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International Journal Of Medical, Pharmacy And Drug Research(IJMPD)

Current Understanding of the Transmission, Diagnosis, and Treatment of H. pylori Infection: A Comprehensive Review

Hend Sadeq Mohammed Aljaberi , Nida Khalid Ansari , Mengqiu Xiong , Hongxin Peng , Bangshun He , Shukui Wang

International Journal of Medical, Pharmacy and Drug Research(IJMPD), Vol-7,Issue-2, March - April 2023, Pages 1-26 , 10.22161/ijmpd.7.2.1

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Article Info: Received: 11 Feb 2023; Received in revised form: 14 Mar 2023; Accepted: 21 Mar 2023; Available online: 28 Mar 2023


H. pylori infection is a prevalent bacterial infection that affects the gastric mucosa of humans, with a prevalence ranging from 30% to 90%, depending on the region. The infection is a significant cause of gastritis, peptic ulcer disease, and gastric cancer. In this comprehensive review, we discuss the current understanding of the transmission, diagnosis, and treatment of H. pylori infection. We describe the risk factors and epidemiology of the infection, along with its pathogenesis, which involves multiple virulence factors that contribute to the colonization and survival of the bacteria in the acidic stomach environment. Diagnostic tests for H. pylori infection include invasive and non-invasive methods, with the choice of test depending on several factors. Treatment of H. pylori infection is aimed at eradicating the bacteria and preventing complications. Antibiotic-based triple or quadruple therapy, in combination with acid-suppressing agents, is the standard treatment, but antibiotic resistance is an emerging problem that needs to be addressed. This comprehensive review provides a useful resource for clinicians, researchers, and public health officials involved in managing H. pylori infection and its associated complications.

Diagnostic, and Treatment, Epidemiology of H. pylori, H. pylori, Risk factors, Pathogenesis.

[1] Kivi, M., Aspects of Helicobacter pylori transmission. 2005: Karolinska Institutet (Sweden).
[2] Marshall, B.J., et al., Attempt to fulfil Koch's postulates for pyloric Campylobacter. Medical Journal of Australia, 1985. 142(8): p. 436-439.
[3] Hooi, J.K., et al., Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology, 2017. 153(2): p. 420-429.
[4] Parsonnet, J., et al., Helicobacter pylori infection and gastric lymphoma. New England Journal of Medicine, 1994. 330(18): p. 1267-1271.
[5] Fischbach, W., Gastric mucosal-associated lymphoid tissue lymphoma. Gastroenterology Clinics, 2013. 42(2): p. 371-380.
[6] Backert, S. and M. Clyne, Pathogenesis of Helicobacter pylori infection. Helicobacter, 2011. 16: p. 19-25.
[7] Marshall, B. and J.R. Warren, Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. The lancet, 1984. 323(8390): p. 1311-1315.
[8] Solnick, J.V. and D.B. Schauer, Emergence of diverse Helicobacter species in the pathogenesis of gastric and enterohepatic diseases. Clinical microbiology reviews, 2001. 14(1): p. 59-97.
[9] Mladenova, I. and M. Durazzo, Transmission of Helicobacter pylori. Minerva gastroenterologica e dietologica, 2018. 64(3): p. 251-254.
[10] Oona, M., et al., Helicobacter pylori infection in children in Estonia: decreasing seroprevalence during the 11‐year period of profound socioeconomic changes. Helicobacter, 2004. 9(3): p. 233-241.
[11] Bürgers, R., et al., Helicobacter pylori in human oral cavity and stomach. European journal of oral sciences, 2008. 116(4): p. 297-304.
[12] Stefano, K., et al., Helicobacter pylori, transmission routes and recurrence of infection: state of the art. Acta Bio Medica: Atenei Parmensis, 2018. 89(Suppl 8): p. 72.
[13] Song, Q., et al., Helicobacter pylori in the Oral Cavity. Digestive diseases and sciences, 2000. 45(11): p. 2162-2167.
[14] Yee, J.K., Are the view of Helicobacter pylori colonized in the oral cavity an illusion? Experimental & Molecular Medicine, 2017. 49(11): p. e397-e397.
[15] Gebara, E., et al., Persistence of Helicobacter pylori in the oral cavity after systemic eradication therapy. Journal of clinical periodontology, 2006. 33(5): p. 329-333.
[16] Kivi, M.r., et al., Concordance of Helicobacter pylori strains within families. Journal of clinical microbiology, 2003. 41(12): p. 5604-5608.
[17] Queralt, N., R. Bartolome, and R. Araujo, Detection of Helicobacter pylori DNA in human faeces and water with different levels of faecal pollution in the north‐east of Spain. Journal of applied microbiology, 2005. 98(4): p. 889-895.
