Clinical effectiveness of IIV and A(H1N1)pdm09 influenza vaccine during pregnancy.
\r\n\tEqually, the interlinkages that the adrenal gland has in the human body create the premises both for the description of the intimate mechanisms that induce adrenal diseases on other tissues and organs and also for strategic considerations when it comes to treatment.
\r\n\r\n\tThis book, which is aimed at both endocrinologists and practitioners in other medical fields, therefore offers an insight into the mysteries of adrenal disease and a comprehensive overview of the current state of knowledge of this gland, providing an easy-to-follow format that focuses on the most important developments in the field of etiopathogenesis, clinical and paraclinical diagnosis, and treatment of these conditions.
",isbn:"978-1-80356-687-0",printIsbn:"978-1-80356-686-3",pdfIsbn:"978-1-80356-688-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"86c26879d83ac24206ed5476b6cde7fd",bookSignature:"Dr. Diana Loreta Paun",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11853.jpg",keywords:"Cushing Syndrome, Etiopathogenesis, Diagnosis, Treatment, Minimally Invasive Technique, Adrenalectomy, Adrenal Diseases, Perioperative Management, Adrenal Cancer, Genetics, Adrenal Mass, Imaging",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 22nd 2022",dateEndSecondStepPublish:"May 26th 2022",dateEndThirdStepPublish:"July 25th 2022",dateEndFourthStepPublish:"October 13th 2022",dateEndFifthStepPublish:"December 12th 2022",remainingDaysToSecondStep:"8 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Practitioner endocrinologist, associate professor, researcher, and manager of the National Institute of Endocrinology in Romania, coordinator of investment research and training projects, funded by European funds. Dr. Paun is a member of The Romanian Association of Clinical Endocrinology, member and president(2011-2012, 2017-2019) of The Romanian Chapter of the AACE (American Association of Clinical Endocrinologists). Dr. Păun was appointed State Advise (2015) and was appointed Presidental Advisor (2019).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"190860",title:"Dr.",name:"Diana Loreta",middleName:null,surname:"Paun",slug:"diana-loreta-paun",fullName:"Diana Loreta Paun",profilePictureURL:"https://mts.intechopen.com/storage/users/190860/images/system/190860.jpg",biography:"PĂUN DIANA LORETA, MD, PhD, FACE\r\nBorn on: February 1st, 1968 on Bucharest\r\nEmployed to: “Carol Davila”, University of Medicine and Pharmacy\r\nPosition: endocrinologist, Ph.D, Associate Professor of Endocrinology\r\nFellow of the American College of Endocrinology\r\nExperience: General Manager of “CI Parhon” Institute of Endocrinology, Bucharest, 2006-2015.\r\nMaster in Public Health\r\nQualifications in: Diabetology, Osteoporosis, Endocrine Ultrasonography, Public Health. Training in molecular biology laboratory techniques – Max-Planck-Institut für Psychiatrie, Dept. of Chemie u. Endokrinologie, München, 2002\r\nOccupational field: Clinical, Educational and Research activities, Management, Healthcare services.\r\nPostgraduate courses in: Informatics, Clinical Endocrinology, Infertility, Sexology, Public Health etc.\r\nProfessional career:\r\nChemistry-Biology High School graduated on 1986, Faculty of Medicine graduated on 1992, Th.Burghele Hospital doctor on probation during 1993–1994\r\nendocrinology resident to CI Parhon Institute of Endocrinology 1994-1998\r\nendocrinologist since 1998\r\nAssistant Professor, Lecturer, Associated Professor of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucuresti, Romania\r\nPublications: papers presented on national and international meetings, articles publishised in well-known journals, author and coauthor in monographs and clinical guides book.\r\nParticipation on research projects and clinical trials: Director and member of the team in research projects and in clinical trials.",institutionString:"Carol Davila University of Medicine and Pharmacy",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"455410",firstName:"Dajana",lastName:"Jusic",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/455410/images/20500_n.jpeg",email:"dajana.j@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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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:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"51552",title:"Maternal Influenza: Infection, Vaccination, and Compelling Questions",doi:"10.5772/64368",slug:"maternal-influenza-infection-vaccination-and-compelling-questions",body:'\nInfluenza is a highly contagious, acute respiratory infection (ARI). Each year, it is estimated that 5–10% of adults and 20–30% of children worldwide will become infected with influenza [1]. Pregnant women and infants are at particular risk for influenza. Influenza infection during pregnancy or during the first 6 months of life is a substantial cause of morbidity. Prevention of influenza in these populations is of global health importance.
\nPregnant women are considered a high-risk group for serious illness and complications from influenza. While annual influenza incidence rates in pregnant women are similar to those of nonpregnant women [2–4], influenza infection is associated with increased morbidity and mortality in this subpopulation, with pregnant women having an increased risk of influenza-attributed hospitalizations compared to nonpregnant women [4, 5]. Most likely this is associated with the interaction of the infection with the physiologic and immunologic changes that occur during pregnancy.
\nPregnancy-associated changes such as decreased lung capacity, reduced tidal volume, and increased cardiac output likely reduce the capacity of the respiratory and cardiac system to respond to the stress of influenza infection [2, 6]. In addition, during pregnancy there is a progressive suppression of cellular (T-cell mediated) immunity. While this immune suppression serves to protect the developing fetus from maternal cytotoxic T-cell immunity, it can impair the maternal response to viral infections such as influenza [7–11].
\nThe combination of these factors contributes to an increased risk of negative outcomes from influenza infection. If respiratory disease develops, especially during the later stages of pregnancy, it can lead to high morbidity among the pregnant women [6, 12–14]. In a study of hospital admissions records of women admitted between 1994 and 2000 with respiratory conditions during pregnancy, the hospitalization rate was 150/100,000, an admission rate considerably higher than that of nonpregnant women (17/100,000) and corresponding to the rate for people aged 65–69 [5]. Healthy pregnant women ages 20–34 were estimated to be 18 times more likely to be hospitalized for influenza than their nonpregnant peers [5].
\nWhile hospitalization rates are increased in all trimesters of pregnancy [4, 15, 16], they are the highest during the third trimester [5, 14, 16–18]. Likewise, there is a strong association of maternal morbidity with this trimester of pregnancy. In a 2003 study, Hartert et al. showed that cardiovascular hospitalization during influenza season increased with each trimester, nearly threefold higher by the third trimester compared to the first trimester [18]. In a study of 8323 healthy pregnant and postpartum women, Lindsay et al. found that the strength of association between influenza exposure and influenza-like illness (ILI) increased as the stage of pregnancy progressed, reporting an odds ratio (OR) of 1.12 (CI, 0.79–1.59) during the first trimester, 1.30 (CI, 0.97–1.73) during the second trimester, and 1.84 (CI, 1.31–2.59) for the third trimester [14]. Other studies have reported that by the third trimester, healthy pregnant women with no comorbidity have the same risk for ILI-associated hospitalization as nonpregnant women with chronic or comorbid conditions [4, 5].
\nPregnant women with comorbid conditions such as asthma, diabetes, heart disease, or chronic obstructive pulmonary disease are even more likely to be hospitalized than are pregnant women without chronic conditions [5, 14, 16–18]. Neuzil et al. reported event rates for influenza for low-risk women of 3, 6, and 10 per 10,000 women months in the first, second, and third trimesters, respectively. The event rate in nonpregnant women was 2 per 10,000 women months. Among women with chronic comorbid conditions, rates of 31, 16, and 21 per 10,000 women months were observed during these trimesters, respectively [4].
\nWhile considerable data demonstrate increased morbidity and hospitalization from seasonal influenza in pregnant women, mortality appears to be rare in healthy pregnant women during non-pandemic seasons [7, 19, 20]. A study of seasonal influenza among pregnant women over an 8-year period reported an average of five deaths per year and a mean mortality ratio of 2.9 per million live births [21]. However, during pandemics, influenza infection presents a significant increased risk of both morbidity and mortality in pregnant women.
\nFor example, during the pandemic of 1918, pneumonia was reported in 50% of previously healthy pregnant women, leading to case-fatality rates of over 50% [22–26]. In the 1957 pandemic, 50% of the women of childbearing age who died of influenza were pregnant. Furthermore, 10% of all influenza deaths during this pandemic occurred in pregnant women, with the majority occurring during the third trimester [23, 24].
