Estimated number of malaria deaths in children under the age of 5 years from year 2000 to 2015 by the WHO region.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6267",leadTitle:null,fullTitle:"Chagas Disease - Basic Investigations and Challenges",title:"Chagas Disease",subtitle:"Basic Investigations and Challenges",reviewType:"peer-reviewed",abstract:"This book contains 11 chapters of significant and updated materials on what we know and what we lack and need in better understanding of Trypanosoma cruzi - a parasite that never dies - and the consequences of Chagas disease as one of the most important neglected parasitic diseases threatening the global health and wellbeing. This book is intended to increase the readers' enthusiasm to explore the four sections of the contents: Section 1 begins with biochemistry, pathophysiology, histo-immunological study, and findings to assist in the diagnosis; Section 2 further investigates the role of vector in propagation of the parasite, the intensity on epidemiology, and the severity on clinical aspects, which help us to be well perceived on the course of disease; Section 3 is seeking beyond modern medicine and what lays in the nature that helps fight against this parasite; and the last section, Section 4, deals with the impacts of public health problem and the control strategies on Chagas disease.",isbn:"978-1-78923-659-0",printIsbn:"978-1-78923-658-3",pdfIsbn:"978-1-83881-369-7",doi:"10.5772/intechopen.69020",price:119,priceEur:129,priceUsd:155,slug:"chagas-disease-basic-investigations-and-challenges",numberOfPages:238,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"564a876f3d20c7740ede73057b5f6fa6",bookSignature:"Veeranoot Nissapatorn and Helieh S. Oz",publishedDate:"September 12th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6267.jpg",numberOfDownloads:9741,numberOfWosCitations:14,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:15,numberOfDimensionsCitationsByBook:2,hasAltmetrics:0,numberOfTotalCitations:38,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 22nd 2017",dateEndSecondStepPublish:"June 12th 2017",dateEndThirdStepPublish:"November 26th 2017",dateEndFourthStepPublish:"December 26th 2017",dateEndFifthStepPublish:"February 26th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"35419",title:"Dr.",name:"Veeranoot",middleName:null,surname:"Nissapatorn",slug:"veeranoot-nissapatorn",fullName:"Veeranoot Nissapatorn",profilePictureURL:"https://mts.intechopen.com/storage/users/35419/images/system/35419.png",biography:"Dr. Veeranoot Nissapatorn is an Associate Professor at the Department of Parasitology, Faculty of Medicine, University of Malaya, Malaysia. \r\nDr. Veeranoot has MBBS (Delhi University, India), DTM&H and MCTM ( Mahidol University, Thailand). \r\nDr. Veeranoot actively involves in the research development with more than 80 publications and her areas of interest are infectious parasitic diseases including epidemiology, clinically relevant, diagnostic challenges, natural products and health awareness including human and animal aspects. \r\nDr. Veeranoot is a member of a different editorial board for journals as well as an active reviewer for over 30 different journals.\r\nDr. Veeranoot has published book chapters and also served as guest Editor, international invited speakers in various conferences and Visiting Professor.",institutionString:"Walailak University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Walailak University",institutionURL:null,country:{name:"Thailand"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"64173",title:"Dr.",name:"Helieh",middleName:null,surname:"S. Oz",slug:"helieh-s.-oz",fullName:"Helieh S. Oz",profilePictureURL:"https://mts.intechopen.com/storage/users/64173/images/5364_n.png",biography:"Dr. Helieh S. Oz has DVM, and MS (U. ILL); Ph.D. (U. MN) and clinical translational research certificate ( U. KY). Dr. Oz is an active member of American Association of Gastroenterology (AGA) and AGA Fellow (AGAF) and Associate in Rome Foundation (Res. Func GI Dis). Dr. Oz is a Microbiologist scientist with expertise in Infectious and inflammatory diseases, drug discoveries, pathogenesis, innate and mucosal Immunity, molecular biology, ROS, and micronutrient. Dr. Oz has over 90 publications in the areas of chronic inflammatory and digestive disorders (pancreatitis, hepatitis, colitis), infectious diseases (e.g. Toxoplasmosis, Trypanosomiasis, Pneumocystis pneumonia) and drug discovery. She has published book chapters including Recent Advances in Toxoplasmosis, 2014. Dr. Oz has served as Lead Guest editor for special issues in journals of Med. Inflam (Gut Inflam Dis, Infect, Nutri 2017); Gastroenterol Res Pract (Gastro Inflam Repair: Role of Microbiome, Infection, Nutri 2016-17) j. Nutrients and guest Co-Editor for J. Pediatric Infect Dis and published multiple articles for different invited special issues. Dr. Oz is a member of the different editorial board for journals and an avid reviewer for several journals.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Kentucky",institutionURL:null,country:{name:"United States of America"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1046",title:"Infectious Diseases",slug:"infectious-diseases"}],chapters:[{id:"61415",title:"Introductory Chapter: Chagas Disease and Its Global Impacts",doi:"10.5772/intechopen.77275",slug:"introductory-chapter-chagas-disease-and-its-global-impacts",totalDownloads:644,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Frederick R. Masangkay, Giovanni DJ Milanez, Helieh S. Oz and\nVeeranoot Nissapatorn",downloadPdfUrl:"/chapter/pdf-download/61415",previewPdfUrl:"/chapter/pdf-preview/61415",authors:[{id:"35419",title:"Dr.",name:"Veeranoot",surname:"Nissapatorn",slug:"veeranoot-nissapatorn",fullName:"Veeranoot Nissapatorn"}],corrections:null},{id:"61955",title:"Biochemical, Cellular, and Immunologic Aspects during Early Interaction between Trypanosoma cruzi and Host Cell",doi:"10.5772/intechopen.77236",slug:"biochemical-cellular-and-immunologic-aspects-during-early-interaction-between-trypanosoma-cruzi-and-",totalDownloads:886,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The close parasite-host relationship involves different aspects such as the biochemical, physiological, morphological, and immunological adaptations. Studies on parasite-host interaction have provided a myriad of information about its biology and have established the building blocks for the development of new drug therapies to control the parasite. Several mechanisms for the parasite invasion have been proposed through in vivo or in vitro experimental data. Since the first histological studies until the studies on the function/structure of the involved molecules, this complex interaction has been roughly depicted. However, new recent strategies as genetic and proteomic approaches have tuned knowledge on how the host reacts to the parasite and how the parasite avoids these host’s reactions in order to survive.",signatures:"Rosa Lidia Solís-Oviedo, Víctor Monteon, Ruth López and Ángel de\nla Cruz Pech-Canul",downloadPdfUrl:"/chapter/pdf-download/61955",previewPdfUrl:"/chapter/pdf-preview/61955",authors:[{id:"227052",title:"Dr.",name:"Rosa Lidia",surname:"Solís-Oviedo",slug:"rosa-lidia-solis-oviedo",fullName:"Rosa Lidia Solís-Oviedo"},{id:"230327",title:"Dr.",name:"Víctor",surname:"Monteón",slug:"victor-monteon",fullName:"Víctor Monteón"},{id:"230328",title:"Dr.",name:"Ángel De La Cruz",surname:"Pech-Canul",slug:"angel-de-la-cruz-pech-canul",fullName:"Ángel De La Cruz Pech-Canul"},{id:"237280",title:"Dr.",name:"Ruth",surname:"López",slug:"ruth-lopez",fullName:"Ruth López"}],corrections:null},{id:"59361",title:"Antiparasitic Mechanisms of the Human Placenta",doi:"10.5772/intechopen.73569",slug:"antiparasitic-mechanisms-of-the-human-placenta",totalDownloads:798,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Trypanosoma cruzi, during vertical transmission, crosses the placental barrier. The trophoblast, a continuous renewing epithelium, is the first tissue of this anatomical barrier to have contact with the parasite. The epithelial turnover, including the trophoblast, is part of the innate immune response due to the fact that pathogens attach to the surface of cells prior invasion. Cellular processes such as proliferation, differentiation, and apoptotic cell death are part of the trophoblast turnover. Interestingly, T. cruzi induces all of them. In addition, the placenta expresses TLRs, whose activation leads to the secretion of pro-inflammatory and immunomodulating cytokines. T. cruzi is recognized by TLR-2, TLR-4, TLR-7, and TLR-9. In the present review, we analyze the current evidence about the trophoblast epithelial turnover, the induction of a specific cytokine profile as a local placental innate immune response, as well as other possible defense mechanisms against the parasite.",signatures:"Castillo Christian, Ana Liempi, Lisvaneth Medina, Ileana Carrillo and\nUlrike Kemmerling",downloadPdfUrl:"/chapter/pdf-download/59361",previewPdfUrl:"/chapter/pdf-preview/59361",authors:[{id:"92753",title:"Dr.",name:"Ulrike",surname:"Kemmerling",slug:"ulrike-kemmerling",fullName:"Ulrike Kemmerling"},{id:"97568",title:"Dr.",name:"Christian",surname:"Castillo",slug:"christian-castillo",fullName:"Christian Castillo"},{id:"221198",title:"Ms.",name:"Ana",surname:"Liempi",slug:"ana-liempi",fullName:"Ana Liempi"},{id:"221199",title:"Dr.",name:"Ileana",surname:"Carrillo",slug:"ileana-carrillo",fullName:"Ileana Carrillo"},{id:"221200",title:"Mrs.",name:"Lisvaneth",surname:"Medina",slug:"lisvaneth-medina",fullName:"Lisvaneth Medina"}],corrections:null},{id:"62165",title:"The Mouse Model as a Tool for Histological, Immunological and Parasitological Studies of Trypanosoma cruzi