Effectiveness of interventions in surveillance programs and monitoring therapy response in clinical management: use of traditional and investigational tools.
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",isbn:"978-1-83969-048-8",printIsbn:"978-1-83969-047-1",pdfIsbn:"978-1-83969-049-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"27349927a8f626359f696ba5472bc2b2",bookSignature:"Ph.D. Shibo Ying",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10240.jpg",keywords:"Enzyme Activity, Intrinsic Disorder, Protein Structure, Transcription Factor, Cell Apoptosis, Cell Proliferation, Cellular Signal Transduction, Gene Regulation, Carcinogenesis, Diagnostic Marker, Prognostic Marker, Therapeutic Target",numberOfDownloads:24,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 7th 2020",dateEndSecondStepPublish:"November 16th 2020",dateEndThirdStepPublish:"January 15th 2021",dateEndFourthStepPublish:"April 5th 2021",dateEndFifthStepPublish:"June 4th 2021",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A young biological researcher in post-translational modifications with extensive overseas experience, the awardee of a Japanese government scholarship, a former research fellow of the German Cancer Research Center, Chinese Society for Cell Biology permanent member and holder of two grants from NSFC.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"306153",title:"Ph.D.",name:"Shibo",middleName:null,surname:"Ying",slug:"shibo-ying",fullName:"Shibo Ying",profilePictureURL:"https://mts.intechopen.com/storage/users/306153/images/system/306153.jpg",biography:"Dr. Shibo Ying is an associate professor in Hangzhou Medical College (China). He graduated and obtained his Ph.D. in Applied Life Sciences from Tokyo University of Agriculture and Technology (Japan) in 2011. He was awarded Japanese government scholarship and he visited University of California at Davis (UCD) as an exchange student in 2010. After his graduation, he became a research fellow at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg (Germany). Dr. Ying acts as a reviewer of many scientific journals and has authored or co-authored over 25 scientific publications. 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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:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"49497",title:"Schistosomiasis – Updating Technologies and Diagnostic Approaches in Surveillance Strategies and Clinical Management",doi:"10.5772/61310",slug:"schistosomiasis-updating-technologies-and-diagnostic-approaches-in-surveillance-strategies-and-clini",body:'Schistosoma infection is a poverty-related parasitic infection, being the second most important neglected tropical disease in the world after malaria. Schistosomiasis is a blood-fluke-induced infection, which may present with acute and chronic disease forms. Schistosomiasis is caused by five distinct Schistosoma species distributed in tropical and subtropical areas. However, imported cases can also been seen in nonendemic areas. Human populations acquire infection after exposure to contaminated fresh water sources like dams, rivers, canals, lakes, and streams. Schistosoma infection falls on a large spectrum of clinical manifestations that ranges from absence of signs and symptoms to severe forms of disease. Although morbidity and mortality have been reduced along the years after use of mass drug administration (MDA) in endemic areas, large populations are still at risk of disability-related outcomes on a daily basis. A broad spectrum of clinical manifestations and also asymptomatic infections are observed [1, 2]. Three major species, Schistosoma haematobium, Schistosoma japonicum, and Schistosoma mansoni, and another two minor species, Schistosoma mekongi and Schistosoma intercalatum, are recognized as the mainly pathogenic Schistosoma species that infect human populations [3, 4]. Parasite transmission occurs after contamination of water collections with Schistosoma eggs eliminated by infected individuals, which further develop in the infective form called cercariae in freshwater snails. The release of Schistosoma cercariae from snails is followed by skin penetration of the definitive hosts (human and nonhuman species like buffalos in the case of S. japonicum or rodents in the case of S. mansoni infection). In the latter, Schistosoma immature forms evolve to adults that lay eggs, which are spread in the definitive hosts and/or eliminated in the environment through excreta, like urine in the case of S. haematobium and stool for the other species. In some areas, nonhuman definitive hosts are also essential to maintain Schistosoma life cycle, such as buffalos for S. japonicum and rodents for S. mansoni [5, 6]. Schistosomiasis world distribution is essentially in tropical and subtropical areas, with more than 90% of infected individuals living in sub-Saharan Africa [7, 8]. However, imported cases of schistosomiasis are also becoming increasingly frequent in nonendemic areas such as Europe. Spotlights were thrown on schistosomiasis in the recent years since elimination is believed to be a reachable goal for some endemic regions on the globe. Education, sanitation policies, and hygiene awareness proved to promote a high impact on infection transmission [9]. Also, field work in different transmission areas shows that chemotherapy plays an evident role in decreasing prevalence, parasite burden, and late morbidity [10].
Recently, a great deal of debate has been done over two main issues in schistosomiasis management in endemic and nonendemic areas: how to accurately diagnosis Schistosoma infections before and after therapy in addition to assess morbidity level. The adoption of promising new diagnostic tools and the development of new markers of disease progression might change the current scenario by improving schistosomiasis clinical management in both community and institutional settings.
