Clinical manifestations of conceptuses resulting from the infection of pregnant women by viral disease.
\r\n\tWithin this scenario, special attention needs to be devoted to financial implications, due to their pervasiveness. Nobody would question the key role that finance plays to complement the real sphere of the economy and that has increasingly attracted both academics and practitioners. As a result, traditional pillars – such as financial markets, products, and institutions – have evolved significantly, with financial innovation fueling further progress over time. The global side of the coin features – among others – financially connected markets, international financial exchanges, and financial conglomerates that provide valuable opportunities in terms of international corporate finance. On the other side, recent advances have involved a wider recourse to ESG factors, allowed forward steps towards a more inclusive financial system, and have made digital finance a must, rather than an option, even though much remains to be accomplished, for instance, to facilitate access to formal financial channels in many underdeveloped regions.
\r\n\r\n\t
\r\n\tThis book aims to examine emerging trends, new perspectives, and empirical applications that deal with globalization and sustainability. The goal is to provide a comprehensive overview of these important concepts as valuable support to successfully meet the challenges and take on the opportunities ahead. At the same time, drawing upon empirical evidence can contribute to bridging the gap between theory and practice, which also fits within the scope of this book.
In this chapter, the practical aspects of the applied basic surgical science of the auricular cartilage are discussed on an evidence-based level according to the most recent researches in the literature.
\nEar pinna (auricle) is an extremely important organ not only for the facial aesthesis but also plays a major role in hearing physiology. Both functions rely primarily on the biomechanical nature of the cartilage. Degrees of inclination and angles at its attachment to the skull determine the shape of the head and the auditory function especially the ability to localize the direction of sound.
\nIn addition, auricular cartilage is vulnerable to many congenital and acquired diseases that require cartilage replacement or excision; this has opened the door for many advances in tissue engineering to happen. Moreover, healthy cartilage of the auricle is a plentiful source of cartilage for reconstruction of the nose, skull base and facial defects.
\nConsequently, comprehensive knowledge about recent advances in literature about basic science of this critical piece of cartilage is of paramount importance. In this chapter, précised, focused and between lines pieces of information will be mentioned, but old and repeated ones will not. The chapter aims to know how basic physiology, pathology, biomechanics and biochemists of the auricular cartilage can be applied to the clinical perspectives. It is not a pure clinical chapter; only related points that can be applied to the clinical practice are discussed.
\nBased on the abovementioned perspectives, the reader of this chapter is expected to acquire detailed knowledge about:
Microarchitecture of the auricular cartilage and applied physiological aspect of the chondrocyte and matrix,
Response of auricular cartilage to relapsing polychondritis as the most common autoimmune disorder affects the auricular cartilage,
Effect of ischemia on the cartilage,
Pathophysiology of infective chondritis and perichondritis,
Molecular biology of invasion of the cartilage by malignancies,
Effect of surgical intervention and trauma on the cartilage,
Healing of auricular cartilage after surgery and trauma,
Healing of the graft in auricle and
Aberration of healing.
Reader also will be provided, at the end of the chapter, with an “at a glance section” that summarizes the most important advances in understandings.
\nThe auricle is a funnel-shaped cartilaginous structure consists of a single thin plate of elastic fibrocartilage covered by skin and it is continuous with the meatus of the external auditory. It is also characterized by ridges and depressions formed by the auricular cartilage; there are five regions caused by this molding such as helix, antihelix, tragus, antitragus and concha [1].
\nAuricular cartilage consists of cartilage cells fill small lacunar spaces in the matrix. Young cells, called chondroblasts, are relatively small and flat and have an irregular edge with pseudopodic-type extensions lodged in the matrix. Postmitotic chondroblasts have intercellular contact and are absorbed with matrix synthesis. The chondrocytes are mature cells that grow and become spheroid with age and lose the extensions [2].
\nThe matrix is composed chiefly of water, proteoglycans, lipids and collagens. The substance is a firm gel, positive to periodic acid-Schiff reaction, and metachromatically to toluidine blue. The glycoproteins are a series of mucoprotein copolymers, conjoined in large lateral chains without rami, of condroitin-4-sulfate glycosaminoglycans, condroitin-6-sulfate and keratin sulfate. The proportions are modified with age, keratan sulfate increases with age [3].
\nThe resistance to compression and the viscoelasticity are referred to their content of glycosaminoglycans, and the resistance to tension of the collagen and elastic fibers content.
\nHowever, porcine and bovine chondrocytes were used for many years in the tissue engineering of human auricular cartilage; human auricular chondrocytes have become the procedures of production of elastic cartilage in vitro. This has changed the future of auricular reconstruction via its marked ability to grow in tissue culture and marked ability to produce matrix of both hyaline and elastic cartilage. Human chondrocytes have the following criteria in the tissue cultures:
They have ability to lay down large amount of elastic cartilage under certain circumstances. Alginate-suspended aggregated chondrocytes produce matrix that contained elastin (the hallmark of the original elastic cartilage) and this amount of auricular elastic cartilage increase markedly with the alginate/collagen-containing hydrogen and enriched with k-elastin [4].
It can also be stimulated with insulin, dexamethasone, or growth factors such as bFGF, PDGFbb, EGF, and IGF(2.3), what is more is their ability to continue growth in the subcutaneous pocket.