Infection",doi:"10.5772/intechopen.77168",slug:"the-mouse-model-as-a-tool-for-histological-immunological-and-parasitological-studies-of-trypanosoma-",totalDownloads:927,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The global expansion of Chagas disease is due to the constant migration of individuals from endemic countries with incidence of vector and nonvector transmission of Trypanosoma cruzi. The disease is present in its various stages: chronological characteristic signs and symptoms of the infection and its mechanism of immune system and cell and tissue damage. The first stage, which lasts 90 days approximately, is diagnosed by direct methods (blood smears stained with Giemsa, fresh and xenodiagnosis). The indeterminate-chronic stage is asymptomatic, but the growth and intracellular binary multiplication of the trypomastigotes continue promoting cell lysis and allowing parasites to infect other cells, with preferential tropism to organs producing mega syndromes such as cardiomyopathy, myocarditis, meningoencephalitis, megaesophagus and megacolon. Inadvertently, this process is repeated for several years leading to Chagas disease. The mouse inoculation allows checking the parasitemia in vivo and the development of the disease in short time (signs, behavior and tropism), histopathological alterations and detection of antibodies in serum. These parameters may vary when using different strains of T. cruzi from different geographical areas; Triatoma species due to their genetic variability are influenced by the environment, nutrition, reservoirs and habitat. The murine model ECA CD-1 has the ability to replicate human findings of Chagas disease.",signatures:"María Elena Villagran-Herrera, José Alejandro Martínez-Ibarra,\nManuel Sánchez-Moreno, Hebert Luis Hernández-Montiel, Ricardo\nFrancisco Mercado-Curiel, Nicolás Camacho-Calderón and José\nAntonio de Diego-Cabrera",downloadPdfUrl:"/chapter/pdf-download/62165",previewPdfUrl:"/chapter/pdf-preview/62165",authors:[{id:"122175",title:"Dr.",name:"Hebert Luis",surname:"Hernández-Montiel",slug:"hebert-luis-hernandez-montiel",fullName:"Hebert Luis Hernández-Montiel"},{id:"210676",title:"Dr.",name:"Maria Elena",surname:"Villagrán Herrera",slug:"maria-elena-villagran-herrera",fullName:"Maria Elena Villagrán Herrera"},{id:"211039",title:"Dr.",name:"José Antonio",surname:"De Diego Cabrera",slug:"jose-antonio-de-diego-cabrera",fullName:"José Antonio De Diego Cabrera"},{id:"211040",title:"Dr.",name:"José Alejandro",surname:"Martínez Ibarra",slug:"jose-alejandro-martinez-ibarra",fullName:"José Alejandro Martínez Ibarra"},{id:"211041",title:"Dr.",name:"Manuel",surname:"Sánchez Moreno",slug:"manuel-sanchez-moreno",fullName:"Manuel Sánchez Moreno"},{id:"211042",title:"Dr.",name:"Ricardo Francisco",surname:"Mercado Curiel",slug:"ricardo-francisco-mercado-curiel",fullName:"Ricardo Francisco Mercado Curiel"},{id:"211043",title:"Dr.",name:"Nicolás",surname:"Camacho Calderón",slug:"nicolas-camacho-calderon",fullName:"Nicolás Camacho Calderón"}],corrections:null},{id:"61401",title:"Transmitter Insect of Chagas Disease in Northwest Mexico: A Comparative Study of the Cuticular Hydrocarbons Profile of Three Populations of Triatoma rubida: Peridomestic, Domestic and Sylvatic",doi:"10.5772/intechopen.77169",slug:"transmitter-insect-of-chagas-disease-in-northwest-mexico-a-comparative-study-of-the-cuticular-hydroc",totalDownloads:757,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In México, biogeography data are available for species of triatomas called Trypanosoma cruzi transmitters; for example, the phyllosoma complex is distributed in several states of the south-central southeast of the country. In contrast, Northwestern Mexico species such as Triatoma rubida are considered sylvatic and in the process of domestication. The lack of research of these northern species of the country has generated an ignorance that contrasts with a growing number of alleged new cases of Chagas disease registered in health institutions in states such as Sonora. From the six species of triatomas that are potential transmitters of the trypanosoma in the state of Sonora, Triatoma rubida is the only one that has recent studies of distribution and transmission capacity. It is important then to know the degree of domesticity of the native species with the capacity of transmission of Trypanosoma cruzi and to define areas of risk. The process of adaptation of the sylvatic triatomines to the peridomestic and the domestic habitat has been understood in terms of environmental and biological variables. In this research, the profile of cuticular hydrocarbons of a peridomestic, domestic and sylvatic population of Triatoma rubida was analyzed and compared.",signatures:"Edgar Alfonso Paredes González, Gerardo Álvarez Hernandez and\nJesús Ortega-García",downloadPdfUrl:"/chapter/pdf-download/61401",previewPdfUrl:"/chapter/pdf-preview/61401",authors:[{id:"211310",title:"Dr.",name:"Jesús",surname:"Ortega-García",slug:"jesus-ortega-garcia",fullName:"Jesús Ortega-García"},{id:"211311",title:"MSc.",name:"Edgar Alfonso",surname:"Paredes-Gonzalez",slug:"edgar-alfonso-paredes-gonzalez",fullName:"Edgar Alfonso Paredes-Gonzalez"},{id:"211568",title:"Dr.",name:"Gerardo",surname:"Álvarez Hernandez",slug:"gerardo-alvarez-hernandez",fullName:"Gerardo Álvarez Hernandez"}],corrections:null},{id:"59652",title:"Eco-Epidemiology of Chagas Disease in Chile",doi:"10.5772/intechopen.74744",slug:"eco-epidemiology-of-chagas-disease-in-chile",totalDownloads:980,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"There are four vector species of Chagas disease in Chile: Triatoma infestans, responsible for the domestic cycle; Mepraia spinolai, the main wild vector; and M. gajardoi and M. parapatrica, two coastal wild species whose importance as vectors is not well known. They are species of dry environments of the central-north region of Chile, whose best predictors of distribution are warm average temperatures and low rainfall. They are found in rock quarries, nests of birds, and small mammals, and T. infestans has sylvatic foci associated with a Bromeliaceae species. While human blood represents 70% of the diet of T. infestans, in M. spinolai this value is 7%, which means that a large part of Chagas disease in Chile is due to T. infestans. However, all species have high percentages of T. cruzi infection. Chagas disease in Chile follows the distribution of T. infestans, and although the cycle of domestic transmission by this vector is interrupted, there is still a constant prevalence and mortality and ascending incidences. Models predict that although climate change will not vary greatly the north-south distribution of vectors, it could increase the reproductive number of the disease, increasing risk areas of Chagas disease.",signatures:"Mauricio Canals Lambarri, Andrea Canals Cifuentes, Salvador Ayala,\nValentina Tapia-Garay and Dante Cáceres Lillo",downloadPdfUrl:"/chapter/pdf-download/59652",previewPdfUrl:"/chapter/pdf-preview/59652",authors:[{id:"52742",title:"Dr.",name:"Mauricio",surname:"Canals",slug:"mauricio-canals",fullName:"Mauricio Canals"},{id:"100193",title:"Dr.",name:"Dante D.",surname:"Cáceres",slug:"dante-d.-caceres",fullName:"Dante D. Cáceres"},{id:"235687",title:"Dr.",name:"Andrea",surname:"Canals",slug:"andrea-canals",fullName:"Andrea Canals"},{id:"235688",title:"MSc.",name:"Salvador",surname:"Ayala",slug:"salvador-ayala",fullName:"Salvador Ayala"},{id:"235689",title:"Dr.",name:"Valentina",surname:"Tapia-Garay",slug:"valentina-tapia-garay",fullName:"Valentina Tapia-Garay"}],corrections:null},{id:"62321",title:"Chagas Cardiomyopathy: Role of Sustained Host-Parasite Interaction in Systemic Inflammatory Burden",doi:"10.5772/intechopen.77980",slug:"chagas-cardiomyopathy-role-of-sustained-host-parasite-interaction-in-systemic-inflammatory-burden",totalDownloads:981,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The economic and social burden associated with Chagas disease morbidity and mortality is regrettably large in Latin America causing more deaths than does any other parasitic disease. Inflammatory dilated cardiomyopathy is, by far, the most important clinical consequence of Trypanosoma cruzi infection. The insidious persistence of this parasite determines chronic myocarditis progression. The clinical outcome is multifactorial and depends on the particular parasite strain and virulence factors, the infective load and route of infection, the parasite ability to by-pass the protective immune response, the intensity and type of immune response during the acute infective phase, and the host genetic background. From the immunological viewpoint, host control of T. cruzi has been shown to depend on both humoral and cell-mediated adaptive responses and from the innate immune system. In this review, we discuss the most relevant literature conveying information on the relevance of identifying a subset of systemic inflammatory molecules as potential markers of cardiovascular risk morbidity and mortality in patients with Chagas disease. Concurrently, a direct role for the parasite in the perpetuation of myocardial inflammation is substantiated. Ultimately, host-parasite interactions determine the course of the ongoing systemic inflammation and the perpetuation of myocardial inflammation in genetically predisposed patients.",signatures:"Rodolfo A Kölliker-Frers, Matilde Otero-Losada, Gabriela Razzitte,\nMariela Calvo, Justo Carbajales and Francisco Capani",downloadPdfUrl:"/chapter/pdf-download/62321",previewPdfUrl:"/chapter/pdf-preview/62321",authors:[{id:"120703",title:"Dr.",name:"Francisco",surname:"Capani",slug:"francisco-capani",fullName:"Francisco Capani"},{id:"205589",title:"Dr.",name:"Rodolfo Alberto",surname:"Kölliker Frers",slug:"rodolfo-alberto-kolliker-frers",fullName:"Rodolfo