**2. Genetic basis of G6PD**

66 Dehydrogenases

*falciparum, P. vivax, P. ovalae, P. malariae and P.knowlesi*—lead to this disease by infecting erythrocytes. Malaria can become a life-threatening condition when it is not treated. Each year, malaria leads to deaths of millions of people all around the world and a large percentage of deaths are seen in Sub-Saharan regions of Africa. As it can be easily seen, malaria and G6PD deficiency share the same geographic distribution. It was shown that G6PD enzyme has various genetic variants and polymorphic frequencies. Highly polymorphic frequencies, which are indicators of G6PD deficiency, are seen in endemic regions for malaria such as Asia, Africa, Central and South America, while in non-endemic regions, these rates decrease, suggesting the relationship between G6PD deficiency and malaria (Haworth*, et al.*, 1988, Organization, 2009, Sutherland*, et al.*, 2010). This relationship reveals two important results. One of them is that G6PD deficiency provides great protection from malaria infection, especially for falciparum infections (Motulsky, 1961, Siniscalco & Bernini, 1961, Ganczakowski*, et al.*, 1995). On the other hand, G6PD deficiency has been recently demonstrated to cause serious problems in fighting against malaria. Primaquine, which is the only drug currently, used in the treatment of Plasmodium infections leads to severe hemolysis in G6PD-deficient patients. This drug may even cause death in G6PD-deficient patients. When primaquine is administered to individuals with G6PD deficiency, its metabolites lead to more severe hemolysis by inducing oxyhemoglobin generation, GSH depletion and stimulation of the hexose monophosphate pathway (Beutler*,*

Therefore, investigations on detection of G6PD deficiency have a vital importance for malaria patients before their treatment with primaquine. On the other hand, the methods that are used for diagnosing G6PD deficiency are unreliable. Even worse is that it is very difficult to distinguish heterozygously-deficient patients from healthy individuals (Peters & Noorden, 2009). All these data indicate that there is an urgent need to develop new methods for reliable detection of G6PD deficiency in order to prevent hemolysis in patients treated with primaquine. Current methods cannot determine primaquine sensitivity in patients with G6PD deficiency every time. However, in our previously researches, we developed a new method for the determination primaquine induced hemolysis *in vitro*. This method provides the determination of G6PD deficiency patients that are susceptible to primaquine independently from the variants of G6PD deficiency. In our studies, it was determined that this method demonstrated high sensitivity for detection of primaquine-induced hemolysis before treatment of malaria patients with primaquine. This chapter aims to represent the relationship between G6PD deficiency and malaria, and to demonstrate the method that has high sensitivity for detection of primaquine-induced hemolysis in patients with malaria whose G6PD enzyme is deficient

This chapter aims to represent the problems in treatment of malaria patients with G6PD deficiency by using primaquine, different methods for determination of G6PD deficiency and a new method to determine primaquine induced hemolysis before treatment of patients

*et al.*, 1955, Bolchoz*, et al.*, 2002, Beutler & Duparc, 2007).

before their treatment with primaquine.

with G6PD deficiency.

G6PD deficiency was identified in 1956 by Carson *et al.* (Alving*, et al.*, 1956), and its Xchromosomal inheritance was discerned in the 1950s by Childs *et al.* (Childs*, et al.*, 1958). G6PD was cloned and sequenced by Persico *et al.*(Persico*, et al.*, 1986, Persico*, et al.*, 1986) in 1986 and independently by Takizawa and Yoshida (Takizawa*, et al.*, 1986) G6PD (Misumi*, et al.*, 1982) is in the hexose monophosphate pathway, the only NADPH-generation process in mature erythrocytes, which lack the citric acid cycle. Deficiency of this enzyme in erythrocytes causes various forms of illnesses such as favism, anemia, chronic nonspherocytic hemolytic anemia, drug-sensitive hemolytic anemia, primaquine sensitivity and jaundice in newborns (Beutler*, et al.*, 1968).

By virtue of fact that G6PD is found in all cells, functional and structural studies have revealed properties of this housekeeping gene (Luzzatto, 2006). G6PD expression level is regulated by hormonal and nutritional factors in only a few tissues. G6PD expression is regulated in liver and adipose tissue, and its activity depends on the rate of fatty acid biosynthesis (Greene, 1993). The G6PD gene region is one of the first regions of the human genome to be completely sequenced (Chen*, et al.*, 1996). The gene encoding G6PD is located near the telomeric region of the distal arm of the X chromosome (Pai*, et al.*, 1980, Szabo*, et al.*, 1984, Patterson*, et al.*, 1987) (band Xq28) and a valuable X-linked genetic marker for determination of X chromosome inactivations (Migeon, 1983). G6PD has various polymorphism sites at the G6PD locus like the colorblindness, Xg blood group and the hemophilia A locus and has close linkage at the X chromosome (Boyer & Graham, 1965, Adam*, et al.*, 1967). G6PD is one of a group of genes including fragile X, (Oberle*, et al.*, 1987) color vision (Motulsky, 1988, Filosa*, et al.*, 1993) hemophilia A (Boyer & Graham, 1965) clasped-thumb mental retardation syndrome (MASA), (Macias*, et al.*, 1992) and dyskeratosis congenita (Arngrimsson*, et al.*, 1993) existing on the distal long arm of the X chromosome.

