Helicobacter pylori Infection in Peptic Ulcer Disease among Young People

Abstract

Peptic Ulcer Disease (PUD) is a common chronic disease of the Gastrointestinal Tract (GIT) worldwide, affecting 87.4 million people with 257,500 mortality turnouts in the year 2015. PUD is a painful open sore that develops in the wall lining of the lower part of the esophagus, the stomach, or the duodenum. PUD has both internal and external causative factors, of which Helicobacter pylori (H. pylori) is a major role player, accounting for 70–95% of its prevalence rate globally. H. pylori infection is acquired generally during the younger ages of life with its various mode of transmission, and with a prevalence rate of 90% in some developing countries, but remains asymptomatic till later years in life. This chapter attempts to provide the overview of H. pylori infection among young people, since they differ from the elderly, in terms of its prevalence rate, its risk factors, its complication rate, its diagnostic tests and managements, and its higher rate of antibiotic resistance.

1. Introduction

1.1 Background

H. pylori (H. pylori) seems to play a significant role in the development of Peptic ulcer disease (PUD), a disease which is said to affect more that 10% of the world’s population [1]. From the global perspective, H. pylori infection affects above 50% of the world’s population, and is known to affect at least one-third of the young people especially children [2, 3]. Up to 90% of the children in the developing countries get infected by H. pylori where as in the developed countries it has 1.8–65% prevalence rate [4]. In some parts of Africa, H. pylori infection rate ranges from 40–90% [4]. Most of the individuals according to knowledge from literature shows that nearly 10% of the children in the developing nations remain asymptomatic after acquiring H. pylori infection [5].

H. pylori is a gram-negative microaerophilic bacterium that affect the mucous lining of the stomach, especially the antrum [6, 7]. H. pylori infection may result in either developing gastric ulcer (70–90%) or duodenal ulcer (90%) or both [1, 8]. H. pylori infection occurs in the early stages of life, but remains asymptomatic, and can live with the affected individual for a long period of time until it is treated [7]. Common signs and symptoms identified with the infection among the young people includes nausea, vomiting, gnawing or burning abdominal pain, intestinal bleeding, gastric reflex, occasional fever, poor appetite, bloating abdomen, frequent burping, tiredness and weakness, and weight loss [5]. The effects of this infection can progress to more complicated form, causing both gastric and extra-gastric conditions if not treated early or left untreated [9]. H. pylori infection causes gastric adenocarcinoma through a progressive sequence of gastritis to atrophy, then intestinal metaplasia, then to dysplasia, and finally to carcinoma [10]. Several gastro-duodenal complications may develop once H. pylori infection is well established [11].

Literature shows that there are both invasive and non-invasive diagnostic investigations that can be used to determine the presence of the infection [2, 12]. The recommended management approach is the screen-and-treat strategies [3]. Usually, the first line of treatment is the triple therapy, and according to researched work has proven to be the best in the management of H. pylori infection among the young people [13]. It has been observed that clarithromycin resistance is the main cause of treatment failure among the affected individuals [14]. Due to the increased rate of antibiotic resistance in the eradication of H. pylori, recommendations have been made for the development, and the use of new vaccines to prevent the infection among young people [13, 14]. Research seems to prove that the infection of H. pylori increases with age, and the rate of infection among the elderly is higher than the youngsters, therefore critical attention must be given to children since 80% of the infection usually occur in childhood which usually persist until adulthood [7].

2. Bacteriology

H. pylori bacterium was first discovered by Marshall and Warren in the year 1983 after they have cultured a gastric biopsy specimen of Peptic ulcer disease patients over a prolonged period of time [15]. This bacterium initially was called Campylobacter until the year 1989, when it was given its currently known name when a sequence of ribosomal features revealed its uniqueness [16]. This essential gastroenterological transforming effort gained global recognition and so won a Noble prize in physiology and medicine in the year 2005 [17]. Literature currently reveals the identification of about 22 more species possessing similar cellular morphology, and test positive for oxidase, catalase and urease test, and in addition have the stomach, and the intestine as their colonizing site in their mammalian host [2].