Alberto Kölliker Frers"},{id:"213940",title:"Dr.",name:"Justo",surname:"Carbajales",slug:"justo-carbajales",fullName:"Justo Carbajales"},{id:"213941",title:"Ms.",name:"Gabriela",surname:"Razzitte",slug:"gabriela-razzitte",fullName:"Gabriela Razzitte"}],corrections:null},{id:"59725",title:"Efficacy and Safety of Chagas Disease Drug Therapy and Treatment Perspectives",doi:"10.5772/intechopen.74845",slug:"efficacy-and-safety-of-chagas-disease-drug-therapy-and-treatment-perspectives",totalDownloads:1003,totalCrossrefCites:3,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Chagas disease, also known as American trypanosomiasis, is a neglected disease caused by the protozoan parasite Trypanosoma cruzi. The disease affects about 6–7 million people worldwide, mostly in Latin America. Although Chagas disease was discovered more than 100 years ago, and the first treatments over 40, only 2 drugs were used to treat this pathology, it is still considered one of the neglected diseases. In this chapter, the subjects related to conventional etiological therapies, benznidazole and nifurtimox, such as the drug, the mechanism of action, the therapy schedule for treatment, efficacy and safety and their adverse effects will be discussed. Additionally, it will address alternative therapies of comorbidities related to the progression of Chagas’ disease in patients with chronic disease, such as heart disease and dysfunction of the digestive system. Finally, novel pharmacological strategies and their related compounds will be reviewed accounting for their progression in pharmacological studies and their success rate.",signatures:"Wilton H. Kawaguchi, Leticia Bonancio Cerqueira, Mariana Millan\nFachi, Michel L. Campos, Iara J. Messias Reason and Roberto\nPontarolo",downloadPdfUrl:"/chapter/pdf-download/59725",previewPdfUrl:"/chapter/pdf-preview/59725",authors:[{id:"55129",title:"Dr.",name:"Roberto",surname:"Pontarolo",slug:"roberto-pontarolo",fullName:"Roberto Pontarolo"},{id:"214073",title:"MSc.",name:"Wilton",surname:"Hideki Kawaguchi",slug:"wilton-hideki-kawaguchi",fullName:"Wilton Hideki Kawaguchi"},{id:"214076",title:"Dr.",name:"Leticia",surname:"Bonâncio Cerqueira",slug:"leticia-bonancio-cerqueira",fullName:"Leticia Bonâncio Cerqueira"},{id:"214077",title:"Dr.",name:"Michel",surname:"Campos",slug:"michel-campos",fullName:"Michel Campos"},{id:"214078",title:"M.Sc.",name:"Mariana Millan",surname:"Fachi",slug:"mariana-millan-fachi",fullName:"Mariana Millan Fachi"},{id:"221550",title:"Dr.",name:"Iara J",surname:"Messias Reason",slug:"iara-j-messias-reason",fullName:"Iara J Messias Reason"}],corrections:null},{id:"61396",title:"New Approaches for Chagas’ Disease Chemotherapy",doi:"10.5772/intechopen.77235",slug:"new-approaches-for-chagas-disease-chemotherapy",totalDownloads:914,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The latest advances concerning drug design and chemotherapy development to combat the Chagas’ disease are discussed. This chapter is based on the metabolic differences between the pathogenic parasite and mammal hosts that led to the progress in the search for novel metabolic pathways in parasites that may be essential for parasite’s survival but with no counterpart in the host. There is a considerable amount of work in the search of more promising molecular targets for drug design. However, the chemotherapy for this disease remains unsolved. It is based on old and fairly not specific drugs associated with long-term treatments, severe side effects, drug resistance, and different strains’ susceptibility. Herein, a thorough analysis of selected molecular targets is described in terms of their potential usefulness for drug design. Therefore, rational approaches to the chemotherapeutic control of American trypanosomiasis describing some useful metabolic pathways are covered. Enzymes involved in ergosterol biosynthesis (squalene synthase, HMG-CoA reductase, farnesyl diphosphate synthase (FPPS), sterol 24-methyltransferase, and sterol 14α-demethylase), trypanothione system (glutathionyl-spermidine synthetase, trypanothione synthetase, and trypanothione reductase), cysteine proteases, trans-sialidase, and so on are discussed. The design of specific inhibitors of these metabolic activities as possible means of controlling the parasites without damaging the hosts is presented.",signatures:"Guadalupe García Liñares",downloadPdfUrl:"/chapter/pdf-download/61396",previewPdfUrl:"/chapter/pdf-preview/61396",authors:[{id:"209880",title:"Dr.",name:"Guadalupe",surname:"Garcia Liñares",slug:"guadalupe-garcia-linares",fullName:"Guadalupe Garcia Liñares"}],corrections:null},{id:"61631",title:"Slowed Development of Natural Products for Chagas Disease, how to Move Forward?",doi:"10.5772/intechopen.77234",slug:"slowed-development-of-natural-products-for-chagas-disease-how-to-move-forward-",totalDownloads:874,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Chagas disease, caused by Trypanosoma cruzi, is considered an endemic disease that affects millions of people causing generating health, economic and social problems. This study provides a review on research and development of new therapies for Chagas based in natural products of plant origin. We observed that there are more than 400 plant species that have been evaluated against different models of Chagas disease, and in some cases, there are interesting results. Challenge that hinders research work is the purification of the active compound and standardization of the chemical profile of whole extracts. The principal common factor that delays clinical testing is the lack of investment for the development of these products at the clinical phase. In the search of a natural, low cost and available drug for Chagas disease, we propose the use of new methodologies to overcome the existing challenges. The use of plant metabolomic technique is proposed as an option with high potential for the identification of biomarkers that could allow the standardization of chemical profiles. Furthermore, we describe the importance of applying good agricultural and manufacturing practices for reaching a successful development of quality phytotherapeutic products.",signatures:"Javier Varela, Hugo Cerecetto and Mercedes González",downloadPdfUrl:"/chapter/pdf-download/61631",previewPdfUrl:"/chapter/pdf-preview/61631",authors:[{id:"211263",title:"Prof.",name:"Mercedes",surname:"Gonzalez",slug:"mercedes-gonzalez",fullName:"Mercedes Gonzalez"},{id:"211266",title:"Dr.",name:"Javier",surname:"Varela",slug:"javier-varela",fullName:"Javier Varela"},{id:"221378",title:"Prof.",name:"Hugo",surname:"Cerecetto",slug:"hugo-cerecetto",fullName:"Hugo Cerecetto"}],corrections:null},{id:"61255",title:"Silent Information Regulator 2 from Trypanosoma cruzi Is a Potential Target to Infection Control",doi:"10.5772/intechopen.77030",slug:"silent-information-regulator-2-from-trypanosoma-cruzi-is-a-potential-target-to-infection-control",totalDownloads:978,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Human trypanosomiasis is a neglected tropical disease caused by protozoan parasites of the genus Trypanosoma. Trypanosoma brucei is responsible for sleeping sickness, also called African trypanosomiasis, while Trypanosoma cruzi causes Chagas disease, or American trypanosomiasis. Together, these diseases are responsible for significant mortality, morbidity and lost productivity in the endemic regions. There are no vaccines and treatments rely on drugs with limited efficacy, high cost, serious side effects and long administration periods. Since these diseases affect mostly the poor, there is no economic interest in the development of new drugs by pharmaceutical companies, and hopes for new treatments rely on public initiatives, public-private partnerships or philanthropic programs. The first step in the discovery of new drugs involves the identification of active molecules as starting points for further development, by either employing whole cells or by specific molecular target screenings. Research efforts undertaken by the authors’ groups have focused on exploiting both strategies in the search for new molecules for trypanosomiasis drug discovery. In this chapter, we focus on Chagas disease and the recently uncovered potential of using sirtuins as targets for infection control.",signatures:"Luís Gaspar, Terry K. Smith, Nilmar Silvio Moretti, Sergio Schenkman\nand Anabela Cordeiro-da-Silva",downloadPdfUrl:"/chapter/pdf-download/61255",previewPdfUrl:"/chapter/pdf-preview/61255",authors:[{id:"157734",title:"Dr.",name:"Terry",surname:"Smith",slug:"terry-smith",fullName:"Terry Smith"},{id:"169577",title:"Dr.",name:"Anabela",surname:"Cordeiro-Da-Silva",slug:"anabela-cordeiro-da-silva",fullName:"Anabela Cordeiro-Da-Silva"},{id:"225032",title:"Dr.",name:"Luis",surname:"Gaspar",slug:"luis-gaspar",fullName:"Luis Gaspar"},{id:"225034",title:"Dr.",name:"Nilmar",surname:"Moretti",slug:"nilmar-moretti",fullName:"Nilmar Moretti"},{id:"225035",title:"Dr.",name:"Sergio",surname:"Schenkman",slug:"sergio-schenkman",fullName:"Sergio Schenkman"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{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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The biofuels like hydrogen, bioethanol, syngas, and many more can be produced which find applications as alternate energy sources and address vital environmental issues related to non-renewable energy sources. These biofuels are very sustainable and eliminating the research gaps can further lead to the commercial production of cyanobacterial biofuels in the market across the world. The range of metabolic products is tremendously valuable as antimicrobial, anticancer, anti-inflammatory, antitumor, antioxidative in nature, which has excellent therapeutic applications.