The neo-cartilage, produced by cultured chondrocytes, does not dedifferentiate or degenerate after long cultivation time (12 weeks) and it has the same immunohistochemistry properties as the native auricular cartilage.
Cartilages can be created in predetermined shapes and dimensions using chondrocyte transplantation on appropriate polymer templates [4].
Ability of human auricular chondrocytes to proliferate in tissue cultures to produce auricular cartilage molds with the same histological and mechanical criteria, and the same predetermined configuration have changed surgical approaches in clinical situations such as anotia, microtia, traumatic loss and cauliflower ears. This also has replaced old-fashioned methods such as costal cartilage grafting, which was mandating the timing of surgery to be delayed until the age of 6–10 [5], and carry the risk of pneumothorax and chest wall deformities [6].
\nAs mentioned earlier, the biochemical composition of matrix is the factor that determines the biomechanical properties such as wear resistance, load bearing and shock absorption [7]. The mechanical properties of the auricular cartilage have not been extensively studied to date, but the Young’s modulus was determined by tension calculating a modulus value for concha and tragal cartilage to be 3.4 and 2.8 MPa, respectively, but the difference was not significant [8]; however, the concha was found to demonstrate a greater Young’s elastic modulus in comparison to the helix [9].
\nIn addition, the final stress relaxation rate was similar for all five regions of the auricular cartilage, suggesting that all regions of the auricle had the ability to reach similar load equilibrium over 15 min (helix 1.78 × 10−4 ± 0.32 MPa/s, antihelix 1.62 × 10−4 ± 0.31 MPa/s, concha MPa/s 1.52 × 10−4 ± 0.23 MPa/s, antitragus 1.46 × 10−4 ± 0.23 MPa/s and tragus 1.46 × 10−4 ± 0.15 MPa/s). The final absolute relaxation was also similar between the five regions of the auricular cartilage, demonstrating that the auricular cartilages could relax to a similar final stress level (helix 0.21 ± 0.02 MPa, antihelix 0.24 ± 0.04 MPa, concha 0.23 ± 0.04 MPa, antitragus 0.21 ± 0.03 MPa and tragus 0.23 ± 0.03 MPa) [8, 9, 10]. Therefore, surgeons can harvest any anatomical part of the auricle for reconstruction.
\nSuch biomechanical properties are mainly due to collagen II fibers in the matrix because Dahl et al. analyzed the bimolecular composition of endogenous auricular cartilage in normal adults, pediatric patients with microtia and pediatric patients with preauricular appendages. Immunohistochemical analysis demonstrated similar levels and distribution of elastin and collagens I and X in all three groups of patients, and reduced expression of collagen II in children with microtia [11]. Collagen II is, also, the main target affected in several diseases and malignancies, which is discussed in the following paragraphs.
\nAs mentioned earlier, reconstructive surgeon should use synthetic or tissue engineered cartilage that provides the anatomical and biomechanical properties of the human auricle to achieve good biocompatibility with the skin [12], adequate mechanical properties prevent deformation of the implant when implanted beneath the skin providing definition of the auricle shape. Also, similar mechanical properties to the surrounding tissue prevent stress at the interface [1]; mechanical mismatch can lead to micromovement between the skin and the implant when subcutaneously implanted [13], thus implant failure and extrusion.
\nThe most common disease of this type is the relapsing polychondritis (RP) that results from autoimmune reaction against collagen fibers of the cartilage. In addition, there is a condition that must be known to differentiate it from malignancies of the skin and cartilage, it is the “chondrodermatitis nodularis chronica helicis” or “Winkler’s disease,” which results from ischemia of the cartilage.
\nRelapsing polychondritis (RP) is a rare multisystem autoimmune disease characterized by recurrent episodes of inflammation and progressive destruction of cartilaginous tissues, elastic cartilage of the ears and nose, hyaline cartilage of peripheral joints, vertebral fibrocartilage and tracheobronchial cartilage [14, 15]. Auricular chondritis occurs in 20% of patients at presentation and in 90% at some point during the course of the disease [15]; therefore, its applied pathophysiology will be discussed with some details in the following context. Etiology of RP is unknown but the pathogenesis is mostly due to an immunologic reaction to type II collagen in all human tissues [16, 17].
\nCollagen type II is the main target of the autoantibodies in RP; therefore, it is the initial step that induces the chondritis; this is approved by the fact that titers against the native type II collagen were substantially higher than titers against constituent alpha-1 (II) chains and antibodies are positive in 30% of cases [17]. This observation suggests that the antibodies were not formed after destruction of cartilage and denaturation of collagen [16]. However, not only autoantibodies against type II collagen have been detected in patients with RP but also autoantibodies against type IX and XI collagen have been found in a patient with RP [18]. In addition, recently auto antibodies against other cartilage proteins such as cartilage oligomeric matrix proteins(COMP) and matrilin-1 have been found; matrilin-1 is a cartilage matrix protein expressed at high levels in the tracheal, nasal, auricular and chondrosternal cartilage [19, 20]. Such antibodies activate both humoral and cellular immunoreaction; there are several evidences to support this [21]:
Damaged cartilage is infiltrated by CD4 + T-cells and plasma cells and contains immune deposits and perichondral infiltrate of lymphocytes and plasma cells with loss of basophilic staining of the cartilage matrix indicating loss of proteoglycans [22].
