Open access peer-reviewed chapter

Helicobacter pylori Infection and Atrophic Corpus Gastritis on Patients with Intellectual Disability: Challenges in the Clinical Translation of Personalized Medicine

Written By

Pekka Kaipainen and Markus Kaski

Reviewed: 08 January 2018 Published: 14 October 2020

DOI: 10.5772/intechopen.73585

From the Monograph

Personalized Medicine, in Relation to Redox State, Diet and Lifestyle

Edited by Faik Atroshi

Chapter metrics overview

633 Chapter Downloads

View Full Metrics


The purpose of this chapter is to clarify the prevalence of Helicobacter pylori infection (HPI) and atrophic corpus gastritis (ACG) in patients with intellectual disability (ID) and review the literature surrounding them. We measured the levels of pepsinogen I, pepsinogen II, gastrin-17b (basal), and Helicobacter pylori antibodies from 243 patients with intellectual disability living in Rinnekoti Research Centre at Lakisto area during 2009–2011. We determined the levels of hemoglobin, mean cell volume (MCV), hematocrit, and the mean amount (MCH) and concentration (MCHC) of red cell hemoglobin, the counts of erythrocytes, leucocytes, and thrombocytes. About 43% had high level of Helicobacter pylori antibodies and 6% ACG. Our results show that Helicobacter pylori infection occurs approximately twice the rate it appears in the normal population. Also, the incidence of ACG was higher among patients with ID than normal population. ID may be a risk of getting the Helicobacter pylori infection (HPI) and ACG. In addition, it was found that the level of thrombocytes was increased in HPI group compared to normal group and decreased in ACG group compared to normal group. This study shows that there is clearly a need to investigate (test) more stomach condition in patients with ID.


  • helicobacter
  • Helicobacter pylori
  • pepsinogen
  • gastritis
  • atrophic corpus gastritis
  • intellectual disability
  • personalized medicine

1. Literature review

1.1. Helicobacter pylori infection

Helicobacter pylori is a common Gram-negative bacterium, which may colonize the human stomach, wherein it can induce various gastroduodenal disorders (chronic gastritis, ulceration, atrophic corpus gastritis, and gastric cancer). However, only a small part of the people, who are colonized, develops associated diseases. It is estimated that H. pylori infection (HPI) affects more than half of the adult population worldwide [1] and is responsible for 75% of all gastric cancer cases [2]. In Finland and many other countries, the prevalence of H. pylori is decreased in last decades, in Finland to the level of approximately 15% of population [3]. Intellectually disabled children are a vulnerable subgroup and may experience higher rates of infections and morbidities [4]. H. pylori infection and gastric cancer occur at higher rates in subjects with ID than in the general population [5]. In institutionalized patients with intellectual disability (ID), Helicobacter pylori infection (HPI) occurs twice the rate it appears in the normal population [6, 7, 8]. It is suggested that the transmission of HPI occur via an oral-oral or fecal-oral pathway. Ohwada et al. [9] concluded that a high frequency of mild norm chromic anemia in institutionalized people with ID was observed. According to them, medications and chronic inflammation may increase the risk of anemia. Telaranta-Keerie et al. [10] noted the prevalence of 3.5 % of population for atrophic corpus gastritis (ACG) and also found that ACG may cause impairment in secretion of intrinsic factor, resulting in vitamin B12 deficiency. Because of these observations, we decided to evaluate the hematological values of our patients with ID. ACG can be autoimmune in origin or it can appear as multifocal atrophic gastritis (MAG) [11, 12]. According to Telaranta-Keerie et al. [10], MAG is always HPI-initiated. Achlorhydric or hypochlorhydric stomach with ACG may result in malabsorption of vitamin B12, micronutrients, and medicines [13]. It is well known that the stomach must be acid in order to absorb B12. Many people already suffer from borderline B12 deficiency—this is a difficult vitamin for the body to assimilate, but essential for normal biochemistry. Therefore, achlorhydria may be associated with vitamin B12 deficiency in the setting of pernicious anemia. Parenteral vitamin B12 may be important in selected patients. Achlorhydria is associated with thiamine deficiency in the setting of bacterial overgrowth [14, 15, 16]. In addition, increasing evidence accumulates that H. pylori infection may interfere with many biological processes and have a role in birth of several other extra-gastroduodenal manifestations including among others iron deficiency anemia, immune thrombocytopenic purpura, metabolic syndrome and diabetes mellitus, nonalcoholic fatty liver disease, coronary artery disease and cerebrovascular disorders [17]. Because of these facts, ACG is important disease to be diagnosed and recognized [18, 19]. It has been observed that Helicobacter pylori infection can cause rumination and numerous other behavioral disorders [20]. Helicobacter pylori are associated with gastric atrophy and gastric carcinoma [21].