The diagnosis of active Schistosoma infection is based on the demonstration of egg excretion by parasitological methods such as Kato-Katz (K-K), which has a low cost and can be performed in field studies. Direct egg detection achieves 100% specificity and high sensitivities parallel with high parasite burden. However, in individuals with less than 100 eggs per gram (epg), parasitological method loses sensitivity. Non-egg excretors are usually underdiagnosed. Furthermore, the assessment of cure rate is unreliable postchemotherapy use [11, 12]. Moreover, the evaluation of the effectiveness of schistosomiasis control or eradication programs after (mass) chemotherapy is distorted. New approaches have been developed and proposed as complementary or in substitution to K-K. New approaches such as DNA detection assays and rapid tests have evolved in the last years [13]. The accurate assessment of schistosomiasis diagnosis, morbidity determination, and therapy response through new technologies became suitable for use in both institutional as well as community settings. The upgrade of diagnostic technology that encompasses the detection of active infection before chemotherapy and monitoring of treatment response will permit advances in public health policies as well as in individual clinical management [14, 15]. Moreover, the assessment of clinical presentation, the disease stage, and the prognosis have been the object of progresses that go side by side with the development of new image diagnostic apparatus. Also, biochemical, immunological, and molecular markers have been tested for the evaluation of fibrosis, vascular damage, and even cancer [16]. The present review aims to discuss the new surveillance strategies and their impact on schistosomiasis clinical management.
The laboratory investigation of Schistosoma infection consists of different techniques, including parasitological, immunological, and molecular biology methods [17-19]. Frequently, diagnostic approaches are also applied on the monitoring of drug response. In addition, the assessment of morbidity levels can be achieved by using image tests and biochemical markers [20-22]. However, the diagnosis of active Schistosoma infection and the monitoring of therapy response as well as the determination of morbidity levels are distinctively assessed at community and institutional settings (Figure 1). Furthermore, in community settings, conventional or investigational tools aim to assess the efficiency of national control programs in the morbidity control and/or elimination of transmission by measuring the prevalence and intensity of infection in intermediary and definitive hosts [23-25]. In contrast, in institutional settings, diagnostic approaches aim to improve clinical management of individual cases.
Schistosomiasis flowchart for clinical management in community and institutional settings. Conventional and new tools to diagnosis, determination of response to therapy, and morbidity assessment are indicated under community and institutional settings in hierarchic order. Bellow conventional tests, new tools were depicted according to the strength of literature evidence (red boxes). Approaches still under investigation and/or diagnostic platforms that show debatable results are inside the gray boxes. PM: parasitological method; US: ultrasonography; PCR: polymerase chain reaction; RDT: rapid test (POC-CCA /POC-CAA); FOB: fecal occult blood; CT: computed tomography; MRI: magnetic resonance imaging.
Traditionally, egg detection by microscopy is the major criteria for active Schistosoma infection [24, 26]. Egg excretion can be detected by parasitological methods such as urine filtration and centrifugation methods in the case of S. haematobium. Since S. japonicum, S. mansoni, S. mekongi, and S. intercalatum eggs are shed in the feces, egg patent infection is detected in fecal samples by parasitological methods such as Kato-Katz test (K-K). The principal characteristics of K-K are as follows: an easy-to-do technique, low cost, reliability, and accurate identification of eggs in the case of Schistosoma species. Also, parasitological methods are quantitative. As a result, parasite load can be estimated. Egg counts correlate with the intensity of being <100 eggs per gram (epg), >100-399 epg, and >400 epg designated as light, moderate, and severe infection, respectively, according to WHO guidelines. Furthermore, the assessment of morbidity levels can also be roughly determined. Based on findings in high endemic areas, the elevated number of eggs was associated with severe forms of disease. Both urine filtration and Kato-Katz test have been applied for diagnosis and monitoring therapy response and used in field studies in areas of transmission as well as in institutional settings. Although Kato-Katz are affordable and suitable for low-income areas with individuals presenting with heavy to moderate infections, Schistosoma infection diagnosis can be quite tricky to detect in individuals with acute schistosomiasis or light infection living in nonendemic and low-endemic areas when based solely on microscopy [27]. Lack of egg shedding, one gender-induced infection, and daily variability are some of the causes that directly interfere with the sensitivity of microscopy, thus compromising the detection of Schistosoma infection and resulting in the underestimation of “real prevalence” [15, 28]. Moreover, the erratic elimination of Schistosoma eggs makes the determination of therapy response uncertain. In addition, some patients may present with severe forms of disease such as neuroschistosomiasis or genital schistosomiasis without any egg excretion detectable [13]. Strategies to overcome the lack of sensitivity of urine filtration and Kato-Katz test include testing replicate samples of urine or stool samples and/or augmenting the number of Kato-Katz slides/sample [29].
Other parasitological methods such as sedimentation, centrifugation, flotation techniques, and miracidium hatching were developed and had improved the diagnosis of light infections by increasing sensitivity [26, 32]. In institutional settings, tissue biopsy such as rectal snips and liver biopsy are largely used to diagnose active infection in non-egg excretors despite its invasiveness [31]. Eventually, surgical specimens reveal previously undiagnosed schistosomiasis. Except for rectal snips, histological examination is not quantitative, lack of information on parasite burden does not preclude clinical assistance.