[18] Bui, D., et al., Serologic evidence for fecal–oral transmission of Helicobacter pylori. The American journal of tropical medicine and hygiene, 2016. 94(1): p. 82.
[19] Santiago, P., Y. Moreno, and M.A. Ferrús, Identification of viable Helicobacter pylori in drinking water supplies by cultural and molecular techniques. Helicobacter, 2015. 20(4): p. 252-259.
[20] Adams, B., T. Bates, and J. Oliver, Survival of Helicobacter pylori in a natural freshwater environment. Applied and environmental microbiology, 2003. 69(12): p. 7462-7466.
[21] Klein, P.D., et al., Water source as risk factor for Helicobacter pylori infection in Peruvian children. The Lancet, 1991. 337(8756): p. 1503-1506.
[22] Salih, B.A., Helicobacter pylori infection in developing countries: the burden for how long? Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association, 2009. 15(3): p. 201.
[23] Goodman, K.J., et al., Helicobacter pylori infection in the Colombian Andes: a population-based study of transmission pathways. American journal of epidemiology, 1996. 144(3): p. 290-299.
[24] ZHANG, Y.Y., et al., ‘true’re‐infection of Helicobacter pylori after successful eradication–worldwide annual rates, risk factors and clinical implications. Alimentary pharmacology & therapeutics, 2009. 29(2): p. 145-160.
[25] Momtaz, H., et al., Study of Helicobacter pylori genotype status in cows, sheep, goats and human beings. BMC gastroenterology, 2014. 14(1): p. 1-7.
[26] Payão, S.L.M. and L.T. Rasmussen, Helicobacter pylori and its reservoirs: A correlation with the gastric infection. World journal of gastrointestinal pharmacology and therapeutics, 2016. 7(1): p. 126.
[27] Engstrand, L., et al., Inoculation of barrier-born pigs with Helicobacter pylori: a useful animal model for gastritis type B. Infection and Immunity, 1990. 58(6): p. 1763-1768.
[28] Handt, L.K., et al., Helicobacter pylori isolated from the domestic cat: public health implications. Infection and immunity, 1994. 62(6): p. 2367-2374.
[29] Rodrigues, M.N., et al., Prevalence of Helicobacter pylori infection in children from an urban community in north-east Brazil and risk factors for infection. European journal of gastroenterology & hepatology, 2004. 16(2): p. 201-205.
[30] Glynn, M.K., et al., Seroincidence of Helicobacter pylori infection in a cohort of rural Bolivian children: acquisition and analysis of possible risk factors. Clinical Infectious Diseases, 2002. 35(9): p. 1059-1065.
[31] Rothenbacher, D., et al., Role of infected parents in transmission of Helicobacter pylori to their children. The Pediatric infectious disease journal, 2002. 21(7): p. 674-679.
[32] Rocha, G.A., et al., Transmission of Helicobacter pylori infection in families of preschool‐aged children from Minas Gerais, Brazil. Tropical Medicine & International Health, 2003. 8(11): p. 987-991.
[33] Malaty, H.M., et al., Evidence from a nine-year birth cohort study in Japan of transmission pathways of Helicobacter pylori infection. Journal of clinical microbiology, 2000. 38(5): p. 1971-1973.
[34] Kivi, M., et al., Helicobacter pylori status in family members as risk factors for infection in children. Epidemiology & Infection, 2005. 133(4): p. 645-652.
[35] Lambert, J.R., et al., High Prevalence of Helicobacter pylori Antibodies in an Institutionalized Population: Evidence for Person--to--Person Transmission. American Journal of Gastroenterology (Springer Nature), 1995. 90(12).
[36] Tindberg, Y., et al., Helicobacter pylori infection in Swedish school children: lack of evidence of child-to-child transmission outside the family. Gastroenterology, 2001. 121(2): p. 310-316.
[37] Tsai, C.J., et al., Helicobacter pylori infection in different generations of Hispanics in the San Francisco Bay Area. American journal of epidemiology, 2005. 162(4): p. 351-357.
[38] Woodward, M., C. Morrison, and K. McColl, An investigation into factors associated with Helicobacter pylori infection. Journal of clinical epidemiology, 2000. 53(2): p. 175-181.
[39] Brenner, H., et al., Active infection with Helicobacter pylori in healthy couples. Epidemiology & Infection, 1999. 122(1): p. 91-95.
[40] Mendall, M., et al., Childhood living conditions and Helicobacter pylori seropositivity in adult life. The Lancet, 1992. 339(8798): p. 896-897.