\r\n\r\n\tThis book envisions elaborating on the recent advancements and the new perspectives in the area of cyanobacterial research on the global platform.
",isbn:"978-1-80356-462-3",printIsbn:"978-1-80356-461-6",pdfIsbn:"978-1-80356-463-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"645b037b086ec8c36af614326dce9804",bookSignature:"Dr. Archana Tiwari",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11800.jpg",keywords:"Algae, Cyanobacteria, Ecological Impact, Carbon Dioxide Mitigation, Biofuels, Hydrogen, Ethanol, Sustainability, Applications, Biomass Valorization, Metabolites, Bioactive Compounds",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 2nd 2022",dateEndSecondStepPublish:"May 3rd 2022",dateEndThirdStepPublish:"July 2nd 2022",dateEndFourthStepPublish:"September 20th 2022",dateEndFifthStepPublish:"November 19th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A Gold medalist and distinction holder in Botany and her research interests include Phycoprospecting Diatoms for wastewater remediation and high-value products.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"13",title:"Immunology and Microbiology",slug:"immunology-and-microbiology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"453624",firstName:"Martina",lastName:"Scerbe",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/453624/images/20399_n.jpg",email:"martina.s@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"6764",title:"Cyanobacteria",subtitle:null,isOpenForSubmission:!1,hash:"87c7d8f86f7c1185aa4dd47c6492951a",slug:"cyanobacteria",bookSignature:"Archana Tiwari",coverURL:"https://cdn.intechopen.com/books/images_new/6764.jpg",editedByType:"Edited by",editors:[{id:"186791",title:"Dr.",name:"Archana",surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],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"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"52685",title:"Challenges of Managing Childhood Malaria in a Developing Country: The Case of Nigeria",doi:"10.5772/65488",slug:"challenges-of-managing-childhood-malaria-in-a-developing-country-the-case-of-nigeria",body:'\nMalaria still remains one of the highest childhood killer diseases, especially in the developing countries of Africa, Southeast Asia, and Eastern Mediterranean regions. In Africa, it is estimated that malaria kills one child every 2 minutes [1]. According to the latest estimates from the World Health Organisation (WHO), there were 214 million new cases of malaria worldwide in 2015 with an estimated 438 000 malaria deaths [1]. Most of these cases (88%) and deaths (90%) were recorded in the African region [1]. Nigeria and the Democratic Republic of Congo, both in African region, accounted for about 40% of the total estimated malaria deaths worldwide. The Southeast Asia and the Eastern Mediterranean regions account for the few remaining cases in that order. The denominator in all these regions, apart from the favourable weather conditions for the breeding of malaria parasite-carrying mosquitoes, is the widespread poverty and systemic inadequacies: lack of political will and poor health systems in many of the countries that make up the regions. In parts of the world where malaria is endemic, severe malaria is mainly a disease of children under the age of 5 years due to the acquisition of specific immunity against plasmodium; the malaria-causing parasite as the child gets older, providing some protection (though incomplete) against malaria [2]. Malaria is endemic in most countries of Sub-Saharan Africa with the children and pregnant women population being the most vulnerable to the disease. Of the estimated 438,000 malaria deaths worldwide, children under the age of 5 years constitute 306,000 (70%) [1].
\nDespite these seemingly very high figures, there has been marked decline in the mortality from malaria. The global cases of malaria declined by 18% from an estimated 262 million in the year 2000 to 214 million in 2015. The death rate decreased by 48% from a global estimate of 839,000 in year 2000 to 438,000 in 2015. In children under the age of 5 years, the number of malaria deaths fell from an estimated 723,000 in year2000 to 306,000 in 2015, a decrease of about 58% (Table 1). This has come through the combined efforts of the World Health Organisation, its Rollback Malaria Partners and the various governments in the different countries afflicted by the malaria scourge.
\nWHO region | \nEstimated malaria deaths by year | \nPercentage reduction | \n|||
---|---|---|---|---|---|
2000 | \n2005 | \n2010 | \n2015 | \n2000–2015 | \n|
Africa | \n694,000 | \n5910,000 | \n410,000 | \n292,000 | \n−58% | \n
Americas | \n400 | \n300 | \n300 | \n100 | \n−66% | \n
Eastern Mediterranean | \n5300 | \n5200 | \n2000 | \n2200 | \n−58% | \n
European | \n0 | \n0 | \n0 | \n0 | \n0 | \n
Southeast Asia | \n19,000 | \n16,000 | \n14,000 | \n10,000 | \n−49% | \n
Western Pacific | \n4,700 | \n2,000 | \n1,600 | \n1,500 | \n−68% | \n
World | \n723,000 | \n614,000 | \n428,000 | \n306,000 | \n−58% | \n
Estimated number of malaria deaths in children under the age of 5 years from year 2000 to 2015 by the WHO region.
Source: World Malaria Report 2015.
To achieve this, the WHO adopted a cost-effective intervention strategy, which comprises a three-pronged approach: vector control, chemoprophylaxis, and case management. The vector control involves the prevention of mosquitoes from acquiring or transmitting infection through the use of long lasting insecticidal nets (LLIN) and indoor residual spray (IRS). Chemoprophylaxis involves the use of antimalarial drugs to suppress and prevent the establishment of infection in the human, whereas case management involves the prompt diagnosis and treatment of malaria.
\nAlthough these strategies are said to be cost effective, the achievements recorded in the fight against malaria has not come at a cheap price. The global cost of fighting malaria increased from the sum of US$ 960 million in year 2000 to a whopping US$ 2.5 billion in 2014 [1]. The majority of these funds were contributed by international partners (donor agencies). In spite of these global efforts and huge funding for malaria control, malaria continues to be a major challenge in these developing countries, especially countries in Sub-Saharan Africa. These challenges in the fight against malaria, with particular attention to case management, are discussed below using Nigeria as a case study.
\nAs the most populous country in Africa, Nigeria contributes the majority of the Africa malaria burden. The country has an estimated total population of approximately 172 million (2014 estimate) with an annual growth rate of about 2.7% and a GDP per capita of US$1091.64 (2014) and inflation rate of 9.0% (2015) [3]. The public health sector in Nigeria is run by the three tiers of government: federal, state, and local governments. The federal government co-ordinates the affairs of the tertiary health facilities and provides overall policy and technical support to the health sector. The state government co-ordinates those of the secondary centres and some state-owned tertiary centres and also lend support to the primary health sector. The local government takes care of the primary health centres, which have gone moribund in many parts of the country. The annual health budget is usually well below 10% of the total budget. For instance; in 2015, it was 6.3%, whereas in 2016, it dropped to about 3.7%. In general, the country’s health system may be described as weak due to inadequate funding and supervision.
