corrective activity being able to accumulate genetic material changes leading to a false positive increase in PCR tests [11]. Thus, it is required to evaluate the necessity of primer redesigning which allows detecting a larger amount of DENV circulating strains worldwide as well as its standardization and assessment.
\n
DENV coinfections along with other microorganisms circulating in the same endemic areas like DENV/plasmodium Sp. may be frequent depending on the disease prevalence in the area, especially if they are transmitted by the same vector in cases like DENV, CHIKV and ZIKV. Some studies have shown infections of Aedes aegypti with MAYV causing a concern about a possible natural transmission of such disease in urban areas [22, 44].
\n
\n
\n
\n
3. Conclusion(s)
\n
Dengue is still a leading public health problem. The diagnostic tests must improve and be standardized in all research and diagnostic laboratories with the use of technology. This will allow having comparable results in different studies and reference centers that contribute to the knowledge development needed to understand transmission mechanisms and DENV propagation and setting preventive and appropriate control measures as well as developing new vaccines and antivirals helping to control this disease.
\n
\n
Acknowledgments
\n
I would like to thank to the U.S. Naval Medical Research Unit Six (NAMRU-6) and the virology and molecular biology laboratory of the Faculty of Biology at the National University of San Marcos for contributing with the photos of the laboratory tests mentioned in this chapter.
\n
Conflict of interest
The authors declare no conflict of interest.
\n
Disclaimer
\n
The views expressed in this laboratory test used in the diagnostic and research of dengue virus: present and future are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.
\n
\n',keywords:"dengue, arbovirus, flavivirus, laboratory test, diagnostic test",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/63211.pdf",chapterXML:"https://mts.intechopen.com/source/xml/63211.xml",downloadPdfUrl:"/chapter/pdf-download/63211",previewPdfUrl:"/chapter/pdf-preview/63211",totalDownloads:1293,totalViews:516,totalCrossrefCites:1,totalDimensionsCites:2,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:74,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"March 27th 2018",dateReviewed:"July 26th 2018",datePrePublished:"November 5th 2018",datePublished:"January 30th 2019",dateFinished:"August 24th 2018",readingETA:"0",abstract:"Dengue is a significant public health problem. There are four dengue virus serotypes identified; however, its diagnosis is difficult due to the existence of many viruses, bacteria, and parasites producing the same clinical presentation, being present in the same geographical area and even producing coinfections. Therefore, determining whether a person has, had, or is infected with dengue virus is of great importance. In order to do so, direct and indirect laboratory tests have been developed to identify the virus or part of its structure that generally detects the antibody response. These techniques are used for diagnosis, epidemiological studies, monitoring, assessment and production of vaccines and antivirals, etc. They range from the use of cell cultures, animal models, inoculation by insects, and serology tests to the use of detection molecular tests and quantification of genetic material that are described in this chapter herein, a brief explanation of this methodology, its strengths and weaknesses, and its application in the dengue research.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/63211",risUrl:"/chapter/ris/63211",book:{id:"7107",slug:"dengue-fever-a-resilient-threat-in-the-face-of-innovation"},signatures:"Juan Samuel Sulca Herencia",authors:[{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",fullName:"Juan Sulca",slug:"juan-sulca",email:"juan_sulca@hotmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Laboratory test",level:"1"},{id:"sec_2_2",title:"2.1. Characteristics of diagnostic tests",level:"2"},{id:"sec_3_2",title:"2.2. Biological samples for dengue studies",level:"2"},{id:"sec_4_2",title:"2.3. Primary and secondary dengue infections and dengue diagnostic",level:"2"},{id:"sec_5_2",title:"2.4. Laboratory test",level:"2"},{id:"sec_5_3",title:"2.4.1. Direct detection methods",level:"3"},{id:"sec_5_4",title:"2.4.1.1. Viral RNA extraction",level:"4"},{id:"sec_6_4",title:"2.4.1.2. Reverse transcription polymerase chain reaction (RT-PCR)",level:"4"},{id:"sec_7_4",title:"2.4.1.3. RT-PCR multiplex to DENV and different microorganism identifications",level:"4"},{id:"sec_8_4",title:"2.4.1.4. Real-time PCR",level:"4"},{id:"sec_9_4",title:"2.4.1.5. Viral isolation in cell lines",level:"4"},{id:"sec_10_4",title:"2.4.1.6. Plaque assay",level:"4"},{id:"sec_11_4",title:"2.4.1.7. Fluorescent focus assay",level:"4"},{id:"sec_12_4",title:"2.4.1.8. Viral isolation in nursing mice",level:"4"},{id:"sec_13_4",title:"2.4.1.9. Inoculation in mosquitoes",level:"4"},{id:"sec_14_4",title:"2.4.1.10. Automated equipment for virus counting",level:"4"},{id:"sec_15_4",title:"2.4.1.11. Enzyme-linked immunosorbent assay (ELISA) for NS1",level:"4"},{id:"sec_17_3",title:"2.4.2. Indirect methods",level:"3"},{id:"sec_17_4",title:"2.4.2.1. IgM ELISA",level:"4"},{id:"sec_18_4",title:"2.4.2.2. IgG ELISA",level:"4"},{id:"sec_19_4",title:"2.4.2.3. IgG inhibition ELISA tests",level:"4"},{id:"sec_20_4",title:"2.4.2.4. IgA ELISA test",level:"4"},{id:"sec_22_3",title:"2.4.3. Neutralization test",level:"3"},{id:"sec_22_4",title:"2.4.3.1. Plaque reduction neutralization test (PRNT)",level:"4"},{id:"sec_23_4",title:"2.4.3.2. Focus reduction neutralization test (FRNT)",level:"4"},{id:"sec_24_4",title:"2.4.3.3. Microneutralization-ELISA",level:"4"},{id:"sec_25_4",title:"2.4.3.4. Immunofluorescence test",level:"4"},{id:"sec_26_4",title:"2.4.3.5. Rapid tests",level:"4"},{id:"sec_29_2",title:"2.5. The animal models for dengue virus",level:"2"},{id:"sec_30_2",title:"2.6. The future of laboratory tests and its connection with dengue studies",level:"2"},{id:"sec_32",title:"3. Conclusion(s)",level:"1"},{id:"sec_33",title:"Acknowledgments",level:"1"},{id:"sec_36",title:"Conflict of interest",level:"1"},{id:"sec_33",title:"Disclaimer",level:"1"}],chapterReferences:[{id:"B1",body:'World Health Organization. Dengue and Severe Dengue [Internet]. 2018. Available from: http://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue [Accessed: 17-05-2018]\n'},{id:"B2",body:'Forshey BM, Guevara C, Laguna-Torres VA, Cespedes M, Vargas J, et al. Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007. PLoS Neglected Tropical Diseases. 2010;4(8):e787. DOI: 10.1371/journal.pntd.0000787\n'},{id:"B3",body:'Gordis L. Epidemiology. 5th ed. Elsevier Saunders: Barcelona; 2014. p. 391\n'},{id:"B4",body:'Donis JH. Evaluación de la validez y confiabilidad de una prueba diagnóstica. Avances en Biomedicina. 2012;1(2):73-81. Available from: http://www.redalyc.org/articulo.oa?id=331328015005\n\n'},{id:"B5",body:'WHO. Dengue guias para el diagnóstico, tratamiento, prevención y control [Internet]. Ginebra: World Health Organization; 2009 [cited 17 May 2018]. Available from: http://www.who.int/iris/handle/10665/44504\n\n'},{id:"B6",body:'Instituto de Medicina Tropical Pedro Kourí. Técnicas de laboratorio para el diagnóstico y la caracterización del virus dengue. La Habana: Instituto de Medicina Tropical Pedro Kourí; 2013. p. 128\n'},{id:"B7",body:'Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, et al. Evaluation of diagnostic tests: Dengue. Nature Reviews Microbiology. 