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Both are of major significance to wild and domestic rabbits and hares causing important environmental harm with significant financial consequences. This is also reflected in the magnitude of scientific literature regarding these diseases and the viruses that cause them namely myxoma virus (MYXV) and rabbit hemorrhagic disease virus (RHDV). MYXV and RHDV belong to two virus families the
There are currently two
Myxomatosis was first observed by Sanarelli [1] in European rabbits (
Following the introduction of the disease in Australia attenuated strains of the virus soon arose [4] this was accompanied by the selection of more resistant rabbits. The comparison of rabbit genomes from before and after the introduction of MYXV has given considerable insight into the host resistance mechanism [6]. Immune related genes have been identified as being determinant in a complex interplay of numerous genes [6]. Based on survival times of laboratory rabbits inoculated with different virus isolates Fenner and colleagues defined five virulence grades 1–5 [4]. Virus isolates of virulence grades 1–2 have over 95% case fatality rates with survival times of less than 13 days for grade 1 or up to 16 days for grade 2 virus. Rabbits infected with grade 5 virus survive while grades 3 and 4 average survival time is 17–29 and 29–50 days respectively. Experimental studies in the decades following virus release showed grade 3 viruses to be most common in both Australia and Europe. Changes in virus virulence occurred rapidly, with less virulent strains detected after one year [4] and a comparison of results from Australia and Europe showing a common trend and highlighted the importance of insect vectors and weather conditions on selection of virus attenuation [4, 5, 7, 8].
Myxoma virus (MYXV) is the virus of reference for the
The MYXV genome is a linear double stranded DNA molecule of 161.8 kb encoding 171 open reading frames (ORFs). The ends of genome are covalently closed forming hairpin terminal loops. The genome of MYXV Lausanne was sequenced completely in 1999 by Cameron et al. [9] and contains inverted terminal repeats (ITRs) of 11.5 kb encoding 12 genes which are therefore diploid. The MYXV genome contains an abundance of genes with potential immunomodulatory functions contained largely in the ITRs while genes the central core of the genome are required for virus replication, transcription and morphogenesis (Figure 1). Genes found in this central region are highly conserved among the poxviruses [12].
Schematic representation of MXYV genome organization. Genes below the black line are designated L and those above the line are R. Immunomodulatory proteins of MYXV shown in darker shade of blue [
There is no treatment for the disease therefore only preventative measures are effective. As the disease is spread most commonly by biting insects (fleas, lice, ticks and mosquitos), insect control has fundamental importance, being the first line of defence on the farm setting. The introduction of new individuals on to a farm or wildlife area should be preceded by quarantine measures and animals showing clinical signs should be isolated. However, the only effective measure for virus control is currently vaccination.
Several vaccines exist against myxomatosis and these can be divided into two types; heterologous and homologous with both types being live attenuated vaccines. The heterologous vaccines use RFV (also denominated Shope fibroma virus). RFV can be used to provide protection against myxomatosis [13] as it is immunologically related to MYXV [14]. However, protection lasts a short time and the heterologous vaccines are considered less immunogenic. Heterologous vaccination is often used to vaccinate juveniles for the first time whilst subsequent vaccinations are administered using homologous vaccines. The homologous vaccines are based on laboratory MYXV strains that have been passaged in embryonated eggs or cell cultures until an attenuated phenotype is attained [15, 16, 17]. Several homologous vaccine strains are available in Europe (eg. SG33, MAV, Borgi, Leon162 among others). Protection with homologous vaccines offers longer lasting immunity than with the heterologous vaccines. Myxoma virus causes immunosuppression in rabbits [18] and one of the main drawbacks to the use of homologous vaccines may be associated with such immunosuppression [18, 19] that could exacerbate underlying subclinical infections.
The genome sequences of various vaccine strains have been studied. While there is no consensus on individual gene mutations that cause the attenuated phenotype in vaccines, several have large regions of the genome absent when compared to the parental strains (Figure 1) [11, 20, 21]. For example, the MYXV vaccine strain SG33 has a genome 13.5 kbp shorter than Lausanne. The deleted region contained genes encoding for M150-M001 proteins (13 genes) including several genes expressing immunomodulatory proteins. The region affected contains a large part of the ITR and the right end of the central genomic region, while other mutations are also present in the genome notably in the open reading frames M011 and M077. SG33 was derived from a French field isolate and subsequent analysis of the genome revealed it to be a recombinant consisting of genomic sequences of the south American Lausanne and the Californian MSW/MSD strains [11]. The MAV vaccine strain (derived by serial passage of strain MSD isolated during an outbreak in California [22] has a 14.2 kbp deletion with respect to Lausanne, affecting both terminal regions flanking the ITRs (genes M006L-M009L and M148R-M008L/R). Interestingly, one European field strain has been sequenced that also contains a large deletion including part of the ITR, isolate Munich-1, this strain is described as virulent. Therefore, the precise mechanisms of attenuation of vaccine strains remain undefined however, the role of the large deletions that include genes involved in immunoregulation seems evident.
The publication of the MYXV genome coupled with advances in recombinant DNA technology and
Novel recombinant bivalent vaccines have been developed using MYXV as a vaccine vector that enable simultaneous vaccination against MYXV and other pathogens in domestic [25, 26] and potentially wild rabbits [27, 28]. The Spanish field strain 6918 showed great promise as a potential vaccine candidate in wild rabbits. A field trail of this vaccine showed that 50% of contact rabbits generated antibodies over a 32-day period. This isolate has also been used as a vector to express the capsid protein of rabbit haemorrhagic disease virus. The potential use of MYXV as a vaccine vector is not limited to use in rabbits. Indeed vectors have been tested in different species [29, 30, 31] including humans for use as an oncolytic virus vector (reviewed in [32]).
Outbreaks of myxomatosis still occur in farmed rabbits although efficient vaccines have been available since the 1980s. One major problem is that field strains are endemic in feral rabbit populations. There is therefore a constant source for virus introduction onto farms through uncontrolled insect vectors. Such outbreaks lead to doubts over the efficacy of current vaccines and the causes of these vaccine breaks have been investigated. Sequence data of field strains causing farm outbreaks show that the virus has not changed sufficiently to render vaccines outdated, indeed under laboratory conditions a traditional vaccine strain proved protective if the vaccinated rabbit generated antibodies [33]. However, the route of administration appeared to be a crucial factor. In this study a group of animals vaccinated subcutaneously failed to seroconvert and were susceptible to fatal infection, while animals vaccinated intradermically showed seroconversion and were protected. The key to controlling such phenomena on the farm setting is surveillance of antibody response following vaccination.
The two strains of the virus initially released in Europe and Australia have been completely sequenced. The reference strain (isolated in Brazil in 1949) known as Lausanne was released in Europe, while the Standard Laboratory Strain (SLS) also termed Moses strain was isolated in Brazil in 1910 and maintained by passage prior to its release in Australia (Moses 1911, reviewed in [5]). The fact that the date, locations, and viral sequence of released strains are known allows for the comparative study of past and present MYXV sequences. Such precise data is unique and have allowed for continental scale virus evolution studies [21, 34, 35]. These studies have demonstrated that MYXV showed high mutation rates, frequent loss of ORFs due to nucleotide insertions or and deletions [21, 34, 35]. The evolution of complete genome sequences of MYXV strains over more than 70 years coupled with the data on virulence and virus phenotypes provided by disease monitoring programs [4] provide a powerful tool for the detailed analysis of the molecular mechanisms of virulence and attenuation. In addition, the study of recombinant knockout viruses, viruses with individual genes removed under laboratory conditions, and subsequent analysis of changes in virulence associated with gene knockouts allows the determination of these mechanisms with much greater precision (reviewed in [21]). Understanding the molecular mechanisms of attenuation will be crucial for the design of better control measures of MYXV.
