Rifampicin dose for chemoprophylaxis [3].
\r\n\t1. Geopolymers chemistry topic describes the chemical reaction models and chemical kinetic of the geopolymerization which occurs after mixing the aluminosilicate raw materials with an alkaline solution.
\r\n\t2. Advanced characterization of geopolymers topic includes innovative technologies applied on geopolymers characterization at the nanoscale level, meant to explain the bond between the reacted and nonreacted particles from the composition.
\r\n\t3. Sustainability with geopolymers topic should provide clear information about the characteristics and applications of the geopolymers which use as raw materials industrial waste. Moreover, environmental impact studies which offer a clear view of the effects produced by geopolymers manufacturing, compared to conventional materials, is included.
\r\n\t4. Geopolymers as functional materials topic will present key aspects in developing geopolymers with tailored properties that increase further the heavy metals adsorption capacity, offering outstanding opportunities for energy-efficient separations and process intensification, in terms of saving energy, reducing capital costs, minimizing environmental impact and maximizing the raw materials exploitation.
\r\n\t5. Reinforced structures topic describe the effects produced by the introduction, in the geopolymers matrix, of different types of reinforcing elements.
Trend of miniaturization of everyday devices increases industry demand for efficient production of miniature parts. Machining production technologies of small-dimension elements by turning, milling, and polishing are well known for a long time. However, these methods are not efficient enough for the great demand for small and handy devices. This makes engineers to search for new methods of microelements manufacturing or to adapt traditional ones for the requirements of miniaturization.
\nMicroforming is an adopted technology of production of small parts by metal forming. This process is characterized by good productivity, high dimensions accuracy, proper surface smoothness, high material usage, and good mechanical properties of manufactured items, which makes it a good alternative to machining. Excepting benefits, microforming also brings some limitations, for example, limited forming possibilities of deformed materials or narrow shapes of obtained elements. Approaches of microforming methods are presented in Figure 1.
\nMicroforming methods [1].
Comparing microforming to traditional forming process, it is obvious that while going to a microscale some process parameters, such as grain size or surface structure, keep constant [2]. Relationships between the dimensions of treated items and morfometric parameters of their microstructure and surface geometry, in billets as well as in tools, are different in macro- and microscale. This leads to the formation of the size effect phenomenon. In the available technological knowledge relating to conventional macroscale forming methods, presence of size effects does not permit direct application into microforming of metals [3–6]. Microforming is defined as the forming of the part features with at least two dimensions in the submillimeter range [3]. Figure 2 presents some microparts made by microforming processes.
\nMechanical microparts formed by microforming [7, 8].
\nFigure 3 presents all the issues which need to be considered in microforming system. There are four factors influencing the material deformation: tool-workpiece interface condition, grain size, workpiece size, and element feature size [7]. These factors further affect the efficiency of microforming system and the quality of manufactured items influencing on such a process parameters as: deformation load, forming stability (scatter of the process variables), defects of deformation, dimensional accuracy, mechanical properties, and the quality of achieved surface.
\nIssues related to size effect in microforming system [7].
The primary problem connected with microforming is the so-called “size effect” ensuing from same miniaturization. The occurrence of unpredictable changes in process parameters, while treating similar scaled workpieces, is called size effect [9]. These effects distinguish described process from conventional methods of metal forming, and significantly influence on the possibilities and limitations of this technology. Sources of size effect formation can be divided into two groups [2, 6]: physical—related to the workpiece size and the forces affecting the process; structural—induced by the microstructure of the material.
\nPhysical sources:
Surface-to-volume (S/V) ratio size effect—with element size decreasing, the S/V ratio increases, which makes the surface effects more crucial.
Forces relation size effect: van der Waals forces, surface tension, and gravitation—these forces can be neglected in conventional forming processes. However, they must be taken into account in the case of microforming, because they are relatively considerable regarding the process forces and can directly affect its conditions.
Structural sources:
Grain size to element thickness size effect—the grain size of metallic materials results from the material properties and determined by the casting condition, the thermal and mechanical treatments. It is impossible to obtain each material with each grain size, thus the grain size cannot be scaled down in parallel to the element dimension. Figure 4 schematically shows microformability of polycrystalline and amorphous materials.
Microformability of polycrystalline and amorphous material [10].
In conventional metal forming operations all treated materials are considered as homogeneous. In microforming processes they are heterogeneous, because of relatively large grains size to the billet volume. As the grain size increases, the grain structure of the billet becomes to be more heterogeneous and the material shows anisotropic behavior in the submillimeter dimensional range. The anisotropic behavior of the workpiece material can directly change local deformation mechanisms as shown in Figure 5.
Surface structure scalability (SSS) size effect—similarly to grain size, it is often not possible to reduce the die and billet surface roughness with the element dimension, due to that the surface structure scalability is the source of size effects. In lubrication as well as in dry conditions, SSS leads to a size-dependent friction behavior.
Backward extrusion of a billet composed of heterogeneous grain structure [3].
Microforming is a relatively young technology, developed in the last two decades, but more and more research centers in the world deal with it. Together with reports of experimental work results, attempts of identified numerical simulating phenomena are undertaken and presented.