2010;8:30-38. DOI: 10.1038/nrmicro2459\n'},{id:"B8",body:'Tang KF, Ooi EE. Diagnosis of dengue: An update. Expert Review of Anti-Infective Therapy. 2012;10(8):895-907. 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Poster 1445\n'},{id:"B14",body:'Saengsawang J, Nathalang O, Kamonsil M, Watanaveeradej V. Comparison of two commercial real-time PCR assays for detection of dengue virus in patient serum samples. Journal of Clinical Microbiology. 2014;52(10):3781-3783\n'},{id:"B15",body:'Waggoner JJ, Abeynayake J, Sahoo MK, Gresh L, Tellez Y, Gonzalez K, et al. Comparison of the FDA-approved CDC DENV-1-4 real-time reverse transcription-PCR with a laboratory-developed assay for dengue virus detection and serotyping. Journal of Clinical Microbiology. 2013;51(10):3418-3420\n'},{id:"B16",body:'Centers for Disease Control and Prevention. Ensayo de RT-PCR en tiempo real para DENV-1-4 de los CDC. Puerto Rico: Centers for Disease Control and Prevention; 2013. p. 56\n'},{id:"B17",body:'Special Programme For Research and Training in Tropical Diseases. Dengue Diagnostic: Proceedings of an International Workshop. ENICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR); 4-6 October 2004. Geneva: WHO/TDR; 2005. (TDR/IRM/DIAG/DEN/05.1)\n'},{id:"B18",body:'Chosewood LC, Wilson DE. Biosafety in Microbiological and Biomedical Laboratories. U.S. Department of Health and Human Services. 5th ed. HHS Publication; 2009. p. 415\n'},{id:"B19",body:'Caceda ER, Kochel TJ. Application of modified shell vial culture procedure for arbovirus detection. PLoS One. 2007;2:e1034\n'},{id:"B20",body:'Rodríguez R, Álvarez M, Guzmán MG, Morier L, Kourí G. Comparison of rapid centrifugation assay with conventional tissue culture method for isolation of dengue 2 virus in C6/36-HT cells. Journal of Clinical Microbiology. 2000;38:3508-3510\n'},{id:"B21",body:'Palomino M, Gutierrez V, Salas R. Estandarización del método de centrifugación en placa para el aislamiento del virus Dengue. 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Presented at VII- Sir Dorabji Tata Symposium Arthropod Borne Viral Infections; March 2007\n'},{id:"B27",body:'Rossi CA et al. Evaluation of viroCyt(R) virus counter for rapid filovirus quantitation. Viruses. 2015;7(3):857-872. DOI: 10.3390/v7030857\n'},{id:"B28",body:'Pal S, Dauner AL, Mitra I, Forshey BM, Garcia P, Morrison AC, et al. Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples. PLoS One. 2014;9(11):e113411. DOI: 10.1371/ journal.pone.0113411\n'},{id:"B29",body:'Yap G, Sil BK, Ng L-C. Use of saliva for early dengue diagnosis. Lopes da Fonseca BA, editor. PLoS Neglected Tropical Diseases. 2011;5:e1046\n'},{id:"B30",body:'Kochel TJ, Watts DM, Halstead SB, Hayes CG, Espinoza A, et al. Effect of dengue-1 antibodies on American dengue-2 viral infection and dengue hemorrhagic fever. Lancet. 2002;360(9329):310-312\n'},{id:"B31",body:'Rainwater-Lovett K, Rodriguez-Barraquer I, Cummings DA, Lessler J. Variation in dengue virus plaque reduction neutralization testing: Systematic review and pooled analysis. BMC Infectious Diseases. 2012;12:233\n'},{id:"B32",body:'Roehrig JT, Hombach J, Barrett AD. Guidelines for plaque-reduction neutralization testing of human antibodies to dengue viruses. Viral Immunology. 2008;21:123-132\n'},{id:"B33",body:'Ngwe Tun MM, Muta Y, Inoue S, Morita K. Persistence of neutralizing antibody against dengue virus 2 after 70 years from infection in Nagasaki. BioResources. 2016;5:188-191\n'},{id:"B34",body:'Fournier C, Duverlie G, Francois C, Schnuriger A, Dedeurwaerder S, Brochot E, Capron D, Wychowski C, Thibault V, Castelain S. A focus reduction neutralization assay for hepatitis C virus neutralizing antibodies. Virology Journal. 2007;4:35. DOI: 10.1186/1743-422X-4-35\n'},{id:"B35",body:'Vorndam V, Beltran M. Enzyme-linked immunosorbent assay-format microneutralization test for dengue viruses. The American Journal of Tropical Medicine and Hygiene. 2002;66:208-212\n'},{id:"B36",body:'Zompi S, Harris E. Animal models of dengue virus infection. Viruses. 2012;4:62-82\n'},{id:"B37",body:'Na W, Yeom M, Choi I, Yook H, Song D. Animal models for dengue vaccine development and testing. Clinical and Experimental Vaccine Research. 2017;6(2):104\n'},{id:"B38",body:'White Paper Provided by Virocyt: An Overview of Virus Quantification Techniques [Internet]. Vaccine Nation. 2018 [cited 19 June 2018]. Available from: http://www.vaccinenation.org/2013/05/07/white-paper-virocyt-overview-virus-quantification-techniques/\n\n'},{id:"B39",body:'World Health Organization. Dengue vaccine: WHO position paper—July 2016. Weekly Epidemiological Record. 2016;91:349-364. Available from: http://www.who.int/wer/2016/wer9130.pdf?ua=1\n\n'},{id:"B40",body:'Forshey BM, Reiner RC, Olkowski S, et al. Incomplete protection against dengue virus type 2 re-infection in Peru. PLoS Neglected Tropical Diseases. 2016;10(2):e0004398. DOI: 10.1371/journal.pntd.0004398\n'},{id:"B41",body:'Ashshi AM. The prevalence of dengue virus serotypes in asymptomatic blood donors reveals the emergence of serotype 4 in Saudi Arabia. Virology Journal. 2017;14:107\n'},{id:"B42",body:'Duong V, Lambrechts L, Paul R, Ly S, Lay R, Long K, et al. Asymptomatic humans transmit dengue virus to mosquitoes. Proceedings of the National Academy of Sciences. 2015;112(47):14688-14693\n'},{id:"B43",body:'Vicente-Santos A, Moreira-Soto A, Soto-Garita C, Chaverri L, Chaves A, Drexler J, et al. Neotropical bats that co-habit with humans function as dead-end hosts for dengue virus. PLoS Neglected Tropical Diseases. 2017;11(5):e0005537\n'},{id:"B44",body:'Long K, Tesh R, Higgs S, Hausser N, Thangamani S, Kochel T, et al. Experimental transmission of mayaro virus by Aedes aegypti. The American Journal of Tropical Medicine and Hygiene. 2011;85(4):750-757\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Juan Samuel Sulca Herencia",address:"juan.sulca4@unmsm.edu.pe",affiliation:'
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1. Introduction
As a common and complex skin condition (Section 1.1), the root causes of psoriasis begin inside our body [1], making it far more than just skin deep. The fact that psoriasis affects the skin’s hydration, barrier structure, function and integrity (Section 1.2) [2] means that a combination of several management strategies (Section 1.3) is usually required in order to alleviate associated symptoms [3, 4]. Topical moisturisers (Section 1.4) represent the first-line defence strategy that forms the backbone of psoriasis management by reducing and relieving both dryness and the associated itch-scratch cycle, enhancing skin hydration, and strengthening barrier function by influencing its subsequent repair and recovery [5, 6, 7] and thus, improving underlying psoriatic symptoms and overall quality of life (QoL) [2].
1.1 Psoriasis at a glance
Psoriasis is a chronic, inflammatory, non-contagious and relapsing skin condition with a strong genetic predisposition and autoimmune pathogenic traits [8]. While psoriasis can present at any age, it most commonly appears for the first time between the ages of 15 and 25 years, and then again between ages of 57 to 60 years [9], affecting both men and women equally [3, 10]. The worldwide prevalence is about 2–5% on average, but varies according to regions and ethnicities [3, 10]. In general, the higher or lower the latitude, the higher the prevalence; people from Asian and African countries are less prone to psoriasis than people from regions further from the equator such as Northern Europe, North America and Australia [10, 11].