A T-cell response specific to peptides found in collagen type II (which contributes 95% of all cartilage collagen) or of matrilin-1 is found in some patients [23].
Over half the patients with RP carry the HLA-DR4 antigen [24, 25].
In one patient, oral administration of collagen type II for desensitization was apparently effective [26].
These reactions lead to severe chondritis by recruiting inflammatory cells to the cartilage, such recruitment is orchestrated by a complex cytokine network [27] such as interferon-Υ, interleukin [IL]-2, and IL-12 [28] in addition to soluble triggering receptor (sTREM-1) expressed on myeloid cells 1, chemokine (C-C motif) ligand 4 (CCL4), vascular endothelial growth factor (VEGF) and matrix metalloproteinases-3 (MMP-3) [29].
\nAs a result of this autoimmune reaction, many proteases are released from the inflammatory cells [21] and by chondrocytes that undergo apoptosis by the effect of MMP-3 [30], causing destruction of cartilage matrix and leading to the characteristic features of RP of the auricle.
\nBecause collagen II is responsible for biomechanical criteria of the auricle, after repeated attacks or sometimes after a single prolonged episode, the cartilaginous structure of the ear is damaged and the pinna not only feels flabby but also may droop or even flop up and down when the patient walks [15]. Pinna also may hardened by calcifications or ossification of the connective scar tissue that replaces the cartilage. Cauliflower ear deformity occurs in about 10% of patients [22].
\nAnother noninfective inflammatory reaction related to the unique criteria of the cartilage in general and auricular cartilage in specific is an inflammatory lesion called chondrodermatitis nodularis chronica helicis. It is a chronic perichondritis, which is thought to be related to limited vascularity at the lateral and anterior aspect of the auricle. The skin is tightly stretched over the underlying cartilage with minimal subcutaneous tissue, which results in limited vascularity and ischemia which is thought to promote the development of this lesion [31]. Another related theory is the perichondrial vacuities which narrows the blood vessels and induce ischemia of the cartilage, leading to the clinical picture of the given disease [32]. Mostly located on the helix, this disease is characterized by a hard nodule which involves the skin and the cartilage of the ear.
\nIschemia also can result from compression on the cartilage as in infection and hematoma, which are discussed in the following paragraphs.
\nPerichondritis and chondritis represent infections of the auricular perichondrium or cartilage. It is caused by blunt or penetrating trauma to the ear or by direct extension from an otitis externa. Penetrating trauma may result from various injuries, including ear piercing, assaults, bites and iatrogenic injuries. Iatrogenic infection occurs when the cartilage and soft tissues of the ear are employed as donor sites for tissue used in the repair of defects of the nose and external ear [33]. The increasingly popular piercing of the ear cartilage as opposed to the lobule may predispose to infection [34], and outbreaks have been reported and Pseudomonas is the most frequent causative organism [35]. Burn of the auricle is the most aggressive form because it makes the cartilage most vulnerable to infective chondritis due to presence of large amount of dead cartilage tissues.
\nWhatever the reason of chondritis, cartilage becomes intensely infiltrated with polymorphonuclear leukocytes and phagocytes, which damage the cartilage via its cytokines and inflammatory mediators [36] such as auricular cartilage, like any cartilage, lack of vascular supply; it is only supplied from the overlaying perichondrium that makes it vulnerable to ischemia and necrosis. In addition, intact perichondrium adds to the problem because it does not allow the inflammatory edema of the cartilage to expand, increasing the pressure on the cartilage which causes more necrosis and end up with cauliflower ear [37]. This pathophysiology must be applied clinically by immediate drainage of abscess and hematoma, and adequate debridement of any dead cartilage [38].
\nCancer of the auricle accounts for around 6% of all cutaneous malignancies, out of which 50–60% are squamous cell carcinoma, 30–40% is basal cell carcinoma (BCC) and 2–6% is malignant melanomas. [39] These malignancies can invade the cartilage of the auricle via several mechanisms but the most recent mechanism rather than the direct tissue pressure effect is the role played by mediators released by the tumors.
\nMatrix metalloproteases (MMP) play an integral role in tumor growth and metastasis; MMPs are a family of zinc-dependent endopeptidases. They allow tumors to grow by degrading matrix barriers of the underlying cartilage and promoting angiogenesis as well as releasing active growth factors and modulating apoptosis; therefore, they are used as tumor markers malignant transformation of keratinocytes [40, 41]. Specifically, MMP-13 is associated with greater metastatic capacity and MMP-11 is linked to increased local invasiveness of SCC of the head and neck. MMP-13 (collagenase 3) preferentially degrades type II collagen found in cartilage [42]. In cSCC, MMP-13 collocates with laminin-5, which is normally founded in the basement membrane to promote keratinocyte motility to the edge of the lesion and subsequently degrades nearby tissue, allowing tumor invasion [43, 44]. Therefore, matrix of the cartilage in the auricle is an important risk factor for the squamous cell carcinoma which releases many proteolytic enzymes to facilitate invasion and spread.
\nCartilage injuries can be caused by several reasons because it is liable to trauma and several surgical procedures; it is capacious source of highly resistant cartilage, it is also liable to several disfiguring congenital anomalies that necessitate plastic surgeries that require grafts to the auricle to close defects [45]. Despite the widely spread use of those grafts in auricular cartilage defects, insufficient union and loss of grafting material through absorption in the long run has regularly been reported [46].