Phenotypic studies of MYXV isolates demonstrated the emergence of attenuated field strains. Analysis of sequences of attenuated strains has revealed that virus attenuation is multifactorial. Such studies reveal there are varied pathways to the evolution of attenuation [2, 35]. Several genes have been shown to be involved but no single common mutation or group of mutations account for similar virus phenotypes. Genome wide analysis of MXYV strains isolated between 1952 and 1999 demonstrated the broad range of genes involved in MYXV evolution [34]. Strains of known virulence grades were included in such studies and although viruses shared virulence grades no common mutations between them were observed [34, 36] with similar results being obtained for Australian and European isolates [35, 36]. A subsequent study of isolates obtained between 2000 and 2021, (following the emergence of RHDV) showed a drastic change in virus evolution, echoing the effects that RHDV had on rabbit populations and highlighting the adaptability of MYXV to persist in the face of ever changing circumstances [37]. A more pronounced virus evolution was detected but once again the complexity behind attenuation/virulence were noted [37] as were the effects of RHDV and climatic conditions on the evolution of spread and transmission [37, 38].
The complexity behind the molecular explanation of attenuation is further exacerbated with the knowledge that individual or combination gene knockout studies have not precisely replicated attenuation in recombinant strains [39]. For example, of the Australian attenuated isolates, Uriarra contains an indel disrupting the M005L/R gene, while Meby codes for a truncated M153R gene. Both genes products play roles in immunomodulation [40, 41] and recombinant viruses with these genes deleted are less virulent (M005 highly attenuated, M153 moderately, [40, 42] respectively). However, reversion studies (replacing defective genes with corrected homologs in the genetic background of the parental attenuated strain) failed to show differences in the virus phenotype. The role of additional subtle mutations occurring in other parts of the virus genome although more difficult to decipher may hold the key to understanding attenuation completely. In the case of European isolates, attenuated strains have also been identified, e.g. Nottingham4-55/1 and the Spanish isolate 6918. Nottingham4-55/1 contains a truncated M150R gene. M150R (also termed myxoma nuclear factor (MNF)) is an immunoregulatory/host range protein [43] and one of the poxviral ankyrin-repeat (ANK-R) protein superfamily members. Recombinant virus with an MNF deletion is attenuated [44]. In addition to being attenuated, the Spanish isolate 6918 was poorly transmitted to contact rabbits demonstrating an additional phenotypic characteristic making it a possible safe vaccine candidate for use in wild rabbits [27, 28, 45]. Genome sequencing of isolate 6918 revealed mutations in four genes (M009L, M036L, M135R and M148R) leading to potential truncation of expressed proteins [46] (Figure 1). The M135R and M148R genes are likely candidates to affect virulence, while mutations in M009L and M036L genes have also been detected in virulent MYXV strains [47] however, the precise relation of these genes with attenuation has yet to be demonstrated. To date reversion studies using European strains have not been documented.
In Europe the disease had a profound effect on rabbit populations including extinctions at local levels [48, 49] and much wider ranging ecological effects [49, 50] especially in the Mediterranean basin where the rabbit is considered a keystone species [51, 52]. Surviving rabbits show immunity [53] therefore disease maintenance requires sufficient susceptible naive juvenile rabbits and outbreaks therefore occur in temporal peaks which are also dependent on the availability of insect vectors which help to spread the virus (reviewed in [5]). In addition to the ecological effect, the rabbit industry (meat and fur) suffers substantial economic losses each year due to rabbit deaths and costs of control measures [54, 55].
Initial diagnosis may be based on the characteristic symptoms presented, however, disease caused by attenuated or respiratory strains maybe mistaken for bacterial infections. Laboratory diagnosis is therefore important and several methods are available for this task (reviewed in [56, 57]). Isolation of the virus in susceptible cell cultures (e.g. RK13 rabbit kidney cells) gives characteristic cytopathic effect but requires several days for confirmation and is therefore accompanied by serological or molecular techniques such as the detection of virus genome by PCR [20]. The most common samples for virus detection are tissue (eyelid, skin lesions, lung etc), swabs (conjunctival or genital) and sera for antibody detection. These techniques maybe complemented by electron microscopy, histology, agar gel immunodiffusion, fluorescent antibody test among others [57]. Detection of the virus genome requires extraction of viral DNA and subsequent PCR analysis and confirmation by sequencing may also be used. Targeted regions vary and include M153R [58] and M135R [59] or M005L/R gene within the TIRs (and therefore diploid) for qPCR [60] or conserved genes such as M022L [61] or M071L [20, 57] for conventional PCR analysis. Such analyses serve to confirm the presence of MYXV DNA, however, additional analysis of more regions are required to distinguish wildtype from vaccine strains [20] or in the absence of genome sequencing, to generate information regarding phylogeny [62, 63]. TIR regions in poxvirus genomes have been shown to be more variable [64], and RFLP analysis of long range PCR-amplified TIR regions from MYXV positive samples also allows for the molecular differentiation of strains [65].
Serological tests exist for the detection of anti-myxoma virus antibodies [19, 66, 67]. This analysis is of particular importance in farmed rabbits where vaccination is used.
Myxoma virus is traditionally termed as being specific to the European rabbit. Soon after its release in Europe however, isolated cases were described in hare species (reviewed in [4]). More recently myxomatosis has been described in hares in the UK [68]. Experimental infections of hares (
Genomic analysis of the MYXV infecting the Iberian hare population showed the genome to contain an additional 2,8 kbp with regards to the reference strain Lausanne (Figure 1). How MYXV gained this genomic region is unknown, but homologous recombination has been demonstrated as a frequently occurring mechanism for poxviruses to gain selective advantage through the acquisition of genetic material from coinfecting viruses [74, 75, 76]. The genomic region present in the hare- infecting MYXV contained 4 full open reading frames which showed homology to MYXV genes M060R, M061R, M064R and M065R. The homologous region within the MYXV genome contains 6 genes, M060R-M065R, therefore homologs to M062 and M063 are missing from the hare specific genomic region. The nature of the ORFs included in the insertion led to two possible explanations: a duplication event of genes M060-M065 had occurred with the subsequent loss of ORFs M062 and M063 [70], or the capture by homologous recombination of this region from an as yet unidentified poxvirus [70, 71]. The exact cause of the species jump has yet to be explained, although the determination of the function of the gene products from within this region is sure to shed light on this phenomenon.
There are two devastating diseases caused by lagoviruses that effect lagomorphs. Rabbit haemorrhagic disease (RHD) and European Brown Hare Syndrome (EBHS), as the names suggest, both were considered species specific. However, recent findings require that this view be revised. Both diseases have been endemic in Europe since the first descriptions in the 1980s (reviewed in [77, 78]). Due to the economic and ecological importance of the European rabbit, RHD has been the subject of most research. But the recent emergence of a lagovirus with broader host range, associated ecological concerns and advances in the molecular biological tools available for the study of these diseases, is changing this dynamic.
Rabbit haemorrhagic disease first came to light in China in 1984 in angora rabbits imported from Europe in what appeared to be the emergence of a novel highly virulent disease that rapidly killed thousands of domestic rabbits. The disease spread throughout China and Korea and reached Europe (Italy) in 1986 (reviewed in [77, 79]).
The first report of cases in Spain, the native home of the European rabbit was in 1988 [80] in domestic rabbits and the disease soon caused epizootic episodes in wild rabbits [81]. The reduction of the wild rabbit population was severe [82] and this had direct effects on specialist predator species such as the endangered Iberian lynx (
RHDV, the etiological agent of RHD, remained endemic in Europe for more than 30 years with a single serotype (RHDV GI.1) prevalent until 2010. Rabbits that survive infection generate a strong long lasting immunity with detectable anti-RHDV antibodies in sera. Young rabbits are not susceptible to the disease caused by RHDV GI.1, however, they may be infected and the mechanism of resistance is not fully understood. The economic effects of the disease in the rabbit farming sector are considerable. Inactivated vaccines (e.g. RHDV infected liver homogenates treated with β-propiolactone) were developed [85, 86] and proved successful in stemming mortalities in commercial rabbitries although due to the natural reservoir of RHDV in wild rabbits, control measures must be consistently maintained. With regards to control it is important to indicate that direct contact between rabbits [87] and fomites (contaminated food and bedding) play an important role in farm outbreaks. In natural infections, the faecal-oral route is considered the preferential mode of virus transmission [88] reviewed in [78]). In the wild, rabbit carcasses are also a major virus source with spread being facilitated by predators and carrion feeding insects [89, 90].
