Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8292",leadTitle:null,fullTitle:"Oral Health by Using Probiotic Products",title:"Oral Health by Using Probiotic Products",subtitle:null,reviewType:"peer-reviewed",abstract:'One of the most prevalent and important health problems in the world is periodontal and plaque-related diseases for which antibiotic drugs with their associated side effects are used as treatment. With increasing resistance to antibiotics and a desire from the general public for "natural" therapies, there is a need to minimize antibiotic use and develop new treatments for oral diseases without antimicrobial agents. Probiotics are viable microorganisms that provide a health benefit to the host when administered in adequate amounts; studies show that probiotics have the potential to modify the oral microbiota and decrease the colony-forming unit counts of the oral pathogens being investigated to prevent or treat oral diseases, such as dental caries and the periodontal diseases. In addition, the identification of specific strains with probiotic activity is required for any oral infectious disease to determine the exact dose, the time of treatment, and the ideal vehicle.',isbn:"978-1-83968-140-0",printIsbn:"978-1-83968-139-4",pdfIsbn:"978-1-83968-141-7",doi:"10.5772/intechopen.78421",price:119,priceEur:129,priceUsd:155,slug:"oral-health-by-using-probiotic-products",numberOfPages:118,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"327e750e83634800ace02fe62607c21e",bookSignature:"Razzagh Mahmoudi",publishedDate:"December 11th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8292.jpg",numberOfDownloads:5892,numberOfWosCitations:8,numberOfCrossrefCitations:10,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:18,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:36,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 12th 2018",dateEndSecondStepPublish:"August 2nd 2018",dateEndThirdStepPublish:"October 1st 2018",dateEndFourthStepPublish:"December 20th 2018",dateEndFifthStepPublish:"February 18th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"245925",title:"Dr.",name:"Razzagh",middleName:null,surname:"Mahmoudi",slug:"razzagh-mahmoudi",fullName:"Razzagh Mahmoudi",profilePictureURL:"https://mts.intechopen.com/storage/users/245925/images/system/245925.jpg",biography:"Razzagh Mahmoudi, DVM, PhD, is an associate professor of Food Hygiene and Safety at Department of Food Safety and Hygiene, Qazvin University of Medical Sciences, Iran. He was Educational Deputy of the Faculty of Public Health from 2016 to 2019 (member of Founding Board at Medical Microbiology Research Center, Qazvin University of Medical Sciences, Iran). He is Editorial Board member of about 5 international journals. His specializations are in molecular food microbiology, functional foods, probiotics and prebiotics, medicinal plants, food chemistry, dairy and meat technology, food and human nutrition. His research field includes molecular food microbiology, natural preservative from medicinal plant and biological source, production of new functional foods, application of natural preservative in dairy and meat products, and innovative pharmacological and nutritional research in new drug production and food production. He published around 180 papers (ISI, Scopus, Pubmed, CAB, CAS, ISC etc), 1 book chapter and 80 abstracts in national and international congresses.",institutionString:"Qazvin University of Medical Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"895",title:"Medical Microbiology",slug:"medical-microbiology"}],chapters:[{id:"69279",title:"Introductory Chapter: Oral Health by Using Probiotic Products",doi:"10.5772/intechopen.89355",slug:"introductory-chapter-oral-health-by-using-probiotic-products",totalDownloads:527,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Razzagh Mahmoudi, Sara Moosazad and Katayoon Aghaei",downloadPdfUrl:"/chapter/pdf-download/69279",previewPdfUrl:"/chapter/pdf-preview/69279",authors:[{id:"245925",title:"Dr.",name:"Razzagh",surname:"Mahmoudi",slug:"razzagh-mahmoudi",fullName:"Razzagh Mahmoudi"}],corrections:null},{id:"68058",title:"Therapeutic Potential of Probiotics and Prebiotics",doi:"10.5772/intechopen.86762",slug:"therapeutic-potential-of-probiotics-and-prebiotics",totalDownloads:1402,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:1,abstract:"Advancement in technology is continued as the time is passed. The biological active ingredients technology is the challenging issues for both the researchers and manufacturers. In last decade, much research has been happened about the potential health benefits of pro and prebiotic ingredients. Probiotics are the live microorganisms when given in adequate amount confer health benefits but the prebiotics are indigestible ingredients that enhance the activity of one or more probiotics in the colon. The therapeutic potential of these two biological active ingredients is the outcome of emerging field of biotechnology. A number of studies indicating therapeutic potential of probiotics regarding gastrointestinal health, cancer, constipation, immunomodulation, Helicobacter pylori, liver disease and urogenital infection have been documented. Similarly, prebiotics also improved helpful for many communicable and non-communicable diseases. It can be seen that advancement in the biotechnology field offer great choice to deliver a marvelous health advantages. Although the market for probiotic and prebiotic food and supplements has been increased in this new era but still need to develop food and supplements containing these two active ingredients with the cooperation of legal bodies of the country.",signatures:"Nabila Gulzar, Iqra Muqaddas Saleem, Saima Rafiq and Muhammad Nadeem",downloadPdfUrl:"/chapter/pdf-download/68058",previewPdfUrl:"/chapter/pdf-preview/68058",authors:[{id:"235261",title:"Dr.",name:"Muhammad",surname:"Nadeem",slug:"muhammad-nadeem",fullName:"Muhammad Nadeem"},{id:"268484",title:"Dr.",name:"Nabila",surname:"Gulzar",slug:"nabila-gulzar",fullName:"Nabila Gulzar"},{id:"278785",title:"Ms.",name:"Iqra",surname:"Muqaddas",slug:"iqra-muqaddas",fullName:"Iqra Muqaddas"},{id:"278786",title:"Dr.",name:"Saima",surname:"Rafiq",slug:"saima-rafiq",fullName:"Saima Rafiq"}],corrections:null},{id:"67675",title:"Gut-Brain Axis: Probiotic, Bacillus subtilis, Prevents Aggression via the Modification of the Central Serotonergic System",doi:"10.5772/intechopen.86775",slug:"gut-brain-axis-probiotic-em-bacillus-subtilis-em-prevents-aggression-via-the-modification-of-the-cen",totalDownloads:1257,totalCrossrefCites:5,totalDimensionsCites:9,hasAltmetrics:1,abstract:"Intestinal bacteria release various neuroactive compounds directly or indirectly regulating brain function to modulate host health and behavior through the gut-brain axis. Probiotics have been used as dietary supplements to target gut microbiota (microbiome) for prevention or therapeutic treatment of various diseases including mental disorders. In our study, chickens were used as an animal model to assess, if dietary supplementation of probiotic, Bacillus subtilis, reduces aggressive behaviors following social challenge. Chickens of an aggressive line were housed in single-hen cages. At 24 weeks of age, the hens were paired with similar body weight to identify the dominance rank (day 0). The subordinate and dominant of each pair were fed a regular layer diet or the diet mixed with 250 ppm probiotics for 2 weeks, then the second behavior test was performed between the same pair (day 14). The display of aggressive behaviors in the regular diet-fed chickens was not affected between the levels at day 0 and day 14, while the frequency of threat and aggressive pecking were reduced in the probiotic-fed chickens compared to the levels at day 0. These results suggest dietary probiotic, Bacillus subtilis, could be a suitable strategy for increasing hosts’ mental health.",signatures:"Heng-Wei Cheng, Sha Jiang and Jiaying Hu",downloadPdfUrl:"/chapter/pdf-download/67675",previewPdfUrl:"/chapter/pdf-preview/67675",authors:[{id:"68434",title:"Dr.",name:"Heng-Wei",surname:"Cheng",slug:"heng-wei-cheng",fullName:"Heng-Wei