\nIn addition, damage associated with traumatic injuries or extensive surgical manipulation is characterized by catastrophic disruption of cartilage matrix integrity and structure, extensive chondrocyte death in the area of cartilage injury, and expansion of this “zone of injury,” which is facilitated by diffusible mediators such as nitric oxide [47]. The main reason behind this is that the body does not heal isolated cartilage damage effectively because blood supply necessary for the initiation and support of the repair process is absent, a lack of sufficient stem cells to repopulate and repair the defect, and chondrocyte cell death in the surrounding cartilage which compromises tissue integrity and interferes with repair tissue integration [47]. Viable chondrocytes near the injury may proliferate, form clusters of new cells, and synthesize new matrix, but chondrocytes cannot migrate readily through cartilage tissue to the site of the injury, and the matrix components they synthesize usually are not sufficient to fill the defect [47]. To conclude, any cartilage wound healing response that does not lead to replacement of type II collagen and proteoglycan synthesis will result in tissue with abnormal morphologic and mechanical properties [48]. Unfortunately, this is the case when the basic healing process of the cartilage was studied.
\nPathophysiology of healing of hyaline cartilage (auricular) can be classified according to the reason of injury:
Postsurgical and posttraumatic healing
General healing process of the cartilage is in the young rabbit, traumatization of cartilage perpendicular to its surface resulted within 3 days in regression and necrosis of the tissue, lining the cut end, which is neighbored by a zone of hyperactivity and increased mitosis. On the seventh day, filaments present in the matrix are arranged in bundles, which demarcate the border between the viable cartilage and the regressive zone; they are continuous with the perichondrial fibers [49], the necrotic material is invaded by macrophages and polymorphonuclear cells from the contiguous exudate. In later stages, this zone has developed into a firm layer of fibrous tissue. After 4–6 weeks, the demarcating fibers will cover the rounded stump, protecting the cartilage fragment. However, all these reactions are absent in adult rabbits making the cartilage not to heal [50].
Healing of grafting to the auricle (healing at interface between graft and auricular cartilage)
Wound healing of the incision surface of the graft was similar to the reaction in the pre-existent cartilage, described earlier. Thus, the scarring occurred on both sides of the junction and therefore, the junction was in most cases, fibrous and not cartilaginous. In addition, the subcutaneous transplant site in the head and neck lead to strong inflammatory reactions and resorption of the bioartificial cartilage in contrast to orthopedic and trauma surgery where the engineered constructs or autologous chondrocytes are placed in the immunoprivileged region of joints [51].
To conclude, the end result of healing depends on the age of the patient, direction and depth of the wound as the following:
Large, complete-thickness defects do not heal easily; normal healing time for ear cartilage piercing is 2 months to 1 year, so intervention is a must [52].
Partial-thickness defects are normally repaired by deposition of fibrous scar tissue.
Small, full-thickness cartilage defects are replaced by fibrocartilage. The mechanism of fibrocartilaginous repair appears to be mediated by proliferation and differentiation of mesenchymal cells of the marrow [53].
Consequently, it is inevitable to find a method that enhances cartilage tissue healing or to replace the damaged cartilage as following:
Biologic grafts such as perichondrium have been successfully used to repair full-thickness defects, probably because the inner layer of the perichondrium, adjacent to the cartilage contains progenitor cells that can differentiate into chondroblasts [52]. However, the outer layer rapidly produces fibrous overgrowth, preventing the good cartilage-to-cartilage connection necessary to restore the mechanical function of the structure [54].
Tissue engineered cartilage molds can be used, as mentioned in Section2.1.
Growth factors to enhance healing such as somatomedin-C have growth-promoting effect on cartilage [46]. In addition, such products that induce chondrogenesis can be produced via gene therapy. Gene therapy approaches to cartilage repair are encouraged by the ability of various gene products to enhance chondrogenesis [55]. Examples include growth factors [56] such as insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β), fibroblast growth factors and various members of the BMP family, as well as transcription factors such as SOX-9 [57], certain signaling molecules such as SMADs [58], and molecules that inhibit apoptosis such as BCL-2 [59]. However, it is still difficult to administer them exogenously to sites of cartilage injury in a sustained and therapeutically useful manner.
Any surgical intervention, especially ear piercing, may complicate with keloid which represent one extreme of aberrant dermal wound healing that is observed only in susceptible individuals following cutaneous injury [60] with higher incidence during puberty and pregnancy, periods with hyperactivity of the pituitary gland [61]. Due to increased release of greater melanocyte stimulating hormone (MSH), keloid formation mainly occurs in parts of the body with high concentrations of melanocytes [62].
\nHistopathologically, keloid is included in the spectrum of fibroproliferative disorders and commonly affects the ears, it has been suggested that keloid scarring is caused by an inability to stop the wound healing process and abnormal response to inflammation by fibroblasts [63, 64]. Scar is densely populated by inflammatory cells, which release fibrogenic factors such as transforming growth factor (TGF)-β1 and -β2. This environment enhances accumulation of ECM, while its degradation is impaired (via decreased levels of TGF-β3 and matrix metalloproteinases [MMP], for example, (MMP-9) [65]. In addition, development of a Th-2 response stimulates fibrogenesis and Th-1 predominance attenuates the tissue fibrosis [66, 67].
