Summary of the different types of diagnostic assays for CPVE diagnosis.
\r\n\tThe development of the interpersonal model and the Kleinian school in the second half of the last century allowed the emergence of an original understanding of the unconscious mind. Within the intersubjective paradigm, the psychoanalytic situation is conceptualized as an interpersonal field to which both the analyst and the patient contribute substantially. We have shown elsewhere how the failure to give a full account of such an intersubjective dimension in both psychoanalytic theory and practice amounts to a core liability in contemporary psychoanalytic discourse.
\r\n\r\n\tThe present book will focus on a few areas where the insufficient development of our discipline is currently apparent: five wounds that mark the body of the psychoanalytic enterprise.
\r\n\r\n\tNew contributions are particularly needed in the following areas: Current conceptualization of the unconscious mind is mechanistic and not suited to incorporate the full network of interpersonal exchanges which unfolds in the analytic room; Furthermore, the development of interpersonal psychoanalysis and the theory of the object relations warrants a greater appreciation of the impact of extratranference relations (e.g., couple, family, peers) on the patient's inner life both within and without the psychoanalytic situation.
\r\n\r\n\tAn integration of theories and models from other psychological paradigms is clearly in order here; the book will also focus on Barangers’ theory of the bi-personal field that makes traditional unipersonal models of the psychoanalytic process untenable. Also, it will help in the understanding of the reciprocal interactions of the two partners in the psychoanalytic dyad in most psychoanalytic institutes the training format relies naively on models from the academic or the professional domains. This fosters rigidity, conformism, and a hierarchical organizational style in the institutional life; e) all over the long span of his creative life Freud showed consistent interest in the application of psychoanalysis to literature, the arts, religion, and politics. Contemporary psychoanalysis is getting more and shyer and is pressed at the margins of social and political debate. The psychoanalytic theory includes unique lore of knowledge about the conscious and unconscious mind. Without it, a comprehensive understanding of human reality will stay out of the reach of contemporary culture.
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Sanz, Cristobalina Mayorga, Ruben Martínez-Aranguren and Pedro M. 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Cruz, Michelle F. Muzitano, Sonia S. Costa and Bartira Rossi-Bergmann",authors:[{id:"64710",title:"Prof.",name:"Bartira",middleName:null,surname:"Rossi-Bergmann",fullName:"Bartira Rossi-Bergmann",slug:"bartira-rossi-bergmann"},{id:"119635",title:"Dr.",name:"Elaine",middleName:null,surname:"Cruz",fullName:"Elaine Cruz",slug:"elaine-cruz"}]},{id:"31793",title:"Cissampelos sympodialis (Menispermaceae): A Novel Phytotherapic Weapon Against Allergic Diseases?",slug:"cissampelos-sympolialis-menispermaceae-a-novel-phytotherapic-weapon-against-allergic-diseases-",signatures:"M.R. Piuvezam, C.R. Bezerra-Santos, P.T. Bozza, C. Bandeira-Melo, G. Vieira and H.F. 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Araujo and M.F. 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CPV-2 causes 100 percent morbidity and mortality rate of 10 percent and 91 percent in adult and young dogs respectively [9]. However, a mortality of 91 percent was reported in experimentally infected dogs that were not treated [10]. CPV-2 affects predominately the younger dogs between 6 weeks and 6 months [8] with an increased susceptibility to puppies less than 6 months. In dogs over the age of 6 months, sexually intact males are more likely (twice) to develop canine parvovirus enteritis (CPVE) in comparison to intact females [11]. The CPV-2 antibody titer transmitted to the newborn via absorbed colostral antibody is 50–60% of the mother’s titer. The half-life of paroviral maternal antibodies is around 10 days [12]. Therefore, puppies are highly susceptible to the CPV-2 infection as the maternal antibody titres start declining. CPVE affects dogs of all ages, although it is more severe in puppies. Puppies can succumb to shock and die within two days after being sick. The most striking symptom of CPV-2 myocarditis is the abrupt mortality in young puppies, generally around the age of 4 weeks [13].
In recent years, CPVE outbreaks caused by multiple CPV-2 variants have been recorded in diverse geographical locations throughout the world. Previously, CPV-2, which could not infect cats, has been replaced by CPV-2 variants that can now infect cats, suggesting that CPV-2 may be capable of spreading between species [14]. Since CPV-2 infects a wide range of wild animals in the order Carnivora, subclinical infection appears to be prevalent. As a result, significant CPV-2 reservoirs in wildlife appear to exist, and transmission of virus between domestic dogs and wildlife appears to be common and bidirectional [15]. Despite the availability of a wide range of immunoprophylactic and antiviral agents to control CPV-2 infections in dogs, many outbreaks have been reported throughout the world, and the disease has remained a major veterinary and economic concern due to the presence of unvaccinated dogs, intervention of active immunization by maternally derived antibodies, and the emergence of a different antigenic variants of CPV-2.