\nFlow stress decreases as workpiece size decreases [5, 11, 12]. Surface grains of the deformed material have lesser constraints compared to internal ones. Distribution of dislocations in surface grain boundaries is different from that of internal. The surface grains have a lower flow stress. When the plastically treated detail size is decreased to microscale and the grain size is relatively large, there are small number of grains constituting the workpiece and the volume fraction of surface grains increases significantly—surface layer model (Figure 6). Analogously, increase of grain size in small element reduces their number in its volume. This leads to decrease of grainy material flow stress in microscale (Figure 7).
\nChange of surface grains volume fraction with decreasing of specimen size—surface layer model [13, 14].
Grain and specimen flow stress size effects in: (a) tensile; (b) compression tests [13, 15].
Similarly to flow stress, fracture strain decreases with the decrease of specimen size [16, 17] and the increase of grain size [12]. This phenomenon was found in tensile tests of wire and thin details. Fracture takes place through the localized shearing in the individual grain (Figure 8) [18–20]. The fracture strain increases also with the decrease of workpiece size in compression of bulk metal [21]. The tensile-tested material in microscale can be considered as a chain and each specimen’s perpendicular section acts as a chain link (Figure 9). Material yields when all the grains in the section yield and the initial yielding occurs at the weakest section consisting of the soft grains [23]. The smaller the number of grains in the section, the higher the probability to find one with a significantly large fraction of soft grains decreasing the fracture strain.
\nScanning electron micrograph of a tensile-tested aluminum wire with a diameter of 25 μm [18].
Schematic illustration of yielding at the weakest section of extended material [22].
Inhomogeneous and anisotropic material behavior causes the irregular flow of formed workpiece geometry with the decrease of its size and the increase of grain size [24]. Chan et al. [12] experimentally presented decrease of flow stress, scatter of obtained data, and inhomogeneous specimen deformation with decrease of the ratio of element size to its grain size. Flow stress decrease because of grain boundary surface area to billet volume ratio gets small and the grain boundary strengthening effect is reduced. In addition, when the workpiece volume contains only a few grains (Figure 10), their size, shape, and orientation affect the deformation process significantly, leading to the scatter of the obtained data, for example stress-strain curves (Figure 11), and to the inhomogeneous billet deformation.
\nMicrostructures of compressed specimens annealed in different temperatures [12].
Flow stress curves of the billets with different grain size [12].
Flow stress size effect (Figure 12) and inhomogeneous deformation behavior were included in FE simulation of microcompression tests. Grain properties composite model was proposed. Grains were divided into several groups with assigned corresponding stress-strain curves. The flow stress curves of the testing samples and the scatter effect can be then estimated based on Eq. (1):
where n is the total number of grains in the billet, Vi is the volume fraction (area fraction in two-dimensional case) of the ith grain, and σi(ε) is the flow stress of the ith grain.
\nIllustration of flow stress size effect [12].
The volume/area fraction of each grain in the testing sample was estimated based on metallographies. The flow stress curves were then assigned to the grains randomly, as it is shown in Figure 13.
\nSpread σ(ε) of the grains flow stress-strain curves [12].
Schematic illustration of the 3D full-scale model with cubic grain.
Stress distribution in the 3D full-scale models with surface-to-grain ratio of 2.8 [12].
Stress distribution in the 3D full-scale models with surface-to-grain ratio 12.5 [12].
3D full-scale simulations using a commercial CAE system, ABACUS, were conducted with eight-node linear brick element. Grain was represented as a cube for simplification (Figure 14). The grain properties identified by Eq. (1) were employed into the models. The grain interior and grain boundary were considered as a single body, while the change of grain boundary strengthening effect due to the change of surface-to-grain ratio was taken into account with varying the mean flow stress of grains. FE simulation of compression of billets consisting of individual grains results showed the inhomogeneous workpiece deformation with the decreasing ratio of specimen size to grain size (Figures 15 and 16). In 3D full-scale model, the asymmetry of the material deformation behavior and grain properties was taken into account. The results showed that the scatter effect of the flow stress curve increases with increasing grain size and the achieved scatter range had a good agreement with the experimental result.
\n\n\n\nMicrostructure of specimens and grain size, λ = specimen radius/grain size [25].
Aggregates of polycrystalline (a) tessellation in 140 Vornoi polyhedral; (b) freely meshed model with 140 subdomains; (c–f) Microstructure mapping on a 1313 × 60 cubic element mesh and domain with subdomain numbers 140, 26, 385, and 2520, respectively [25].
Voronoi tessellation can be adopted to describe the polycrystalline aggregate [25–27]. Lu et al. [25] proposed a mixed material model based on modified Hall-Peth relationship, surface layer model, and grained heterogeneity (e.g., grain size, shape, and deformability). Pure copper compression experiment was performed (Figure 17). Generated virtual microstructures which can be implemented in the commercial FE code are presented in Figure 18.
\n\nThe deformed part can be represented by a space tessellation into 3D Voronoi diagram which describes grain boundary [25]. Voronoi diagram is defined as n distinct regions, Vi based on an open set Ω, and n different seeds zi (i = 0, 1,…, n − 1) such as:
where d is the function of distance. Voronoi polyhedra are the influence zones of these grains that are their mass center.
\n\nProfile of specimens after compression, (a) homogenous model with λ = 1.6, (b) λ = 7.5, (c) λ = 3, (d) λ = 1.6, (e) λ = 0.85 [25].