\nIncreased rates of morbidity and mortality in pregnant women also were observed more recently during the 2009 influenza A(H1N1)pdm09 pandemic. In fact, the first reported death of an adult in the United States during this pandemic was a pregnant woman [27]. Of the 45 deaths reported early in the pandemic, 6 (13.3%) were pregnant women, all of whom developed viral pneumonia and respiratory distress syndrome [27–29].
\nA study of pregnant US women with confirmed or probable influenza during the first month of the outbreak reported 11/34 cases (32.4%) resulted in hospitalization—admissions rates four times higher than those in the general population [30]. Deaths were reported in all three trimesters and were independent of preexisting risk factors. In a California study, pregnant women who were hospitalized with or died from pH1N1 were less likely than nonpregnant women to have a predisposing or comorbid medical condition [31].
\nA review of published studies following the 2009 pandemic documented that pregnant women were disproportionately represented among hospitalizations, ICU admissions, and deaths. The 120 papers that were included in the review reported 3110 pregnant women from 29 countries with A(H1N1)pdm09 influenza infection, including 1625 (52.3%) who were hospitalized with 2009 H1N1, of whom 378 (23.3%) were admitted to an ICU and 130 (8%) died [32]. Pooling the data from all of the studies included in the review, the authors reported that pregnant women, who represent approximately 1% of the population of United States and Australia, accounted for 6.3% of hospitalizations, 5.9% of ICU admissions, and 5.7% of deaths [32].
\nUsing data from the Centers for Disease Control (CDC) and the Pregnancy Mortality Surveillance System, Callaghan et al. estimated the total burden of pregnancy-related mortality resulting from the 2009 to 2010 pandemic. Confirmed and possible deaths resulting from A(H1N1)pdm09 infection represented the leading cause of pregnancy-related mortality in the United States between the months of April 2009 and June 2010. Of 915 total pregnancy-related deaths during this period, 12% of pregnancy-related deaths were attributed to influenza, 75 (8.2%) classified as confirmed influenza A(H1N1)pdm09 deaths, and 34 (3.7%) classified as possible influenza infection deaths [33]. The authors calculated the pregnancy-related morality ratio for confirmed and possible influenza deaths at 2.2 per 100,000 live births. This represents a significant burden of mortality. The number of deaths (109) during the 2009–2010 influenza season was 20 times greater than the mean number (5) of annual possible influenza deaths reported in a 1998–2005 cohort of pregnancy-related deaths in non-pandemic years [33].
\nInfants born to influenza-infected women during the pandemic also experienced increased risks of poor clinical outcomes, mostly due to preterm birth. Reports of preterm birth rates ranged from 15 to 30% among infected women [32, 34–36]. Infection with A(H1N1)pdm09 was associated with increased risk of cesarean delivery [32]. In most cases, cesarean delivery was an attempt to improve worsening maternal status rather than out of concern for the infant [32]. Siston et al. reported a cesarean delivery rate of 58% in pregnant women with 2009 H1N1 compared to a baseline cesarean rate of 30.5% [32, 34, 37]. While cesarean deliveries were commonly described, it is likely that this rate was over-reported, since many of the studies reported only severely affected women. Many deliveries were emergencies and performed outside of controlled operating room settings, indicating the urgent nature of these deliveries and the critical status of the women [32].
\nWhile there is no clear consensus on transplacental transmission of influenza virus or direct viral effects on the fetus [2], the spread of virus beyond the respiratory tract during acute infection is unusual, and vertical transmission, although documented [38–40], appears to be rare [41, 42]. However, even in the absence of vertical transmission, adverse fetal effects can occur, most likely due to the systemic maternal immune response to the infection [43, 44]. Studies have documented inflammatory responses in fetal tissues in response to influenza infection. Such responses could impact the maternal-fetal interface, the placenta, or the fetus directly, leading to pregnancy loss [43]. In addition to direct damage from inflammatory responses, it is hypothesized that maternal hyperthermia can result in adverse fetal outcomes [28, 45]. Maternal hyperthermia during the first trimester of pregnancy, regardless of the cause, has been associated with an increased risk for neural tube defects [46], while fever during labor has been associated with adverse outcomes including neonatal seizures, cerebral palsy, encephalopathy, and death [2, 47–50].
\nIn a large population-based study of influenza infection in over 100,000 women, Hansen et al. observed an increased risk for fetal abnormalities (e.g., central nervous system malfunctions in the fetus, chromosomal abnormalities, suspected damage to the fetus from viral disease) was present in both seasonal (OR 1.53, CI, 1.19–1.95) and pandemic infections (OR 1.48, CI, 1.27–1.73) [51].
\nA review and meta-analysis of 33 studies published from 1953 to 2013 of first-trimester influenza exposure found that influenza exposure during the first trimester of pregnancy was associated with an increase in congenital abnormalities [adjusted odds ratio (AOR) 2.00, CI, 1.62–4.28]. Anomalies included neural tube defects [odds ratio (OR) 3.33, CI, 2.05–5.40], hydrocephaly (OR 5.74, 1.10–30.00), congenital heart defects (OR 1.56, 1.13–2.14), cleft lip (OR 3.12, CI, 2.20–4.42), digestive system anomalies (OR 1.72, CI, 1.09–2.68), and limb reduction defects (OR 2.03, CI, 1.27–3.27) [52]. A major limitation of this study concerns the fact that it defined influenza exposure as any reported influenza, influenza-like illness, or fever with or without clinical confirmation. The inclusion of wide clinical symptoms without laboratory confirmation of influenza likely resulted in overestimation of the number of infants exposed to influenza during gestation. It therefore cannot be determined whether congenital abnormalities were associated with general, all cause hyperthermia or whether influenza infection poses a unique and specific risk for these outcomes. Nonetheless, these observations suggest that prevention of influenza during the first trimester of pregnancy may reduce risk for congenital abnormalities.
\nFetal demise is associated with influenza infection as well. Women with influenza, especially those with pneumonia, had high rates of spontaneous abortion and preterm birth, with 52% of pregnancies ending in spontaneous abortion or preterm delivery during the 1918 pandemic [22, 23, 25].
\nUsing a large nationwide registry, Haberg et al. examined the risk of fetal death after maternal exposure to pandemic influenza infection. The researchers found that pregnant women with a clinical diagnosis of influenza had a nearly twofold increase in the risk of fetal death (adjusted hazard ratio, 1.91; 95% CI, 1.07–3.41) as compared to women who were not exposed to influenza [53].
\nPierce et al. assessed perinatal outcomes of maternal A(H1N1)pdm09 infection. The authors found that perinatal mortality was higher in infants born to infected women than in infants of uninfected women (39 per 1000 live births versus 7 per 1000 total births, respectively,
Infants younger than 6 months of age are at a heightened risk for serious illness from influenza, exhibiting the highest rates of severe influenza compared to other pediatric populations [41]. This age group has higher rates of hospitalization, more prolonged ICU stays, and higher fatality rates (0.33 per 100,000 children) than almost any other age group [55–59]. In the United States, estimates of hospitalization rates for young infants (less than 6 months of age) range between 1.8 and 7.2 per 1000 infants, higher than reported rates of hospitalization for children up to 4 years of age (0.14 per 1000) [60] and people 65–80 years of age (0.56–2.13 per 1000) [60–63]. Childhood deaths associated with influenza are most frequent in infants during the first months of life, with mortality rates in infants 0–6 months old more than four times higher than those in older children [59].
\nLibster et al. [64] documented particularly high mortality rates for infants during the 2009 H1N1 pandemic in Argentina. Of 251 infants and children hospitalized with confirmed A(H1N1)pdm09 infection, 13 (5%) died, for an overall death rate of 1.1 per 100,000 children. Infants were at particularly high risk for fatality, representing the highest death rate at 7.6 per 100,000 children. By comparison, this death rate was 10 times the reported US infant death rate during the relatively serious seasonal influenza season of 2003–2004 [59, 64].
\nTaken together, these observations highlight the impact of influenza on infants, especially the youngest, and underscore the need for prevention in this vulnerable population.
