This book is supported by the Major Science and Technology Program for Water Pollution Control and Treatment (2017ZX07108-001) and National Key R&D Program of China (2017YFC0406004).",isbn:"978-1-78984-910-3",printIsbn:null,pdfIsbn:"978-1-83881-843-2",doi:"10.5772/intechopen.81771",price:1e5,priceEur:1e5,priceUsd:1e5,slug:"emergency-operation-technologies-for-sudden-water-pollution-accidents-in-the-middle-route-of-south-to-north-water-diversion-project",numberOfPages:130,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"cd61e407dc2dc5a74ffe354b294f71a8",bookSignature:"Xiaohui Lei",publishedDate:"December 19th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/8874.jpg",numberOfDownloads:3254,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:1,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:2,isAvailableForWebshopOrdering:!1,dateEndFirstStepPublish:"October 1st 2018",dateEndSecondStepPublish:"October 22nd 2018",dateEndThirdStepPublish:"December 21st 2018",dateEndFourthStepPublish:"March 11th 2019",dateEndFifthStepPublish:"May 10th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"282118",title:"Dr.",name:"Xiaohui",middleName:null,surname:"Lei",slug:"xiaohui-lei",fullName:"Xiaohui Lei",profilePictureURL:"https://mts.intechopen.com/storage/users/282118/images/8105_n.png",biography:"Prof. Xiaohui Lei works at the China Institute of Water Resources and Hydropower Research. He is currently the leading expert in water resources allocation and scheduling in China. Over the past 10 years, he focused his work on the integrated regulation of multiple water projects. Prof. Lei solved a number of complex problems including uncertainty of hydrological forecasting, curse of dimensionality and multi-objectives of water resource scheduling, nonlinearity, and strong coupling of engineering control. Currently, he holds many university positions in China, including those at Hohai University, Taiyuan University of Technology, Chang’an University, etc. He is also the Chairman of Cascade Reservoirs and Water System Operations Working Group in the International Association for Hydro-Environment Engineering and Research (IAHR), the Director of Water Cycle and Operation Specialized Committee in the Chinese National Committee on Large Dams (CHINCOLD), and Deputy Secretary General of Water Diversion Specialized Committee in the Chinese Hydraulic Engineering Society (CHES), etc.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"866",title:"Water Pollution",slug:"water-pollution"}],chapters:[{id:"64500",title:"Introduction - Emergency Operation Technologies for Sudden Water Pollution Accidents",doi:"10.5772/intechopen.82239",slug:"introduction-emergency-operation-technologies-for-sudden-water-pollution-accidents",totalDownloads:661,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Xiaohui Lei, Hezhen Zheng and Lingzhong Kong",downloadPdfUrl:"/chapter/pdf-download/64500",previewPdfUrl:"/chapter/pdf-preview/64500",authors:[{id:"282118",title:"Dr.",name:"Xiaohui",surname:"Lei",slug:"xiaohui-lei",fullName:"Xiaohui Lei"},{id:"280920",title:"Dr.",name:"Hezhen",surname:"Zheng",slug:"hezhen-zheng",fullName:"Hezhen Zheng"}],corrections:null},{id:"64478",title:"Simulation Technology for Hydrodynamic and Water Quality in the Main Canal",doi:"10.5772/intechopen.82022",slug:"simulation-technology-for-hydrodynamic-and-water-quality-in-the-main-canal",totalDownloads:612,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The hydrodynamic and water quality simulation technology can be used for predicting the pollutant diffusion process after a sudden water pollution accident, and for analyzing the effect of emergency operation measures. The MRP features a long route, a variety of buildings, etc.; therefore, a set of hydrodynamic and water quality models that are applicable to the main canal of the MRP was independently developed based on 1-D open canal hydrodynamic and water quality theory and with various types of buildings as inner boundaries. Through calibration and verification, these models can be applied to the simulation of hydraulic and water quality response process under any operation conditions in the main canal of the MRP.",signatures:"Yu Tian, Hezhen Zheng, Xiaohui Lei and Wei Dai",downloadPdfUrl:"/chapter/pdf-download/64478",previewPdfUrl:"/chapter/pdf-preview/64478",authors:[{id:"280920",title:"Dr.",name:"Hezhen",surname:"Zheng",slug:"hezhen-zheng",fullName:"Hezhen Zheng"}],corrections:null},{id:"64429",title:"Traceability Technology for Sudden Water Pollution Accidents in Rivers",doi:"10.5772/intechopen.82023",slug:"traceability-technology-for-sudden-water-pollution-accidents-in-rivers",totalDownloads:568,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The traceability technology for sudden water pollution accidents can be used for fast, accurate identification of a pollution source in the river. A correlation optimization model with the pollution source position and release time as its parameters is established based on hydrodynamic calculation and on the coupling relationship between forward concentration probability density and backward position probability density; and the solution of the model is realized by using a differential evolution algorithm (DEA). A coupled probability density method is to convert the traceability of a sudden water pollution accident into the optimization of two minimum values. This method is simple in principle and easy in solution, realizing the decoupling of parameter of the pollution source. The concept of gradient is introduced to the differential evolution algorithm, improving the efficiency of searching process. The proposed method of traceability was applied to the emergency demonstration project of the SNWDMRP. The results indicate that the model has good efficiency of traceability and high simulation precision and that traceability results have a certain guiding significance to the emergent regulation and control of sudden water pollution events in a river.",signatures:"Weihong Liao, Zhiguo Gan, Jiabiao Wang and Hezhen Zheng",downloadPdfUrl:"/chapter/pdf-download/64429",previewPdfUrl:"/chapter/pdf-preview/64429",authors:[{id:"280922",title:"Dr.",name:"Jiabiao",surname:"Wang",slug:"jiabiao-wang",fullName:"Jiabiao Wang"}],corrections:null},{id:"64626",title:"Emergency Operations of Sudden Water Pollution Accidents",doi:"10.5772/intechopen.82021",slug:"emergency-operations-of-sudden-water-pollution-accidents",totalDownloads:784,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Emergency operation technologies can help to make reasonable operation measures of hydraulic structures, which are important to control the scope of the effect arising from an event and reduce the harm caused thereby. The main canal of MRP is divided into three parts in case of sudden water pollution accidents: the accident pool, the upstream section of the accident pool, and the downstream section of the accident pool. For each part, the target and strategy for emergency operation technologies are discussed. With regard to an accident pool, multiple kinds of check gate closing methods, synchronous, asynchronous, identical speed, and different speed are put forward; for the upstream section, a new method of equal-volume operation is introduced; and for the downstream section, three emergency operation methods are proposed. The simulation result of case study shows that the methods raised in this chapter can be used to determine suitable emergency operation measures.",signatures:"Jin Quan, Lingzhong Kong, Xiaohui Lei and Mingna Wang",downloadPdfUrl:"/chapter/pdf-download/64626",previewPdfUrl:"/chapter/pdf-preview/64626",authors:[{id:"280923",title:"Dr.",name:"Lingzhong",surname:"Kong",slug:"lingzhong-kong",fullName:"Lingzhong Kong"}],corrections:[{id:"64890",title:"Erratum - Emergency Operations of Sudden Water Pollution Accidents",doi:null,slug:"erratum-emergency-operations-of-sudden-water-pollution-accidents",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"64608",title:"Emergency Management System for Sudden Water Pollution Accidents",doi:"10.5772/intechopen.82020",slug:"emergency-management-system-for-sudden-water-pollution-accidents",totalDownloads:630,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The emergency management system for sudden water pollution accidents of the main canal is the integrated application of the aforesaid three key technologies and is the key to verify the effect of practical application of these technologies. 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Modern implantable devices (pacemakers, defibrillators, tools for continuous monitoring and resynchronization therapy) and treatment methods, including minimally invasive surgery (ablation, implantation), have been developed for managing cardiac rhythm and avoiding heart failure. In addition to electrical pacing, ablation is an effective minimally invasive surgical method for reducing and blocking arrhythmic phenomena, both as an independent treatment method or in conjunction with pacing therapy. 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He is also a member of the European Heart Rythm Association.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"62780",title:"Prof.",name:"Mart",middleName:null,surname:"Min",slug:"mart-min",fullName:"Mart Min",profilePictureURL:"https://mts.intechopen.com/storage/users/62780/images/system/62780.jpg",biography:"Mart Min is a full professor and leading scientist at the Thomas Johann Seebeck Department of Electronics, Tallinn University of Technology, Estonia. He received a Diploma Engineer’s qualification in Electronics from the same university in 1969, and a Ph.D. in Measurement Science from Kyiv Polytechnic, Ukraine in 1984. From 1992 to 1993 he was a guest scientist and professor at the Technical University of Munich and Bundeswehr University, Germany. From 2007 to 2010 he was a leading scientist at the international research group of the Institute of Bioprocessing and Analytical Measurement Technique, Germany. 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Dr. Cismaru began his electrophysiology fellowship at the Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, France, after finishing his cardiology certification with stages in Clermont-Ferrand and Dinan, France. He began working at the Rehabilitation Hospital\\'s Electrophysiology Laboratory in Cluj-Napoca in 2011. He is an experienced operator who can implant pacemakers, CRTs, and ICDs, as well as perform catheter ablation of supraventricular and ventricular arrhythmias such as ventricular tachycardia and ventricular fibrillation. He has been qualified in pediatric cardiology since 2022, and he regularly performs device implantation and catheter ablation in children. 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1. Introduction
Heavy metals are natural elements that have a high atomic weight and a density at least five times that of water, due to their high degree of toxicity, some such as Arsenic (As), Cadmium (Cd), Chromium (Cr), Lead (Pb), Copper (Cu), nickel (Ni), selenium (Se) Zinc (Zn) and Mercury (Hg) are considered harmful to health and the environment, raising concerns for setting up adequate prevention or restoration measures that reduce these risks. A special topic of global interest is the residual concentrations of heavy metals since some studies have shown that heavy metals, especially because are considered bioaccumulative in various matrices (range from ng kg−1 to less than 10 mg kg−1) [1].