\nNigeria, being a tropical country, has one of the best combinations of adequate rainfall, temperature, and humidity, allowing for the breeding and survival of the female anopheline mosquitoes, the malaria vector. Most (97%) of the malaria in Nigeria are mainly due to
Malaria remains a major public health problem in Nigeria. It accounts for more cases and deaths than in any other country in the world. There are an estimated 100 million malaria cases with over 300,000 deaths per year in Nigeria [5]. Malaria accounts for 60% of outpatient visits and 30% of hospitalizations among children under 5 years of age in Nigeria [5]. This implies a huge loss in terms of financial resources and man hours and in the case of the school age child, loss of school hours [6–8].
\nIn line with the World Health Organization recommendation, the country has adopted the Test, Treat, and Track (3T) strategy with all suspected cases of malaria properly diagnosed using Rapid Diagnostic Tests or microscopy, treated promptly with recommended artemisinin-based combination therapy (ACT) if the result is positive and documented [4].
\nWHO has identified early diagnosis as the first step in the treatment of malaria. This is necessary to prevent progression of the disease to severe forms. Malaria does not have any specific symptoms and signs and as such may mimic several tropical childhood illnesses [9]. These include bacterial sepsis, enteric fever, pneumonia, meningitis, urinary tract infection, otitis media, and pharyngitis. This makes the specificity of clinical diagnosis of malaria very poor and thus gives room for indiscriminate use of antimalarials especially in endemic areas. In some cases, malaria may co-exist with any of these other conditions [10–13], necessitating more competent health personnel in the management. Studies [14–16] have shown that treatment based on clinical information alone leads to over diagnosis and over treatment of malaria. In addition, there may be increased morbidity and possible death from the neglected disease causing the child’s symptoms.
\nEven with the unreliability and consequences of reliance on clinical information alone for malaria diagnosis, a large proportion of healthcare providers in Nigeria still treat malaria presumptively [14, 17, 18]. The 2013 Nigeria Demographic and Health Survey indicated that the average rate of antigen or parasite detection in children before treatment was 11.1% [19]. Reasons adduced for the presumptive diagnosis by the healthcare providers included delay in getting a blood microscopy from hospital laboratories, unavailability of malaria rapid diagnostic test (mRDT), reliance on blood tests create an impression of incompetence of the health personnel, as well as malaria being the first suspect in any child with fever since malaria is endemic in Nigeria [17]. According to WHO, less than half of the suspected malaria cases in most malaria endemic regions are truly infected with malaria parasite, hence their insistence on laboratory confirmation before treatment [1].
\nIn line with the WHO policy, the national malaria guideline of Nigeria recommends the confirmation of all suspected cases of malaria by parasitological testing either with microscopy or by the use of mRDT. This is particularly important as accurate diagnosis before treatment will enhance a more targeted therapy, reduce the duration of illness, and may even prevent death from treatment of another disease as malaria. It will help prevent drug resistance and also enhance the diagnosis and case management of other diseases that may mimic malaria in children since the exclusion of malaria will mean a search for the cause of illness. Apart from saving lives, both money and man hours are saved.
\nThe challenge with this confirmation test is mainly that of availability and willingness to go for test before treatment. Microscopy, which still remains the gold standard, is fast disappearing from many health facilities. The reasons range from inability to acquire new or replace old and damaged microscopes to absence of a qualified microscopist. In addition, ready availability of reagents and slides for use with the microscopes, where available may be a problem. There is also the need for quality assurance, which is virtually non-existence in most health facilities in the country. Another important consideration is the need for electrical power, which is a big issue in the country. The alternative is the mRDT, which is an antigen detection test. Three antigens:
Since the introduction of RDT kits, there has been increased knowledge of mRDT by healthcare givers and increasing availability at health facilities, but its regular utilization to confirm suspected cases of malaria by these health workers prior to treatment is not encouraging [17, 26]. Another major concern is the fact that a good number of these mRDTs have high false negative results at lower antigen titre (200–500 parasites/ml) [20, 23]. For the detection of
In consonance with the WHO recommendation on the treatment of malaria, the Nigerian government adopted the use of artemether-lumefantrine (AL) for the treatment of uncomplicated malaria and artesunate-amodiaquine (AA) as alternative [4]. For severe falciparum malaria treatment, the drug of choice is intravenous artesunate with parenteral artemether or quinine as alternatives where intravenous artesunate is not available. For settings where a complete treatment of severe malaria is not feasible, a pre-referral treatment with intramuscular or rectal artesunate or intramuscular quinine in this order of preference is recommended.
\nAlthough the Nigerian government had adopted AL and AA as the first and second line respectively, several brands of other ACTs are widely available and used in the country. These include artesunate-mefloquine, dihydroartemisinin-piperaquine, artemisinin-piperaquine, and artesunate-sulfadoxine pyrimethamine. Regardless of the constellation of ACT antimalarial drugs available, many children still receive monotherapy notably chloroquine and sulfadoxine-pyrimethamine especially among the lower socioeconomic class and those with uneducated or under educated parents [17, 29]. Other commonly used antimalarial monotherapy in children include oral artesunate, amodiaquine, halofantrine, and oral quinine and paludrine [29, 30]. The drawback in this practice is the progression to severe malaria with its consequences, which include prolonged hospitalization, increased cost of treatment, avoidable blood transfusions, and even death. The frequent prescription of concomitant medications in the form of different antipyretics, sometimes multiple, haematinics, multivitamin preparations, and antibiotics, which are mostly inappropriate also add to the cost of treatment and burden of medications for the child [29]. In Sub-Saharan Africa, the proportion of children aged under 5 years, who received an ACT, is estimated to have increased from less than 1% in 2005 to 16% in 2014, but still falls substantially short of the target of universal access for malaria case management [1]. One important reason for this poor situation is that a greater proportion of children with fever are treated outside the health sector.
\nIn Nigeria, only about 35% of children receive treatment at government health facilities [19]. The rest are treated by the patent medicine vendors (PMV), pharmacy shops, private health facilities, or by traditional medicine practitioners. In the light of this, the government of Nigeria with the assistance of Roll back Malaria partners and donor agencies tried to scale up the treatment of malaria through the engagement of the private sectors, especially the PMVs whom they have trained in some states of the federation and the provision of pre-packaged, age-specific antimalarials for easier dosing [19]. A study by Berendes et al. [31] in the northern part of Nigeria showed that patent medicine vendors are not reliable in the treatment of malaria because most PMVs were ignorant of and lacked training about new treatment guidelines that had endorsed ACTs as first-line treatment for uncomplicated malaria. They stocked and dispensed monotherapy to patients with suspected malaria. However, another study [32] in the southern part of the country showed an improved knowledge of ACT by PMVs, but yet other non-recommended antimalarial drugs such as chloroquine were still sold to customers without prescription. Another worrisome trend is the prevalent use of various forms of herbal medications in the treatment of malaria even in urban areas [7, 33, 34]. Some of these herbal preparations, which mostly do not have standard dosage, have the potential to cause liver or kidney damage [35].
\nThe cost of malaria treatment is also a contributing factor to the non-use of ACT because this remains high for the average Nigerian. In 2009, the cost of treating a child was about US$6.58, which was mostly on out of pocket expenses [8]. Although a national health insurance scheme is available, only a very small percentage of the population, mainly federal civil servants and staff of big companies, have access to it.
\nAnother major challenge with the treatment of malaria in Nigerian children is the high rate of fake and substandard antimalarial drugs [36, 37]. This brought about a lot of confusion to the healthcare provider regarding the possibility of co-morbidities when the child failed to respond to the proper treatment. This may lead to the administration of unwarranted antibiotics while the child deteriorates from untreated malaria. However, the situation has improved significantly in recent times [36]. The rate of fake and substandard drugs in the country improved from about 41% in 2002 to about 10% in 2010 [36]. The fight is still ongoing by the country’s National Agency for Food and Drug Administration and Control (NAFDAC) to eradicate fake drugs from the country.
\nNigeria being a developing country has its fair share of children with chronic diseases, such as malnutrition, HIV/AIDS, and sickle cell anaemia. These children equally suffer from malaria, which is usually more severe than in the normal child [38–40]. Managing such children could pose a great challenge. Apart from the complications such as severe anaemia, which are more prevalent in these children [38–40], concurrent management of the underlying disease in the face of challenging finances often result in difficult decisions.
\nChildren with severe malaria anaemia suffer greatly due to the difficulty in obtaining safe blood for transfusion. The primary health facilities and many private facilities do not have logistics to store blood. Patients requiring blood transfusions in these facilities are either referred to tertiary centres or made to purchase blood from private blood banks at very exorbitant prizes, some of which the safety are not guaranteed. In some cases, the child may be unable to make it alive to the referred centre. Those who do often face many logistic challenges ranging from cost of processing to provision of donor to replace the transfused blood.
\nLate presentation usually results in delay in initiation of the right and adequate treatment. No doubt this contributes significantly to the malaria mortality in children. Factors responsible may include poverty, inadequate home treatment, and lack of access to standard treatment centres. Certain traditional beliefs such as association of fever with teething and growth may also delay presentation. Likewise, the increasing belief in unorthodox treatment such as herbal medications and faith-based healing may also lead to delays in presentation.