A 3D domain is decomposed into a certain number of subdomains. Then, the seeds are spread into these subdomains. Assuming the center of a cube is (x, y, z), the seed will lie λδa/2 away from the central point. The coordinate of the seed position should be (x + λδa/2, y + λδa/2, z + λδa/2). δ is the maximum distance between the seed and the cubic center, and λ is a random number between −1 and 1. Both δ and λ are the so-called shape factors which will determine the shapes of the Voronoi cells. A critical distance d between different seeds is defined to prevent each seed from being too close to another. After that, 3D Voronoi polyhedra can be generated by taking these seeds as the generating points [25].
\n\nObtained from nanoindentation hardness of grains was used to identify the deformability of individual grain inside the billet. Applying developed material model, the microcompression test of pure copper was numerically simulated (Figure 19) using commercial the FEM software ANSYS/LS-DYNA. Numerical analyses results show that the scatter of deformation behavior becomes significant with decreasing factor λ, where λ is the specimen radius/grain size.
\n\n\nSpringback increases with decreasing ratio of workpiece thickness to grain size [15, 28]. Liu et al. [15] used the pure copper sheet foils with the thickness from 0.1 to 0.6 mm as the testing material for tensile test and microbending (Figure 20). It was founded that the springback angle increases with the decreasing metal element thickness. This is consistent with the conventional bending knowledge specific for macroscale bending. Increase in the scatter of springback angle with decreasing sheet thickness was also found. It was concluded that the main reason for that is elastic anisotropy of surface grain due to grain orientation difference.
\nLeft: Three-point bending test device and tooling; Right: Influence of grain size on springback angle [15].
Grained heterogeneity in workpiece with: (a) 13 grains; (b) 25 grains; and (c) 75 grains [29].
Fang et al. [29] conducted numerical simulation to investigate the size effect of the springback, which occurs after the micro-V-bending in terms of Voronoi tessellation. A finite element model of the micro-V-bending has been designed by using the ABAQUS/Standard commercial software. The workpiece grain sizes of 98, 152, and 201 μm have been adopted in the FE model (Figure 21) to recognize the relationship between the size effect and springback angle during the V-bending process. Voronoi tessellation can imitate the microstructure of materials, and represents grained heterogeneity graphically in FE models. Grains were divided into three groups with assigned corresponding stress-strain curves (Figure 22). Simulation results display the inhomogeneous deformation behavior during micro-V-bending process and also show that springback effect increases with grain size (Figure 23).
\n\nLeft: Flow stress curves of the grains in workpiece with grain size 152 μm; Right: Micro-V-bending FE model with workpiece grain size 152 μm [29].
Left: Micro-V-bending result after unloading; Right: Springback angle with different grain size [29].
Changes of interfacial friction with the decrease of element size in microforming process can be estimated based on the size-scaled ring compression test [5] and double-cup extrusion (DCE) [30]. The friction is recognized based on the comparison between the geometry of the deformed sample and the finite element simulations results. Change of friction factor with decreasing workpiece size in the DCE process in lubricated conditions is presented in Figure 24. It can be seen that the friction increases with the scaled down workpiece size [30].
\nTo recognize the frictional behavior in microforming, the asperity deformation process needs to be taken into account. Surface topography evolution process is shown in Figure 25. Before the tool touches the workpiece surface, there is a layer of lubricant on the whole contact surface (Figure 25a). When the tool presses the workpiece surface, some lubricant is trapped in the roughness valleys, which results in the formation of the so-called closed lubricant pockets (Figure 25b). In the CLPs, a hydrostatic pressure is thus generated and part of the deformation load is shared by the lubricant. Under this condition, material slides along the tooling surface with low friction. At the workpiece edges the lubricant is squeezed out from the roughness valleys and the so-called open lubricant pockets (OLPs) are then created. At the OLPs, the flattened asperities support deformation load and they become to be the real contact areas (RCAs), which increases the interfacial friction (Figure 25c). Open and closed pockets model application in FE simulation is presented in Figure 26 [32]. Presence of CLP and OLP results in the nonuniform deformation of material asperities surface affects the surface properties of the formed microelement.
\nThe formed geometries in different size-scaled achieved in double-cup extrusion tests [31].
The evolution of workpiece surface asperities in deformation process [32].
2D sketch of OLPs, RCAs, and CLPs [32].
The increase of OLP fraction with the decrease of workpiece size [7].
End surface topographies of the specimens (Ø1 × 1.5 mm) with the asperity size of: (a) 25 μm; and (b) 10 μm [32].
Increase of friction with miniaturization is related to the increase of OLP fraction (Figure 27). The influence of different sizes of asperity on the change of the compressed surface topography is shown in Figure 28. The thickness of OLP rim decreases with the increase of asperity size. This reveals that the efficiency of lubricant in load supporting is higher in the surface with large asperities. More lubricant can be then trapped in the roughness valleys, resulting in the increase of the CLP area fraction.
\nMaterial tends to flow backwards (higher cup) with the decrease of the workpiece size when the fine-grained material is used [31]. Coarse grain size (Figure 29, case 0.5 mm) is larger than the cup wall thickness, which makes the material flow forward easily (longer shaft). Deformation behavior of fine- and coarse-grained samples in microdouble-cup extrusion is showed in Figure 30.
\nThe experimental results of the combined forward rod—backward cup extrusion [31].
Microstructures of the microformed parts in microdouble-cup extrusion with different grain sizes. (a) 20 and (b) 150 μm [33].
