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(Molière - 1622-1673, The Imaginary Invalid, Act III).
In his work devoted to analyzing the theme of health, Ivan Illich addressed the medicalization of society, the harms caused by the medical apparatus, the so-called iatrogenesis, including drug iatrogenesis, which he also listed as the cause of hospital admissions [1].
Revisited more than 40 years after its publication, the work ‘Medical Nemesis’ still proves to be thought provoking and current. More than stimulating reflection, it has the strength to motivate the investigation of several of the aspects it addresses, so that one can know, for example, whether iatrogeneses related to hospital admissions are still a public health problem, a topic that has been extensively discussed. Extensive investigation [2, 3, 4].
Although adverse drug events (ADE) often include errors that occurred before and during hospitalization, even the correct prescriptions can present iatrogenesis, a situation that occurs when they cause more harm than good. In addition to the direct losses to patients, ADEs influence to increase the already unsustainable costs of health systems.
Therefore, iatrogenesis is not just a result of an error in the prescription. It is relatively common to have a correct diagnosis and prescription, but undesirable results due to several aspects. One of them has the explanation for the adverse effect in genetics. The literature also refers to writing iatrogenesis, when difficult to read writing causes potential or real problems to patients [5].
On the other hand, the contribution of drugs towards the cure or control of various diseases is undisputed, with a direct impact on prolongation and quality of life.
The association between drugs and different responses to treatments explained by individuals’ genetic variants is an ancient discovery, confirmed by several scientists since the beginning of the last century [6]. The knowledge arising from the human genome project has led to advances in several fields of modern science, but it is in the field of Health, in particular, that its applicability has been growing in a promising way [7].
In Health, the discoveries of genomics have contributed to improve the assertiveness of diagnoses, prognoses and treatments, including those related to the ingestion of medications, which makes pharmacogenetics one of the main manifestations of the so-called precision medicine.
It may sound inconsistent to relate Ivan Illich - an iconoclast of health technologies and an opponent of everything that stimulates the medicalization of society - with pharmacogenetics, after all, one of the most advanced technologies. However, this new branch of science, which constitutes one of the most promising forms of the applicability of genomic findings, can respond to an important problem highlighted by the author (adverse drug reaction) that causes discomfort in people and increases the already unsustainable costs of the health system, especially when such effects result in hospital admissions [8].
The purpose of this article is to revisit Ivan Illich’s thinking and discuss the currentness of his complaints regarding the inconveniences arising from the use of drugs, especially in their impact on hospitalization, and also reflect on the potential of pharmacogenetics to mitigate adverse events related to drugs that victimize people.
In the text that follows, it begins with a brief presentation of Illich’s story. Thereafter, a digression is made on the association between the concepts of medicalization and iatrogenesis, to then make quick considerations about social iatrogenesis, considering the effects of this phenomenon on society. After presenting the consequences of iatrogenesis as proposed by Illich, from a fluent literature review, an update of the findings is made, providing evidence that the problem shows to be current and relevant nowadays. A quick conceptual presentation of pharmacogenetics is followed by examples of its clinical consequences in specific pharmacological groups.
Born in Austria in 1926, Ivan Illich is the owner of an extraordinary life trajectory. He resided in Florence, Italy, where he studied Natural Sciences with a specialization in inorganic chemistry and crystallography. In Rome, he graduated in Philosophy and Theology, and was ordained a priest. Subsequently, he completed a doctoral degree in Medieval History at the University of Salzburg [9], Austria, and a post-doctoral degree at the Princeton University, USA. At the Vatican, he would be used in diplomatic functions, but in 1951 he preferred to be a parish priest in New York, USA. The parish served the Puerto Rican community, which led him to occupy, in 1956, the vice-rectory at the Catholic University of Puerto Rico [10]. He traveled alone through South America and in 1961 created, in Cuernavaca, in Mexico, a center for studies and preparation of missionaries for Latin America. Finally, in Bremen, Germany, he was a visiting professor - as, indeed, at several world-renowned universities - and died on December 2, 2002 [11]. Due to the plurality of themes that he studied, explained in greater detail and which he published on, he was considered a polymath - “an individual who knows a lot, who studies or who knows many sciences”, in addition to polyglot, having mastered 10 different languages [9].
He was a controversial and polemical critic of the most diverse topics, such as education, transportation and health [12]. Due to disagreements with the Catholic Church, which also did not skimp on its critical approaches, he ended up leaving the priesthood in 1969 [11]. Most importantly, he wrote books and defended innovative and radical ideas in the field of education. In the health area, he used his restless and brilliant mind for a remarkable reflection, materialized in the publication, in 1974, of the work ‘
The term “medicalization” (which has not yet been included in the main Brazilian dictionaries) can be considered a polysemic word, if not with different meanings, but certainly with different connotations. Some authors even associate the term with a positive attribute, as in the case of AIDS, when the entire health production chain mobilized, in an unusual way until then, to understand the etiology of the disease, learn to diagnose and develop treatments, first to avoid deaths and then to prolong life and to provide greater well-being to people affected by the referred disease [13].
In his approach, Illich made no concessions to the eventual positive aspect of what he called the “medicalization of life”, which he called as unhealthy for producing a “morbid society”.
Continuing in his critique on “medicalization”, he found that epidemiologists were unable to prove, for example, that early intervention altered the survival rate of patients affected by breast cancer. Likewise, he questioned the treatments for lung cancer, whose medical interventions brought more expenses and more suffering, without changing the survival rate - constantly mentioning the studies and articles that supported his conclusions [1].