Canine parvovirus infection is caused by
Schematic representation of
The virus is nonenveloped having icosahedral symmetry and is 25 nm in diameter. The CPV virus is made up of the sixty protein subunits containing VP1 (5–6 units) and VP2 (54–55 units). The protein structure is made up of antiparallel β-barrel (8-stranded) capsid. The viral replication occurs inside the nucleus of multiplying cells and therefore the intranuclear inclusion bodies are formed during the infection. The viral capsid structure is made up of spike at the three-fold axes of the icosahedral unit, a 15-Å depression around the five-fold axes and two-fold axes is formed. Antigenic determinant regions have been plotted to the three-fold protrusion and the two-fold depression are related to the host cell features [17]. The surface of the capsid is composed of four loops inserted between the strands, resulting in spike-like protrusions around threefold axes of approximately 22 Å. The antigen neutralization site, also known as epitope A, is composed of loops 1 and 2 of one VP2 and loop 4 of a threefold related molecule [21]. The molecular weight (MW) is around 5.5 to 6.2 × 106 Da. There is an equal ratio of protein to nucleic acid.
NS1 is the largest non structural protein in CPV-2, and it is primarily involved in viral replication and pathogenicity [22]. NS1 is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis by inducing an antitumor immune response in different tumor models [23]. A recent study demonstrated the amino acid residues of T598 and T601 in the C-terminal phosphorylation sites of NS1 protein, involved in replication and pathogenicity of CPV-2 [24].
In the 1970s, CPV-2 emerged as a novel pathogen in dogs. Since then, CPVE has been reported across all the continents [25, 26]. Other related viruses such as Feline panleukopenia virus (FPV), Mink enteritis virus (MEV), Raccoon parvovirus (RPV) are closely related to the CPV-2 [27]. Mutations in the canine transferrin receptor (TfR) type-1 lead to adaptation of CPV-2 in different species 2 [28, 29]. There is more than 98% genome homology reported in the CPV and FPV nonetheless infect different species and have typical antigenic capsid and haemagglutination (HA) properties [28, 30]. The mutations in different amino acid positions have led to the effective adaptation in the new hosts [30]. There are over five to six mutations in the VP2 residue of the CPV-2 and FPV and also 375 and 323 amino acid position regulates the pH functionality of HA [31, 32]. CPV-2a (Asn CPV-2a) replaced CPV 2 in 1980s in the USA and various European countries. CPV 2a can infect the cats which was not a feature of CPV 2. CPV 2a has been displaced by the CPV-2b (426Asp) which was first reported in USA in 1982 and CPV-2c (426Glu) variant in Italy [31, 33]. Although two variants, CPV-2a and 2b had been identified much earlier, however, the third variant CPV-2c had been recognized in early 2000 [33]. Thereafter it has been reported frequently from many different countries. In addition, new CPV-2a and new CPV-2b have also been documented due to non-synonymous substitution at 297 residues (Ser to Ala) of VP2 protein [34]. In India, CPV-2a has recently become the most prevailing antigenic type among all variants. Recent emergence of new antigenic variants that differ significantly from the current vaccine strains is a matter of concern for efficacy of vaccine [35].
The CPV is of two types: CPV-1, commonly known as minute virus of canine and accountable for gastrointestinal and respiratory infection of dogs whereas, CPV-2, most pathogenic type and is responsible for severe gastroenteritis/hemorrhagic gastroenteritis, in young puppies as well as adult dogs.
It is quite difficult to distinguish the clinical diseases caused by CPV-2 variants owing to its overlapping nature of signs and symptoms. These variants are believed to produce similar pathogenicity however; some studies showed that severity of clinical manifestations is influenced by variants of CPV-2 based on clinical, hematological, serological and histopathological examinations [36, 37].
Although puppies under 6 months of age are highly susceptible, adult dogs with insufficient immunity are also considered as high risk to the CPVE. CPV-2 can persist in the environment for more than a year, enabling susceptible dogs to pick up infection from CVP-2 contaminated feces, vomitus, or fomites. Although the feco-oral route is considered as primary path of disease transmission, infection through the oro-nasal route is also common in naive or under-immunized dogs due to ingestion of viruses shed in the vomitus or feces of CPV-2-infected animals [38]. However, direct contact or environmental contamination may also play a role [39]. Breed predisposition and seasonal prevalence of the disease are subject to considerable variations in wide geographical areas [40, 41].
Doberman, Rottweiler, and German shepherd (GS) dogs have been reported to be more susceptible to CPVE than other breeds [42]. Due to inherited immunodeficiency, the exotic breeds, German Sphered and Doberman, are more susceptible than the other breeds [43]. German shepherd has the highest CPV infection rate (70%) followed by the Doberman (55%) [44]. A cytokine bioassay revealed that the magnitude of TNF-α production by peripheral blood monocytes was greatest in dogs with a breed-related risk for CPVE. When compared to mixed breeds, highly susceptible breeds such as Rottweiler and Doberman Pinscher produce more TNF-α in response to LPS stimulation [45]. Increased TNF activity is predictive of mortality in naturally occurring CPVE infection in veterinary medicine [46]. Therefore, it has been hypothesized that dogs with a breed-related risk of developing CPVE, a disease associated with sepsis, would have a greater pro-inflammatory cytokine response to endotoxin [45].