H. pylori is a helical-shaped, unipolar, multiflagellate, slow growing, microaerophilic, Gram-negative motile bacterium [7]. This bacterium typically is 0.5 to 1.0 μm in width, and can be 2.5 to 5 μm long [17]. H. pylori possesses smooth and round end surface from which evolves one to six polar-sheath flagella [18]. Age, growth conditions, and specie type can cause the spiral wavelength of the organism to vary [17]. Chocolate agar or blood agar are none selective agar media, and selective agars like Skirrow’s brooded in a humidifier, micro-aerobic of 5% oxygen at the degree centigrade of 35 to 37, are some media agars on which the bacterium H. pylori can be cultured for 3 to 7 days [2]. It has been found that old, stressed or mal-nutritious and prolong air exposure of cultured cells can become idle or inactive coccoid which enhances its survival in feces, and even in water outside of the human host [17].

Irrespective of the hostile condition of the human stomach, H. pylori has the ability to colonize a specific biological micro niche within the gastric lumen, survive, and persist for a long period of time, if not treated effectively as compared to other microorganisms that thrives well in very low pH environment [7, 12, 15]. Research has proofed that H. pylori is mostly observed to be attached to the superficial epithelial cells of the gastric mucous layer without serious invasion of the stomach tissues of its host [13]. There are various essential features possessed by H. pylori that efficiently enhance its survival in the acidic condition of the stomach, causing infection [13]. This disease-causing microorganism uses its unipolar flagella to establish colonization, penetrate, and make significant movements between two regions of the stomach avoiding its acidic pressure [7, 15]. Studies have shown that H. pylori can cause significant interference to the human host’s antigen presenting process, and subvert the pattern recognition of the innate and adapted immunity [15]. H. pylori can also thrive undisturbed by the acidic content of the stomach by secreting urease, which is able to set a conducive pH environment of 4–8.5 for its survival [15].

3. Epidermiology

H. pylori infection is among the world’s commonest health problem, having more than 50% victims of the global population [7]. Epidemiological studies have revealed the fact that H. pylori infection prevalence is directly associated with its high incidence rate and long-term existence [2]. H. pylori infection compared with other related infectious disease has a high prevalence rate in the world [17]. Between the developed and developing nations of the world, H. pylori infection prevalence rate differs across the various regions [7]. Developed countries have been proven to experience less prevalence rate of H. pylori infection than the developing countries [17]. Researcher have observed that in a year about 0.5% of individual in the developed nations fall victim to H. pylori infection, but increases in the developing nations with the rates ranging from 3–10% [2, 19].

Among children in the developing countries, the prevalence rate of H. pylori infection ranges from below 10–80% [16], and from 1.8–65% among children in the developed countries [4]. It has been understood by epidemiological studies that some regions in the Eastern Asia and Latin American have recorded a prevalence rate of 80% among young individuals before 20 years, and places like UK, USA, or Australia records the prevalence rate of 40% within 30 to 40 years [7]. In the United States, observation has been made that H. pylori infection is rare among children lower than 10 years, but increases to 10% between the ages of 18 and 30 [7, 20]. In various nations like Canada, Netherlands, Mexico, Portugal, Asia, and Turkey according epidemiological studies have recorded H. pylori infection rate of 38, 32, 52, 84, 54–76%, and 82% respectively among children and adults [13, 21].

Data has revealed that individuals inhabiting industrialized countries have H. pylori infection rate ranging from 30–40% [13]. Also, among the non-Hispanic blacks and Hispanics, the infection of H. pylori is known to be common to individuals within any age group [2]. The African continent has been identified to have recorded a prevalence rate of 51% with regards to H. pylori infection [13]. Within the African countries like Ethiopia, Morocco, and Iran both children and adults according to studies have prevalence rate of 65, 75, and 54% respectively [13]. Organized data over the years have shown that H. pylori infections occurs within the early years of life, and increases with age [4]. By the first year of life in some developing countries, there is a prevalence rate of 20%, which increases to 50% by the age of 10 [2]. A research in Uganda showed that H. pylori infection varies with increasing age of 1–5 years, 6–10 years, and 11–15 years with 16.2, 27.2, and 36.71% as their respective prevalence rate [4]. The prevalence rate of H. pylori infection as revealed by studies in Nigeria, Indonesia, and Yemen were 89.7, 10.0, and 8.9% respectively [11].