In 2010 atypical outbreaks of RHD were detected. The virus responsible for these outbreaks was initially recognized in France [91] and termed a new variant of RHDV, where outbreaks affecting vaccinated rabbits caused concern. The variant was later detected in Spain, where isolates of the virus were used to show susceptibility of young rabbits, demonstrate major antigenic differences with regards to RHDV GI.1 and the presence of virus in the intestine [92]. Another considerable difference with the disease caused by this virus when compared to classic RHDV GI.1 is the level of mortality. RHDV GI.1 typically shows mortality rates of 80–90% in adult rabbits [93] with no mortality in kits, while the variant RHDV showed approximately 10% in adult rabbits and up to 50% in kits. The terms variant and RHDVb were first used to identify this virus [91, 92]. Subsequent publications used the terms RHDVb and RHDV2. In order to avoid confusion and bring order to the nomenclature system for the lagoviruses, Le Pendu et al., put forward a new scheme where by RHDVb/RHDV2 was termed
Given the novel characteristics of RHDV GI.2 it was unsurprising that the virus continued to spread. By 2013, the virus had been detected throughout France, Spain, Portugal and was present in Italy [95, 96, 97]. RHDV GI.2 and has since spread to pandemic proportions and has been detected on the continents of Europe, Africa, Asia, Australia and North America.
The lack of full cross protection induced by previous contact with RHDV GI.1 strains contributed to the rapid spread of RHDVGI.2 in Europe [98, 99], resulting in high mortality rates among wild populations soon after its emergence. Therefore, vaccines based on RHDVGI.2 containing inactivated liver extracts have been produced to aid in control of the disease in domestic rabbits.
The observation of partial protection between GI.1 and GI.2 was supported by data from RHDV GI.2 infections in Australia where mortality was detected in RHDV domestic vaccinated animals [100] and contributed to its rapid spread in the wild [101]. Currently, it appears as though RHDV GI.2 has become the predominant RHDV on the Iberian Peninsula [102, 103], and also on mainland Australia replacing endemic strains of RHDV GI.1 [100]. While this may lead to environmental and economic benefits in Australia [104] the establishment of this virus in Europe poses an important problem for the conservation of the European rabbit, particularly in smaller populations [105, 106] and for the preservation of reliant predators [107].
The presence of anti-RHDV antibodies in rabbit populations is indicative of circulation of RHDV. However, in 1995, antibodies reactive with RHDV were detected in rabbits that showed no clinical signs of RHDV infection [108]. This finding was substantiated by the identification of a non-pathogenic calicivirus (termed rabbit calicivirus - RCV) [109]. RCVs were subsequently detected in Australia [110] and France [111]. RCV lagoviruses, are genetically related to RHDV although they demonstrate different cell tropism and are apathogenic. While RHDV target organs are lung, liver and spleen, RCV was found predominantly in the intestine. The presence of RCV has been argued as having a protective effect on rabbit populations facing RHDV outbreaks and may have been a determining factor in the speed of spread of RHDV in Europe and Australia [112], however the levels of protection vary and are likely dependent on differing levels of cross reactive and timing of infections [111, 113].
European Brown Hare Syndrome Virus (EBHSV) GII.1 has been detected in many European countries and Argentina having emerged in Sweden in the early 1980s and Denmark in 1982 (reviewed in [114, 115, 116, 117, 118, 119, 120, 121], although retrospective studies have demonstrated that the virus was present before this time [122, 123]. EBHSV causes disease in brown hares (
The identification of hare caliciviruses (HaCV) GII.2 related to EBHSV have further shown the large diversity and complexity that exists for this genera of virus [129, 130, 131, 132]. HaCV has been detected in duodenum or faeces of healthy hares in Italy, France, Austria, Germany and Australia (also weakly detected in liver) [129, 130, 131, 132, 133]. The virus is considered to be non-pathogenic based the health status of animals from which the samples were obtained and the target organ, however, virulence phenotypes have not been published. Expanding our knowledge on these viruses will undoubtedly help decipher their role in protecting populations of lagomorphs from pathogenic viruses and in the emergence of novel viruses through recombination events.
As lagoviruses EBHSV and HaCV have the same genome organisations (Figure 4) and virion morphologies as RHDV, however they form separate genetic groups following phylogenetic analysis and are antigenically different from RHDV [123, 134, 135, 136, 137]. RHDV GI.2 has also been detected as highly virulent in different hare species [138] either as a result of spill-overs from closest rabbit populations or from hare to hare transmission. These findings have highlighted the need for studies into virus cross species infections in lagomorphs [130, 132]. Recent detection of RHDV GI.2 and EBHSV GII.1 recombinant viruses [139] highlight the capacity for evolution of the lagoviruses and indicate the importance of continued vigilance in order to protect vulnerable lagomorph species.
Lagoviruses are non-enveloped icosahedral single-stranded positive-sense RNA viruses [87, 140, 141]. As well as the morphological features of virions all lagoviruses share a common genome organisation, have conserved genomic features and express two ORFs as shown in Figure 2.
Schematic representation of a lagovirus genome and the main genomic features shared amoung the lagoviruses. Fragments of sequence alignments from indicated isolates show: 5′ nontranslated region (NTR), polyprotein translation start site, subgenomic RNA initiation sites, termination upstream ribosomal binding site (TURBS) core sequence and termination/reinitiation site required for VP10 translation [
ORF 1 expresses a polyprotein that is processed to form non-structural mature peptides and VP60 the major structural capsid protein (also termed VP1 in the literature). ORF 2 encodes VP10 a minor structural protein, also termed VP2. Lagoviruses also share conserved polyprotein processing sites (Figure 3) and. Transcribe a VPg-linked subgenomic RNA from which VP60 and VP10 are expressed. The ORFs for VP60 and VP10 overlap and expression of VP10 occurs via a termination/reinitiation mechanism (Figure 3).
Schematic representation of conserved motifs located in the ORF 1 encoded polyprotein and amino acid alignments showing conserved proteolytic processing sites among lagoviruses.
RHDV GI.1 is the lagovirus that has been most extensively characterised and is therefore the virus of reference for this genus. The virus genome is approximately 7.4 kb in length. Viral particles are small (35–40 nm diameter) and contain genomic (gRNA) and subgenomic RNA (sgRNA) which is collinear with the 3′ end of the genomic RNA [143, 144, 145]. Both RNAs are polyadenylated at the 3′ end. At their 5′ region they are covalently linked to the VPg (virus genome-linked) protein [146] (Figure 2) which may act as a substitute for cap during RHDV translation [147]. Genomic RNA contains two open reading frames (ORFs): ORF1 codes for a polyprotein of 257 kDa, which after a post-translational cleavage by a viral protease results in 7 non-structural proteins (p16, p23, p37 (NTPase), p29, p13 (VPg), p15 (protease), p58 (RNA-dependent RNA polymerase) (also termed non-structural proteins (NS) 1–7) and the major capsid protein (VP60) [144, 145, 148]. The RNA sequences encoding ORF1 and ORF2 overlap by 20 nucleotides. The reading frame of ORF2 is shifted with respect to ORF1 and codes for the minor capsid protein (VP10) which is 10–12 kDa. VP10 (also termed VP2 in some publications in accordance with norovirus nomenclature) is translated by a termination/reinitiation mechanism [142], dependent on a TURBS (termination upstream ribosome-binding site) element (core sequence GUGGGA) located within the VP60 coding sequence [149]. The role of VP10 protein has been linked with viral replication regulation and promotion of apoptosis for the liberation of virions from infected cells [145, 150]. The biological role of non-structural proteins has been studied by sequence analysis and functional studies, as well as being based on previous knowledge gathered from members of the
By far the most well characterized of the RHDV proteins is VP60. It is the major structural component of virions, responsible for receptor binding, is highly immunogenic and the target of neutralizing antibodies. VP60 is expressed from subgenomic RNA in infected cells facilitating sufficient levels for virion assembly. High levels of sgRNA make it a good target for diagnostic RT-PCRs and its variability due to immune selection befit subsequent sequence analysis. Sequence data from partial and full-length fragments of VP60 encoding RNA have been the basis for comparative sequence analysis.