\nTo conclude, author summarizes this chapter in the following points, which include the latest research findings in literature about the above discussed issue.
\n\n
Both functions of the auricle, atheistic and hearing, rely primarily on the biomechanical nature of its cartilage.
Human auricular chondrocytes have become the procedures for the production of elastic cartilage in vitro because they lay down large amount of elastic cartilage under certain circumstances.
Cartilage of human chondrocytes culture is resistant to degeneration even after long time and it has the same immunohistochemistry properties the native auricular cartilage.
The final stress relaxation rate is similar for all five regions of the auricular cartilage; all regions of the auricle had the ability to reach similar load equilibrium over 15 min.
Biomechanical properties of the auricular cartilage are mainly due to collagen II fibers in the matrix which is defective in patients of congenital auricular malformations.
Implants must have the same mechanical properties of the cartilage otherwise mechanical mismatch can lead to micromovement between the skin and the implant thus implant failure and extrusion.
Collagen type II is the main target of the autoantibodies in relapsing polychondritis (RP); therefore, it is the initial step that induces the chondritis.
Recently, autoantibodies against cartilage oligomeric matrix proteins (COMP) and matrilin-1 have been found in patients of (RP).
However, not many experiments, oral administration of collagen type II for desensitization in (RP) is apparently effective.
Chondrodermatitis nodularis chronica helicis is proven to be partially due to ischemia of the cartilage.
Intact perichondrium in auricular perichondritis and hematoma adds to the problem because it does not allow the inflammatory edema or blood, respectively, to expand, increasing the pressure on the cartilage, which causes more necrosis and end up with cauliflower ear.
MMP-13 (collagenase 3) preferentially degrades type II collagen found in cartilage.
In cSCC, MMP-13 collocates with laminin-5, which is normally found in the basement membrane to promote keratinocyte motility to the edge of the lesion and subsequently degrades nearby tissue, allowing tumor invasion.
Chondrocytes cannot migrate readily through cartilage tissue to the site of the injury, and the matrix components they synthesize usually are not sufficient to fill the defect.
Healing of the cartilage depends on the age of the patient, direction and depth of the wound; large, complete-thickness defects do not heal easily and intervention is a must.
Subcutaneous transplant site in the head and neck lead to strong inflammatory reactions and resorption of the bioartificial cartilage in contrast to orthopedic and trauma surgery where the engineered constructs or autologous chondrocytes are placed in the immunoprivileged region of joints.
Keloid is one extreme of aberrant dermal wound healing that is observed only in susceptible individuals following cutaneous injury.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization on March 11, 2020 [1]. The infection rate caused by the virus increased exponentially in 2020 until March 13, 2021, registering 119,165,535 confirmed cases and 2,641,567 deaths [2].
Pregnant and puerperal women have been considered groups at risk of morbidity and mortality since the beginning of the COVID-19 pandemic because of the physiological and immunological changes that can increase the risk of complications in respiratory infections and the knowledge of unfavorable outcomes in pregnant women and their newborns in infections caused by other coronaviruses, SARS, Middle East respiratory syndrome, and influenza [3, 4, 5, 6].
Some adverse outcomes of SARS-CoV-2 infection observed during pregnancy include admission to the intensive care unit (ICU) or death. However, the clinical evolution of COVID-19 in most women is not serious, resembling the general population [7, 8].
Initially, there was no evidence of vertical transmission due to COVID-19 during pregnancy [3, 5, 6]. During the pandemic, several studies concluded that there was this possibility [9, 10], with one confirmed case of vertical transmission occurrence [11]. However, all of them suggested that further studies should be conducted on the subject, as it is a recent disease and the number of participants in the published studies is small.
There is strong evidence that other viral infections cause neurological and behavioral changes in the fetus, such as the influenza virus related to schizophrenia [12]. Other viral infections, such as the Zika virus (ZIKV), can cause malformations, including microcephaly [13].
Therefore, outpatient monitoring of children exposed to the SARS-CoV-2 virus during pregnancy is vital to understand the impacts of the disease on the growth and development of these children.
A narrative review was carried out using the keywords: COVID-19, SARS-CoV-2, vertical transmission, perinatal infection and offspring. In addition to the search for other viral infections: influenza, herpes simplex, rubella, cytomegalovirus and human immunodeficiency virus (HIV). The authors searched the Pubmed, Medline, and Google Scholar databases, reviewed the available articles, and determined which articles were most relevant to the project.
Pregnancy is a risk factor for infection by the influenza virus. During the 1918 (Spanish flu) and 1957 (Asian flu) pandemics, mortality in pregnant women was high. During the 1918 pandemic, a 27% mortality rate was recorded, and in 1957, it corresponded to 50% of deaths in women of reproductive age [14]. In seasonal influenza periods, an increased risk of hospitalization was observed in pregnant women at any stage of pregnancy, even without associated comorbidities [15].
There were higher rates of premature births, small for gestational age newborns, and stillbirths in hospitalized pregnant women than those in outpatient treatment [16]. Regarding the occurrence of malformations in the fetuses, the possibility of its teratogenic effect with the occurrence of neural tube defects, cleft lip and palate, and congenital heart disease was evaluated. A direct effect of the virus was unlikely to be the cause of these malformations, since control of fever with antipyretics, and the use of periconceptional folic acid in pregnant women with influenza reduced the risk of these malformations in their offspring (Table 1) [17].