\nA large body of evidence collected over several decades demonstrates that pregnant women and young infants are at increased risk for complications from influenza, making control of influenza infection in these populations an important public health challenge. Influenza vaccines have been used since 1945 and currently are the primary strategy for preventing influenza infection [65].
\nDue to the frequent changes of the influenza viral antigens, a vaccine is formatted during the end of the previous season to include the specific antigens of the influenza strains expected to circulate in the following season, with a goal of conferring protection against the upcoming season’s strains. Each year, the trivalent inactivated influenza vaccines (IIV3) are formulated to contain three viral components: two influenza A subtypes and one influenza B virus. In 2012, the US Food and Drug Administration (FDA) approved the use of a quadrivalent influenza vaccine (IIV4). The quadrivalent vaccine contains two influenza A subtypes and two influenza B subtypes. In 2009, a monovalent H1N1 vaccine was prepared because the newly recognized strain was identified too late in the season to be included in the trivalent seasonal vaccines [66].
\nThe current inactivated influenza vaccines (IIVs) are composed of inactivated (killed) virus that has been chemically disrupted and purified to form a split-inactivated virus preparation. Such split-virus vaccines contain purified HA and NA antigens and have fewer side effects and reactions than inactivated whole virus vaccines. The IIVs currently available in the United States are split virus or subunit virus similar to the split virus [66].
\nThe other vaccine available in the United States is a live, attenuated influenza vaccine (LAIV). This vaccine is composed of live, attenuated, cold-adapted, temperature-sensitive virus administered directly into the nasal passage. The type A and B strains of influenza in this vaccine can replicate in the nasal passages, stimulating an immune response, but cannot replicate in the lower respiratory tract [67]. While LAIV has been licensed in the United States since 2003, it is not recommended for use in pregnant women [68].
\nA strategy to increase the effectiveness of IIVs is the addition of adjuvants. Adjuvants are compounds that stimulate the immune system to mount a more robust and protective response to the vaccine. The most commonly used adjuvants in influenza vaccines are the oil-based compounds AS03 and MF59. Adjuvants can allow for the use of lower doses of antigen, resulting in more available doses of vaccine, which may be useful in times of high demand such as during pandemics. While adjuvanted vaccines are not approved for use in pregnant women in the United States, in Canada, and in many European countries, the pandemic vaccine was formulated with adjuvant and administered to pregnant women [69].
\nVaccination of pregnant women with IIV has taken place since the 1960s. Universal recommendation for vaccinating woman at all stages of pregnancy has been recommended by the CDC’s Advisory Committee on Immunization Practices (ACIP) since 2004 [65, 70, 71] and by the World Health Organization (WHO) since 2005 [1]. The Advisory Committee on Immunization Practices does not preferentially recommend a specific formulation—trivalent or quadrivalent—of the influenza vaccine [72]. In response to the 2009 H1N1 pandemic, the WHO placed pregnant women, along with caregivers of infants younger than 6 months old, healthcare and emergency services personnel, individuals between 6 months and 24 years, and those aged 25 years or older with chronic medical conditions, in the highest priority group to receive vaccines [73].
\nThe American College of Obstetrics and Gynecology (ACOG) considers prevention of influenza to be an “essential element of prenatal care” [74]. In full support of the ACIP recommendations, ACOG issued new guidelines in September of 2010 stating that all unvaccinated pregnant women at any gestational age be vaccinated against influenza [74].
\nIt is well documented that the antibody (Ab) response to influenza vaccine in pregnant women is similar to that of age-matched, nonpregnant women [75–79]. These observations support a conclusion that influenza vaccination will lead to an effective immune response in pregnant women and thereby provide an important tool in prevention of influenza in this population.
\nPregnant women and neonates are high-risk groups for complications from influenza infection. Control of influenza in this population is an important public health concern. However, due in part to ethical concerns related to enrolling pregnant women in clinical studies, experimental data on influenza vaccination during pregnancy has been scarce, and the quality of the evidence is not consistently high overall [80].
\nPrior to 2010, there were few well-designed studies specifically addressing vaccine effectiveness in pregnant women. From 1964 to 2008, four studies specifically addressed vaccine effectiveness in pregnant women (Table 1). These studies covered eight different influenza seasons and included 51,547 pregnant women.
\n\nDuring a 1962–1963 outbreak of Asian influenza, Hulka measured vaccine effectiveness in pregnant women by asking immunized and nonimmunized patients if they had experienced influenza symptoms during the influenza season. While fewer immunized than unimmunized patients reported respiratory illness with fever (11% versus 20%, respectively), there was no significant difference in reports of respiratory illness between these patients [76].
\nBlack et al. assessed vaccine effectiveness in almost 50,000 pregnant women across five influenza seasons. Vaccine effectiveness was determined by the number of outpatient visits for ILI or hospitalization for influenza or pneumonia. Using these outcomes, the risk of medical visit for respiratory symptoms was no different between vaccinated and unvaccinated women, and hospitalization was rare in both groups [81]. Using the adjusted hazard ratios (AHR = 1.151; CI, 0.979–1.352) from this study, Skowronski and De Serres calculated a vaccine effectiveness of −15% (CI, −35 to 2%) for this study population [7].
\nIn a retrospective case-control study of five influenza seasons (1995–2003), Munoz et al. estimated the potential protective effect of vaccination by recording the occurrence of acute respiratory infection (ARI) in vaccinated and unvaccinated women. The researchers reported a nonsignificant (
Study | \nStudy period | \nParticipants | \nOutcomes measured | \nInfluenza vaccine protection | \n
---|---|---|---|---|
Hulka [76] | \n1962–1963 | \n544 pregnant women -363 immunized -181 nonimmunized 176 nonpregnant women -138 immunized -38 nonimmunized | \nIncidence of influenza-like illness (ILI) | \nNonsignificant reduction in incidence of ILI (20% versus 11%) | \n
Black et al. [81] | \n1997–2002 | \n49,585 pregnant women -3707 immunized -45,878 nonimmunized | \nMedical visit for respiratory symptoms | \nNo difference in medical visits ( Adjusted hazard ratio = 1.151; (CI, 0.979–1.352) Clinical effectiveness: −15% Excluding medical visits for asthma, no difference ( Adjusted hazard ratio = 1.001 (CI, 0.838–1.196) Clinical effectiveness: 0% | \n
Munoz et al. [117] | \n1998–2003 | \nPregnant women -252 immunized -826 nonimmunized | \nMedically attended acute respiratory illness (ARI) | \nNonsignificant trend toward lower incidence of ARI (22.6% versus 18.9%; Clinical effectiveness: −20% (CI, −59.5 to 9%) any time during pregnancy 39% (CI, −56 to 76%) during peak of influenza season | \n
Zaman et al. [79] | \n2004–2005 | \n340 pregnant women -172 immunized with TIV -168 immunized with pneumococcal vaccine | \nRespiratory illness with fever | \nSignificant reduction of respiratory illness with any fever: Risk difference: −14.2 (CI, −25.5 to 2.9) Clinical effectiveness: 35.8% (CI, 3.7–57.2%) Reduction in respiratory disease with fever over 38 °C: Risk difference: −7.3% (CI, −14.5 to 0.1%) Clinical effectiveness: 43.1% (CI, −9.0 to 70.3%) | \n
Madhi et al. [83] | \n2011–2012 | \n2116 pregnant women -1062 immunized with IIV3 -1054 received placebo | \nRT-PCR- confirmed influenza | \nClinical effectiveness: 50.4% (CI, 14.5–71.2%) | \n
Thompson et al. [84] | \n2010–2012 | \nPregnant women -100 with confirmed influenza -192 with ARI negative for influenza -200 control negative for influenza | \nRT-PCR- confirmed influenza | \nClinical effectiveness: 44% (CI, 5–67%) compared to influenza-negative controls 53% (CI, 24–72%) compared to ARI-negative controls | \n
Richards et al. [101] | \n2009–2010 | \n1125 vaccinated 1581 non-vaccinated (unadjuvanted vaccine) | \nRT-PCR or medical visit during pregnancy with influenza-related ICD-9 diagnosis code | \nClinical effectiveness: 61.5% (CI, 15.5–82.5%) | \n
Haberg et al. [53] | \n2009–2010 | \n117,347 pregnant women (adjuvanted vaccine) | \n\n | Clinical effectiveness: 70% (AHR, 0.30; (CI), 0.25–0.34) | \n
Clinical effectiveness of IIV and A(H1N1)pdm09 influenza vaccine during pregnancy.