The ratio of tool asperity size to the formed element size increases with decrease of workpiece size and the increase of grain size [22, 34, 35]. Die workpiece interface effects become significant in microforming. Geiger et al. [31] has shown that the use of the traditional friction coefficient or friction factor can lead to erroneous results in microscale. Some of the researchers have taken into account the impact of degree of a tool roughness on the material deformation process in numerical analysis. Challen et al. [36] presented the friction model for rough contact of plastic material with a rigid tool. Model is based on a simplified geometry of the tool surface, whose actual profile reflects a triangular wave (Figure 31). The surface roughness used in the model is the average of the asperities parameters measured in the experiment.
\nTriangular wave surface roughness model [36].
In that way, using a commercial FE system DEFORM, geometry of the tool surface was modeled in experimentally verified simulations of the forward microextrusion processes [37, 38] (Figure 32), where a significant influence of container roughness on the material flow was shown.
\nFlow nets of microextruded metal rods with a tool surface characterized by: (a) constant friction factor; (b) and (c) rigid triangular waves [39].
Vidal-Sallé et al. [40, 41] modeled die roughness in the form of a rigid triangular wave and the wave of interconnected arcs—model machined by turning surfaces in FE simulations of cylinder compression (Figure 33).
\nPlastic strain distribution in the compressed billet for perfect sliping [41].
Jeon et al. [42, 43] modeled die surfaces in the form of rigid sinusoidal curve in numerical simulation of the ring compression (Figure 34) as opposed to the use of the traditional empirical friction coefficient or factor. This finite-element-based model has been validated experimentally in terms of loads and metal flow using the ring test and actual surface measurements. The curve was referenced to the parameter Ra and the friction factor was determined as m = f(a,t).
\nTool surface geometric model with using an elliptical profile [42].
The scatter of the measured material properties (Figure 35) (e.g., flow stress, material deformation behavior) increases with the increase of grain size and the decrease of the workpiece size. This phenomenon is the resulted of different properties of individual grains and their less number in the workpiece volume [11, 44]. The deformation behavior of a single grain has an anisotropic nature. When the specimen size decreases and the grain size stays constant, there will be a small number of grains in the specimen volume and so the number of microstructural features decreases. The uniform distribution of different grains no longer exists. Each grain with each property plays a significant role to the overall material deformation behavior. Different crystallographic orientations, different shapes, and sizes of neighboring grains lead to inhomogeneous deformation, which result in the scatter of achieved material properties.
\nSchematic illustration of the modeling of the scatter effect with a normal distribution function [12].
The hardness distribution of the formed billet becomes to be no uniform in microforming (Figure 36) when the grain size is coarse [45, 46]. More even material flow and hardness distribution can be achieved using the ultrafine-grained material. This implies the potential applications of the ultrafine-grained materials in metal microforming processes.
\nLeft: Illustration of nanoindentation; Right: statistical distribution of α-value, α—ratio of the hardness at each class to the average hardness [25].
Billet formability increases with the decrease of workpiece size for a constant grain size [21]. It needs a larger strain to initiate cracking in microforming (Figure 37). Common assumption is that the damage energy to initiate fracturing is the same in macro- and microscale. The flow stress decreases with the billet size, so the larger deformation is needed to obtain the critical damage energy in microforming.
\nDifferent size-scaled central headed parts [21].
Microforming is considered as an economically competitive process for production of metallic microcomponents. The scaling down of a forming system from macro to micro leads to the occurrence of size effect. This phenomenon differs microforming from forming in macroscale and do not allow applying conventional knowledge. The anisotropic properties of each grain, the random nature of grain distribution, and orientation as well as tool surface roughness become significant. This leads to the inhomogeneous deformation and the scatter of the achieved flow stress. Experimentally recognized size effects, such as flow stress size effect, deformation behavior size effect, or interfacial friction size effect are numerically modeled, giving the ability to more accurately identify their mechanics and to predict the results of the microforming process.
\nFor the microforming process simulations, commercial FE systems such as DEFORM, QFORM, ABACUS, or ANSYS/LS-DYNA are used. Nonlinear code ADINA (developed by KJ Bathe and his team at MIT Mechanical Engineering) may be also recommended to solve some of the complex multiphysical micromechanics phenomena associated with metal forming. Grain structures are modeled based on metallographies or using Voronoi tessellation and the tool surface roughness using rigid waves. Ortiz atomistic models of material behavior based on atomistic energy laws may be an alternative way to resolve the mechanics of microforming of metals.
\nAlthough the polycrystalline material deformation behaviors have been extensively studied and adopted in numerical simulations, the size effects physics is not yet thoroughly understood. The influence of size effect on deformation mechanics in microforming processes is still a challenging issue to be investigated.
\nThis chapter has been carried out in the framework of the S/WM/1/2015 statutory work and financed from the Ministry of Science and Higher Education funds.
\nMycobacterium leprae (M. leprae) is an acid fast bacilli that is the causative agent of leprosy disease which mainly effects the skin and peripheral nerves. In olden times leprosy was common in temperate climates (e.g. Europe), today it is mainly confined to tropical and subtropical regions. Mode of transmission in leprosy is mainly through inhalation of droplets containing the bacteria. But skin contact is also claimed by many leprologists. The disabilities and deformities associated with leprosy due to neuropathy leads to long-term consequences, including. This in turn is associated with stigma.
The immunity of the host plays an important role in disease progress and control. Thus, fortunately 95% of patients exposed to M. leprae will not develop this disease. The variation in incubation period ranges from 2 to 20 years, or even longer.