Albeit the availability of diverse parasitological methods and tissue biopsies as alternatives to the reference test (Kato-Katz), nonparasitological methods were also developed to overcome microscopy false-negative results. This is the case of immunological tests, which have become more useful for showing active infections in recently exposed individuals, such as travelers or chronically infected immigrants residing in nonendemic areas [32]. In areas of transmission, immunodiagnosis is a suitable tool for surveillance in low endemic areas [29]. Several immunodiagnostic tests were developed, but currently the ELISA-based assays using egg antigen, cercarial, or adult worm antigens have been extensively used [33]. In addition, recombinant proteins and peptides have been potential targets [34-36]. Despite its infrequent use in National Programs for Schistosomiasis Control, serology is a potent auxiliary diagnostic approach that permits the diagnosis of non-egg excretors. However, the presence of active infection may be undermined by persistent reactivity despite successful treatment [13, 29]. Although immunoreactivity does not correlate with the intensity of infection, data have demonstrated that isotypic immunoresponse may reflect morbidity levels [37, 38].
Moreover, rapid tests (RDT) for the detection of Schistosoma antigens like circulating cathodic (CCA) and anodic (CAA) antigens and DNA detection assays have proven to be an advanced and feasible strategy for diagnosing Schistosoma infection despite the absence of their use as routine diagnostic approaches [13, 39]. See detailed comments in Table 1. During active infection, gut-produced Schistosoma glycoproteins - POC-CCA and POC-CAA - are detectable in the blood, urine, and stool. At individual level, results revealed that both CAA and CCA ELISA-based assays can be quite sensitive to detect active infection early after exposure in travelers even in the cases of light infections. Also, the tests allow a quantitative assessment of antigen levels, which correlates with the intensity of infection [40]. Point-of-care platforms (POC) have been applied to estimate infection prevalence with high accuracy in field studies in high and moderate endemic areas [41, 42]. Although research groups claim that CCA and CAA might be a suitable substitute for Kato-Katz test, its performance is still debatable in low endemic areas [43, 44]. RDT for hematuria (urogenital schistosomiasis), fecal occult blood (FOB), and calprotectin detection (entero-schistosomiasis) are also point-of-care approaches, which have been shown to have fair association with egg-patent infections with dual use as diagnostic tools and markers of morbidity [25, 45]. Although strong evidences support the usage of hematuria detection by RDTs, larger studies are still necessary to establish the usefulness of FOB and/or calprotectin detection in cases of light infection commonly found in low endemic areas.
Sanitation and community health education in addition to chemotherapeutic intervention are measures that effectively contribute to the control and/or elimination of Schistosoma infection in several endemic areas and the resolution or attenuation of progressive forms of disease at individual level [10, 46, 47]. However, the determination of the effects of these measures, in particular, drug intervention, still presents as a challenge (Table 1). Tests like microscopy have low sensitivity and underestimate cure rates especially in non-egg excretors. Day-to-day variations in egg excretion contribute to the misdiagnosis of schistosomiasis elimination after treatment [15]. The evaluation of drug response in individuals previously diagnosed by tissue biopsies is also troubled since the procedures might be invasive like brain or spinal cord biopsies in neuroschistosomiasis [48]. In immunoreactive egg and non-egg excretors submitted to PZQ treatment, it was shown that reactivity against several proteins mostly related to parasite musculature or glycolytic metabolism is enhanced after therapy [49]. Immunoreactivity might persist for long periods of time despite effective drug response, although seroconversion may occur in some individuals. Nonetheless, in low-endemic areas, immunodiagnosis has proven to be a valuable tool for schistosomiasis surveillance [50]. Changes in immunoreactivity in controlled areas can be used as an indicator of maintained transmission and/or active infection in community settings [51]. Therefore, the assessment of drug response is a hot topic in the schistosomiasis and development of new tools became an urgent matter (Table 1). Investigations have shown a potential role in drug response assessment with the use of rapid tests and DNA detection assays [14, 52].