4. Risk factors and mode of transmission

According to researched works, it has been understood that the increased H. pylori infection rate among the elderly is a direct mirror image of many early years of poor living conditions of the youngsters [2]. A study conducted in Bangladesh revealed lower infection rate of 4.9% among children living with family members below four, than those from the household having more than three members, corresponding to a rate of 19.4% [4]. Literature have established that socioeconomic status and childhood living conditions are highly associated with H. pylori infections [2]. Epidemiological studies have proven the fact that school going children, international adoptees, immigrant children are at high risk of developing H. pylori infection [4, 13]. It has also been identified that high risk children are those that usually swim in or drink from rivers, streams, ponds as well as consume raw vegetables. Generally, the major factors that put most children at risk of H. pylori infection includes poor personal and environmental hygiene, overcrowding areas, low socio-economic status, poor quality of drinking water, and eating of contaminated foods [7, 16, 22]. The level of urbanization also accounts for the variation of the prevalence rate of H. pylori infection among nations [11].

Microbiological strategies used in various studies have revealed that the microorganism H. pylori can be found in contaminated environment and ground water, as well as in animals such as domestic cats and sheep worldwide [2, 7]. Irrespective of the fact that literature provides few information on the mode of transmission of the bacterium, epidemiological studies strongly support oral-oral, fecal-oral, and person-person, as well as zoonotic transmission [2, 4]. Infection routes limited to person-person transmission during the early stages of life could be possible from mothers, caretakers, nursery attendance, and family members to babies [3, 4]. Researched observations have been made that in the acquisition of H. pylori infections, genetic susceptibility is also possible [7, 13]. According to studies, exposure to diverse sources of H. pylori infection increases with the increasing ages of children [4, 23].

5. Pathosysiology

The stomach remains the primary colonization site for the bacterium H. pylori [6]. Though clear-cut understanding of the pathophysiology of H. pylori infection is not well known, it has been identified to cause both gastric and duodenal ulcers with multiple factors coming into play [2]. Literature has revealed the fact that 95% of duodenal ulcer and 70–80% of gastric ulcers are associated with H. pylori infection [24]. There are four main strategic activities used by the bacterium H. pylori to facilitates its successful colonization, persistent infection, and disease pathogenesis [25]. The first of these basic but important strategies is its ability to survive within the stomach acidic condition, by producing urease to disrupt the acidic environment, making it suitable and conducive to survive; secondly, its flagella facilitate movement to the epithelium cells of the stomach lining in order to attach itself, as well as to detect and live in the low pH region of the stomach; thirdly, it attaches the self to the host epithelial cells by adhesins preventing frequent displacement; and the fourth strategy is cell destruction or tissue damage, and this is done by the release of toxins called Cag A and Vac A [11, 25]. As the bacterium presents the self in the stomach lumen, it then localizes the self to the antrum and corpus for adaptation, so as to avoid the acidic condition of the stomach and to cause persistent infection [11]. Evidenced-based research works shows that cascades of destructive processes arise from the microorganism H. pylori’s interactions with the gastric epithelium of its host [26].

6. Clinical manifestation

Data have shown that about 30–35% of the individuals affected with H. pylori do not show any symptoms, especially among the young people [27]. Yet still it has been established that H. pylori infection tends to leave its victims with some form of gastric and entero-gastric manifestations [8]. According to studies, the combination of different factors like the host genetics, bacteria characteristics, and the environment account for the experience of various clinical manifestations by the affected individuals [13]. The manifestations that accompany H. pylori infection can either be associated with gastritis or Peptic ulcer disease [5]. Common signs and symptoms known to come along with this infection among the young people includes nausea, vomiting, gnawing or burning abdominal pain, intestinal bleeding, gastric reflex, occasional fever, poor appetite, bloating abdomen, frequent burping, tiredness and weakness, and weight loss [5, 23].