It was also worth using drug treatments as an example, stating that the evaluation of the advantages (benefits) and disadvantages (undesired effects) caused by the drugs could be null or even negative, an aspect that even today seems to remain unnoticed, if not neglected.
This preamble on “medicalization” was used by Illich in his book to make way towards the concept of iatrogenesis, formed by the Greek words iatros (doctor) and genesis (origin). He thus defined iatrogenic disease as one that characterizes all the clinical conditions of which physicians, drugs, laboratories or hospitals - any medical apparatus, anyways, are pathogenic agents.
In the chapter he called Social Iatrogenesis, Illich dealt with issues that are still disturbing today and that are frequently addressed in the field of public health.
He affirmed, for example, that “the level of health did not improve even when medical expenses increased”, and was supported by studies that showed that although the USA allocated a considerable percentage of its GDP in the health system (7.4%, in 1974), they were not able to obtain good indicators, because the life expectancy of adult men paradoxically declined in that country [1].
The percentage of GDP invested in health by the United States in health reached an incredible 17.1% in 2013 [14]. Although health expenditures in that country lead the world statistics by far, however, Americans, as Illich emphasized, are not able to obtain a counterpart in health indicators, as for example, the life expectancy at birth (79 years) where they appear in the 34th position [14].
It is worth mentioning, based on this evident American paradox,, a vernacular created by Illich, “counterproductivity” [15], which he defined as “the paradoxical effect of overproduction and overconsumption”, to verify and exemplify that the global volume of vehicles, designed to allow greater speed in travel, ends up stopping circulation on the roads public; the global volume of education prevents children from expanding their curiosity, intellectual courage and sensitivity; and that the global volume of “medicalization” reduces the level of health (ILLICH, 1975, p. 70).
No less interesting, still to characterize the “medicalization” of society, it was the record that the author already made at that time about the wonder that technology caused in people, impelling them to believe that health increased as they had access to prostheses, drugs, hospitalizations and examinations for preventive controls.
A similar finding was recorded, more than twenty years later, by the American cardiologist Bernard Lown, who was discouraged after investing a lot of time in the collection of a detailed medical history, which gave him exactly the diagnosis, to see that the patient appears to be incredulous. But when he took him to an examination room, where he had an old-fashioned fluoroscope with an image intensifier, with an instrument panel similar to that of an airplane, he saw the patient impressed and saying with his buttons: “Ah, how nice it is to be in such a well-equipped medical office.” Dr. Lown concludes, without hiding the nonconformity, that “the puerile faith in the magic of technology is one of the reasons why the public has been tolerating the dehumanization of medicine” [16].
In a recent publication, Atul Gawande, when dealing with aging and end-of-life care, also identifies the fetish that technology awakens in people, who are not encouraged to seek advice from a geriatrician, but who await with unquestionable expectation the invention of a device that doctors implant in them, for example, in the chest, hoping to reduce discomfort and prevent them from ending up, dependent on care, in a nursing home [17].
In general, it is common for people not to feel treated if the doctor does not request for an examination or does not prescribe a drug. On the contrary, they value the use of technologies, preferably the most up-to-date and sophisticated ones, without awareness of the iatrogenesis that tests and medications so often provoke.
“Medicalization” also reveals itself as a true outsourcing of care for one’s own health, when people renounce the possibility of taking preventive care, eliminating bad habits, to surrender to the medical arsenals, the side effects of medicines and imaging tests, in addition to choosing hospitals as a safe place to obtain health, forgetting the risk of exposure to nosocomial infection, iatrogenesis of the most harmful.
Illich was radical and rebellious in renouncing “medicalization”, so coherent and determined in his conviction, that he suffered for ten years from a brain tumor, the cause of his death, giving up the therapies available at the time, using only opiates to relieve the pain and accepting to live with a huge bulge on his right face that even startled his interlocutors [18].
Iatrogenesis caused by drugs is usually studied based on factors related to the prescription: whether it is foreign to the therapeutic relationship; if it is at odds with the clinical diagnosis; whether the doses or duration of treatment are inadequate; whether undesirable, harmful or unexpected effects occur; if there is morbidity or mortality and if interactions between drugs occur that are harmful to the patient [19]. In addition, iatrogenic episodes occur even when prescriptions follow clinical protocols and drug labels, for the simple reason that people do not react in the same way, even if they have the same diagnoses.
In addressing some causes of iatrogenesis caused by drugs, Illich highlighted some factors not directly linked to the doctor-patient relationship as described above, but to other external aspects, such as the role of the pharmaceutical industry, whether in spending on advertising and commercial promotion with doctors, but mainly in stimulating the overconsumption of medicines, which increases the potential for damage related to the intake of medicines.
These aspects are still a current phenomenon and have been echoed by several authors, who denounce even the manipulation of academic studies, the creation of diseases that no longer admit any healthy individual [20], treating as medical problems which are non-medical [13], inventing diseases to sell their drugs [21], even considering that “a healthy person is just an undiagnosed patient” [22].
The laboratories’ obsession with increasing the consumption of medications seems to have no limit, as can be seen in the encouragement of prescription classified as off label, when manufacturers convince doctors to prescribe drugs for indications other than those approved regulatory agencies at the time of their registration. The pharmaceutical industry does this by preparing articles and paying researchers to put their names in these “studies”, with the explicit aim of increasing sales, as Marcia Angell, a Harvard professor, reported in a hard-hitting publication [23].
In ‘Medical Nemesis’, Illich pointed out that 3 to 5% of all hospitalizations in the United States of America (USA) had as a main reason, bad drug reaction. And that, once hospitalized, 18 to 30% of patients experienced an adverse reaction caused by a drug substance, doubling the length of hospital stay (ILLICH, 1975, p. 25).