[41] Brown, L.M., et al., Helicobacter pylori infection in rural China: demographic, lifestyle and environmental factors. International journal of epidemiology, 2002. 31(3): p. 638-645.
[42] Kuepper‐Nybelen, J., et al., Patterns of alcohol consumption and Helicobacter pylori infection: results of a population‐based study from Germany among 6545 adults. Alimentary pharmacology & therapeutics, 2005. 21(1): p. 57-64.
[43] Salaün, L., S. Ayraud, and N.J. Saunders, Phase variation mediated niche adaptation during prolonged experimental murine infection with Helicobacter pylori. Microbiology, 2005. 151(3): p. 917-923.
[44] Malaty, H.M., et al., Age at acquisition of Helicobacter pylori infection: a follow-up study from infancy to adulthood. The Lancet, 2002. 359(9310): p. 931-935.
[45] Aspholm-Hurtig, M., et al., Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin. Science, 2004. 305(5683): p. 519-522.
[46] Rothenbacher, D., et al., Role of Lewis A and Lewis B blood group antigens in Helicobacter pylori infection. Helicobacter, 2004. 9(4): p. 324-329.
[47] Yamaoka, Y., et al., Helicobacter pylori infection in mice: role of outer membrane proteins in colonization and inflammation. Gastroenterology, 2002. 123(6): p. 1992-2004.
[48] Magnusson, P.K., et al., Gastric cancer and human leukocyte antigen: distinct DQ and DR alleles are associated with development of gastric cancer and infection by Helicobacter pylori. Cancer research, 2001. 61(6): p. 2684-2689.
[49] Hartland, S., et al., A functional polymorphism in the interleukin-1 receptor-1 gene is associated with increased risk of Helicobacter pylori infection but not with gastric cancer. Digestive diseases and sciences, 2004. 49(9): p. 1545-1550.
[50] Björkholm, B., et al., Gnotobiotic transgenic mice reveal that transmission of Helicobacter pylori is facilitated by loss of acid-producing parietal cells in donors and recipients. Microbes and infection, 2004. 6(2): p. 213-220.
[51] Salama, N.R., B. Shepherd, and S. Falkow, Global transposon mutagenesis and essential gene analysis of Helicobacter pylori. Journal of bacteriology, 2004. 186(23): p. 7926-7935.
[52] Perez-Perez, G., et al., Evidence that cagA+ Helicobacter pylori strains are disappearing more rapidly than cagA− strains. Gut, 2002. 50(3): p. 295-298.
[53] Nilsson, C., et al., Correlation between cag pathogenicity island composition and Helicobacter pylori-associated gastroduodenal disease. Infection and immunity, 2003. 71(11): p. 6573-6581.
[54] Cardenas, V.M., et al., Iron deficiency and Helicobacter pylori infection in the United States. American journal of epidemiology, 2006. 163(2): p. 127-134.
[55] Everhart, J.E., et al., Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States. The Journal of infectious diseases, 2000. 181(4): p. 1359-1363.
[56] Goh, K.-L. and N. Parasakthi, The racial cohort phenomenon: seroepidemiology of Helicobacter pylori infection in a multiracial South-East Asian country. European journal of gastroenterology & hepatology, 2001. 13(2): p. 177-183.
[57] Asaka, M., et al., Gastric cancer. Helicobacter pylori: physiology and genetics, 2001: p. 481-498.
[58] Yeh, J.M., et al., Exploring the cost‐effectiveness of Helicobacter pylori screening to prevent gastric cancer in China in anticipation of clinical trial results. International journal of cancer, 2009. 124(1): p. 157-166.
[59] Torres, J., et al., A comprehensive review of the natural history of Helicobacter pylori infection in children. Archives of medical research, 2000. 31(5): p. 431-469.
[60] Agarwal, P.K., et al., Prevalence of Helicobacter pylori infection in upper gastrointestinal tract disorders (dyspepsia) patients visiting outpatient department of a hospital of North India. Journal of family medicine and primary care, 2018. 7(3): p. 577.
[61] Lacy, B.E. and J. Rosemore, Helicobacter pylori: ulcers and more: the beginning of an era. The Journal of nutrition, 2001. 131(10): p. 2789S-2793S.
[62] Gold, B.D., Helicobacter pylori infection in children. Current Problems in Pediatrics, 2001. 31(8): p. 247-266.
[63] De Oliveira, A.M.R., et al., Seroconversion for Helicobacter pylori in adults from Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1999. 93(3): p. 261-263.
[64] Ernst, P.B. and B.D. Gold, The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annual review of microbiology, 2000. 54: p. 615.