These last components are generated mainly by human activities such as mining, emissions, agriculture, and industrial waste; some studies mention that in high concentrations heavy metals such as Cd, Cr, and Pb can have potential toxic effects, for example, some studies they have observed that they could interact with the to the growth and general metabolism of humans and animals [2]. Also, it was reported that mean concentrations of heavy metals could affect the biodiversity through their bioaccumulation in different organisms, although it has been observed that this also depends on the type of ecosystem, the exposure time and other environmental factors [3]; such as, some reports suggest that the disposal mechanisms could also depend on the balance between sorption and desorption, as well as the natural dynamics of the soils on which they are deposited, the soil constituents (inorganic and organic), and the chemical nature of the soil. Compound [4].
Many studies have found that waste dumps are sources of heavy metals, most have reported As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, although the receptor organs are diverse, due to the conditions of storage, disposal, and importance in food production, the treatment of soils and aquifers contaminated by these compounds has gained interest in the last decade [5, 6, 7]. The disposition that each of them could have to the environment, can be measured in terms of leachates, whose composition varies from one site to another since they regularly are created by the biodegradation of waste, in some cases, depending on their diffusion capacity in the soil, they could pollute both groundwater and surface water [8]. Numerous studies have emphasized the importance of remediating these sites, mentioning that feasible and long-term alternatives must be created, especially, that guarantee low exposure of these pollutants in places that have a population immersed or that are destined for activities of the primary sector [5].
Heavy metal contamination and pesticides is a serious problem worldwide due to their toxicity, furthermore, assessing the impacts is very complex due to the fact that many species have cumulative and non-biodegradable properties, but cases have been reported, in which certain species of plants could be indicators of these pollutants [6, 8]; also, although some organisms usually transport or extract them from a matrix, they only transform it to other oxidation states in the soil, in terms of bioremediation, some technologies take advantage of this behavior to reduce their mobility and toxicity, however, if they are not remediated sites, metals can reach humans [9, 10, 11].
However, although it has been shown that these methods tend to control various types of organic or inorganic pollutants in the long term [12, 13, 14], some studies have warned about the risk factor of those plant species that tend to be hyperaccumulative and can also be a food source for some grazing or wild species (it has been reported that the concentration of Cd or Pb metals in hyperaccumulating plants is usually between 10 and 100 times higher than that of the soil) [15, 16].
Vetiver grass is a perennial herb of the Poaceae family, native to India. It is a plant that has been cultivated for many years in Asia, especially in India [17], can grow in a wide range of climatic conditions, and if planted correctly can be used anywhere in tropical, subtropical or Mediterranean climates [18].
Compiled by Méndez-Cano [19]; the plant vetiver is a perennial herb that forms dense clumps Figure 1; it has sterile inflorescences and seeds and reproduces vegetatively It can withstand extreme droughts due to the high salt content in the sap of its leaves, it can withstand extreme droughts due to the high salt content in the sap of its leaves and also flooding for long periods. It grows in a wide range of soils with different levels of fertility, it is tolerant to extreme climatic variations, such as prolonged droughts, floods and temperatures ranging from −9–55°C. It grows in soils, including rocky soils, and can also be grown in hydroponic conditions. It tolerates pH levels between 3.3 and 12.5, as well as saline, acidic, alkaline and sodic media with a high load of nutrients and heavy metals. It is classified as a C4 type plant due to its high atmospheric CO2 fixation capacity.
Figure 1.
Chrysopogon zizanioides.
Recent research compares the variability in biomechanical properties of Chrysopogon zizanioides, including tensile strength, Young’s modulus and strain at break, which have a direct implication to root reinforcement to slope [20], interesting studies reveal that biomass extracted from the roots of the species can be used as activated carbon. This work offers an innovative and environmentally safe approach to control porosity in biomass-derived activated carbon (BAC) materials for energy storage applications [21]. Natural fibers as compared to synthetic fibers are having higher strength, rigidity and also in supporting the structural load of matrix. Vetiver fiber is used as reinforcement for the polymer composites with polypropylene and polyethylene as matrix material [22].
Authors demonstrate the application of vetiver grass has been widely promoted in tropical regions as a cost-effective and environmental-friendly solution for slope stabilization and erosion control for many years. Despite its potential, vetiver grass utilization has not been widely accepted by disadvantaged agricultural communities at landslide hazard areas [23].
Also floating Hydroponic System (FHS) is a potential and cost-effective technique for wastewater treatment. Vetiver is a more efficacious material for phytoremediation due to its physiological and morphological properties [24].
Although there are reports of several species discovered with high potential for phytoremediation, vetiver is a grass species that meets all the criteria required to eliminate contaminants in water and soil, but are few reports of use [12]; an important point is that this plant can survive under hydroponic conditions, has been used for a long time in water and soil conservation [25, 26, 27], in the rehabilitation and restoration of landfills, as in the phytoremediation of leachates, it survives under hydroponic conditions [28]. Many species have been reported as metal phytoremediators but few have been reported to be able to adapt to extreme altitude, climate, variable pH, and exposure conditions in eutrophic systems; thus, it is of great importance to continue studying native species to identify potential alternative phytoremediators [29]. For these reasons, in this study, we present a review of the importance of vetiver, its characterization, and its potential use as a remediation alternative.
2. General characteristics of vetiver (Chrysopogon zizanioides)
Vetiver belonging to the Poaceae family, native to India [19]. Is one of the few species of grass that meets all the criteria necessary to eliminate contaminants [28]. Regarding its morphological characteristics, it’s a tall grass (1–2 m) with abundant vegetative growth, characterized by a massive, finely structured and deep root apparatus, capable of reaching 3–4 m deep in the first year [27]. For this trait, vetiver grass is well known for its effectiveness in controlling erosion and sediments [30].
It has long, narrow leaves that produce a thick growth barrier that cuts and separates runoff water. This type of growth also allows vetiver to act as an effective filter by trapping sediments and contaminants linked to them such as heavy metals and some pesticide residues [31]. One of the most useful physiological characteristics of vetiver is its high tolerance to high concentrations of heavy metals such as Al, B, Ba, Be, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, S, Se, Tl, V, and Zn [12, 13, 19, 31, 32]. In Figure 2, shows a summary of the morphological characteristics of vetiver plant, and heavy metals to tolerant.
Figure 2.
Morphological characteristics of vetiver (C. zizainoides).