The authors of this study speculate that while the receipt of an influenza vaccine may not prevent infection, it is likely to reduce the severity of the disease. However, they provided no data on clinical severity or evidence of such an association with vaccination status. Since there was no confirmation of influenza infection in most patients with ARI, it is impossible to confirm whether clinical symptoms were associated with influenza infection or with other respiratory viruses.
\nIn 2008, Zaman et al. published the first randomized, double-blind, controlled clinical trial (RCT) of influenza vaccine in pregnant women. In this study, 340 pregnant women were randomized to receive either trivalent influenza vaccine (IIV3) or pneumococcal polysaccharide vaccine during the third trimester of pregnancy. This study was part of The Mother’s Gift project, a randomized trial with the primary goal of assessing the safety and immunogenicity of pneumococcal vaccines. Therefore, the control arm consisted of mothers who received the pneumococcal vaccine, providing a control for an active, non-influenza vaccine. The authors measured nonspecific respiratory illness with fever and found that vaccinated women were significantly less likely to have respiratory illness, reporting a clinical effectiveness of 35.8% (CI, 3.7–57.2%) for respiratory illness with any fever and 43.1% for fever over 38 °C (CI, −9.0 to 70.3%) [79].
\nAll of these studies share the common weakness that they use clinical symptoms, and not laboratory-confirmed influenza, as the primary outcome. Influenza vaccines are specifically targeted to influenza viruses. Many other respiratory pathogens can cause symptoms similar to influenza, but influenza vaccines are not designed to prevent other causes of influenza-like illness. Hence, clinical symptoms without laboratory confirmation are nonspecific outcomes. Interpretation and quantification of true vaccine effectiveness using only clinical outcomes are problematic, potentially leading to inaccurate estimates of effectiveness. For this reason, laboratory confirmation, either by reverse transcription polymerase chain reaction (RT-PCR) or viral culture, remains the best diagnostic tool for confirming influenza and evaluating vaccine efficacy (VE) and effectiveness.
\nIn 2014, two studies began to address this deficiency in the literature. The research teams estimated influenza vaccine effectiveness in preventing illness among pregnant women using laboratory-confirmed (RT-PCR) influenza as the primary outcome.
\nMadhi et al. examined maternal and fetal outcomes in 2116 HIV-negative South African women during the 2011–2012 influenza season. 1062 women who received IIV3 were compared to women who received a placebo. Overall vaccine effectiveness at preventing laboratory-confirmed (RT-PCR) influenza in this population was 50.4% (CI, 14.5–71.2) [83].
\nUsing a large health plan database, the Pregnancy and Influenza Project evaluated seasonal vaccine efficacy during the 2010–2011 and 2011–2012 influenza seasons. The authors compared the proportion of vaccinated women among 100 RT-PCR-confirmed influenza cases with the proportion vaccinated among 192 women with ARI who tested negative for influenza, and 200 controls matched by season, site, and trimester [84]. The adjusted vaccine efficacy against influenza was of 44% (CI, 5–67%) using the influenza-negative controls and 53% (CI, 24–72%) for the ARI-negative controls [84].
\nThe 2009 A(H1N1) pandemic provided an opportunity to improve understanding of influenza vaccination during pregnancy. The pandemic allowed an evaluation of the effectiveness of maternal vaccination during an influenza season in which there was a high rate of viral circulation, as well as a close match between the vaccine strain and the circulating viral strain. Pregnant women were prioritized to receive the vaccine and were strongly advised to be vaccinated [85], resulting in higher than usual vaccination rates [86].
\nSince the 2009 pandemic, a number of studies have examined monovalent pandemic A(H1N1) vaccination of pregnant women. Synthesizing evidence from this new and expanding database should increase our understanding of maternal influenza vaccination. While most of these studies measured either seroconversion and hemagglutinin inhibition (HAI) titers [87–92] or safety and/or birth outcomes [93–100], two studies specifically examined clinical efficacy of pandemic A(H1N1) vaccine during pregnancy.
\nIn a retrospective cohort study, Richards et al. evaluated influenza infection in 1125 vaccinated and 1581 non-vaccinated women. In this study, influenza infection was defined as testing positive for influenza by RT-PCR or having a medical visit during pregnancy with influenza-related
A separate population-based study of 117,347 pregnant women in Norway estimated that vaccination during the second or third trimester of pregnancy resulted in a 70% reduction in influenza diagnosis following vaccination with adjuvanted A(H1N1) vaccine (adjusted hazard ratio, 0.30; CI, 0.25–0.34) [53].
\nWhile there is significant heterogeneity among these eight clinical studies, presenting wide-ranging estimates of vaccine effectiveness in pregnant women (from −15 to 70%), the evidence of effectiveness data based on laboratory-confirmed influenza is mounting and compelling. The cumulative evidence to date provides three studies showing significant clinical effectiveness during seasonal influenza years, 35.8% against respiratory disease in a RCT [79], 50.4% protection against laboratory-confirmed influenza in a RCT [83], and one large data-base study documenting VE of 44–53% [84]. Two studies of vaccine effectiveness during the 2009 A(H1N1) pandemic estimated VE of 61.5% (unadjuvanted) and 70% (adjuvanted), suggesting that vaccination during a pandemic season may offer more benefit than during non-pandemic years.
\nThese more recent estimates using laboratory-confirmed endpoints are well within the reported vaccine effectiveness for healthy, nonpregnant adults. When combined with the well-documented observation that the antibody response to influenza vaccine in pregnant women is similar to that of nonpregnant women, all current evidence suggests that efficacy of influenza vaccines in pregnant women is similar to the nonpregnant population.
\nAn important secondary benefit of maternal vaccination appears to be protection of infants from influenza infection during the first months of life, providing an important two-for-one benefit since no influenza vaccine is licensed or recommended for infants younger than 6 months of age.
\nMaternal vaccination has potential to protect newborns due to the transfer of maternal immunity. Transplacental transfer of antibodies occurs throughout pregnancy, with highest levels during the last 4–6 weeks of gestation [102, 103]. Antibodies (specifically IgG) cross the placenta from mother to fetus during the final weeks of pregnancy, while infants acquire additional immune protection during breastfeeding, when the main class of immunoglobulin transferred in breast milk is IgA [104].
\nSeveral studies have demonstrated transplacentally acquired antibodies after natural influenza infection in the mother. One study examined the cord sera of 26 infants who had culture-confirmed influenza when younger than 4 months of age. The authors found a direct correlation between the gestational age at the time of infection and the level of antibody in the cord serum (
During the 1979 influenza epidemic, infants of mothers with serum antibody to influenza (seropositive) were compared to infants of mothers who were seronegative [106]. The infants of seropositive mothers had higher specific serum antibody (IgG) titers against the HA influenza protein than did infants of seronegative mothers. Good correlation was found between maternal antibody titers and titers in infants (correlation, 0.81). No such correlation was found for non-immune mothers and their infants (correlation, 0.24) [106]. However, this study showed no difference in incidence of influenza infection, although infants of immune mothers showed delayed onset of symptoms and shorter duration of illness, suggesting that passive maternal immunization may delay onset and severity.
\nWhen evaluating vaccination response to influenza, a serum antibody titer of ≥1:40 against the HA protein is considered to be clinically relevant, resulting in a 50% decrease in symptomatic infection and, therefore, serving as a correlate of protective immunity [107]. Recent analysis of published data indicates an even higher level of clinical protection, estimating that 70% of participants are protected at a titer of 1:40, with protection increasing gradually with higher titers [108].
\nIn the absence of a widely accepted immune correlate of protection for influenza, the analysis of hemagglutinin inhibition (HAI) seroprotection rates is generally considered a useful indicator of protection in vaccinated persons. There are challenges associated with using this antibody titer as a correlate of protection in infants, however, particularly since this correlate was determined in healthy adults [41, 107]. In any event, the US Food and Drug Administration (FDA) uses this HAI antibody titer in evaluation of influenza vaccines, making the HAI antibody titer the standard used by most investigators [40], including those examining vaccine protection in neonates.