[65] Kuipers, E., Exploring the link between Helicobacter pylori and gastric cancer. Alimentary pharmacology & therapeutics, 1999. 13: p. 3-11.
[66] Kuipers, E., J. Thijs, and H. Festen, The prevalence of Helicobacter pylori in peptic ulcer disease. Alimentary pharmacology & therapeutics, 1995. 9: p. 59-69.
[67] Kusters, J.G., A.H. Van Vliet, and E.J. Kuipers, Pathogenesis of Helicobacter pylori infection. Clinical microbiology reviews, 2006. 19(3): p. 449-490.
[68] Maaroos, H.-I., et al., An 18-year follow-up study of chronic gastritis and Helicobacter pylori: association of CagA positivity with development of atrophy and activity of gastritis. Scandinavian journal of gastroenterology, 1999. 34(9): p. 864-869.
[69] Flores, S.E., et al., Helicobacter pylori infection perturbs iron homeostasis in gastric epithelial cells. PLoS One, 2017. 12(9): p. e0184026.
[70] Kato, S., et al., Helicobacter pylori sabA gene is associated with iron deficiency anemia in childhood and adolescence. PloS one, 2017. 12(8): p. e0184046.
[71] Rockey, D.C., et al., AGA technical review on gastrointestinal evaluation of iron deficiency anemia. Gastroenterology, 2020. 159(3): p. 1097-1119.
[72] Sipponen, P., et al., Prevalence of low vitamin B12 and high homocysteine in serum in an elderly male population: association with atrophic gastritis and Helicobacter pylori infection. Scandinavian journal of gastroenterology, 2003. 38(12): p. 1209-1216.
[73] Correa, P., M.B. Piazuelo, and M.C. Camargo, The future of gastric cancer prevention. Gastric cancer, 2004. 7(1): p. 9-16.
[74] Uemura, N., et al., Helicobacter pylori infection and the development of gastric cancer. New England journal of medicine, 2001. 345(11): p. 784-789.
[75] Blaser, M.J. and J.C. Atherton, Helicobacter pylori persistence: biology and disease. The Journal of clinical investigation, 2004. 113(3): p. 321-333.
[76] Danesh, J., R. Collins, and R. Peto, Chronic infections and coronary heart disease: is there a link? The lancet, 1997. 350(9075): p. 430-436.
[77] El-Omar, E.M., et al., Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature, 2000. 404(6776): p. 398-402.
[78] Eaton, K.A. and S. Krakowka, Effect of gastric pH on urease-dependent colonization of gnotobiotic piglets by Helicobacter pylori. Infection and immunity, 1994. 62(9): p. 3604-3607.
[79] Sobala, G., et al., Acute Helicobacter pylori infection: clinical features, local and systemic immune response, gastric mucosal histology, and gastric juice ascorbic acid concentrations. Gut, 1991. 32(11): p. 1415-1418.
[80] Kuipers, E.J., et al., Increase of Helicobacter pylori--Associated Corpus Gastritis during Acid Suppressive Therapy: Implications for Long--Term Safety. American Journal of Gastroenterology (Springer Nature), 1995. 90(9).
[81] El-Omar, E.M., et al., Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology, 1997. 113(1): p. 15-24.
[82] Consensus, N., Helicobacter pylori in peptic ulcer disease. JAMA, 1994. 272: p. 65-69.
[83] Suerbaum, S. and P. Michetti, Helicobacter pylori infection. New England Journal of Medicine, 2002. 347(15): p. 1175-1186.
[84] Rothenbacher, D. and H. Brenner, Burden of Helicobacter pylori and H. pylori-related diseases in developed countries: recent developments and future implications. Microbes and Infection, 2003. 5(8): p. 693-703.
[85] Pereira, M.-I. and J.A. Medeiros, Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas. World journal of gastroenterology: WJG, 2014. 20(3): p. 684.
[86] Zucca, E., et al., Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 2013. 24: p. vi144-vi148.
[87] Malfertheiner, P., et al., Management of Helicobacter pylori infection—the Maastricht IV/Florence consensus report. Gut, 2012. 61(5): p. 646-664.
[88] Floch, P., F. Mégraud, and P. Lehours, Helicobacter pylori strains and gastric MALT lymphoma. Toxins, 2017. 9(4): p. 132.
[89] Cammarota, G., et al., Helicobacter pylori reinfection and rapid relapse of low-grade B-cell gastric lymphoma. The Lancet, 1995. 345(8943): p. 192.
[90] Talley, N.J. and R.H. Hunt, What role does Helicobacter pylori play in dyspepsia and nonulcer dyspepsia? Arguments for and against H. pylori being associated with dyspeptic symptoms. Gastroenterology, 1997. 113(6): p. S67-S77.