The X-linkage of the G6PD gene has important implications. This linkage is very stable and linkage with other group locuses is similar in all mammals (Luzzatto & Battistuzzi, 1985, Group, 1989, Luzzatto, 1989, Beutler, 1990). In mice, X-linkage of G6PD was shown by Epstein (Epstein, 1969). Epstein concluded that the G6PD gene is X-linked in the mouse; its synthesis occurs in the oocyte and is dosage-dependent. G6PD is a sex-linked and very polymorphic gene in populations in which males have only one allele (hemizygous) and females have two G6PD alleles. Thus, females can be either normal or deficient (homozygous), or intermediate (heterozygous) phenotypes, whereas males can be either normal or G6PD-deficient phenotype (Luzzatto, 2006). The frequency of the deficient phenotype is higher in males than females owing to males being hemizygous, in which one allele of the gene expresses the deficient phenotype; to arise in females, G6PD-deficiency needs two deficient alleles. However, hemizygous deficient males and homozygous express the same degree of enzyme deficiency level. Since deactivation of one X-chromosome in embryological development in heterozygous females have two populations of red cells (G6PD-normal and G6PD-deficient), with a wide range of total G6PD enzyme activity depending on the relative proportions. If one of the alleles contains deficiency, as a result of

random deactivation of X-chromosomes, about half of the cells will be normal and the other half will be deficient, although there is a wide range of variation around that average (Nance, 1964, Rinaldi*, et al.*, 1976). For this reason, total G6PD activity in heterozygous females can show variability between near-normal to near-deficient (Luzzatto & Battistuzzi, 1985, Segel, 2000). Deactivation of X-chromosome actualizes at random. Correspondingly, binomial distribution would be expected in deficiency level; the extent of this distribution depends on X-inactivation time in embryonic tissue and the number of cells in the embryo. Furthermore, random deactivation of one X-chromosome engenders genetic mosaics in heterozygous females (Luzzatto, 2006). As a result, G6PD mutations show the typical mendelian X-linked inheritance (Adam, 1961), severe G6PD deficiency is much more common in males than in females, and X-chromosome inactivation in heterozygous females for two different G6PD alleles indicate somatic cell mosaicism (Beutler*, et al.*, 1962, Gall*, et al.*, 1965).

Glucose-6-Phosphate Dehydrogenase

Deficiency and Malaria: A Method to Detect Primaquine-Induced Hemolysis *in vitro* 69

177 bp upstream of the translation-initiating codon (Martini*, et al.*, 1986). The G6PD activity and mRNA quantity differ between tissues (Nagel & Roth, 1989, Greene, 1993). S1 nuclease and primer extension analyses of mouse G6PD mRNA indicate that when the transcriptional start site regulated with lipogenesis in liver and adipose tissue, in kidney G6PD is expressed constitutively (Ho*, et al.*, 1988); this quantity potentially depends on oxidative stress, tissue specific differences and reductive biosynthesis reactions (Nagel & Roth, 1989, Greene, 1993). Some different mRNA forms of G6PD mRNA have been found, but their functions are completely unknown. The alternatively spliced form has been documented (Hirono & Beutler, 1988, Hirono & Beutler, 1989, Cappellini*, et al.*, 1993), but this mRNA frame contains 138 nucleotides (Mason*, et al.*, 1988, Persico*, et al.*, 1989, Bautista*, et al.*, 1992, Tang*, et al.*, 1994). Some researchers (Kanno*, et al.*, 1989) suggested that in reality, G6PD translation product made from two separate mRNAs as a result of study to be based on an artifact (Henikoff & Smith, 1989, Beutler*, et al.*, 1990, Mason*, et al.*, 1990, Yoshida & Kan, 1990).

Up to 450 G6PD variants have been identified depending on the enzyme kinetics, physicochemical characteristics, and other parameters (Luzzatto & Battistuzzi, 1985, Chen*, et al.*, 1991). Nearly 300 variants of these have been confirmed by the World Health Organization (1967). Point mutations and small deletions trigger defects in the enzyme structure. These structural defects cause altered activity, instability of the enzyme or

G6PD is a typical cytoplasmic, housekeeping enzyme and has been found in all cells from liver to kidney and organisms, from prokaryotes to yeasts, to protozoa, to plants and animals (Luzzatto & Battistuzzi, 1985, Antonenkov, 1989, Glader, 1999, Notaro*, et al.*, 2000). Inactive form of G6PD is a monomer with 515 amino acids and has a molecular weight of over 59 kDa (Rattazzi, 1968). The primary structure of the G6PD enzyme in humans has been determined from the sequence of full-length cDNA clones (Persico*, et al.*, 1986). Furthermore, the tertiary structure of the enzyme has been determined (Au*, et al.*, 1999). Dimer structure of the two subunits in the enzyme are symmetrically located across a

