Helicobacter Pylori Infection
- Author: Luigi Santacroce, MD; Chief Editor: BS Anand, MD more...
Helicobacter pylori (see the image below) is a ubiquitous organism that is present in about 50% of the global population. Chronic infection with H pylori causes atrophic and even metaplastic changes in the stomach, and it has a known association with peptic ulcer disease. The most common route of H pylori infection is either oral-to-oral or fecal-to-oral contact.
Signs and symptoms
In general, patients infected with H pylori are asymptomatic, and no specific clinical signs have been described. When signs and/or symptoms are present, they may include the following:
Hunger in the morning
See Clinical Presentation for more detail.
In patients with suspected H pylori infection, the following laboratory studies may aid in the diagnosis:
H pylori fecal antigen test: Very specific (98%) and sensitive (94%); positive results obtained in the initial stages of infection; can be used to detect posttreatment eradication
Carbon-13 urea breath test: Concentration of the labeled carbon is high only when urease is present in the stomach, a reaction possible only with H pylori infection
H pylori serology: High (>90%) specificity and sensitivity; useful for detecting a newly infected patient but not a good test for follow-up of treated patients
Antibiogram: Useful in geographic areas with a high resistance rate against metronidazole and clarithromycin [1, 2] ; these antibiotics should not be recommended as first-line drugs in such areas
There is no staging system for H pylori infection, but the following steps in the disease process are well described:
Intestinal metaplasia: May evolve into dysplasia
Gastric adenocarcinoma: Consider ultrasonography and esophagogastroduodenoscopy (EGD) in patients with gastric MALTomas (mucosa-associated lymphatic tissue lymphomas) for more precise staging of the disease
Imaging studies are not helpful in the diagnosis of H pylori infection. However, they may be useful in patients with complicated disease (eg, ulcer disease, gastric cancer, MALToma).
EGD: Often necessary in patients with symptoms of peptic ulcer disease to view the condition of the mucosal lining of the stomach and duodenum
Biopsy plus EGD: To obtain biopsy specimens from the gastric antrum and to perform a histologic examination on the obtained specimens
Echography plus EGD: Mandatory in patients with positive biopsy results for gastric MALTomas to allow a more precise staging of the disease
See Workup for more detail.
Only treat patients with a positive test result for H pylori infection. It is important to consider possible antibiotic resistance when selecting the treatment regimen.
The US FDA and international organizations have approved several triple therapy regimens for the treatment of H pylori infection in patients with gastric and duodenal peptic ulcer disease, as follows:
Omeprazole, amoxicillin, and clarithromycin (OAC) for 10 days
Bismuth subsalicylate, metronidazole, and tetracycline (BMT) for 14 days
Lansoprazole, amoxicillin, and clarithromycin (LAC), for either 10 days or 14 days
All the eradication treatments have a high incidence of certain adverse effects (eg, nausea, metallic taste). If skin rash, vomiting, or diarrhea occurs, discontinue treatment.
Other medications used in the management of H pylori infection include the following:
Antidiarrheals (eg, bismuth subsalicylate)
Proton pump inhibitors (eg, lansoprazole, omeprazole)
H2-receptor blockers (eg, ranitidine, famotidine)
Surgical intervention is not required for patients with H pylori infection, but it may be a consideration for patients with severe complications, such as cancer.
In 1983, Warren (a biologist) and Marshall (a clinician) described Helicobacter pylori (HP). At first, they named the bacterium Campylobacter pyloridis. Later, it was named Campylobacter pylori. Since then, a large number of reports have been produced on H pylori and its pathogenetic potential.
In fact, although peptic ulcer disease is the most studied disease related to H pylori infection, this bacterium is seemingly involved in the pathogenesis of several extragastric diseases, such as mucosa-associated lymphoid tissue lymphomas (MALTomas), coronaritis (inflammation of coronary arteries), gastroesophageal reflux disease (GERD), iron deficiency anemia, skin disease, and rheumatologic conditions. However, at present, many of these associations remain largely uncertain, and the debate to confirm or refute causality related to these associations is still open.