The term ‘psoriasis’ encompasses several distinct clinical forms of the disease, the most common and well-known of which is psoriasis vulgaris, also known as plaque psoriasis. Given the ubiquity of psoriasis vulgaris relative to other forms of the disease, our focus in this chapter will be on this particular form.
The pathogenesis of psoriasis is multifactorial, with genetics being a primary contributor, especially in those with early onset of the disease. Many of the candidate genes are either involved in antigen presentation, immune cell signalling and activation, or skin barrier function, suggesting an intricate interplay between dendritic cells, T cells and the main skin cell type, known as keratinocytes [12, 13]. Several other factors can either initiate and/or exacerbate psoriasis flare-ups. These include: (a) trauma induced by various physical, chemical and inflammatory skin disruptions (e.g., abrasions, incisions, rubbing); (b) bacterial (e.g., Staphylococcus aureus) and viral infections; (c) the use of certain medications or drugs (e.g., lithium, blood pressure reducing medications); (d) poor lifestyle habits such as excessive alcohol consumption and smoking; and (e) stress [10, 13, 14].
Psoriasis manifests in several distinct clinical forms according to appearance and the body part affected but predominantly presents as well-demarcated salmon pink plaques (dry and piled up skin cells) and/or lesions with silvery-white scale, accompanied by skin tightness, itchiness, a burning sensation and, in severe cases, even bleeding [1, 3, 10, 13, 15]. These plaques typically appear in a symmetrical distribution and affect extensor areas such as the elbows, knees, lower back, limbs, the scalp, tips of the fingers and toes, palms and soles, the fingernails and toenails, and occasionally, the genitals [3, 10, 13, 14, 15]. Patients suffering from psoriasis are frequently categorised into two main groups: (1) mild or moderate psoriasis (most common category; affecting 3–10% of total body area) and (2) severe psoriasis (rare; affecting more than 10% of total body area). Such categorisation primarily depends on the following three aspects: (1) the clinical severity score (also known as Psoriasis Area Severity Index—PASI) of the plaques, which is an assessment tool based on the degree of plaque redness, thickness, itchiness and scaling; (2) the percentage of affected body surface area (BSA); and (3) patient QoL [13, 14, 16].
As alluded to in the introduction, psoriasis is not only a skin condition, it also involves multiple organ systems (e.g., cardiovascular, hepatic, respiratory and haematological) and people with psoriasis regularly display a broad spectrum of symptoms and significant co-existing conditions such as obesity, cardiovascular disease, non-alcoholic fatty liver disease, cancer, diabetes and metabolic syndrome, with rates being especially elevated in those with more severe psoriasis [1, 13]. For example, diabetic patients with psoriasis appear to be more likely to require pharmacological management and suffer from micro- and macrovascular diabetes complications than diabetic patients without psoriasis [17].
1.2 Skin barrier alterations in psoriasis
The barrier function of the skin resides in the outermost layer of the epidermis, known as the stratum corneum (SC) and is linked to the protein enriched corneocyte (dead keratinocytes lacking vital cellular organelles) layers and the intercellular membrane lipid matrix mostly composed of ceramides, cholesterol and free fatty acids [18, 19, 20, 21]. Corneocytes are continually and efficiently replaced to maintain skin hydration, flexibility and structural integrity, and to repair any perturbation and damage [21]. Continuous exposure to environmental insults such as harsh climatic conditions (e.g., extreme temperatures, wind) and chemicals (e.g., harsh detergents and soaps) can significantly impact the skin’s structural and functional properties, which in turn can cause acute or chronic damage of the skin barrier resulting in unfavourable changes in skin morphology and physiology over time [19, 20, 22, 23, 24].
Skin dryness is a major underlying problem of the dysfunctional psoriatic skin barrier as it reflects an abnormal and defective desquamation (shedding) process, where corneocytes are shed as visible scales, causing the cosmetically unattractive rough texture associated with dry skin and excessive transepidermal water loss (TEWL), ultimately leading to discomfort and itchiness. Such compromised, dry and fragile skin that is unable to efficiently bind and hold water is also susceptible to the penetration of irritants, allergens and microorganisms that can result in irritation, inflammation and infection [3, 10, 13, 14, 15, 19, 20, 22, 23, 24].
Normally, healthy skin cells mature and are shed from the skin’s surface every 28 to 30 days [25]. However, when psoriasis develops, these skin cells mature much faster, usually in 3 to 6 days, and subsequently move to the skin surface. Due to such a rapid turnover of skin cells, it is possible that even live and healthy cells can reach the surface and accumulate with the dead cells. Instead of being shed, the skin cells pile up, causing the development of thick plaques that are characteristic of psoriasis [14]. There are two main schools of thought as to the exact pathological process that leads to the development of such psoriatic plaques, however, neither of these can stand independently from each other. The first considers psoriasis primarily as an unregulated condition of excessive growth and regeneration of skin cells, characterised by abnormal keratinocyte differentiation and hyperproliferation. Such a problem is simply seen as a ‘fault’ of the epidermis and its keratinocytes [3, 14, 26]. The second considers psoriasis as an immune-mediated skin condition in which the excessive regeneration of skin cells is secondary to factors produced by the immune system, suggesting that the inflammatory mechanisms are immune-based and most likely initiated and maintained primarily by T cells found within the deeper layer of the skin, the dermis [14, 27, 28]. Given that keratinocytes, dendritic cells and activated T cells are all crucial to the development and persistence of psoriatic plaques, the pathophysiology of psoriasis cannot be explained by the role of a single cell type exclusively – it is likely a dynamic and complex interplay between those cell types. Furthermore, the contribution of each cell type is equally essential in different phases (e.g., initiation, formation, maintenance) of psoriatic alterations. Therefore, the exact sequence of events that lead to the development of psoriatic plaques remains unknown [28].
1.3 Management of psoriasis
Choosing the best management strategy for psoriasis can often be problematic and frustrating for both patients and healthcare professionals, and usually there are several factors to consider: the type, severity and localisation of the condition; the patient’s age and medical history; the impact the disease has on QoL; and the patient’s expected goals [1]. Before embarking on a management strategy, it is absolutely crucial to establish expectations and goals. The ‘ideal’ goal would be complete clearance of psoriatic plaques but this is currently not achievable in most patients. Thus, it is necessary to set a minimal target to allow modification of the management strategy if the target is not achieved within a set time [29]. In very basic terms, management for ‘generalised’ psoriasis follows a 1-2-3 step-ladder approach (Figure 1), starting with topical therapies (e.g., topical moisturisers) (Section 1.4) followed by phototherapy and then systemic medications that can include a range of oral drugs and small biologicals [1, 10, 30].
Figure 1.
Schematic of psoriasis 1-2-3 step-ladder management approach [1, 10, 30].
Topical therapy as monotherapy is useful in psoriasis patients with a mild to moderate condition. Topical moisturisers are also used as an adjuvant strategy for moderate to severe psoriasis that is concurrently treated with either phototherapy or systemic medications [10].
Phototherapy represents a second-line defence strategy in the management of psoriasis (Figure 1). It involves exposure of the psoriatic skin to ultraviolet (UV) radiation, which can decrease the appearance of plaques on the skin [10, 31]. Many types of phototherapy have been developed and used for the treatment of psoriasis over the last few decades. Broadband ultraviolet B light (BB-UVB, 290–320 nm) was the first such therapy developed, but was later replaced by narrowband ultraviolet B light (NB-UVB, 311 nm) as the latter is more effective than the former. The excimer laser/lamp of 308 nm was next invented and used as a monochromatic (single wavelength) UVB source for psoriasis treatment. The advantage of using excimer is its targeting ability that can spare unaffected skin while providing high doses targeted directly at psoriatic skin [32]. In short, phototherapy acts by causing cutaneous immuno-suppression, slowing down excessive growth of skin cells and altering cytokine expression [10, 31]. The drawbacks to phototherapy include the extensive time investment that is required; usually, three to five therapy sessions per week are needed, with the total therapy period ranging from approximately 2–3 months. Additionally, the response to phototherapy can vary from individual to individual, and there can be health implications to consider, such as the risk of skin cancer [10].