Some studies mention that the dense and finely structured root of this plant creates an ideal environment for microbiological processes in the rhizosphere, these characteristics also make vetiver a good alternative for stabilizing river banks and road embankments and preventing erosion [31]. However, the efficiency and cost-effectiveness in water and soil conservation, particularly in the treatment of wastewater, were only recognized in the decade of the 80s when its outstanding physiological and morphological characteristics were identified [31], but these distinctive features, make it an effective phytoremediator species for the treatment of various types of contaminants; also these attributes, together with its high biomass production, type of reproduction, and adaptations to climate changes, also make vetiver an ideal species for the phytoremediation not only of soil but also of artificial systems such as wetlands [12].
3. Methods for the characterization of heavy metals in phytoremediation
The different techniques applied for the characterization of heavy metals are presented in Table 1.
Technique
Characteristics
References
Atomic Absorption Spectroscopy (AAS)
Identify at least 70 elements in quantities as low as 10–14 g, high selectivity.
One of the techniques that can be used for the identification of heavy metals is Atomic Absorption Spectroscopy (AAS), this analytical technique is widely used to determine more than 70 elements in solution and in different matrices, in quantities as low as 10–14 g with reasonable selectivity, little manipulation, and minimum sample size. It can indirectly identify anions and organic compounds [33, 34]. This technique is older than ICP-OES (Inductively Coupled Plasma Optical Emission Spectroscopy), and various authors have reported studies comparative with other methods cited in environmental regulations [12, 28, 38], some mention that it makes it possible to quantitatively determine the chemical elements that constitute a material quickly, precisely, and accurately [7, 13, 39].
To convert solid and liquid samples into aqueous solutions for analysis with ICP-OES and AAS, it is necessary to eliminate all organic material to avoid interferences and obtain the analytes of interest at detectable concentrations [12, 38, 40, 41, 42, 43]. Acid digestion is a necessary process in the identification of metals, which is done by acid decomposition at high temperatures [36] or using mixtures of HNO3 and H2O2 [37].
Another method used is X-Ray Fluorescence spectroscopy (XRF). It can identify analytes or other components of interest and it is thus very useful for qualitative analysis. It is currently used in the fields of archeology, forensic sciences, medicine, geology, coatings, materials, electronics, pharmaceutics and environmental sciences, used this method to perform qualitative and quantitative analyses of heavy metals [35, 44].
4. Vetiver: potential use in phytoremediation
Several authors have achieved the mitigation of different types of heavy metals using vetiver grass (Table 2) and determined the amount of Cr absorbed from the residual sludge of a tanning facility and found a concentration of 596.92 mg kg−1 in the leaf tissue [38], others studies showed that the effect on vetiver of having a concentration of As of 225 mg kg−1 is a slight yellowing of the leaves and a small decrease in biomass [36]; these results confirm that this grass can survive successfully in soils moderately contaminated by As [31].
The capacity of vetiver to remove contaminants has also been tested using compost leachate, an experiment that was allowed to stand for 112 days without aeration, showed that the concentration of Cd, Cu, Fe, and Pb decreased after the treatment with vetiver, and therefore can be used to for the bio-purification of compost leachate [42]; others study evaluated the efficiency of vetiver in the absorption of metals based on the translocation and bioaccumulation factors, the results revealed that roots have a high uptake capacity for Cd, Pb, and Zn, however, there was a low translocation of metals such as Cd, As, Ni, and Pb towards the aerial part of the plant and accumulation of Zn in the roots was the highest at 100% [28].
However, some similar reports found a highs amount of Fe accumulated in the roots, despite this, the results show that vetiver is a good phythostabilizer and potential accumulator of heavy metals since in the roots they also found the presence of Al, Cu, Mn, Zn, Cr, and Ni, but in concentrations, inferiors to Fe [13]. In research similar, the absorbed metals were found to be in order Fe > Pb > Cu > Mn > Zn, the results also showed that as the length and density of the roots increases, so does the absorption of heavy metals, but suggest being careful if in the site intends to develop other species, due to the competition of Fe and its importance in the physiological processes of plants [12].
In 2007, a study assessed the efficiency of the vetiver grass in the phytoextraction of Cr, Cu, Pb, and Zn in order to establish whether this plant could be considered a good hyperaccumulator of those heavy metals. Phytoextraction experiments showed that vetiver was little efficient in the uptake of Cr and Cu (less than 0.1% in shoots and roots after 30 days for both metals), but highly efficient in the uptake of Pb and Zn (0.4% in shoots and 1% in roots for Pb and 1% in both shoots and roots for Zn, after 30 days), for these reasons, vetiver grass can be considered a good enough “hyperaccumulator” of Pb and Zn [41].
In 2013, other researchers measured the ability to remove heavy metals from industrial wastewater. Vetiver were grown on four samples of industrial wastewater taken from a milk factory, a battery manufacturing plant, an electric lamp plant, and an ink manufacturing plant, the results indicated that could tolerate and grow in wastewater [24].
On the other hand, some studies have evaluated the efficiency of vetiver in the treatment of leachates with the aim of reducing chemical oxygen demand, total suspended solids, total dissolved solids and total organic carbon in municipal landfill leachates. The results revealed a removal efficiency of approximately 90% [45]. A relevant study evaluated the differences in tolerance and accumulation of boron between reed (Phragmites australis L.), cattail (T. latifolia L.) and vetiver, these plants survived concentrations of B of up to 250, 500, and 750 mg L−1, respectively, therefore, vetiver showed the highest tolerance to B [40]. Thus, the evidence described above confirms the phytoremediation potential of the vetiver grass, the findings of different studies have confirmed the potential of vetiver as a phytoremediation plant for use in the removal of heavy metals from contaminated soils [12, 46, 47] and in the rehabilitation of landfills [35]. Although it is not an aquatic plant, vetiver can grow and survive under hydroponic conditions [48] and can be used to remediate eutrophic waters, wastewater from pig farms [49], and waste leachates [50].
Further studies could focus on increasing the uptake of heavy metals using, for example, chelating agents [41] and explore the ability of vetiver to participate in the remediation of other pollutants such as endosulfan [49]. The dense growth of vetiver roots can prevent erosion and landslides and act as a natural barrier that could be used in landfill cells to prevent leachates from infiltrating the aquatic mantle, regardless of the impermeable barrier (geomembrane) that is commonly used in landfills.
5. Conclusions
The new trends in the restoration of degraded soils, wastewater and even leachates generated from urban waste include phyto-management as part of a Circular Economy model which is an attractive and viable alternative that is already being explored by different companies; it is based on the principles of preservation and optimization of natural resources, as well as improving the efficiency of production systems by eliminating or reducing environmental contaminants. Therefore, phytoremediation can be considered a circular economy strategy because it aims to reduce both the entry of materials and the production of waste.
In different matrices water, soil, air there are inorganic contaminants which include trace elements that are essential for the growth and development of plants, heavy metals and some non-metallic elements such as As and B are also included. Toxicity varies according to many factors, such as the chemical form of the elements, concentration, persistence among other factors, some compounds can be transformed to their less toxic forms such as Cr. Chrysopogon zizanioides is a hyper-accumulator species with a sometimes unpleasant appearance and its growth capacity makes it ideal for phytoremediation.
Based on group experience we know that this species can survive, tolerate, absorb and transform. Also based on the literature we know that there must be periods of acclimatization of the species for its transformation and or ideal absorption of the compounds. Due to previous knowledge about the phytoremediation process, which is an integral methodology where at the same time the species phytovolatilizes, rhizofiltration, phytodegrades. Due to the characteristics of the species, it can be a permeable membrane to prevent or sequester toxic elements to the water table, but thanks to the life cycle of this species it can absorb significantly contaminated by its modular growth. However, dead leaves may contain some compounds that cannot be degraded and these should be confined or incinerated to ensure that they do not return to the soil.
The essential oil extracted from vetiver roots can be used in the perfume industry, vetiver leaves can be used for roofing of rustic houses and the plant is already used as a fire barrier because it keeps growing even after being burned. In addition, the use of vetiver has the purpose of improving the management of degraded spaces and their restoration through innovative phytoremediation techniques. Vetiver could be used in many countries throughout the world due to its economical accessibility and ability to adapt to different climatic conditions, as well as its capacity to remove different types of pollutants as has already been evidenced.