The association of chronic H pylori infection with alterations in gastric mucosal cell proliferation is recognized worldwide. In addition, H pylori can produce and release several bioactive factors that may directly affect the stomach's parietal cells, which produce hydrochloric acid, and enterochromaffinlike (ECL) cells (ie, G cells and D cells), which produce gastrin and somatostatin, respectively. Evidence suggests that H pylori inhibits D cells and stimulates G cells. H pylori has some control mechanisms that are able to switch the transcription of different genes on or off when needed. Two histology images are presented below.
A strong association has been reported between H pylori infection and gastric lymphoma and adenocarcinoma of the body and antrum of the stomach. Some cofactors may play a key role in determining such diseases. Whether H pylori eradication can decrease the risk of cancer remains unknown.
H pylori infection occurs more frequently in developing countries than in industrialized countries. H pylori strains differ in their potential to cause diseases. Although anyone can develop a microscopic gastritis, only a minority of infected persons develop ulcers or other diseases.
Some Helicobacter -like organisms (HLOs) have been detected by specific polymerase chain reaction tests. The first of these HLOs was described in ferrets and is called Helicobacter mustelae. Helicobacter hepaticus has been described in Syrian hamsters. These HLOs are useful for researching H pylori infection modalities.
The most common route of H pylori infection is either oral-to-oral (stomach contents are transmitted from mouth to mouth) or fecal-to-oral (from stool to mouth) contact. Parents and siblings seem to play a primary role in transmission.
In a susceptible host, H pylori results in chronic active gastritis that may lead, in turn, to duodenal and gastric ulcer disease, gastric cancer, and MALTomas. H pylori infection causes chronic active gastritis, which is characterized by a striking infiltrate of the gastric epithelium and the underlying lamina propria by neutrophils, T and B lymphocytes, macrophages, and mast cells. Mast cells, usually responsible for the immune response balance, may be important effector cells in the pathogenesis of gastritis. However, H pylori does not seem to invade the gastric mucosa, although evidence suggests that the mucus layer provides a niche wherein the germ is protected from gastric secretions.
The release of host cytokines after direct contact of H pylori with the epithelial cells of the gastric lining could recall the inflammatory cells in the infected area. One study demonstrated that the gastric epithelium, when infiltrated by neutrophils and macrophages in the lamina propria, highly expresses 2 neutrophil chemotactic factors: gro-alpha and interleukin-8. In addition, the interferon-gamma inducible protein–10 (IP-10) and the monokine induced by interferon-gamma (MIG), 2 selective chemotactic factors for T lymphocytes, are expressed by the endothelium and mononuclear cells of the gastric mucosa in patients with H pylori -related gastritis. According to the same study, gro-alpha and interleukin-8 may have a central role in neutrophils trafficking from the vessels to the mucosal epithelium, while IP-10 and MIG determine T lymphocyte recruitment into the mucosa.
Another hypothesis states that H pylori may recall immune cells from afar because of its own molecules, such as urea or lipopolysaccharide (LPS). Outer-membrane permeability is a function mediated by LPS. Despite the presence of bacterial LPS in biologically active quantities in the gastric mucosa, the mechanisms by which it may recall the immune cells are still unknown. According to one hypothesis, H pylori may induce the production of autoantibodies against the host's gastric lining.
The LPS of H pylori shows certain blood group antigens, such as Leb, Lex, Ley, and H-type I. Such antigens are thought to represent important virulence factors involved in the adhesive process of the germ. Leb constitutes an adhesin, and differences exist in the Le compositions of adherent and nonadherent bacteria. This, perhaps, accounts for a relationship between adhesion and Le expression. Hage and colleagues identified the BabA protein (Blood group antigen-binding Adhesin) in H pylori that interacts with gastric mucus binding Leb antigens, confirming the relationship. As a consequence, H+ bridges may be formed, strongly anchoring the bacterium to the gastric mucosa.
In addition, any Le antigen shows phase variation leading to the spontaneous and random switching on and off of the expression of these antigens. For example, the H-type I antigen seems to be the result of a reversible singular nucleotidic deletion/insertion in a tract of a glycosyl transferase gene. The LPS of the H pylori also seems to influence tumoral proliferation of ECL cells, stimulating the intracellular polyamine biosynthesis pathway and ornithine decarboxylase activity by the activation of a CD14 receptor on the ECL cell.