Although RHDV is not cultivatable
VLPs have been used to characterize this protein structurally, determine its antigenicity and study receptor binding [159, 160, 161, 162, 163, 164]. Additionally, purified wildtype virus particles have been used to determine an atomic model by cryo-electron microscopy [165].
RHDV GI.2 isolates are antigenically distinct from RHDV GI.1 and agglutinate human erythrocytes, to differing degrees, [92, 166, 167, 168]. Hemagglutination is dependent on the presence of ABH blood group antigens and these molecules have been proposed as receptor components of the binding pathway [169]. Indeed, the species specific nature of these molecules may explain susceptibility to different lagoviruses [170].
Virions are composed of 90 dimers of VP60 which form 32 cup-shaped depressions on the surface of virions (from which comes the name Calici- from the latin calix or cup) [165, 171]. Each monomer of VP60 consists of a shell (S) domain, which is buried inside the virion structure, and flanked by the N-terminal arm (NTA) and the so-called hinge which links the S domain to the protruding (P) domain that correspond to C-terminal region and is exposed on the virion surface [166, 172, 173, 174]. The hinge allows P and S domains a certain grade of flexibility on their tridimensional disposition [165]. The P domain contains determinants for virus-host receptor interactions and antigenic diversity [165, 166]. In addition, this region can be further subdivided into the subdomains P1 and P2, P2 contains the hypervariable region of the protein which allows for the selection of variants that can escape immune detection or antibody neutralization.
The marked antigenic differences observed between RHDV GI.1 and RHDV GI.2 [168], explain the lack of efficient protection against RHDV GI.2 afforded by RHDV GI.1 inactivated vaccines [91, 92], as well as, the capacity of RHDV GI.2 to overcome immunity derived from natural infections with RHDV GI.1 [101]. Since the emergence of RHDV GI.2 the development of diagnostic tools has been a very important issue and different techniques and methodologies have been improved for specific detection of RHDV GI.2 [168, 175, 176, 177].
Although perceived as a novel virus (GI.1) in the initial 1984 outbreak, retrospective serological analysis [108] and sequence analysis [178, 179, 180, 181] have cast doubt on this assumption. Molecular clock analysis suggest the virus emerged before it was officially detected [182]. These studies back the theory that RHDV or similar viruses existed in less virulent forms or went unnoticed and were circulating in the rabbit population long before the emergence of RHDV as a major concern [183]. Whether GI.1 and GI.2 arose from non-pathogenic viruses, through recombination events, or through species jumps remains to be determined [184, 185, 186].
Genetic diversity among pathogenic RHDV isolates has been the subject of intense study with the capsid protein (partial or complete) being the main target. Recent advances in sequencing techniques has allowed full genome analysis in retrospective studies and demonstrate the importance of analysing complete genomes [187, 188].
Studies on the evolution of RHDV GI.1 in Europe showed low levels of sequence variation [183, 189] in the years following its emergence although it was possible to define distinct phylogenetic groups. In the 12 years following the emergence of RHDV GI.1 in France six genogroups were identified [190, 191] (now termed GI.1a-d). Genogroup 6 or RHDVa (GI.1a) is an antigenic variant first isolated in Italy [192]. Although antigenically distinct with a sequence similarity in the VP60 gene of 93%, GI.1 based vaccines provided protection against this highly pathogenic virus [191, 192].
The evolution of RHDV has followed a different trend in Spain compared to the rest of Europe. Only GI.1d strains (previously genogroup 1) have been detected in samples collected between 1988 and 2010. This may be due to a smaller number of samples being analysed, however, unlike in the rest of Europe, GI.1 strains were still being detected in the Iberian Peninsula in 2010. RHDVa was detected once in Spain in domestic rabbits [193] but does not appear to have been widespread and has not been detected in wild rabbits. In Australia the Czech strain V-351 (an RHDV GI.1) escaped from testing facilities in 1995. The sequence of virus circulating in Australia changed little in the first years following its escape [194], however, the study of RHDV sequences spanning the subsequent 16 years revealed its evolutionary tendency on this continent. Although subject of more than 3500 independent releases during this time, positive selection suggested the evolution of strains capable outcompeting freshly released strains and spreading in the presence of non-pathogenic rabbit calicivirus (RCV)-A1 (also GI.4a) [195]. In order to more effectively compete against the presence of RCV-A1, the antigenic variant RHDVa-K5 (GI.1a-K5) was released in 2014. Australian RHDV GI.1 strains gained virulence reflecting the selection of viruses [196] based on effective transmission, the immunological status of existing population, landscape and weather amongst others.
Phylogenetic analysis suggested that RHDV GI.2 is genetically distant from RHDV GI.1 and is more closely related to RCV apathogenic viruses [91, 92]. The origin of RHDV GI.2 is unclear and cannot be explained by genetic evolution from previously described lagoviruses or recombination of existing strains [197, 198]. Silverio and colleagues [197] using sequences analysis and mean substitution rates have estimated the presence of a common ancestor for GI.2 just a few years prior to its first detection [197]. Experimental infections have demonstrated that RHDV GI.2 has gained virulence showing higher mortality rates in both adults and kittens [98, 199], than the strains obtained in 2011 or 2012 soon after its emergence [98, 199]. This could indicate an evolutionary tendency of the virus, indeed, Capucci and colleagues (2017) [199] hypothesized that this could be similar to what occurred for RHDV GI.1 strains in Australia [196], RHDV GI.2 having evolved in their natural hosts and, since their emergence in 2010, selection pressure may have favoured strains with higher pathogenicity.
Recombination, along with mutation, is an important mechanism for the evolution of RNA viruses since it uses existing genetic diversity to create new genomic combinations. Novel RHDV virus genomes arising from natural recombination of existing strains have been detected in RHDV isolates [200, 201, 202, 203, 204]. Recent genomic analysis reveals that these events are more common than once envisaged [200]. and due to the high frequency of occurrence [195, 197, 200, 201, 202, 203, 205] this might indicate an important role in their origin and emergence of pathogenicity. Indeed, Silverio and colleagues [197] indicated that the occurrence of recombination fits both theories currently proposed for the emergence of pathogenicity in lagoviruses: (1) the evolution from a pre-existing non-pathogenic virus that acquired pathogenicity or (2) following a species jump [198]. Especially in the case of the highly frequent recombination events observed for the novel RHDVGI.2 and its ability to cross the species boundaries [99, 138, 206, 207, 208]. This also has been supported by Lopes and colleagues [187], who related the detection of a recombinant RHDVGI.2 in an Iberian hare with a species jump [187].
The number of combinations of genomes being observed is striking and reveals a complicated panorama. How these events shape the spread and pathogenicity of RHDV remains to be determined.
In recent years, recombination events in different regions of RHDV genomes have been identified. The existence of recombinant RHDV that contain structural genes from RHDV GI.1 and non-structural genes belonging to non-pathogenic lagovirus (GI.4) have been identified [202]. In some cases, the recombination event occurred inside the non-structural region [187]. Two types of RHDV GI.2 recombinant strains have been identified, both with their structural proteins VP60 and VP10 originating from GI.2, while their non-structural proteins originated from GI.1 or non-pathogenic strains (GI.4) [103, 187, 197].