Cheng"},{id:"270234",title:"Prof.",name:"Sha",surname:"Jiang",slug:"sha-jiang",fullName:"Sha Jiang"},{id:"283995",title:"Dr.",name:"Jiaying",surname:"Hu",slug:"jiaying-hu",fullName:"Jiaying Hu"}],corrections:null},{id:"67656",title:"Oral Health by Using Probiotic Products",doi:"10.5772/intechopen.86714",slug:"oral-health-by-using-probiotic-products",totalDownloads:855,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"One of the most prevalent and important health problems in the world is periodontal and plaque-related diseases that antibiotic drugs are used with their side effects as their treatment. With increasing resistance to antibiotics and a desire from the general public for “natural” therapies, there is a need to minimize antibiotic use and develop new treatments for oral diseases without antimicrobial agents. Probiotics are viable microorganisms which provide a health benefit to the host when administered in adequate amounts; studies show that probiotics have the potential to modify the oral microbiota and decrease the colony-forming unit (CFU) counts of the oral pathogens being investigated to prevent or treat oral disease, such as dental caries and the periodontal diseases. In addition, the identification of specific strains with probiotic activity is required for any oral infectious disease, in order to determine the exact dose, the time of treatment, and the ideal vehicle.",signatures:"Razzagh Mahmoudi, Sara Moosazad and Katayoon Aghaei",downloadPdfUrl:"/chapter/pdf-download/67656",previewPdfUrl:"/chapter/pdf-preview/67656",authors:[{id:"245925",title:"Dr.",name:"Razzagh",surname:"Mahmoudi",slug:"razzagh-mahmoudi",fullName:"Razzagh Mahmoudi"}],corrections:null},{id:"67420",title:"Metabolite Multiprobiotic Formulas for Microbial Health",doi:"10.5772/intechopen.86449",slug:"metabolite-multiprobiotic-formulas-for-microbial-health",totalDownloads:828,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"On example of Lactobacillus and Bifidobacterium strains, approaches in creation of human multistrain probiotic metabolite mixtures for different goals were proposed. Human probiotic lectin systems (LS) (mucosal, others) reveal functions needed for organism. Advanced features of such systems include capability to recognize synthetic polymeric polyvalent glycoconjugates (GC)—imitators of natural ones (modified polysaccharides, glycoantigens of medical significance). Probiotic lectin systems function as imitators of multipro-/sym-/synbiotics in their resulting actions. They serve as carriers of the biotope glycoconjugate décor including glycoprebiotics, glycometabiotics, glycodrugs, and agents supporting décor organization and resistance. Probiotic lectin systems represent new perspective system agents to improve the health of mucosal microbiocenoses (MB) organized as communicative bodies to be corrected according to the principle “there is body—there are diseases.” They act as metabolomebiotics according to the principle “the network in the network.” They deepen biotope resistance allowing quicker return to balance. They support prophylactic and therapeutic procedures directed to prolong aging and improve quality of life. Multistrain metabolite constructions can predict perspective cellular formulas of multipro-/synbiotics for prophylaxis, supporting and accompanying therapy. Approaches developed are universal. They are useful in the study of any Gram-positive and eukaryotic (yeasts and yeast-like fungi) mono- and mixed cultures. The methodological principles proposed and described are of value for extended fields of clinical microbiology and medical bio-/nanotechnology.",signatures:"Mikhail V. Lakhtin, Vladimir M. Lakhtin, Vladimir A. Aleshkin and Stanislav S. Afanasiev",downloadPdfUrl:"/chapter/pdf-download/67420",previewPdfUrl:"/chapter/pdf-preview/67420",authors:[{id:"150430",title:"Prof.",name:"Vladimir",surname:"Lakhtin",slug:"vladimir-lakhtin",fullName:"Vladimir Lakhtin"},{id:"150462",title:"Prof.",name:"Stanislav",surname:"Afanasiev",slug:"stanislav-afanasiev",fullName:"Stanislav Afanasiev"},{id:"150463",title:"Prof.",name:"Vladimir",surname:"Aleshkin",slug:"vladimir-aleshkin",fullName:"Vladimir Aleshkin"},{id:"271355",title:"Dr.",name:"Mikhail",surname:"Lakhtin",slug:"mikhail-lakhtin",fullName:"Mikhail Lakhtin"}],corrections:null},{id:"67537",title:"Gut Microbiota and Obesity: Prebiotic and Probiotic Effects",doi:"10.5772/intechopen.86672",slug:"gut-microbiota-and-obesity-prebiotic-and-probiotic-effects",totalDownloads:1024,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Malnutrition through excessive food consumption is a worldwide pandemic. Changes in lifestyle, diet and physical activity have resulted in an exponential increase in the number of obese people around the world. Multiple factors influence the development of this disease, and recently it has been suggested that gut microbiota (GM) plays an important role in nutrient absorption and energy regulation of individuals, thus affecting their nutritional status. It has been proven that gut microbiota is different in individuals with a normal nutritional status compared to those who are obese. Therefore, to study bacterial populations that make up the microbiota and to understand how prebiotics and probiotics affect the increase of these bacteria has become a promising alternative to treat obesity. This chapter looks at defining the established relationship between probiotics, prebiotics and gut microbiota that develop in obese people and people of normal weight, with the aim of providing future dietary recommendations to treat this medical condition.",signatures:"Silvana Cisternas León, Paula Carrasco Vergara, Alejandra Cruz Neira, Ricardo Muñoz Maldonado, Carolina Díaz Araneda and Marcia Rivas Zuñiga",downloadPdfUrl:"/chapter/pdf-download/67537",previewPdfUrl:"/chapter/pdf-preview/67537",authors:[{id:"223462",title:"MSc.",name:"Silvana",surname:"Cisternas",slug:"silvana-cisternas",fullName:"Silvana Cisternas"},{id:"274374",title:"MSc.",name:"Alejandra",surname:"Cruz",slug:"alejandra-cruz",fullName:"Alejandra Cruz"},{id:"274375",title:"MSc.",name:"Carolina",surname:"Díaz",slug:"carolina-diaz",fullName:"Carolina Díaz"},{id:"274376",title:"MSc.",name:"Ricardo",surname:"Muñoz",slug:"ricardo-munoz",fullName:"Ricardo Muñoz"},{id:"274377",title:"Prof.",name:"Marcia",surname:"Rivas",slug:"marcia-rivas",fullName:"Marcia Rivas"},{id:"274379",title:"MSc.",name:"Paula",surname:"Carrasco",slug:"paula-carrasco",fullName:"Paula Carrasco"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:{id:"17",series:{id:"11",title:"Biochemistry",issn:"2632-0983",editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}}},tags:null},relatedBooks:[{type:"book",id:"548",title:"Antibiotic Resistant Bacteria",subtitle:"A Continuous Challenge in the New Millennium",isOpenForSubmission:!1,hash:"f8a58b7ebbb9cd01db5c16fbf9f80b44",slug:"antibiotic-resistant-bacteria-a-continuous-challenge-in-the-new-millennium",bookSignature:"Marina Pana",coverURL:"https://cdn.intechopen.com/books/images_new/548.jpg",editedByType:"Edited by",editors:[{id:"77349",title:"Dr.",name:"Marina",surname:"Pana",slug:"marina-pana",fullName:"Marina Pana"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5193",title:"Probiotics and Prebiotics in Human Nutrition and Health",subtitle:null,isOpenForSubmission:!1,hash:"facfb45c80773cd5151d8f53b902be39",slug:"probiotics-and-prebiotics-in-human-nutrition-and-health",bookSignature:"Venketeshwer Rao and Leticia G. 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1. Introduction
It is well known that specific human leukocyte antigen (HLA) class II alleles are associated with susceptibility to many autoimmune diseases [1]. However, the mechanisms by which specific HLA class II molecules control the immune response in autoimmune diseases have been unclear. On the other hand, autoantibodies are produced in most autoimmune diseases and cause clinical manifestations of the diseases. It has also been an enigma how autoantibodies targeting self-antigens cause the autoimmune diseases. Arase et al. discovered a novel function of HLA class II molecules which are involved in the pathogenesis of certain autoimmune diseases [2, 3, 4, 5].