\nAlthough majority of Nigerians reside in the rural areas, only a small proportion of health facilities are located there and these are mainly primary and secondary care facilities. Likewise, fewer personnel are available in these rural communities. As a result, most patients with severe forms of malaria will need to travel some distance with all the attendant challenges such as bad roads.
\nDespite all these numerous challenges plaguing the management of malaria in Nigerian children, there have been significant gains in the fight against malaria as evidenced by the improved indices. Thanks to all the Rollback Malaria partners operating in the country. However, a lot of commitment and willingness to translate what is on paper to action is still expected from the Nigerian government.
\nFirst is to strengthen the health systems at all levels from primary to tertiary in order to restore the hopes of the numerous Nigerians who die because they cannot afford standard private health facility treatments. This should include the recruitment and adequate training and retraining of healthcare personnel in all the primary and secondary care centres to be able to make proper diagnosis and treat malaria cases. Also, adequate equipping of all the government health facilities with diagnostic facilities and eradication of the “out of stock syndrome” for antimalarial drugs.
\nThere should be strengthening of the already on-going awareness creation through the media to sensitize the public on the need to seek care early and at government approved health facilities.
\nThere should be continuous appraisal of the antimalarial drugs and mRDTs in the country with a view of identifying and expunging the substandard and fake ones. The large number of different brands of ACTs and in the country need to be pruned down to just a few quality and trusted brands.
\nPeriodontitis has prevailed in human history from the dawn of civilization and still is a major cause of tooth loss in adult population. The etiology of periodontal disease (PD) is complex in nature, and it is a multifactorial disease, which is largely influenced by genetic, environmental, and microbial factors [1]. The periodontal disease begins at the gingiva and progress downwards and affects the tooth-supporting structures, i.e., periodontal ligament, cementum of the root, and alveolar bone. The clinical features of periodontitis are bleeding from the gums, pus discharge, dull gnawing pain, bad breath, mobility of teeth, pathological tooth migration, gingival recession, and exfoliation of teeth in severe cases.
\nPeriodontal disease results from a complex interplay between the subgingival biofilm and the host immune inflammatory event, which develop in the gingival and periodontal tissues in response to the challenge presented by the bacteria [2]. The bacteria may initiate the disease, but the progression is host immune-mediated, and several inflammatory cells and enzymes are released which have a detrimental effect on other cells, tissues, and organ systems. There is a shift from healthy nonpathogenic flora to a huge virulent and infectious anaerobic flora in the periodontal disease. These bacteria and their toxins and various pro-inflammatory mediators penetrate into systemic circulation. The penetration of bacterial toxins and host-mediated immunomodulatory mediators into systemic circulation can have a toxic effect on the cells and organs elsewhere in the body. Environmental, physical, social, and host stresses may affect and modify disease expression through a multitude of pathways.
\nSystemic diseases tend to increase the periodontitis progression and can complicate the treatment of periodontal diseases. Periodontal infection may significantly enhance the risk for certain systemic diseases or alter the natural course of systemic conditions. There is a two-way relationship between periodontal disease and systemic disease or condition in an individual. The influence of periodontal infection on systemic disease and condition documented includes coronary heart disease (CHD) and CHD-related events such as angina, infarction, atherosclerosis, and other vascular conditions; stroke; diabetes mellitus; preterm labor, low birth weight delivery, and preeclampsia; and respiratory conditions such as chronic obstructive pulmonary disease [3].
\nAdverse pregnancy outcomes have been attributed to infections and inflammatory conditions in the vagina and elsewhere in the body. The potential role of chronic bacterial infections elsewhere in the body remote from the fetal-placental unit, which may influence the health and growth of babies in the placenta, has been studied immensely. This realization that infection in any part of the body can affect the placenta has led to the idea that periodontal disease can be a possibility in adverse pregnancy outcome. Local elevation of pro-inflammatory prostaglandins and cytokines due to “chronic gram-negative infection” in the periodontal diseases can be a risk factor [4]. Periodontal diseases have shown to increase the systemic levels of some of these inflammatory mediators [5]. Periodontal disease has a possibility to influence pregnancy outcome through an indirect mechanism, involving inflammatory mediators or a direct bacterial assault on the amnion and causing preterm low birth weight babies (PLBW). This chapter highlights the bi-directional relationship between pregnancy, pregnancy outcome, and periodontal disease.
\nWilliam Hunter, a British physician in 1900, first developed the idea that oral microorganisms were responsible for a wide range of systemic conditions that were not easily recognized as being infectious in nature. Hunter also identified gingivitis and periodontitis as foci of infection and advocated the extraction of teeth with these conditions to eliminate source of sepsis. He also thought that oral organisms had specific actions on different tissues and that these organisms were acted by producing toxins, thereby resulting in low-grade superinfection that produce systemic effect over prolonged periods. The Hunter theory became widely accepted, thereby leading to wholesale extraction of teeth. The focal infection theory fell into disrepute during the 1940s and 1950s when widespread extraction failed to reduce or eliminate the systemic conditions. However, Hunter ideas did encourage extensive research in the areas of microbiology and immunology. The Hunter theories are being revived today in light of recent research demonstrating links between oral and systemic health. Today’s era of evidence-based medicine and dentistry provides an excellent environment in which to examine the possible relationship between oral infection and systemic disorders.
\nThe first association between periodontal disease and preterm low birth weight babies was documented by Offenbacher and colleagues in 1996 using a case-control study design. The study by Offenbacher et al. [6] suggested that maternal periodontal disease could lead to a sevenfold increased risk of delivery of a preterm low birth weight infant. Human case-control studies have demonstrated that women who have low birth weight infants as a consequence of either preterm labor or premature rupture of membranes tend to have more severe periodontal disease than mothers with normal birth weight infants [7].
\nEvery pregnant woman who is carrying a live baby in her womb wishes to deliver a healthy baby. There are numerous genetic, pathological, and environmental factors that can affect the growth and development of the baby in the womb. During the course of a normal pregnancy, a series of profound and dynamic physiological changes occur in both the mother and developing baby [8]. Pregnancy and parturition involve a complex series of molecular and biological events for mother and fetus. Pregnancy by itself does not cause periodontal diseases, but the hormonal changes during pregnancy accentuate the gingival response to plaque and modify resultant clinical picture.
\nMedical science aims at reducing the risk factors involved in the growth and development of a baby in the womb. Adverse pregnancy outcomes including preeclampsia, preterm delivery, intrauterine growth restriction, and fetal demise affect a significant number of pregnancies and are a major source of both maternal and neonatal morbidity and mortality. The Centers for Disease Control and Prevention (CDC) advocates that babies born with less than 5.5 pounds or 2.5 kg will be at risk of long-term health problems such as delayed motor skills, social growth, or learning disabilities. Babies born, at least 3 weeks, earlier than its due date have also risk for retarded growth and development [9]. Respiratory problems, vision and hearing loss, or feeding and digestive problems are other problems associated with preterm and low birth weight babies.
\nAdverse pregnancy outcomes (APOs) are serious events that every year cause the death or disability of many newly born infants worldwide [10]. The most common adverse pregnancy outcomes are represented by low birth weight (LBW), preterm birth (PTB), and preeclampsia (PE). Adverse pregnancy outcomes represent an important health issue which affects not only the infant but also the mother, and more than half a million women die each year from related causes. About 10–15% of maternal death during pregnancy is associated with PE and eclampsia, which could affect the liver, kidneys, brain, and the clotting system.
\nWorld Health Organization (WHO) in 1995 defined low birth weight (LBW) as any live birth of <2500 g and very low birth weight to be <1500 g. WHO defines preterm birth as any live birth at <37 weeks of gestation period [11, 12]. More than 33% of the infant mortality is attributed to the preterm low birth weight (PTLW), and surviving infants also have increased morbidity to congenital, neurological disabilities, and various developmental defects.
\nLittle reduction in incidence of adverse pregnancy outcomes has occurred despite advances in technology, promotion of prenatal care, and continued scientific efforts. Investigations to detect the potential causative factors for adverse pregnancy outcome include infection and/or inflammation in the reproductive tract and at sites remote from the feto-placental unit. The relationship between adverse pregnancy outcomes and maternal periodontal infections has been studied extensively over the past 10 years, as periodontal infection is most prevalent in populations with highest risk of adverse pregnancy outcomes.
\nPreviously, it was believed that there was little or no exposure of the mother to the immunologically foreign cells of the fetus. It is now clarified that there is considerable mixing of maternal and fetal cells, especially at the maternal-fetal interface.
\nOne of the major alterations in the immune system during pregnancy is partial dampening of the mother’s cell-mediated immune responses associated with T-helper type 1 (Th1) lymphocytes. Stimulated Th2 cells produce an array of cytokines, such as interleukin-4, interleukin-5, and interleukin-10, which suppress cell-mediated immune responses [13, 14, 15]. The mechanisms of this partial shift in the Th1/Th2 balance favoring Th2-mediated immune responses are not fully understood but are partly dependent on changes in progesterone, estrogen, and chorionic gonadotropin during pregnancy [8, 16].