7. Complications

From literature review, it has been well proven that H. pylori infection comes along with both gastric and extra-gastric complications which are likely to be developed by the infected young person [28]. These various complications are due to late eradiation of the infection, and most of the times resulting from its asymptomatic nature at the early stage, as younger children hardly develop complications [11, 29]. The large range of gastric complications of H. pylori infection includes severe recurrent abdominal pain, gastric esophageal reflux (GER), gastric mucosa-associated lymphoid tissue lymphoma (MALT), Peptic ulcer disease, gastric adenocarcinoma, chronic gastritis, and others [4]. Also, some extra-gastric conditions that may be present in the delay eradication of the infection among the young people includes iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, diabetes mellitus, coronary heart disease, normal tension glaucoma and others [9, 28].

Studies reveal that more than 50% of the children in Europe affected with H. pylori experience retarded growth [24]. Different literatures have presented with the fact that young people who have acquired H. pylori infection have 1–2% life time risk of developing stomach cancer, whiles 60–70% are likely to develop gastric mucosa-associated lymphoid tissue lymphoma (MALT) [19, 24, 29, 30]. Complications like gastric cancer resulting from H. pylori infection has been proven to be a significant health problem in the world, as identified to be the third most major cause of cancer-related mortality of 723,100 in the year 2012 [11].

8. Diagnostic investigations

Scientists have done their possible best to make available various scientific means to help diagnose individuals who have been infected with H. pylori [6]. Although H. pylori infection can be acquired globally, regular test for the presence of H. pylori among individuals are not recommended due to the fact that most patients do not develop significant gastro duodenal disease [2]. The European Helicobacter Study Group recommended that diagnostic investigation should be done for children with family history of Peptic ulcer disease, and chronic abdominal pain [2]. Testing and eradication therapy is only requested for infected individuals who are suspected of developing Peptic ulcer disease so as to reduce the rate of antibiotic resistance [13]. According to literature, the various diagnostic investigations have been categorized into invasive or endoscopic test and non-invasive or non-endoscopic test [2, 6].

Non-invasive scientific methods include Urea breath test with a sensitivity rate of 90–96% and specificity rate of 88–98%, Antibody test has sensitivity rate of 88–94% and specificity rate of 74–88% [2, 12], and Fecal Antigen test which also has sensitivity rate of 91–96% and specificity rate of 95–96% [31]. Invasive diagnostic test is also made up of histology, and it has a sensitivity rate of 93–96% and specificity rate of 98–99%, Culture has a sensitivity rate of 80–98% and specificity rate of 100%, Rapid Urea test has a sensitivity rate of 88–95% and specificity rate of 95–100%, as well as Polymerase Chain reaction which has a sensitivity rate above 95% and specificity rate also above 95% [2]. As revealed by studies, two or more tests are very much required to accurately establish the present of the bacterium H. pylori [3, 22]. Also, non-invasive methods are more reliable among the young people before and after treatment, whereas the invasive ones are difficult to perform among younger children [3, 5, 31, 32].

9. Management

The management of the infection H. pylori is based on three main criteria including destroying the micro bacterium H. pylori, treating the ulcer present either in the stomach or duodenum, and to prevent the recurrent of the infection which can be possible after 7 to 14 days of treatment [33]. Studies have shown that the only effective management strategy to reduce H. pylori associated with gastric cancer and extra-gastric complication is the eradication regimen [11]. In 70–95% of the cases, eradication of the microorganism is successful whereas 50–80% of the cases progress into cancers [33]. The triple therapies have been reported to have sufficient therapeutic rate of 85–90% [34, 35]. Antibiotics such as Amoxicillin, Clarithromycin, Metronidazole, Tetracycline, or Tinidazole can be used to kill the bacterium [33]. Dexlansoprazole, Esomeprazole, Lansoprazole, or Omeprazole can be used to decrease the secretion of gastric acid within the stomach by blocking its production source [33]. Cimetidine, Famotidine, Nizatidine, or Ranitidine is usually used to inhibit histamine that mediate the production of the gastric acidic content that is likely to erode the wall lining of the stomach [33]. Among individuals with H. pylori infection, surgery as treatment is not an option, but can be recommended only for victims that are developing severe complications like the malignancies [34].