This review will focus on the autoantibodies associating with the novel function of HLA class II molecules and the pathogenesis of antiphospholipid syndrome (APS).
2. The novel function of HLA class II molecules and autoimmune diseases
The classical function of HLA class II molecules is to present antigen peptides, derived from exogeneous proteins digested in lysosomes, to helper T-cells and by that to activate them.
Endogenous proteins, on the other hand, are formed and folded in the endoplasmic reticulum (ER). Correctly folded proteins are essential for cell survival and function. Therefore, it is believed that misfolded proteins generated in the ER are never transported to the extracellular space, because such proteins are eliminated by ER-associated degradation (ERAD).
However, Arase et al. discovered that misfolded proteins can be rescued from ERAD and transported to the cell surface without being processed into peptides. This process occurs in the ER via an association between the misfolded proteins and the peptide-binding groove of HLA class II molecules [2].
In addition, misfolded proteins complexed with HLA class II molecules of disease-susceptible alleles have been found to serve as targets of autoantibodies in certain autoimmune diseases, and to be involved in the disease pathogenesis. For example, immunoglobulin (Ig) G heavy chain complexed with HLA-DR and myeloperoxidase complexed with HLA-DR are major targets for autoantibodies in patients with rheumatoid arthritis and microscopic polyangiitis, respectively [3, 5].
3. The conventional concepts of antiphospholipid antibodies in APS
APS is diagnosed both by the presence of clinical manifestations, including vascular thrombosis and pregnancy morbidity, and by the presence of antiphospholipid antibodies (aPLs) which present a laboratory criteria for APS [6]. Laboratory criteria for APS include IgG and IgM anticardiolipin antibodies (aCLs), IgG and IgM anti-β2-glycoprotein I (aβ2GPI) antibodies, and lupus anticoagulant (LAC). aPLs are thought to recognize linear β2-glycoprotein I (β2GPI), which undergoes conformational changes from the circular form of β2GPI by binding to negatively charged phospholipids [7], and cause APS by interacting with vascular endothelial cells [8]. Therefore, β2GPI bound to negatively charged phospholipids or negatively charged plates is used clinically to detect autoantibodies in APS patients [9]. However, because autoantibodies against the β2GPI complexed to negatively charged phospholipids or high binding plates are detected in less than half of patients with clinical manifestations of APS [10, 11, 12], these facts suggest that additional targets of autoantibodies may exist. Furthermore, because β2GPI is a secreted protein, it cannot be universally present on the cell surface. Therefore, there might be other specific molecules which present β2GPI on the surface of vascular endothelial cells.
4. The discovery of a novel autoantibody against β2GPI/HLA-DR complex in APS
We found that 293 T cells co-transfected with β2GPI and HLA-DR expressed both β2GPI and HLA-DR on the cell surface by flow cytometry analysis (Figure 1) [4]. Conversely, 293 T cells transfected with only β2GPI did not express β2GPI on the cell surface, because β2GPI is a secreted protein (Figure 1) [4]. Immunoprecipitation and immunoblotting experiments revealed that full-length β2GPI proteins, but not peptide fragments of β2GPI, formed a complex with HLA-DR, and that these full-length β2GPI/HLA-DR complexes were present on the cell surface [4].
Figure 1.
Monoclonal anti-phospholipid antibody binds to β2GPI/HLA-DR complex on the cell surface. 293 T cells transfected with only β2GPI did not express β2GPI on the cell surface, and human monoclonal anti-phospholipid antibody (EY2C9) did not bind to these cells (the upper 3 histograms and 1 scheme). When β2GPI was co-transfected with HLA-DR into 293 T cells, β2GPI was expressed on the cell surface and was recognized by EY2C9 monoclonal antibody (the lower 3 histograms and 1 scheme). Abbreviations: HLA, human leukocyte antigen; β2GPI, β2-glycoprotein I; aPL mAb, anti-phospholipid monoclonal antibody.
Furthermore, flow cytometry analysis revealed that not only the monoclonal antiphospholipid antibody derived from an APS patient (EY2C9), but also antibodies in the sera of APS patients can bind to the β2GPI/HLA-DR complexes, even in the absence of phospholipids [4].
5. Autoantibodies targeting β2GPI/HLA-DR complex are involved in the pathogenesis of APS
Immunofluorescence staining and in situ proximity-ligation assay (PLA), which detect close proximity (less than 40 nm) between two molecules [13], showed that β2GPI and HLA-DR were co-localized in endothelial cells of the placental decidua vessels from APS patients with spontaneous abortion. In contrast, no co-localization of β2GPI and HLA-DR was observed in placental tissues obtained from patients without APS [4].
In addition, we found that monoclonal antibody EY2C9 exhibited complement-mediated cytotoxicity against 293 T cells expressing β2GPI together with the APS susceptibility allele HLA-DR7, however the cytotoxicity was not detected against 293 T cells expressing HLA-DR7 alone or against those transfected with β2GPI alone [4].
HLA class II expression on endothelial cells is known to be induced after exposure to cytokines, such as IFN-γ and TNF-α [14]. Therefore, inflammatory stimuli can induce HLA class II expression on vascular endothelial cells, and HLA class II molecules transport structurally altered β2GPI, which has high affinity for the peptide-binding grooves of the alleles of HLA class II. Autoantibodies against β2GPI/HLA class II complexes may damage vascular endothelial cells expressing β2GPI/HLA class II complexes in a complement-dependent manner and cause clinical manifestations of APS, including vascular thrombosis and pregnancy complications. In this way, β2GPI/HLA class II complexes and autoantibodies against the complexes may be involved in the pathogenesis of APS.
6. Alleles of HLA-DR complexed with β2GPI affect susceptibility to APS
HLA-DR4, HLA-DR7, and HLA-DR13 have been reported as susceptibility alleles for APS [15, 16, 17, 18]. However, the mechanism by which these HLA class II alleles increase susceptibility to APS has remained an enigma.