Activation of the enzyme requires NADP+ tightly binding to dimer or tetramer formation of enzyme. G6PD catalyses the first step of the oxidative pentose phosphate pathway and controls reaction velocity (Wrigley*, et al.*, 1972). In this first step, while G6PD catalyses the conversion of glucose 6-phosphate (G6P) to 6-phosphogluconolactone, at the same time it reduces NADP to NADPH (Au*, et al.*, 1999, Turner, 2000). Human G6PD has no activity with nicotinamide adenine dinucleotide (NAD) as coenzyme. Also, G6P is very specific for its substrate compared to other hexose phosphates (e.g., galactose 6-phosphate or mannose 6-phosphate) (Luzzatto & Battistuzzi, 1985, Glader, 1999). The G6P binding site is nearby lysine 205 in tertiary structure of the enzyme, and this amino acid has a critical role in electron transfer (Bautista*, et al.*, 1995). The NADP binding site is located nearby 38 to 43 amino acids; this region constitutes the Nterminus in tertiary structure encoded in exon 3. This site is important for stability of G6PD (Au*,*

decreased affinity of G6PD for its substrates (Luzzatto, 2006).

**3. Structure of G6PD and enzymatic properties**

complex interface of β-sheets (Au*, et al.*, 1999).

The total length of the gene is about 18.5 kb on the X chromosome (xq28) and contains 13 exons. Exon 13 is about 800 nucleotides long and contains the translation stop codon (Nagel & Roth, 1989, Greene, 1993). The protein-coding region is divided into 12 segments, ranging in size from 12 to 236 bp (Martini*, et al.*, 1986). Exon and intron numbers and the exon sizes and sequences are conserved in higher eukaryotes (Nagel & Roth, 1989, Greene, 1993). The first exon contains no coding sequence and intron 2 between exons 2 and 3 is extraordinarily long, extending for 9,857 bp. The function of this long intron is unknown; it may be important for transcription or processing because compressed versions of the G6PD gene still have this largest intron in some species (Chen*, et al.*, 1991, Mason*, et al.*, 1995).

The sequence of the whole G6PD gene is known (Chen*, et al.*, 1991). G6PD sequence analogy between humans and mice or rats is 87%. The analogy between the mouse and rat cDNA sequences is greater than humans with 93% similarity. Most of the sequence dissimilarity is in the 3´- UTR region, which has 600 nucleotides on average and contains a single polyA site (Nagel & Roth, 1989, Greene, 1993). G6PD gene promoter is embedded in a CpG island that starts about 680 nucleotides upstream of the transcription initiation site, extending about 1,050 nucleotides downstream of the initiation site, and ends at the start of the first intron (Chen*, et al.*, 1991). CpG island is conserved between some species (Martini*, et al.*, 1986, Toniolo*, et al.*, 1991), and has highly enriched guanine and cytosine residues, like characteristically in other housekeeping genes and this island appears to be preserved between humans and mice (Toniolo*, et al.*, 1991).

The promoter of the G6PD gene contains a TATA-like, TTAAAT sequence, and a great number of stimulatory protein 1 (Sp1) elements (Philippe*, et al.*, 1994, Rank*, et al.*, 1994, Franze*, et al.*, 1998, Hodge*, et al.*, 1998). These Sp1-binding sites are essential for promoter activity (Philippe*, et al.*, 1994). Deletion analysis has uncovered that the "essential" segment of the promoter is only about 150 bp (Ursini*, et al.*, 1990).

The transcribed region from the initiation site to the poly(A) addition site covers 15,860 bp. (Chen*, et al.*, 1991). The major 5'-end of mature G6PD mRNA in several cell lines is located 177 bp upstream of the translation-initiating codon (Martini*, et al.*, 1986). The G6PD activity and mRNA quantity differ between tissues (Nagel & Roth, 1989, Greene, 1993). S1 nuclease and primer extension analyses of mouse G6PD mRNA indicate that when the transcriptional start site regulated with lipogenesis in liver and adipose tissue, in kidney G6PD is expressed constitutively (Ho*, et al.*, 1988); this quantity potentially depends on oxidative stress, tissue specific differences and reductive biosynthesis reactions (Nagel & Roth, 1989, Greene, 1993). Some different mRNA forms of G6PD mRNA have been found, but their functions are completely unknown. The alternatively spliced form has been documented (Hirono & Beutler, 1988, Hirono & Beutler, 1989, Cappellini*, et al.*, 1993), but this mRNA frame contains 138 nucleotides (Mason*, et al.*, 1988, Persico*, et al.*, 1989, Bautista*, et al.*, 1992, Tang*, et al.*, 1994). Some researchers (Kanno*, et al.*, 1989) suggested that in reality, G6PD translation product made from two separate mRNAs as a result of study to be based on an artifact (Henikoff & Smith, 1989, Beutler*, et al.*, 1990, Mason*, et al.*, 1990, Yoshida & Kan, 1990).

Up to 450 G6PD variants have been identified depending on the enzyme kinetics, physicochemical characteristics, and other parameters (Luzzatto & Battistuzzi, 1985, Chen*, et al.*, 1991). Nearly 300 variants of these have been confirmed by the World Health Organization (1967). Point mutations and small deletions trigger defects in the enzyme structure. These structural defects cause altered activity, instability of the enzyme or decreased affinity of G6PD for its substrates (Luzzatto, 2006).