\nIn a study examining transplacental transfer of antibody in response to vaccination, Englund et al. studied women during the last trimester of pregnancy who were vaccinated with IIV3 (A/Sichuan/H3N2, A/Taiwan/H1N1, B/Victoria). Maternal immunization resulted in the transfer of influenza-specific IgG to the infants. When measured at the time of delivery, the levels of antibody transferred were high, with between 87 and 99% of antibody detectable in the mother also detectable in the infant [78]. The antibody titers to at least two of the three influenza antigens (influenza H3N2 and influenza B) remained significantly elevated up to 2 months of age [78].
\nSumaya and Gibbs vaccinated pregnant women and reported a similar correlation, finding that cord blood HAI antibody in infants correlated with titers of vaccine-stimulated HAI antibody in mothers, with HAI antibody detected in 54% of newborn serum and 73% of maternal serum [75]. This study did not examine infant influenza infection as an outcome, so the study was unable to correlate serum antibody levels with clinical outcome.
\nWhile these previous studies demonstrated that maternal antibody appears to be transferred to infants following both natural infection and vaccination, neither study discussed whether the level maternal antibody was high enough to confer protective immunity to the infant [41, 107]. Using HAI titer as a correlate of immunity, Steinhoff et al. did conduct an RCT of maternal influenza vaccine. Serum samples were obtained from 311 mothers before vaccination and at delivery and from 292 infants at birth at 10 weeks and 20–26 weeks later [109]. The proportion of mothers with a protective antibody titer (HAI ≥ 1:40) at the time of delivery was 88% for A/New Caledonia (H1N1), 98% for A/Fujian (H3N2), and 45% for B/Hong Kong. Similar proportions of infants had protective antibody titers at birth [109].
\nYamaguchi et al. also examined the immune responses to influenza vaccination during pregnancy by measuring the effect of influenza vaccination (IIV3) in pregnancy, including maintenance of the specific antibody response, and the efficiency of transplacental transfer of the antibody to the fetus. The study included 125 pregnant women, 71 in their second trimester and 54 during the third trimester of pregnancy. The authors reported that vaccination at any time during pregnancy yielded protective levels of antibody in both maternal and fetal blood [110].
\nIn a prospective study examining the immunogenicity and transplacental transmission of antibodies in pregnant women in Asia, Lin et al. enrolled 46 pregnant women who received a single dose of IIV3. Twenty-eight days after vaccination, the seroprotection rate in vaccinated women against H1N1, H3N2, and influenza B was 91.3, 84.8, and 56.5%, respectively [111].
\nSeveral additional studies have demonstrated transplacental antibody transfer following maternal vaccination with pandemic H1N1 vaccine. Three studies evaluated adjuvanted A(H1N1) vaccines, and two studied nonadjuvanted A(H1N1)vaccine. All five of the studies documented protective levels of antibody in significant percent of infants (79–95%).
\nZuccotti et al. followed 69 mother-infant pairs. The women were vaccinated during their third trimester of pregnancy with MF59-adjuvanted influenza A(H1N1) vaccine. All of the mothers had HAI antibody titers at or above 1:40 at the time of delivery and throughout the 5 months of follow-up. Ninety-five percent of the infants had HAI antibody titers at or about 1:40 at both birth and 2 months of age. By 5 months of age, the proportion of infants with titers of 1:40 dropped to 81.2% [89], suggesting that passively acquired antibody at levels thought to be protective is transferred and persists for at least 5 months.
\nIn a separate study performed at three sites in the UK, researchers followed infants born to mothers who were vaccinated with AS03-adjuvanted H1N1 vaccine during the second or third trimester of pregnancy. This study found that 79% of the infants of vaccinated mothers had serum antibody titers at or higher than 1:40 compared to a background immunity in 19% of infants of unvaccinated women (
Helmig et al. evaluated the serological response of a cohort of women immunized with adjuvanted A(H1N1) vaccine or by natural infection with A(H1N1)pdm09. The authors detected protective antibody levels (>1:40) in a significant number 17/19 (89.5%) of newborns born to vaccinated mothers (
In a study of nonadjuvanted A(H1N1) vaccine, Tsatsaris et al. measured Ab titers in cord blood of 88 infants born to women vaccinated with a single dose of monovalent A(H1N1) vaccine. The researchers reported 95% (CI, 89–99%) of infants have protective levels of antibody (>1:40) at birth [114], and Fisher et al. also reported protective levels of Ab in cord blood of infants following maternal vaccination with 2009 monovalent A(H1N1) [115].
\nTaken together, these studies provide an important proof of concept for transplacentally acquired antibody, from either natural infection or vaccination of their mother, to potentially protect young infants from influenza infection and present maternal immunization as a promising strategy for reducing influenza infection in infants.
\nOver the past 11 years, nine studies have been published evaluating the effect of maternal immunization on influenza in 97,656 infants across 15 influenza seasons. Six of these studies showed clinical protection; three studies did not (Table 2).
\nStudy | \nStudy period | \nParticipants | \nOutcomes measured | \nProtection by maternal influenza vaccine | \n
---|---|---|---|---|
Black et al. [81] | \n1997–2002 | \n49,585 pregnant women | \nHospitalization for pneumonia and influenza | \nNo difference in risk for hospitalization ( Adjusted hazard ratio: 0.956 (CI, 0.889–1.029) Clinical effectiveness: 4% (CI, –3 to 11%) No difference in risk including otitis media visit ( Adjusted hazard ratio: 0.938 (CI, 0.777–1.132) Clinical effectiveness: 6% (CI, –13 to 22%) | \n
Munoz et al. [117] | \n1998–2003 | \n225 infants of immunized mothers 826 infants of nonimmunized mothers | \nHospitalization or clinic visits for respiratory conditions | \nNo difference in hospitalization During first month, infants of immunized moms had more clinic visits for bronchitis ( No other differences | \n
France et al. [116] | \n1995–2001 | \n3160 infants of immunized mothers 37,969 infants of nonimmunized women | \nMedically attended acute respiratory illness (ARI) | \nNo reduction in clinic visit rates Incident rate ratio: 0.96 (CI, 0.86–1.07) | \n
Zaman et al. [79] | \n2004–2005 | \n316 infant-mother pairs followed for 24 weeks | \nClinic visits for respiratory illness Laboratory-confirmed influenza before 24 weeks of age (confirmation by rapid test) | \n63% effective at preventing laboratory-confirmed influenza in infants up to 6 months old (CI, 5–85%) 29% effective in preventing febrile illness (CI, 6.9–45.7%) 42% effective in preventing clinic visit (CI, 18.2–58.8%) | \n
Benowitz et al. [118] | \n2000–2009 | \nInfants less than 12 months old -220 cases -430 matched controls | \nLaboratory-confirmed influenza (confirmation by direct fluorescent antibody (DFA) test) | \n91.5% effective at preventing hospitalization of infants less than 6 months of age ( No significant effect on infants older than 6 months | \n
Eick et al. [120] | \n2002–2005 | \n1169 infant-mother pairs | \nLaboratory-confirmed influenza (confirmation by viral culture, fourfold rise in HAI antibody in cord serum or rapid test) | \nLaboratory-confirmed influenza decreased among infants born to vaccinated women compared to controls Risk ratio 0.59 (CI, 0.37–0.93) Clinical effectiveness: 41% Hospitalization Risk ratio 0.61 (CI, 0.45–0.84) Clinical effectiveness: 39% | \n
Poehling et al. [126] | \n2002–2009 | \nInfants less than 6 months old hospitalized with fever or respiratory symptoms -151 cases -1359 controls | \nLaboratory-confirmed influenza (confirmation by viral culture or PCR) | \nHospitalized infants whose mothers were immunized were 45–48% less likely to have laboratory-confirmed influenza Adjusted odds ratio (OR) 0.52 (CI, 0.30–0.91) | \n
Sugimura et al. [127] | \n2010–2011 | \n200 infants from birth to 6 months of age -106 infants of vaccinated mothers -90 infants of unvaccinated mothers | \nLaboratory-confirmed influenza (confirmation by rapid test) | \nSignificant difference in incidence of influenza between infants of vaccinated versus unvaccinated mothers ( | \n
Madhi et al. [83] | \n2011–2012 | \n2046 infants -1026 infants of vaccinated mothers - 1023 infants of placebo mothers | \nLaboratory-confirmed influenza RT-PCR | \nVaccine efficacy of 48.8% (CI, 11.6–70.4%) | \n
Clinical effectiveness of maternal vaccination for protection of infants.