To address this issue, we analyzed the ability of different HLA-DR alleles to transport β2GPI to the cell surface and found that HLA-DR7 and HLA-DR4 could transport much higher levels of β2GPI than other HLA-DR alleles recognized by the EY2C9 monoclonal antibody [4]. These results indicated that a binding affinity of β2GPI to each HLA-DR allele is important for autoantibody recognition of β2GPI/HLA-DR complexes and is associated with differences in susceptibility to APS between different HLA-DR alleles.
7. A method for quantifying serum levels of autoantibodies against β2GPI/HLA-DR complexes
We developed and modified a method to measure serum levels of autoantibodies against β2GPI/HLA-DR complexes (anti-β2GPI/HLA-DR) [4, 19].
Green fluorescent protein (GFP)-labeled β2GPI/HLA-DR complex-expressing 293 T cells and DsRed-labeled HLA-DR-expressing 293 T cells were generated by transient transfection [19]. A serum sample from a patient in whom anti-β2GPI/HLA-DR were detectable after a 106-fold dilution was used as a standard serum. The anti-β2GPI/HLA-DR level of a standard serum was defined as 1,000 units. The mean fluorescence intensity (MFI) of IgG binding to transfected cells in the sample sera was analyzed by flow cytometry. Specific IgG binding to the β2GPI/HLA-DR complex was calculated by subtracting the MFI of IgG binding to HLA-DR-expressing cells from β2GPI/HLA-DR complex-expressing cells. Serum levels of anti-β2GPI/HLA-DR in each sample were calculated from the standard curve generated by measuring specific IgG binding to the β2GPI/HLA-DR complex in serially diluted standard serum.
8. Autoantibody against β2GPI/HLA-DR complex is a promising novel biomarker for APS
In our previous study, we measured serum levels of anti-β2GPI/HLA-DR in stored sera from 120 patients with APS, most of whom had a history of vascular thrombosis, and found that 83% of the 120 patients had autoantibodies directed against β2GPI/HLA-DR complexes. Furthermore, about 50% of the APS patients who tested positive for anti-β2GPI/HLA-DR (< 99th percentile values measured in sera of 100 healthy subjects) were negative for both IgG aCLs and IgG aβ2GPI antibodies [4]. Another recent study also showed that 27% of 111 patients with idiopathic chronic limb ulcers who were negative for aPLs possessed anti-β2GPI/HLA-DR [20]. These results suggest that anti-β2GPI/HLA-DR are associated with APS manifestations, even in patients who do not meet the diagnostic criteria for APS because they are negative for conventional aPLs.
The latest prospective, multicenter, cross-sectional study, of 227 couples with recurrent pregnancy loss (RPL), which is one of the clinical manifestations of APS, revealed that 22.9% (52/227) of women with RPL tested positive for anti-β2GPI/HLA-DR (< 99th percentile values measured in sera of 208 healthy, fertile control women) [19]. In this study, anti-β2GPI/HLA-DR were detected most frequently in women with RPL among other commonly recognized risk factors for RPL, i.e., uterine malformation, thyroid dysfunction, chromosomal abnormality, aPLs positive, low factor XII activity, low protein S activity, and low protein C activity (Figure 2). Importantly, 53.3% (121/227) of women with RPL had no commonly accepted risk factors for RPL, and 24 of these 121 (19.8%) women with unexplained RPL were positive for anti-β2GPI/HLA-DR (Figure 2). In addition, 45 of the 227 women with RPL (19.8%) were positive for at least one of the 5 conventional aPLs meeting the diagnostic criteria for APS in this study, i.e., IgG aCL (8.8%), IgM aCL (6.2%), IgG aβ2GPI (3.1%), IgM aβ2GPI (1.3%), and LAC (2.6%). The rate of positivity for anti-β2GPI/HLA-DR was the highest (22.9%) of the 5 aPLs that met the diagnostic criteria for APS. Notably, 35 (67.3%) of the 52 women with RPL who were positive for anti-β2GPI/HLA-DR, were negative for APS laboratory criteria (Figure 3).
Figure 2.
Risk factors for recurrent pregnancy loss (RPL) among 227 women with RPL. All women with RPL enrolled in this study attended evaluations to identify commonly accepted risk factors for RPL. Black pie slices indicate the frequencies of women with RPL who were also positive for anti-β2GPI/HLA-DR (n = 52). Abbreviations: aPLs, antiphospholipid antibodies.
Figure 3.
Positivity for anti-β2-glycoprotein I /HLA-DR antibodies (anti-β2GPI/HLA-DR) and antiphospholipid antibodies (aPLs) in 227 women with recurrent pregnancy loss (RPL). Numbers in the Venn diagram represent the number of women who had unique or nonunique results in tests for aPLs and anti-β2GPI/HLA-DR. abbreviations: Ig, immunoglobulin; HLA, human leukocyte antigen; β2GPI, β2-glycoprotein I; aβ2GPI, anti-β2-glycoprotein I antibody; aCL, anti-cardiolipin antibody; LAC, lupus anticoagulant.
On the other hand, the presence of multiple aPLs and LAC positivity has been reported to be strongly associated with the severity of clinical manifestations of APS [21, 22, 23, 24, 25, 26]. In our study, all 3 women with RPL who had double or triple aPLs positivity were also positive for anti-β2GPI/HLA-DR, and the 2 with triple positivity had very high anti-β2GPI/HLA-DR levels (927.5 units and 330.7 units). First of both women experienced early-onset HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) at 14 weeks of gestation, and the second experienced a thromboembolism with cerebral infarction [19]. Multiple positivity for aPLs may be associated with higher levels of anti-β2GPI/HLA-DR, and these conditions may be closely associated with the severity of the clinical manifestations of APS.
9. The future perspectives of the clinical use of autoantibodies targeting β2GPI/HLA-DR complexes
The standard treatment for pregnant women with APS is combination therapy with heparin and low-dose aspirin (LDA) [27], and the same therapy could also be effective in the treatment of women with RPL and anti-β2GPI/HLA-DR positivity. A cohort study is already underway to assess the efficacy of LDA and/or heparin therapy in such women. The history of vascular thrombosis and obstetric complications, including hypertensive disorders of pregnancy and fetal growth restriction, has not been investigated in prospective studies. Future studies assessing whether anti-β2GPI/HLA-DR are associated with thrombosis, hypertensive disorders of pregnancy, and fetal growth restriction are needed.
Further understanding of these novel autoantibodies associated with novel function of HLA class II molecules will provide new insights into the etiology of not only APS but also other autoimmune diseases and might lead to development of new treatment strategies for these diseases.