In 1997, Tomb and coworkers completely sequenced the H pylori genome, and some differences were found in gene encoding factors that are likely to interact with the host, such as surface proteins. Two of the most important genes of H pylori are VACA and CAGA. The VACA gene codes for the Vac-A cytotoxin, a vacuolating toxin. Most H pylori strains (60%), by unexplained causes, do not produce this protein. The CAGA gene codes for the Cag-A protein, which seems to stimulate the production of chemotactic factors for the neutrophils by the gastric epithelium of the host. A certain proportion of H pylori strains (40%), by unexplained causes, does not produce this protein.
After the exposure to CAGA -positive H pylori strains, an increase in catalase, glutathione peroxidase, and superoxide dismutase activity has been reported. This increase is associated with fewer DNA adducts and reduced susceptibility of the gastric cells to the irreversible injuries from reactive oxygen species (ROS) compared with exposure to CAGA -negative H pylori strains. Such alterations of the ROS scavenging enzymes may partly account for the increased risk of gastric cancer in individuals with H pylori infection.
A relationship among CAGA/Cag-A, VACA alleles, and the Le subtype of H pylori strains has been reported, as has a link between these and the redox status of the gastric mucosa. For example, H pylori is able to induce apoptosis in epithelial cells and T lymphocytes. The CAGA -positive strains of H pylori seem to be able to increase FASL expression in T lymphocytes (up-regulation of FASL on such cells is redox-sensitive), which facilitates a selective killing of the T lymphocytes. This molecular mechanism may have a key role in the persistence of CAGA -positive strains.
In addition, H pylori up-regulates caspases 3, 6, 8, and 9. Caspases 3 and 9 in epithelial cells are fundamental in inducing apoptosis. The expression of some bacterial genes is acid-regulated, as reported for the FILA gene (responsible for the H pylori motility) that codes for a sigma factor required for transcription of the flagellin gene FLAA. Flagella and urease are very important for the colonization of the gastric mucosa by the bacterium.
Note the following:
H pylori infection causes atrophic and even metaplastic changes in the stomach.
The bacterial adhesion appears to result in tyrosine phosphorylation and is specific for gastric cells.
The adhesion of H pylori to the gastric cells causes a direct decrease in mucosal levels of glutathione, a fundamental molecule in the maintenance of the cellular redox status and in the molecular regulation of host immune responses. However, the LPS of H pylori may induce the production of autoantibodies that are able to worsen the atrophy in the corpus mucosa and cause a concomitant increase in parietal cell antibodies. Such events are accompanied by a decrease in anti- H pylori immunoglobulin titers. This process leads to a scenario of severe atrophy without bacterial colonization combined with high levels of autoantibodies against gastric parietal cells.
A number of reports show the close association between H pylori infection and low-grade gastric MALTomas.
Giannakis and colleagues demonstrated that H pylori may adapt to gastric stem cells, influencing their biology and contributing to tumorigenesis of the stomach. 
United States statistics
The frequency of H pylori infection may be linked to race. White persons account for 29% of cases, and Hispanic persons account for 60% of cases.
H pylori is a ubiquitous organism. At least 50% of all people are infected, but an exact determination is not available, mostly because exact data are not available from developing countries. H pylori may be detected in approximately 90% of individuals with peptic ulcer disease; however, less than 15% of infected persons may have this disease.
Race-, sex-, and age-related statistics
The pathogenetic role of H pylori may differ depending on the geography and race. White persons are infected with H pylori less frequently than persons of other racial groups. The prevalence rate is approximately 20% in white persons, 54% in African American persons, and 60% in Hispanic persons.
No sex predilection is known; however, females have a higher incidence of reinfection (5-8%) than males.
H pylori infection may be acquired at any age. According to some epidemiologic studies, this infection is acquired most frequently during childhood. Children and females have a higher incidence of reinfection (5-8%) than adult males.
The prognosis is usually excellent, even in patients with complications, such as gastric MALToma. However, the prognosis becomes poor for patients who develop squamous cell esophageal cancer or gastric carcinoma.
The rate of reinfection is very low (1-2%); however, children and females have a higher incidence of reinfection (5-8%)
The mortality rate related to H pylori infection is not precisely known, but it seems to be minimal (ie, approximately 2-4% of all infected people). Mortality is due to the complications of the infection, such as gastric ulcer perforation or MALTomas of the GI tract. Otherwise, the morbidity of H pylori infection can be very high.