The decision to progress to systemic therapy (Figure 1) should be based not only on objective disease severity (where PASI ≥10% or QoL index ≥10% or BSA ≥10%; indicating more than 10% of involvement of the skin) [33], but also on social and psychological factors. The patient should understand the risks (e.g., higher risk and more adverse effects) (Figure 2) associated with systemic medications and should be allowed to determine whether the risk of therapy outweighs the benefit [10]. Indications for systemic therapy include widespread plaque psoriasis, erythrodermic (potentially life-threatening inflammation) psoriasis, or the need for repeated hospitalisation for topical therapy. The therapies for extensive and severe forms of psoriasis usually have long-term side effects [34].
Figure 2.
The order in which management strategies for psoriasis should be implemented [10, 34].
The order in which these management strategies are employed should progress in a stepwise fashion from lowest to highest risk (Figure 2), hence, the concept of a management ladder (Figure 1). The management strategy with the fewest side-effects (e.g., topical moisturisers) should be employed first. If this strategy proves ineffective or if the psoriasis is more severe, strategies with greater toxicity (e.g., phototherapy and systemic medications) may be initiated (Figure 2) [10, 34].
1.4 Topical moisturisers are the backbone of psoriasis management
Most topical moisturisers are specifically formulated to promote and maintain healthy skin, but may also serve to manage dry and itchy skin conditions such as psoriasis. Moisturisers are crucial to achieving a reduction in clinical signs of irritation and dryness, scaling and roughness, and a decrease in perceived feelings of tightness and itching [6, 20, 35, 36]. There are no specific rules on what is the best or ‘correct’ type of topical moisturiser to use. Since topical moisturisers are effectively used either as cosmetics (providing basic skin moisturisation) or therapeutics (e.g., managing psoriasis and preventing its exacerbation), the patients’ considerations will be mainly influenced by their personal preferences and lifestyle, and the nature and severity of their skin condition. Individual patient preferences and history may have an impact on the choice of moisturiser or moisturising base to use. A psoriasis patient presenting with severe dryness may benefit most from an occlusive ointment, yet their distaste for this particular base may dissuade them from using the product consistently, which could lead to increased morbidity. Conversely, while a lotion or cream may not provide as much hydration as an ointment, the patient’s preference for such ingredient base may improve compliance and, therefore, outcome. Patient expectation can also impact the choice or use of moisturiser. Despite wide management options being available, psoriasis is still an incurable disease, so expectation needs to be carefully managed. Complete psoriatic plaque clearance and relief from symptoms is often very difficult, if not impossible, a fact that can lead to patient dissatisfaction, as well as poor adherence and compliance with the current management options [10, 37].
The ‘ideal’ topical moisturiser (Figure 3) is one that the user prefers and will use regularly and liberally, keeping in mind that it should be: (a) cosmetically acceptable and elegant; (b) absorbed rapidly providing immediate skin moisturisation and achieve the intended cosmetic and/or therapeutic effect(s); (c) free from common irritants and allergens such as fragrance, colour and soap to minimise irritation and aggravation of the skin or underlying skin condition; and (d) non-sensitising, non-comedogenic (will not block pores), long-lasting [36, 38] and pH-balanced [39].
Figure 3.
The ‘ideal’ topical moisturiser characteristics [36, 38, 39, 40, 41].
The efficacy of topical moisturisers is related to its basic skin moisturisation and ‘conditioning’ benefits, as well as its therapeutic effects. This is achieved most commonly through a well-designed combination of fundamental and specialty ingredients and actives, formulated and delivered in a range of topical formulations (Section 3) [20, 40, 41].
2. The evolution of moisturisers: from fundamental ingredients to tailored products
The evolution of topical moisturisers is basically equivalent to an odyssey from fundamental ingredients (e.g., emollients, humectants, occludents, excipients) [6, 35, 42] (Section 2.1) to specialty molecules (e.g., ceramides, Panthenol, nicotinamide) [6, 35] (Section 2.2) and functionally distinct actives (e.g., corticosteroids, tar-based ingredients, keratolytics) [43, 44] (Section 2.3). Therefore, understanding the interplay and synergism amongst different ingredients as well as being familiar with their ever expanding biophysical effects is essential to get a cosmetically acceptable and/or therapeutically stable tailored product (Section 3) with the desired impact on both healthy and diseased skin [6, 35].
2.1 Fundamental ingredients
Topical moisturisers usually contain, at a minimum, one or a combination of the key moisturising ingredients, namely emollients (e.g., dimethicone) (Section 2.1.1), humectants (e.g., glycerin) (Section 2.1.2) and occludents (e.g., petrolatum/petroleum jelly) (Section 2.1.3), as well as numerous excipients (e.g., penetration enhancers, preservatives, pH adjusters) to stabilise the formulation (Section 2.1.4). Additional ingredients often include selected specialty ingredients (Section 2.2) and actives (Section 2.3). Ingredient selection, and moisturiser composition and formulation are crucial considerations when choosing an appropriate moisturiser. Specifically for psoriasis, these considerations can determine whether the product will repair and strengthen or further deteriorate the psoriatic skin barrier [6, 35, 45].
2.1.1 Emollients
Emollients are used to improve the appearance and texture of skin by filling in the crevices between corneocytes. This contributes to increased softness, smoothness and suppleness of the skin and improves its overall appearance [42, 46, 47]. The most common types of emollients are silicones such as dimethicone, which is a hypoallergenic and non-comedogenic polymer and is used extensively in topical moisturisers. It exerts a protective effect on the skin by locking in moisture and decreasing TEWL [48]. Dimethicone’s low surface energy and highly flexible silicone polymer backbone allows for effective spreading on the skin and a pleasant skin feel. The physical and aesthetic properties of silicones can be controlled by varying the chain length and molecular weight of the polymer. As chain length increases, the viscosity of silicones also increases, and vice-versa. Low viscosity means that the silicone is able to spread quickly and easily while providing a light, silky skin feel, whereas higher viscosities enable silicones to form more persistent hydrophobic (water-repelling) films with good water barrier properties [49].
2.1.2 Humectants
Humectants are hygroscopic (water-attracting) substances that are able to increase the water content of the skin by enhancing water absorption from the underlying skin layers, namely the deeper epidermis and dermis. Humectants penetrate the SC readily and act like biological sponges that promote water retention in the skin [47]. In addition, humectants are also able to hydrate the SC by absorbing water from the external environment. As a consequence, the SC tends to have greater water content in areas in which humectants are localised [42, 46, 47].
Glycerin is the most widely-studied and used humectant. It is also an endogenous component of the human skin. Glycerin is transported from the dermis through the keratinocytes by a transmembrane water/glycerol transport protein, Aquaporin 3 (AQP3) [50, 51, 52], and its hygroscopic properties enable it to increase the water holding capacity of an impaired SC. Glycerin functions in a way similar to the skin’s own natural moisturising factor (NMF), which is an essential skin process responsible for appropriate SC hydration, barrier homeostasis, desquamation and plasticity. When used topically, glycerin protects the skin from irritant-associated skin conditions and accelerates recovery of irritated skin, while also improving overall skin hydration. Topical glycerin also helps barrier recovery through corneocyte desquamation regulation and is able to restore skin hydration at low usage levels (from as little as 2% v/v up to 10% v/v) [47, 52].
2.1.3 Occludents
Occludents are lipohilic (lipid-loving) substances that form a protective film on the skin and restrict TEWL, trapping water in the skin’s uppermost layers and protecting against moisture loss [42, 46, 47, 53]. The most commonly used occludent, petrolatum or petroleum jelly (a long, aliphatic/straight chain of hydrocarbons) [54], can enter the intercellular space of the SC and become part of its lipid structure to provide internal occlusion of the SC, resulting in an increased barrier to water loss. In this regard, petrolatum is often considered to be the most effective moisturising ingredient for dry skin [42, 46, 47, 53].