\n',keywords:"Autoantibody, β2-glycoprotein I, HLA class II, recurrent pregnancy loss",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/76422.pdf",chapterXML:"https://mts.intechopen.com/source/xml/76422.xml",downloadPdfUrl:"/chapter/pdf-download/76422",previewPdfUrl:"/chapter/pdf-preview/76422",totalDownloads:117,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:44,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"December 20th 2020",dateReviewed:"March 31st 2021",datePrePublished:"April 23rd 2021",datePublished:"May 4th 2022",dateFinished:"April 23rd 2021",readingETA:"0",abstract:"We have found that a novel autoantibody against β2-glycoprotein I (β2GPI)/human leukocyte antigen (HLA) class II complexes (anti-β2GPI/HLA-DR) is involved in the pathogenesis of antiphospholipid syndrome (APS). It was also found that many APS patients who were negative for conventional antiphospholipid antibodies (aPLs) possessed anti-β2GPI/HLA-DR. These results suggested that anti-β2GPI/HLA-DR measurements may be more sensitive for diagnosing APS than conventional aPLs tests. Recurrent pregnancy loss (RPL) is one of the clinical manifestations of APS. Therefore, a prospective, multicenter, cross-sectional study were conducted to assess whether anti-β2GPI/HLA-DR is also associated with RPL. This study of 227 couples with RPL revealed that 22.9% (52/227) of RPL women tested positive for anti-β2GPI/HLA-DR, and 24 (19.8%) of the 121 couples with unexplained RPL tested positive for anti-β2GPI/HLA-DR. Interestingly, thirty-five of the 52 (67.3%) RPL patients who were positive for anti-β2GPI/HLA-DR possessed no conventional aPLs of criteria. This novel autoantibody against β2GPI/HLA class II complexes may be a major risk factor for RPL, and it may be a promising biomarker for diagnosing APS.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/76422",risUrl:"/chapter/ris/76422",book:{id:"10322",slug:"antiphospholipid-syndrome-recent-advances-in-clinical-and-basic-aspects"},signatures:"Kenji Tanimura, Yuki Sasagawa, Masashi Deguchi, Noriko Arase, Hisashi Arase and Hideto Yamada",authors:[{id:"84210",title:"Prof.",name:"Hideto",middleName:null,surname:"Yamada",fullName:"Hideto Yamada",slug:"hideto-yamada",email:"yhideto@med.kobe-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kobe University",institutionURL:null,country:{name:"Japan"}}},{id:"251833",title:"M.D.",name:"Kenji",middleName:null,surname:"Tanimura",fullName:"Kenji Tanimura",slug:"kenji-tanimura",email:"taniken@med.kobe-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"344837",title:"Dr.",name:"Yuki",middleName:null,surname:"Sasagawa",fullName:"Yuki Sasagawa",slug:"yuki-sasagawa",email:"kitchen14daiou@yahoo.co.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kobe University",institutionURL:null,country:{name:"Japan"}}},{id:"344838",title:"Prof.",name:"Masashi",middleName:null,surname:"Deguchi",fullName:"Masashi Deguchi",slug:"masashi-deguchi",email:"deguchi@med.kobe-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kobe University",institutionURL:null,country:{name:"Japan"}}},{id:"344839",title:"Dr.",name:"Noriko",middleName:null,surname:"Arase",fullName:"Noriko Arase",slug:"noriko-arase",email:"norikoa@biken.osaka-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Osaka University",institutionURL:null,country:{name:"Japan"}}},{id:"344840",title:"Prof.",name:"Hisashi",middleName:null,surname:"Arase",fullName:"Hisashi Arase",slug:"hisashi-arase",email:"arase@biken.osaka-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Osaka University",institutionURL:null,country:{name:"Japan"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The novel function of HLA class II molecules and autoimmune diseases",level:"1"},{id:"sec_3",title:"3. The conventional concepts of antiphospholipid antibodies in APS",level:"1"},{id:"sec_4",title:"4. The discovery of a novel autoantibody against β2GPI/HLA-DR complex in APS",level:"1"},{id:"sec_5",title:"5. Autoantibodies targeting β2GPI/HLA-DR complex are involved in the pathogenesis of APS",level:"1"},{id:"sec_6",title:"6. Alleles of HLA-DR complexed with β2GPI affect susceptibility to APS",level:"1"},{id:"sec_7",title:"7. A method for quantifying serum levels of autoantibodies against β2GPI/HLA-DR complexes",level:"1"},{id:"sec_8",title:"8. Autoantibody against β2GPI/HLA-DR complex is a promising novel biomarker for APS",level:"1"},{id:"sec_9",title:"9. The future perspectives of the clinical use of autoantibodies targeting β2GPI/HLA-DR complexes",level:"1"}],chapterReferences:[{id:"B1",body:'Jones EY, Fugger L, Strominger JL, Siebold C. 2006. MHC class II proteins and disease: a structural perspective. Nat Rev Immunol6:271-282'},{id:"B2",body:'Jiang Y, Arase N, Kohyama M, Hirayasu K, Suenaga T, Jin H, Matsumoto M, Shida K, Lanier LL, Saito T, Arase H. 2013. Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules. Int Immunol25:235-246'},{id:"B3",body:'Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H. 2014. Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility. 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Prevalence of diverse antiphospholipid antibodies in women with recurrent spontaneous abortion. Fertil Steril80:1276-1278'},{id:"B24",body:'Galli M, Luciani D, Bertolini G, Barbui T. 2003. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood101:1827-1832'},{id:"B25",body:'Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE. 2012. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum64:2311-2318'},{id:"B26",body:'Gebhart J, Posch F, Koder S, Perkmann T, Quehenberger P, Zoghlami C, Ay C, Pabinger I. 2015. Increased mortality in patients with the lupus anticoagulant: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS). Blood125:3477-3483'},{id:"B27",body:'RPL EGGo, Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Nelen W, Peramo B, Quenby S, Vermeulen N, Goddijn M. 2018. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open2018:hoy004'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Kenji Tanimura",address:null,affiliation:'
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Japan
Department of Immunochemistry, Research Institute for Microbial Disease, Osaka University, Japan
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Japan
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1. Introduction
As human beings are born, the aging process begins. There are many phases of life from being a neonate, infant toddler, adolescent, teenager, young adult, youth and then old age. As people age, there are challenges and problems associated with aging including health. The health needs of the elderly need to be cared for by medical doctors specially trained to care for the elderly persons who require special communication skills. Old age is a period in the lives of the elderly for rest after a long life of activity and service [1]. In some communities and societies, socio-cultural referents are used to define old age such as family status if the person has become a grandparent, physical appearances such as the appearance of gray hair and wrinkles [2].
Geriatric medicine is still a new medical specialty in most parts of the world; like any other career choice, there are still gaps in the knowledge, awareness and uptake as a profession [3, 4]. The elderly face a lot of challenges [5] physically, medically, socially, economically and otherwise. Geriatric medicine differs from typical adult medicine because it focuses specifically on the unique needs and health challenges of older adult [6]. There is generally a paucity of specialized healthcare services for the elderly in Africa, some of the reasons may be lack of training in most African countries, unawareness of the peculiar needs of the elderly and lack of human and material resources [7]. Geriatric medicine is important because most doctors deal with elderly patients no matter their specialty [8, 9].