Recombination has been reported in Iberian GI.2 genomes, with a breakpoint at the RdRp/VP60 boundary (Figure 4) within ORF1. This breakpoint was associated with several independent recombination events involving non-pathogenic strains, GI.1 and/or GI.2 resulting in different genomic combinations that persisted in the Portuguese wild rabbit populations [187, 197], and recombinant strains detected in Azores Islands and Australia [103, 202, 209]. The homology between the subgenomic RNA (encodes structural genes) and the 3′ end of the genomic RNA (encodes non-structural and structural genes) generates a hotspot of recombination at the junction between non-structural and structural genes [200, 202]. Silverio and colleagues [197] identified new RHDVGI.2 recombinants with a recombination breakpoint located near the p16-p23 (NS1/NS2) boundary (nucleotide positions 355–471), [197]. Also, they detected the occurrence of triple recombinants constituted by the NS1 non-structural protein similar to a nonpathogenic lagovirus, a GI.1b backbone for the remaining non-structural proteins and GI.2 as the donor for the structural protein. Mutations in NS1 sequences has been implicated as a factor in increased virulence of GI.1 isolates [196].
Schematic diagram of recombinant lagovirus genomes. In the example shown recombinant Lagovirus europaeus/GI.1P-GI.2 indicates a recombination detected between a GI.1 and a G2 strain; P standing for polymerase.
Prior to the emergence of RHDV GI.2, lagoviruses were considered species specific, RHDV was specific to the European rabbit and EBHSV was specific to the European brown hare [126]. However, increasing numbers of RHDVGI.2 infections in different species of rabbits and hares have been reported casting doubt on this clear differentiation. Initially considered as transient spill-over events, more widespread infections of GI.2 in a number of hare species have raised concerns that this virus has an ampler species tropism. The first detection occurred in 7 Cape hares (
Different species of hare infected by RHDV GI.2, showed very similar clinical signs typical of European brown hare syndrome (EBHS): hyperaemic trachea sometimes containing uncoagulated blood, hepatitis necrosis, splenomegaly and congestion of other organs and tissues [99, 138, 206, 215].
Retrospective studies have also blurred the line defining species susceptibility to RHDV and EBHSV. Lopes and colleagues [218], identified the presence of RHDV in archival samples from Iberian hares found dead in the 1990s in Portugal with signs of an EBHS-like disease [218]. These authors demonstrated that RHDV GI.1 strains in these two cases were phylogenetically closely related to those circulating at that time and in the same areas in rabbit populations. These results would support the theory of that virus dissemination and high infection pressure in the environment could favour spillover events of infection of European brown hares with RHDV GI.2 [99, 206, 210, 211].
Analysis of RHDV GI.2 positive hares sampled in 2013 [210] have shown the existence of co-infection by EBHSV GII.1 and RHDV GI.2. This is an important issue in epidemiology and evolution, especially the potential emergence of recombinant EBHSV/RHDV GI.2 strains.
Species susceptibility to lagoviruses may be variable and this may reflect different species-specific host factors such as glycan expression for viral attachment [170]. With respect to this, several studies indicate that, as for noroviruses [219], specific binding between lagoviruses and glycans, particularly those of the HBGAs found in the upper respiratory tract and intestines of rabbits, is the first step of the viral infection [169, 220, 221]. Rabbits have different types of HBGAs and different virus strains show variable affinity to these molecules. Subtle changes in those attachment factors, e.g. through mutations, cause individual animals or even complete species can become more or less susceptible to the virus [169, 222, 223]. So, a possible explanation for overcoming species barriers could be the genetic variation of the capsid protein VP60 which alters the binding to histo-blood group antigens [223] that are considered as being important entry points for the virus [169, 221]. Other factors that could affect RHDV GI.2 infection in different species, such as concurrent subclinical infections, parasitic infestations, malnutrition or habitat detriment [138].
A major concern regarding animal viruses are zoonotic infections. While viral zoonosis from rabbits or hares have not been commonly documented both, rabbits and hares are susceptible to infections that can infect humans including rabies, hepatitis E virus and herpes. Rabbit susceptibility to rabies was used to great benefit when Louis Pasteur endeavoured to create a rabies vaccine in the 1890s. Although susceptible to fatal rabies infection, rabbits are a spillover host. The most commonly documented source of infection in rabbits is from racoons, therefore the disease should be considered in areas where racoon rabies is endemic.
Hepatitis E virus has been detected in domestic and wild rabbits and the European brown hare in Europe and Asia, raising concerns as to whether lagomorphs maybe a reservoir for human infections [224, 225]. Although a recent study did not detect the presence of HEV in wild lagomorphs in Spain [226]. HEV belongs to the Hepeviridae virus family and has a non-segmented RNA genome comprising 3 ORFs. There are 4 genotypes, genotypes 1 and 2 cause human infections while genotpyes 3 and 4 affect wildlife species. Rabbit HEV is genotype 3. Liver or bile are the target organ for diagnosis using RT-PCR used to detect virus genome and specific ELISA to detect antibodies in sera. This pathogen should be considered when handling wild lagomorphs.
Humans have been cited as the source of herpes virus infection in pet rabbits. With a fatal outcome the infections were the result of contact with a human with a cold sore lesion. Post-mortem analysis revealed HSV infection [227].
Naturally occurring herpes virus infections of lagomorphs have been detected in rabbit and hare species, as outlined in Chapter 1 of this book. Five putative species of Leporid herpesvirus have been described to date. Leporid herpesvirus types 1 and 3 have been isolated from
There are two species of the papillomavirus that infect lagomorphs. The first, previously termed Rabbit Papillomavirus (Shope papilloma virus or cottontail rabbit papilloma virus), predominantly infects the cottontail rabbit (
Several viruses have been implicated as contributing factors in rabbit enteritis complex (REC; also referred to as enterocolitis or enteritis complex). REC is a complex disease of the intestine in predominantly young rabbits although the precise causes are not known it is a multifactorial disease in which bacteria, virus, parasites and environmental factors are known to be important. The presence of several RNA viruses of notable concern has recently been analysed in this regard. Rotavirus, coronavirus, astrovirus and hepatitis E virus all cause enteric disease and may potentially be of concern [235].
Rotaviruses are an important group of segmented-genome double-stranded RNA viruses of the family
Rabbit coronavirus was first described in 1961 following electron microscope detection of coronavirus particles and heart was described as the target organ [240]. Subsequently immunoelectron microscopy was used to detect Rabbit enteric coronavirus and virus was isolated [241]. Rabbit enteric CoV was detected in fecal matter during wet market surveillance in China. The characterisation of RbCoV provided the complete genome sequence (RbCoV HKU14-1 genbank accession number JN874559) has shown it to be a Betacoronavirus and reported cases detect RbCoV has also been implicated as a factor in REC. RT-PCR and RT-qPCR have been developed targeting the RdRp gene.
During the current SARS-CoV2 pandemic the potential for infection of animal hosts and the establishment of reservoirs has been of great concern. Molecular modelling studies suggest that the rabbit ACE2 molecule shares structural similarities with human ACE2 and could therefore act as a receptor for SARS-CoV2 virus entry leading to speculation that rabbit may be susceptible to infection [242]. Laboratory rabbits inoculated under experimental conditions with SARS-CoV2 were asymptomatic and low levels of infectious virus was recovered from nasal swabs up to 7 days post infection [243]. Such findings emphasize the need for strict biosafety control measures on domestic rabbit farms. At the time of writing no naturally occurring cases of SARS-CoV2 have been reported in rabbits.
Astroviruses (family
Metagenomic virome studies have shown the presence of astrovirus in rabbits from Australia and highlighted the potential for spread by insect vectors [245]. However, more analysis is required to determine the pathogenesis of this virus in rabbits.