Leprosy has been successfully eliminated as a public health problem in 2000 globally and at the national level in 113 countries out of 122 by 2005 [1]. Elimination of leprosy is defined by World Health Organization as a point prevalence below 1 per 10,000 population [2]. However, the number of new patients diagnosed with leprosy is still significant, at more than 200,000 in 2016 globally. The new case detection rate of the disease (NCDR) is only slowly declining (Figure 1) [3].
Trend in case detection and case detection rate, by WHO region, 2006–2016 [3].
The long incubation period, silent symptoms, long duration MDT and unavailability of effective vaccine makes this disease difficult to identify, treat and eradicate. To add to the misery the stigma associated with the disease is another challenge. In such circumstances, prevention and control of disease gains utmost importance.
In 2017, 192,713 patients were on treatment globally which makes the prevalence rate of 0.25 per 10,000 population [4]. Total of 210,671 new cases were reported in same year from 150 countries making NCDR of 2.77 per 100,000 population. Figure 2 below shows the trends over the past decade (2008–2017) in new case detection of leprosy cases globally in the reporting countries of World Health Organization (WHO) [4].
Country-wise trends of detection of new leprosy cases from 2008 to 2017 [4].
The three main goals of control of leprosy are
To detect the pathology early and treat the patient completely.
To prevent the transmission to the others.
To prevent the disabilities and other complications.
Thus the following modalities are adopted to control leprosy:
Medical measures
Social support
Program management
Evaluation
The control of leprosy starts with the estimation of size and magnitude of the problem. Most common epidemiological survey method of collection of data is “Quick random sample survey.” Information about the prevalence of leprosy, age and sex-wise distribution, various forms of leprosy and the health facilities available should be gathered. Roughly the total prevalence of leprosy in an area would be about 4 times that of the cases found among school children [5, 6]. These estimates are essential to plan, implement and to evaluate the results of the control program.
The objective is to detect all the cases as early as possible and to register them. Active case finding is important as the disease is symptomless in the early stages. Cases can be detected by the Contact surveys, Group surveys and Mass surveys. Contact surveys consists of examination of all household contacts with a lepromatous case, particularly children, in areas with prevalence less than 1 per 1000. Contact surveillance of households is recommended for a minimum period of 10 years after case is declared bacteriologically negative, and for 5 years in households with a non-lepromatous case from the time of diagnosis of the index case. Group surveys are done in areas where prevalence of leprosy is more than 1 in 1000 population. This consists of screening certain groups such as school children, slum dwellers, military recruits, industrial workers, etc. through “Skin camps.” Lastly, mass surveys consists of examination of each and every individual by house-to-house visits in hyperendemic areas (prevalence – 10 or more per 1000 population). These are generally carried out by repeated annual examinations of school children which yield better results at relatively low cost [5, 6]. The data of each case is entered in the standardized proforma developed by WHO.
Since an effective vaccine is unavailable for leprosy the secondary prevention (early treatment) becomes more important. Until 1981, Dapsone (Diamino Diphenyl Sulphone—DDS) was used to treat leprosy which resulted in the development of resistance and relapse, making leprosy control difficult.
Multidrug Therapy: In 1982, WHO recommended Multidrug Therapy (MDT) for all leprosy patients. Introduction of MDT has opened a new avenue in the control of leprosy in the world. Aim of MDT is to convert the infectious case into noninfectious as soon as possible, so as to reduce the reservoir of infection in the community.
The main objectives of MDT are:
To ensure early detection of the cases.
To interrupt the transmission of infection.
To prevent drug resistance, relapse and reaction.
The advantages of MDT over dapsone monotherapy are:
Shorter duration of treatment,
Better patient compliance,
High cure rate,
Cost-effectiveness and
Ease in health delivery system.
There are two types of MDT regimens used depending on the symptoms and signs shown by the patients - Paucibacillary (PB) and Multibacillary (MB). Recommended Regimens are discussed below [3, 5, 6, 7]:
i. Multibacillary leprosy:
MDT is recommended for following groups of patients:
All smear positive cases.
Skin lesions more than five in number.
More than one nerve trunk thickening.
All cases of relapse/reactivation and all cases who have been treated with Dapsone monotherapy earlier.
The drugs used in Multibacillary MDT and dosages are:
Rifampicin: 600 mg once monthly, supervised.
Dapsone: 100 mg daily, self administered.
Clofazimine: 300 mg once monthly, supervised and 50 mg daily, self administered.
Duration of treatment for Multibacillary leprosy is 12 months, can be extended to 18 months and continued where possible up to smear negativity. Sometimes LL/BL patients with high bacilli may need 2–3 years or more of MDT for achieving bacteriological negativity.
ii. Paucibacillary leprosy:
The drugs and dose schedule is:
Rifampicin 600 mg once a month for 6 months supervised.
Dapsone 100 mg daily for 6 months self administered.
Paucibacillary leprosy is treated for 6 months.
MDT is not contraindicated in patients with HIV infection.
Each MDT blister pack contains tablets for 4 weeks treatment. For easy identification color coding of the blister pack is done, that is, with different colors for multibacillary and paucibacillary cases both in adults and children.
The treatment in both PB and MB cases varies depending on the age of the patient. The patients between 10 to 14 years are treated as paediatric cases, while >14 years are considered adult. The standard treatment regimen for MB leprosy in adults is given for 12 months. The drugs in each blister pack are (Figure 3):
Two capsules of Rifampicin of 300 mg (600 mg once a month) to be taken as single dose under supervision.