\nNeutrophils in the peripheral circulation of pregnant women exhibit a significant reduction in myeloperoxidase, respiratory burst activities, and phagocytosis [8]. All of these inhibitory effects on neutrophils are most marked during the second and third trimesters [17, 18]. The postpartum readjustment of the mother’s immune system occurs soon after birth, with rapid re-establishment of several Th1-associated and other pro-inflammatory host responses (Table 1). The phenomenon of return of immunological response after postpartum has been termed the “immune reconstitution syndrome” [15].
\nComponents | \nChanges in host response | \n
---|---|
Innate immunity | \n|
Monocytes and neutrophils | \nEffect on cellular immunity via enhanced phagocytosis and superoxide anion generation (respiratory burst); increased expression of CD14 | \n
Natural killer cells | \nEffect on cellular immunity via downregulation of cytotoxic activity by progesterone-induced blocking factor and IL-10; decreased IFN-c production | \n
Complement | \nEffect on humoral immunity by increased C3, C4, and C1q levels and elevated levels of complement regulatory proteins including membrane cofactor protein (CD46), decay accelerating factor (CD55), and CD59 | \n
Acute-phase reactants | \nEffect on humoral immunity via increased levels of acute-phase reactants (e.g., fibrinogen and ceruloplasmin) | \n
Adaptive immunity | \n|
T cells | \nEffect on cellular immunity via enhanced Th2 (e.g., IL-4, IL-10) and Th3 (i.e., TGF-b) and suppressed Th1 (IFN-c, IL12) responses Effect on humoral immunity via increased T cell-dependent immunoglobulin production | \n
B cells | \nEffect on cellular immunity via increased Th2-induced B-cell activity IL, interleukin; IFN, interferon; Th1, T-helper type 1 lymphocytes; Th2, T-helper type 2 lymphocytes; TGF, transforming growth factor | \n
Innate and adaptive immunity changes during pregnancy [8].
IL, interleukin; IFN, interferon; Th1, T-helper type 1 lymphocytes; Th2, T-helper type 2 lymphocytes; TGF, transforming growth factor.
Pyogenic granuloma (PG) or pregnancy tumor is a non-specific inflammatory lesion of the skin and mucous membranes. PG occurs in both males and females as inflammatory lesion on skin or mucous membrane. PG occurs approximately 0.5–2.0% of pregnant women with gingival lesions developing in interdental gingiva (Figure 1). They are also called pregnancy tumors or granuloma gravidarum. The lesion frequently presents as a rapidly growing gingival mass that may bleed profusely when touched. Based on histological features, it is a highly proliferative vascular lesion resembling granulation tissue. The etiological triggers for pyogenic granuloma are unknown; most lesions are associated with the presence of local irritants or trauma [19]. The pathogenesis of the lesion has been linked to female sex hormones, which stimulate increased local synthesis of angiogenic factors such as vascular endothelial growth factor and angiopoietin-2 [8]. Clinical complaints with pregnancy-associated pyogenic granulomas include gingival bleeding, tenderness, and esthetic problems. Treatment may include surgical removal, especially if the lesion is large and symptomatic [19, 20]. However, in many cases, the lesions undergo partial or complete resolution after delivery, especially if local irritants are removed [8].
\nA case of pyogenic granuloma in maxillary right lateral incisor region in a 9-month pregnant woman.
Experimental gingivitis study of women during pregnancy and at 6 months postpartum showed that there was more gingival inflammation during pregnancy despite no significant differences in plaque scores. Cross-sectional studies indicate that 100% of women develop gingivitis between 3 and 8 months of their pregnancy, with a gradual decrease after parturition [21]. In some cases, the gingival inflammation is very severe and may be accompanied by gingival tenderness and profuse bleeding. Longitudinal studies have demonstrated that, during pregnancy, probing depths increase as the gingival inflammation increases. The increase in probing depths has been attributed to movement of the gingival margin in a coronal direction because of inflammation-induced swelling of the gingiva. Most authors have found that there is usually no permanent loss of clinical attachment [22, 23]. Individuals, especially those who have chronic periodontitis prior to becoming pregnant, tend to have increased rate of progression of periodontitis. Several standard cultural microbiological studies have shown that estrogen and progesterone changes associated with pregnancy have an effect on the composition of the subgingival microbiota. Some of the periodontal pathogens that apparently blossom under the selective pressure of pregnancy-associated steroids are
Diverse array of pathogens that have the potential to cause periodontal tissue damage have been found in pregnant and parous women through microbiological studies using DNA probes [24, 25]. Several types of spirochetes, including
Gingivitis and periodontitis are plaque-induced periodontal diseases, which are multifactorial infections involving innate and adaptive immune responses of the host toward tooth-associated microbial biofilms (plaque). Pregnant women undergo a lot of physiological and immunological changes during pregnancy. These changes in pregnancy have profound effects on the host-parasite interactions found in microbial infections. The exact mechanisms responsible for the increased gingival inflammation during pregnancy are not fully understood. It is clear that perturbations in neutrophil function, modifications in cellular and humoral immunity, hormone-induced changes in cellular physiology, and local effects on microbial ecology all play crucial roles [8].
\nGestational diabetes mellitus (GDM) refers to the detection of glucose intolerance or raised blood glucose level, for the first time during pregnancy in a woman. Gestational diabetes occurs in approximately 7% of women during pregnancy, and it is a multifactorial disease. GDM has been associated with a long list of risk factors [26]. The increased blood sugar levels make the pregnant woman more susceptible for periodontal diseases.
\nPeriodontitis and diabetes are both risk to each other, and studies have proved that increased diabetes was correlated with increased severity of periodontitis. Studies have been conducted on association of microorganisms and gestational diabetes, and contradictory results are obtained. Several study groups concluded that there appears to be an association between periodontal disease and gestational diabetes mellitus, but prospective studies with large enough sample sizes are required to confirm a relationship [8].
\nPreeclampsia is a condition characterized by hypertension, with blood pressure higher than 140/90 mmHg, and the patient also suffers from peripheral edema and proteinuria (i.e., urinary excretion of ±300 mg protein in 24 h) [27, 28]. Eclampsia occurs when there is a failure to control physiological abnormalities in a pregnant woman leading to convulsions, coma, and death of the mother.
\nMultiple factors are involved in the etiology of preeclampsia including infection, genetic susceptibility, immune responses, abnormal placentation secondary to hypoxia and impaired arterial remodeling, and a markedly enhanced systemic inflammatory burden. Increased risk of preeclampsia is seen with elevated serum levels of C-reactive protein; periodontal infections contribute to the increased C-reactive protein level [29, 30]. Therefore, it is biologically plausible that periodontal infections could play a part in the multifactorial etiology of preeclampsia. The link between periodontal disease and risk of preeclampsia is proved only in few populations and has not been confirmed in all populations [8].
\nPeriodontal disease (PD) per se causes little clinical features and goes unnoticed until late in disease status. The tissue destruction is characterized by the formation of periodontal pocket that acts as reservoirs for bacterial colonization in the dentogingival environment.
\nMultiple factors have been associated with preterm baby (PB) and/or LBW such as smoking, drug use, high or low maternal age, low socioeconomic strata, inadequate prenatal care, low maternal body mass index (BMI), hypertension, genitourinary tract infections, cervical incompetence, diabetes, low nutritional status, stress, and multiple pregnancies [31]. However, more than 50% of the cases do not show the presence of these risk factors and are still affected by PB and/or LBW [15]. The search continues for other causes including the presence of the chronic infectious diseases like periodontal infection.
\nThe hypothesis that infection remote from the fetal-placental unit may influence PLBW has led to an increased awareness of the potential role of chronic bacterial infections elsewhere in the body. Periodontal disease is associated with a “chronic gram-negative infection” of the periodontal tissues which results in long-term local elevation of pro-inflammatory prostaglandins and cytokines [8] and an increase in the systemic levels of some of these inflammatory mediators [20]. Hence, periodontal disease has a potential to influence PLBW through an indirect mechanism, involving inflammatory mediators or a direct bacterial assault on the amnion [28].
\nMultiple factors have been associated with the delivery of preterm and low birth weight infants. The evidence suggests that an infectious etiology is the main cause for a large percentage of cases for preterm birth. Genitourinary tract infections, such as bacterial vaginosis, and inflammatory mediators resulting from such infections have been considered a biologically plausible pathway for preterm labor and premature rupture of the membranes. Alternatively, it was hypothesized that preterm low birth weight may be indirectly mediated through distant infections resulting in translocation of bacterial vesicles and lipopolysaccharide (LPS) in the systemic circulation. However, the exact mechanisms for the proposed relationship remain unclear. The periodontal infection is initiated by predominantly gram-negative, anaerobic, and microaerophilic bacteria that colonize the subgingival area. Host defense mechanisms play integral role in the pathogenesis of periodontal disease. It has been postulated that the association between periodontal disease and preterm low birth weight (PLBW) may have similar pathogenic mechanisms as other maternal infections [32]. Inflamed periodontal tissues produce significant amounts of pro-inflammatory cytokines, mainly interleukin 1 (IL-1b), IL-6, prostaglandin E2, and tumor necrosis factor-alpha (TNF-α), which may have systemic effects on the host, leading to premature rupture of membrane. Hence, periodontal disease has the potential to influence preterm low birth weight through an indirect mechanism involving inflammatory mediators or a direct bacterial assault on the amnion [8, 33] (Figure 2).