Viral disease | Clinical manifestation |
---|---|
Influenza | Premature birth, small for gestational age newborns, stillbirths, pregnant woman hospitalization, fetus malformation, schizophrenia |
Rubella | Congenital rubella syndrome (CRS), abortion, stillbirth, restricted urterine growth |
Herpes simplex | Triad: cutaneous, neurological and ophthalmic symptoms |
CMV | Intrauterine growth restriction, hepatosplenomegaly, microcephaly, chorioretinitis, petechiae, jaundice, thrombocytopenia, anemia |
HIV infection | Miscarriages, stillbirths, perinatal mortality, intrauterine growth restriction, low birth weight, chorioamnionitis |
Zika virus | Intrauterine growth restriction, small for gestational age, brain malformation, microcephaly, eye and hearing abnormalities, hypospadias, cryptorchidism, micropenis |
COVID-19 | Intense inflammatory response and placenta hypoxia can lead to abortions, pre-eclampsia, prematurity, IUGR |
Clinical manifestations of conceptuses resulting from the infection of pregnant women by viral disease.
Influenza infection in the first trimester of pregnancy increased the risk of schizophrenia by seven times. There was no increased risk in the other trimesters of pregnancy, according to a nested case–control study of 64 participants who were born from 1959 to 1966 and had psychiatric disorders 30 to 38 years later [12].
A cohort study of 196,929 children conducted in California did not find an increased risk of autism spectrum disorder (ASD) in offspring of pregnant women with influenza. In addition, there was no statistically significant relationship of ASD in children whose mothers received influenza vaccination in the first trimester [18].
There are two types of herpes viruses: HSV-1 and HSV-2. The latter is predominantly sexual and the etiologic agent of 70–85% of neonatal infections. Although transplacental or upward transmembrane transmission of HSV from the mother to the fetus during pregnancy is uncommon (about 5%), the rate of perinatal transmission during labor and delivery is 80–90%. The risk of neonatal infection is higher in HSV infections that start in late pregnancy (30–50%) than in early pregnancy (1%) [19, 20].
Intrauterine infection is clinically present in the fetus as a characteristic triad of cutaneous (vesicles, erosions, and scars), neurological (intracranial calcifications, microcephaly, and meningoencephalitis), and ophthalmic symptoms (microphthalmia and chorioretinitis). The clinical manifestations of neonatal peripartum and postpartum infection are found in the skin, eyes, and/or mouth (45%) and central nervous system (CNS; 30%) or as disseminated infection (25%). Regarding mortality and neurological prognosis, mortality is higher in disseminated infection cases (approximately 30%), and a worse neurological prognosis occurs in cases with CNS involvement (50%). In the treatment of neonatal HSV, high doses of intravenous acyclovir are indicated, which improves the prognosis and reduces the occurrence of neurological sequelae and delayed child development (Table 1) [19, 21].
It is an acute viral disease caused by the RNA Rubella virus of the Togaviridae family. Its clinical characteristics in healthy adults are often self-limited and include low fever, maculopapular rash, lymphadenomegaly, and oropharyngeal pain. The rates of asymptomatic cases range from 25–50% [22].
In pregnancy, maternal infections can determine a poor prognosis for the conceptus, especially when it occurs in the first trimester of pregnancy, which can result in congenital rubella syndrome (CRS), abortion, stillbirth, congenital malformations, and restricted uterine growth of the conceptus. The chances of malformation are 81% and 25% in the first and second trimesters, respectively. Rubella immunization is considered the best measure to combat this infection in the world. CRS has already been significantly eliminated in the USA; however, it cannot be said that it has been completely controlled, since outbreaks are still reported around the world [14].
Rubella virus infection findings can be found from prenatal life to later manifestations after the child’s birth and development. Among them, it can cause ocular alterations (cataract, microphthalmia, glaucoma, pigmentary retinopathy, and chorioretinitis), cardiac malformations (peripheral pulmonary artery stenosis, patent duct artery, or ventricular septal defects), and CNS alterations (microcephaly). Children who survive the neonatal period may have severe developmental disabilities (e.g., visual and hearing impairments) and an increased risk of developmental delay, even autism. In the long term, congenital rubella infection may determine an increased risk of endocrinopathies, such as thyroiditis and insulin-dependent diabetes mellitus (Table 1) [23, 24].
CMV, like other viruses in the Herpesviridae family, causes a primary infection and remains latent in the body. Primary infection is generally harmless, but it can be fatal in immunocompromised patients and cause serious fetal damage due to vertical transmission, which can occur intrauterine during childbirth through cervical and blood secretions and postnatally through breastfeeding. Thus, identifying infection in pregnant women is important [25].
In 1–4% of pregnant women, seroconversion to CMV occurs, with most women being seropositive before pregnancy, which does not prevent the infection in about 60% of babies during pregnancy. In newborns, 0.2%–2.5% are infected in utero, and most are asymptomatic (90–80%). About 10–20% of neonates have symptoms at birth, such as intrauterine growth restriction (IUGR), hepatosplenomegaly, microcephaly, chorioretinitis, petechiae, jaundice, thrombocytopenia, and anemia. Of them, 20–30% progress to death, mainly from disseminated intravascular coagulation, liver dysfunction, or bacterial infection. Even asymptomatic children at birth can present sequelae of neurological development, such as mental retardation, motor impairment, sensorineural hearing loss, or visual impairment (Table 1) [26, 27].