Virome studies have also identified novel lagomorph bocaparvoviruses (genome sequence genbank accession number NC_028973) [246], picornavirus, caliciviruses amounst others [245]. The relevance of these viruses to the sanitary status of lagomorphs should be monitored. Such metagenomic studies offer novel insights into the viruses of these species and indicate the complexity of multifactorial conditions. The molecular tools that can be garnered will undoubtedly improve our understanding of the viral diseases of lagomorphs.
The detection of recent cross species transmissions of both MYXV and RHDV between lagomorph species, both sporadic and widespread and findings from the analysis of historic samples are changing our view on the species susceptible to these diseases. Rabbit and hare species are genetically and immunologically similar and, in many regions, live sympatrically, key factors when considering virus species jumps. Soon after the release of MXYV in 1950 hares were known to be susceptible to this disease, however, no large-scale infections were documented until 2018. RHDV GI.1 emerged in 1984 in the European rabbit and this was the only lagomorph species apparently affected until the emergence of RHDV GI.2 in 2010. What has driven these changes to occur is a matter for study and the effect of these species jumps on lagomorph populations has yet to be seen. Thanks to the great effort of historic surveillance studies and careful sample archiving, the molecular evolution of these viruses is being discovered.
Metagenomic studies have also identified novel lagomorph viruses. Through such studies and continued surveillance therapeutics to lesser known lagomorph viruses and a better understanding of animal health will ensue. We may now be entering a new era in the study of the viruses that infect lagomorphs which will further our understanding on the complexity of virus-host relationship.
FP received funding from the Spanish Ministry for Science Innovation and Universities (grant number AGL2017-83395-R) and INTERCUN and the Ayuntamiento Ribera de Arriba, Asturias, Spain. ICS received a pre-doctoral grant from the Spanish Ministry for Science Innovation and Universities (reference number PRE2018-087157). KPD and JMMA acknowledge funding from the Spanish Ministry for Science Innovation and Universities (reference number PID2020-120349RB-100).
“The authors declare no conflict of interest.”
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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It has been argued that platforms provide reef-like habitat that increases the growth and survival rates of fishes by increasing prey availability and affording shelter for protection from predators, provide additional spawning substrate, and by acting as a visual attractant for organisms not otherwise dependent upon hard bottom. Platforms differ from most natural habitats, and from traditional artificial reefs, in that their vertical profile extends upward through the water column into the photic zone and the sea surface. Increased habitat quality on, or immediately around, oil and gas platforms are thought to be derived from increased in situ food production associated with encrustation by fouling organisms. In this chapter, we address the issue of how to evaluate the role of artificial reefs by first establishing levels of evaluation for individual fish species found on oil and gas platforms in the GOM. The levels of evaluation relate to the amount and adequacy of the available information, which was populated with an extensive literature and data search. Three levels of assessment are established, analogous to the levels of analysis established National Oceanographic and Atmospheric Administration (NOAA) Fisheries for identification of Essential Fish Habitat. More than 1300 documents, including reports, stock assessments, other gray literature, and papers published in the primary literature, were used to complete this chapter. When available, published literature was the preferred source of information.",book:{id:"5210",slug:"fisheries-and-aquaculture-in-the-modern-world",title:"Fisheries and Aquaculture in the Modern World",fullTitle:"Fisheries and Aquaculture in the Modern World"},signatures:"James H. Cowan and Kenneth A. Rose",authors:[{id:"139993",title:"Dr.",name:"James",middleName:"Howard",surname:"Cowan, Jr.",slug:"james-cowan-jr.",fullName:"James Cowan, Jr."}]},{id:"50363",doi:"10.5772/62876",title:"The Brown Seaweeds Fishery in Chile",slug:"the-brown-seaweeds-fishery-in-chile",totalDownloads:1734,totalCrossrefCites:4,totalDimensionsCites:10,abstract:"Chilean fishery of brown algae includes species belonging to the genus Lessonia, Durvillaea, and Macrocystis, which can be found along the coast, ranging latitudes from 18° to 55°S. The exploitation of these seaweeds is done mainly in the Northern coast because the environmental conditions of this region decrease initial production costs. Brown algae are exploited from natural populations and exported to international markets as row material, source of alginates, widely utilized in diverse manufacturing processes and industries. International demand for Chilean kelps has produced sustained increase in harvest during the last decade, reaching more than 390,000 dry tons/year. This chapter approaches the most relevant aspects of the brown seaweed fishery in Chile which covers a wide range of the Southeast Pacific coast, considering the number of commercial species, its abundance and distribution, knowledge achieved on their ecology and biology regarding management, and conservation of these resources, and finally, provides tools for stakeholders and policy makers directed to sustainable management of natural kelp beds occurring in the cold temperate seas.",book:{id:"5210",slug:"fisheries-and-aquaculture-in-the-modern-world",title:"Fisheries and Aquaculture in the Modern World",fullTitle:"Fisheries and Aquaculture in the Modern World"},signatures:"Julio A. Vásquez",authors:[{id:"180745",title:"Dr.",name:"Julio",middleName:null,surname:"Vásquez",slug:"julio-vasquez",fullName:"Julio Vásquez"}]},{id:"55984",doi:"10.5772/intechopen.69471",title:"Deep-Water Sharks, Rays, and Chimaeras of Brazil",slug:"deep-water-sharks-rays-and-chimaeras-of-brazil",totalDownloads:1597,totalCrossrefCites:2,totalDimensionsCites:9,abstract:"The deep-water fishery in Brazil is currently in expansion due to depletion of most neritic economic species. This increasing deep-water effort brings concern on the bycatch impact, its specific composition, the need for capture’s evaluation and development of bycatch reduction devices. The impact is particularly aggressive on deep-water elasmobranchs, which have an extreme ecological k-strategy due to their reproductive constraints (lower fecundity and late first maturity age). Scientific deep-water surveys and intensive research programs (REVIZEE) along the past decade indicate that Brazilian elasmobranch diversity is higher than previously imagined. However, the deep-water fishery threatens this poorly known community of sharks and rays on the Brazilian continental slope as they become bycatch of a fast-growing and uncontrolled fishery. The recent study case of the monkfish (Lophius gastrophysus) fishery dynamics, well presented and discussed by the Brazilian scientific community, provided evidence of the need of bycatch-specific monitoring programs and fast-response fishery regulations. The present work discusses the Brazilian deep-water elasmobranch bycatch problem under the light of its biological diversity and completely unknown population status. Suggestions and management considerations are presented in order to coordinate and manage the establishment and growth of this deep-water fishery in Brazil.",book:{id:"5895",slug:"chondrichthyes-multidisciplinary-approach",title:"Chondrichthyes",fullTitle:"Chondrichthyes - Multidisciplinary Approach"},signatures:"Getulio Rincon, Rodrigo Cordeiro Mazzoleni, Ana Rita Onodera\nPalmeira and Rosangela Lessa",authors:[{id:"205621",title:"Dr.",name:"Getulio",middleName:null,surname:"Rincon",slug:"getulio-rincon",fullName:"Getulio Rincon"},{id:"206465",title:"MSc.",name:"Rodrigo",middleName:null,surname:"Mazzoleni",slug:"rodrigo-mazzoleni",fullName:"Rodrigo Mazzoleni"},{id:"206466",title:"MSc.",name:"Ana Rita",middleName:null,surname:"Palmeira",slug:"ana-rita-palmeira",fullName:"Ana Rita Palmeira"},{id:"206467",title:"Dr.",name:"Rosangela",middleName:null,surname:"Lessa",slug:"rosangela-lessa",fullName:"Rosangela Lessa"}]},{id:"56228",doi:"10.5772/intechopen.70028",title:"A Review of the Mitogenomic Phylogeny of the