Results from a recent meta-analysis by Lender and colleagues suggest that the reduction of H pylori infection in developed nations may be contributing to the rise in obesity in those countries. Using 49 studies, with data from 10 European nations, Japan, the United States, and Australia, the investigators found a significant inverse correlation between the rates of obesity/overweight and the prevalence of H pylori infection. Mean rates for obese and overweight individuals were 46.6% and 14.2%, respectively, whereas the mean prevalence of H pylori infection was 44.1% (range, 17%–75%). The authors acknowledge, however, that the study does not prove that the reduced prevalence of H pylori has directly impacted obesity rates. The association, they admit, could be more complex; it may be, for example, that hygiene factors that encourage H pylori infection may also somehow discourage obesity.[7, 8]
Complications include the following:
Gastric adenocarcinoma is the most severe consequence of an H pylori infection.
Gastric MALToma may be treated with H pylori eradication therapy and has a better prognosis than gastric adenocarcinoma. A significant difference exists between the therapeutic response of MALTomas restricted to the mucosa and other, more infiltrating lesions. The only predictive factor for disease regression seems to be the absence of nodal involvement.
H pylori infection is associated with squamous cell esophageal cancer.
H pylori may play an important role in idiopathic thrombocytopenic purpura. This is due to anti-CagA antibodies that cross-react with platelet antigens.
According to some reports, H pylori eradication may cause peptic esophagitis, probably due to a protective action of the bacteria on the cardia area.
Educate patients with a high risk for gastric cancer about clinical control methods and, if H pylori -positive, to begin eradication therapy. However, patients must be educated about the adverse effects of the therapy in order to impress upon them the importance of compliance with the full regimen in order to prevent antibiotic resistance and relapse.
Horiki N, Omata F, Uemura M, et al. Annual change of primary resistance to clarithromycin among Helicobacter pylori isolates from 1996 through 2008 in Japan. Helicobacter. 2009 Oct. 14(5):86-90. [Medline].
Fallone CA. Epidemiology of the antibiotic resistance of Helicobacter pylori in Canada. Can J Gastroenterol. 2000 Nov. 14(10):879-82. [Medline].
Hage N, Renshaw JG, Winkler GS, Gellert P, Stolnik S, Falcone FH. Improved expression and purification of the Helicobacter pylori adhesin BabA through the incorporation of a hexa-lysine tag. Protein Expr Purif. 2015 Feb. 106:25-30. [Medline]. [Full Text].
Tomb JF, White O, Kerlavage AR, et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997 Aug 7. 388(6642):539-47. [Medline].
Giannakis M, Chen SL, Karam SM, et al. Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci U S A. 2008 Mar. 105(11):4358-63. [Medline].
Pullen LC. Does H pylori Eradication Explain Rising Obesity?. Medscape Medical News. Jun 9 2014. [Full Text].
Lender N, Talley NJ, Enck P, et al. Review article: associations between Helicobacter pylori and obesity - an ecological study. Aliment Pharmacol Ther. 2014 Jul. 40(1):24-31. [Medline].
Luther J, Dave M, Higgins PD, Kao JY. Association between Helicobacter pylori infection and inflammatory bowel disease: A meta-analysis and systematic review of the literature. Inflamm Bowel Dis. 2009 Sep 16. epub ahead of print. [Medline].
Jackson L, Britton J, Lewis SA, et al. A population-based epidemiologic study of Helicobacter pylori infection and its association with systemic inflammation. Helicobacter. 2009 Oct. 14(5):108-13. [Medline].
Hsu PI, Wu DC, Chen WC, et al. Randomized controlled trial comparing 7-day triple, 10-day sequential, and 7-day concomitant therapies for Helicobacter pylori infection. Antimicrob Agents Chemother. 2014 Oct. 58 (10):5936-42. [Medline].
Greenberg ER, Anderson GL, Morgan DR, et al. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial. Lancet. 2011 Aug 6. 378(9790):507-14. [Medline].
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 May. 59(5):572-8. [Medline].
Apostolopoulos P, Koumoutsos I, Ekmektzoglou K, et al. Concomitant versus sequential therapy for the treatment of Helicobacter pylori infection: a Greek randomized prospective study. Scand J Gastroenterol. 2016 Feb. 51 (2):145-51. [Medline].