Vertical transmission by HIV can occur during pregnancy, childbirth, and during breastfeeding. Test implementation for HIV detection in prenatal care, antiretroviral therapy (ART) use during pregnancy and by the newborn after birth, elective cesarean delivery indication, and breastfeeding contraindication reduce the risk of HIV transmission to the baby from 40% to less than 1% in the USA [28].
Children exposed but not infected to HIV during pregnancy have a worse prognosis than those who are not since their mothers are more likely to have low CD4+ cell counts, detectable viremia, and higher morbidity. In addition, the effects on fetal development due to maternal immune dysfunction and the potential dysfunction of hereditary mitochondria in the fetus due to the exposure of women with HIV in early childhood to ART are unknown [29]. Adverse results in pregnancy associated with HIV infection can result in miscarriages, stillbirths, increased perinatal mortality, IUGR, low birth weight, and chorioamnionitis [30]. In symptomatic pregnant women, an increase in premature births has been observed (Table 1) [28].
ZIKV is a flavivirus transmitted by mosquitoes, mainly by
One cohort study evaluated 244 pregnant women with confirmed ZIKV infection during pregnancy and reported that 223 (91.4%) babies were born alive. Of these, 216 babies had clinical follow-up after birth, of which 130 (60%) children had blood and/or urine samples obtained for ZIKV detection using the real-time polymerase chain reaction (RT-PCR) technique. Results revealed that 13% of the children who underwent brain imaging exams had structural brain abnormalities such as microcephaly, 5.5% who underwent ophthalmological evaluation had ocular changes, and 12.1% who underwent additive evaluation had an abnormal result. In addition, 7.7% were born small for gestational age, which may be associated with IUGR. Meanwhile, 19% who underwent neurological exams had an abnormality in the first 6 months of life. Neurodevelopment assessments carried out after 1 year of age showed that 13.2% had severe developmental delay (Table 1) [33].
At the beginning of the pandemic, the clinical manifestations of COVID-19 in pregnant women and babies were unknown. Some studies concluded that the evolution of SARS-CoV-2 infection in pregnant and nonpregnant women was similar [6, 34]. A case–control study compared the clinical evolution of COVID-19 between pregnant women with and without COVID-19 and observed that pregnant women with mild symptoms of COVID-19 have a similar evolution to those without the disease. However, pregnant patients with severe or critical illness have worse results. The risk factors for a worse maternal and neonatal outcome include black and Hispanic race, advanced maternal age, obesity, comorbidities (diabetes mellitus and chronic hypertension), and admission to the COVID-19-related antepartum [35].
Immune responses in pregnancy induce that pregnancy is a risk factor for SARS-CoV-2 infection. In both normal and COVID-19-infected pregnancies, maternal immune responses occur as a result of decreased lymphocytes, inhibitory natural killer cell receptor activation such as NKG2A, and increased inflammatory cytokines (interferon-ɣ, interleukin (IL)-2, IL-6, IL-7, IL-10, and tumor necrosis factor-α) [36, 37]. In addition, the angiotensin-converting enzyme 2 is the receptor for SARS-CoV-2 and is widely expressed in the female reproductive system (ovary, uterus, vagina, and placenta) and fetal tissues; therefore, vertical transmission of COVID-19 is possible [38, 39].
The fetuses of mothers infected with SARS-CoV-2 may be exposed to an intense inflammatory response, which can induce placental or fetal damage. Nonspecific anatomopathological changes were observed in SARS-CoV-2 infected placentas, and the most common finding was poor placental perfusion on the maternal side due to maternal hypoxia secondary to severe pulmonary infection by COVID-19. Both maternal immune response and poor placental perfusion can result in abortions, pre-eclampsia, prematurity, and IUGR [37, 40].
A study that evaluated the fetal inflammatory response in newborns of mothers infected with COVID-19 in the third trimester observed an increase in IL-6 in the fetuses, which may determine adverse sequelae of neurological development, including autism, psychosis, and long-term sensorineural deficits. However, longitudinal studies are needed to validate these associations (Table 1) [37, 41].
Only one study confirmed the vertical intrauterine transmission. In the case report described by Vivanti et al., the pregnant woman was in her last trimester of pregnancy (35 weeks) when she developed symptoms and was diagnosed with COVID-19. Cesarean delivery was indicated because of fetal distress. The conceptus was resuscitated at birth and transferred in invasive mechanical ventilation to the ICU. The virus was investigated and detected by RT-PCR from the amniotic fluid, placental tissue, bronchoalveolar lavage fluid, blood, and nasopharyngeal and anal swabs. The conceptus evolved with neurological manifestations similar to those described in adult patients with COVID-19 [11].
A review study evaluated 108 pregnant women confirmed with COVID-19 and found that 86 had pregnancy resolution. Of the newborns, 75 were tested for SARS-CoV-2 using RT-PCR, and only one was positive (1.3%). The test was collected at 36 h of life. The patient presented a good clinical evolution with reports of lymphopenia and increased liver enzymes in laboratory tests. The average gestational age of the 86 pregnancies evaluated was 36 weeks and 1 day. One baby died at birth (1.1%), and one pregnancy resulted in intrauterine death (1.1%). In both cases, the mothers had severe COVID-19. Seven babies (8.1%) required admission to the neonatal ICU [42].