Chondrichthyes",slug:"a-review-of-the-mitogenomic-phylogeny-of-the-chondrichthyes",totalDownloads:1469,totalCrossrefCites:6,totalDimensionsCites:9,abstract:"The phylogenetic analysis of the Chondrichthyes has been the subject of intense debate over the past two decades. The principal relationships within the group based on the analysis of morphological traits are inconsistent with the available molecular topologies, and the phylogeny of these animals is highly controversial, at all levels, ranging from superorders to families and even the genera within families. With the recent development of new generation sequencing (NGS), many phylogenies are now being inferred based on the complete genome of the species. In 2015 and 2016 alone, around 21 new elasmobranch genomes were made available in GenBank. In this context, the principal objective of the present study was to infer the phylogeny of the sharks and rays based on the complete mitochondrial genomes available in the literature. A total of 73 mitogenomes of chondrichthyan species were analyzed. The phylogenetic trees generated rejected the “Hypnosqualea” hypothesis and confirmed the monophyly of the Neoselachii and Batoidea as sister groups of the sharks. These mitogenomic analyses provided ampler and more complete insights into the relationships between the sharks and rays, in particular, the topologies obtained by the analyses revealed a number of incongruities in certain groups of sharks and rays, and the interrelationships between them.",book:{id:"5895",slug:"chondrichthyes-multidisciplinary-approach",title:"Chondrichthyes",fullTitle:"Chondrichthyes - Multidisciplinary Approach"},signatures:"Divino Bruno da Cunha, Luis Fernando da Silva Rodrigues‐Filho and\nJoão Bráullio de Luna Sales",authors:[{id:"104512",title:"Dr.",name:"Luis Fernando",middleName:null,surname:"Rodrigues-Filho",slug:"luis-fernando-rodrigues-filho",fullName:"Luis Fernando Rodrigues-Filho"},{id:"205219",title:"Dr.",name:"Divino Bruno",middleName:null,surname:"Da Cunha",slug:"divino-bruno-da-cunha",fullName:"Divino Bruno Da Cunha"},{id:"205690",title:"Dr.",name:"João Bráullio De",middleName:null,surname:"Luna Sales",slug:"joao-braullio-de-luna-sales",fullName:"João Bráullio De Luna Sales"}]},{id:"52331",doi:"10.5772/64252",title:"Setting Up Traceability Tools for the Indonesian Blue Swimming Crab Fishery: A Case Study in Southeast Sulawesi",slug:"setting-up-traceability-tools-for-the-indonesian-blue-swimming-crab-fishery-a-case-study-in-southeas",totalDownloads:1678,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"The Indonesian blue swimming crab fishery developed rapidly during the 1990s to become an important source of income for coastal communities. The blue swimming crab (BSC) in 2015 is the third highest export commodity in Indonesia, primarily to USA markets. Southeast (SE) Sulawesi is a relatively minor area for blue swimming crab production (approximately 1200–2000 mt per annum), in which only a subset of Asosiasi Pengelolaan Rajungan Indonesia (APRI) members are active, and it may be a conducive region in which to conduct a pilot activity to form a fisheries management structure that demonstrates the benefits that can be achieved via collaboration. The control document (CD) is a traceability and documentation process to be implemented by all of the segments of the supply chain (collectors/cooking stations, miniplants, and processors) in order to promote compliance to new Ministry and Marine Affair (MMAF) regulations and generate the records and documents of the supply chain application and verification of the new regulations. The self-recorded logbook by the fishermen and miniplant, as the point in the supply chain, could help with a meaningful and long-term solution to the fishery management in Southeast Sulawesi. This is the first trial of CD in Indonesia and could be a good model for BSC fishery in other region in Indonesia.",book:{id:"5210",slug:"fisheries-and-aquaculture-in-the-modern-world",title:"Fisheries and Aquaculture in the Modern World",fullTitle:"Fisheries and Aquaculture in the Modern World"},signatures:"Hawis Madduppa, Zairion, Siti Nuraini, Kuncoro Nugroho and\nBambang Arif Nugraha",authors:[{id:"180161",title:"Dr.",name:"Hawis",middleName:null,surname:"Madduppa",slug:"hawis-madduppa",fullName:"Hawis Madduppa"},{id:"185944",title:"Dr.",name:"Zairion",middleName:null,surname:"Zairion",slug:"zairion-zairion",fullName:"Zairion Zairion"},{id:"185945",title:"Mrs.",name:"Siti",middleName:null,surname:"Nuraini",slug:"siti-nuraini",fullName:"Siti Nuraini"},{id:"185946",title:"Mr.",name:"Bambang Arif",middleName:null,surname:"Nugraha",slug:"bambang-arif-nugraha",fullName:"Bambang Arif Nugraha"},{id:"185947",title:"Mr.",name:"Kuncoro Catur",middleName:null,surname:"Nugroho",slug:"kuncoro-catur-nugroho",fullName:"Kuncoro Catur Nugroho"}]}],mostDownloadedChaptersLast30Days:[{id:"50289",title:"Effect of Special Fish Feed Prepared Using Food Industrial Waste on Labeo rohita",slug:"effect-of-special-fish-feed-prepared-using-food-industrial-waste-on-labeo-rohita",totalDownloads:2276,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"All food processing industries generate wastes of varying nature in significant quantities. Managing these wastes so as to minimize the impact on the environment is the prime concern. The concept of waste has undergone much change in recent times, with the focus being on utilizing the waste materials as inputs for generation of new or reusable products. Vegetable and fruit wastes are generated in significant quantities and are easily available at minimal charge. The comparative utilization of these wastes as a dietary ingredient was assessed employing the Labeo rohita fingerlings as the test species. The study was conducted over a period of 60 days. Orange peels and potato peels are characterized, and then, formulation of orange peel feed (OPF) and potato peel feed (PPF) was carried out. Market common fish feed (CFF) was taken as a control. The three test diets were designated as CFF, OPF and PPF. Feeding was done once daily. The water quality parameters such as dissolved oxygen, water temperature pH, total alkalinity, total hardness; calcium hardness and magnesium hardness as well as growth response were monitored at fortnightly intervals. The quality of water was maintained by periodic partial replenishment over the period of study. On termination of the trial, higher growth response was recorded in the PPF treatment. The initial and final weight and length of fishes was recorded. The results shows significant growth in PPF and OPF showed brighter body scales than other two feed. Fishes were very healthy and normal throughout the study period indicating no adverse effect on their health. No infection whatsoever was noted during 60 days of experimental period.",book:{id:"5210",slug:"fisheries-and-aquaculture-in-the-modern-world",title:"Fisheries and Aquaculture in the Modern World",fullTitle:"Fisheries and Aquaculture in the Modern World"},signatures:"Sanyogita R. Verma and Shanta Satyanarayan",authors:[{id:"183699",title:"Dr.",name:"Verma",middleName:"Rajroop",surname:"Sanyogita",slug:"verma-sanyogita",fullName:"Verma Sanyogita"},{id:"185353",title:"Dr.",name:"Shanta",middleName:null,surname:"Satyanarayan",slug:"shanta-satyanarayan",fullName:"Shanta Satyanarayan"}]},{id:"51124",title:"Fishery Status and Taxonomy of the Carangids (Pisces) in the Northern Arabian Sea Coast of Pakistan",slug:"fishery-status-and-taxonomy-of-the-carangids-pisces-in-the-northern-arabian-sea-coast-of-pakistan",totalDownloads:1950,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The objectives of this study were i) to evaluate number of existing members of the family Carangidae in the area ii) to establish a distinguishable and lucid key based on the taxonomic characteristics, meristic count and otolith description. In this study, thirty-six species were collected from the main fish landing facilities between 2012~2015. Fish body colour, taxonomic characteristics, fin rays and otolith shape description were used to identify each species. Otolith description comprises of shape of ostium, sulcus and margins of anterior and posterior surface along with distinct definite shape possess by each species make it easier for identification.",book:{id:"5210",slug:"fisheries-and-aquaculture-in-the-modern-world",title:"Fisheries and Aquaculture in the Modern World",fullTitle:"Fisheries and Aquaculture in the Modern World"},signatures:"Nazia Qamar, Sher Khan Panhwar and Ghazala Siddiqui",authors:[{id:"182414",title:"Dr.",name:"Sher Khan",middleName:null,surname:"Panhwar",slug:"sher-khan-panhwar",fullName:"Sher Khan