The consultation of more recent studies confirms the relevance of this relationship, as was verified in the assessment of patient admissions in the Department of Cardiology and Pulmonology, in a large hospital in the Netherlands [24]. The authors conclude, after evaluating 2,000 hospitalizations by pharmacists and epidemiologists, that 19% of hospital admissions were motivated by adverse drug reactions (using the World Health Organization definition for this type of occurrence) and this percentage may reach 29% if hospitalizations classified as possibly iatrogenic are also considered.
An observational study carried out at a University Hospital in Spain sought to estimate the prevalence of negative results associated with drugs as a cause of hospitalization, by means of a random choice carried out by lot, which resulted in the analysis of 163 patients [25]. In 16.6% of the studied cases (27 patients) admission to the hospital was caused mainly by an adverse reaction due to use of the drug, of which 88.9% were considered preventable. The study concluded that hospitalizations motivated by an adverse reaction to medications had a high prevalence and most would be preventable through pharmacotherapeutic follow-up.
Another cross-sectional study, also conducted in Spain, evaluated patients who were hospitalized from the emergency services of a hospital. We sought to assess the negative results associated with the use of drugs that motivated hospitalization, to know the drugs that appeared more frequently and to assess the economic impact of these occurrences [26]. The conclusion was that 19.4% of hospitalizations occurred as a direct consequence of negative clinical results associated with the use of drugs, 65% of which were considered preventable. In addition, it was observed that the antineoplastic and immunosuppressive therapy groups motivated 38% of these adverse reactions. It was also found that 20.4% of the patients needed to be treated in an intensive care unit. Finally, it was found that the expense incurred was 237,377 euros (estimated annualized cost of 15,568,952 euros).
In the case of illnesses caused by Adverse Drug Events (ADE), in a meta-analysis 39 studies were selected (out of a total of 153) that evaluated the incidence of severe or even fatal ADE in American hospitals [27]. The conclusion was that the incidence of serious (6.7%) and fatal events (0.32%) was considered expressively high. Although the authors of the study noted the caveat that the results should be viewed with caution, because of the heterogeneity between the studies and possible bias in the samples, they warn that these data suggest that the adverse reaction to drugs represents an important health problem public in the United States of America (USA).
In a review article on adverse events (AE) in medical and hospital care, it was noted that ADEs are the most frequently identified, in addition to being also the most underreported [28]. In another evaluation carried out in a teaching hospital, which sought to estimate the frequency of this occurrence, it was observed that 14.6% of the 240 hospitalizations evaluated were motivated by ADE [29].
In England, a prospective observational study conducted in two large general hospitals sought to assess the cause of hospitalization in 18,820 patients hospitalized over a six-month period, seeking to identify which of these admissions were due to ADE, in addition to other aspects related to them. The prevalence obtained was 6.5% (1,225 cases), with 80% of this total directly related to an adverse drug reaction. The study concludes that this is an important problem considering morbidity, mortality and extra costs attributed to the studied events [30].
In Brazil, an original study focused on hospital admissions related to intoxication and adverse effects of drugs in children under one year of age. The retrospective analysis of the Authorizations for Hospital Admissions (AHA) of the Unified Health System (SUS), from 2003 to 2005, identified that a total of 1,063 children under one year of age were hospitalized as a direct or indirect consequence of drug-related intoxications or adverse effects [31].
Elderly patients are more susceptible to this type of occurrence due to the overuse and concomitant use of various drugs, administration errors and changes in the organism that interfere with pharmacodynamics and pharmacokinetics [32]. Although more vulnerable, the occurrence of iatrogenic disease in the elderly has not been studied in the dimension that the problem represents, since the population considered elderly is characterized by having multiple chronic diseases, is usually treated by many doctors and ends up being more subject to hospitalization and medical or surgical procedures [33].
Studies that analyze the relationship between pharmacotherapy and hospitalization of the elderly population also confirm that the occurrence rates are significantly high and are largely preventable [34]. Many of these hospital admissions for elderly patients are attributed to known drugs and occur because of drug interactions, which can also be prevented [35].
In the analysis of emergency hospitalizations for ADE in older adults, it was also found that they resulted from commonly used drugs and relatively few occurred due to the use of drugs considered to be high risk or inappropriate, which allows us to infer that such occurrences would also be preventable [36].
There are numerous studies that list hospital admissions due ADE and invariably conclude that we are facing an important public health problem, which not only reduces the patient’s quality of life but generates unnecessary expenses for hospitals [37] and, consequently, for the health system. Although the hospitalizations that are attributed to ADE vary in relation to the percentage, the findings are always significant when studying the causes of hospitalizations [38].
Adverse reactions to medications, even in cases of diagnosis, prescriptions and correct administration, can be explained by the trial-and-error methodology, which is still decisive in medical practice.
It should be emphasized that the search for the definition of the most appropriate drug and dosage makes use of experimenting with people’s reactions, and while pursuing the patient’s benefit, it often produces harmful effects. In the next topic, the potential contributions of knowledge of genomics to mitigate the harmful effects of iatrogenesis caused by drugs and their possible repercussions on people and health systems will be discussed.
The sequencing of the human genome has revolutionized biology in several fields of study. Until 2012, 67% of global investments in genome sequencing technologies were directed to pure research and 11% to field of health. The projection for 2017 pointed out that investments in health would channel 39% of resources, mainly due to the reduction in the cost of exams and the applicability in medical practice, diagnosis and treatment [7]. That is, the field of health is the one that increasingly uses the potential of next generation sequencing.