The incubation period of CPV-2 infection ranges from 4 to 14 days. The infected dogs start to shed virus few days prior to the visible clinical signs and shedding of virus gradually declines 3–4 weeks postexposure [47]. Following entry into the body, the CPV-2 rapidly multiply in oropharyngeal lymph node, thymus and mesenteric lymph node, resulting in viremia within one week of exposure. After that, the virus attacks rapidly multiplying cells of crypts of intestine, epithelium of the tongue, oral cavity, bone marrow, and cardiac myocytes, besides lung, spleen, liver, and kidneys [48]. The key pathogenic event in CPV-2 infection is the virus-induced destruction of enterocyte, leading to mucosal barrier disruption, and villous atrophy. This causes profuse vomiting and hemorrhagic diarrhea, nutrient malabsorption, dehydration/hypovolemia, metabolic acidosis and/or alkalosis. The disruption of mucosal barrier allows bacterial translocation from intestinal compartment to systemic circulation, resulting in septicemia, endotoxemia, systemic inflammatory response syndrome as well as hypercoagulability [49]. The CPV-2 infection in the thymus and bone marrow precursor cells results in loss of thymic cortex and profound leucopenia, respectively [48]. Death may occur due to multi-organ failure when the affected dogs remain unattended [40, 49]. Previously, myocarditis was thought to be the acute cause of death in young puppies however, this form nowadays occurs rarely because of widespread CPV vaccination of dogs. The concurrent infections with parasitic, virus, or bacterial intestinal pathogens or stressors may aggravate the disease [50, 51, 52].
The degree of clinical manifestations may vary with age, breed, and immune status, duration of illness and virulence of virus. The clinical signs of dogs with CPV infection are nonspecific in nature and resembles to gastritis and enteritis. The most notable clinical signs of CPVE are lethargy, depression, weakness, lack of appetence, bouts of vomiting, and diarrhea. The diarrhea is characterized by foul-smell and mucoid to purely hemorrhagic because slugging of intestinal mucosa and bleeding. The excessive loss of fluid during vomiting and diarrhea causes marked dehydration that results in development of hypovolemic shock. Occasionally, intussusception occurs due to intestinal dysmotility. Neurologic signs in puppies with CPVE may result from hypoxia secondary to myocarditis, hypoglycemia, or intracranial thrombosis or hemorrhages [52]. The bacterial translocation from intestine to systemic circulation can cause fever, systemic inflammatory response syndrome and septic shock with hypotension and organ failure [40, 48]. Apart from diarrhea, respiratory distress, pulmonary congestion and edema, alveolar and bronchiolar hemorrhage and convulsions are also occasionally manifested due to hypovolemia, endotoxic and septicemic shock [8, 53]. The malabsorbtion of nutrients and inadequate storage of glycogen in muscle and liver result in hypoglycemic encephalopathy which leads to seizures. On hospital admission, the prognosis is poor in CPVE dogs with intussusception, systemic inflammatory response syndrome and severe leucopenia.
Virus isolation is considered as a gold standard for any viral disease diagnosis. In case of CPV-2 different cell lines like CRFK (Crandell Rees feline kidney), MDCK (Madin-Darby canine kidney) and A-72 are used for the isolation and propagation of the virus. The adapted virus causes distinct cytopathic effect in infected cell lines as cell rounding, aggregation, and necrosis of the affected cells. This requires the presence of special laboratory and is laborious [54].
It is an expensive technique for the detection of the virions by negative staining in the stool samples or culture isolated virus. Immunoelectron microscopy can also be done by using CPV-specific antibodies. The need of expensive electron microscope makes it out of reach for regular usage [55].
The property of the CPV to cause agglutination of the pig, cat or rhesus monkey red blood cells at 4°C is used for detection of the CPV. The reciprocal of the maximum dilution of virus exhibiting ample agglutination of erythrocytes (mat formation) is designated as HA titer. The HA titer of more than 1:32 is usually considered as specific for CPV-2 [56].
The use of electric current allows the rapid movement of antigen and antibody towards each other resulting into the formation of precipitation line quicker than simple diffusion reaction. This technique is not commonly used but have been utilized for the prevalence of CPV infection in clinically suspected dogs [57].
In this test, an antibody tagged with fluorescent dye is employed for detection of specific CPV antigen. Mostly it is used as direct FAT for the diagnosis of CPVE but is not used routinely for diagnostic purpose [58].
This is a commonly used test utilizing antigen–antibody interactions employing specific antigen or antibody and is mostly useful under the field conditions. Here, the property of agglutination of polystyrene beads coated with either specific antigen or antibody on their surface is used with anti-CPV monoclonal and polyclonal antibody to detect CPV-2 in the stool samples. Earlier it has been used for both qualitative and quantitative evaluation of CPV in suspected dog feces. Also, a recombinant VP2 protein-based LAT for determination of immune status in dogs against CPV-2. Besides LAT, a slide agglutination inhibition test has been used to detect the presence of CPV-specific antibodies by utilizing the agglutination property of CPV-2 [59].
This method is developed for the detection of CPV-2. SIT is an antibody typing system based on the ability of viral antibodies to bind with the virus and prevents the virus from binding to RBC. SAT is used for antigen detection by serially diluting the clinical sample and then incubating it with a fixed amount of RBC containing virus surface receptors. The virus particles in the sample bind to the RBC and form a lattice that can be seen visually [60].
It is an enzyme-based immunoassay involving antigen–antibody interactions to screen a large number of samples at a time. Recombinant VP2 protein-based indirect ELISAs has been developed to detect and quantify antibodies against CPV-2. Novel polyclonal antibody-based antigen capture ELISA using rabbit anti-CPV hyperimmune sera as capture antibody and guinea pig anti-CPV hyperimmune sera as detector antibody has been also developed. IgY-based ELISA comprising of the chicken egg yolk-derived has been developed for the detection of both antigen and antibodies. Different commercial ELISA kits are currently available for CPV-2 antigen and antibody detection [61].