It has been identified that the first-line eradication management for standard triple therapy must be Amoxicillin, Clarithromycin, and Proton-pump inhibit (PPI) for a time period of 14 days [34, 36]. PPI, Metronidazole, Amoxicillin, and Clarithromycin have been proven to have eradication efficiency rate of 84.3% [11]. In order to confirm the complete eradication of H. pylori infection, treated patients must be tested again even after management [13]. Higher weight-based doses of Proton-pump inhibitor (PPI) management regimen are what young children need as against the adolescents and the elderly, and it has also been proved to be very efficient in dealing with the eradication of the infection [13]. However, the test-and-treat management strategy is less recommended for young patients below the age of 14 years [36]. Studies have shown that washing of hands thoroughly and frequently, drinking of safe water, as well as eating well prepared foods can help prevent the infection of H. pylori among the youngsters [5]. Recently, studies have recommended the addition of iron therapy in the management and establishment of H. pylori infection eradication [10]. In the eradication therapy strategy, sequential therapy has been proven to command positive results of more than 90% efficiency [10]. The duration of the eradication therapy is also very much important, and research studies as well as commendation from the European and United States indicates that 14 days of sequential treatment is the most potent among the durations 7,10, or 14 days [37].

10. Rate of antibiotics resistance

There are few numbers of antibiotics used in the treatment of H. pylori infection among children [36]. The increase rate of antibiotic resistance to the management of H. pylori infection has become obvious [38]. Therefore, recommendations have been made that drug susceptibility test is to be conducted before treatment so as to identify the corresponding regimen needed for accurate management [3]. A study conducted in Cameroon in the year 2019 revealed that Amoxicillin and Metronidazole have the highest resistance rate of 97.14% and 97.85% respectively, and so recommendation was made that they should be avoided as components of the triple therapy in the eradication of H. pylori infection especially among the young people [38]. In countries like Nepal and Bangladesh, Metronidazole resistance rate recorded by studies were 88 and 84% respectively [11]. Another study conducted in Vietnam showed that Clarithromycin, Levofloxacin, and Tetracycline have the resistance rate of 34.1, 29.7, and 17.9% respectively [39]. Common treatment strategies for H. pylori eradication have been observed to have a failure rate of 20% [37].

The resistance rate of Clarithromycin increased from 13% in the year 2006 to 21% by the year 2016 [39]. Countries such as China, Turkey, Japan and Italy, and Sweden and Taiwan have recorded Clarithromycin resistance rate of 50, 40, 30, and 15% respectively [10]. A study conducted among isolates revealed a multiple drug resistance pattern of 42.57% double therapy, 15.71% triple therapy, and 5.71% quadruple therapy [38]. There is a high antibiotic resistance rate in H. pylori infection than in other bacteria, due to the increase misuse and overuse of antibiotics for the treatment of other infections in most developing nations [11]. Some contributing factors such as inability to responding to treatment, and gastric suppressant inadequacy results in antibiotic resistance among young people [34]. Due to the great impact of the resistance in the treatment of H. pylori, World Health Organization (WHO) in the year 2017 identified it as part of the common cause of community-acquired infection [11]. It has been recommended that second line therapy be included in the eradication of H. pylori since the first line therapy has been observed to have about 20% rate of failure [37].

11. Conclusion

Numerous factors might play different roles in the development of Peptic ulcer disease, but one significant biological factor that has been associated with the occurrence of this global gastrointestinal health problem is the H. pylori. Poor socioeconomic status, poor personal and environmental hygiene, drinking contaminated water, eating contaminated food, and overcrowded arears have been identified to make school going children more prone to developing H. pylori infection at the early stages of life. H. pylori infection is associated with gastritis, and gastric ulcers. Therefore, early detection and effective treatment of the infection is needed to well establish its eradication and further prevent any clinical complications likely to develop in the later years of life. In the aspect of prevalence rate, complications, rare occurrence of malignancies, age-specific problems with diagnostic test and drugs, as well as for increased rate of antibiotic resistant, children differ from the elderly in terms of H. pylori infection. Therefore, some recommendations for the elderly may not be relevant to the youngsters.

Acknowledgments

Extending sincere gratitude to all authors and publishers of the books and articles used as reference in this research work. Good wishes to all who will find this researched work useful in their various field of study. Many appreciations and gratitude to the sponsors and funders of this researched work. Thank you.