Acknowledgments
Grateful for the postgraduate scholarship from the National Council of Science and Technology (CONACyT) -Mexico (430983), the Catedra-CONACyT 781 and DAIP-UGto Project # 811/2016. The authors also thank Promotora Ambiental (S.A. de C.V.) for the financial support provided and for the permission to use their facilities.
Conflicts of interest
The authors declare no conflict of interest.
Nomenclature
Al
aluminum
B
boron
Ba
barium
Be
beryllium
Cd
cadmium
Co
cobalt
Cr
chromium
Cu
copper
Fe
iron
Mg
magnesium
Mn
manganese
Ni
nickel
Pb
lead
S
sulfur
Se
selenium
Tl
thallium
V
vanadium
Zn
zinc
\n',keywords:"vetiver, leachate, phytoremediation, metals, hyperaccumulation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/76888.pdf",chapterXML:"https://mts.intechopen.com/source/xml/76888.xml",downloadPdfUrl:"/chapter/pdf-download/76888",previewPdfUrl:"/chapter/pdf-preview/76888",totalDownloads:158,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:33,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"April 25th 2021",dateReviewed:"May 4th 2021",datePrePublished:"May 24th 2021",datePublished:"April 20th 2022",dateFinished:"May 24th 2021",readingETA:"0",abstract:"Many researchers have demonstrated the advantages of plants in the phytoremediation of soils and waters contaminated with heavy metals, herbicides, pesticides, leachates, etc. The unique morphological characteristics of Chrysopogon zizanioides, commonly known as vetiver, make it a hyperaccumulator of metals; its roots can store high concentrations of heavy metals such as As, Cd, Cr, Cu, Hg, Ni, Pb, Se, and Zn, and it has thus been successfully used in the field of environmental protection. This chapter presents the importance of vetiver, its characterization, and its potential use as phytoremediation potential for toxic elements in contaminated matrices.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/76888",risUrl:"/chapter/ris/76888",book:{id:"10681",slug:"biodegradation-technology-of-organic-and-inorganic-pollutants"},signatures:"Sebastián A. Ramos-Arcos, Edith G. González-Mondragón, Eduardo S. López-Hernández, Ana R. Rodríguez-Luna, Carlos M. Morales-Bautista, Selene Lagunas-Rivera and Sugey López-Martínez",authors:[{id:"347802",title:"Ph.D.",name:"Carlos M.",middleName:null,surname:"Morales-Bautista",fullName:"Carlos M. Morales-Bautista",slug:"carlos-m.-morales-bautista",email:"carlos.morales@ujat.mx",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"418682",title:"Dr.",name:"Selene",middleName:null,surname:"Lagunas-Rivera",fullName:"Selene Lagunas-Rivera",slug:"selene-lagunas-rivera",email:"dummy+418682@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"418683",title:"Dr.",name:"Sugey",middleName:null,surname:"López-Martínez",fullName:"Sugey López-Martínez",slug:"sugey-lopez-martinez",email:"dummy+418683@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"418684",title:"Dr.",name:"Sebastian A.",middleName:null,surname:"Ramos-Arcos",fullName:"Sebastian A. Ramos-Arcos",slug:"sebastian-a.-ramos-arcos",email:"dummy+418684@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"418685",title:"Dr.",name:"Edith G.",middleName:null,surname:"González-Mondragón",fullName:"Edith G. González-Mondragón",slug:"edith-g.-gonzalez-mondragon",email:"dummy+418685@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"418686",title:"Dr.",name:"Eduardo S.",middleName:null,surname:"López-Hernández",fullName:"Eduardo S. López-Hernández",slug:"eduardo-s.-lopez-hernandez",email:"dummy+418686@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"418687",title:"Dr.",name:"Ana R.",middleName:null,surname:"Rodríguez-Luna",fullName:"Ana R. Rodríguez-Luna",slug:"ana-r.-rodriguez-luna",email:"dummy+418687@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. General characteristics of vetiver (Chrysopogon zizanioides)",level:"1"},{id:"sec_3",title:"3. Methods for the characterization of heavy metals in phytoremediation",level:"1"},{id:"sec_4",title:"4. Vetiver: potential use in phytoremediation",level:"1"},{id:"sec_5",title:"5. Conclusions",level:"1"},{id:"sec_6",title:"Acknowledgments",level:"1"},{id:"sec_9",title:"Conflicts of interest",level:"1"},{id:"sec_8",title:"Nomenclature",level:"1"}],chapterReferences:[{id:"B1",body:'Tchounwou, P. B.; Yedjou, C. G.; Patlolla, A. K.; & Sutton, D. J. Heavy metal toxicity and the environment. Molecular, clinical and environmental toxicology. 2012; 133-164. DOI: 10.1007/978-3-7643-8340-4_6'},{id:"B2",body:'Subhashini, V.; & Swamy, A. V. V. 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DOI: 10.1007/s11356-019-04505-7'},{id:"B31",body:'Truong, P. Vetiver system for environmental protection. Vetican Consulting, Brisbane. 2019'},{id:"B32",body:'Cruz López, C. A. D. L.; Ramos Arcos, S. A.; & López Martínez, S. Efecto de la adición de ácidos orgánicos sobre la bioacumulación de Plomo, Talio y Vanadio en Chrysopogon zizanioides creciendo sobre suelos contaminados de un relleno sanitario. Nova scientia. 2018; 10(21), 403-422. DOI: 10.21640/ns.v10i21.1582'},{id:"B33",body:'Ogunfowokan, A. O.; Adekunle, A. S.; Oyebode, B. A.; Oyekunle, J. A. O.; Komolafe, A. O.; & Omoniyi-Esan, G. O. Determination of heavy metals in urine of patients and tissue of corpses by atomic absorption spectroscopy. Chemistry Africa. 2019; 2(4), 699-712. DOI: 10.1007/s42250-019-00073-y'},{id:"B34",body:'Paul, V.; Pandey, R.; Ramesh, K. V.; & Meena, R. C. Atomic Absorption Spectroscopy (AAS) for Elemental Analysis of Plant Samples. 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Food Chemistry. 2019; 273, 159-165. DOI: 10.1016/j.foodchem.2017.12.074'},{id:"B38",body:'Torres Rodríguez, D.; Cumana, A.; Torrealba, O.; & Posada, D. Uso del vetiver para la fitorremediación de cromo en lodos residuales de una tenería. Revista Mexicana de Ciencias Agrícolas. 2010; 1, 175-188'},{id:"B39",body:'Cedeño Ochoa, C. J. Metales en agua por Plasma Acoplado por Inducción (Cd, Cr, Cu, Ni, Pb, Zn). Instituto de Hidrología, Meteorología y Estudios Ambientales. Ministerio de Ambiente, Vivienda y Desarrollo Territorial-República de Colombia. 2006'},{id:"B40",body:'Xin, J.; & Huang, B. Comparison of boron uptake, translocation, and accumulation in reed, cattail, and vetiver: an extremely boron-tolerant plant, vetiver. Plant and Soil. 2017; 416, 17-25. DOI: 10.1007/s11104-017-3186-0'},{id:"B41",body:'Antiochia, R.; Campanella, L.; Ghezzi, P.; & Movassaghi, K. The use of vetiver for remediation of heavy metal soil contamination. Analytical and bioanalytical chemistry. 2007, 388, 947-956. DOI: 10.1007/s00216-007-1268-1'},{id:"B42",body:'Ibezute, A. C.; Tawari-Fufeyin, P.; & Oghama, O. E. Analysis of pollution removal from compost leachate by vetiver grass (L.) Nash plant (Vetiveria zizanioides). Resources and Environment. 2014; 4, 268-273'},{id:"B43",body:'Benavides Montoya, A. Problemática y alternativas tecnológicas para la remoción de arsénico en la obtención de agua potable. Curso impartido en el Centro de Investigación de Materiales Avanzados. México. 2013'},{id:"B44",body:'Hansen, T. H.; Laursen, K. H.; Persson, D. P.; Pedas, P.; Husted, S.; & Schjoerring, J. K. Micro-scaled high-throughput digestion of plant tissue samples for multi-elemental analysis. Plant Methods. 2009; 5, 12. DOI: 10.1186/1746-4811-5-12'},{id:"B45",body:'Pazoki, M.; Abdoli, M. A.; Karbassi, A.; Mehrdadi, N.; & Yaghmaeian, K. Attenuation of municipal landfill leachate through land treatment. Journal of Environmental Health Science and Engineering. 2014; 12(1), 12. DOI: 10.1186/2052-336X-12-12'},{id:"B46",body:'Kočevar Glavač, N.; Djogo, S.; Ražić, S.; Kreft, S.; & Veber, M. Accumulation of heavy metals from soil in medicinal plants. Arhiv za Higijenu Rada i Toksikologiju. 2017; 68, 3, 236-244. DOI: 10.1515/aiht-2017-68-2990'},{id:"B47",body:'Borowczak, M.; & Hołtra, A. The content of heavy metals in soils and plants around the waste landfill in Siechnice (Poland). In E3S Web of Conferences 2017. Vol. 17. EDP Sciences. DOI: 10.1051/e3sconf/20171700009'},{id:"B48",body:'Xia, H.; Liu, S.; & Ao, H. A study on purification and uptake of garbage leachate by vetiver grass. In: Proc. of the 2nd International Conference on Vetiver, Thailand. 2000'},{id:"B49",body:'Abaga, N. O. Z.; Dousset, S.; Munier-Lamy, C.; & Billet, D. Effectiveness of vetiver grass (Vetiveria zizanioides L. Nash) for phytoremediation of endosulfan in two cotton soils from Burkina Faso. International Journal of Phytoremediation. 2014; 16, 95-108. DOI: 10.1080/15226514.2012.759531'},{id:"B50",body:'Kong, X.; Lin, W.; Wang, B.; & Luo, F. Study on vetiver’s purification for wastewater from pig farm. In Proc. Third International Vetiver Conference, Guangzhou, China. 2003'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Sebastián A. Ramos-Arcos",address:null,affiliation:'