**Author details**

Isabel Cristina Affonso Scaletsky Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Brazil

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**61**

1979;**3**:95-99

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Kaper JB, Black RE, Bravo N, Levine MM. Detection of an adherence factor of enteropathogenic

*Escherichia coli* with a DNA probe. The Journal of Infectious Diseases.

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*AI-Based Approach for Lawn Length Estimation in Robotic Lawn Mowers DOI: http://dx.doi.org/10.5772/intechopen.97530*

one of which is used for controlling the lawn grass cutter and another is for its mobility. These controllers are powered by the same battery, and therefore, battery wastage depends on their usages. The subsystem, "Lawn Grass Length/Not Lawn Grass Estimator" is newly developed.

The robo-mower is used for experiments by attaching sensors, a single-board computer, a personal computer and peripheral devices on the robo-mower, as shown in **Figure 3**. All these devices are managed by an ROS (robot operating system) running on the personal computer. The robo-mower can be autonomously driven; however, it is controlled using a Bluetooth controlling device in the experiments to increase the accuracy of the experiments. A camera can be used as a sensor, but it is inadequate for the experiments due to its high cost of image processing software and hardware. In the experiments, it will be shown that no camera is needed for the required estimation.


**3.2.1 Emotion-focused coping strategies**

Essentially, there are conscious and intentional cognitive strategies that originate in an attempt to combat emotional distress, such as distraction, 'shutting down' and passive avoidance on one hand, looking for sympathy, turning to religious faith and positive reappraisal on the other. Endler and Parker (1990) describe emotion-orientated coping as comprising emotional reactions that are self-orientated but that may actually increase stress levels since they fail to actively reduce stress and may instead heighten the negative emotional component of the stress experience. Examples of such maladaptive reactions include blaming oneself for being too emotional, worrying about what one is going to do, or getting angry.

### **3.2.2 Problem-focused coping strategies or task-orientated coping**

There are the ways in which individuals consciously seek social support and elicit help from others: direct action, confrontation, planning and information seeking are all examples of this group. It involves using a problem-solving approach to eliminate stressors. For example, perceiving a demanding schedule as being stressful and deciding to use time management skills as a means to prioritise one's demands would be an example of taskorientated coping.

#### **3.2.3 Avoidance-orientated coping**

The coping strategies that are based on distraction and social diversion are characterised here. This coping style involves turning away from the stressors, possibly by ignoring it, psychologically distancing oneself from it, or engaging in another task. An avoidance coping style may not effectively eliminate stress since this style of coping does not actively reduce stress. However, engaging in substitute tasks may be beneficial as a means of temporarily removing oneself from stress until a patient is more able to actively face stress issues and implement a task-orientated coping style (Endler & Parker, 1990). Recent research findings have suggested that the use of an avoidance-orientated coping style may serve a protective function for individuals that are in situations in which they are not able to control the stressor that they are faced with (Simon-Thomas et al, 2001). For example, children that were exposed to the stressor of parental argument (stressor that they cannot control) were found to be protected/ buffered from the effects of inter-parental conflict on child internalising behaviours if they engaged in avoidance-orientated coping. Thus, depending upon the nature of the stressor, avoidance-orientated coping may be seen as either maladaptive or adaptive.

#### **3.2.4 Adaptive involuntary coping strategies**

Defence mechanisms reduce conflict and cognitive dissonance during sudden changes in reality caused by the illness. If such changes are not adjusted for they can result in disabling anxiety and depression. Adaptive defences operate in a hierarchical way: trough distortion or denial (immature defence level), repression, intellectualisation and reaction formation (intermediate defences), or at a higher adaptive level through self-assertion, affiliation, sublimation and humour.

#### **3.2.5 Coping hierarchy**

With the advent of measures that sought to investigate the nature, structure, and correlates of coping, theoreticians and researchers alike have begun to shift their views to focus more

Essentially, there are conscious and intentional cognitive strategies that originate in an attempt to combat emotional distress, such as distraction, 'shutting down' and passive avoidance on one hand, looking for sympathy, turning to religious faith and positive reappraisal on the other. Endler and Parker (1990) describe emotion-orientated coping as comprising emotional reactions that are self-orientated but that may actually increase stress levels since they fail to actively reduce stress and may instead heighten the negative emotional component of the stress experience. Examples of such maladaptive reactions include blaming oneself for being too emotional, worrying about what one is going to do, or

There are the ways in which individuals consciously seek social support and elicit help from others: direct action, confrontation, planning and information seeking are all examples of this group. It involves using a problem-solving approach to eliminate stressors. For example, perceiving a demanding schedule as being stressful and deciding to use time management skills as a means to prioritise one's demands would be an example of task-

The coping strategies that are based on distraction and social diversion are characterised here. This coping style involves turning away from the stressors, possibly by ignoring it, psychologically distancing oneself from it, or engaging in another task. An avoidance coping style may not effectively eliminate stress since this style of coping does not actively reduce stress. However, engaging in substitute tasks may be beneficial as a means of temporarily removing oneself from stress until a patient is more able to actively face stress issues and implement a task-orientated coping style (Endler & Parker, 1990). Recent research findings have suggested that the use of an avoidance-orientated coping style may serve a protective function for individuals that are in situations in which they are not able to control the stressor that they are faced with (Simon-Thomas et al, 2001). For example, children that were exposed to the stressor of parental argument (stressor that they cannot control) were found to be protected/ buffered from the effects of inter-parental conflict on child internalising behaviours if they engaged in avoidance-orientated coping. Thus, depending upon the nature of the

stressor, avoidance-orientated coping may be seen as either maladaptive or adaptive.