1.2. The role of epidemiology in understanding the health effects of Helicobacter pylori in intellectual disability

H. pylori infection appears to be almost universal among certain groups of people with intellectual disability and appears to be a relatively silent condition in this population, even in those with more virulent strains [22]. The ID is potentially at risk of significant but preventable morbidity and mortality from the disease consequences of this infection [23]. The efficacy of standard treatment protocols appear lower than that in the general population, and in some, the side effects are more prominent [24]. The diagnosis of H. pylori infection can be made with reasonable clinical certainty using the fecal antigen test (and serology under some conditions) or, in those with greater abilities, using the urea breath test [25]. Although eradication of infection does not change the level of maladaptive behavior or intellectual disability, it may reduce the risk of the disease consequences of H. pylori. Given the clinical silence of the infection, the virulence of the strains, the acceptability of the diagnostic tests, and knowledge of the risk factors for infection, despite a possible lower eradication rate and higher rate of side effects, a strong argument can be made to proactively screen for and treat H. pylori infection among groups of people with intellectual disability who have a history of institutionalization, greater levels of intellectual disability or maladaptive behavior, or live with flatmates with hypersalivation or fecal incontinence [5].

Intellectually disabled children are a vulnerable subgroup and may experience higher rates of infections and morbidities [4]. H. pylori infection and gastric cancer occur at higher rates in subjects with ID than in the general population [5, 7]. Many children with ID and neurological impairments are not able to co-operate with performance of noninvasive test such as UBT [7]. In addition, because of limitations in their intellectual and adaptive functioning, such children are unable to report their symptoms. Behavior of people with ID is often difficult to explain and reactions may be similar on physical and emotional stress that is why they may be misunderstood and over medicated. One of the main reasons to begin this research study in our research center—Rinnekoti Research Centre—was the fact that patients with ID very often have difficulties to recognize, localize and indicate their symptoms. Although life-long H. pylori associated morbidities are well known, relatively few studies have addressed the status of H. pylori infection in people with ID [5].

1.3. Helicobacter infection and gastric neoplasia

As discussed above, Helicobacter pylori are one of the world’s most common pathogens with a colonization of about 60% of the general population [26, 27]. It is estimated that H. pylori infection affects more than half of the adult population worldwide [1] and is responsible for 75% of all gastric cancer cases [2]. No mode of transmission is fully known, however, many factors may contribute such as socio-economic and poor living standards, poor nutrition and physical activity, and possibly poor access to health services. However, most individuals never develop clinical disease [28].

Gastrointestinal problems in handicapped children with neurodevelopmental disabilities are chronic and present long-term management problems. These conditions include dysphagia (60%), chronic pulmonary aspiration (41%), gastroesophageal reflux (32%), abdominal pain and gastritis (32%), constipation (74%), and malnutrition (33%) [29]. Growth failure and malnutrition are common in children with cerebral palsy, particularly in those with spastic quadriplegia, of which 85% report feeding problems [30, 31]. In addition, 20–30% of hemiplegic and diplegic cerebral palsy children are underweight for age [26, 32]. There are multifactorial causes: insufficient food intake, feeding problems, increased nutrient losses from vomiting or diarrhea, and alterations in energy requirements in epileptic or metabolic syndromes where increased muscle tone or involuntary movements are seen. What is now clear is that undernutrition in cerebral palsy is often correctable and that providing a balanced diet and better nutrition can result in improvement in long-term spasticity, appearance, and effect of these children [33].

Good number of studies have been published in persons with intellectual disability, however, large-scale scientific studies have not been published with a population case-control study [22, 32, 34]. Harris et al. [35] (10) reported that hospital residents under 40 years of age had a 87% prevalence of HP compared with 24% for controls, whereas the overall prevalence for all ages was 87% for residents, and 43% for controls in hospital residents with severe learning disabilities. A larger study including 338 intellectually disabled and 254 controls from Holland (12) found a prevalence of 5% in children and 50% in the elderly in the general population, whereas 83% of the disabled and 27% of the healthy employees were infected. The presence of HP was significantly associated with male gender, longer duration of institutionalization, an IQ below 50, rumination, and a history of upper abdominal symptoms. Another study was conducted to determine the occurrence of HP infection in persons, who presented with severe dyspeptic symptoms and to monitor clinically the effect of treatment [36]. Over a 1-year period, a total of 43 persons (total population in care was 224) had severe dyspeptic symptoms and 42 persons (98%, 26 males, 16 females, mean age 45 years, mean institutionalization 20 years) had HP.

1.4. Treatment regimens used for H. pylori eradication

H. pylori infection is most likely acquired by ingesting contaminated food and water, and through person to person contact. H. pylori infections are usually treated with antibiotics to help prevent the bacteria from developing a resistance to any particular antibiotic. Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20–30% of patients [37]. Most persons who are infected with H. pylori never suffer any symptoms related to the infection; however, H. pylori causes chronic active, chronic persistent, and atrophic gastritis in adults and children. Infection with H. pylori also causes duodenal and gastric ulcers. Infected persons have a two- to six-fold increased risk of developing gastric cancer and mucosal-associated-lymphoid-type (MALT) lymphoma compared with their uninfected counterparts. The role of H. pylori in nonulcer dyspepsia remains unclear [38]. Therapy for H. pylori infection consists of 10 days to 2 weeks of one or two effective antibiotics, such as amoxicillin, tetracycline (not to be used for children <12 years), metronidazole, or clarithromycin, plus either ranitidine bismuth citrate, bismuth subsalicylate, or a proton pump inhibitor [39, 40]. H pylori eradication rates were higher for a 7-day antibiotic regimen containing lansoprazole, amoxicillin, and clarithromycin (LAC), when used as first-line therapy compared with levofloxacin, amoxicillin, and lansoprazole (LAL) [39]. Yoon et al. [40] investigated the efficacy of a moxifloxacin-containing triple therapy as second-line therapy for H. pylori infection as well as the effect of treatment duration and antibiotic resistance on the eradication rate [40].