Clofazimine 3 capsules of 100 mg each to be consumed once a month as single dose under supervision and 50 mg daily for next 28 days.
Dapsone 100 mg as single dose and then daily once for 1 month.
MDT for adult MB type of leprosy [2, 7].
The standard adult treatment regimen for PB leprosy is (Figure 4):
Rifampicin: 600 mg once a month.
Dapsone: 100 mg daily.
Duration: 6 months (6 blister packs of 28 days each).
MDT for adult PB type of leprosy [2, 7].
Treatment regimen for MB leprosy in children (ages 10–14 years) is (Figure 5):
Rifampicin: 450 mg once a month.
Clofazimine: 150 mg once a month, and 50 mg every other day.
Dapsone: 50 mg daily.
Duration: 12 months (12 blister packs of 28 days each).
MDT for pediatric MB type of leprosy [2, 7].
Treatment regimen for PB leprosy in children (ages 10–14 years) is (Figure 6):
Rifampicin: 450 mg once a month.
Dapsone: 50 mg daily.
Duration: 6 months (6 blister packs of 28 days each).
MDT for pediatric PB type of leprosy [2, 7].
MDT is provided free-of-charge globally through an agreement between a pharmaceutical company and WHO. WHO manages distribution of MDT to countries in coordination with national leprosy programs.
Clinical surveillance of the patients after completion of treatment is an important part of MDT to ensure complete cure. For paucibacillary cases follow up for at least once a year for 2 years after completion of treatment and for multibacillary cases at least once a year for 5 years [3, 4, 5].
Early diagnosis of cases, aggressive treatment and proactive measures to avoid complications and disabilities is the backbone for the success of any comprehensive program. In addition to accurate reporting and control measures, effective preventions will be needed to achieve elimination. Search for an effective vaccine either to be used alone or in combination with a drug has been going for a long time.
Presently BCG (Bacillus Calmette-Guerin) is the only vaccine that has shown some protection against M. leprae bacillus. A single dose of BCG gives 50 percent or higher protection against the disease. It is the most widely used vaccine in the world, yet the degree of protection it confers is not yet confirmed. The meta-analysis of many experimental studies concludes that the vaccine gives approximately 26% protection against leprosy. But the protection level decreases with time. To overcome this problem more than one dose of vaccine is advised.
Other variants of vaccination are also suggested.
Adding killed M. leprae to BCG: Various modifications have been suggested, such as the addition of killed M. leprae to BCG. This method almost doubles the vaccine efficacy in some populations as concluded by few studies. But the same cannot be said for patients below 15 years.
Vaccination with M. indicus pranii (Mycobacterium W): This strain discovered in India. Testing of the MIP vaccine took place in 2005 and showed that it was effective for seven to 8 years, after which a booster dose would be needed to maintain the immunity. Recently the vaccine was approved by the Drug Controller General of India to be rolled out in a project involving five districts in the states of Bihar and Gujarat, where there are high rates of leprosy. Leprosy patients and their close contacts will benefit from this project, making India the first country in the world to have a large-scale leprosy vaccination initiative [8].
Another milestone in prevention of leprosy is the discovery of the vaccine candidate, called LepVax. Scientists at Infectious Disease Research Institute (IDRI), along with national and international collaborators including the National Hansen’s Disease Program and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, with financial support from American Leprosy Missions, have developed this leprosy vaccine. Based on the preclinical studies, the LepVax, has progressed to Phase I clinical testing in the United States, the first stage of safety testing in human volunteers. The clinical trial is focused not only on safety but also evaluates the immune response of the individual to the vaccine.
Indian cancer research center (ICRC) bacilli: Another variant belonging to the M. avium intracellulare group, the ICRC bacilli are thought to induce lepromin conversion in lepromatous leprosy patients and in lepromin-negative leprosy-free individuals. Its efficacy was reported to be 65.5 percent [8].
M. vaccae: The studies with this soil-dwelling mycobacterial species combined with BCG showed to provide greater protection against leprosy, but a Vietnamese trial contradicted the results [8].
M. Habana: This bacilli has been reported to induce lepromin conversion when used as a live vaccine in monkeys, and protected mice against the development of leprosy [8].
Chemoprophylaxis alone provides two-year protective window while effective immunization will provide a much broader protective window. Thus many studies and research is going on to provide both chemoprophylaxis and immunization for immediate and short-term protection and longer-term protection respectively. This strategy could have better impact and distinct appeal in controlling and preventing leprosy. Such trials could also provide a gateway for the assessment and implementation of new emerging vaccines (Figure 7).
Locations of leprosy vaccine testing.
Chemoprohylaxis using effective antibiotics focuses on providing protection to people at risk such as close contacts – family members, neighbors, co-workers, health care providers for lepers etc. Due to the stigma of disease the leprosy cases are found in clusters in all endemic regions, rather than being evenly dispersed over the whole area. Thus these high risk people can be identified and prophylaxis provided along with secondary prevention strategies. The process includes focused surveillance, contact tracing, early diagnosis and treatment. This helps in reducing the incidence and breaking the chain of transmission.
Chemoprophylaxis, as recommended by WHO Guideline Development Group (GDG), is done using single dose rifampicin (SDR) for contacts of leprosy patients both in adults and children of 2 years of age and above. Before starting the drug leprosy and TB disease are to be excluded. There should be no contraindications also for the use of rifampicin.