\n\t\t\t\t\n\t\t\t\n\t\t\t | \n\t\t\t\tTraditional Tools\n\t\t\t | \n\t\t\t\n\t\t\t\tInvestigational Tools\n\t\t\t | \n\t\t|||
\n\t\t\t\tCommunity Settings\n\t\t\t | \n\t\t\t\n\t\t\t\tTests\n\t\t\t | \n\t\t\t\n\t\t\t\tCharacteristics/Observations\n\t\t\t | \n\t\t\t\n\t\t\t\tTests\n\t\t\t | \n\t\t\t\n\t\t\t\tCharacteristics / Observations\n\t\t\t | \n\t\t|
\n\t\t\t\tVector control\n\t\t\t | \n\t\t\tLight Exposure Test (Cercarial shedding detection) | \n\t\t\tFor determination of transmission control, elimination or erradication. Inaccurate. no species identification; Test does not detect prepatent infections; no assessment of early post-control measures in snail infection rates. | \n\t\t\tAntigen Detection | \n\t\t\tDetection in 2nd week post-infection (pi); secretion by live larvae; group specific. Not commercially available assays. | \n\t\t|
\n\t\t\t | \n\t\t\t | \n\t\t\t | DNA- based assays | \n\t\t\tDetection in 1st week pi; quantitation of parasite load (real -time PCR; specie-specific identification. Mapping foci of vector snails and monitoring transmission. In house assays. | \n\t\t|
\n\t\t\t\tNon-human Hosts\n\t\t\t | \n\t\t\tParasitological Methods (Egg detection) | \n\t\t\tTraditional methods which are simple, cheap and effective for Schistosoma detection. | \n\t\t\tCCA-dipsticks (urine lateral flow test) Serology (IgG/IgM) | \n\t\t\tDetection of active infection independent of patent egg-excretion in primate non-humans. Only determination of genus but not species. Defines exposure to Schistosoma. In chimpanzee populations serology present high sensitivity but reactivity may persist for years after infection has been cleared. Comercial available test. \n\t\t\t | \n\t\t|
Humans Hosts Sanitation / Education | \n\t\t\tQuestionaries Parasitological Methods (Egg detection) Serology | \n\t\t\tQuestionnaries are applied to identify high - risk populations and permits assessment of Schistosoma infection Parasitological tests are quantitative methods. Low price per test. Used for Screening sentinel populations like school children.See more comments below. | \n\t\t\tDNA- based assays1\n\t\t\t | \n\t\t\tIdentification and mapping of Schistosoma endemic areas. DNA based assays are powerful tools for detection of Schistosoma active infections. DNA detection show better performance even in light infection (low parasite loads) or despite absence of egg excretion. Mostly tested in “small” studies. \n\t\t\t | \n\t\t|
\n\t\t\t\tChemotherapy\n\t\t\t | \n\t\t\tParasitological Methods (Egg detection) | \n\t\t\tMicroscopy is highly sensitive and specific to detect egg-patent infections. Day-to-day variations on egg excretion is a limitation. Absence of egg excretion post-treatment may not represent response to therapy. Cure rates determined in different S. mansoni and S.haematobium infections are variable (49.2 to 98.40%) [53, 54]. Understimates reinfection and also incomplete cure. | \n\t\t\tDNA-based assays1\n\t\t\t | \n\t\t\tDNA detection has higher sensitivity after use of chemotherapy. Persistent DNA amplification in both egg excretors and non-egg excretors strongly suggest no response to therapy. Presents good performance compared to parasitological methods to determine effect of MDA. Cure rates calculated by different DNA - based assays in distinct populations and by different Schistosoma species may varie from 21.1 - 30.7 to 75.6% [55, 15]. Persistence of DNA amplification until 6 months and post- 6 months after treatment might suggest incomplete infection and reinfection, respectively DNA-based assays for Schistosoma infection detection are not currently commercially available. | \n\t\t|
\n\t\t\t | Serology | \n\t\t\tLoss of sensitivity of microscopy has been replaced in some control programs by serology which may remain reactive for extended periods post effective drug use. In areas submitted to several rounds of chemotherapy, low and/or absence of reactivity might represent control of infection.Long periods of obsevation are necessary to determine Schistosoma infection “real status”. Reinfection or incomplete cure may not be assessed. | \n\t\t\tRapid Test | \n\t\t\tPOC-CCA maintains higher sensitivity than parasitological methods after PZQ use. However, specificity may be compromised by the presence of persistent low reactivity ( trace positive samples) post-chemotherapy.Cure rates may vary from 23.3 - 26.1 to 40.7- 47.8% [42, 54] \n\t\t\t | \n\t\t|
\n\t\t\t\tInstitutional Settings \n\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t | |
\n\t\t\t\tChemotherapy\n\t\t\t | \n\t\t\tParasitological Methods (Egg detection) | \n\t\t\tAssessment of post-therapy response by parasitological methods in clinical wards has similar advantages and limitations as in community settings. In immigrants (long gone from endemic areas) and recently exposed travelers, absence of egg excretion pre-therapy represent an obstacle. Ova detection is inappropriate to determine therapy response in these groups. See above other coments. | \n\t\t\tDNA-based assays1\n\t\t\t | \n\t\t\tDNA-based assays are a reliable tool to detect response to therapy in distinct clinical specimens. Absence of DNA amplification correlates with response to therapy in individuals treated in Travel Medicine Clinics [56].In case of therapy failure, maintained DNA amplification correlate with persistence of clinical signs, symptoms and pathological abnormalities associated to therapy failure [57]. Usefulness of DNA-based assays to detect past infection incomplete cure for non re-exposed individuals has to be established with large studies [58]. | \n\t\t|
\n\t\t\t | Tissue Biopsy | \n\t\t\tNo viable eggs in rectal snips show good correlation with response to therapy. However, tissue biopsy (rectal snips, liver biopsies) are invasive procedures. And, lack of ova detection may not represent absence of active infection [59]. | \n\t\t\t\n\t\t\t | \n\t\t | |
\n\t\t\t | Serology | \n\t\t\tImmunoreactivity persistence for years after effective therapy is the major limitation. Negative seroconversion representes response to therapy and it is observed in some individuals [56]. But, assessment of therapy failure is mostly difficult [59]. | \n\t\t\t\n\t\t\t | \n\t\t | |
\n\t\t\t\tTransplant\n\t\t\t | \n\t\t\tTissue Biopsy | \n\t\t\tDonnor and organ-recipients from endemic areas with /without transaminase alterations can be screened by tissue biopsy [60]. But, negative tissue samples do not rule out active infection. | \n\t\t\tDNA- based assays1\n\t\t\t | \n\t\t\tFurther studies are necessary. | \n\t\t
Effectiveness of interventions in surveillance programs and monitoring therapy response in clinical management: use of traditional and investigational tools.