Defence mechanisms reduce conflict and cognitive dissonance during sudden changes in reality caused by the illness. If such changes are not adjusted for they can result in disabling anxiety and depression. Adaptive defences operate in a hierarchical way: trough distortion or denial (immature defence level), repression, intellectualisation and reaction formation (intermediate defences), or at a higher adaptive level through self-assertion, affiliation,

With the advent of measures that sought to investigate the nature, structure, and correlates of coping, theoreticians and researchers alike have begun to shift their views to focus more

**3.2.2 Problem-focused coping strategies or task-orientated coping**

**3.2.1 Emotion-focused coping strategies**

getting angry.

orientated coping.

**3.2.3 Avoidance-orientated coping**

**3.2.4 Adaptive involuntary coping strategies**

sublimation and humour.

**3.2.5 Coping hierarchy**

on the hierarchical nature of coping. Three broad levels have been implicated: (a) coping styles that reflect global, dispositional, macroanalytic tendencies (e.g., monitoring-blunting, vigilance-avoidance, approach-avoidance); (b) coping strategies or modes that reflect an intermediate level in this hierarchy, and are typically indicated by summative scores on coping scales (e.g., confrontation, seeking social support, planful problem solving); and (c) coping acts or behaviors that reflect specific, situation-determined, microanalytic responses that are often indicated by individual item endorsement on a coping scale (Endler & Parker, 1990; Krohne, 1996; Schwarzer & Schwarzer, 1996).

The literature on coping with chronic illnesses and disabilities has, likewise, generated much insight into the nature and structure of coping efforts directed at diffusing or removing the stress engendered by the associated trauma, loss, and pain. Results from these and other studies strongly suggest that coping plays a significant role during the process of psychosocial adaptation to both sudden and gradual onset of chronic illnesses and disabilities. More specifically, these results indicate that: (a) a wide range of coping efforts has been employed by persons with disabilities to deal with the stresses engendered by their conditions; (b) these numerous efforts, both problem-solving and emotional-focused coping, as well as engagement- and disengagement- type coping have been found to be adaptive; (c) different coping efforts assume different roles and are, therefore, differentially employed to regulate stressful emotions and solve problems during the adaptation process; (d) coping efforts have played both a direct role (i.e., are directly linked to measures of psychosocial adaptation to disability) and a mediator role (i.e., act as mediators between sociodemographic variables, personality attributes, disability-related factors, environmental conditions, and outcomes of psychosocial adaptation); and (e) different disabling conditions imply different functional (e.g., mobility, manipulation, fatigue, cognitive) limitations, medical courses and prognostic indicators (e.g., deteriorating, unpredictable, stable), related health problems, treatment modalities, and psychosocial reactions. Individuals cognitively appraise the situation in terms of its personal significance, and then look at the resources and options they have available. This notion helps to appreciate the variability in individual coping reactions. The coping strategies adopted by an individual are quite unique; they include the way one perceives threatening experiences and reacts to stressful events, how one manages ones emotions and how one attempt to solve problems.

#### **3.2.6 Age and gender differences**

The effectiveness of coping strategies across the lifespan has been another area of clinical interest. Contrary to suggested belief that individuals become less efficient at coping with the demands of life as they get older, research into success of coping revealed immunity to the age process. Thus, in a recent study investigating age variance in coping across a broad range of stressors in a sample of more than 2,000 men ranging in age from the late 40s to over 90, there were no significant age differences in the reporting of negative emotional states in response to stressors, nor perceived efficacy in coping (Dunkin & Amano, 2005). In relation to gender differences, women appear to report positive and negative affects more vividly than men. In one study (Diener et al, 1999), gender accounted for 13 percent of the variance of the intensity of reported emotional experiences. There is also considerable evidence that women are more likely to use formal helping systems than are other groups, especially men and people of colour. One recent study addressed the natural coping systems of male and female students in largely young, Euro-American sample (Slattery et al, 2002).