In a retrospective cohort study of 48,639 infants, Black et al. found that infants born to vaccinated women had the same risk of hospitalization for influenza or pneumonia as infants of unvaccinated women (CI, 0.889–1.029). They also reported that maternal vaccination was not a significant determinant of risk for ILI or otitis media [81].
\nFrance et al. followed 3160 infants of immunized mothers and 37,969 infants of nonimmunized mothers from 1995–2001 and during four specific seasonal periods: peak influenza, respiratory syncytial virus predominant, periseasonal, and summer weeks [116]. They found no difference in medically attended ARI (incident rate ratio for peak influenza season 0.96, CI, 0.86–1.07), concluding “maternal influenza vaccination did not reduce visit rates during any of the four time periods and did not delay the onset of first respiratory illness” [116].
\nIn a study that included an examination of data over five influenza seasons, Munoz et al. reported similar results, finding no difference in hospitalizations for respiratory illness during the peak of influenza season between infants of vaccinated mothers versus infants of non-vaccinated mothers [117].
\nWhile the three earlier studies above found no benefit to infants from maternal vaccination, a more recent matched case-control study of infants less than 12 months old admitted to hospitals for seasonal influenza between 2000 and 2009 reported maternal vaccination to be 91.5% effective (CI, 61.7–98.1%,
Eick et al. conducted a study in the White Mountain and Navajo reservations over three influenza seasons, November 2002 to September of 2005. In this prospective cohort study, the effect of influenza vaccine during pregnancy on influenza infection in infants was compared between infants of vaccinated women and those born to non-vaccinated women. The authors analyzed 83 confirmed influenza cases. Of these cases, seven (86%) were confirmed by serology, ten (12%) by viral culture, and two (2%) by rapid influenza testing. Using these three measures of influenza infection, the authors reported a 41% reduction in the risk of laboratory-confirmed influenza for infants born to vaccinated women (RR 0.59, CI, 0.37–0.93) and a 39% reduction in the risk of ILI hospitalization (RR 0.61, CI, 0.45–0.84) [120].
\nThe authors of this study pooled the results from three different assay methods, each with different sensitivities, to document influenza infection. Pooling assays with differing diagnostics represents a limitation of this study. Likewise, the use of serology to document influenza in most (86%) of cases represents a weakness of this study. The authors describe serological documentation of influenza infection as a fourfold or greater increase in HAI antibody in serum collected at 2–3 or 6 months compared with previous serum specimen [120]. Significant limitations have been reported regarding the use of serology in diagnosing influenza in adult patients that have been vaccinated with inactivated vaccines [121–123]. Using serology to document influenza infection in young infants presents additional complications.
\nInfants under 6 months of age have immature, immunologically inexperienced immune systems. Since their ability to produce antibody in response to infection is often delayed or completely absent, many of their serum antibodies are maternally derived. More than 50 years ago, the use of serology for diagnosis of influenza in infancy was questioned. During an influenza outbreak in Glasgow in 1953, fourfold increases in antibody were found in only 20% of infants admitted to pediatric pneumonia wards (as compared to 30% of adult cases) [124]. In two different outbreaks, antibody production was absent or considerably delayed in infected children under 18 months of age, even when virus could be isolated [125]. These observations illustrate the difficulties inherent in using serology to document influenza infection in young infants.
\nIn the only randomized, blinded clinical study to assess infant protection, Zaman et al. reported a vaccine effectiveness of 63% (CI, 5–85%) against laboratory-confirmed influenza in infants up to 6 months of age [79]. Influenza was confirmed by rapid test (Z Stat Flu), which was reported to have a specificity of 80–90% and a sensitivity of 70–72% for type A and type B influenza. When respiratory illness and fever were used as measure of disease, the reported effectiveness was 29% (CI, 7–46%) [79].
\nA recent study sought to determine whether maternal vaccination during pregnancy was associated with a reduced risk or laboratory-confirmed influenza hospitalizations in 1510 infants over seven consecutive influenza seasons (2002–2003 through 2008–2009) and across three diverse geographic regions of the United States [126]. Of the 1510 infants hospitalized with fever or respiratory symptoms, 151 (10%) had laboratory-confirmed (by viral culture or RT-PCR) influenza. The proportion of infants who were influenza positive varied significantly across influenza seasons, from 3% in 2006–2007 to 15% in 2003–2004. The percentage of women who were vaccinated also varied by season, from 10% in 2003–2004 to 38% in 2008–2009.
\nAmong influenza-positive infants during all study years, 12% of their mothers reported being vaccinated during pregnancy, while 20% of mothers of influenza-negative infants reported receiving a vaccination [126], yielding an adjusted odds ratio of 0.52 (CI, 0.30–0.91) and suggesting that infants whose mothers received influenza vaccines during pregnancy were 48% less likely to have laboratory-confirmed influenza than infants of unvaccinated women [126].
\nIn a randomized, placebo-controlled trial of influenza vaccination in South Africa, Madhi et al. followed 1026 infants born to women who received IIV3 and 1023 infants born to placebo recipients. The attack rate of influenza was lower among infants of vaccinated mothers (1.9%) than among those whose mothers received placebo vaccine (3.6%), yielding a vaccine effectiveness of 57.5% (CI, 7.6–70.4) in this population [83].
\nIn a prospective study, Sugimura et al. assessed the incidence of fever and laboratory-confirmed influenza in newborns whose mothers were vaccinated during pregnancy with IIV3. Two hundred infants were followed from birth to 6 months of age. Fever was noted in 36 (34%) of the infants in the vaccinated group and 47 (52.2%) of infants born to unvaccinated mothers (
The reviewed studies assessed hospitalization, clinic visits, ARI, or laboratory-confirmed influenza as primary outcomes. Rationale for influenza vaccination often includes additional secondary outcomes such as reduction of absenteeism for household contacts, secondary infections, acute otitis media, or community transmission of influenza. While these outcomes are important in measuring the broad impact of influenza, they do not provide accurate assessment of vaccine efficacy or effectiveness. Such an assessment is essential for evidence-based, reasoned development of public health policy and decision-making about influenza prevention.
\nIn summary, the evidence for newborn protection through maternal vaccination is encouraging, but several studies exhibit methodological limitations. The results of studies measuring rates of ARI, clinic visit, or hospitalization range from no vaccine effect up to 42% effectiveness [81, 116, 117]. The six studies that used some form of laboratory-confirmed influenza (rapid tests, viral culture, or PCR) as the primary outcome are more encouraging, reporting vaccination effectiveness ranging from 41 to 91.5% [79, 83, 118, 120, 126, 127].
\nWhile outcomes and study designs differ, in general the data to date suggest that maternal vaccination has the potential to decrease influenza illness in newborns. As such, maternal immunization during pregnancy should continue to be recommended and encouraged for all women.
\nInfluenza is a complex disease. For centuries it has eluded complete understanding or control. Constantly evolving and catching us by surprise, influenza is a perpetually emerging disease. The main tool for prevention of influenza is vaccination, the cornerstone for prevention of influenza disease. However, unlike many other vaccines, the effectiveness of influenza vaccines remains moderate to marginal across all populations [128], and in addition, the vaccines need to be administered every year. A universal influenza vaccine providing broad and long-lasting protection continues to be elusive.
\nThese realities—difficult enough in the general population—are even more challenging to understand during pregnancy. Particularly complex is determining how, or if, the changing immune responses over pregnancy vis-a-vis influenza season and vaccination schedules impact vaccine effectiveness and disease outcomes in pregnant women.