2.1.4 Excipients
Non-active ingredients, commonly termed excipients, are extensively used in the formulation of topical moisturisers and typically make up the majority (≥90%) of topical product content [41, 55]. By their physicochemical nature, different classes of excipients are used to enhance the functionality of active ingredients in therapeutic products, as well as to aid with formulation challenges. Excipients are often used to: (1) improve solubility to allow incorporation of an active; (2) control the release, penetration and permeation of an active; (3) improve the overall aesthetics of the product to increase patient compliance; (4) improve active and product stability; (5) prevent microbial growth and contamination (e.g., preservatives) and (6) balance the pH of water-based moisturisers, so that they are compatible with the skin’s naturally slightly acidic pH [41].
2.1.4.1 Penetration enhancers
Penetration enhancers are chemicals that readily disrupt the structure of the SC and are commonly used to facilitate active (drug) delivery. The cutaneous inflammation experienced by patients with psoriasis promotes hypersensitivity and also suppresses skin barrier function. Therefore, the effective delivery of anti-inflammatory actives such as corticosteroids, aided by appropriate penetration enhancers, can bring about a net improvement in the skin’s barrier function [41]. Many penetration enhancers, like propylene glycol, are also solvents, and so can be used alone or in combination with other penetration enhancers to help facilitate both the partitioning into and the passage through the SC. However, care must be taken when selecting and using chemical penetration enhancers since their excessive use can potentially lead to systemic absorption of the active [41, 56]. As such, a careful tradeoff must be made between delivering a therapeutic active dose and protecting the integrity of the skin barrier. Penetration enhancers composed of short chain fatty acids, such as propylene glycol, are thought to integrate into the hydrophilic regions of the packed SC lipids and increase the solubility of this domain for the permeant [41], yet at high concentrations (above 10%) they can irritate the skin [41, 57, 58]. In contrast, penetration enhancers composed of long chain fatty acids like oleic acid insert themselves between the hydrophobic lipid tails to increase the fluidity of the SC lipid bilayers [41].
2.1.4.2 Preservatives
Preservatives are essential components of water-based topical moisturiser formulations and skincare products in general, as they protect products from potentially harmful bacteria. Without preservatives, water-based products would have a very short shelf life and would, for the most part, have to be stored at lower temperatures [59, 60]. Parabens such as methyparaben and propylparaben are arguably the most commonly used preservative ingredients. They have antimicrobial efficacy against a broad spectrum of yeasts, moulds and bacteria, although they are most effective against gram-positive organisms such as S. aureus [61]. While parabens exact mechanism of action is not well understood, it is thought to involve the disruption of a pathogen’s cell membrane transport processes [62] and the inhibition of DNA/RNA synthesis [63] but it is generally believed that their inhibitory effects on membrane transport and mitochondrial functional processes are key to their antimicrobial actions [64]. The popularity of parabens is based on several advantages when compared to alternative preservatives, including their broad spectrum of antimicrobial activity, stability over a wide temperature and pH range, low degree of systemic toxicity, low frequency of sensitisation, sufficient water solubility, well documented safety record and their lack of odour, taste or colour [59, 60].
2.1.4.3 pH adjusters
In addition to the chemical stability of the ingredients and the formulation itself, pH is a crucial consideration for topical moisturisers. Not only is the absolute pH value important, but the buffer capacity is also crucial to the skin’s natural acid mantle. The buffer capacity describes the ability of a formulation to keep the pH value almost constant or as close to the skin’s natural pH as possible [65, 66]. This can be achieved by adding pH adjusters to the formulation [66]. The natural pH of the skin surface of most parts of the body is slightly acidic and in the range of pH 4.1–5.8 [66], a feature that can have significant impacts on how the skin reacts to the product. It is a generally accepted fact that the use of alkaline or non pH-balanced products such as soaps, cleansers and creams will lead to skin barrier impairment with a concomitant pH increase in both healthy and diseased skin. The duration of this increase in skin pH depends on skin condition, frequency of application and the composition of the product. Therefore, every skincare product is a potential skin surface pH modifier and the pH of such products must be adjusted to a physiological pH during its development [67]. Some of the most commonly used pH adjusters for topical moisturisers include aminomethyl propanol and citric acid. Aminomethyl propanol is a synthetically produced pH adjuster that is classed as an aliphatic alcohol. It is commonly used in topical formulations due to its safety profile when used in low concentrations [68, 69]. Citric acid is a weak alpha hydroxy acid (AHA) that is naturally occurring in plants and animals. The majority of citric acid comes from citrus fruits, like oranges, lemons, grapefruit and limes. When used and applied in small amounts, it serves as an effective pH adjuster [70].
2.2 Specialty/complimentary ingredients
The newest generation of topical moisturisers for psoriasis also routinely contains specialty or complimentary ingredients in addition to the fundamental moisturiser components detailed in Section 2.1. Common examples of such ingredients include: (1) ceramides that help to replenish the deficient lipids in psoriatic skin [71], (2) the versatile Panthenol (Pro-vitamin B5), which is a skin protectant with moisturising and anti-inflammatory properties [72, 73] and (3) the ‘wonder molecule’ nicotinamide (also known as niacinamide and Vitamin B3), which is one of the most widely used complimentary ingredients in topical moisturisers [74, 75].
2.2.1 Ceramides
Ceramides, alongside cholesterol and free fatty acids, are the predominant components of the SC and comprise 30–40% of the SC lipid matrix by mass. They are composed of long chain sphingoid bases (e.g., sphingosine) which are linked to long chain free fatty acids. Incorporating the skin’s naturally occurring ceramides such as ceramide I (ceramide EOP) and ceramide III (ceramide NP) in topical moisturisers can help to improve both healthy and psoriatic skin by replacing decreased or even depleted ceramide levels [76]. A functional SC plays an indispensable role in ensuring the skin’s flexibility and structural integrity. The ordered alignment and organisation of the lipid bilayers within the SC forms a closed system to prevent TEWL in psoriatic plaques and makes the SC more impermeable. Therefore, even a subtle change or disturbance in the amount, physicochemical characteristics and organisation of the SC ceramides can potentially initiate and/or exacerbate psoriasis [71, 77].
2.2.2 Panthenol
Panthenol is a biologically active component of the B vitamin-complex, which is a basic component of the skin, hair and nails. When applied topically, Panthenol is efficiently absorbed into the epidermis and quickly converted into pantothenic acid, which is then converted to Acetyl Coenzyme-A (Acetyl CoA). Acetyl CoA is an essential mediator of many biochemical reactions within skin cells, and is necessary for optimal energy levels, barrier function, moisturisation, elasticity and strength [72, 73]. Furthermore, Panthenol can act as both an emollient and a humectant. As an emollient, it can help seal cracks in the skin, keeping water locked in, which in turn contributes to skin softness and smoothness. As a humectant, it can bind to and hold water effectively, reducing the amount of TEWL through the skin and helping it maintain moisture, softness and elasticity [72, 73, 78].
2.2.3 Nicotinamide
Nicotinamide, which easily penetrates the skin, is fast becoming a ubiquitous topical skincare ingredient in a range of moisturiser formulations. A number of clinical trials [79, 80, 81] show that the concentration of topical nicotinamide products can go up to 10%, but desired effects can be achieved with concentrations as low as 2–5% [79]. Nicotinamide provides a long list of skin care benefits with its use, including its ability to: (1) support the skin barrier structure and function by facilitating the formation of ceramides and keratin [74, 75]; (2) improve the skin’s tone and texture [82]; and (3) boost the effectiveness of moisturisers in general [75]. For example, when formulated in a combination with glycerin, a nicotinamide-containing moisturiser can very effectively improve the integrity of the SC and thus reduce skin dryness over time [75, 83]. In addition, nicotinamide has also been shown to have anti-inflammatory and antioxidant properties, the latter of which may help to reduce the harmful effects of UV radiation, photoageing and oxidative stress [84]. The appropriate concentration of topical nicotinamide for each individual may depend on their skin type and condition, keeping in mind that in some instances, high levels of nicotinamide can cause an allergic reaction for people susceptible to skin allergies [85].