IC assays or Lateral flow assays are strip-based devices utilized for the detection of a target analyte in test samples. Colloidal gold nanoparticles are commonly used in synthesis of the probe (conjugate) in majority of these strip-based points of care assays. Different components used are the sample pad, conjugate pad, nitrocellulose membrane, absorbent pad and a plastic cassette. These tests are now used routinely for the parvovirus diagnosis in affected dogs. A number of lateral flow assay-based commercial kits are available for rapid detection of both CPV-2 antigen in feces and antibodies in serum, which are also available in the market. These are helpful in the field and gives rapid results within 10–15 mins. Recombinant VP2 protein based immunochromatography tests has also been developed based on the rapid detection of CPV-2 [62].
It is an immunological test which uses charging of test antigen on to a nitrocellulose or PVDF membrane followed by detection using specific antibody against the antigen and an enzyme labeled secondary antibody which forms a color on addition of an insoluble substrate. It is helpful as on the spot assay for CPV diagnoses. It has been developed for detection of CPV-2 using hyperimmune sera raised against the whole virus/recombinant VP2 protein. Commercial dot ELISA kits are also available for evaluating IgM response against CPV-2 after vaccination or infection [63].
PCR is a molecular diagnostic assay which is used for the detection of viral nucleic acid and is relatively more sensitive than other conventional tests. Diverse antigenic types of the CPV can be distinguished by employing strain-specific primer or nested PCR or restriction enzyme analysis of the PCR. Also strain differentiation may be carried out with the help of oligonucleotide sequencing of the amplified gene [64].
This has also been reported for the detection of CPV nucleic acid. Here hybridization with CPV-specific biotin or radiolabelled probe is carried out onto the CPV nucleic acid charged nitrocellulose paper or nylon membrane from suspected samples and then formation of color and band in the radiograph indicates the presence of the virus [65].
It uses an isotopic-labeled probe for both the detection and tracking of CPV nucleic acid in affected morbid tissue specimens thus,using more incubation time for development of the positive reaction [66].
This technique can be employed to quantitate CPV-2 in samples using either TaqMan probe technology or SYBR Green method. It is used for strain differentiation of concurrent infection using Multiplex Real-time PCR; and also, to differentiate vaccine strain from wild CPV strains. Different multiplex assays real-time PCR has been validated for the presence of CPV, FPV and PPV [67].
It is used for the detection and typing of the known point mutations/single nucleotide polymorphism based on variable size of PCR-amplified products specific to a particular allele. In this PCR basically 2 pairs of primers are used (2 inner and 2 outer specific primers matching to individual allele type) in a single PCR tube and there are no post-PCR protocols used as restriction enzyme digestion (PCR-RFLP) and sequencing therefore they provide an economical confirmation. ARMS-PCR is a well-known technique frequently employed for phenotypic association and single nucleotide polymorphism (SNP) studies. This has been used for CPV detection and its antigenic typing [54].
It contains a stable electrically neutral peptide backbone and the PNA-DNA hybridization assay are relatively more sensitive and specific than TaqMan-based real-time PCR for CPV differentiation [68].
The assay is a sensitive and rapid technique used for amplification of DNA and thereby pathogen detection in an hour by using the DNA polymerase by autocycling strand displacement action by boiling at persistent temperature (60–65°C) in water bath. Usually, 2 sets of primers bind to 4 to 6 different regions of target viral DNA. LAMP has field application as there is no need for any thermocycler to carry out the target gene amplification. The amplification of VP2 gene of CPV-2 by LAMP assay has been developed. LAMP assay along with lateral flow dipstick (LFD) and LAMP-ELISA are also used for CPV DNA detection [69].
It is a convection-based method using a hydrolysis probe for detection of CPV-2 and its antigenic variants. The reaction mixture is sequentially allowed to pass in an automatic manner through variable temperature zones in a capillary tube which undergoes thermocyclic phase to amplify the DNA and the probe hydrolysis produces optical output providing the result within an hour [70].
This technique makes use of both conventional PCR and isothermal amplification as in LAMP and is completed within one and a half hour. Here mostly an exogenous sequence from an unrelated species or of botanical origin is incorporated at the 5′ end into the primer sequences used in PSR if a human or veterinary pathogen is targeted. PSR has been successfully used to detect all CPV antigenic variants with ten-fold higher sensitivity than traditional PCR [71].
It is a probe-based assay that uses melting curve analysis to detect and differentiate between CPV-2 variants. This assay consists of 2 TaqMan probes namely FAM labeled and HEX labeled. The FAM-labeled probe sequence is perfectly complementary to CPV-2a, with a 1 bp mismatch to CPV-2b and a 2 bp mismatch to CPV-2c. The HEX-labeled probe has complete complementarity with the original CPV-2 and a 1-bp mismatch with the other variants. This method is also capable of detecting samples containing more than one variant without sequencing [72].
Aptamers emerged as a good alternative to antibodies as affinity reagents. Recently, ssDNA aptamers that specifically bind with the recombinant VP2 (rVP2) protein of CPV-2 with affinity in the nanomolar range have been reported. The ssDNA aptamers specific to CPV-2 (rVP-2) were selected by the Systematic evolution of ligands through exponential enrichment (SELEX) method and their target binding was assessed by dot blot and enzyme-linked oligonucleotide assay (ELONA). Aptamers with high binding affinity and specificity against rVP-2 could be employed in diagnostics for rapid detection of CPV-2 [73].