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. [Medline].
Papastergiou V, Georgopoulos SD, Karatapanis S. Treatment of Helicobacter pylori infection: meeting the challenge of antimicrobial resistance. World J Gastroenterol. 2014 Aug 7. 20 (29):9898-911. [Medline].
Malfertheiner P, Bazzoli F, Delchier JC, Celiñski K, Giguère M, Rivière M, et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet. 2011 Mar 12. 377(9769):905-13. [Medline].
Gisbert JP, Castro-Fernandez M, Perez-Aisa A, Cosme A, Molina-Infante J, Rodrigo L, et al. Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures. Aliment Pharmacol Ther. 2012 Apr. 35 (8):941-7. [Medline]. [Full Text].
Liu X, Wang H, Lv Z, Wang Y, Wang B, Xie Y, et al. Rescue Therapy with a Proton Pump Inhibitor Plus Amoxicillin and Rifabutin for Helicobacter pylori Infection: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2015. 2015:415648. [Medline]. [Full Text].
Lee SB, Yang JW, Kim CS. The association between conjunctival MALT lymphoma and Helicobacter pylori. Br J Ophthalmol. 2008 Apr. 92(4):534-6. [Medline].
Aanpreung P. Suggestive parameters for eradication therapy in children with Helicobacter pylori gastritis. J Med Assoc Thai. 2005 Nov. 88 Suppl 8:S21-6. [Medline].
Adachi K, Hashimoto T, Komazawa Y, et al. Helicobacter pylori infection influences symptomatic response to anti-secretory therapy in patients with GORD--crossover comparative study with famotidine and low-dose lansoprazole. Dig Liver Dis. 2005 Jul. 37(7):485-90. [Medline].
Alexander GA, Brawley OW. Association of Helicobacter pylori infection with gastric cancer. Mil Med. 2000 Jan. 165(1):21-7. [Medline].
Ceponis PJ, Jones NL. Modulation of host cell signal transduction pathways by Helicobacter pylori infection. Can J Gastroenterol. 2005 Jul. 19(7):415-20. [Medline].
Chelimsky G, Czinn SJ. Helicobacter pylori infection in children: update. Curr Opin Pediatr. 2000 Oct. 12(5):460-2. [Medline].
Cheng TY, Lin JT, Chen LT, et al. Association of T-cell regulatory gene polymorphisms with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma. J Clin Oncol. 2006 Jul 20. 24(21):3483-9. [Medline].
Chitsazi MT, Fattahi E, Farahani RM, e al. Helicobacter pylori in the dental plaque: is it of diagnostic value for gastric infection?. Med Oral Patol Oral Cir Bucal. 2006 Jul 1. 11(4):E325-8. [Medline].
Craanen ME, Blok P, Dekker W, et al. Helicobacter pylori and early gastric cancer. Gut. 1994 Oct. 35(10):1372-4. [Medline].
Davydov L, Cheng JW. The association of infection and coronary artery disease: an update. Expert Opin Investig Drugs. 2000 Nov. 9(11):2505-17. [Medline].
Demirel A, Oncel S, Caydere M, et al. Helicobacter pylori infection in gastrectomy specimens. The Internet Journal of Gastroenterology 2000; 1 (1). [Full Text].
Dunn BE, Cohen H, Blaser MJ. Helicobacter pylori. Clin Microbiol Rev. 1997 Oct. 10(4):720-41. [Medline].
Eaton KA, Benson LH, Haeger J, et al. Role of transcription factor T-bet expression by CD4+ cells in gastritis due to Helicobacter pylori in mice. Infect Immun. 2006 Aug. 74(8):4673-84. [Medline].
El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000 Mar 23. 404(6776):398-402. [Medline].
Ercan I, Cakir BO, Uzel TS, et al. The role of gastric Helicobacter pylori infection in laryngopharyngeal reflux disease. Otolaryngol Head Neck Surg. 2006 Jul. 135(1):52-5. [Medline].
Fallone CA, Barkun AN, Friedman G, et al. Is Helicobacter pylori eradication associated with gastroesophageal reflux disease?. Am J Gastroenterol. 2000 Apr. 95(4):914-20. [Medline].