Combination drug therapy regimens commonly used to treat H. pylori infection includes a proton pump inhibitor (PPI) plus clarithromycin plus amoxicillin or metronidazole and a proton pump inhibitor plus a bismuth compound plus metronidazole plus tetracycline. However, all medicines have side effects. But many people don’t feel the side effects or they are able to deal with them [38, 41, 42].

1.5. Helicobacter pylori infection and oxidative stress

Oxidative stress results from the damaging action of reactive oxygen species. These molecules react with proteins, lipids, or DNA, altering their structure and causing oxidative damage to the cells. Reactive oxygen species (ROS) are produced during normal and physiological process, which inevitably leads to the generation of oxidative molecules: superoxide (O2_), hydrogen peroxide (H2O2), or hydroxyl radical (•OH). Oxidative stress is implicated in a large number of diseases: cancer (oxidative damage to DNA causes mutations that can lead to carcinogenesis), atherosclerosis (atherosclerotic plaques are made from oxidized fat), and neurodegenerative diseases (oxidative damage is a central component of nerve cell destruction). Indicators of oxidative stress have been detected in muscles and blood of ID patients. Oxidative damage can alter the blood-brain barrier, which could explain some of the cognitive problems experienced by patients.

There is an increasing evidence that microbial pathogens induce oxidative stress in infected host cells [43, 44, 45] and this may represent an important mechanism leading to epithelial injury in H. pylori infection [46].

Oxidative stress could well play a role in the altered epithelial proliferation, increased apoptosis, and increased oxidative DNA damage [47, 48, 49] associated with H. pylori infection.

Evidence for this includes increased levels of reactive oxygen species (ROS) measured in the mucosae of infected patients [48, 50, 51]. While activated, ROS-releasing phagocytic leukocytes recruited to the gastric mucosa during infection represent one obvious source of oxidative stress [43, 50].

The mechanism of tissue damage and cell proliferation in H. Pylori infection remains unknown, although cytokines, chemokines, growth factors, including nitric oxide synthase and potent neutrophil. Derive reactive oxygen metabolism have all been proposed to contribute to such damage [52, 53, 54]. HP infection is associated with the increased production of free radicals in the gastric mucosa [50]. Accumulated free radicals in the tissue initiate lipid peroxidation of cell membranes and threaten cell integrity. Antioxidant may be useful in HP-related mucosal disease [47]. Evidence suggests that microbial pathogens induce oxidative stress in infected host cells [43, 44, 45], which represents an important mechanism causing damage to the epithelial in H. pylori infection [55]. Helicobacter pylori is the major cause of acute and chronic gastritis, gastric, and duodenal ulcer and increased incidence of gastric adenocarcinoma and elevated gastric mucosa lymph proliferation. Reactive oxygen species have been suggested as one of the main causes of cell injury in H. pylori associated gastritis. H. pylori mutants that are defective in RuvC have increased sensitivity to DNA-damaging agents and to oxidative stress, exhibit reduced survival within macrophages, and are unable to establish successful infection in a mouse model [56].


2. Research study

2.1. Material and methods

GastroPanel test (Biohit Oyj, Helsinki) was used. The test consisted of measurement of plasma pepsinogen I, pepsinogen II (PG I, PG II and PG I/PG II ratio), H. pylori IgG antibodies (HpAb) and gastrin-17-basal by the ELISA method. Test results, together with a short interpretation of the results are created by the GastroSoft software. The GastroSoft software uses an algorithm that is based on the levels of PG I, PG II, HpAb, and gastrin-17-basal in plasma as measured by GastroPanel. When the results showed a low PG I level (<30 μg/l) and/or a low PG I/PG II ratio (<3), the GastroSoft interpretation was “moderate or severe atrophic corpus gastritis”. Cases fulfilling these criteria were considered to have advanced ACG. If PG I level and PG I/PG II ratio were normal but the patient had an elevated HpAb result (≥30 EIU), this was interpreted as “nonatrophic H. pylori gastritis”. When the levels of all the biomarkers were within their reference ranges (PG I ≥ 30 μg/l and PG I/PG II ratio ≥ 3, HpAb below 30 EIU), the GastroSoft interpretation was “healthy, normal stomach mucosa”.