It is primarily used for most viral genome identification and confirmation. Thus, considered as a gold standard for the antigenic typing of CPV variants. The amplified PCR product is either directly sequenced or cloned which is sequenced in a sequencer utilizing apt primers. The sequence data is analyzed using the appropriate bioinformatics database. Either nucleotide or amino acid sequence data or even both could be employed to recognize the evolutionary analysis of CPV-2 isolates from different geographical sites [74].
It is an analytical device which detects the DNA/RNA/protein/enzymes and alters it to the detectable electrical signals. A biosensor for CPV detection has been established by means of quartz crystal microbalance biosensor and ProLinker B [75]. Summary of different types of diagnostic assays are listed in the Table 1.
Diagnosis | Specimen | Diagnostic assay used | Feature | Remarks |
---|---|---|---|---|
CPV antigen | Feces or rectal swab | ELISA | High specificity Low sensitivity | Feces or rectal swab |
Haemagglutination assay | Low-cost and rapid. | Sensitivity and specificity vary | ||
Tissues or morbid samples | Necropsy specimens | Histopathology | Different histopathological techniques and IHC may be used. | Differential diagnosis with other enteric infections |
Viral DNA | Feces or rectal swab or any tissue | Polymerase chain reaction (PCR);qPCR | Efficient in diagnosing even minute amount of viral genome, can be quantified; Antigenic typing | Sensitivity and specificity vary. Vaccine virus shedding occurs upto weeks after immunization leading to false positives results. Inhibitory components may lead to false negative results. |
Virus | Feces or rectal swab or any tissue | Virus isolation | Confirmatory diagnosis | Requires special facility |
Virus particles | Feces or rectal swab or any tissue | Electron microscopy | Confirmatory diagnosis | Requires special facility, expensive |
Summary of the different types of diagnostic assays for CPVE diagnosis.
Commercially available kits are mostly based on antigen–antibody reactions, such as ELISA, dot ELISA, and immunochromatographic strip-based assays (Table 2).
Sl. No. | Test | Company | Principle | Reference |
---|---|---|---|---|
1 | SNAP parvo antigen test | IDEXX, United States | ELISA | [76] |
2. | Rapid Immunochromatographic (IC) strip test | ADDBIO, Korea | Immunochromatography test | [43, 77, 78] |
3. | Witness Parvo Test Kit | Zoetis, United states | Rapid Immuno Migration (RIM™) technology. | [79] |
4. | Fassisi® Parvo | Fassisi, Gottingen, Germany | Lateral flow immunoassays | [80] |
5. | FASTest parvo card | Vet lab, UK | Lateral flow immunoassays | [55] |
6. | 4 CPV Antigen Rapid Test Kit | Ubio Biotechnology systems Pvt. Ltd., India | Lateral flow immunoassays | [79] |
7. | Anigen Rapid CPV Ag Test Kit® | Bionote, Dongtan, South Korea | Lateral flow immunoassays | [80] |
8. | ImmunoRun CPV antigen detection kit | Biogal- Galed labs, Israel | Immunochromatographic assay | [79] |
9. | Primagnost® Parvo H + K | Dechra, Aulendorf, Germany | Lateral flow immunoassays | [80] |
10. | Canine Parvovirus & Distemper IgMAntibody Test Kit | Biogal Galed Laboratories Acs Ltd., Israel | Immunocomb | [79] |
11. | Vetexpert Rapid Test CPV Ag® | Vetexpert, Vienna, Austria | Lateral flow immunoassays | [80] |
List of commericially available kits for CPV-2 detection.
In absence of effective and appropriate antiviral drugs, the most universal therapeutic regimen for CPVE is supportive and symptomatic care until vomiting and diarrhea have resolved. Because of long-term illness of CPVE infected dogs, the challenges faced by the pet owners are cost of treatment and hospitalization. In private practice settings, the treatment cost may be huge, indicating that financial constraints may be a factor in disease-related euthanasia [81]. Therefore, fatality of CPVE is documented more in socioeconomically underprivileged areas, where level of education and financial opportunity for care and vaccination are not adequate [82]. Although the survival rate of CPVE in hospitalized and outpatient dogs is debatable, a recent prospective, randomized trial found no significant differences in survival (90% vs. 80%, P = 0.66) or duration of hospitalization (4.6d vs. 3.8d, P = 0.20) between inpatient and outpatient dogs [83]. However, given the possible risks of long-term hypoglycemia and leukopenia, aspiration pneumonia, edema, and intussusception in CPVE dogs, hospitalization appears to be the better option over outpatient treatment [84].
The principal components of supportive and symptomatic therapy include 1) fluid therapy and oncotic support, 2) antibiotics, 3) antiemetics, and 4) nutritional support. A wide range of other treatment measures including, though not limited to, antiviral treatments and pain management have been assessed in the past or are currently under investigation regarding their potential utility in CPVE.