1DNA based assay - conventional PCR, real-time PCR and LAMP (Loop-mediated isothermal amplification)
RDTs for antigen detection have been largely used for population studies to evaluate posttherapy response and efficacy [42, 43]. In areas of moderate and high endemicity, therapy response represented by decrease or disappearance of antigen detection may represent cure. However, in light infections, rapid test accuracy is reduced with maintained antigen detection in individuals without infection. The use of antigen detection assays is a debatable matter to measure posttherapy response. In contrast, DNA assays seem to be a suitable marker of drug response. Cure is determined by the absence of DNA amplification postchemotherapy use, while persistent DNA amplification correlates with nonresponse to therapy [15].
Schistosomiasis presents as a large spectrum of manifestations and disease severity during acute and chronic phases. Usually, imaging tests and/or biological markers are required to confirm diagnosis, to assess morbidity, and to stage disease progression [21, 22]. Image tests such as ultrasonography became revolutionary to assess urogenital S. haematobium infection and S. mansoni liver disease [61]. In both community and institutional settings, conventional ultrasound (US) examination is a well-standardized test to assess bladder and liver fibrosis, which is the hallmark of disease progression in urinary and intestinal schistosomiasis, respectively [62-65]. US predicts disease prevalence rates and is a reliable noninvasive indicator of morbidity levels which aloud disease staging [64, 66]. However, morbidity measurement in a multivariate clinical manifestation infection like schistosomiasis is no easy task. Targeting one compartment to measure schistosomiasis morbidity might not be enough since some clinical presentations can affect a single compartment like in neuroschistosomiasis and others. In intestinal Schistosoma infection, independent hepatosplenic forms are the most common clinical presentation after asymptomatic S. mansoni infection. However, in contrast to hepatic schistosomiasis, the study of disease progression by using image and/or biochemical markers is still poorly developed [21]. Promising new approaches such as capsule endoscopy have been introduced, but large-scale studies are still necessary to evaluate the usefulness of the method [67]. In hepatosplenic forms, vascular gastropathy and colopathy can be indicators of portal hypertension severity [68]. The assessment of vascular alterations in superior gastrointestinal tract are used to determine schistosomiasis levels of morbidity through the use of upper digestive endoscopy in association with conventional ultrasonography and Doppler imaging [66]. In institutional settings, transient elastography, magnetic resonance, and computerized tomography might give supplementary information regarding fibrosis progression and vascular status, although standardization is necessary especially for disease staging [22, 69]
In community settings, concerns have been increasing on the effectiveness of schistosomiasis control interventions like MDA over the years. The low accuracy of the reference test to detect active Schistosoma infection and the improper estimates of cure rates jeopardize the truthful analysis of drug intervention, which compromises the effectiveness of surveillance systems. In clinical settings, underdiagnosed schistosomiasis and inadequate morbidity assessment also increase the burden on public and private health systems. In order to change this scenario, new diagnostic tools, markers of treatment response, and morbidity assessment have been developed over the years showing promising results. Nonetheless, efforts still have to be made to find a single cheap and easy-to-do approach that is suitable and reliable for diagnosis, treatment evaluation, and disease staging in community and institutional settings.
Ferrimagnetism is similar to ferromagnetism in many ways [1, 2, 3, 4]. They all have hysteresis curves as the applied magnetic field changes, resulting in the saturation magnetization (\n
The hysteresis (B-H) curves for (a) hard ferrimagnetism and (b) soft ferrimagnetism. The remnant polarization (\n\n\nB\nr\n\n\n) and the coercive field (\n\n\nH\nc\n\n\n) for the hard ferrites should be as large as possible. On the other hand, for the soft ferrites, the remnant polarization (\n\n\nB\nr\n\n\n) and the coercive field (\n\n\nH\nc\n\n\n) are very small or even close to zero.