University Juárez Autonomous of Tabasco, México
'},{corresp:null,contributorFullName:"Edith G. González-Mondragón",address:null,affiliation:'
Institute of Agroindustry, Technological University of the Mixteca, Mexico
'},{corresp:null,contributorFullName:"Eduardo S. López-Hernández",address:null,affiliation:'
University Juárez Autonomous of Tabasco, México
'},{corresp:null,contributorFullName:"Ana R. Rodríguez-Luna",address:null,affiliation:'
University Juárez Autonomous of Tabasco, México
'},{corresp:null,contributorFullName:"Carlos M. Morales-Bautista",address:null,affiliation:'
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1. Introduction
Highlights
Within TB drug discovery, drug repurposing is a growing field and has established several viable candidates from ‘old’ drugs for further investigation.
Drug repurposing for TB could improve therapeutic interventions in low to middle income countries and is an ideal approach due to the saving of time, effort, and most importantly, money.
The use of computational techniques, including virtual screening of known drugs, have been shown to accelerate the process.
This approach has the potential to lead to the identification of novel drug targets in M. tuberculosis, which could initiate new target-based discovery programs.
Tuberculosis (TB) has been, and continues to be a global health threat, and remains the leading cause of death due to a single infectious agent (M. tuberculosis), having claimed ~1.4 million lives in 2019 alone [1]. In the past 2 years, the Covid-19 pandemic has further exacerbated the threat of TB mainly due to a decrease in TB case detection, with trajectories predicting an increase of ~1 million additional new cases per year from 2020 to 2025 [1]. Furthermore, considering the increasing prevalence of drug resistant (DR) (Rif resistant-RR, multidrug resistant-MDR, and extensively drug resistant- XDR) forms of TB infections, the need for more effective treatment strategies has not been direr. The current standard treatment regimen for drug-susceptible (DS) TB has been in use for decades and includes a combination of four drugs: isoniazid (Inh), rifampicin (Rif), ethambutol (Emb) and pyrazinamide (Pza) for 2 months and a further 4 months of only Inh and Rif (Figure 1 [2, 3]). The treatment of DR-TB is more complicated and can take up to 18 months, depending on the resistance profile of the infection. Although available, several challenges are faced during the treatment of TB disease. Most notable is the duration and complexity of treatment, toxicity and in the case of HIV-TB coinfection, the possible adverse interactions between anti-TB drugs and antiretrovirals. Despite these challenges, treatment success rates of 85% and 57% have been reported for DS- and DR-TB respectively in 2019 [1]; however, these will not be sufficient to meet the milestones setup as part of the End TB Strategy which include a 90% reduction in incidence rates and 95% reduction in mortality by 2035 compared to 2015 [4]. Optimization and implementation of innovative tools including new drug and treatment regimens are predicted to significantly improve this outlook.
Figure 1.
Current drugs used for the treatment of TB. Adapted from [2, 3] (CC BY 2.0).
The past 20 years have seen considerable progress in the TB drug discovery arena, with 13 new compounds currently in clinical trials (https://www.newtbdrugs.org/pipeline/clinical). The highlights of TB drug discovery include Bedaquiline (Bdq), Delamanid and, most recently, Pretomanid (PA-824). Within the last 9 years, these were the first three new drugs to be approved for the treatment of TB since the discovery of Rif in the 1960’s. Although currently only approved for the treatment of DR-TB, both Bdq and PA-824 are being tested as part of novel combination regimens for the treatment of DS-TB. Further highlighting the progress of the TB drug discovery field, the pre-clinical pipeline is also rich in new compounds.
The current scope of the drug discovery and development pipeline is promising; however, the development of a novel drug is a complicated, laborious, and expensive endeavour. From initial screening to clinical usage, the development of a new compound can take up to 15 years and cost more than $1 billion (Figure 2) [5, 6]. In addition, there is a high attrition rate of hit compounds during the discovery cascade and clinical trials, further adding to the difficulty of getting novel antimicrobials into the clinic [5, 6, 7]. To overcome some of the challenges faced during conventional drug discovery programs, a strategy that has been gaining more interest in recent years is “Drug Repurposing”.
Figure 2.
A comparison of the time taken to get into the clinic when using a traditional drug discovery approach versus a drug repurposing approach. ADMET: Absorption, distribution, metabolism, excretion and toxicity. Adapted from [5].
Drug repurposing is the process of identifying novel uses of existing drugs for the treatment of disease outside of the scope of the original medical indication. It is also referred to as drug repositioning, redirecting, re-tasking, reprofiling or recycling [8, 9]. This strategy offers several advantages over a conventional drug discovery approach, including (i) reduced risk of failure, (ii) quicker development times, (iii) less investment and lower average costs, and (iv) the possibility of identifying new targets and/or pathways for further investigation (Figure 2) [8, 9, 10]. Drug repurposing has been successfully applied to several diseases and conditions including HIV, cancer and arthritis [9]. While offering notable advantages over a conventional approach, candidate compounds discovered via drug repurposing are still subject to regulatory requirements prior to therapeutic implementation. These requirements include compound acquisition and licencing, development/optimization for the new application via clinical trials and registration with the relevant regulatory bodies (Figure 2).
Repurposing is not new to the treatment of TB. The backbone of the current regimen, Rif, belongs to the rifamycin group of antibiotics [11]. Rifamycins were originally developed for broad-spectrum antibacterial activity and through structure–activity relationship studies, was shown to have the greatest growth inhibitory effect against mycobacteria [11, 12]. The mechanism of action (MoA) of rifamycins involves the inhibition of DNA-dependent RNA polymerase, thus interfering with transcription. While the main application is for DS-TB, Rif has also been used for other bacterial infections e.g. treatment of staphylococcal endocarditis, eradication of group A beta-hemolytic streptococci from pharyngeal carriages and as prophylaxis for close contacts of paediatric patients with Haemophilus influenzae or Neisseria meningitidis infections [13]. In recent years, drug repurposing has once again gained traction for novel TB treatments, evidenced by 6 different repurposed drugs currently being evaluated in Phase II or III clinical trials [1]. Following an analysis of the published literature related to drug repurposing for TB, the repurposed drugs that are currently in the pre-clinical and clinical pipeline, their molecular mechanisms and therapeutic applications will be discussed further.