The development of severe hypovolemia is the first impact of pathophysiology in dogs with CPVE, hence re-establishment of the circulating volume is the utmost need [85]. The hypokalemia, hypochloremic metabolic alkalosis, hypoglycemia, hypoproteinemia and loss of oncotic pressure in circulation are the major fluid and electrolyte abnormalities during episode of diarrhea and vomition in acute CPVE [86]. The most aggressive therapies consisting of administration of intravenous (IV) fluids to restore intravascular fluid volume status, replenish interstitial fluid losses, maintenance of hydration and oncotic support. A balanced isotonic crystalloid solution (eg, Lactated Ringers) should be used for initial restoration of intravascular volume and rehydration, with a rate titrated to improve perfusion parameters such as capillary refill time, mucosal color, pulse character, and mean arterial pressure or lactate concentrations. Apart from fluid administration, potassium need to be supplemented in hypokalemic patients whereas, 25% dextrose at the dose rate of 1-2 mL/Kg body weight followed by addition of 2.5–5% dextrose in the crystalloid fluids will be required for hypoglycemic patients with blood glucose level < 60 mg/dL. Initially, the fluid is administered at the dose rate of 80–90 mL/kg with a boluses of 15–20 mL/kg over 15–20 minutes to counter the hypovolemic shock and, to improve the fluid perfusion. After that, the maintenance dose for daily fluid depends on the body weight (kg) and percent of dehydration. The volume (L) required to correct the daily fluid loss is calculated as body weight (Kg) × % dehydration. Generally, 40–60 mL fluid for each kg body weight is considered as ideal maintenance dose. Since fluid absorption through subcutaneous route is impaired in hypovolemic patients, intravenous access is considered as choice of fluid treatment. However, intraosseous or jugular catheter are considered as appropriate option in severe hypovolemic or interstitially dehydrated patients [87].
In CPVE, protein loosing enteropathy attributes to pronounced hypoalbuminemia (<2 g/dL) and/or hypoproteinemia (<4 g/dL) resulting in peripheral edema, pleural or abdominal effusions [88]. In that case, provision of oncotic support in the form of either natural or synthetic colloids are very important to minimize the morbidity and mortality of patients [89]. For correction of hypoalbuminemia, fresh plasma (20 mL/kg) or fresh-frozen plasma (6.6–11 mL/kg IV or 3 doses administered intraperitoneally 12 hours apart) and canine-specific albumin concentrate are used [90]. The concentrated human albumin products can also be used but the risk of immune reaction is the major limitation. If further oncotic support is required, hydroxyethyl starch (20–30 mL/kg/d) can be given, depending on clinician choice [6]. Sometimes, administrations of whole blood (20 mL/kg, within 4 hours) or packed RBCs are needed in severe anemic dogs with CPVE.
Apart from fluid and electrolyte imbalance, emesis is another clinical manifestation in CPVE. So, antiemetic treatment is warranted in CPVE otherwise persistent vomition may enhance the duration of hospital stay and further aggravates the condition of patient. The clinical efficacy of number of antiemetics in CPVE had been investigated with varying degree of results. The earlier studies showed that metoclopramide, a dopaminergic antagonist, was found to be effective in reducing episode of vomition by exerting a prokinetic effect in the upper intestinal tract and blocking the chemoreceptor trigger zone when administered as a bolus or as a constant-rate infusion in dogs. The ondasetron or dolasetron, the serotonin receptor antagonists, are also found effective in reducing the number of vomiting events [85]. Recently, a substantial antiemetic effect of maropitant, an antagonist of neurokinin1 receptors, by stimulation of either central or peripheral emetic pathways has been reported in dogs however, the efficacy of maropitant in CPVE has yet to be thoroughly investigated [91]. The administration of maropitant once daily, singly or in combination with metoclopramide, is very effective in reducing vomition in CPVE [5].
Translocation of bacteria from intestinal compartment to systemic circulation is very common in CPVE because of villous collapse and disruption of the mucosal barrier. The translocation with concurrent marked neutropenia leads to a high risk of septicemia and endotoxemia. Additionally, hypotension from fluid loss and sepsis make dogs with CPVE at high risk of developing acute kidney injury. Therefore, parenteral administration of broad-spectrum bactericidal antibiotics is necessary in dogs with CPVE. Ampicillin and cefoxitin as single-agent treatments or in combination with enrofloxacin are the choice antimicrobials against Gram-positive and negative bacteria [85]. Aminoglycosides may also be considered in well-hydrated animals otherwise it may be avoided due to its inherent risk of nephrotoxicity. Puppies with CPVE often have comorbidities, including gastrointestinal parasitism. Hence, antiparasite therapy should be initiated once the puppy can tolerate oral therapies [6].
Restoration of early mucosal integrity and prevention of bacterial translocation from gut compartment to systemic circulation are very important for faster recovery of dogs with CPVE. Enteral feeding is reported to improve the mucosal integrity and faster repair, resulting in lower possibilities for bacterial translocation [8]. In earlier study, it was demonstrated that early enteral nutrition via nasoesophageal catheter starting 12 hours post-admission led to clinical improvement, significant weight gain, and improved gut barrier function was more early as compared to withholding of the traditional food until cessation of vomiting for 12 hours [92].
Severe vomition, enteritis, and or concurrent intussusception in CPVE are the possible reasons for abdominal pain. Hence, analgesic treatment to reduce visceral pain is one the important aspect in therapeutic management in CPVE. Partial mu-agonists such as buprenorphine (0.01–0.02 mg/kg IV every 8 hours) or an agonist–antagonist such as butorphanol (0.1–0.2 mg/kg/h) are the preferred analgesics over the pure mu agonists as opioid analgesics can promote ileus and vomiting. The α-2 agonists that promote extreme vasoconstriction and limit gastrointestinal perfusion, and non-steroidal anti-inflammatory drugs that impair gastrointestinal and renal perfusion, both are not indicated [93].