\nA recent critique by Savitz et al. calls into question our most basic understanding of influenza infection during pregnancy, with a particular critique on the quality of the evidence for a benefit of maternal vaccination in prevention of harm from seasonal influenza [129]. Savitz et al. discuss the complications inherent in many current research practices, which serve to limit our understanding of the true picture of maternal influenza. Central to this critique is the notion that both pregnancy and influenza have temporal components; influenza typically is seasonal, with a 2–3-month period of circulation each year. But pregnancy has trimesters, each with distinct fetal developmental stages along with physiological and immunological changes in the expectant mother. To complicate this further, the risk of adverse outcomes from influenza infection is not equal across all trimesters of pregnancy. Therefore, optimizing risk and benefit of vaccination during pregnancy is complicated and likely requires reexamination of influenza risk and benefit across trimesters in association with months of influenza circulation [129].
\nA recent WHO review of influenza throughout pregnancy found insufficient data from comparable studies to discern which specific weeks, months, or trimesters influenza poses increased risk to pregnant women [130]. Savitz et al. assert that “As with all time dependent states, pregnancies must be followed longitudinally. There needs to be a week-by-week consideration of the pregnancy with regard to vaccination status and circulating influenza viruses” [129].
\nAside from complications associated with potential differences in virus exposure across the trimesters of a pregnancy, risks posed to pregnant women also may differ according to the specific strain circulating during a given season, and, likewise, the immune response to vaccination also could differ based on strain [131].
\nEven when taking yearly strain differences into account, variation in immune responses across trimesters adds yet another complicating variable. It is widely accepted that the immune response to influenza vaccine in pregnant women is indistinguishable from that of nonpregnant women and that gestational age appears to have no effect on antibody response [75, 76, 132, 133].
\nFindings from more recent studies suggest that we may need to entertain a more nuanced approach to our understanding of the maternal immune response to influenza vaccination—precisely because immunogenicity and seroconversion may not tell the entire story.
\nIn a 2011 study, Ohfuji et al. reported a lower seroprotective antibody response to pandemic A(H1N1) vaccine in pregnant women who had received prior seasonal influenza vaccine and suggested that the potential interference between pH1N1 and seasonal vaccination needed additional investigation [15]. Schlaudecker et al. directly compared immunogenicity of inactivated influenza vaccine in pregnant versus nonpregnant women and found that pregnancy modified antibody responses to the vaccine [134]. They demonstrated a significantly decreased postimmunization HAI geometric mean titer and a nonsignificantly decreased geometric mean ratio (fold increase) to influenza A antigens after influenza vaccine, even though overall seroconversion and seroprotection rates were comparable between the two groups of women. In a 2013 blinded randomized control study, Bischoff et al. found that the immune response to an adjuvanted pandemic A(H1N1) vaccine in pregnant women was decreased compared with nonpregnant women [133]. Sperling et al. examined HAI titers over pregnancy and found that timing of vaccination did not alter response, although there was a trend toward lower responses during the first trimester and six weeks postpartum [135].
\nA small study of 36 women during the 2012–2014 flu seasons suggests that T-follicular helper (Tfh) cell response to vaccination was highest during the first trimester of pregnancy. Tfh cells are required for the generation of high-quality antibody-producing B cells. Their expansion has been shown to be a predictor of response to influenza vaccination outside of pregnancy suggesting that immunologic changes during pregnancy may impact vaccine response. Notably, there was no significant expansion of Tfh after vaccination during either the second or third trimester [136].
\nIn a study aimed to determine the optimal timing for vaccination within the second or third trimesters of pregnancy, Yamaguchi et al. reported that serum antibody levels in vaccinated women depended not on gestational stage but on the amount of time elapsed, since vaccination antibody titers decreased with time [110]. This observation is supported by other studies documenting that influenza-specific antibodies after vaccination are typically short lived [115].
\nTwo separate studies of vaccine effectiveness in nonpregnant adults during the 2011–2012 influenza season also suggest that vaccine effectiveness wanes with time since vaccination [137, 138]. In both of these studies, vaccination effectiveness waned in people who were vaccinated 93 days—around 3 months—or more before presentation of symptoms. A similar observation was made by Fisher et al. who demonstrated a significant linear decline over time in HAI titers after pH1N1 infection or vaccination (
Taken together, these observations support a consensus that pregnant women are capable of mounting a robust immune response to influenza vaccination during the second and third trimester of pregnancy. Experimental evidence during the first trimester is less clear, due in part to a limited number of studies on influenza vaccination during the first trimester.
\nThere is increasing evidence suggesting that—regardless of initial vaccine response—the level of vaccine-mediated anti-influenza-specific antibodies decreases with time. This waning of antibody implies that women vaccinated during the first trimester of pregnancy might be
Cross-placental transfer of immunity occurs when antibodies cross the placenta via active transport, particularly in the final weeks of pregnancy. It is logical to assume that vaccine-induced maternal antibody transmitted to the fetus will provide protection to the infant during the first months of life, and several studies document increased antibody titers in infants of vaccinated mothers [120].
\nComparable to studies of vaccinated mothers, researchers have demonstrated that the titers of influenza-specific antibodies in newborns, while not affected by trimester of maternal vaccination (within second or third trimester), do wane with time and are short lived [75]. Tsatsaris et al. also noted a trend toward lower cord blood antibody titer associated with longer intervals between maternal vaccination and delivery. A similar observation was made by Yamaguchi et al. who reported that transfer rate from the maternal blood to the fetal blood at time of delivery tended to be inversely correlated with duration of gestation postvaccination [110]. Some additional studies have hinted at lower cord blood titers among infants of women vaccinated in the first trimesters, but it is unclear if this is clinically significant [131].
\nTaken together, these studies serve to highlight the complicated nature of immunity particularly during pregnancy in response to vaccination and invite further virological and epidemiological studies to confirm and fully understand these observations and to correlate changes in antibody titer with clinical outcomes in both mothers and infants. As our understanding evolves, we may need to develop a more nuanced approach—one that takes into consideration the trimester of exposure to both circulating virus and vaccines—to optimize vaccine effectiveness during the period of highest risk of influenza disease.
\nThe recommendation to vaccinate all pregnant women regardless of gestational age is motivated in part by operational concerns. Timing of the influenza vaccine campaigns occurs in the fall in temperate regions. Pregnancy, on the other hand, occurs throughout the year. Since pregnancy presents a period of regularly scheduled and repeat visits, a more tailored approach to influenza vaccine coverage may be appropriate in order to stack the odds in favor of the highest level of protection for both mother and infant.
\nThe impact of influenza infection on pregnant women and newborns is well documented. The increased risk for morbidity and mortality has resulted in the universal recommendation that pregnant women be vaccinated for influenza at any stage of pregnancy [65]. Evidence to date suggests that influenza vaccination during pregnancy is similarly effective as in the nonpregnant population. Pregnant women mount robust immune response that correlates with clinical efficacy. This immunity then is transferred to the fetus during gestation, providing clinical benefit to infants less than 6 months of age. And while not a component of this review, there is substantial evidence that influenza vaccines are safe during all stages of pregnancy with no evidence of risk of adverse pregnancy outcome linked to influenza vaccines [3, 65, 131, 139, 140].
\nGaps remain in our understanding of influenza risk over all seasons and trimesters, of maternal immunity, and of optimal timing of vaccination. To this end, in January of 2015, the Bill and Melinda Gates Foundation held a meeting of global stakeholders in the maternal influenza field. Participants identified a need for stronger evidence regarding, among other issues, the burden of disease and maternal immunization efficacy [141]. Expanding this evidence base will allow for a deeper understanding of influenza in this population and the development of more robust and efficacious public health approaches toward this disease.
\nLandslide and slope failures are very dangerous and caused a lot of damages to the people all over the world every year. Environmentally friendly approach to improve the soil condition is necessary for the sustainable global environment. The traditional methods to protect the land against the geo-disasters such as landslide and liquefaction are mainly mechanical or chemical approach to soil and are not environment friendly. Nature has provided a significant biologically based solution to some of the challenges that vex geotechnical infrastructure systems. Recent studies on applications of bio-mediated soil improvement methods have proved the viability of the approach for effective performance and environmental sustainability. The potential outcomes of these studies have shown greater promise of exploring a wider application of the technique in geotechnical engineering. The great promise of the use of biological treatments has been demonstrated in many applications, such as improving the shear strength and decreasing the permeability of soils [1, 2, 3, 4, 5] improvement in strength and durability of concrete and morter, remediation of cracks in buildings [6, 7, 8, 9, 10]; improvement in engineering properties of soil and cementation of sand column [11, 12, 13, 14, 15, 16]. However, the uniformity of biocementation inside the soil is not well-known yet.