2.3 Active ingredients
Alongside moisturisers, topical therapeutic products for psoriasis that contain active ingredients can also utilise both the fundamental (Section 2.1) and specialty (Section 2.2) ingredients to compliment the active component of the product or provide additional skin conditioning benefits. Common examples of actives indicated for the management of psoriasis include corticosteroids (e.g., hydrocortisone, clobetasone butyrate, mometasone furoate) (Section 2.3.1), tar-based actives (e.g., coal tar, pine tar) (Section 2.3.2) and keratolytics (e.g., salicylic acid) (Section 2.3.3). While these active ingredients are included to treat specific symptoms or characteristics of psoriasis such as inflammation, itch and plaque build-up, the use of a moisturising base can help to dramatically improve patient outcomes [6, 35]. While non-active moisturisers containing only fundamental ingredients are an important adjuvant therapy of classical psoriasis treatment modalities and used as supportive treatment in relapse-free phases [6, 35, 50], a moisturising base containing a topical corticosteroid will be able to not only manage the inflammation associated with psoriasis but also reduce the dryness and itch, and the accompanying scratch response that can significantly worsen disease morbidity [86].
2.3.1 Corticosteroids
Corticosteroids play a key role in the management of psoriasis. In this context, their mechanism of action involves the reduction of skin redness and the expression of anti-inflammatory mediators, as well as achieving an improvement and/or clearance of psoriatic plaques (Figure 4) [87]. These effects are exerted via intracellular corticosteroid receptors, which regulate gene transcription, including several that code for pro-inflammatory mediators. Topical corticosteroids are classified based on their skin vasoconstrictive activity, ranging in strength (potency): (a) super potent/ultrahigh (e.g., clobetasol propionate 0.05%); (b) high (e.g., mometasone furoate 0.1%); (c) moderate (medium) (e.g., betamethasone valerate 0.1%) [43, 86] and (d) low (e.g., hydrocortisone 1.0%) [43]. Choosing a corticosteroid with appropriate potency plus the appropriate topical formulation should be based on the disease severity and area affected, and the patient’s preference and age [88]. Lower potency corticosteroids such as hydrocortisone should be used on the face, intertriginous areas, and areas that are susceptible to steroid atrophy (e.g., forearms) [88, 89]. In adults, higher potency corticosteroids such as clobetasone butyrate and mometasone furoate are generally recommended as initial therapy [86, 88, 90]. Areas with thick, chronic plaques often require management with ultrahigh-potency corticosteroids. In numerous randomised clinical trials [4, 91, 92, 93, 94], different potency topical corticosteroids were effective and safe at 2 to 4 weeks in the management of mild to severe plaque psoriasis. Evidence on the efficacy of topical corticosteroids for the management of psoriasis varies greatly due to the differences in study designs, patient populations, corticosteroid class and concentration, adverse effects and outcomes [86].
Figure 4.
The choice of management strategy for psoriasis is driven by the skin’s dryness and itchiness; inflammation and redness; scaliness and thickness [6, 35, 45, 86, 87, 91, 99].
2.3.2 Tar-based actives
Tars represent one of the first therapies developed in the history of psoriasis [87]. In fact, pine tar has probably been produced in Scandinavia since the Iron Age and its use in medicine was first described by Hippocrates more than 2000 years ago in ancient Greece to treat a range of skin conditions because of its soothing and antiseptic properties [95]. Pine tar should not be confused with coal tar, which has been produced from coal for approximately a 100 years. Today, it is available in various formulations, from gels, to lotions and soap-free bars [96]. As an effective anti-inflammatory, antibacterial and antifungal substance, topical pine tar has been used in topical formulations for a long time to relieve itchiness and inflammation associated with a range of dry, itchy, flaky or inflamed skin conditions (Figure 4), particularly eczema and psoriasis, with minimal safety risk [96]. Furthermore, both coal tar and wood tars such as birch and beech are also available as topical anti-psoriatic ingredients in different topical formulations [87, 97]. Due to its inherent chemical composition and complexity [98], the mechanism of action of coal tar is not well understood, but it likely suppresses DNA synthesis and reduces keratinocyte proliferation. Coal tar is often used as either a monotherapy or in combination with other management strategies [87, 97]. Pine tar is thought to exert its effect by reducing DNA synthesis and mitotic (cell division) activity, which promotes a return to normal keratin development [96]. Tar-based formulations are indicated for the management of chronic, stable forms of plaque-type psoriasis and scalp psoriasis, whereas their use might be limited in sensitive areas such as around the genitals due to their irritation potential [87].
2.3.3 Keratolytics
Keratolytics (Figure 4) such as salicylic acid are readily used as active ingredients in many topical formulations, but may have particular utility when it comes to psoriasis as the disease is characterised by a build-up of keratinocytes on the skin. Keratolytics promote the physiologic skin shedding process and also decrease cell-to-cell cohesion in the SC, in effect loosening the glue that keeps keratinocytes together [87, 99]. Salicylic acid has been shown to aid in the removal of excessive keratin in psoriatic plaques and to produce desquamation of the SC while being safe to use and not effecting qualitative or quantitative changes in the structure of the viable epidermis [100]. It is often used as either monotherapy or as part of combination therapy to reduce the size and scale of psoriatic plaques [15, 100]. Keratolytics have proven to be particularly effective in reducing psoriatic plaque thickness if prescribed several days prior starting a first-line treatment (i.e., corticosteroids) for localised psoriasis or in specific areas such as the scalp [87, 99].
3. The necessity of topical moisturiser formulation modality: lotion, gel, cream and ointment
While the specific ingredients used in topical moisturisers or active therapeutics containing moisturising ingredients are important to effectively manage psoriasis, it is equally important to consider the base used to ensure that the product functions as intended. The most common bases include lotions, gels, creams and ointments, and each is distinguished by unique composition and properties that can have significant impact on the cosmetic and/or therapeutic effects they exert on psoriatic skin (Figure 5). An important initial factor to consider is the skin’s dryness. Very dry skin will likely benefit from an occlusive ointment or cream to trap in moisture, often at the expense of product feel (and as a result, patient compliance) whereas mild to moderately dry skin can often be managed with a lotion or cream, which tend to be more appealing and thus may make for a product that is more readily used. In reality, patients often require more than one topical moisturiser formulation; a less greasy, cosmetically-acceptable product such as a lotion or light cream for use during the day and a heavier or greasier formulation such as an ointment or gel for night-time use [6, 35, 36].
Figure 5.
A range of basic blend and tailored blend topical moisturiser formulations: Lotions, gels, creams and ointments, each distinguished by its unique composition, ingredient combination, and cosmetic and/or therapeutic effects they exert on psoriatic skin, resulting in a range of skin benefits.
3.1 Combination of basic blend and tailored blend topical moisturisers for the management of psoriasis
The commonly used topical formulation blends, either basic or tailored (Figure 5), can provide efficacy through divergent pathways. As these formulation blends contain a unique combination of ingredients (Section 2) they can potentially act through different mechanisms. As a result, there is a scientific rationale for their use in the management of psoriasis, either individually or in combination. This rationale assumes that such formulation blends are selected on the basis of their individual mechanism of action and the biophysical effects they exert on psoriatic skin, which may offer the possibility of synergistic efficacy as well as a reduction in the occurrence of cosmetic problems and side effects (Figure 6) [99].
Figure 6.
Efficacy, relapse rate, side effects and cosmetic problems associated with the use of basic blend moisturisers that contain no actives, tailored blend moisturisers that contain actives such as keratolytics and tar-based actives (coal tar and/or pine tar), and therapeutics with moisturising ingredients and actives such as corticosteroids in the management of psoriasis. Scored on a scale from zero (0) to three (3): 0 denotes little or no change/effect; 3 denotes great and frequent change/effect [102].