The influence of genetics on how people react differently to drugs has been observed for at least five decades. Recent knowledge brought by genomics has an invaluable support potential to medicine, for doctors, geneticists and for the pharmaceutical industry, in the use of personalized treatments [39].
In the case of drugs, therapeutic inefficacy or pharmacological toxicity has frequently been observed due to the presence of some metabolizing enzymes in drugs, in which drugs can interfere as inhibitors or inducers of these enzymes, an activity that varies between individuals and that can be determined by DNA analysis [40]. Genetic variability, therefore, can affect how a drug can be absorbed, activated, metabolized or excreted from the organism [41].
The reaction to the same drug varies from person to person depending on weight, age, gender, liver and kidney function, interactions between drugs, type of disease and genetic factors. The drug goes through two major processes in the organism, called pharmacokinetics and pharmacodynamics. Pharmacogenetics seeks to study how the drug passes through these processes, establishing the link between metabolism and individual differences in people’s DNA [42].
This metabolization can occur in different ways. In addition to the normal metabolizers, which respond as expected to the dosage of the package insert leaflet, there are slow metabolizers, which, due to reduced enzyme activity, are at risk of accumulating toxic levels and are more exposed to adverse reactions. Ultra-rapid metabolizers tend to require higher doses and are subject to the inefficacy of pharmacological therapy [41]. In addition, there is the intermediate metabolizer, which can benefit from the dose of the package insert leaflet but which can also be subject to the inefficacy of drug therapy.
The inclusion of genetic tests in the routine of medical practice is one of the main objectives of the
CPIC defines the terms pharmacogenetics and pharmacogenomics, which are sometimes used interchangeably by some authors. Pharmacogenetics is the study of the genetic influence on the response to the drug, normally considering one or only a few genes involved. Pharmacogenomics is the study of the variation of how genomics influences the response to the drug, considering the sequencing of the entire human genome1.
Pharmacogenetics emerged as a diagnostic tool that uses genetic information to guide pharmacotherapy decisions, improving the clinical outcome, giving rise to personalized clinical decisions [45].
These terms also differ according to their origin. Pharmacogenetic expression was coined by Friedrich Vogel in 1959 [46]. The word pharmacogenomics appears logically after the Human Genome Project.
Pharmacogenetics associates variability to drug response to hereditary aspects after the identification of some pharmacogenes [47]. Pharmacogenomics is one of the first clinical applications of the post-genomic era and expands this dimension to even point to the development of personalized drugs [48].
The following are some examples of the applicability of the use of pharmacogenetics in drug treatments widely used in psychiatry, cardiology and oncology.
The main causes of individual variability in response to the same dose of a drug are: age, biological factors, immunological factors, interactions between drugs and genetic factors [49]. Pharmacogenetics studies the role of genetics in variability of drug response.
This response can vary from potentially lethal adverse reactions to the equally serious lack of therapeutic efficacy.
Genetic variability plays an important role in pharmacokinetics (absorption, distribution, metabolism and excretion) and in pharmacodynamics, that is, in the interaction of the drug with the target and in the relationship between its concentration and its effect [50].
Currently, many studies are published that relate drugs to individuals’ genetic variants. In psychiatry, in the case of initial treatment for depression, about 30 to 40% of patients do not respond adequately to the prescribed medication, and it can take up to six weeks to characterize that it is not effective [51], exposing the patient to a long period therapy based on trial and error, with a high chance of adverse reactions.
The use of knowledge of the presence of variants in the genes involved in the metabolism of antidepressants such as CYP2D6 can provide the physician with an important subsidy in the choice of medications and in the definition of the dosages used in the treatment of depression [52].
The genetic variability of the drug response, depending on the type of metabolizer, is very high, as shown in Figure 1, which shows the demonstration of the main marker genes (CYP2D6 and CYP2C19) for antidepressants and anxiolytics [53].
Genetic variability of enzymes that metabolize drugs. Source:
Considering the Extensive Metabolizer (MS) as one that obtains an adequate response with the dose of the package insert, the window of variability is very large in relation to the Ultra-Rapid Metabolizer (UM) and the Poor Metabolizer (PM), especially, as shown in Figure 1 in the cases of the psychotherapeutic drugs, Escitalopram and Desipramine.
Several important drugs used in the treatment of heart disease are already the subject of studies on pharmacogenetics, especially in anticoagulants, antihypertensive agents, antiarrhythmics and statins.
Warfarin is the most commonly used oral anticoagulant in the world and aims to prevent thromboembolism. Warfarin therapy is often associated with a high risk of increased bleeding, especially during the initial phase of treatment. The CYP2C9 gene is responsible for the metabolic degradation of the activity of this drug and the VKORC1 gene is responsible for the activation of vitamin K-dependent coagulation factors. When inhibiting VKORC1, Warfarin produces the anticoagulant effect [54].
Although the consequences of undue dosages are always serious, the dose of Warfarin is usually adjusted by the trial-and-error method, or by considering other clinical parameters obtained in conventional laboratory tests. The optimal dose of warfarin varies greatly between patients. If the dose is too strong, the risk of serious bleedings increases, and if it is too weak, the risk of stroke increases. It is estimated that two million Americans start treatment with warfarin annually [55].
A study that sought to describe the frequency and characteristics of ADEs, which led people to seek emergency care in the USA, concluded, among other findings, that the second drug that motivated the occurrence was warfarin, just behind the insulins [56].
Another study that evaluated the bleeding complications caused by the use of anticoagulants concluded that the drug has been used in an increasing proportion and that bleeding has been a predominant reaction, in addition to being an important cause of mortality [57].