2. State of the art
In order to assess what the current scientific field entails, a network analysis was conducted from the Web of Science database (All Databases) using the search terms: repurpose* (repurposed, repurposing), tuberculosis and drug* (drugs). A total of 424 publications were identified within the search criteria and it is evident from Figure 3 that there has been an increase in research involved with the repurposing of old drugs in the fight against TB. In 2020, 77 manuscripts were published related to this topic, and this is expected to further increase in 2021. Additionally, VOS viewer, was used to assess specific keywords within the total number of publications (https://www.vosviewer.com/). The co-occurrences of all keywords were counted using a full counting method. The minimum keyword occurrence was set to three and out of the 416 identified keywords, 35 met the selection criteria. The third most occurring keyword, after “M. tuberculosis” and “Tuberculosis”, was “in vitro”, which indicates that this field of enquiry is still at an early stage (Figure 4). This is reiterated by the increase in publications on repurposing in recent years (Figure 3) as well as the identification of “drug repositioning” in Figure 5. Interestingly, the only drug that satisfied the selection criteria was thioridazine, an antipsychotic drug. It would be expected that additional repurposed drugs will occupy this space as more data becomes available and clinical trials are completed.
Figure 3.
A steady incline in recent years of the number of scientific articles, related to the search topic “repurposing drugs for tuberculosis”. The bars represent the number of published articles according to year. The year 2020 accounts for 18.2% of the published articles related to this topic. (web of science (https://www.webofknowledge.com)).
Figure 4.
Bibliographic network analysis of the keywords in published scientific articles, using the search terms “repurposing drugs for tuberculosis” (web of science – All databases). The circles indicate 35 of the most re-occurring keywords, while the size of the circles represents the importance of the keyword. The lines represent the interconnectivity of the keywords (www.vosviewer.com).
Figure 5.
A time-correlation analysis of the published material related to the search terms. An increase in articles mentioning “drug repurposing”, “host-directed therapies” and “adjunctive therapy” can be seen. A trend towards computational approaches, including “docking” is also evident (www.vosviewer.com).
3. Repurposed drugs in the clinical development pipeline
There are approximately thirty chemical compounds currently being investigated in the global TB drug pipeline, of which 15 are classified as repurposed and will be discussed further.
3.1 Linezolid, Sutezolid, Delpazolid and TBI-223
Linezolid, also known as Zyvox, is a first-generation oxazolidinones which are a class of antibiotics that inhibits bacterial protein synthesis. Linezolid works by binding to a site on the bacterial ribosome thereby preventing the formation of a functional 70S ribosomal unit which is an essential component of the bacterial translation process [14, 15, 16, 17]. Linezolid was initially approved for the treatment of infections originating from Gram-positive bacteria and used primarily in the treatment of complicated skin infections such as methicillin-resistant Staphylococcus aureus (MRSA). Although linezolid exhibits good antimycobacterial properties, its use is limited to DR-TB as its long term toxicity profile have been associated with neurological disorders resulting from nerve damage as well as immunosuppression resulting from decreased production of vital immune cells required for host defence [16, 17]. Analogues of Linezolid namely Sutezolid, Delpazolid, Posizolid, Contezolid and TBI-223 are second-generation oxazolidinones that are showing promising potential as antimycobacterial agents. This is due to enhanced safety profiles and reduced toxicity compared to Linezolid as well as more potent activity against mycobacteria in vitro. Studies and clinical trials for these analogues are ongoing with the hopes that they may also be effective in shortening current TB treatment regimens [16, 18, 19].
3.2 Moxifloxacin, Gatifloxacin, levofloxacin and DC-159a
Moxifloxacin and Gatifloxacin are fourth-generation broad-spectrum antibiotics belonging to the family of fluoroquinolone drugs. The main function of this class of antimicrobials is to inhibit the bacterial enzymes DNA gyrase and topoisomerase IV which are crucial for DNA duplication events such as transcription, recombination and cell replication [16, 18, 19]. They were initially approved for the treatment of a number of bacterial infections of the skin, stomach and lungs and along with levofloxacin has also shown promise as an effective and safe candidate for inclusion in the current TB treatment regimen [16, 20]. This is mainly because of their potent antimycobacterial activity as studies have shown that they can significantly improve sputum culture conversion rate and clinical outcome of TB treatment as well as reduce TB resurgence after treatment [17, 21]. These antimicrobials are currently being evaluated as a possible replacement for Isoniazid or Ethambutol in patients with poor tolerability as they were shown to exhibit potent antimycobacterial activity in vitro [16]. Moxifloxacin, Gatifloxacin and Levofloxacin are the most commonly prescribed fluoroquinolone drugs used to treat patients with MDR-TB. Despite these analogues displaying enhanced antimycobacterial activity in vitro and in vivo, levofloxacin was shown to be more cost-effective, and therefore more accessible in resource-limited high burden settings [18]. In comparison to moxifloxacin, gatifloxacin and levofloxacin, DC-159a, a relatively new fluoroquinolone analogue was shown to exhibit enhanced bactericidal activity against MDR-TB both in vitro and in vivo and may therefore be a promising new therapeutic candidate for reducing treatment time for both MDR- and drug-sensitive (DS)-TB [22, 23].
3.3 Clofazimine and TBI-166
Clofazimine is an antibiotic belonging to the class of Riminophenazines that is currently approved for the treatment of leprosy [19, 24]. Clofazimine possesses both antimicrobial and anti-inflammatory properties and although its mechanism of action is still unclear, the outer membrane of bacteria appears to be the primary target of this inhibitor [19]. Although Clofazimine has shown good activity against MDR- and XDR-TB, its efficacy in humans is still under investigation specifically concerning long term use and its major adverse effect of causing skin discoloration [25]. Clofazimine is mainly utilised in combination with other drugs in the second-line treatment of drug-resistant TB and has been classified as a Group 5 medicine by the WHO [24]. TBI-166 a new generation analogue of Clofazimine was demonstrated to exhibit superior antimycobacterial activity in comparison to its predecessor as well as reduced skin discoloration and is currently in a Phase 1 clinical trial [25, 26].
3.4 Sanfetrinem (Trinem beta-lactam)
Sanfetrinem cilexetil is an orally available tricyclic beta-lactam developed by Glaxo Smith Kline (GSK) in the early 1990’s with broad antibacterial activity on both Gram-negative and Gram-positive bacteria. The development of this drug was halted after phase 2 clinical trials. However, it has recently been identified as a potential beta-lactam against M. tuberculosis, with an MIC of 1.5 μg/mL against H37Rv and an intracellular MIC of 0.5 μg/mL in THP1 monocytes. Furthermore, it has been reported that the drug showed potent activity against a range of susceptible and resistant clinical isolates with an MIC90 of 1–4 μg/mL. In an in vivo investigation, sanfetrinem cilexetil was comparable to meropenem and amoxicillin/clavulanate [27]. Similar to other carbapenems, it targets the cell wall by inhibiting the formation of peptidoglycan [28]. This drug is currently under pre-clinical investigation with a planned phase 1 clinical trial.
3.5 Spectinamide 1810 (Spectinamide)
Spectinamides are semisynthetic derivatives of spectinomycin with a narrow spectrum activity against M. tuberculosis and present its activity through selective inhibition of the bacterial S16 ribosomal subunit. One factor that contributes to their potent antitubercular activity is the evasion of efflux through the Rv1258c efflux pump. This feature makes spectinamides promising candidates against MDR TB, which have been shown to upregulate efflux pumps [29]. Two derivatives, 1599 and 1810 were investigated for their combinational effect in an infected mice model co-currently administering different combinations of the derivatives with Bdq, Emb, Inh, levofloxacin, linezolid, moxifloxacin, PA-824, Pza, and Rif. The researchers showed that spectinamide 1599 showed synergistic activity in combination with rifampicin and pyrazinamide [30]. Spectinamide 1810 is currently in pre-clinical investigation and being developed by Microbiotix, Inc.
3.6 Meropenem, Faropenem (Carbapenem Beta-lactam)
Meropenem is a carbapenem-type beta-lactam antibiotic which has shown bactericidal activity against susceptible and resistant M. tuberculosis strains. In combination with clavulanate, it was able to sterilise cultures within 14 days [31]. Meropenem is used in the treatment of a variety of bacterial infections. One phase 2 clinical trial on newly diagnosed TB has been completed, and an additional two trials are currently recruiting suitable candidates.