A study of nine case series and two case reports evaluated 65 mothers confirmed for COVID-19 and 57 newborns. The report revealed that 31% of cases had fetal distress, and 38% of pregnant women had a premature birth. Neonatal complications were breathing difficulties or pneumonia (18%), low birth weight (13%), skin rash (3%), disseminated intravascular coagulation (3%), asphyxia (2%), and perinatal death (3%). Twenty-seven newborns underwent RT-PCR for SARS-CoV-2 by nasopharyngeal swab. Of them, four were positive: one newborn was healthy, and three had pneumonia and positive results on nasopharynx and anal swabs on days 2 and 4 of life. The question remains whether some of the maternal and neonatal complications reported are due to the virus and not iatrogenic, for example, the indication for cesarean delivery determining premature birth [43].
The infection by the SARS-CoV-2 virus presents neurological manifestations, which can be a consequence of cardiorespiratory failure and metabolic abnormalities triggered by the infection, direct invasion of the virus, or an autoimmune response to the virus. Among the neurological symptoms observed were headache, ageusia, anosmia, dizziness, myalgia/myositis, and stroke [44, 45]. The effects of this neurotropism of the virus should be investigated in children, especially in newborns whose mothers were infected during pregnancy, since its consequences on children’s neurological development are unknown. In addition, the effects of infection according to the trimester of pregnancy are unknown, leaving doubt about the prognosis of children of mothers infected in the first trimester, in relation to other periods of pregnancy (Table 2).
COVID-19 study | Neonate clinical manifestation |
---|---|
Wong YP, Khong TY, Tan GC, 2021 | Poor placenta perfusion: abortions, pre-eclampsia, prematurity and IUGR |
Cavalcante M, Cavalcante C, Sarno M, Barini R, Kwak-kim J, 2021 | |
Wong YP, Khong TY, Tan GC, 2021 | Increase in IL-6: autism, psychosis and long-term sensorineural deficits |
Liu P, Zheng J, Yang P, Wang X, Wei C, Zhang S, et al., 2020 | |
Vivanti AJ, Vauloup-Fellous C, Prevot S, Zupan V, Suffee C, Do Cao J, et al., 2020 | Conceptus evolved with neurological manifestations similar to those described in adults patients with COVID-19 |
Zaigham M, Andersson O, 2020 | Outcome of death at birth and intrauterine death of fetuses from mothers confirmed for COVID-19 |
Zimmermann P, Curtis N, 2020 | Fetal distress, premature birth, breathing difficulties, pneumonia, low birth weight, skin rash, disseminated intravascular coagulation, asphyxia and perinatal death |
Studies that evaluated the clinical manifestations in newborns born to mothers confirmed with COVID-19.
International Health Security, also called “global health security” or “public health security”, has as its main objective to maintain humanity’s well-being through prevention. Its focus is not only on diseases (infectious, chronic), it also encompasses social determinants of health, bioterrorism, climate change, cybersecurity in health and other situations.
COVID-19 is a threat to international health security, as it has repercussions in all aspects of human health, physical, social and mental well-being, as the disease causes death, sequelae, compromised mental health and social of individuals.
In children, in addition to the impact of the absence of face-to-face classes in schools and social interaction, the impact of intrauterine SARS-CoV-2 infection on their neurological and body development is still uncertain. Being an item of extreme importance to International Health Security.
It is vital to monitor the growth and proper development of children exposed to COVID-19 during pregnancy since whether or not vertical transmission occurs is still uncertain, and if confirmed, fetal prognosis should be improved through diagnosis to determine early consequences. Several viral infections during pregnancy can compromise the health of the fetuses in the short, medium, and long term.
The authors declare no conflict of interest.
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Beloborodova",profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",slug:"oxidoreductase",publishedDate:"February 17th 2021",editedByType:"Edited by",bookSignature:"Mahmoud Ahmed Mansour",hash:"852e6f862c85fc3adecdbaf822e64e6e",volumeInSeries:19,fullTitle:"Oxidoreductase",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour",profilePictureURL:"https://mts.intechopen.com/storage/users/224662/images/system/224662.jpg",institutionString:"King Saud bin Abdulaziz University for Health Sciences",institution:{name:"King Saud bin Abdulaziz University for Health Sciences",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9742",title:"Ubiquitin",subtitle:"Proteasome Pathway",coverURL:"https://cdn.intechopen.com/books/images_new/9742.jpg",slug:"ubiquitin-proteasome-pathway",publishedDate:"December 9th 2020",editedByType:"Edited by",bookSignature:"Xianquan Zhan",hash:"af6880d3a5571da1377ac8f6373b9e82",volumeInSeries:18,fullTitle:"Ubiquitin - Proteasome Pathway",editors:[{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9002",title:"Glutathione System and Oxidative Stress in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9002.jpg",slug:"glutathione-system-and-oxidative-stress-in-health-and-disease",publishedDate:"August 26th 2020",editedByType:"Edited by",bookSignature:"Margarete Dulce Bagatini",hash:"127defed0a50ad5ed92338dc96e1e10e",volumeInSeries:17,fullTitle:"Glutathione System and Oxidative Stress in Health and Disease",editors:[{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:3},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:8},{group:"subseries",caption:"Chemical Biology",value:15,count:10}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:3},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:301,paginationItems:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. 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. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. 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