From what we tried to describe, there is no doubt that we are dealing with a class of drugs (anticoagulants) of special relevance, which deserves all possible care in the prescription process, mainly due to the high potential for harm to patients and the cost it entails for the health system, as ADE almost always require hospital admissions.
In another case–control study in the USA, we sought to assess whether the genotyping test for patients starting warfarin treatment could reduce the incidence of hospitalizations due to bleeding or thromboembolism. Compared with the control group over a six-month period, one of the main conclusions was that genotyped patients had a 43% lower risk of hospitalization for bleeding or thromboembolism. The authors conclude that genotyping for the anticoagulant reduces the risk of hospitalization for hemorrhage or thromboembolism in patients who start outpatient treatment with warfarin, with great statistical and clinical significance. They further defend that doctors should seriously consider the use of pharmacogenetic tests for patients who are starting treatment with the referred drug [58].
It should also be noted that oral anticoagulants are among the most sensitive to drug interactions, especially when taken simultaneously with antidepressants [59]. In these cases, the influence of metabolization between drugs must be observed by clinicians and pharmacists, without obviously disregarding the adverse events arising from these interactions.
More recent studies seek to evaluate new algorithms that increase assertiveness in warfarin prescription. Such algorithms associate genetic variables with age, gender, body mass, vitamin K levels and thyroid function. At the current stage, studies should also be developed that also consider geographic areas and ethnic groups, in order to guarantee greater therapeutic efficacy, mitigate adverse reactions to the drug and reduce hospitalizations motivated by it [60].
In the case of statins, used in the control of cholesterol and in the prevention of cardiovascular diseases. Its use is widespread today, but the prescriptions ignore the effects of the presence of polymorphisms in the SLCO1B1 gene, in charge of synthesizing a family of proteins inside the cells for their metabolism and therapeutic action.
Several studies have been and are being carried out to verify how patients metabolize the different types of statins, some more or less indicated according to the phenotype of each individual, in order to avoid the side effects that in the case of statins are manifested mainly in myopathies that can worsen patients’ living conditions.
Currently, at least 7 types of statins can be prescribed: atorvastatin, fluvastatin, lovastatin, pravastatin, pitavastatin, rosuvastatin and simvastatin. Although these different types share the same mechanism of action, they have differences in their chemical structures and pharmacokinetic profiles. Chemical structures end their solubility in water and influence the way they are absorbed, distributed, metabolized and excreted [61]. The patient can metabolize each of these different types of statins differently, an aspect that can be revealed by the pharmacogenetic test.
As an area responsible for the main cause of death in the world, drug therapy for Cardiovascular Diseases is the focus of attention in pharmacogenetic studies also for other drugs related to it. In addition to those already mentioned, there are plenty of studies relating genetic variants to the way we process antiplatelet drugs such as Clopidogrel, aspirins and antihypertensive drug [62].
Minimizing toxicity while maximizing efficacy is a common goal for the treatment of any condition, but its importance is even more evident in the case of oncology, due to the severe nature of the disorders and the aggressive toxicity caused by chemotherapeutic agents, in addition to the risk of relapse cancer or disease progression. The challenge of achieving an optimal therapeutic index is especially relevant for the elderly population, due to age-related changes in metabolism and the interaction with concomitant medications [63].
Over the past decade, advances in pharmacogenetics and pharmacogenomics have revealed the relationship between genetic variables and individual differences in drug responses. A large part of these advances has been made in the field of antineoplastic therapy.
Periodically, the American agency U. S. Food and Drug Administration (FDA) updates drug labels and edits table with related pharmacogenomic biomarkers. In 2016, 166 drugs (55 of them for cancer treatments) made up the table in which the FDA defines it as mandatory or in which it at least recommends the pharmacogenetic test, before the first prescription [64]. The variable reaction to drugs in the forms of unresponsiveness and adverse effect, and the motivation to use them better are the basis for one of the main objectives of the so-called personalized medicine, more recently disseminated as precision medicine.
Currently, iatrogenesis classified as adverse events, including those caused by drugs, are still an important public health problem, as has been demonstrated.
In response to the effects of these events, which are almost always harmful to people and those who offend the cost of assistance, pharmacogenetics, which emerged to improve the assertiveness of treatments to the point of being able to personalize them, may also contribute to minimize iatrogenesis, including the most serious ones requiring hospital admissions.
Although this goal is promising, there are still many challenges in implementing pharmacogenetic tests in clinical practice. First, concomitant factors such as diet, age and drug interactions affect pharmacokinetics and pharmacodynamics, increasing the complexity of assessing biomarkers in each patient. Second, the nature of the heterogeneity of clinical conditions presents a considerable therapeutic challenge. For example, in the case of cancer, treatment choices based on a biomarker present in a single biopsy sample may not be sufficient. Third, the definition of gene panels for each case is another area that needs to be developed, in order to facilitate the interpretation of clinicians [65].
The adoption of pharmacogenetic tests in routine clinical practice has been very scarce, particularly in Brazil. The main barriers to its implementation in the medical clinic are the lack of doctors’ knowledge about the applicability in prescriptions, in addition to the provision of clear and accessible recommendations, based on proven evidence, as CPIC has been trying to do [66].
It is noteworthy that another difficulty of great relevance has been the lack of studies that demonstrate the positive cost-effectiveness of its application [67].
However, the continuous fall in the costs of sequencing allows us to project a not-too-distant future in which the realization of the exome (mapping the approximately 20,500 genes currently known), in early life, will allow a continuous revisit to the genetic results, which will be available and applicable in medical clinic for life [43], including the specificity of drug reaction.