Panhwar"},{id:"184264",title:"Dr.",name:"Nazia",middleName:null,surname:"Qamar",slug:"nazia-qamar",fullName:"Nazia Qamar"},{id:"184265",title:"Prof.",name:"Ghazala",middleName:null,surname:"Siddiqui",slug:"ghazala-siddiqui",fullName:"Ghazala Siddiqui"}]},{id:"50583",title:"Trawl Selectivity in the Barents Sea Demersal Fishery",slug:"trawl-selectivity-in-the-barents-sea-demersal-fishery",totalDownloads:1693,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter provides a general overview of the Barents Sea demersal trawl fishery. First, it reviews historical catch levels and current biomass status of four commercially important demersal species (cod, haddock, Greenland halibut, and redfish) and includes an overview of their management plan that has been carried out by the Joint Norwegian–Russian commission. Then, it presents the evolution of the technical regulations for improving size selectivity in this fishery and describes current challenges in gear selectivity. Later, this chapter describes the concept of size selectivity, introduces the selective parameters that define a selection curve, and progressively introduces different parametric models that describe the selection process. The most common experimental methods and gear used to collect selectivity data are described, and their advantages and disadvantages are discussed. Finally, this chapter describes an alternative, or a complementary method, to the conventional estimation of trawl selectivity—the FISHSELECT method. This method is based on morphology measurements and fish penetration models to estimate the selective properties of different mesh shapes and sizes at different mesh openings, which are later used to provide simulation-based prediction of size selectivity. FISHSELECT has already been applied to four important species of the Barents Sea Demersal Fishery, and the results have in all cases showed to be coherent with the results obtained from sea trial results.",book:{id:"5210",slug:"fisheries-and-aquaculture-in-the-modern-world",title:"Fisheries and Aquaculture in the Modern World",fullTitle:"Fisheries and Aquaculture in the Modern World"},signatures:"Eduardo Grimaldo, Manu Sistiaga, Bent Herrmann and Roger B.\nLarsen",authors:[{id:"107079",title:"Dr.",name:"Eduardo",middleName:null,surname:"Grimaldo",slug:"eduardo-grimaldo",fullName:"Eduardo Grimaldo"},{id:"185311",title:"Dr.",name:"Manu",middleName:null,surname:"Sistiaga",slug:"manu-sistiaga",fullName:"Manu Sistiaga"},{id:"185312",title:"Dr.",name:"Bent",middleName:null,surname:"Herrmann",slug:"bent-herrmann",fullName:"Bent Herrmann"},{id:"185313",title:"Prof.",name:"Roger B.",middleName:null,surname:"Larsen",slug:"roger-b.-larsen",fullName:"Roger B. Larsen"}]},{id:"50363",title:"The Brown Seaweeds Fishery in Chile",slug:"the-brown-seaweeds-fishery-in-chile",totalDownloads:1731,totalCrossrefCites:4,totalDimensionsCites:10,abstract:"Chilean fishery of brown algae includes species belonging to the genus Lessonia, Durvillaea, and Macrocystis, which can be found along the coast, ranging latitudes from 18° to 55°S. The exploitation of these seaweeds is done mainly in the Northern coast because the environmental conditions of this region decrease initial production costs. Brown algae are exploited from natural populations and exported to international markets as row material, source of alginates, widely utilized in diverse manufacturing processes and industries. International demand for Chilean kelps has produced sustained increase in harvest during the last decade, reaching more than 390,000 dry tons/year. This chapter approaches the most relevant aspects of the brown seaweed fishery in Chile which covers a wide range of the Southeast Pacific coast, considering the number of commercial species, its abundance and distribution, knowledge achieved on their ecology and biology regarding management, and conservation of these resources, and finally, provides tools for stakeholders and policy makers directed to sustainable management of natural kelp beds occurring in the cold temperate seas.",book:{id:"5210",slug:"fisheries-and-aquaculture-in-the-modern-world",title:"Fisheries and Aquaculture in the Modern World",fullTitle:"Fisheries and Aquaculture in the Modern World"},signatures:"Julio A. Vásquez",authors:[{id:"180745",title:"Dr.",name:"Julio",middleName:null,surname:"Vásquez",slug:"julio-vasquez",fullName:"Julio Vásquez"}]},{id:"50462",title:"Direction of Fisheries (SUISAN) Education from a Historical Perspective in Japan",slug:"direction-of-fisheries-suisan-education-from-a-historical-perspective-in-japan",totalDownloads:1424,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Fishing, aquaculture, and food processing is collectively referred to as “SUISAN”, and the term was translated to “fisheries” in the Meiji period. Fisheries education in Japan was at its dawn. Fisheries education was necessary for improvement of local fisheries subsistence. Fisheries education was performed, centering on nurturing of mid-career engineers for deep-sea fishing after 1950s. However, when the Heisei period in the 1990s started, “participatory = citizen involvement type fisheries education” was promoted extensively. Future establishment of a Japanese version of Sea Grants is desired to promote citizen involvement in fisheries education with systematized involvement of universities, research institutions, aquaria, and local people.",book:{id:"5210",slug:"fisheries-and-aquaculture-in-the-modern-world",title:"Fisheries and Aquaculture in the Modern World",fullTitle:"Fisheries and Aquaculture in the Modern World"},signatures:"Tsuyoshi Sasaki",authors:[{id:"180712",title:"Dr.",name:"Tsuyoshi",middleName:null,surname:"Sasaki",slug:"tsuyoshi-sasaki",fullName:"Tsuyoshi Sasaki"}]}],onlineFirstChaptersFilter:{topicId:"40",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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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. 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He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. 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She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorThree:null},{id:"90",title:"Human Development",coverUrl:"https://cdn.intechopen.com/series_topics/covers/90.jpg",isOpenForSubmission:!0,annualVolume:11974,editor:{id:"191040",title:"Dr.",name:"Tal",middleName:null,surname:"Dotan Ben-Soussan",slug:"tal-dotan-ben-soussan",fullName:"Tal Dotan Ben-Soussan",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBf1QAG/Profile_Picture_2022-03-18T07:56:11.jpg",biography:"Tal Dotan Ben-Soussan, Ph.D., is the director of the Research Institute for Neuroscience, Education and Didactics (RINED) – Paoletti Foundation. 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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",institutionURL:null,country:{name:"India"}}}]},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",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",institutionURL:null,country:{name:"India"}}}]},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. 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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}]},{type:"book",id:"7839",title:"Malaria",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7839.jpg",slug:"malaria",publishedDate:"December 11th 2019",editedByType:"Edited by",bookSignature:"Fyson H. Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",biography:"Dr. Kasenga is a graduate of Tumaini University, Kilimanjaro Christian Medical College, Moshi, Tanzania and Umeå University, Sweden. He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). Dr. Kasenga is married to Grace and blessed with three children, a son and two daughters: Happy, Lettice and Sungani.",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}]}]},openForSubmissionBooks:{paginationCount:1,paginationItems:[{id:"11478",title:"Recent Advances in the Study of Dyslexia",coverURL:"https://cdn.intechopen.com/books/images_new/11478.jpg",hash:"26764a18c6b776698823e0e1c3022d2f",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"June 30th 2022",isOpenForSubmission:!0,editors:[{id:"294281",title:"Prof.",name:"Jonathan",surname:"Glazzard",slug:"jonathan-glazzard",fullName:"Jonathan Glazzard"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:36,paginationItems:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82212",title:"Protein Prenylation and Their Applications",doi:"10.5772/intechopen.104700",signatures:"Khemchand R. 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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). 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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