3.7 Thioridazine (phenothiazine)
Thioridazine was a drug used in the treatment of anxiety disorders and schizophrenia. Manufactured by Novartis, it was removed from the market in 2005 due to associated cardiac arrhythmias and other adverse effects. The removal of this drug had a devastating effect on patients being treated for schizophrenia, and a study in Finland indicated a doubling of hospital admitted relapsed patients after the withdrawal of the drug [32]. Thioridazine was coincidentally the only drug that appeared in the network analysis on the topic of repurposing drugs for TB (Figures 2 and 3). It has shown in vitro bactericidal activity against susceptible and resistant strains of M. tuberculosis as well as intracellular activity on human macrophages with limited cellular toxicity [33, 34]. A retrospective study on a trial conducted in Argentina on 17 XDR-TB patients revealed the potential use of this drug in a last-resort treatment. Thioridazine was combined with linezolid and moxifloxacin. Although clinically relevant adverse effects (neurotoxicity and haematological disorders) were observed, and two patients had to have the treatment halted, the combination was able to achieve negative cultures in 15 patients and status of “cured” in 11 patients. The authors have recommended the use of this combination for compassionate use [35].
4. Repurposed drugs in discovery
Numerous ongoing projects are in pre-clinical development across the globe, with collaborative research groups spanning across both industry and academia. Many of these groups form part of the Tuberculosis Drug Accelerator (TBDA) program. Selected repurposed drugs that are currently in pre-clinical development, and which have been assessed in vitro or in vivo will be discussed further. It is worth noting that several computational screening programs of approved drugs are also ongoing against known targets in M. tuberculosis.
4.1 Carprofen and Oxyphenbutazone
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that are generally used to relieve pain and reduce inflammation, mainly functioning by inhibiting the activity of cyclooxygenase enzymes involved in the regulation of inflammation and blood clotting [19]. In mouse models of TB, the common NSAIDs namely aspirin and ibuprofen were shown to decrease both the size and number of lung lesions and bacillary load as well as improve survival rates [36]. Studies have revealed that analogues in this family namely Carprofen and Oxyphenbutazone were found to exhibit bactericidal activity against mycobacteria through inhibition of mycobacterial drug efflux mechanisms and biofilm growth [19, 36]. Both their antimicrobial and anti-inflammatory properties combined with their low likelihood of adverse effects following administration make them very strong candidates for repurposing as TB treatment.
4.2 Disulfiram
Disulfiram is a nontoxic drug belonging to the family of Carbamates. It is primarily used to treat chronic alcohol addiction, but has demonstrated potent antimycobacterial activity against clinical isolates, MDR and XDR strains [19, 37]. Moreover, it was demonstrated that the bactericidal activity of Disulfiram is synergistically enhanced in the presence of the metal ion copper, with the mechanism of action of this compound still under investigation [37].
4.3 Metformin (Biguanides)
Metformin, a biguanide drug approved for glycaemic control in patients suffering from Type II diabetes mellitus, falls within the group of host-directed therapies against TB. Multiple adjunctive activities have been investigated. In vitro studies have shown a potentiation of the standard TB drugs, an increased immune response and mediation of phagosome-lysosome fusion. The phagolysosome fusion leading to the inhibition of bacterial growth is due to the expression of AMP-activated protein kinase, which in turn increases the production of mitochondrial reactive oxygen species (mROS) [38, 39]. The adjunctive properties and potential in TB treatment have been captured in two reviews [40, 41]. A phase II clinical trial investigating the safety and tolerability of metformin in TB/HIV patients is yet to start, and the investigation is planned to be completed in 2024.
4.4 Metronidazole (Nitroimidazole)
Metronidazole is a broad-spectrum antibiotic used in the treatment of gastrointestinal infections. Some parasitic infections including amebiasis, giardiasis and trichomoniasis are also treated by this drug [42]. The exact mechanism of this drug has not been fully elucidated, but it has been hypothesised that the drug renders its action through the blocking of nucleic acid synthesis via an intermediate of metronidazole and through the production of a toxic metabolite in anaerobic bacteria through the reduction of the nitro group by the redox potential of the electron transport chain [43]. It has been shown that metronidazole was able to inhibit the growth of mycobacterial bacilli under anaerobic non-replicating conditions but showed no activity under aerobic conditions [44]. In vivo studies in macaques (a non-human primate model), showed similar efficacy of inhibiting reactivation of latent TB, as compared to a combination of isoniazid and rifampicin [45]. In a phase 2 clinical trial investigating the effect of metronidazole vs. placebo on pulmonary MDR-TB, some efficacy was observed in sputum smears after 1 month of treatment, but the benefit was not sustained past 2 months of treatment. The study was ultimately halted due to the occurrence of peripheral neuropathies within the test subject group [46]. Although metronidazole is associated with several adverse effects, other and newer nitroimidazoles are extremely important within the clinical pipeline against TB. These include pretomanid and delamanid which are both part of multiple phase 2 and 3 clinical trials.
Entacapone and tolcapone are two catechol-O-methyltransferase inhibitors used as an adjunct in the treatment of Parkinson’s disease. Both have shown some activity against M. tuberculosis with a relatively high minimum inhibitory concentration (MIC) of 260 μM observed for entacapone, which was significantly lower than the cytotoxic concentration [47]. Their proposed mechanism against TB is what makes these molecules an interesting class to investigate. The mechanism is similar to isoniazid; however, they do not need enzymatic activation to bind to the enoyl–acyl carrier protein reductase (InhA) target. Furthermore, it has been proposed that it might be a possible treatment in MDR-TB, as it could evade the KatG activation associated with isoniazid resistance in many resistant strains [19, 47].
5. Target-based repurposing
An additional benefit of drug repurposing is the potential to identify or validate vulnerable targets and/or pathways that can be exploited for further drug development [8, 9, 10]. Bortezomib is the first human proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma [48]. Using a target mechanism-based whole-cell screen, bortezomib was identified as an inhibitor of the mycobacterial caseinolytic protease (ClpP1P2), with growth inhibitory activity, thus validating it as a druggable target [49]. Further investigations have focused on structural modifications of bortezomib to increase selectivity for the mycobacterial ClpP1P2 complex over the human proteasome while maintaining antimycobacterial activity [49, 50, 51]. The M. tuberculosis DosRST two-component regulatory system is important for survival under non-replicating conditions which is thought to contribute to the required prolonged therapy for TB, and is therefore considered a promising target for drug development [52]. Artemisinin is used for the treatment of Malaria and was identified as an inhibitor of M. tuberculosis DosRST during a whole-cell phenotypic high throughput screen and is currently in the hit-to-lead phase of drug development [52, 53]. In addition to the identification of promising repurposed drugs by whole-cell screening, recent efforts have focused on computational modelling and virtual screening of known drugs against targets of interest. Using this approach two drugs were identified as inhibitors of M. tuberculosis DNA gyrase (GyrB): echinacoside which has been investigated for the treatment of Parkinsons and Alzheimers, and epirubicin which is a treatment for breast cancer [54, 55, 56]. Virtual screening has also identified Sulfadoxine, Pyrimethamine, Lifitegrast and Silfenadil as inhibitors of M. tuberculosis MurB or MurE, enzymes involved in peptidoglycan synthesis [57].
6. Conclusion and future prospects
The need for novel treatment strategies for TB is becoming more urgent if the goal of a TB-free world is to be realised. While the current treatment regimens have a success rate of 85% for DS-TB, there is, unfortunately, an increase in the incidence of DR-TB, which only has a treatment success rate of 57% and harsh side-effects for patients [1]. The drug discovery pipeline is relatively rich with new material; however, the conventional screening and development strategies have led to the identification of multiple chemical scaffolds that inhibit the same targets, referred to as promiscuous targets e.g. DprE1, MmpL3 and QcrB [58]. Furthermore, the global economic climate has significantly reduced the available funding for scientific research and due to the low return on investment, several pharmaceutical companies no longer support in-house drug discovery programs for infectious diseases [6], further hampering the quest for new drugs with novel targets. To this end, drug repurposing provides an appealing strategy with several advantages as outlined above. The success of Rif, Linezolid and the fluoroquinolones provides strong support for drug repurposing for the treatment of TB. The high number of repurposed drugs in the discovery phase of compound development and in advanced clinical trials suggests that this strategy is becoming more widely accepted in the TB research community and has good potential for success. Furthermore, with the continual advances in computational biology and open sharing of compound data across disease areas, it is not unreasonable to expect a boost in drug repurposing research in the future. This could possibly further reduce the time and cost to develop repurposed TB drugs, and aid in trying to meet the global goals of eradicating TB.