The use of the findings of pharmacogenetics may not be a redeeming strategy in the solution of all drug iatrogeneses, reported more than forty years ago by Ivan Illich, because other factors, as mentioned here, interfere in the metabolism of drugs. But their adoption may significantly mitigate the deaths and suffering caused by them, in addition to replacing the practice of trial and error in prescriptions and dosimetry - a notable imperfection in medical practice and the health system.
Although the imperfections must all be credited to the author, I would like to put on record my utmost gratitude to Prof. Dr. Vera Lucia Luiza for the countless suggestions, tireless revisions and diligent guidance in the preparation of the article.
Although acute appendicitis is one of the most common causes for acute surgical abdomen accounting for 250,000 appendectomies in the United States every year, a large number of other clinical conditions can mimic the presentation of this acute surgical emergency [1]. Those conditions include a variety of gastrointestinal, vascular, genitourinary and gynaecological diseases. It is very important to consider those mimics when assessing patients presenting to the emergency department (ED) with acute right-sided abdominal pain.
The use of imaging modalities such as abdominal and pelvic ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) can be crucial in assessing those equivocal cases with vague nonspecific symptoms. The use of imaging in those circumstances not only aids in ruling in the diagnosis of acute appendicitis but also helps in differentiating other forms of pathology contributing to patient’s symptoms.
The most common imaging modality used in patients with right-sided abdominal pain is abdominal and pelvic CT, which has a sensitivity of 97% and a specificity of 98% [2, 3].
Classical features suggestive of appendicitis on CT include concentric and thickened appendiceal wall, the presence of an appendicolith, fat stranding, mesenteric lymphadenopathy and the presence of surrounding fluid. The presence of other features such as appendiceal wall defect, extraluminal air or localised abscess is more suggestive of a perforated appendix.
Ultrasound abdomen and pelvis is the second most common imaging modality used in patients presenting with acute abdominal pain in whom there is a degree of clinical uncertainty. Ultrasound has a sensitivity of 78% and a specificity of 83% [4]. It is the most preferred imaging modality in pregnancy and paediatric age group due to the inherent risk of radiation associated with computed tomography. Features suggestive of appendicitis on ultrasound include dilated (>6 mm outer diameter) non-compressible appendiceal wall, hyperechoic appendicolith with posterior acoustic shadowing, peri appendiceal fluid collection and mural hyperaemia on colour flow Doppler mode. Although it is the preferred imaging modality in pregnancy, it can be extremely challenging to interpret the images given the distorted abdominal and pelvic viscera especially in the third trimester of pregnancy.
When it comes to the elderly population presenting with acute abdominal pain, choosing the best Imaging modality can be extremely challenging due to the high mortality risk associated with false-negative imaging. The incidence of acute appendicitis in patients older than 50 years of age is only 15% when compared to younger patients where the incidence doubles to 30% [5]. Despite the declining incidence of acute appendicitis with advancing age, there is an increase in mortality rate from 1% in young patients to almost 8% in patients over 65 years of age [5]. This high mortality rate in the elderly age group can be explained by the increased incidences of appendicitis complications such as the development of appendicular abscess and perforation. There is also a considerable decline in the imaging diagnostic accuracy with advancing age as studies have shown that the percentage of patients with positive histological evidence of appendicitis drops from 78% to 64% in patients older than 65 years of age [6]. The use of enhanced CT scan for imaging in the elderly population is superior to ultrasound imaging. The low sensitivity, and negative predictive value along with the increased number of false-negative imaging in patients with complicated appendicitis make the ultrasound modality less preferable when it comes to choosing the best imaging modality. Due to the aforementioned reasons, the Jerusalem guidelines recommend the use of CT with IV contrast in patients older than 60 years old with an Alvarado score ≥ 5 and a negative ultrasound study [7]. This recommendation taking into account the risk of radiation where the number of performed CT scans after a negative ultrasound is reduced by 50% [7, 8]. It is also worth mentioning that the use of ultrasound is very important in screening elderly patients presenting to the Emergency Department with abdominal pain for an aortic abdominal aneurysm which a vascular emergency that can mimic appendicitis. The current recommendation by the UK Royal College of Emergency Medicine (RCEM) is for the Emergency Physician to perform an ultrasound scan on any patient older than 50 years presenting with abdominal pain [9].
The use of magnetic resonance imaging (MRI) depends on accessibility as it differs from one hospital to another. The presence of other more readily accessible imaging modalities such as computed tomography and ultrasound makes the use of magnetic resonance less popular. Features suggestive of appendicitis on MRI include the presence of dilated appendix (>7 mm outer diameter), fat stranding and restricted diffusion.
Terminal ileitis caused by Crohn’s disease and Backwash ileitis associated with Ulcerative colitis both can present with right lower abdominal pain mimicking acute appendicitis. Typical age group is from 15 to 30 years and clinical presentation usually include symptoms of diarrhoea and bloody stool. IBD cannot be diagnosed via a blood test, however routine blood tests checking for pro-inflammatory markers such as raised white cell count (WCC), C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR) may aid in supporting the diagnosis and monitoring the disease activity later on.
Although colonoscopy remains the investigation of choice for confirming the diagnosis, the use of radiological imaging is warranted when colonoscopy is not accessible.
As per imaging choice, IBD is best evaluated with either CT or MRI enterography and classical findings include bowel wall thickening of more than 3 mm, mucosal hyperenhancement, fat stranding and engorged vasa recta known as “Comb” sign. Management of IBD includes both surgical and non-surgical treatment depending on the severity, the extent of the disease and the presence of complications.