Farag TH, Stoltzfus RJ, Khalfan SS, et al. Helicobacter pylori infection is associated with severe anemia of pregnancy on Pemba Island, Zanzibar. Am J Trop Med Hyg. 2007 Mar. 76(3):541-8. [Medline].
Fiorini G, Vakil N, Zullo A, Saracino IM, Castelli V, Ricci C, et al. Culture-Based Selection Therapy for Patients Who Did Not Respond to Previous Treatment for Helicobacter pylori Infection. Clin Gastroenterol Hepatol. 2012 Dec 23. [Medline].
Fischbach W. Primary gastric lymphoma of MALT: considerations of pathogenesis, diagnosis and therapy. Can J Gastroenterol. 2000 Nov. 14 Suppl D:44D-50D. [Medline].
Fock KM, Katelaris P, Sugano K, et al. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol. 2009 Oct. 24(10):1587-600. [Medline].
Freston JW. Management of peptic ulcers: emerging issues. World J Surg. 2000 Mar. 24(3):250-5. [Medline].
Garcia-Altes A, Rota R, Barenys M, et al. Cost-effectiveness of a 'score and scope' strategy for the management of dyspepsia. Eur J Gastroenterol Hepatol. 2005 Jul. 17(7):709-19. [Medline].
Gatopoulou A, Mimidis K, Giatromanolaki A, et al. Impact of Helicobacter pylori infection on histological changes in non-erosive reflux disease. World J Gastroenterol. 2004 Apr 15. 10(8):1180-2. [Medline].
Graham DY. Therapy of Helicobacter pylori: current status and issues. Gastroenterology. 2000 Feb. 118(2 Suppl 1):S2-8. [Medline].
Graham DY, Lew GM, Lechago J. Antral G-cell and D-cell numbers in Helicobacter pylori infection: effect of H. pylori eradication. Gastroenterology. 1993 Jun. 104(6):1655-60. [Medline].
Graham DY, Lew GM, Malaty HM, et al. Factors influencing the eradication of Helicobacter pylori with triple therapy. Gastroenterology. 1992 Feb. 102(2):493-6. [Medline].
Graham DY, Malaty HM, Evans DG, et al. Epidemiology of Helicobacter pylori in an asymptomatic population in the United States. Effect of age, race, and socioeconomic status. Gastroenterology. 1991 Jun. 100(6):1495-501. [Medline].
Guslandi M. Stool immunoassay for Helicobacter pylori is not specific enough. BMJ. 2000 Jun 3. 320(7248):1541. [Medline].
Howden CW, Hunt RH. Guidelines for the management of Helicobacter pylori infection. Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. Am J Gastroenterol. 1998 Dec. 93(12):2330-8. [Medline].
Jamieson GG. Current status of indications for surgery in peptic ulcer disease. World J Surg. 2000 Mar. 24(3):256-8. [Medline].
Jia CL, Jiang GS, Li CH, Li CR. Effect of dental plaque control on infection of Helicobacter pylori in gastric mucosa. J Periodontol. 2009 Oct. 80(10):1606-9. [Medline].
Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. 2006 Jul. 19(3):449-90. [Medline].
Leinonen M, Saikku P. Infections and atherosclerosis. Scand Cardiovasc J. 2000. 34(1):12-20. [Medline].
Lewis JD. Population screening and treatment of Helicobacter pylori. Gastroenterology. 2000 Dec. 119(6):1795-7. [Medline].
Logan R. Epidemiology could yield new ways to manage H. pylori infection. Lancet. 1999 Sep 18. 354(9183):1006. [Medline].
Lopes AI, Victorino RM, Palha AM, et al. Mucosal lymphocyte subsets and HLA-DR antigen expression in paediatric Helicobacter pylori-associated gastritis. Clin Exp Immunol. 2006 Jul. 145(1):13-20. [Medline].
Mesquita MA, Lorena SL, Almeida JR, et al. One-week dual therapy with ranitidine bismuth citrate and clarithromycin for the treatment of Helicobacter pylori infection in Brazilian patients with peptic ulcer. World J Gastroenterol. 2005 Jun 21. 11(23):3566-9. [Medline].
Mueller A, Sayi A, Hitzler I. Protective and pathogenic functions of T-cells are inseparable during the Helicobacter-host interaction. Discov Med. 2009 Aug. 8(41):68-73. [Medline].