The objective of this research is to look at the difference of mechanism of biocementation between the Toyoura sand and silica sand no. 4 through scanning electron microscope and x-ray CT analysis.
There are several ideas of ground improvement method utilizing microbial metabolism, among which the calcium carbonate method has been vigorously researched in Japan and abroad recently due to the applicability to the real ground and the formation of solid matter derived from microorganisms. (ATCC 11859) used in this study as a source of microorganism [16, 18]. The characteristic of this microorganism is that it has the function of decomposing urea called urease enzyme. In addition, it is known that this microorganism has pressure, temperature, salt tolerance and alkali resistance, and it has a relatively strong resistance under various ground environments. The chemical reaction at that time is shown below. Cementation action between particles is caused by calcium carbonate precipitated between the soil particles, of the applied ground.
Two types of sands were used in the experiment to compare the effects of the size of the particles on biocementation. Toyoura sand and silica sand no. 4 were used for biocementation. The grain size analysis of those sands is shown in Figure 1. The particle size of silica sand is larger than Toyoura sand.
Grain size analysis of Toyoura sand and silica sand used in the experiment.
The shear strength properties measured by using direct simple shear test apparatus. The sample dimension used was 60 mm x 22.6 mm. The samples have been sheared by above mentioned apparatus under three normal loads magnitudes, namely10, 30 and 50 kN/m2. The samples under the same load magnitude have been sheared at least three times. The constant velocity of magnitude 0.2 mm/min was applied. The test is finished when the shear strain reaches 26% (Figure 2).
Direct simple shear test apparatus.
The scanning electron microscope (SEM) analysis was carried out by using JSM-7600F and consequently analyzed the energy dispersive spectroscopy (EDS) to observe the surface of the bio-cemented soil particles and the mineral amount in different samples.
X-ray CT scan was carried out of the treated samples after 1 week of treatment for both Toyoura sand and silica sand to observe the location of the calcite generation.
Figure 3 illustrates that the result if the X-ray CT scan of the 1 week bio-treated sand samples. It was observed that in silica sand the amount of CaCO3 was more than that of Toyoura sand. The shape of the sand particles has influence to generate the amount of calcite [17, 18, 19, 20, 21, 22]. Another thing was observed that the amount of calcite was more in the lower portion than the upper portion of the samples. The bacteria and the nutrient was applied from the surface of the sample and this has made the influence to precipitate the calcite at the lower portion more as liquid flows through the pore spaces.
X-ray CT analysis (left photo Toyoura sand and right photo silica sand).
Figure 4 shows that the scanning electron microscopic view of the biotreated sand after 1 week of treatment. It was observed that the shape of the crystal is different in Toyoura and Silica sand. This type of shape of crystal might be give some influence on the strength of the biotreated sand.
Scanning electron microscope (SEM) analysis of the Toyoura (left) and silica (right)sand.
Figure 5 displays the EDS analysis of the biotreated soil samples. Rhombohedral crystal (calcite) was present on the surface of the particle and Ca element was extracted from the element mapping, and the tendency that calcium carbonate is widely distributed on the surface of the particle of silica sand than Toyoura sand.
EDS analysis of Toyoura (left) and silica (right) sand.
Figure 6 shows the relationship between Pca and depth of Toyoura sand and silica sand. As shown in Figure 1, the particle size was larger than Toyoura sand, and it was considered that calcium carbonate covered and enlarged around the particle. Rhombohedral crystal (calcite) was present on the surface of the particle and Ca element was extracted from the element mapping, and the tendency that calcium carbonate is widely distributed on the surface of the particle of silica sand than Toyoura sand. An aggregate of rhombohedral crystals with a grain diameter of rhombohedral crystal (calcite) of 10 μm to 50 μm was observed. A spherical crystal (vaterite) different from rhombohedral crystal was observed in Toyoura sand. In silica sand, existence of spherical crystal (vaterite) could not be confirmed. In addition, it was considered that the transition from vaterite to calcite was proceeding in silica sand. As the Toyoura sand and the silica sand, the shape of the particle is different they also influenced the shape of crystals.
Relation between calcium production and depth.
From Figure 6 it was confirmed that silica sand Ca (calcium) element increased as compared with Toyoura sand under the same treatment condition. Since the particle size of silica is larger than Toyoura sand, calcium carbonate covers the particle surface particles, and the amount of Ca (calcium) element is higher than Toyoura sand. It was considered that it increased shear test by calcium carbonate method.
Figures 7 and 8 show the relation among the shear stress and shear strain and volumetric strain by direct simple shear test of Toyoura sand and silica sand, respectively. It shows the stress–strain relation of Toyoura sand the stress–strain relation of Toyoura sand cemented 1 Week by bio-treatment. It was observed that the shear stress value increased by 1.3 to 2.0 times in the case of no addition of microorganisms of silica sand and Toyoura sand and addition of microorganisms with 1 Week. An increase in shear stress was confirmed and from the point of comparison the shear stress of Toyoura sand was higher than the silica sand.
Relation between shear stress and shear strain and volumetric strain of Toyoura sand without (left) and after 1 week of treatment.
Relation between shear stress and shear strain and volumetric strain of silica sand without (left) and after 1 week of treatment.
Figure 9 shows the relationship between the shear strength and the normal stress determined from Figures 7 and 8. Table 1 shows the cohesion force c (kN / m2) and internal friction angle φ (°) under each condition. From Figure 9, it was confirmed that the silica sand has increased cohesion force c (kN/m2) and internal friction angle φ (°) because precipitation of calcium carbonate on the particle surface increases the frictional force of the particle surface and the increase in density due to calcium carbonate particles. From the tendency that calcium is widely distributed, it was considered that shear stress and cohesion could be increased [23, 24, 25, 26]. In the Toyoura sand, the shear stress increased, but the cohesion was decreased. In the Toyoura sand, precipitation of calcium carbonate on the particle surface was partially precipitated, and the calcium carbonate played the role of fine grain. After the test, Pca (%) was measured, and the calcium carbonate precipitation ratio to the sand mass was 1.8 to 2.4% The results are shown in Table 2. In the solidification period 1 Week by the calcium carbonate method, an average of 2% calcium carbonate precipitation could be confirmed. The slope stabilization has been also carried out by using the native bacteria and found that the soil strength has been increased significantly to protect the landslide.
Relation between shear stress and normal stress.
Silica No 4 Sand | Toyoura Sand | Silica No 4 1 Week | Toyoura 1 Week | |
---|---|---|---|---|
35.9 | 30.9 | 57.2 | 57.4 | |
c (kN/m2) | 12.38 | 12.19 | 15.07 | 6.56 |
Cohesion and degree of internal friction of Toyoura and silica sand without and 1 week of treatment.
Stress | Pca (%) | |
---|---|---|
Silica No 4 1 Week | Toyoura 1 Week | |
10 (kN/m2) | 2.13 | 1.99 |
30 (kN/m2) | 2.06 | 1.84 |
50(kN/m2) | 2.37 | 2.04 |
Amount of calcite generation after 1 week.
It was observed through the X-ray CT and SEM-EDS analysis that the effect of particle size on bio-cementation was great. The amount of calcite generation is more in silica sand than in the Toyoura sand. In addition, it was confirmed that calcium carbonate precipitated was more in the lower part than in the upper part by infiltrating the bacteria and nutrient from the surface. It was evaluated that the precipitation distribution of calcium carbonate inside the specimen could be confirmed by X-ray CT. It was confirmed that from 10 μm to 50 μm calcite of rhombohedral crystal and vaterite of spherical crystal could be confirmed in the crystalline state of calcium carbonate in Toyoura and silica sand, respectively. It was seen the increase of 1.3 to 2.0 times of shear stress after 1 week of biotreated by using
The author acknowledged the financial help to conduct this research from the Soil Science Foundation.
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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. 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The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/414005",hash:"",query:{},params:{id:"414005"},fullPath:"/profiles/414005",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()