\nSchematic representation of role of bacterial infection in preterm labor.
The inflammation and infection caused during the periodontal disease is not just limited to the oral cavity but also enters the systemic circulation. The systemic immune response gets activated due to the episodes of bacteraemia and dissemination of endotoxins from periodontal pockets. Systemic circulation may induce pro-inflammatory cytokine production due to the presence of bacteria or bacterial endotoxins in the systemic circulation. IL-6 and C-reactive protein that are released during chronic low-grade inflammation are further activated due to presence of cytokines in the systemic circulation. The endothelial dysfunction may result due to inflammatory response of endothelial cells. The immune response plays a pivotal role in maintaining a healthy equilibrium between the mother and fetus, during pregnancy. The specific immune response is shifted toward a Th2-type immune response, and the inflammatory response is also activated, during a normal pregnancy. During pregnancy there is an increase in expression of activation markers on monocytes and granulocytes, differences in monocyte cytokine production, and increased circulating levels of pro-inflammatory cytokines and inflammatory markers, such as C-reactive protein.
\nPeriodontitis sites and subjects harbor specific microorganisms or groups of microorganisms.
The absence of the mother’s IgG antibody against organisms of the red complex is associated with an increased risk of premature birth of the baby. Mothers without a protective red complex IgG response coupled with a fetal IgM response to orange complex microbes had the highest rate of prematurity. This evidence suggests the concept that prematurity in pregnant women may be due to systemic dissemination of oral organisms that translocate to the fetus in the absence of a protective maternal antibody response and trigger preterm babies. The high prevalence of elevated fetal IgM to
No definitive conclusions can be arrived about periodontal disease (PD) treatment during pregnancy. Attempts to improve oral health in women during pregnancy have not reduced adverse pregnancy outcome (APO). No reduction in APOs was observed with standard PD therapy during pregnancy in several large clinical randomized controlled trials [36].
\nThe dilemma of performing periodontal treatment during pregnancy to reduce the APOs has not been answered. Periodontal treatment even if undertaken during pregnancy will not be thorough and completely eradicate the disease process, due to fear of bacteraemia which may cause APO. Pre-conception period is most appropriate time for periodontal treatment. Periodontal treatment to create a healthy mouth before conception may reduce the occurrence of APOs. The local and systemic inflammation caused by periodontal pathogens may not be controlled by periodontal treatment during pregnancy. Periodontal treatment before pregnancy (for nulliparous women) or in the period between pregnancies (for multiparous women) may reduce APOs [37].
\nThere was a deep-seated bias in the medical/dental community against nonsurgical periodontal interventions during pregnancy [38]. After long-term studies and analysis, the medical and dental fraternity is in a general agreement that pregnant patients can safely undergo dental cleaning [39]. Interventions to reduce the morbidity and mortality associated with preterm birth can be classified as primary, secondary, and tertiary. All interventions examined by existing studies on the effects of periodontal therapy on pregnancy outcomes can be classified as secondary interventions [38]. It has been known for many years that nonsurgical periodontal therapy is effective in reducing the increased amount of periodontal inflammation associated with pregnancy [33, 40, 41]. Data clearly show that this therapy is safe and does not trigger an increase in adverse pregnancy outcomes. It has not been shown that routine nonsurgical periodontal therapy decreases the incidence of these outcomes. In general, women assigned to the periodontal treatment groups showed statistically significant improvements in their periodontal assessments.
\nPregnancy in woman brings about profound changes in innate and adaptive immunity of the mother and fetus; these changes play a major role altering the clinical course of a number of infectious diseases, including periodontal diseases. The severity of gingival and periodontal diseases increases during the course of normal pregnancy. Gingival inflammation and tissue response toward the microbial plaque is exaggerated during pregnancy due to the hormonal factors and is accepted by the scientific community. Pregnant women with previously existing periodontal disease will have increased destruction of the periodontal structures. The gingival changes observed during pregnancy return to normal limits immediately after delivery of the baby, if the local irritants are removed; this phenomenon is called as “immune reconstitution syndrome.” Gestational diabetes which occurs in certain pregnant women can increase the risk for periodontal diseases, and it should be well controlled by treating gynecologist. Preeclampsia if not detected and treated can cause serious condition eclampsia leading to convulsions, coma, and death of the mother.
\nLarge numbers of epidemiological studies suggest that periodontal infection is a modest risk factor for several adverse pregnancy outcomes. The studies conducted to link between periodontal diseases and adverse pregnancy outcomes have had contradictory results, as they were carried out in different sets of populations or with different study designs. It is better to consider periodontal disease as a risk factor for adverse pregnancy outcome, as thorough oral health maintenance helps the pregnant women attain a better oral health which is part of general health.
\nControversies in the academic community regarding the treatment of periodontal problems have been eradicated. It is well accepted that oral prophylaxis and nonsurgical periodontal therapy can be rendered to pregnant women in the second trimester.
\nPeriodontal diseases go unnoticed in the initial stages of disease process. The inflammatory load of periodontal disease can enter the systemic circulation and can be a risk factor for several host tissues and physiological activities. There is definite link between periodontal diseases and adverse pregnancy outcomes, through direct or indirect mechanisms. The direct action of perio-pathogenic organisms on amnion and indirect action through systemic circulation by production of inflammatory mediators can be risk for adverse pregnancy outcomes.
\nI have no “conflict of interest” in publishing this chapter.
I would like to acknowledge my colleague, Dr. Sameer Zope, and thank Dr. Divyanee Doshi, my postgraduate student, for all the help in completing this chapter.
\nThese Terms and Conditions outline the rules and regulations pertaining to the use of IntechOpen’s website www.intechopen.com and all the subdomains owned by IntechOpen located at 5 Princes Gate Court, London, SW7 2QJ, United Kingdom.
',metaTitle:"Terms and Conditions",metaDescription:"These terms and conditions outline the rules and regulations for the use of IntechOpen Website at https://intechopen.com and all its subdomains owned by Intech Limited located at 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK.",metaKeywords:null,canonicalURL:"/page/terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
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\\n\\nIntechOpen has no formal affiliation to any external sites that link to www.intechopen.com, unless otherwise specifically stated. As such, it is not responsible for content that appears on any such sites. The inclusion of any link to IntechOpen does not imply endorsement by IntechOpen. Use of any such linked website is done solely at the user's own discretion.
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\n\nWe employ the use of cookies. By using the IntechOpen website you consent to the use of cookies in accordance with IntechOpen’s Privacy Policy. Most modern day interactive websites use cookies to enable the retrieval of user details for each visit. On our site, cookies are predominantly used to enable functionality and ease of use for those visiting the site.
\n\nIn no circumstances shall IntechOpen or its suppliers be liable for any damages (including, without limitation, damages for loss of data or profit, or due to business interruption) arising out of the use, or inability to use, the materials on IntechOpen's websites, even if IntechOpen or an IntechOpen authorized representative has been notified orally or in writing of the possibility of such damage. Some jurisdictions do not allow limitations on implied warranties, or limitations of liability for consequential or incidental damages; consequently, these limitations may not apply to you.
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\n\nIntechOpen has no formal affiliation to any external sites that link to www.intechopen.com, unless otherwise specifically stated. As such, it is not responsible for content that appears on any such sites. The inclusion of any link to IntechOpen does not imply endorsement by IntechOpen. Use of any such linked website is done solely at the user's own discretion.
\n\nWe reserve the right of ownership over our entire website www.intechopen.com, and all contents. By using our services, you agree to remove all links to our website immediately upon request. We also reserve the right to amend these Terms and Conditions and our linking policy at any time. By continuing to link to our website, you agree to be bound to, and abide by, these linking Terms and Conditions.
\n\nIf you find any link on our website, or any linked website, objectionable for any reason, please Contact Us. We will consider all requests to remove links but will have no obligation to do so.
\n\nWithout prior approval and express written permission, you may not create frames around our web pages or use other techniques that alter in any way the visual presentation or appearance of our website.
\n\nIntechOpen may revise its Terms of Service for its website at any time without notice. By using this website, you are agreeing to be bound by the current version of all Terms at the time of use.
\n\nThese Terms and Conditions are governed by and construed in accordance with the laws of the United Kingdom and you irrevocably submit to the exclusive jurisdiction of the courts in London, United Kingdom.
\n\nCroatian version of Terms and Conditions available here
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