Globally, the population is aging. It is therefore necessary that aged persons are healthy and physically active [10]. This longevity is due to several factors such as good sanitation, access to good healthcare, more people are getting educated, healthy eating and access to funds to provide the necessities of life. Some persons may become less physically active when they age. However, there is a connection between being less physically active and becoming frail [11]. Aging takes place throughout the lifetime, as it creates an opportunity to improve and preserve the physical, health, mental well-being and improve the quality of life. The aging of the population leads to various challenges, which may be economic and social. Also, the health of the person getting older may be affected as the elderly is predisposed to certain illnesses. Governments globally need to set up the right policies that will address the challenges faced by the aged [11]. Some senior citizens are discriminated against in their communities in Africa especially if they are women and childless. Other social challenges senior citizens encounter in Africa are social isolation, elder abuse, neglect and abandonment. This is common because nursing homes and long-term care facilities are not common in Africa. Even in communities where they are available, they are underutilized. Geriatric care cannot be complete without the provision of long-term care facilities [12]. The populace needs to be educated and enlightened on the need for long-term care [12]. This is because the long-term care will provide relief for family members who have elderly persons that are frail or cannot carry out the activities of daily living by themselves or need assistance. Elderly persons in Africa generally encounter several difficulties in which their health, well-being and mental state are affected [13]. This is due to health system inadequacies and lack of care for older persons and unavailable long-term care facilities for older persons. Older persons in Africa are well respected [14]. Older women perform other roles in Africa especially carrying for their grandchildren especially if the mother of their grandchildren has passed away [14]. They are employed as babysitters and nannies. Sometimes they travel overseas to care for their grandchildren so that their children can go to work and not pay for child care.
As times are changing, many young people are getting formal employment, there will be an increased demand for long-term care facilities inform of nursing homes to care for the elderly [12]. This will help the elderly to maintain good health and access social support. Though, even the available nursing homes in some African communities are underutilized. This is due to several factors, people are not aware of their existence, beliefs and myths about nursing homes and discrimination and humiliation of people who take their elderly ones to nursing homes [15]. Some of the nursing homes in Africa are managed by religious organizations. In Africa, elders are cared for by their offspring, grandchildren and extended family members [12, 14].
2. Population aging
Population aging is a worldwide phenomenon with economic and social consequences, and it follows a decline in both birth and death rates [5, 16, 17, 18, 19, 20]. Globally, there is an increase in the number of elderly persons who will require geriatric care [5, 8, 17, 18, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30]. They make up a large number of the population in every country. This worldwide increase in the number of aged persons will increase the importance of the geriatric medicine specialty [26]. This is because old age comes with certain challenges, and chronic illnesses will become a major global public health challenge [19]. The increase in longevity is linked to the reduction in the death rate due to improved health systems and interventions [18, 28, 31].
Globally in 2017, the number of persons aged 60 years and above was 962 million, and this figure is expected to double by 2015 [2, 18, 20]. Population aging will have an impact on healthcare delivery both positively and negatively as there will be a shift from acute to chronic diseases associated with old age and the likelihood of a shortage of healthcare workers specially trained to look after the aged [19, 32, 33]. Like any other group of individuals in society, the aged require constant interaction with people around them [5]. Generally, in most societies and cultures including Africa, it is expected that older people are relieved from normal labour and allowed rest from active economic activities [1]. The aging population is of great concern for the health sector as health challenges are common among the elderly [17, 34] with different patterns of presentation which therefore requires special medical skills [8, 35].
3. Demography of elderly persons in Africa
It is not news that there are older persons in Africa. Worldwide, it is estimated in 2019 that there were 1 billion persons who are 60 years and above [36]. However it is estimated that this number will rise to 2 billion by 2050, there is also speculation that there shall also be an increase in the number of people that will live up to 80 years and beyond [37]. The number of older persons is increasing dramatically, especially in countries that are still developing. Most of which are African countries [38]. It is estimated by the United Nations that by the year 2045, there will be more people that will be over the age of 65 years which will outnumber the number of persons that will be below 15 years [38]. Older persons in recent times consist of a significantly larger population. In Africa, it was estimated in 2009 that 53.8 million individuals are aged 60 years and above [38]. Generally, few persons are trained in geriatric medicine and gerontology to care for the aging population in Africa.
4. Who is an elder?
The elderly are also known as senior citizens, the aged, older persons and elder statesmen. There is no precise and accurate definition of who is an elder [39] as there are different definitions for the elderly by several international organizations, and it varies from society to society [40]. The United Nations agreed that the cut-off age for an older person is someone who is 60 years and above [1, 2, 41], while the World Health Organization defines an elder to be 65 years and above [42, 43]. Most developed countries have accepted the chronological age of 65 years as a definition of elderly individuals [5, 42, 44]. In some countries, the definition of old age is linked to the age of retirement from the government civil service [5, 21]. For instance, the cut-off age for elderly persons in Nigeria is 60 years as this is the age for retirement from the Nigerian federal and state civil service. Though with the various definitions of old age or who is an elder, there is no general agreement on the age when a person becomes old [5].
5. Aging in Africa
Older persons play important roles in African societies as the African cultural systems give them high status [45]. They preserve cultural values, transmit knowledge and skills, dissolve conflicts and disagreements and also educate the young [2, 46]. The typical older adult in developing countries lives in poverty [7]. In some African countries, the kin of elderly people accuse them of witchcraft that they are the cause of misfortunes in the family [29]. This is worst for elderly women who do not have any living child; sometimes these older women are ostracized, tortured or even killed [29].
Over half of persons aged 60 years and above in Africa resided with a child either their biological children or grandchild [23] as the family and friends care for older persons [46]. Older persons in most African societies are accorded much respect [46]. Sometimes older persons are not called directly by their names. They are called mama, for women and papa or baba for men depending on the country. They are addressed as mothers or fathers irrespective of whether they have children or not. In Nigeria, there are different tribes and each tribe has a prefix added to the name of an older person. Among the Ibani people of Grand Bonny Kingdom and Opobo in Rivers State, Nigeria, the prefix ‘Ada’ is used for older men and ‘Aya’ for older women. Among the Igbo tribe of Eastern Nigeria, the prefix ‘Dede’ is used for older men and ‘Dada’ for older women. Baba is the prefix used for older men among the Yoruba people of Western Nigeria. It is an insult and also seen as a sign of disrespect in most African countries to address an older person directly by their names. The respect of older persons is also seen in several cultures including greeting and acknowledging them. For instance, among the Ibani tribe of southern Nigeria, a man must remove his hat when greeting an elder especially if the older is a man. Among the Yoruba, an older person is greeted by a female kneeling down or a male prostrating on the ground. This shows that Africans hold the older person in high esteem and these traditions have been passed down from generation to generation.
In Africa, the chronological definition of the older person sometimes causes some problems as due to illiteracy, most dates of birth are not recorded [5, 40]. Sometimes historic events are used to estimate the age. In some African countries, aging is associated with retirement and the receipt of pension [1]. Though not all African older persons have been involved in formal work, older persons in Africa are involved in transmitting oral, culture and traditions from one generation to another [2]. In Africa and other countries, senior citizens may be perceived as burdens due to their disability or dependence [21].
The elderly also known as older persons or senior citizens are persons aged 60 years and over [47]. Some others define the elderly as persons aged 65 years and above. In Nigeria, 60 years is used as this is the age of retirement from the Nigerian government civil service. Few other professionals in Africa retire above the age of 60 such as judges and lecturers.
Elderly persons are well respected as they are believed to be full of wisdom. During family and community conflicts, they are made head of locally constituted panels to deliberate on issues that range from marriage disputes, sibling rivalry and land disputes. Their verdicts are respected and taken as the final even if the decision is not reasonable. Most elderly persons in Africa do not have any form of pension or retirement benefits. They are cared for by their family members who are their biological children, nephews and nieces, community members and sometimes members of religious organizations. Therefore, they need social support as this will in turn affect their health and psychological well-being, mental health, quality of life, independence, interpersonal relationship and personality [48]. This is because social support will reduce boredom and loneliness. There will also be a reduction in elder abuse, neglect and mental health problems such as anxiety and depression.