Like other viral infections, prophylaxis is the cornerstone for prevention of CPV in dogs. Although, an adequate number of killed and live CPV vaccines are marketed by pharmaceuticals but vaccines sometimes fail to protect completely due to poorly responding breeds (Rottweilers and Doberman pinschers), variation in genetic makeup of field and vaccine viruses, interference by presence of maternal antibodies and adjunct factors [94]. Therefore, development of some suitable antiviral drugs is utmost important for effective management of the CPVE in its acute illness stage. Till now, only few antiviral drugs have been evaluated for its clinical efficacy against CPVE. In an earlier placebo-control study, the therapeutic efficacy of Oseltamivir, a neuraminidase inhibitor, in CPVE had been evaluated and noted that Oseltamivir did not produce any additional benefit in terms of reduction of mortality or duration of hospitalization except some improvements in body weight and hemogram in dogs with CPV-illness [95]. In another study on naturally infected dogs, a promising anti-CPV activity of recombinant feline interferon-ω (rFeIFN-ω) has been recorded as compared to placebo-group. The intravenous administration of rFeIFN-ω at the dose rate of 2.5 mU/kg daily for consecutive three days remarkably reduced the clinical symptoms and mortality [96, 97]. Although the drug is currently available for use in Europe and Australia, the high price and frequent non-availability are major limitations. Recently, another antivital drug, Acyclovir, guanine analogue commonly used to treat herpes simplex virus infection, have been shown to improve the disease conditions [98]. Further, an
Passive immunization with specific antibodies against enteric viral infections in animals confers significant protection, reduces diarrhea and virus shedding and increase survival rates [101]. Thus, the of immunotherapeutics in viral infections is promising treatment approach because of lower adverse effects as well as no chance of any resistance as in antiviral drugs. The passive immunization by means of oral or intravenous administration of IgY specific for CPV-2 shows the protective effect in dogs challenged with the virus [102]. The reduction of clinical scores, duration of symptoms and mortality and improvement of body weight gain has been reported by anti-CPV-2 IgY therapy in experimentally produced CPVE [103]. Recent study reported that chicken IgY- single chain fragment variables (scFv) generated against the virus capsid protein could be a promising therapeutic target against CPV [104, 105]. Aside from IgY, the neutralization of CPV by anti-feline panleukopenia virus antibodies is also reported from an
The key physiopathological alterations of CPVE are destruction of intestinal crypts, neutropenia, secondary bacterial translocation, immunosuppression due to thymus atrophy, sepsis and systemic inflammatory response syndrome in puppies [6, 109]. Therefore, immunomodulators could be an option to enhance therapeutic efficacy of supportive treatment. A recent study demonstrated that subcutaneous administration of human dialyzable leukocyte extract-h (hDLE) along with supportive therapy in puppies with CPVE significantly increased the leukogram and reduced the clinical score, duration of hospitalization, mortality as compared to supportive therapy alone [110].
Leukopenia is one of the most important prognostic indicators of mortality in dogs with CPVE. Hence, stimulation of bone marrow and improvement of leukogram in peripheral circulation are considered as strategic approaches to reduce the CPVE associated mortality. Enhancement of endogenous canine G-CSF (cG-CSF) concentrations by exogenous administration of human G-CSF (hGCSF) and cG-CSF is reported to stimulate bone marrow, resulting in improvement of neutrophil counts in puppies with CPV infection [111]. However, the use of hG-CSF and cG-CSF may not necessarily improve survival [112, 113].
The interferon (IFN)-ω, a type I IFN (similar to IFN-α), is known for its antiviral, anti-proliferation, and antitumor activities. A notable therapeutic effect of rIFN-ω on CPV-infected dogs is reported [114]. Additionally, the promising therapeutic potential of other type I (IFN-α, IFN-β, IFN-ε, and IFN-κ) and III (IFN-λ) IFNs in CPVE has also been reported [115].
Recently, anti-CPV activity of the serum derived transfer factors (TFs), low molecular weight (<5000 daltons) biological response modifiers has been documented. It imparts therapeutic benefit in CPVE by altering the cytokine response of the host [116].
Probiotics, primarily comprised of live microorganisms in fermented foods, protect gut from acute diarrhea through adherence and colonization on gut mucosa [117]. Therapeutic efficacy of probiotics has been verified in dogs with CPV associated illnesses [118]. In an earlier study, oral administration of probiotic preparations as an adjunct therapy to young dogs with CPVE has shown faster resolution of clinical signs, improved leukogram and decreased mortality as compared to supportive treatment alone [119]; whereas, no benefit with respect to length of hospital stay or case fatality was recorded in other study [120].