Other important considerations for the implementation of this chemoprophylaxis by programs are:
Adequate management of contacts.
Consent of the index case to disclose his/her disease.
An RCT found that SDR reduces risk of leprosy over 5–6 years in leprosy contacts. For every 1000 contacts treated with SDR, there were four leprosy cases prevented after 1–2 years and three cases prevented after 5–6 years.
Recommended dosage schedules for SDR are given in Table 1.
Age/weight | Rifampicin single dose |
---|---|
Adults (≥15 years) | 600 mg |
10–14 years | 450 mg |
Children 6–9 years (weight ≥ 20 kg) | 300 mg |
Children <20 kg (≥2 years) | 10–15 mg/kg |
Rifampicin dose for chemoprophylaxis [3].
The limitations of this approach are:
The protection is approximately for only 2 years.
High bacillary load cannot be eliminated using single dose.
Specific screening test needed to distinguish between contacts with high and low bacillary load.
Among communicable diseases, leprosy remains a leading cause of peripheral neuropathy and disability in the world, despite extensive efforts to reduce the disease burden. It is an important aspect of leprosy control. It means the medical, surgical, social, educational, and vocational restoration as far as possible of treated patients to normal activity so that they resume their place in the home, in society and industry [5, 6, 7]. Early treatment helps in disability limitation.
Rehabilitation: WHO has defined rehabilitation as “the combined and coordinated use of medical, social, educational and vocational measures for training and retraining the individual to the highest possible level of functional ability.”
Preventive rehabilitation consists of prevention of development of disabilities in a leprosy patient by early diagnosis and prompt treatment. But once the patient becomes handicapped and suffers from the damage caused, should be trained and retrained to the maximum functional ability so that the patient becomes useful to self, to the family and to community at large by various measures such as medical (physical), surgical, psychological, vocational and social rehabilitation (Flow chart 20.10).
Health education is given to the patient, to the family and to the community at large about leprosy. The education should be directed to ensure general public and patients help them develop their own actions and efforts to change the perception about the disease and seeking professional help whenever required. Early recognition of symptoms, prompt diagnosis, health seeking behavior, personal care, treatment adherence and rehabilitation are important aspects of health education. The key messages included are about the cause of disease and the complete cure available to encourage people for early diagnosis and treatment. It also aims at helping people to change their attitude and behavior by removing the misunderstandings and misconceptions. Mass Health education also helps to eradicate social stigma, social ostracism and social prejudice associated with leprosy which is the biggest hindrance for the eradication of disease.
The complications of the disease cause disfigurement and disabilities which in turn gives way to the stigma and strong discrimination of these patients. This results not only in physical and social isolation also financial dependency, ultimately forcing the leprosy patients to beg on streets for their survival. To address this issue WHO introduced the strategy of community-based rehabilitation (CBR). This intended to enhance the quality of life for lepers with disabilities through community initiatives. Community participation and using local resources to support the rehabilitation of people with disabilities within their own communities is the foundation of this concept [9, 10].
“Enhanced Global Strategy for Further Reducing the Disease Burden due to Leprosy for 2011–2015” was launched in 2009 by the World Health Organization. The target of the program was to reduce Grade 2 Disability rate (G2DR) in leprosy patients by at least 35% by the end of 2015 (G2DR is the number of new cases with grade 2 disability per 100,000 population). Since the elimination of leprosy in 2005, the prevalence is very less and thus G2DR has been proposed as an indicator. The advantage of G2DR as indicator is that, it is less susceptible to operational factors such as detection delay and is a more robust marker for mapping cases of leprosy in any country. This will also help the program implementers to focus on interventions that reduce visible deformities by enhancing early detection and treatment of leprosy patients and ultimately reduce the number of new leprosy cases in the population. However by the end of 2015, only Thailand was able to achieve this target [11].
In 2016, WHO launched the “Global Leprosy Strategy 2016–2020: Accelerating towards a leprosy-free world” [9].
The program aims to reinvigorate efforts to control leprosy and avert disabilities, especially among children still affected by the disease in endemic countries.
The strategy is built around three major pillars:
Strengthen government ownership and partnerships;
Stop leprosy and its complications; and
Stop discrimination and promote inclusion.
The strategy of this program is:
To sustain expertise and increase the number of skilled leprosy staff;
To improve the participation of affected persons in leprosy services;
To reduce visible deformities and stigma associated with the disease;
To call for renewed political commitment and enhanced coordination among partners;
To highlight the importance of research and improved data collection and analysis.
The key interventions needed to achieve these targets include:
Early case detection especially in children before visible disabilities occur thus reduce transmission;
In highly endemic areas or communities detection of disease among higher risk groups through campaigns;
Improving health care coverage and access for marginalized populations such as poor patients, patients in the difficult to reach areas and the areas of conflicts.
Customization of the strategic interventions in endemic countries is permitted to suit the national plans to meet the new targets. E.g. Screening all close contacts of persons affected by leprosy; initiating a shorter and uniform treatment regimen; and incorporating specific interventions against stigmatization and discrimination.
Its ultimate goal of this program is to further reduce the global and local leprosy burden, that is, (a) zero disabilities in children with leprosy-affected, (b) G2DR less than one per million population and (c) repeal of laws that discriminate leprosy patients of their rights.