2.2. Laboratory determinations and reagents

Vacuette serum tubes were used to obtain serum samples and vacuette K2EDTA tubes were used to obtain hematological samples. Hemoglobin, mean cell volume (MCV), hematocrit, erythrocytes, thrombocytes, and leukocytes were assayed with Sysmex KX-21 N analyzer. All used reagents were reagent grade. All laboratory determinations were controlled with the control samples from Labquality Ltd., Helsinki, Finland. All enzyme immunoassays were done with BP 800 reader.

2.3. Study population

The study material consisted of blood samples from patients with intellectual disability (243 individuals). Patients with ID lived in groups containing 6–8 persons during 2009–2011. Age was from 10 to 80. The whole group consisted 157 male and 86 female patients with ID. Sanitary facilities were common for each group as normal family living. The personnel taking care of these patients was living with them for 24 hours per day with 8–10 hours shifts.


3. Results

We measured the levels of pepsinogen I, pepsinogen II, gastrin 17-beta, and Helicobacter pylori antibodies from 243 patients with intellectual disability (157 male patients and 86 female patients). Results are shown in Tables 1 and 2 and Figures 14. The prevalence of subjects with ACG, HPI, and normal stomach mucosa is shown in Table 1. Among male patients, 7% had ACG, while among female patients, 4.7% had ACG. 6.2% of all patients had ACG. Among male patients, 45.2% had HPI, while among female patients, 39.5% had HPI. About 43.2% of all patients had HPI. Among male patients, 47.8% had normal stomach mucosa, while among female patients, 55.8% had normal stomach mucosa. About 50.6% of all patients had normal stomach mucosa (Table 1). Differences in the levels of pepsinogen II, PG I/PG II, and Helicobacter pylori antibodies between HPI group and normal group were statistically extremely significant. Differences in the levels of pepsinogen I, PG I/PG II, and Helicobacter pylori antibodies between ACG group and normal group were also statistically extremely significant. Differences in the levels of hemoglobin, hematocrit, erythrocytes, and leucocytes between HPI group and normal group were not statistically significant. The level of thrombocytes was increased in HPI group compared to normal group and decreased in ACG group compared to normal group. These differences were statistically significant. Differences in the MCHC, MCH, and MCV were not statistically significant between these groups. Same results were between ACG group and normal group (Table 2).

Table 1.

Prevalence of subjects with advanced atrophic corpus gastritis (ACG), elevated Helicobacter pylori antibodies, and normal stomach mucosa in male and female patients with ID.

Table 2.

Five gastro and eight hematological parameters in groups with advanced corpus gastritis (ACG), Helicobacter pylori antibodies (HPI), and healthy stomach mucosa (normal).

Figure 1.

The levels of pepsinogen I on 243 patients with ID.

Figure 2.

The levels of pepsinogen II on 243 patients with ID.

Figure 3.

The levels of Gastrin 17-b on 243 patients with ID.

Figure 4.

The levels of H. pylori antibodies on 243 patients with ID.


4. Discussion

This study provides an overview of the best available evidence on the prevalence of H. pylori infection obtained from patients with intellectual disability.

The level of ID and environmental factors may be related to the risk of infection with H. pylori [7]. According to Merrick, 43 persons (total population in care was 224) had severe dyspeptic symptoms. Wallace et al. [7] showed that adults with ID may be at risk of infection with HPI. According to their results, a long period of institutionalization living with other patients predisposes to HPI. Helicobacter pylori among patients with ID living in hospitals are common [7]. In institutionalized patients with intellectual disability (ID), Helicobacter pylori infection (HPI) occur twice the rate it appears in the normal population [6, 7, 8]. However, this trend has not been before observed in Finland. The patients with ID lived in groups containing 6–8 persons. Sanitary facilities were common for each group as normal family living. It is suggested that the transmission of HPI occur via an oral-oral or fecal-oral pathway. The mechanism of transmission of this pathogen is not known exactly. But it is known that the rate of this disease is increased with age and other living conditions. According to our findings, patients with ID and age of 50 and living for a long time in group residences are high at risk to get Helicobacter pylori infection and also so atrophic corpus gastritis. Because well-being of patients with ID is important, we decided to determine also the hematological values of these people. We did not find any big differences between the patients with healthy and sick stomach mucosa. The count of thrombocytes was increased in HPI group and decreased in ACG group. Thrombocytes have an important role in inflammation [57]. They participate in inflammatory response to H. pylori infection by activation and aggregation as well as acting as a source of inflammatory mediators and modulating the activity of other inflammatory cells in stomach mucosa [58]. The volume of thrombocytes may be increased during infection. Their persistent activation and enhanced destruction production process during infection may lead to decreased amounts of them [59]. However, it seems that there lacks association between H. pylori infection and various markers of systemic inflammation including thrombocyte/lymphocyte ratio in adults with chronic asymptomatic H. pylori infection [60]. Helicobacter pylori infection and its consequences may be severe to people with ID. Wallace et al. [7] concluded that if this infection leads to increased levels of maladaptive behavior, this could result in loss of social opportunities, sedative drug use and so decrease of well-being. The mental pressure among workers in institutions for people with ID will increase. Böhmer et al. [61] and Schryver et al. [62] found that Helicobacter pylori infection is an occupational risk in healthcare workers working in institutions for people with ID. This observation gives the reason to also investigate all workers taking care of patients with ID.