Soft magnetic materials include electrical steels and soft ferrites [3, 4]. Unlike the ferromagnetic metals which are conductors, soft ferrites have low electric conductivity, i.e., they are dielectric materials. The electrical steels have extensive applications in low-frequency systems, such as generators, motors, and transformers, while the soft ferrites are suitable for the high-frequency applications, such as circulators, isolators, phase shifters, and high-speed switches.
\nThis chapter will focus on the properties of the soft ferrites and their applications at high-frequency systems. The ferrites are crystals having small electric conductivity compared to ferromagnetic materials. Thus they are useful in high-frequency devices because of the absence of significant eddy current losses. Ferrites are ceramic-like materials with specific resistivities that may be as much as 1014 greater than that of metals and with dielectric constants around 10 to 16 or greater. Ferrites are made by sintering a mixture of metal oxides and have the general chemical composition MO·Fe2O3, where M is a divalent metal such as Mn, Mg, Fe, Zn, Ni, Cd, etc. Relative permeabilities of several thousands are common [5, 6]. The magnetic properties of ferrites arise mainly from the magnetic dipole moment associated with the electron spin [2].
\nThe magnetic dipole moment precesses around the applied DC magnetic field by treating the spinning electron as a gyroscopic top, which is a classical picture of the magnetization process. This picture also explains the anisotropic magnetic properties of ferrites, where the permeability of the ferrite is not a single scalar quantity, but instead is a generally a second-rank tensor or can be represented as a matrix. The left and right circularly polarized waves have different propagation constant along the direction of the external magnetic field, resulting in the nonreciprocity of a propagating wave. Since the permeability should be treated as a tensor (matrix), not a scalar permeability, it is generally much difficult to understand and to have intuition, even for the researchers.
\nThe properties of ferrites are very intriguing. Without a DC bias magnetic field \n
Figure 2 shows the Larmor precession with the circularly polarized fields [7]. Circular polarization may be referred to as right handed or left handed, depending on the direction in which the electric (magnetic) field vector rotates. For a right-hand circularly polarized (RHCP) wave, the fields rotate clockwise at a given position from the source looking in the direction of propagation. The magnetic dipole moment m processes around the \n
Larmor precession of a magnetic moment m around the applied DC bias field H0 (\n\n=\n\nH\n0\n\n\nz\n̂\n\n\n) with (a) a right-hand circularly polarized (RHCP) wave and (b) a left-hand circularly polarized (LHCP) wave. The frequency of the Larmor precession in both cases are the same, i.e., the Larmor frequency \n\n\nω\n0\n\n\n\n\n=\n\nμ\n0\n\nγ\n\nH\n0\n\n\n\n\n. \n\n\nH\nt\n+\n\n\n and \n\n\nH\nt\n−\n\n\n are the transverse components of the incident waves which rotate clockwise (RHCP) and counter-clockwise (LHCP) from the source viewpoint looking in the direction of propagation. The thumb points the direction of the wave propagation, and the fingers give the rotation of the transverse components [7].
A linearly polarized incident wave can be decomposed into RHCP and LHCP waves of equal amplitude. The orientation of the linearly polarized wave changes after the wave propagates a certain distance because of the distinct propagation constants. The phenomenon is the famous Faraday’s rotation [5, 6]. This unique property has various applications, such as phase shifters, isolators, and circulators. However, it is difficult to follow for students and even researchers in that the permeability is a tensor, not just a simple proportional constant.
\nHere we consider the simplest case for the pedagogic purpose—a circularly polarized plane wave is normally incident upon a semi-infinite medium. The wave characteristics such as the propagation constant k and the wave impedance Z are associated with the permeability μ, which is a tensor for the ferrite medium [5]. By finding the preferred eigenvalues, it will be shown that the properties of μ depend on the DC bias field \n
The permeability \n
Since the torque is equal to the time change rate of the angular momentum, we have
\nBy comparing Eqs. (1) and (2), we obtain
\nA large number of the magnetic dipole moment \n
M and H in Eq. (4) differ slightly from m and \n
Since the AC terms have an exp(−iωt) dependence, by substituting Eq. (5) and (6) into Eq. (4) the transverse component terms read
\n\n\n
where \n
The eigenvectors corresponding to these two eigenvalues are the right-hand circularly polarized wave (RHCP, denoted as +) and the left-hand circularly polarized wave (LHCP, denoted as -), respectively. The symbols, + and -, represent positive helicity and negative helicity, respectively. The LHCP wave has a relatively mild response over the entire frequency range. On the contrary, the RHCP wave has a much more dramatic response.
\nThe permeabilities of the RHCP and LHCP waves are
\nEq. (12) has a singularity when the wave frequency \n
For a resonant cavity with a quality factor (\n
the permeability for the RHCP wave now reads
\nTo conduct a complete simulation of a ferrite device, we need to know its complex permittivity, the saturation magnetization, and the resonance linewidth. We will discuss how to characterize the ferrite’s properties in the next section.