Rheumatoid Arthritis: A Historical and Biopsychosocial Perspective 209

psychological wellbeing. Much of this work has focused on the health and wellbeing of chronically ill patients with musculoskeletal illnesses such as rheumatoid arthritis. Scharloo and colleagues (Scharloo et al, 1998) presented data showing that patients with rheumatoid arthritis, chronic obstructive pulmonary disease and psoriasis achieve significantly better functioning when cope by seeking social support and believe in controllability and curability of the disease. Support from family and close companions can help to increase individual's sense of control of their symptoms, as this kind of empowerment helps people

While today we celebrate the advances in clinical science and in therapeutics, the enigmatic nature of RA still gives way to conceptualisation disparity. Indeed, despite some significant gains in the areas of immunopathology and genetics, Landré Beauvais' first clinical description of rheumatoid arthritis in 1800 encompasses most of what we know about this disease today. Where no single factor can provide a satisfactory explanation of a disorder in question, the biopsychosocial approach helps to position the multiple layers of existing knowledge in relation to it. Laboratory studies of inflammation and genetics provide the scientific basis of mainstream treatments, although the speciality still lacks good clinical and

In conclusion, our predecessors are to be congratulated for providing a platform for future developments. There are compelling data to suggest that the combination of earlier use of disease modifying treatments, attention to coexisting conditions and patient's coping and illness perception, that are considered to be important contributing factors in the relationship between physical and psychological factors in RA. The evolution and refinement of the newer therapies will allow more patients to realistically strive for disease remission and return of function in the near future. Rheumatologists of tomorrow are to be encouraged to carefully sift through the complex information generated during assessment process and to focus clinical and therapeutic developments where they can best be

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**4. Conclusion**

**5. References**

They found significant gender-specific pattern in the use of coping strategies and their perceived effectiveness. The authors reported that females were significantly more likely than males to seek appropriate help and try to solve the problem, but also to use eating, cleaning, shopping, crying and praying. Interestingly enough, males were more likely to report using sex and masturbation in their attempt to cope than females. Both sexes described avoiding others, doing nothing, and ignoring the problem as least helpful.

#### **3.2.7 Cultural aspects of coping**

Cultural aspects of coping emerge as a new dimension in the ethnically diverse world today. Native Americans, for example, tend to turn to spiritual leaders and extended family (informal helping system) rather than to formal helping systems such as therapists (LaFramboisie, 2000). Similar findings have been reported for African Americans and Hispanic cultures (Sue & Sue, 1997); in England the Government's race equality strategy (Department of Health UK, 2003) have illustrated how local African community avoid statutory care systems and try to contain problems in their homes long beyond the expected point of seeking outside help. This could be a result of natural difficulty with disclosing problems or sharing emotions in this group or inadequacy of existing services to address their psychological needs. In his timely review Brendan Kelly (Kelly, 2003) highlighted that globalisation and large-scale social changes could induce a wave of 'anomie'in migrants, that is in essance a breakdown of social values (Durkheim, 1947). For Durkheim, in 1897 anomie arised more generally from a mismatch between personal or group standards and wider social standards, or from the lack of a social ethic, which produced moral deregulation and an absence of legitimate aspirations. For migrants living in a state where societal standing is compromised and social ties are broken, anomie becomes a nurtured condition that has detrimental effects on their coping capacity.

#### **3.3 Illness perception**

Patients do not respond to treatment in a predictable manner and show a wide variation in perception of causation. Individual preconceptions determine help seeking, compliance and treatment outcome, yet clinicians rarely explore these issues. Early exploration of illness perceptions may enhance health behaviour and maximise the impact of intervention.

Lay illness representations often diverge from the clinician's understanding of the presenting problem and strongly influence treatment behaviour. Perception of the significance of decline in social functioning, including some losses in valued activities, which an individual regards as being important, e.g. visiting the family, going away on holiday is an important factor that only recently has been emphasised by Katz & Yelin (1995). In their 4-yr longitudinal study they found that patients' perception of a decline in valued activities by 10% was followed by a seven-fold increase in depression over the subsequent year. The self-regulation model (Leventhal et al, 1980) suggests that the cognitive and emotional aspects of illness perception guide the response to illness and determine the effectiveness of coping. Furthermore, five components of illness perception have been recognised: the identity of the illness (i.e., the symptoms and their labels); the perceived consequences of the illness; the illness's causation; its likely time line and the potential for control and cure (Lau et al, 1989).

Studies investigating the relationship between illness perceptions and coping show that the way affected people deal with their illness has great influence on their physical and psychological wellbeing. Much of this work has focused on the health and wellbeing of chronically ill patients with musculoskeletal illnesses such as rheumatoid arthritis. Scharloo and colleagues (Scharloo et al, 1998) presented data showing that patients with rheumatoid arthritis, chronic obstructive pulmonary disease and psoriasis achieve significantly better functioning when cope by seeking social support and believe in controllability and curability of the disease. Support from family and close companions can help to increase individual's sense of control of their symptoms, as this kind of empowerment helps people act on their own behalf in relation to their dealings with RA (Delzell, 2011).


**1. Introduction**

#### **1.1 Background of the study**

In parallel with the line of feeding 9.8 billion people by 2050, agricultural productions are largely expanding and intensifying [1]. The agricultural sector that made a living for 65% of poor working adults living in the developing world [2], includes the largest segment of society afflicted with the greatest amount of pesticide exposure [3]. Farmers and farmworkers put themselves at risk of pesticide poisoning during the production process [4]. They are routinely exposed to toxic pesticides via spray, drift or direct contact with pesticide residues on treated crops or soil [5].

Excessive and indiscriminate use of the most infamous synthetic organic chemicals, specifically chlorinated hydrocarbons like DDT, left a long-lasting imprint on every atom on earth since the beginning of the green revolution to date [6]. Despite the early alarming signs on the gruesome effects of these chemicals, such as the sharp decline of the bald eagle and other birds in the highest trophic levels of the food chain [7], the ascendency of using these chemicals pressed onward. This entailed unintentional pesticide exposure to the general population via food consumption [3, 8].