In sub-Saharan Africa, most elderly women are not unemployed, therefore, they do not benefit from any form of social security, and hence, they are vulnerable [13]. Older persons in Africa are sometimes accused as the cause of misfortunes that happens or is experienced by their siblings and sibling children, especially if the older person is a woman and childless.
Older persons tend to retire to their rural areas and villages when they retire from formal employment. Social amenities of life are absent in most African villages such as electricity, good pipe bore water and in recent times the internet and mobile telecommunication services. They do not have access to healthcare when they retire to the village as most of the healthcare facilities in Africa are located in urban areas and cities. The elderly are sometimes termed as witches and wizards that possess spiritual powers to inflict evil on whomsoever they want.
6. Education and training in geriatric medicine in Africa
Doctors who are specialists in geriatric medicine are known as geriatricians. There are few hospitals in Africa that provide special care for the elderly with a unit division or department of geriatric medicine. Such units are manned by doctors who have either trained abroad either in Europe or the United States of America in geriatric medicine or generalist either internal medicine physicians or family doctors with interest in caring for the elderly. There is a dilemma in Africa if generalists with an interest in caring for the elderly should be referred to as geriatricians.
Globally, there are few geriatricians. In a study among medical graduates to find out those interested in geriatrics in medical schools in the United Kingdom, only 0.9% (0.4% males, 1.3% females) after 1 year of qualification and 1.5% (1.2% males, 1.9%) females after 5 years were interested in becoming geriatricians [26].
Geriatrics is not relatively popular among medical students [9], especially in Africa where most medical students are not even exposed to geriatric medicine in medical school. In another study in South Africa, only 6.6% wanted to specialize in geriatric medicine [16].
Geriatric medicine is a relatively new medical subspecialty in most parts of the world including Africa [16, 49]. It is complex to train as a geriatrician [50]. Unlike many other physicians who have a high proportion of older patients in their practice, geriatricians place a high premium on improving the function of their patients and not just treating the disease [51]. Globally, there are several models of specialty training to become a geriatrician [6]. Some doctors enrol in residency training in geriatric medicine. Another career pathway is to complete the residency in either internal medicine or family medicine depending on what is obtainable in the country and then train in a 1 year clinical fellowship [6]. Another career pathway is to complete a postgraduate degree that is Diploma, Masters or Doctor of Philosophy (PhD) in geriatric medicine [6]. Another pathway which is that some African doctors have done is to write the diploma in geriatric medicine examination of the Royal College of Physicians of London. In Canada, only candidates certified by the Royal College of Physicians and Surgeons of Canada in internal medicine may be eligible for certification in geriatric medicine [52].
In most countries, geriatric medicine is hardly included in undergraduate training [16]. This may be due to the lack of geriatricians. Specialization in geriatric medicine has traditionally been within internal medicine but a trend in some countries is for geriatricians to be trained within family medicine [16]. Medical training should embrace a multidisciplinary perspective team with particular attention given to the special care needs of the elderly persons reflecting the fact that they include medical conditions unique to this age group [30]. Development of geriatric care should be enhanced in undergraduate and also at postgraduate levels of training [26]. A Diploma in Geriatric Medicine is awarded by the Royal College of Physicians of London. The examination is designed to give recognition of competence in the provision of care of older people to general practitioners, trainees, middle-grade doctors working in non-consultant career posts in departments of geriatric medicine and other doctors with interest in or responsible for the care of older people [53]. Some Africans have passed this examination.
7. Geriatric care in Africa
Formalized care for the elderly is not adequate and well developed in Africa. There are few geriatricians in Africa including few training centres dedicated to the training for geriatric medicine. However, there are few training centres in African countries such as South Africa. In Nigeria, the training in geriatric medicine is still new and only a few hospitals are accredited by the West African College of Surgeons for the training of geriatricians in Africa. This is done after success in the junior residency emanations. Most geriatricians working in Africa have been trained overseas. In developed countries, some other doctors who have an interest in the care of the elderly but do not have the opportunity to have specialist training in geriatric medicine have attended refresher courses in geriatric medicine. There are family doctors and physicians who have gained their experience in geriatric medicine by interest in the specialty and devoting their time and energy to caring for the elderly. Most African societies are becoming urbanized, and this is affecting the care of older persons making them vulnerable, dissolution of the structure of the family and lack of access to good healthcare [13]. Even with experience in caring for older persons, their knowledge will be limited because they do not have any specialists training in geriatric medicine [38].
In a study conducted by Dotchin et al., on the services and training in geriatric medicine in Africa, in most African communities, there are limited specialist healthcare services for older persons [38]. Several medical specialties are encompassed in geriatric medicine such as family medicine, internal medicine, emergency medicine, surgery and dermatology. Geriatric medicine as a specialty is not taught in medical schools [38]. Governments in developing countries have an important role in the provision of healthcare for elder persons [12]. The governments need to enact policies and laws that will protect the vulnerability of senior citizens. Care of the elder citizens is not of importance to the policymakers in most African countries.
There are few geriatric centres or units in Africa. This may be because there are few training centres for geriatric medicine in Africa. In Nigeria, for instance, as at the time of writing this book, there is the Tony Anenih Geriatric Centre at the University College Hospital, Ibadan; Care of Elderly Person’s Unit (CEPU) at the University of Port Harcourt Teaching Hospital and the Geriatric Unit at the University of Benin Teaching Hospital, Benin City, Edo State. The Geriatric Unit of the University of Benin Teaching Hospital was created in October; 2013 [7]. Other Nigerian hospitals have a special clinic for older persons but are not organized by the hospital management as a geriatric unit or department. In the face of limited resources, it is possible to establish a functional geriatric unit and achieve best practices in resource-limited settings by investing in improving available human resources and infrastructure [7].
In Nigeria, there is no organized training for geriatric medicine but doctors with an interest in caring for the elderly practice geriatric medicine and care for the health needs of the elderly. This includes family doctors and physicians. Anesthetists with an interest in geriatric medicine practise geriatric anesthesia. Few Nigerian doctors have trained to be geriatricians in the United Kingdom and the United States of America or have passed the diploma in geriatric medicine examination of the Royal College of Physicians. In March 2016, the University College Hospital, Ibadan, Nigeria, organized a 2 week certificate course on geriatric medicine to train family doctors and physicians in geriatric medicine. This introductory training to geriatric medicine has been done for some years after the maiden one.
Nursing homes are long-term care facilities for vulnerable groups of people for example children, motherless babies, the disabled, mentally retarded and the elderly. These are not common in Nigeria as most Nigerian nursing homes are established and managed by religious organizations and/or non-governmental organizations. Institutional homes for the elderly have their problems, therefore the residents need medical care. In Africa, due to the culture of the people, the elderly resist being kept in a home either as daycare or for long-term care instead they are to be taken care of by their children or other relatives [54]. This is also applicable to Nigeria as the Nigerian elderly are still cared for by their families [55]. One of the reasons why in countries such as Nigeria, the elderly person will not be kept in a long-term home is the belief that the elderly will place a curse on whoever brings the idea and support any placement in the long-term care facility or children or other family members [55].