Proujansky et al. [20] stated that rumination may be a possible symptom of Helicobacter pylori infection. Rumination occurs more frequently in patients with ID. Dentists play the important role in finding patients with rumination. From these patients, it is important to investigate Helicobacter pylori infection and treat it. Ohwada et al. [9] found that the prevalence of anemia was increased on patients with ID. According to their results, most patients showed a normocytic norm chromic anemia pattern. They say that medications and inflammation may increase the risk of anemia. We did not find differences on hemoglobin levels between the patients with normal and sick mucosa of stomach. We need more research on this field.

Wallace et al. [63, 64] reported that 7% of institutionalized adults with ID treated for Helicobacter pylori infection and test negative at the end of treatment are at risk of reinfection. They suggest that patients with ID should retest at an interval of approximately 3–5 years after apparent eradication. More research is needed to evaluate the effects of Helicobacter pylori infection on pain and use of drugs on patients with ID. Taking care of this infection, we can probably increase the level of well-being of these patients and so to decrease the physical and physiological pressure of workers in institutions for people with ID. Many studies have explored the association of H. pylori with hypermethylation of specific genes [65, 66] as well as hypomethylation of genes [67, 68]. Further research is required to elucidate the exact mechanisms of inflammation and tumor suppression, which might provide new opportunities for personalized treatment options.

The poor prognosis of patients with a negative H. pylori status might be the result of a more aggressive form of gastric cancer [69, 70]. The present study demonstrates that H. pylori positivity is a beneficial prognostic indicator in patients with intellectual disability, independent of other clinic pathologic variables. In clinical practice, patients with curatively resected gastric cancer who are negative for H. pylori may need more careful follow-up and more aggressive antitumor treatment to prolong life expectancy. Further research is required to elucidate the exact mechanisms of inflammation and tumor suppression, which might provide new opportunities for personalized treatment options. We believe that the current prospective study is the first to confirm H. pylori status as a favorable prognostic factor in a large number of intellectual disability patients with Helicobacter pylori infection and atrophic corpus gastritis in Finland, thus validating the effect of H. pylori infection status on survival in intellectual disability patients.

Antibiotic susceptibility should be checked in all patients, ideally, before the start of eradication treatment. The knowledge of local antibiotic resistance and consumption pattern is important in selecting a reliable regimen [71, 72, 73]. Future development for H. pylori therapy should be directed to overcome individualized antibiotic resistance. Warneke et al. [74] investigated various phenotypic and genotypic biomarkers of gastric cancer (GC) and concluded whether these biomarkers are suitable for the identification of GC subtypes, are they of prognostic significance, and should any of these biomarkers be considered to tailor patient treatment in the future. There remains a need to better understand the prognostic factors affecting the cure rate of Helicobacter pylori infection might lead to the development of novel prevention strategies and therapeutic targets. Therefore, personalized medical approach will likely increase the cure rate of H. pylori infection [75].

A complete history could also do away with the need for additional testing and increased medical expenses for the patient and the healthcare system as a whole.



We would like to thank all the patients who lived at Rinnekoti Research Centre during 2009–2011. Also we want to thank the laboratory workers of Rinnekoti and we are grateful for a financial help of Rinnekoti Foundation and Finnish Brain Foundation.