In Ethiopia, the agricultural sector is a source of livelihood for more than 80% of the population and represents more than three quarters of national exports [9], which impacts that almost 80% of the population in Ethiopia contributes to posing negative health issues to both humans and the environment, leading to the prevalence of acute and chronic health issues among people in the whole population [10, 11]. Hence, addressing this problem will have practical benefits for Ethiopia and will contribute to understanding of this widespread phenomenon among farmers almost in the whole country.

Unsafe practices exhibited by farmers in Ethiopia included the frequent mixing of highly toxic pesticides, unsafe storage and unsafe transport methods [12], unsafe disposal of empty pesticide containers [10**]**, spraying while barefooted, using obsolete pesticides [13**]**, selling illegal, expired, hazardous, unknown, repacked pesticides in small containers without any labeling, manufacturing or expiry date by unauthorized and untrained people in shops and local village in open markets [13], reusing empty insecticide containers for food and potable water, washing pesticide-contaminated work clothing with the family clothes and using highly toxic insecticides to treat head lice, fleas, bedbugs, and even to try to cure open wounds using malathion and (DDT), sometimes with fatal results [14].

Few researches in Ethiopia were conducted concerning the same area of study [10–12, 15], and further studies about pesticide use and pesticide-related illnesses are needed to develop more effective approaches for protecting farmers from pesticide exposure and moving the targets towards organic farming, resulting in having a healthy community free of disabilities and other dysfunctional diseases.

#### **2. Material and methods**

#### **2.1 Study area**

The study was conducted at Finchawa and Tullo rural kebeles in Hawella Tula sub city, which is located in Hawassa City Administration, Sidama, Ethiopia. Tullo and Finchawa are considered the catchment area of Lake Hawassa. The area lies on 1728 meters above sea level. The land form is plain [16], and has tropical savanna climate with two seasons [17]**.** The mean annual temperature is 20.9 °C with

**95**

*Limited Knowledge and Unsafe Practices in Usage of Pesticides and The Associated Toxicity...*

mean rainfall 997.6 mm [17]. The type of soils around Lake Hawassa in general is Andisols. A source of information about the type of soil in the study area is Hawassa University, Agricultural Campus. The two main crops cultivated in both areas are

A cross-sectional survey with both qualitative and quantitative data collection research design were employed. The study was conducted between June and September 2020. The study also applied concurrent triangulation in data collection, where both qualitative and quantitative data were collected in one phase of the research study and equally weighted. A concurrent triangulation procedure is the model mostly employed when researchers first consider mixed methods as it results in a shorter data collection time period [18]. The three different primary data sources used in this study were a standardized questionnaire, key informant

A supportive letter was given from the College of Natural and Computational Science, Biology Department, Hawassa University, to get the permission of the respective directions to select the study participants and conduct the interviews in extension offices, health institutions and hospitals. Two days of training were allocated to train four experienced data collectors. The training focused on explaining the purpose of the study, the meaning and interpretation of some scientific terminologies in each question, and obtaining consent from every single participant. The data collectors were experienced and capable of speaking the local languages (Amharic and Sidamingia). The four data collectors conducted door-to-door visits based on a list of members of the households to get responses and fill in the questionnaire. The list of householders was coded and their names were not mentioned for anonymity and confidentiality. In-depth interviews with officials and physicians were conducted by the researchers with the help of a professional translator who

All data was coded and analyzed using SPSS version 25. Descriptive statistics were used to summarize frequencies and proportions, and results were presented in tables and charts. A multiple logistics regression model was employed to determine the effect of the independent variables on farmers' knowledge and the prevalence of self-reported toxicity symptoms. Multiple logistic regression was employed due to its powerful statistical way of modeling a binomial outcome for categorical data [19]. Chi-square, as well as Hosmer and Lemeshow tests, were firstly used before running the logistic regression test to measure the association between the independent and dependent variables and to check whether the model fits the data or not respectively. The data was summarized using the odds ratio, 95% confidence

The study employed a multi-stage sampling technique due to the advantage it gives of using more than one stage and combine several sampling techniques. The multi-stage sampling in this study entitled four stages. In the first stage, the

*DOI: http://dx.doi.org/10.5772/intechopen.96093*

**2.2 Study design and data collection tools**

interview and a document review.

spoke both Amharic and English languages.

**2.5 Sampling technique and sample size determination**

**2.4 Data analysis**

interval at .05 alpha levels.

**2.3 Methods of data collection**

corn and ensete.

#### *Limited Knowledge and Unsafe Practices in Usage of Pesticides and The Associated Toxicity... DOI: http://dx.doi.org/10.5772/intechopen.96093*

mean rainfall 997.6 mm [17]. The type of soils around Lake Hawassa in general is Andisols. A source of information about the type of soil in the study area is Hawassa University, Agricultural Campus. The two main crops cultivated in both areas are corn and ensete.