Acknowledgments
V. S. acknowledges the support from the South African Medical Research Council (SAMRC).
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This approach has led to producing a newer class of compounds which not only saves time and investment in developing newer drugs but is also effective in identifying drug candidates with novel mechanisms to treat multi-drug resistant strains. The repurposed drugs moxifloxacin, linezolid, and clofazimine are used to treat extensively drug-resistant TB when first- and/or second-line drugs fail. The chapter covers a detailed background on the current status of the repurposed drugs in the TB drug-discovery pipeline and discusses a potential way forward.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/79440",risUrl:"/chapter/ris/79440",signatures:"Nicole C. Cardoso, Carel B. Oosthuizen, Nashied Peton and Vinayak Singh",book:{id:"10881",type:"book",title:"Drug Repurposing",subtitle:"Molecular Aspects and Therapeutic Applications",fullTitle:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",slug:"drug-repurposing-molecular-aspects-and-therapeutic-applications",publishedDate:"June 1st 2022",bookSignature:"Shailendra K. Saxena",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-958-0",printIsbn:"978-1-83969-957-3",pdfIsbn:"978-1-83969-959-7",isAvailableForWebshopOrdering:!0,editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"423041",title:"Dr.",name:"Vinayak",middleName:null,surname:"Singh",fullName:"Vinayak Singh",slug:"vinayak-singh",email:"vinayak.singh@uct.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Cape Town",institutionURL:null,country:{name:"South Africa"}}},{id:"435887",title:"Dr.",name:"Nicole C.",middleName:null,surname:"Cardoso",fullName:"Nicole C. Cardoso",slug:"nicole-c.-cardoso",email:"nikki.cardoso@uct.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Cape Town",institutionURL:null,country:{name:"South Africa"}}},{id:"435888",title:"Dr.",name:"Nashied",middleName:null,surname:"Peton",fullName:"Nashied Peton",slug:"nashied-peton",email:"N.Peton@uct.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Cape Town",institutionURL:null,country:{name:"South Africa"}}},{id:"435889",title:"Dr.",name:"Carel B.",middleName:null,surname:"Oosthuizen",fullName:"Carel B. Oosthuizen",slug:"carel-b.-oosthuizen",email:"carel.oosthuizen@uct.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Cape Town",institutionURL:null,country:{name:"South Africa"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. State of the art",level:"1"},{id:"sec_3",title:"3. Repurposed drugs in the clinical development pipeline",level:"1"},{id:"sec_3_2",title:"3.1 Linezolid, Sutezolid, Delpazolid and TBI-223",level:"2"},{id:"sec_4_2",title:"3.2 Moxifloxacin, Gatifloxacin, levofloxacin and DC-159a",level:"2"},{id:"sec_5_2",title:"3.3 Clofazimine and TBI-166",level:"2"},{id:"sec_6_2",title:"3.4 Sanfetrinem (Trinem beta-lactam)",level:"2"},{id:"sec_7_2",title:"3.5 Spectinamide 1810 (Spectinamide)",level:"2"},{id:"sec_8_2",title:"3.6 Meropenem, Faropenem (Carbapenem Beta-lactam)",level:"2"},{id:"sec_9_2",title:"3.7 Thioridazine (phenothiazine)",level:"2"},{id:"sec_11",title:"4. Repurposed drugs in discovery",level:"1"},{id:"sec_11_2",title:"4.1 Carprofen and Oxyphenbutazone",level:"2"},{id:"sec_12_2",title:"4.2 Disulfiram",level:"2"},{id:"sec_13_2",title:"4.3 Metformin (Biguanides)",level:"2"},{id:"sec_14_2",title:"4.4 Metronidazole (Nitroimidazole)",level:"2"},{id:"sec_15_2",title:"4.5 Tolcapone, Entacapone (catechol-O-methyltransferase (COMT) inhibitor)",level:"2"},{id:"sec_17",title:"5. Target-based repurposing",level:"1"},{id:"sec_18",title:"6. Conclusion and future prospects",level:"1"},{id:"sec_19",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'WHO. Global Tuberculosis Report 2020. Geneva: World Health Organization; 2020. Available from: https://www.who.int/publications/i/item/9789240013131'},{id:"B2",body:'NIAID. Tuberculosis, which results from an infection with Mycobacterium tuberculosis, can usually be cured with a combination of first-line drugs taken for several months. 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Impact of metformin on the risk and treatment outcomes of tuberculosis in diabetics: A systematic review. BMC Infectious Diseases. 2019;19(1):1-11. Available from: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-4548-4 [cited 2021 Aug 29]'},{id:"B41",body:'Naicker N, Sigal A, Naidoo K. Metformin as host-directed therapy for TB treatment: Scoping review. Frontiers in Microbiology. 2020;29:435'},{id:"B42",body:'Dingsdag SA, Hunter N. Metronidazole: an update on metabolism, structure–cytotoxicity and resistance mechanisms. The Journal of Antimicrobial Chemotherapy. 2018;73(2):265-279. Available from: https://academic.oup.com/jac/article/73/2/265/4565576 [cited 2021 Aug 30]'},{id:"B43",body:'Hernández Ceruelos A, Romero-Quezada LC, Ruvalcaba Ledezma JC, López CL. Therapeutic uses of metronidazole and its side effects: An update. European Review for Medical and Pharmacological Sciences. 2019;23(1):397-401'},{id:"B44",body:'Wayne LG, Hayes LG. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infection and Immunity. 1996;64(6):2062-2069. Available from: https://journals.asm.org/journal/iai [cited 2021 30]'},{id:"B45",body:'Lin PL, Dartois V, Johnston PJ, Janssen C, Via L, Goodwin MB, et al. From the cover: Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(35):14188. Available from: /pmc/articles/PMC3435210/ [cited 2021 Aug 30]'},{id:"B46",body:'Carroll MW, Jeon D, Mountz JM, Lee JD, Jeong YJ, Zia N, et al. Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis. Antimicrobial Agents and Chemotherapy. 2013;57(8):3903. Available from: /pmc/articles/PMC3719751/ [cited 2021 Aug 30]'},{id:"B47",body:'Kinnings SL, Liu N, Buchmeier N, Tonge PJ, Xie L, Bourne PE. 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Open Access Funding
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Indexing and listing across major repositories, see details ...
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Long-term archiving
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Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
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Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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+5,700 OA books published
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The simulation results demonstrate that angiostatin has the capacity to regulate and inhibit the formation of new blood vessels and has an obvious impact on the morphology, growth rate, and the branches of microvascular network inside and outside the metastatic tumor. Heterogeneous blood perfusion, widespread interstitial hypertension, and low convection within the metastatic tumor have obviously improved under the inhibitory effect of angiostatin, which suits well with the experimental observations. They can also result in more efficient drug delivery and penetration into the metastatic tumor. 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These changes lead to disorder of regulation of cerebral circulation and development of cerebral hypoperfusion resulting in the secondary brain damage. Ependymal disruption, periventricular edema, and compression of the periventricular capillaries can be developed. Ischemia of the white matter can be developed due to hypoperfusion. But it is reversible if treated early and adequately. Transcranial Doppler sonography enables to determine hemodynamic parameters of cerebral circulation in various physiological and pathophysiological conditions. As transcranial Doppler sonography has been regarded to be noninvasive and appropriate for bedside treatment, it can also be applied in children at any age. The goal of this chapter is to assess changes of cerebral circulation in children with hydrocephalus and application of data from scientific studies of intracranial dynamics in children with hydrocephalus in clinical practice. 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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. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"26",type:"subseries",title:"Machine Learning and Data Mining",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11422,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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