Sometimes, some of the residents of the nursing homes are abandoned and neglected by their relatives. In this modern day, where young people both men and women have to be involved in circular work or businesses that keep them away from home, specialized long-term institutions are necessary to care for the vulnerable groups of people in the society including the elderly.
8. Conclusions
There are a rising number of people getting older and living up to 60 years and above. This group of people in Africa is faced with several challenges, and they are prone to vulnerability. They are faced with health and social problems. This is worst for women who are single as they are sometimes ostracized and even called witches. There are few geriatricians in Africa; however, most countries are developing strategies for various forms of training in geriatric medicine such as postgraduate courses, fellowship, refresher courses and workshops. There is need for more research on the elderly in Africa. The different states in the African continent should enact policies and laws to protect senior citizens in Africa.
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Introduction",level:"1"},{id:"sec_2",title:"2. Population aging",level:"1"},{id:"sec_3",title:"3. Demography of elderly persons in Africa",level:"1"},{id:"sec_4",title:"4. Who is an elder?",level:"1"},{id:"sec_5",title:"5. Aging in Africa",level:"1"},{id:"sec_6",title:"6. Education and training in geriatric medicine in Africa",level:"1"},{id:"sec_7",title:"7. Geriatric care in Africa",level:"1"},{id:"sec_8",title:"8. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Baloyi ME. A pastoral investigation into some of the challenges associated with ageing and retirement in the south African context. Indie Shriflig Art. 49 (3) Art # 1866. 10 pages. DOI: 10.4102/ids.v.49.3.1866'},{id:"B2",body:'United Nations High Commissioner for Refugees, The United Nations Refugee Agency. Working with Older Persons in Forced Displacement. Geneva. 2013. Retrieved from: www.unhcr.org. [Accessed: October 2019]'},{id:"B3",body:'Byszewski A, Bezzina K, Latrous M. 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New York: Springer Science; 2013. pp. 11-51'},{id:"B28",body:'Chaudhary P, Lamba N. Critical review of geriatric care in Ayurveda with special reference to Jara. International Research Journal of Pharmacy. 2017;8(4):5-8'},{id:"B29",body:'Towards Long-Term Care Systems in Sub-Saharan Africa: WHO Series on Long-Term Care. Geneva: World Health Organization; 2017 www.who.int License: CCBY-NC-SA.3.0190. assessed October 2018'},{id:"B30",body:'Keller I, Makipaa A, Kalenscher TM, Kalache A. Global Survey on Geriatrics in the Medical Curriculum. Geneva: World Health Organization; 2002 www.who.int assessed October 2018'},{id:"B31",body:'Vellas B, Morleg JE. Geriatrics in the 21st century. Journal of Nutrition and Healthy Aging. 2018;22(2):186-190'},{id:"B32",body:'Musunuru K, Mallela J. A systematic review on the role of healthcare administration in geriatric care. Open Journal of Geriatric Medicine. 2018;4(2):1-3'},{id:"B33",body:'Nishinaga M. Comprehensive geriatric assessment and team intervention. JMAJ. 2007;50(6):461-466'},{id:"B34",body:'Wilber ST, Gerson LW, Terrel KM, Carpenter CR, Shah MN, Heard K, et al. Geriatric emergency medicine and the 2006 Institute of Medicine reports from the committee on the future of emergency care in the US health system. Academy of. Emergency Medicine. 2006;13(12):1345-1351 www.aemj.org assessed October 2018'},{id:"B35",body:'Fisher JM, Garside M, Hunt K, Lo N. Geriatric medicine workforce planning: A giant geriatric problem or has the tide turned? Clinical Medicine. 2014;14(2):1026'},{id:"B36",body:'World Health Organization. Ageing. www.who.int'},{id:"B37",body:'Ssensamba JT, Mukuru M, Nakafeero M, Sseryonga R, Kiwanuka SN. Health systems readiness to provide geriatric friendly care services in Uganda: A cross-sectional study. BMC Geriatrics. 2019;19:256. DOI: 10.186/s12877-019-1272-2'},{id:"B38",body:'Assumcao M, Pinto S, Jose H. Public and health policy for the aged in Africa to the south of Saraa. Revista Brasileira de Enfermagem. 2020;73(Suppl 3):e20190313. DOI: 101590/0034-7167-2019-0313'},{id:"B39",body:'Singh S, Bajorek B. Defining elderly in clinical practice guidelines for pharmacotherapy. Pharmacy Practice. 2014;12(4):489-490 www.pharmacypractice.org accessed October 2018'},{id:"B40",body:'Ayokunle AM, Oyeyemi FT, Onipede W, O TF, Olagunju AE, Makinde GB, et al. The definitions and onset of an old person in South-Western Nigeria. Educational Gerontology. 2015;41(7):494-503. DOI: 10.1080/03601277.2014.1003492'},{id:"B41",body:'www.un.org Assessed October 2018'},{id:"B42",body:'www.who.int Assessed October 2018'},{id:"B43",body:'Raveendra L. A clinical study of geriatric dermatoses. Our Dermatology Online. 2014;5(3):235-239'},{id:"B44",body:'Sobokta L, Schneider SM, Berner YN, Cederholm T, Krznaric Z, Shenkin A, et al. ESPENN guidelines on parenteral nutrition: Geriatrics. Clinical Nutrition. 2008;28:461-466'},{id:"B45",body:'Adeleke RO, Adebowale TO, Oyinlola O. Profile of elderly patients presented with psychosocial problems in Ibadan. MOJ Gerontology and Geriatrics. 2017;1(1):26-36'},{id:"B46",body:'Abanyam NL. The changing privileges and challenges of older persons in contemporary African society. Global Journal of Art and Human Social Science. 2013;1(41):34-43'},{id:"B47",body:'Asagba A. Research and the formulation and implantation of ageing policy in Africa: The case of Nigeria. British Society of Gerontology. 2005;16(2):39-41'},{id:"B48",body:'Gyasi RM, Phillips DR, Abass K. Social support networks and psychological well-being in community-dwelling older Ghanaians cohorts. International Psychogeriatrics. 2019;31(7):1047-1057'},{id:"B49",body:'The American Geriatric Society. Why Geriatrics as a Career Choice? www.americangeriatrics.org Assessed October 2018'},{id:"B50",body:'The Canadian Geriatrics Society. Geriatric Medicine Profile. www.canadiangeriatrics.ca Assessed October 2018'},{id:"B51",body:'Misha AA. The concept of successful aging. International Journal of Human and Health Sciences. 2017;01(01):22-25'},{id:"B52",body:'Royal College of Physicians and Surgeons of Canada. Objectives of Training in the Subspecialty of Geriatric Medicine. www.royalcollege.ca'},{id:"B53",body:'Royal College of Physicians of London. The Diploma in Geriatric Medicine. www.rcplondon.ac.uk Assessed October 2018'},{id:"B54",body:'Adedokun MO. Caring for the elderly: Towards a better community. European Journal of Educational Services. 2010;2(3):283-291'},{id:"B55",body:'Okoye UO. Community-based care for homebound elderly persons in Nigeria. A policy option. International Journal of Innovative Research in Science, Engineering and Technology. 2013;2(12):7086-7091'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Dabota Yvonne Buowari",address:"dabotabuowari@yahoo.com",affiliation:'
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