The disturbance in oxidant/antioxidant equilibrium is evident in CPV-gastroenteritis and oxidative stress is believed to link with pathogenesis of CPVE [121]. Hence, addition of antioxidants in supportive therapy has emerged as a promising therapeutic option to improve the response of treatment in viral diseases. Treatment with
An interest in natural products including herbs, plants and their extracts/metabolites as antiviral drug candidates has increased in the last few decades especially due to rising emergence of antimicrobial resistance globally and potential side-effects of many antimicrobials [123]. Very recently, anti-parvoviral activity of propolis, a traditional Chinese medicine, prepared from honeybee hives has been documented [124]. The
Alteration in the gut microbiome is reported in enteric viral diseases including CPVE and other gastrointestinal diseases in dogs [125]. The disruption of gut microbiota leads to impediment in the enterocyte nutrition, immune regulation, protective barrier function, and gastrointestinal motility [126]. Therefore, restoration or re-establishment of the microbiota could have a good interest therapeutically. Recently, a randomized clinical trial showed that administration of fecal microbiota (10 g feces diluted in 10 mL of sterile 0.9% saline) obtained from healthy donor rectally at 6–12 hours post-admission caused faster resolution of diarrhea, shortened the duration of hospitalization and reduced the mortality in young dogs with CPVE when compared with standard therapy alone [126].
A modified live virus (MLV) and an inactivated vaccine are the two types of CPV-2 vaccines currently available [94]. Administration of the vaccine should start at 6 to 8 weeks of age and then every 2–4 weeks until 16 weeks of age or older. For dogs that are 16 weeks or older, 2 doses of vaccination are recommended with an interval of 2–4 weeks [127]. A recombinant vaccine based on virus-like particles (VLPs) is being developed, which has the advantage of becoming highly immunogenic and safe [128]. Peptide vaccines containing major antigen neutralizing region N terminal of VP2 are also under developmental stage [129]. A single-dose vaccination of Vaccinia virus encoding CPV2-VP2 elicited substantial antibody responses and provided comparable protection for dogs with attenuated CPV2 vaccine. This vaccine could be used as a promising vaccine candidate to prevent CPV-2 infection in dogs [130].
CPV-2 is one of the most significant viral enteropathogens of canines causing high morbidity and mortality and manifested by vomition and severe acute haemorhagic gastroenteritis. Prompt symptomatic therapy will increase survivability of infected puppies but vaccination is best way to prevent the disease in dogs. Despite the pups are protected through vaccination from the pregnant bitch, it is more vulunerable to CPV-2 infection as maternal antibody titers started declining. Despite the availability of high sensitive and specific diagnostic approaches and the effective prophylactics such as modified live virus and inactivated vaccines, a large number of outbreaks are still reported in wide geographical areas across the globe in both vaccinated and unvaccinated dogs. The future studies should be taken up towards vaccination failures, occurrence of CPV-2 in different canine species and the emergence of antigenic variants of the CPV-2 involved in the outbreaks.
All the authors acknowledge and thank to their Institute.
The authors declare no conflict of interest.
This compilation is a book chapter written by its authors and required no substantial funding to be stated.
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Analytical method validation, thinking about the maximum relevant processes for checking the best parameters of analytical methods, using numerous relevant overall performance indicators inclusive of selectivity, specificity, accuracy, precision, linearity, range, limit of detection (LOD), limit of quantification (LOQ), ruggedness, and robustness are severely discussed in an effort to prevent their misguided utilization and ensure scientific correctness and consistency among publications.",book:{id:"6379",slug:"calibration-and-validation-of-analytical-methods-a-sampling-of-current-approaches",title:"Calibration and Validation of Analytical Methods",fullTitle:"Calibration and Validation of Analytical Methods - A Sampling of Current Approaches"},signatures:"Tentu Nageswara Rao",authors:[{id:"220824",title:"Dr.",name:"Tentu",middleName:null,surname:"Nageswara Rao",slug:"tentu-nageswara-rao",fullName:"Tentu Nageswara Rao"}]},{id:"58596",title:"Linearity of Calibration Curves for Analytical Methods: A Review of Criteria for Assessment of Method Reliability",slug:"linearity-of-calibration-curves-for-analytical-methods-a-review-of-criteria-for-assessment-of-method",totalDownloads:8095,totalCrossrefCites:19,totalDimensionsCites:44,abstract:"Calibration curve is a regression model used to predict the unknown concentrations of analytes of interest based on the response of the instrument to the known standards. Some statistical analyses are required to choose the best model fitting to the experimental data and also evaluate the linearity and homoscedasticity of the calibration curve. Using an internal standard corrects for the loss of analyte during sample preparation and analysis provided that it is selected appropriately. After the best regression model is selected, the analytical method needs to be validated using quality control (QC) samples prepared and stored in the same temperature as intended for the study samples. Most of the international guidelines require that the parameters, including linearity, specificity, selectivity, accuracy, precision, lower limit of quantification (LLOQ), matrix effect and stability, be assessed during validation. 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Ils are typically more environmentally-friendly solvents than the classic organic solvents having low volatility, flammability and toxicity. The chapter presents various applications of ILs in liquid chromatography.",book:{id:"11204",title:"Analytical Liquid Chromatography - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11204.jpg"},signatures:"Victor David and Serban C. Moldoveanu"},{id:"80336",title:"Perspective Chapter: Advantages of Ion Mobility Coupled with HPLC/UPLC",slug:"perspective-chapter-advantages-of-ion-mobility-coupled-with-hplc-uplc",totalDownloads:58,totalDimensionsCites:0,doi:"10.5772/intechopen.102380",abstract:"Ion mobility is a new separation technique that can be coupled with high performance liquid chromatography (HPLC) or ultra-performance liquid chromatography (UPLC). Variances in cross-sectional ionic areas of different molecules create differential speeds through a gas allowing for millisecond separations. 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He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation"},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. 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