\nHere we will discuss the measurement of the most important properties of ferrites, including the dielectric properties (\n
Ferrites are ceramic-like materials with relative dielectric constants around 10 to 16 or greater. The resistivities of ferrites may be as high as 1014 greater than that of metals. Since ferrites are dielectric materials. The dielectric properties (\n
Figure 3 shows the ideal of the field enhancement method. Figure 3(a) shows the resonant frequency as functions of the dielectric constant (\n
(a) Resonant frequency versus dielectric constant based on full-wave simulations. The solid curve can be divided into three regions: low, transition, and ultrahigh. The dashed line is simulated with a much thinner sample of 1.00 mm in thickness, which exhibits the properties similar to those of perturbation. (b) Schematic diagram of the field enhancement method. It consists of a cylindrical resonant cavity and a metal rod. The sample is placed on the top of the metal rod. The metal rod focuses and enhances the electric field significantly. An SubMiniature version A (SMA) 3.5-mm adapter couples the wave from the top of the cavity [11].
Ferrites have a strong response to the applied magnetic field. The magnetic properties of ferrites arise mainly from the magnetic dipole moment associated with the electron spin. Relative permeabilities of several thousands are common. The saturation magnetization (\n
The hysteresis curve regarding the magnetization \n\nM\n\n and the internal bias \n\n\nH\n0\n\n\n. When the applied internal magnetic field \n\n\nH\n0\n\n\n is large enough, the magnetization will be saturated, denoted as (\n\n\nM\ns\n\n\nor\n\n4\nπ\n\nM\ns\n\n\n). When \n\n\nH\n0\n\n\n decreases to zero, the remnant polarization is denoted as \n\n\nM\nr\n\n\n. The polarization will change sign (from positive to negative) when \n\n\nH\n0\n\n\n is greater than \n\n−\n\nH\nc\n\n\n which is called the coercive field.
The idea is to place the sample at the maximum of the H-field. It exhibits resonant absorption when the internal bias field is changed to \n\n\nH\nr\n\n\n. By changing the magnetic field, we will obtain the absorption. \n\n\nH\n1\n\n\n and \n\n\nH\n2\n\n\n are associated with the 3-dB absorption. The difference between these two values is the resonance linewidth \n\nΔ\nH\n\n.
Note that the saturation magnetization is denoted as \n
The loss of ferrite material is related to the linewidth, \n
The idea is normally implemented using a TE10n (n even) cavity in the X-band region [9, 12]. The test sample is placed at the H-field maximum. The sample is spherical with a diameter of approximately 0.040 inches, which is much easier to estimate than the internal bias field \n
The three key parameters are obtained in three experimental setups under different sizes and geometries of the samples. If the samples’ properties are slightly different or the machining error is not negligible, the error will be large or even unacceptable. The ultimate goal is to integrate the measurements and to extract the parameters using one experimental setup. The three key parameters will be used in the design of the microwave ferrite devices in the next session.
\nThe ferrites are crystals having small electric conductivity compared to ferromagnetic materials. Thus they are useful in high-frequency situations because of the absence of significant eddy current losses. Three commonly used ferrite devices are discussed below. These are phase shifters, circulators, and isolators [13, 14, 15, 16].
\nThe phase shifters are important applications of ferrite materials, which are two-port components that provide variable phase shift by changing the bias magnetic field. Phase shifters find application in test and measurement systems, but the most significant use is in phase array antenna where the antenna beam can be steered in space by electronically controlled phase shifters. Because of the demand, many different types of phase shifters have been provided. One of the most useful designs is the latching nonreciprocal phase shifter using a ferrite toroid in the rectangular waveguide. We can analyze this geometry with a reasonable degree of approximation using the double ferrite slab geometry.
\nFigure 6 shows the full-wave simulation for a two-port phase shifter using high-frequency structure simulator (HFSS, ANSYS). A standard waveguide WR-90 is employed with a width of 22.86 mm and height of 10.16 mm. The field patterns are displayed in Figure 6(a) for an empty waveguide and a waveguide with two ferrite slabs. The phase difference \n
Simulation results. (a) The field pattern to the left is for the empty waveguide. The right figure shows field strength with ferrites. (b) The phase difference \n\nΔ\nϕ\n\n as a function of the internal bias field \n\n\nH\n0\n\n\n.
Circulator, a nonreciprocal device, has been widely used in various microwave systems. Figure 7 schematically shows the function of a stripline circulator. The circulator is, in general, a three-port device. If the incident wave is injected from Port 1, then the wave will ideally go to Port 2, while Port 3 will be isolated as shown in Figure 7(a). On the other hand, if the wave is injected from Port 2, it will go to Port 3 and isolate from Port 1 as shown in Figure 7(b). There are three figures of merit for a circulator: transmission, reflection, and isolation. The transmission from Port 1 to Port 2 should be as high as possible, i.e., the insertion loss should be as small as possible. The reflection received at Port 1 due to the incident wave of Port 1 (S11) and the isolation from Port 1 to Port 3 (S13) should be as small as possible. The nonreciprocity of the circulator can be used to protect the oscillators from the damage of the reflected power in plasma or material processing systems. It can also be used to separate the transmitted and the received waves in radar or communication systems [13, 14, 15, 16, 17].