Topical moisturiser formulation blends and topical therapeutics with moisturising bases (Figure 5) can be used in a deliberate sequence individually or in combination (and even with other management options such as phototherapy and systemic medications) with the aim of achieving initial efficacy for the management of psoriasis followed by a safe maintenance regimen. This management strategy maximises the efficacy of each product while helping to minimise relapse rate, cosmetic problems and long term side effects (Figure 6) [99, 101, 102].
Now, when we are familiar with a range of basic blend and tailored blend topical moisturiser formulations and their unique composition and ingredient combination (as explained above) (Figure 5), an example of a management strategy for psoriasis would be as follows: first, the use of a topical therapeutic with a moisturising base containing a topical steroid potent enough for the severity of the disease (e.g., hydrocortisone for mild, mometasone furoate for moderate to severe) or pine-tar active, at the maximum therapeutic dose, with the main aim of promptly controlling psoriasis flare-ups accompanied by redness and inflammation. This first step can then be followed by the use of a topical moisturiser formulation blend in which a well-tolerated ingredient such as a keratolytic is introduced to reduce psoriatic plaque thickness and scaling. Finally, by using a cosmetically beneficial basic topical moisturiser formulation, the patient can remain indefinitely on a maintenance regimen that aims for continuous hydration of the skin as well as improvements in skin suppleness, flexibility and strength, and the minimisation of dryness and itchiness (Figure 4).
While moisturisers are important tools in the management of psoriasis, their use comes with some challenges such as patient perspectives [10] as described in Section 1.4, and some general and more specific concerns regarding the development, uses and regulations of novel anti-psoriatic topical formulations [99]. These include the following amongst many others: (1) heterogeneity in psoriatic plaque thickness, (2) management of psoriasis in different groups of patients (e.g., elderly, pregnant women, children, immuno-compromised patients) requires a few specific care factors and considerations (e.g., prolonged use of topical corticosteroids may lead to thinning of the skin in elderly patients) [10], (3) the safety and efficacy of novel moisturisers when used in combination with existing and established therapies [99] and (4) regulatory requirements and classifications of topical moisturisers, be they cosmetic or therapeutic [103, 104].
4. Conclusions
Psoriasis is a chronic skin condition characterised primarily by dysfunctional skin barrier integrity, dry and itchy skin, and the development of scaly plaques. Being defined as a multifactorial skin condition caused by an interaction between various genetic and environmental factors, psoriasis requires a 1-2-3 step-ladder combination approach of therapeutics to treat the condition and topical moisturisers to alleviate the symptoms.
Therapeutics like topical corticosteroids are not moisturisers themselves, but benefit from having a moisturising base and fundamental and complimentary moisturising ingredients. Therefore, understanding the interplay and synergism amongst different ingredients as well as being familiar with their advantageous biophysical effects and potential adverse effects is essential to get a range of cosmetically acceptable and/or therapeutically stable products with desired impact on both healthy and psoriatic skin.
Topical moisturisers are a key part of psoriasis management and come in various formulations such as lotions, gels, creams and ointments. By using such formulations readily and frequently, the patient can remain on a daily maintenance regimen that aims for continuous hydration of the skin as well as improvements in skin’s functionality, structural strength, visual and tactile attributes as well as minimisation of dryness and itchiness.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"active, excipient, formulation modality, ingredient, management, basic moisturiser, tailored moisturiser, psoriatic plaque, skin barrier",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80041.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80041.xml",downloadPdfUrl:"/chapter/pdf-download/80041",previewPdfUrl:"/chapter/pdf-preview/80041",totalDownloads:68,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 29th 2021",dateReviewed:"December 10th 2021",datePrePublished:"February 4th 2022",datePublished:null,dateFinished:"January 15th 2022",readingETA:"0",abstract:"The aim of this chapter is to provide an overview of basic and tailored topical moisturisers and discuss how and why they form the backbone for the management of psoriasis. Our discussion begins by describing the main characteristics of psoriasis and by indicating how alterations in the skin’s integrity and barrier function contribute to the initial development of psoriasis and subsequent changes in psoriasis phenotype. Next, we address the evolution of topical moisturisers to ever more sophisticated and beneficial products, and describe the key biophysical effects exerted on the psoriatic skin by their active ingredients, as well as the myriad benefits offered by fundamental and specialty ingredients. Furthermore, we delineate how topical moisturiser formulation modalities can help to improve compromised skin barrier function and to alleviate the symptoms of psoriasis, cosmetically and/or therapeutically as well as discuss the associated concerns and challenges encountered along the way.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80041",risUrl:"/chapter/ris/80041",signatures:"Dalibor Mijaljica, Fabrizio Spada and Ian P. Harrison",book:{id:"11087",type:"book",title:"Psoriasis",subtitle:null,fullTitle:"Psoriasis",slug:null,publishedDate:null,bookSignature:"Associate Prof. Shahin Aghaei",coverURL:"https://cdn.intechopen.com/books/images_new/11087.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-376-4",printIsbn:"978-1-80355-375-7",pdfIsbn:"978-1-80355-377-1",isAvailableForWebshopOrdering:!0,editors:[{id:"64024",title:"Associate Prof.",name:"Shahin",middleName:null,surname:"Aghaei",slug:"shahin-aghaei",fullName:"Shahin Aghaei"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Psoriasis at a glance",level:"2"},{id:"sec_2_2",title:"1.2 Skin barrier alterations in psoriasis",level:"2"},{id:"sec_3_2",title:"1.3 Management of psoriasis",level:"2"},{id:"sec_4_2",title:"1.4 Topical moisturisers are the backbone of psoriasis management",level:"2"},{id:"sec_6",title:"2. The evolution of moisturisers: from fundamental ingredients to tailored products",level:"1"},{id:"sec_6_2",title:"2.1 Fundamental ingredients",level:"2"},{id:"sec_6_3",title:"2.1.1 Emollients",level:"3"},{id:"sec_7_3",title:"2.1.2 Humectants",level:"3"},{id:"sec_8_3",title:"2.1.3 Occludents",level:"3"},{id:"sec_9_3",title:"2.1.4 Excipients",level:"3"},{id:"sec_9_4",title:"2.1.4.1 Penetration enhancers",level:"4"},{id:"sec_10_4",title:"2.1.4.2 Preservatives",level:"4"},{id:"sec_11_4",title:"2.1.4.3 pH adjusters",level:"4"},{id:"sec_14_2",title:"2.2 Specialty/complimentary ingredients",level:"2"},{id:"sec_14_3",title:"2.2.1 Ceramides",level:"3"},{id:"sec_15_3",title:"2.2.2 Panthenol",level:"3"},{id:"sec_16_3",title:"2.2.3 Nicotinamide",level:"3"},{id:"sec_18_2",title:"2.3 Active ingredients",level:"2"},{id:"sec_18_3",title:"2.3.1 Corticosteroids",level:"3"},{id:"sec_19_3",title:"2.3.2 Tar-based actives",level:"3"},{id:"sec_20_3",title:"2.3.3 Keratolytics",level:"3"},{id:"sec_23",title:"3. The necessity of topical moisturiser formulation modality: lotion, gel, cream and ointment",level:"1"},{id:"sec_23_2",title:"3.1 Combination of basic blend and tailored blend topical moisturisers for the management of psoriasis",level:"2"},{id:"sec_25",title:"4. Conclusions",level:"1"},{id:"sec_29",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Augustin M, Alvaro-Gracia JM, Bagot M, Hillmann O, van de Kerkhof PC, Kobelt G, et al. A framework for improving the quality of care for people with psoriasis. Journal of the European Academy of Dermatology and Venereology. 2012;26(4):1-16. DOI: 10.1111/j.1468-3083.2012.04576.x'},{id:"B2",body:'Maroto-Morales D, Montero-Vilchez T, Arias-Santiago S. Study of skin barrier function in psoriasis: The impact of emollients. Life (Basel). 2021;11(7):651. DOI: 10.3390/life11070651'},{id:"B3",body:'Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. International Journal of Molecular Sciences. 2019;20(6):1475. 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Department of Scientific Affairs, Ego Pharmaceuticals Pty Ltd, Braeside, Victoria, Australia
Department of Scientific Affairs, Ego Pharmaceuticals Pty Ltd, Braeside, Victoria, Australia
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Does your institution already have a budget for covering Open Access publication costs?