This refers to bowel inflammation caused by bacteria, viruses or parasites. Patients commonly present with abdominal pain, tenesmus and diarrhoea. Stools are often purulent and mixed with mucous and blood. Commonly implicated organisms include
This is an inflammation of the bowel that occurs after radiotherapy. Symptoms include diarrhoea, nausea, vomiting and abdominal pain. Most cases of radiation enteritis resolve spontaneously a few weeks after treatment ends however for some it can extend for months and years after the termination of treatment. CT and MRI findings include bowel wall thickening with luminal narrowing, small bowel obstruction and sometimes the presence of a fistula between the bowel and the bladder or the vagina.
Also known as Typhlitis is an acute life-threatening condition that affects immunocompromised patients such as patients with HIV disease or those who are on immunosuppressive therapy. The aetiology involves mucosal damage secondary to ischemia and secondary bacterial infection with a predilection for the caecum and ascending colon. Patients may present with abdominal pain, diarrhoea, vomiting and fever. Typhlitis is commonly associated with Neutropenia. Early diagnosis and management are crucial to prevent complications such as perforation and sepsis. Classical CT findings include dilated caecum with circumferential wall thickening, peri-colic fluid collection and pneumatosis. Management includes bowel rest and antibiotic therapy.
This is commonly seen in patients over the age of 40, where small bulging pouches also known as diverticula, form at the weakest portion of the bowel. Diverticulitis is the term used when there is associated inflammation of the diverticula. Symptoms include abdominal pain, vomiting and fever. Risk factors include aging, smoking, low fibre diet, obesity and sedentary life. Laboratory blood tests checking for raised inflammatory markers are useful in making the diagnosis of diverticulitis. Classical features of diverticulitis on CT include bowel wall thickening with infiltration of adjacent mesenteric fat. Managing patients with uncomplicated diverticular disease involves the introduction of low-fibre diet and antibiotics. Surgery is reserved for patients with complications such as perforation, diverticular abscess or fistula formation.
This is caused by congenital anomaly characterised by the presence of the vitelline duct which normally connects the yolk sac to the midgut during the fetal development. It occurs in 2–3% of the general population [10]. Inflammation of Meckel’s diverticulum usually caused by enterolith and symptoms include abdominal pain, rectal bleeding and vomiting.
CT findings include the identification of a blind-end tubular structure protruding from the antimesenteric side of the distal ileum, wall thickening, hyperenhancement and fat stranding. Management is surgical resection of the diverticulum.
This is a life-threatening emergency where there is an abnormal dilatation of the abdominal aorta due to vascular wall weakness. This abnormal dilation (1.5 times its normal diameter or greater than 3 cm) of the aorta is commonly seen involving the infrarenal part of the abdominal aorta. AAA is a fatal condition where mortality is about 80% with leaking aneurysm and only half of the patients survive 30 days post emergency repair [11]. AAA is more common in men and the risk factors implicated in the aetiology are the same factors contributing to atherosclerosis such advancing age, diabetes, hypertension, hypercholesterolemia and smoking history. Clinical presentation of AAA includes a variety of symptoms such as abdominal pain, back pain, groin pain, and a pulsating abdominal mass. Ultrasound aorta remains the gold standard for screening patients for AAA in the emergency setting and the UK Royal College of Emergency Medicine (RCEM) recommends that all emergency physicians are to perform ultrasound aorta in all patients who are over the age of 50 presenting with abdominal pain. Disadvantages for ultrasound include difficult studies due to the patient’s body habitus, or the presence of overlying bowel obscuring the visualisation of the aorta. Another downside to the use of ultrasound is its operator dependability and the inability to exclude any aneurysmal leak. CT aortogram is a highly acute study that can confirm the presence and the size of an aneurysm which aids in planning surgery. Management of AAA involves either open repair or endovascular aneurysm repair (EVAR) depending on the fitness of patients for surgery and the morphology of the aneurysm.
This refers to small bowel injury secondary to insufficient blood supply which can be acute or chronic. Patients with mesenteric ischemia can present with diarrhoea, rectal bleeding, abdominal pain, especially after eating, and unintentional weight loss due to the fear of eating and vomiting. Risk factors include atrial fibrillation, heart failure and chronic kidney disease. Early CT findings include mesenteric oedema, bowel dilation and wall thickening, mesenteric stranding and the presence of an adjacent solid organ infarction. Treatment depends on the cause of ischemia and as such can be medical or surgical however if it is a late presentation the only treatment is surgical since there is a risk of necrotic bowel.
Urolithiasis or kidney stone disease can present with a right lower abdominal pain mimicking acute appendicitis. Careful consideration for the presence of obstructive uropathy is very important to prevent kidney injury. CT Urinary system is the gold standard imaging when assessing patients with suspected urolithiasis. CT findings include the identification of a high attenuation calculus within the urinary system with or without hydroureter and hydronephrosis, ureteral wall thickening and adjacent fat stranding.
Ultrasound can be used in patients with ureteric colic to identify any features of hydronephrosis. The only disadvantage of ultrasound imaging is its operator dependability. Conservative treatment is indicated for patients with stones measuring less than 4 mm.
Pyelonephritis or kidney infection is commonly caused by ascending urinary tract infection with the most commonly implicated organism being
This medical emergency occurs when pregnancy happens outside the uterus and needs to be excluded in all women of reproductive age who present with abdominal pain. Blood and urine beta-HCG measurement is crucial in making the diagnosis. The absence of an intrauterine gestational sac on transvaginal ultrasound along with a high beta-HCG, intrapelvic fluid and a delayed period should raise the possibility of an ectopic pregnancy. Ultrasound features include the detection of a yolk sac or a live embryo outside the uterus makes the diagnosis. Other features include the detection of a hyperechoic ring around the adnexal gestation sac also known as the “tubal ring” sign. If detected early, methotrexate can be administered to terminate the ectopic pregnancy. Surgical intervention is indicated in the case of methotrexate contraindication, ruptured ectopic or in patients with hemodynamical instability.