\nSchematic diagrams of the operation of a stripline circulator. (a) The incident wave is injected from Port 1 and the transmitted wave ideally goes to Port 2. (b) The incident wave from Port 2 will go to Port 3. The color spectrum is the electric field pattern inside the ferrite disks. It is a three-port, nonreciprocal device. A full-wave solver, high-frequency structure simulator (HFSS), is used [18].
In addition to the stripline circulator, there are other types such as the microstrip circulator and the waveguide circulator. The microstrip circulator is similar to the stripline circulator in many ways. Here we show a waveguide circulator which is capable of high-power operation. Figure 8(a) shows the structure of the nonreciprocal device and the simulated electric field strength. The simulation parameters are described in the caption. The circulator is, in general, a three-port device. If the incident wave is injected from Port 1, then the wave will ideally go to Port 2, while Port 3 will be isolated as shown in Figure 8(b). On the other hand, if the wave is injected from Port 2, it will go to Port 3 and be isolated from Port 1 as shown in Figure 8(b).
\n(a) Schematic diagrams of the operation of a waveguide circulator. A full-wave solver, HFSS, is used with the saturation magnetization (\n\n4\nπ\n\nM\ns\n\n\n) is 1600 G, the dielectric constant\n\n\nε\n′\n\n\n is 13.0, and the resonance linewidth \n\nΔ\nH\n\n is 10 Oe. The radius and thickness of the ferrite disks in rust red are R = 21.0 mm and t = 5 mm, respectively. The waveguide is a standard WR 340 with 86.36 × 43.18 mm2. The electric field pattern is displayed in color. (b) Simulation results of the waveguide circulator like the one in Part (a). The solid red curve is the transmission or insertion loss; the blue curve represents the reflection loss, and the black is the isolation.
The isolator is one of the useful microwave ferrite components. As shown in Figure 9, the isolator is generally a two-port device having unidirectional transmission characteristics (nonreciprocity). From Port 1 to Port 2 (S21), the forward transmission is high (i.e., low insertion loss in Figure 9(a)). However, from Port 2 to Port 1 (S12), the reverse transmission is low (i.e., high isolation in Figure 9(b)). Besides, the reflection (S11 and S22) should be as low as possible. The simulation parameters in Figure 9 are the same as Ex. 9.2 of Pozar’s textbook [5]. The simulation parameters and the sample’s geometry are described in the caption.
\nThe simulated field strength for a two-port isolator using the full-wave solver. (a) The high forward transmission (S21) and (b) the low reverse transmission (S12). The saturation magnetization (\n\n4\nπ\n\nM\ns\n\n\n) is 1700 G, the dielectric constant \n\n\nε\n′\n\n\n is 13.0, and the resonance linewidth \n\nΔ\nH\n\n is 200 Oe. The length and thickness of the ferrite are L = 24.0 mm and t = 0.5 mm.
An isolator is commonly used to prevent the high reflected power from damaging the precious and expansive microwave source. For example, the impedance of a plasma system changes a lot when the plasma is ignited. The radical change of the impedance will result in impedance mismatch and cause serious reflection which might kill the source instantly. An isolator can be used in place of a matching or tuning network. However, it should be realized that the reflected power will be absorbed by the ferrite of the isolator, as shown in Figure 9(b). When the ferrite absorbs the reflected energy, the temperature will rise and the performance will be compromised. Therefore, a simple isolator can be implemented by using a circulator with one port well terminated [19]. For example, if Port 3 in Figure 8(a) is matched with water load, the power injected from Port 2 will go to Port 3 and will be isolated from Port 1. The power handling capability can be improved.
\nCirculator and isolator can be implemented using the self-bias [20, 21, 22], just like the latch phase shifter (\n
Ferrimagnetism and ferromagnetism share many magnetic properties in common, such as hard and soft magnets, but the conductivity differentiates these two materials. Ferrites are ceramic materials and suitable for the high-frequency operation. The electromagnetic properties of ferrite materials are difficult to understand in that the magnetic susceptibility is a tensor and depends on the saturated magnetization \n
The complex permittivity \n
At high-power operation, the ferrite devices will be heated. The spin wave linewidth may be taken into account. Besides, the ferrites will become paramagnetism when the temperature exceeded the Curie temperature. These two factors are important for high-power operation, which are not considered in this chapter.
\nThis chapter was supported in part by the Ministry of Science and Technology of Taiwan and in part by China Steel Company/HIMAG Magnetic Corporation, Taiwan. The author is grateful to the Taiwan Branch of ANSYS Inc. for technical assistance and to Dr. Hsein-Wen Chao and Mr. Wei-Chien Kao for their assistance in the full-wave simulation. Dr. Hsin-Yu Yao and Mr. Shih-Chieh Su are appreciated for the discussion of the ferrites’ characterization.
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\n\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\n\nPolicy last updated: 2018-09-11
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