  1. 1. Parkin DM. International variation. Oncogene. 2004;23:6329-6340
  2. 2. de Martel C, Ferlay J, Franceschi S, Vignat J, et al. Global burden of cancers attributable to infections in 2008: A review and synthetic analysis. The Lancet Oncology. 2012;13:607-615
  3. 3. Rehnberg-Laiho L, Rautelin, H, Koskela P, Sarna S, Pukkala E, Aromaa A, Knekt P, Kosunen U. Decreasing prevalence of helicobacter antibodies in Finland, with reference to the decreasing incidence of gastric cancer. Epidemiology and Infection. 2001;126(1):37-42
  4. 4. Jeevanandam L. Perspectives of intellectual disability in Asia: Epidemiology, policy, and services for children and adults. Current Opinion in Psychiatry. 2009;22:462-468
  5. 5. Kitchens DH, Binkley CJ, Wallace DL, Darling D. Helicobacter pylori infection in people who are intellectually and developmentally disabled: A review. Special Care in Dentistry. 2007;27:127-133
  6. 6. Merrick J, Aspler S, Dubman I. Helicobacter pylori infection in persons with intellectual disability in residential care in Israel. ScientificWorldJournal. 2001;6:1264-1268
  7. 7. Wallace RA, Webb PM, Schluter PJ. Environmental, medical, behavioural and disability factors associated with Helicobacter pylori infection in adults with intellectual disability. Journal of Intellectual Disability Research. 2002;46(Pt 1):51-60
  8. 8. Wallace RA, Schluter PJ, Forgan-Smith R, Wood R, Webb PM. Diagnosis of Helicobacter pylori infection in adults with intellectual disability. Journal of Clinical Microbiology. 2003;41(10):4700-4704
  9. 9. Ohwada H, Nakayama T, Nara N, Tomono Y, Yamanaka K. An epidemiological study on anemia among institutionalized people with intellectual and/or motor disability with special reference to its frequency, severity and predictors. BMC Public Health. 2006;6:85. DOI: 10.1186/1471-2458/6/85
  10. 10. Telaranta-Keerie A, Kara R, Paloheimo L, Härkönen M, Sipponen P. Prevalence of undiagnosed advanced atrophic corpus gastritis in Finland: An observational study among 4256 volunteers without specific complaints. Scandinavian Journal of Gastroenterology. 2010;45(9):1036-1041
  11. 11. Correa P. Helicobacter pylori and gastric carcinogenesis. The American Journal of Surgical Pathology. 1995;19(Suppl 1):37-43
  12. 12. Valle J, Kekki M, Sipponen P, Ihamäki T, Siurala M. Longterm course and consequences of Helicobacter pylori gastritis. Results of a 32-year follow-up study. Scandinavian Journal of Gastroenterology. 1996;31:546-550
  13. 13. Cater RE 2nd. The clinical importance of hypochlorhydria (a consequence of chronic Helicobacter infection): Its possible etiological role in mineral and amino acid malabsorption, depression, and other syndromes. Medical Hypotheses. 1992;39(4):375-383. PMID: 1494327
  14. 14. Iijima K, Sekine H, Koike T, Imatani A, Ohara S, Shimosegawa T. Long-term effect of Helicobacter pylori eradication on the reversibility of acid secretion in profound hypochlorhydria. Alimentary Pharmacology and Therapeutics. 2004;19(11):1181-1188
  15. 15. Drake WM, Innes DF. Primary gastric lymphoma presenting with vitamin B12 deficiency and achlorhydria. The American Journal of Gastroenterology. 1996;91(12):2605-2606
  16. 16. Svendsen JH, Dahl C, Svendsen LB, Christiansen PM. Gastric cancer risk in achlorhydric patients. A long-term follow-up study. Scandinavian Journal of Gastroenterology. 1986;21(1):16-20
  17. 17. Tsay FW, Hsu PI. H. pylori infection and extra-gastroduodenal diseases. Journal of Biomedical Science. 2018;25(1):65
  18. 18. Correa P, Haenszel W, Cuello C, Zavala D, Fontham E, Zarama G. Gastric precancerous process in a high risk population: Cohort follow-up. Cancer Research. 1990;50:4737-4740
  19. 19. Sipponen P, Kekki M, Haapakoski J, Ihamäki T, Siurala M. Gastric cancer risk in chronic atrophic gastritis: Statistical calculations of cross-sectional data. International Journal of Cancer. 1985;35:173-177
  20. 20. Proujansky RM, Shaffer SE, Vinton NE, Bachrach SJ. Symptomatic Helicobacter pylori infection in young patients severe neurologic impairment. The Journal of Pediatrics. 1994;125:750-752
  21. 21. Howden CW. Clinical expressions of Helicobacter pylori infection. American Journal of Medicine. 1996;100:27-32
  22. 22. Kindermann A, Lopes AI. Helicobacter pylori infection in pediatrics. Helicobacter. 2009;14(Suppl 1):52-57
  23. 23. Mauk JE. Helicobacter pylori infection in neurologically impaired children. The Journal of Pediatrics. 1995;126(5Pt1):849
  24. 24. Redeen S, Petersson F, Tornkrantz E, Levander H, Mardh E, Borch K. Reliability of diagnostic tests for Helicobacter pylori infection. Gastroenterology Research and Practice. 2011;2011:940650
  25. 25. Bytzer P, Dahlerup JF, Eriksen JR, Jarbol DE, Rosenstock S, Wildt S. Diagnosis and treatment of Helicobacter pylori infection. Danish Medical Bulletin. 2011;58:C4271
  26. 26. Cave DR. How is Helicobacter pylori transmitted? Gastroenterology. 1997;113(6 Suppl):S9-14