*C2 Contributory Relational:*

The second style in the relational set is the contributory style. People who favor this style prefer to work behind the scenes to help others achieve their goals. A sense of accomplishment and success exists when the "front" person or group accomplishes "his"/"her"/"their" task. The contributory relational achieving style involves "partnering" in the other person's or group's goal, with the understanding that the major and/or public accomplishment belongs to the "front" person or group. Mentoring in the family, school, and workplace are examples of this style.

*C3 Vicarious Relational:*

Third in the relational domain is the vicarious style. People who prefer this style derive a genuine sense of accomplishment from the success of others with whom they identify. Individuals who call upon the vicarious style do not "get into the act" themselves. As spectators or supporters, rather than direct participants, their sense of pride in the success of others with whom they identify is sufficient reward.


**3. Conclusions**

increase in survival without increased neonatal morbidity has been observed in preterm infants born between 25 and 28 weeks [6]. Therefore, increased survival of these newborns makes them more susceptible to developing acute and chronic morbidities such as intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, chronic lung

About 80% of premature children are born between 32 and 37 weeks of gestation, which is known as moderate/late preterm. About 10% of these children are born between 28 and 32 weeks of gestation, the rest correspond to births before 28 weeks. Among the former, which has a comparatively lower risk compared to those of a lower gestational age, some die unnecessarily due to the lack of simple and essential care, such as heat and nutrition [7]. Babies born between weeks 32 and 37 have at least seven times the risk of neonatal mortality and a 2.5 times higher risk of postneonatal infant mortality [8]. Similarly, in the 28–32 week group in lower income countries, more than half of the children die; many could survive without intensive care [7].

Consequently, for neonates to face the risk of death, as well as their short- and long-term morbidity, basic prevention measures such as timely diagnosis and early treatment should be included, taking into consideration the most frequent risks and problems in these patients.

The risk of death is greater on the first day of life and it has been confirmed that the proportion of deaths occurring during the first week of life are constant in all regions and economic environments. This highlights the urgent need to provide timely and high-quality care from the moment of birth. The time between a potentially harmful event and death can be very short and the first minute after birth (golden minute) is the crucial window for neonatal resuscitation. In general, all newborns are vulnerable after childbirth, which is a key point for growth and development. The highest risk of death is concentrated immediately after birth and in the first days of life. For most newborns, essential care is required, which the mother will ideally provide, such as providing warmth, a clean and safe environment, and providing nourishment through breastfeeding. However, in premature or low birth weight babies, the care requirements are greater since these children are especially vulnerable to thermal instability,

In particular, premature babies are especially vulnerable and can become hypothermic in a matter of minutes, which increases the risk of respiratory distress, hypoglycemia, infections, and death. Problems related to childbirth and premature delivery are predominant causes of early neonatal mortality, while infections are more common in the late neonatal period [9].

Due to the abovementioned, temperature is an aspect of basic care for newborns. This is considered fundamental because hypothermia increases the probability of early and late neonatal death [10–12]. Consequently, by providing appropriate thermal conditions during delivery, immediate care, and in intensive care rooms, the risk of hypothermia is reduced and neonatal survival is improved. In this sense, differences have been observed in admission temperatures between extreme and moderate preterm infants, and it has been confirmed that extreme

**2. Neonatal care and the main problems in newborns**

difficulty breathing, feeding limitations, and the risk of infections.

disease, and neurosensory disorders, among others.

4 Selected Topics in Neonatal Care

The scenario shown with some examples of frequent problems and interventions involved in neonatal care highlights the need for a complex and comprehensive therapeutic approach. Neonatal care interventions that have been effective in improving the survival of hospitalized newborns and considered a priority are: the use of antenatal corticosteroids to prevent neonatal RDS, early initiation of breastfeeding, umbilical cord care, and kangaroo care in premature babies [24]. Additionally, processes to improve the quality of neonatal care are considered key points for nutrition, use of medicines, central line care, respiratory care, and care in the delivery room with the aim of reducing the incidence of necrotizing enterocolitis, growth deficit, mortality, sepsis, chronic lung disease, brain damage, and retinopathy of prematurity [25]. Other aspects of special attention in timely neonatal care, particularly in neonatal intensive care, include hemodynamic monitoring and respiratory care.

[6] Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. Journal of the American Medical Association. 2015;**314**:1039-1051. DOI: 10.1001/jama.2015.10244 [7] Lawn JE, Davidge R, Paul VK, von XS, de Graft JJ, Costello A, et al. Born too soon: Care for the preterm baby. Reproductive Health. 2013;**10**(Suppl 1):S5. DOI: 10.1186/1742-

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[11] Garcia-Munoz RF, Rivero RS, Siles QC. Hypothermia risk factors in the very low weight newborn and associated morbidity and mortality in a neonatal care unit. Anales de

[12] Wilson E, Maier RF, Norman M, Misselwitz B, Howell EA, Zeitlin J, et al. Admission hypothermia in very preterm infants and neonatal mortality and morbidity. The Journal

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[18] Van Haltren K, Malhotra A. Characteristics of infants admitted with hypoglycemia to a neonatal unit. Journal of Pediatric Endocrinology & Metabolism. 2013;**26**:525-529. DOI:

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