Author declares no conflict of interest.
IntechOpen aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. We uphold a flexible Copyright Policy, guaranteeing that there is no transfer of copyright to the publisher and Authors retain exclusive copyright to their Work.
',metaTitle:"Publication Agreement - Monograph",metaDescription:"IntechOpen aims to guarantee that original material is published while at the same time giving significant freedom to our authors. For that matter, we uphold a flexible copyright policy meaning that there is no transfer of copyright to the publisher and authors retain exclusive copyright to their work.",metaKeywords:null,canonicalURL:"/page/publication-agreement-monograph",contentRaw:'[{"type":"htmlEditorComponent","content":"When submitting a manuscript, the Author is required to accept the Terms and Conditions set out in our Publication Agreement – Monographs/Compacts as follows:
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\\n\\nSubject to the following Article, the Author grants to IntechOpen, during the full term of copyright, and any extensions or renewals of that term, the following:
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\\n\\nThe Author shall obtain written informed consent for publication from those who might recognize themselves or be identified by others, for example from case reports or photographs.
\\n\\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Author and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
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\\n\\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licences in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author confirms that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) the Author has the authority to enter into this biding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\\n\\nThe Author agrees to indemnify IntechOpen harmless against all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\\n\\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\nTERMINATION
\\n\\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Author and/or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Author and/or any Co-Author (being a private individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any Co-Author (as a corporate entity) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\\n\\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
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\\n\\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
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\\n\\nIntechOpen agrees to offer free online access to readers and use reasonable efforts to promote the Publication to relevant audiences.
\\n\\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\nIntechOpen has the right to include/use the Author and Co-Authors names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Work and has the right to contact the Author and Co-Authors until the Work is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\nMISCELLANEOUS
\\n\\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by, or on behalf of, the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\\n\\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or their duly authorized representatives.
\\n\\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\\n\\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\\n\\nPolicy last updated: 2018-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'When submitting a manuscript, the Author is required to accept the Terms and Conditions set out in our Publication Agreement – Monographs/Compacts as follows:
\n\nCORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\nSubject to the following Article, the Author grants to IntechOpen, during the full term of copyright, and any extensions or renewals of that term, the following:
\n\nThe foregoing licenses shall survive the expiry or termination of this Publication Agreement for any reason.
\n\nThe Author, on his or her own behalf and on behalf of any of the Co-Authors, reserves the following rights in the Work but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Work as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Author, and any Co-Author, confirms that they are, and will remain, a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Work and all versions of it created during IntechOpen's editing process, including all published versions, is retained by the Author and any Co-Authors.
\n\nSubject to the license granted above, the Author and Co-Authors retain patent, trademark and other intellectual property rights to the Work.
\n\nAll rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the specific approval of the Author or Co-Authors.
\n\nThe Author, on his/her own behalf and on behalf of the Co-Authors, will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Work as a consequence of IntechOpen's changes to the Work arising from the translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits as determined by IntechOpen.
\n\nAUTHOR'S DUTIES
\n\nWhen distributing or re-publishing the Work, the Author agrees to credit the Monograph/Compacts as the source of first publication, as well as IntechOpen. The Author guarantees that Co-Authors will also credit the Monograph/Compacts as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Work.
\n\nThe Author agrees to:
\n\nThe Author will be held responsible for the payment of the agreed Open Access Publishing Fee before the completion of the project (Monograph/Compacts publication).
\n\nAll payments shall be due 30 days from the date of issue of the invoice. The Author or whoever is paying on behalf of the Author and Co-Authors will bear all banking and similar charges incurred.
\n\nThe Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Work worldwide for the full term of the above licenses, and shall provide to IntechOpen, at its request, the original copies of such consents for inspection or the photocopies of such consents.
\n\nThe Author shall obtain written informed consent for publication from those who might recognize themselves or be identified by others, for example from case reports or photographs.
\n\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Author and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
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\n\nThe Author and Co-Authors confirm and warrant that the Work does not and will not breach any applicable law or the rights of any third party and, specifically, that the Work contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy.
\n\nThe Author and Co-Authors confirm that: (i) the Work is their original work and is not copied wholly or substantially from any other work or material or any other source; (ii) the Work has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) Authors and any applicable Co-Authors are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) Authors and any applicable Co-Authors have not assigned, and will not during the term of this Publication Agreement purport to assign, any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licences in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author confirms that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) the Author has the authority to enter into this biding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\n\nThe Author agrees to indemnify IntechOpen harmless against all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\n\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\nTERMINATION
\n\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Author and/or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Author and/or any Co-Author (being a private individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any Co-Author (as a corporate entity) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\n\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
\n\nIntechOpen’s DUTIES AND RIGHTS
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen agrees to provide publishing services which include: managing editing (editorial and publishing process coordination, Author assistance); publishing software technology; language copyediting; typesetting; online publishing; hosting and web management; and abstracting and indexing services.
\n\nIntechOpen agrees to offer free online access to readers and use reasonable efforts to promote the Publication to relevant audiences.
\n\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\nIntechOpen has the right to include/use the Author and Co-Authors names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Work and has the right to contact the Author and Co-Authors until the Work is publicly available on any platform owned and/or operated by IntechOpen.
\n\nMISCELLANEOUS
\n\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by, or on behalf of, the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\n\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or their duly authorized representatives.
\n\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\n\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\n\nPolicy last updated: 2018-09-11
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