Nakajima S, Krishnan B, Ota H, et al. Mast cell involvement in gastritis with or without Helicobacter pylori infection. Gastroenterology. 1997 Sep. 113(3):746-54. [Medline].
O'Morain C, Montague S. Challenges to therapy in the future. Helicobacter. 2000. 5 Suppl 1:S23-6; discussion S27-31. [Medline].
Padol S, Yuan Y, Thabane M, et al. The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis. Am J Gastroenterol. 2006 Jul. 101(7):1467-75. [Medline].
Peach HG, Barnett NE. Determinants of basal plasma gastrin levels in the general population. J Gastroenterol Hepatol. 2000 Nov. 15(11):1267-71. [Medline].
Pratt JS, Sachen KL, Wood HD, et al. Modulation of host immune responses by the cytolethal distending toxin of Helicobacter hepaticus. Infect Immun. 2006 Aug. 74(8):4496-504. [Medline].
Reyrat JM, Rappuoli R, Telford JL. A structural overview of the Helicobacter cytotoxin. Int J Med Microbiol. 2000 Oct. 290(4-5):375-9. [Medline].
Rodrigues MN, Queiroz DM, Bezerra Filho JG, et al. Prevalence of Helicobacter pylori infection in children from an urban community in north-east Brazil and risk factors for infection. Eur J Gastroenterol Hepatol. 2004 Feb. 16(2):201-5. [Medline].
Santacroce L, Bufo P, Latorre V, et al. [Role of mast cells in the physiopathology of gastric lesions caused by Helicobacter pylori]. Chir Ital. 2000 Sep-Oct. 52(5):527-31. [Medline].
Smoot DT, Mobley HL, Chippendale GR, et al. Helicobacter pylori urease activity is toxic to human gastric epithelial cells. Infect Immun. 1990 Jun. 58(6):1992-4. [Medline].
Stahler FN, Odenbreit S, Haas R, et al. The novel Helicobacter pylori CznABC metal efflux pump is required for cadmium, zinc, and nickel resistance, urease modulation, and gastric colonization. Infect Immun. 2006 Jul. 74(7):3845-52. [Medline].
Tsai CJ, Perry S, Sanchez L, et al. Helicobacter pylori infection in different generations of Hispanics in the San Francisco Bay Area. Am J Epidemiol. 2005 Aug 15. 162(4):351-7. [Medline].
Tytgat GN. Review article: Helicobacter pylori: where are we and where are we going?. Aliment Pharmacol Ther. 2000 Oct. 14 Suppl 3:55-8. [Medline].
Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983 Jun 4. 1(8336):1273-5. [Medline].
Vaira D, Gatta L, Ricci C, et al. Peptic ulcer and Helicobacter pylori: update on testing and treatment. Postgrad Med. 2005 Jun. 117(6):17-22, 46. [Medline].
Wang X, Wattiez R, Paggliacia C, et al. Membrane topology of VacA cytotoxin from H. pylori. FEBS Lett. 2000 Sep 15. 481(2):96-100. [Medline].
Watts TL. Smoking, Helicobacter pylori, and periodontitis. BMJ. 2006 Jun 24. 332(7556):1513. [Medline].
Wotherspoon AC. A critical review of the effect of Helicobacter pylori eradication on gastric MALT lymphoma. Curr Gastroenterol Rep. 2000 Dec. 2(6):494-8. [Medline].
Chao CY, Wang CH, Che YJ, Kao CY, Wu JJ, Lee GB. An integrated microfluidic system for diagnosis of the resistance of Helicobacter pylori to quinolone-based antibiotics. Biosens Bioelectron. 2016 Apr 15. 78:281-9. [Medline].
Lee YC, Chiang TH, Liou JM, Chen HH, Wu MS, Graham DY. Mass eradication of Helicobacter pylori to prevent gastric cancer: theoretical and practical considerations. Gut Liver. 2016 Jan 23. 10 (1):12-26. [Medline].
Kono Y, Okada H, Takenaka R, et al. Does Helicobacter pylori exacerbate gastric mucosal injury in users of nonsteroidal anti-inflammatory drugs? A multicenter, retrospective, case-control study. Gut Liver. 2016 Jan 23. 10 (1):69-75. [Medline].