Another medical emergency that should be considered in all women of reproductive age presenting with severe abdominal pain. It is caused by twisting of the ovary around its supporting ligaments cutting the blood supply to the ovary and fallopian tube. Ovarian torsion commonly occurs in patients with ongoing gynaecological pathology such as ovarian cysts, tumours, enlarged corpus luteum or in patients who are undergoing ovarian stimulation for assisted fertilisation. Ultrasound is the first line of imaging and features suggestive of torsion include increased ovarian size more than 4 cm in diameter, heterogeneous appearance due to oedema and haemorrhage, and the detection of a cyst or an ovarian mass. Doppler Arterial and venous flow can be helpful when compared to the other non-affected side. Management includes surgical de-torsion of the ovary and debridement of any necrotic tissue.
This condition occurs when there is a sudden haemorrhage into an ovarian cyst. Ultrasound findings usually depend on how old the haemorrhage is. Most classical feature on ultrasound is a finely septated fishnet pattern caused by the fibrin bands. Management is usually conservative.
This refers to the infection of the female reproductive system caused most commonly as a result of untreated ascending sexually transmitted infections. Most commonly implicated organisms are
This refers to one-sided abdominal pain that is associated with mid-cycle ovulation. Mittelschmerz means “middle pain” in German. If the pain occurs on the right side of the abdomen, it can mimic acute appendicitis. In most cases, mittelschmerz does not warrant any medical treatment.
Although the diagnosis of acute appendicitis is essentially clinical, familiarisation with other causes of acute abdominal pain that can mimic appendicitis is equally important especially in females and those with the extremes of age. Here we present a plethora of gastrointestinal, urological, vascular, infectious, and gynaecological conditions that can be similar in presentation to acute appendicitis. The supplementary use of appropriate laboratory tests and radiological imaging can be pivotal where there is clinical uncertainty, not only aiding in confirming the diagnosis of appendicitis or its associated complications but also in identifying other alternative pathology. Routine blood tests that include a full blood count (FBC) and c-reactive protein (CRP) can aid in the diagnosis of acute appendicitis as evidenced by the presence of raised white cell count and CRP. Although raised inflammatory markers can raise the likelihood for clinically suspected acute appendicitis, it is non-specific and less helpful where the clinical presentation is inconclusive and other differential diagnoses are equivocal. A urinalysis also should be considered in all patients with suspected acute appendicitis as part of their workup since it is an important bedside test when assessing for potential renal or urology pathologies such as the presence of blood in urolithiasis or nitrites and leukocytes in urinary tract infection (UTI).
Special consideration is warranted for female patients presenting with abdominal pain as the presence of an underlying gynaecological pathology can potentially complicate the clinical picture and affect the diagnostic accuracy. In this special category of patients, it is particularly important to check the blood or urine samples for beta Human chorionic gonadotrophin hormone (Beta-hCG) in all female patients of childbearing age presenting to the Emergency Department with acute abdominal pain to exclude ectopic pregnancy. Ultrasound remains the first line of imaging in investigating gynaecological pathology (transvaginal ultrasound) and in the paediatric age group due to the inherent risk of radiation associated with CT imaging.
Another special consideration is given to the elderly population where the incidence of acute appendicitis is less common. In assessing elderly patients, it is of a high priority to exclude time-critical conditions such as ruptured abdominal aortic aneurysm and bowel ischemia. The current recommendation by the Royal College of Emergency Medicine in the UK is for the emergency physician to perform an ultrasound aorta in all patients who are older than 50 years presenting with acute abdominal pain to rule out abdominal aortic aneurysm (AAA). A follow up dedicated CT aortogram may be required if the patient is hemodynamically stable to confirm the diagnosis of abdominal aortic aneurysm and to evaluate for any potential leak. Bowel ischemia is another time-critical emergency where there is a compromise to the bowels blood supply. Risk factors for bowel ischemia include diabetes, hypertension, smoking, hypercholesterolemia and atrial fibrillation (AF). It is important to consider the diagnosis of bowel ischemia in all patients who are older than 50 years presenting with a sudden onset of severe abdominal pain along with a raised serum lactate level reflecting organ hypoperfusion. CT abdomen and pelvis with IV contrast or a dedicated CT angiography remains the best imaging technique for all hemodynamically stable patients in whom bowel ischemia is suspected.
As discussed above a variety of clinical conditions can mimic acute appendicitis and familiarisation with those alternative conditions is crucial when deciding what imaging modality will best suit the patient assessment thus increasing the diagnostic accuracy and ensuring optimal care to all patients.
I have received no financial funding or grants for this paper.
I declare no conflict of interest.
I dedicate this work to my beloved wife and parents who have both supported me throughout my career in emergency medicine. I will always appreciate their love, affection, patience and encouragement.
AA | Acute appendicitis |
AAA | Abdominal aortic aneurysm |
US | Ultrasound |
CT | Computed tomography |
MRI | Magnetic resonance imaging |
WCC | White cell count |
CRP | C-reactive protein |
ESR | Erythrocyte sedimentation rate |
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\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\\n\\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\\n\\nLast updated: 2020-11-27
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
\n\nCo-Author: All other Authors of the Chapter besides the Corresponding Author.
\n\nIntechOpen: IntechOpen Ltd., the Publisher of the Book.
\n\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\n\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\n\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\n\nLast updated: 2020-11-27
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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. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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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. 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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. 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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. 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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. 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