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Randomized Controlled Trials (RCT) and Real World Evidence (RWE) studies resulted in recent Statements of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) in the year 2020. Case reports and studies of a single-centre in Czech Republic are reported. The authors demonstrate the impact of (1) multiple doses of rapid insulin, (2) multiple doses of rapid or ultrarapid insulin analogs (3) continuous subcutaneous insulin infusion (CSII) (4) incretin receptor agonists, (5) fixed combination of insulin degludec with liraglutide (IDegLira) and (6) SGLT2 inhibitor dapagliflozin, on plasma glucose concentration, HbA1c, body mass and patient satisfaction. The importance of therapeutic patients’ education and technology (personal glucometers, continuous/flash glucose monitors, insulin pens/pumps) is emphasized. Most of the observations were already published. Hence, individually adopted education, lifstyle, technical equipment, incretin receptor agonists and/or metformin and/or gliflozins and/or insulin analogs appear to be the core of an effective pathophysiologic approach. Scientific conclusions from RCTs, RWE trials and own clinical case reports may prevail over clinical inertia and induce early implementation of effective methods into routine T2D treatment.",book:{id:"9517",slug:"type-2-diabetes-from-pathophysiology-to-cyber-systems",title:"Type 2 Diabetes",fullTitle:"Type 2 Diabetes - From Pathophysiology to Cyber Systems"},signatures:"Rudolf Chlup, Richard Kaňa, Lada Hanáčková, Hana Zálešáková and Blanka Doubravová",authors:[{id:"278357",title:"Prof.",name:"Rudolf",middleName:null,surname:"Chlup",slug:"rudolf-chlup",fullName:"Rudolf Chlup"},{id:"346119",title:"Dr.",name:"Richard",middleName:null,surname:"Kaňa",slug:"richard-kana",fullName:"Richard Kaňa"},{id:"346120",title:"BSc.",name:"Lada",middleName:null,surname:"Hanáčková",slug:"lada-hanackova",fullName:"Lada Hanáčková"},{id:"346121",title:"BSc.",name:"Hana",middleName:null,surname:"Zálešáková",slug:"hana-zalesakova",fullName:"Hana Zálešáková"},{id:"346122",title:"Dr.",name:"Blanka",middleName:null,surname:"Doubravová",slug:"blanka-doubravova",fullName:"Blanka Doubravová"}]},{id:"61064",title:"Secretions of Human Salivary Gland",slug:"secretions-of-human-salivary-gland",totalDownloads:2766,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"The salivary glands play an important role in our body by the virtue of its ability to secrete saliva. Saliva has a role to play in maintaining the health of the oral cavity and for carrying out physiological functions like mastication, taste perception, speech etc. It also acts as a mirror to the systemic status of an individual owing to its ability to act as a diagnostic fluid for detecting a number of conditions and diseases. Saliva is a potential noninvasive diagnostic fluid for detection of a number of biomarkers of disease and health. Advancement in diagnostic methods has helped in identifying biomarkers of disease in saliva. In order to understand and diagnose pathological changes, a thorough understanding of the salivary gland anatomy, physiology and regulation of its secretion is warranted. This chapter aims to provide the basic understanding of the secretions of saliva.",book:{id:"6246",slug:"salivary-glands-new-approaches-in-diagnostics-and-treatment",title:"Salivary Glands",fullTitle:"Salivary Glands - New Approaches in Diagnostics and Treatment"},signatures:"Anahita Punj",authors:[{id:"226076",title:"Dr.",name:"Anahita",middleName:null,surname:"Punj",slug:"anahita-punj",fullName:"Anahita Punj"}]},{id:"63301",title:"Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake",slug:"role-of-pi3k-akt-pathway-in-insulin-mediated-glucose-uptake",totalDownloads:3541,totalCrossrefCites:11,totalDimensionsCites:27,abstract:"Glucose uptake is regulated by several mechanisms, where insulin plays the most prominent role. This powerful anabolic hormone regulates the transport of glucose into the cell through translocation of glucose transporter from an intracellular pool to the plasma membrane mainly in metabolically active tissues like skeletal muscles, adipose tissue, or liver (GLUT4). This translocation occurs through multiple steps of PI3K/AKT signaling pathway. In this chapter, we will focus on molecular events leading to GLUT4 translocation, starting with activation of insulin receptors through signaling cascade involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) and finally, the action of their effectors. We will present regulatory mechanisms and modulators of insulin-mediated glucose uptake.",book:{id:"7061",slug:"blood-glucose-levels",title:"Blood Glucose Levels",fullTitle:"Blood Glucose Levels"},signatures:"Ewa Świderska, Justyna Strycharz, Adam Wróblewski, Janusz Szemraj, Józef Drzewoski and Agnieszka Śliwińska",authors:null},{id:"70711",title:"Fetal Growth Restriction",slug:"fetal-growth-restriction",totalDownloads:3104,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Fetal growth defect is classified into intrauterine growth restriction (IUGR) and small-for-gestational-age (SGA) fetus based on the estimated fetal weight percentile and Doppler hemodynamic parameters. IUGR pathophysiology and etiology are complex and diverse, highlighting placental insufficiency as a paradigm, which explains its association with other entities of great clinical importance such as preeclampsia. The poor long- and short-term perinatal and postnatal results associated with this context make it necessary to establish an early diagnosis and a therapeutic strategy, which can be challenging due to the compromise between the threat of intrauterine permanence and the prematurity problem. Consequently, a systematic and protocolized diagnostic-therapeutic management, based on scientific evidence, is necessary to determine whether obstetric intervention through a preterm delivery is advisable to improve the perinatal outcomes of these patients.",book:{id:"8224",slug:"growth-disorders-and-acromegaly",title:"Growth Disorders and Acromegaly",fullTitle:"Growth Disorders and Acromegaly"},signatures:"Edurne Mazarico Gallego, Ariadna Torrecillas Pujol, Alex Joan Cahuana Bartra and Maria Dolores Gómez Roig",authors:[{id:"202446",title:"Ph.D.",name:"Maria Dolores",middleName:null,surname:"Gómez Roig",slug:"maria-dolores-gomez-roig",fullName:"Maria Dolores Gómez Roig"},{id:"311835",title:"Dr.",name:"Edurne",middleName:null,surname:"Mazarico",slug:"edurne-mazarico",fullName:"Edurne Mazarico"}]}],onlineFirstChaptersFilter:{topicId:"178",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81751",title:"NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications",doi:"10.5772/intechopen.102552",signatures:"Anielle C.A. Silva, Eliete A. Alvin, Lais S. de Jesus, Caio C.L. de França, Marílya P.G. da Silva, Samaysa L. Lins, Diógenes Meneses, Marcela R. Lemes, Rhanoica O. 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For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",slug:"oct-applications-in-ophthalmology",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Michele Lanza",hash:"e3a3430cdfd6999caccac933e4613885",volumeInSeries:2,fullTitle:"OCT - Applications in Ophthalmology",editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null}]},{type:"book",id:"6843",title:"Biomechanics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6843.jpg",slug:"biomechanics",publishedDate:"January 30th 2019",editedByType:"Edited by",bookSignature:"Hadi Mohammadi",hash:"85132976010be1d7f3dbd88662b785e5",volumeInSeries:4,fullTitle:"Biomechanics",editors:[{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",institutionURL:null,country:{name:"Canada"}}}]}]},openForSubmissionBooks:{},onlineFirstChapters:{},subseriesFiltersForOFChapters:[],publishedBooks:{},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{}},subseries:{item:{},onlineFirstChapters:{},publishedBooks:{},testimonialsList:[]},submityourwork:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],subseriesList:[],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/143644",hash:"",query:{},params:{id:"143644"},fullPath:"/profiles/143644",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)}()