  27. 27. Cilley RE, Brighton VK. The significance of Helicobacter pylori colonization of the stomach. Seminars in Pediatric Surgery. 1995;4(4):221-227
  28. 28. Mitchell H. The epidemiology of Helicobacter pylori. Current Topics in Microbiology and Immunology. 1999;241:11-30
  29. 29. Del Giudice E, Staiano A, Capano G, et al. Gastrointestinal manifestations in children with cerebral palsy. Brain & Development. 1999;21:307-311
  30. 30. Stallings VA, Cronk CE, Zemel BS, et al. Body composition in children with spastic quadriplegic cerebral palsy. The Journal of Pediatrics. 1995;126:833-839
  31. 31. Stallings VA, Zemel BS, Davies JC, et al. Energy expenditure of children and adolescents with severe disabilities: A cerebral palsy model. American Journal of Clinical Nutrition. 1996;64:627-634
  32. 32. Lubani MM, Al-Saleh QA, Teebi AS, Moosa A, Kalaoui MH. Cystic fibrosis and Helicobacter pylori gastritis, megaloblastic anaemia, subnormal mentality and minor anomalies in two siblings: A new syndrome ? European Journal of Pediatrics. 1991;150(4):253-255
  33. 33. Patrick J, Boland M, Stoski D, et al. Rapid correction of wasting in children with cerebral palsy. Developmental Medicine and Child Neurology;1986(28):734-739
  34. 34. Dellavecchia C, Guala A, Olivieri C, et al. Early onset of gastric carcinoma and constitutional deletion of 18p. Cancer Genetics and Cytogenetics. 1999;113(1):96-99
  35. 35. Harris AW, Douds A, Meurisse EV, Dennis M, Chambers S, Gould SR. Seroprevalence of Helicobacter pylori in residents of a hospital for people with severe learning difficulties. European Journal of Gastroenterology & Hepatology. 1995;7(1):21-23
  36. 36. Morad M, Merrick J, Nasri Y. Prevalence of Helicobacter pylori in persons with intellectual disability in a residential care center in Israel. Journal of Intellectual Disability Research. 2002;46(2):141-143
  37. 37. Graham DY, Qureshi WA. Antibiotic-resistant H. pylori infection and its treatment. Current Pharmaceutical Design. 2000;6(15):1537-1544
  38. 38. Soll AH. Medical treatment of peptic ulcer disease. Practice guidelines. [Review]. JAMA. 1996;275:622-629. [published erratum appears in JAMA 1996 May 1;275:1314]
  39. 39. Liou JM, Lin JT, Chang CY, et al. Levofloxacin-based and clarithromycin-based triple therapies as first-line and second-line treatments for Helicobacter pylori infection: A randomised comparative trial with crossover design. Gut. 2010;59(5):572-578
  40. 40. Yoon H, Kim N, Lee BH, et al. Moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori infection: Effect of treatment duration and antibiotic resistance on the eradication rate. Helicobacter. 2009 Oct;14(5):77-85
  41. 41. European Helicobacter pylori Study Group. Current European concepts in the management of H. pylori information. The Maastricht consensus. Gut. 1997;41:8-13
  42. 42. Hunt RH. Helicobacter pylori: from theory to practice. Proceedings of a symposium. The American Journal of Medicine. 1996;100(5A) supplement
  43. 43. Giri DK, Mehta RT, Kansal RG, Aggarwal BB. Mycobacterium avium-intracellulare complex activates nuclear transcription factor-κB in different cell types through reactive oxygen intermediates. Journal of Immunology. 1998;161:4834-4841
  44. 44. Schweizer M, Peterhans E. Oxidative stress in cells infected with bovine viral diarrhoea virus: A crucial step in the induction of apoptosis. The Journal of General Virology. 1999;80:1147-1155
  45. 45. Sipowicz MA, Chomarat P, Diwan BA, Anver MA, Awasthi YC, Ward JM, Rice JM, Kasprzak KS, Wild CP, Anderson LM. Increased oxidative DNA damage and hepatocyte overexpression of specific cytochrome p450 isoforms in hepatitis of mice infected with Helicobacter hepaticus. The American Journal of Pathology. 1997;151:933-941
  46. 46. Smoot DT, Elliott TB, Verspaget HW, Jones D, Allen CR, Vernon KG, Bremner T, Kidd LC, Kim KS, Groupman JD, Ashktorab H. Influence of Helicobacter pylori on reactive oxygen-induced gastric epithelial cell injury. Carcinogenesis. 2000;21:2091-2095
  47. 47. Baik S-C, Youn H-S, Chung M-H, Lee W-K, Cho M-J, Ko G-H, Park C-K, Kasai H, Rhee K-H. Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa. Cancer Research. 1996;56:1279-1282
  48. 48. Clement MV, Pervaiz S. Reactive oxygen intermediates regulate cellular response to apoptotic stimuli: An hypothesis. Free Radical Research. 1999;30:247-252
  49. 49. Farinati F, Cardin R, Degan P, Rugge M, Mario FD, Bonvicini P, Naccarato R. Oxidative DNA damage accumulation in gastric carcinogenesis. Gut. 1998;42:351-356
  50. 50. Davies GR, Simmonds NJ, Stevens TRJ, Sheaff MT, Banatvala N, Laurenson IF, Blake DR, Rampton DS. Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo. Gut. 1994;35:179-185
  51. 51. Drake IM, Mapstone NP, Schorah CJ, White KLM, Chalmers DM, Dixon MF, Axon ATR. Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: Relation to gastric mucosal ascorbic acid concentrations and effect of H. pylori eradication. Gut. 1998;42:768-771
  52. 52. Harris PR, Mobley HL, Perez-Perez GI, Blaser MJ, Smith PD. Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production. Gastroenterology. 1996;111(2):419-425
  53. 53. Gionchetti P, Vaira D, Campieri M, Holton J, Menegatti M, Belluzzi A, Bertinelli E, Ferretti M, Brignola C, Miglioli M, et al. Enhanced mucosal interleukin-6 and -8 in Helicobacter pylori-positive dyspeptic patients. The American Journal of Gastroenterology. 1994;89(6):883-887
  54. 54. Mannick EE, Bravo LE, Zarama G, Realpe JL, Zhang XJ, Ruiz B, Fontham ET, Mera R, Miller MJ, Correa P. Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: Effect of antibiotics and antioxidants. Cancer Research. 1996;56(14):3238-3243
  55. 55. Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, Dirden-Kramer B, Boldogh I, Ernst PB, Crowe SE. Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infection and Immunity. 2007 Aug;75(8):4030-4039
  56. 56. Loughlin MF, Barnard FM, Jenkins D, Sharples GJ, Jenks PJ. Helicobacter pylori mutants defective in RuvC Holliday junction resolvase display reduced macrophage survival and spontaneous clearance from the murine gastric mucosa. Infection and Immunity. 2003;71(4):2022-2031
  57. 57. Thomas MR, Storey RF. The role of platelets in inflammation. Thrombosis and Haemostasis. 2015;114:3449-458
  58. 58. Kalia N, Bardhan KD. Of blood and guts: Association between Helicobacter pylori and the gastric microcirculation. Journal of Gastroenterology and Hepatology 2003;18(9):1010-1017
  59. 59. Umit H, Umit EG. Helicobacter pylori and mean platelet volume: A relation way before immune thrombocytopenia? European Review for Medical and Pharmacological Sciences. 2015;19(15):2818-2823
  60. 60. Kim TJ, Pyo JH, Lee H, Baek SY, Ahn SH, Min YW, Min BH, Lee JH, Son HJ, Rhee PL, Kim JJ. Lack of association between helicobacter pylori infection and various markers of systemic inflammation in asymptomatic adults. Korean Journal of Gastroenterology. 2018;72(1):21-27
  61. 61. Böhmer CJM, Klinkenberg-Knol EC, Kuipers EJ, Niezen-de Boer MC, Schreuder H, Schuckink-Kool F, Meuwissen GM. The prevalence of Helicobacter pylori infection among inhabitants and healthy employees of institutes for the intellectual disabled. The American Journal of Gastroenterology. 1997;92:1000-1004
  62. 62. Schryver ADE, Cornelis K, Winckel M, Moens G, Devlies G, Derthoo D, Van SM. The occupational risk of Helicobacter pylori infection among workers in institutions for people with intellectual disability. Occupational and Environmental Medicine. 2008;65:587-591
  63. 63. Wallace RA, Schluter PJ, Webb PM. Recurrence of Helicobacter pylori infection in adults with intellectual disability. Internal Medicine Journal. 2004a;34:131-133
  64. 64. Wallace RA, Schluter PJ, Webb PM. Effects of Helicobacter pylori eradication among adults with intellectual disability. Journal of Intellectual Disability Research. 2004b;48(7):646-654
  65. 65. Shin CM, Kim N, Lee HS, et al. Changes in aberrant DNA methylation after Helicobacter pylori eradication: A long-term follow-up study. International Journal of Cancer. 2013;133:2034-2042
  66. 66. Shin CM, Kim N, Park JH, et al. Prediction of the risk for gastric cancer using candidate methylation markers in the non-neoplastic gastric mucosae. The Journal of Pathology. 2012;226:654-665
  67. 67. Yoshida T, Kato J, Maekita T, et al. Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis. Gastric Cancer. 2013;16:488-497
  68. 68. Yuasa Y, Nagasaki H, Oze I, et al. Insulin-like growth factor 2 hypomethylation of blood leukocyte DNA is associated with gastric cancer risk. International Journal of Cancer. 2012;131:2596-2603
  69. 69. Hur H, Lee SR, Xuan Y, et al. The effects of Helicobacter pylori on the prognosis of patients with curatively resected gastric cancers in a population with high infection rate. Journal of the Korean Surgical Society. 2012;83:203-211. DOI: 10.4174/jkss.2012.83.4.203
  70. 70. McColl KE. Clinical practice. Helicobacter pylori infection. The New England Journal of Medicine. 2010;362:1597-1604
  71. 71. Bang CS, Baik GH. Attempts to enhance the eradication rate of Helicobacter pylori infection. World Journal of Gastroenterology. 2014 May 14;20(18):5252-5262
  72. 72. De Francesco V, Giorgio F, Hassan C, et al. Worldwide H. pylori antibiotic resistance: A systematic review. Journal of Gastrointestinal and Liver Diseases. 2010;19:409-414
  73. 73. Duck WM, Sobel J, Pruckler JM, et al. Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States. Emerging Infectious Diseases. 2004;10:1088-1094
  74. 74. Warneke VS, Behrens HM, Haag J, Balschun K, Böger C, Becker T, Ebert MP, Lordick F, Röcken C. Prognostic and putative predictive biomarkers of gastric cancer for personalized medicine. Diagnostic Molecular Pathology. 2013;22(3):127-137
  75. 75. Uotani T, Miftahussurur M, Yamaoka Y. Effect of bacterial and host factors on Helicobacter pylori eradication therapy. Expert Opinion on Therapeutic Targets. 2015;6:1-14

Written By

Pekka Kaipainen and Markus Kaski

Reviewed: 08 January 2018 Published: 14 October 2020