[91] Moayyedi, P., et al., Eradication of Helicobacter pylori for non‐ulcer dyspepsia. Cochrane Database of Systematic Reviews, 2005(2).
[92] Öztekin, M., et al., Overview of Helicobacter pylori Infection: Clinical Features, treatment, and nutritional aspects. Diseases, 2021. 9(4): p. 66.
[93] Wroblewski, L.E. and R.M. Peek, Helicobacter pylori, cancer, and the gastric microbiota. Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract, 2016: p. 393-408.
[94] Eaton, K., D. Morgan, and S. Krakowka, Motility as a factor in the colonisation of gnotobiotic piglets by Helicobacter pylori. Journal of Medical Microbiology, 1992. 37(2): p. 123-127.
[95] De Brito, B.B., et al., Pathogenesis and clinical management of Helicobacter pylori gastric infection. World journal of gastroenterology, 2019. 25(37): p. 5578.
[96] Shibayama, K., et al., Metabolism of glutamine and glutathione via γ‐glutamyltranspeptidase and glutamate transport in Helicobacter pylori: possible significance in the pathophysiology of the organism. Molecular microbiology, 2007. 64(2): p. 396-406.
[97] Malfertheiner, P., M. Venerito, and C. Schulz, Helicobacter pylori infection: new facts in clinical management. Current treatment options in gastroenterology, 2018. 16(4): p. 605-615.
[98] Abadi, A.T.B. and J.G. Kusters, Management of Helicobacter pylori infections. BMC gastroenterology, 2016. 16(1): p. 1-4.
[99] Safavi, M., R. Sabourian, and A. Foroumadi, Treatment of Helicobacter pylori infection: Current and future insights. World journal of clinical cases, 2016. 4(1): p. 5.
[100] Ayala, G., et al., Exploring alternative treatments for Helicobacter pylori infection. World journal of gastroenterology: WJG, 2014. 20(6): p. 1450.
[101] Meyer-Rosberg, K., et al., The effect of environmental pH on the proton motive force of Helicobacter pylori. Gastroenterology, 1996. 111(4): p. 886-900.
[102] Turbett, G.R., et al., Purification and characterization of the urease enzymes of Helicobacter species from humans and animals. Infection and immunity, 1992. 60(12): p. 5259-5266.
[103] Ha, N.-C., et al., Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nature structural biology, 2001. 8(6): p. 505-509.
[104] Dunn, B.E., et al., Purification and characterization of urease from Helicobacter pylori. Journal of Biological Chemistry, 1990. 265(16): p. 9464-9469.
[105] Clyne, M., A. Labigne, and B. Drumm, Helicobacter pylori requires an acidic environment to survive in the presence of urea. Infection and immunity, 1995. 63(5): p. 1669-1673.
[106] Jones, M.D., Y. Li, and D.B. Zamble, Acid-responsive activity of the Helicobacter pylori metalloregulator NikR. Proceedings of the National Academy of Sciences, 2018. 115(36): p. 8966-8971.
[107] Wen, G., et al., Helicobacter pylori infection downregulates duodenal CFTR and SLC26A6 expressions through TGFβ signaling pathway. BMC microbiology, 2018. 18(1): p. 1-11.
[108] Hathroubi, S., J. Zerebinski, and K.M. Ottemann, Helicobacter pylori biofilm involves a multigene stress-biased response, including a structural role for flagella. MBio, 2018. 9(5): p. e01973-18.
[109] Dunne, C., B. Dolan, and M. Clyne, Factors that mediate colonization of the human stomach by Helicobacter pylori. World journal of gastroenterology, 2014. 20(19): p. 5610-5624.
[110] Chmiela, M., N. Walczak, and K. Rudnicka, Helicobacter pylori outer membrane vesicles involvement in the infection development and Helicobacter pylori-related diseases. Journal of biomedical science, 2018. 25(1): p. 1-11.
[111] Ronci, M., et al., Identification and characterization of the α-CA in the outer membrane vesicles produced by Helicobacter pylori. Journal of enzyme inhibition and medicinal chemistry, 2019. 34(1): p. 189-195.
[112] Turner, L., et al., Helicobacter pylori outer membrane vesicle size determines their mechanisms of host cell entry and protein content. Frontiers in immunology, 2018. 9: p. 1466.
[113] Tsutsumi, R., et al., Attenuation of Helicobacter pylori CagA· SHP-2 signaling by interaction between CagA and C-terminal Src kinase. Journal of Biological Chemistry, 2003. 278(6): p. 3664-3670.
[114] Fischer, W., Assembly and molecular mode of action of the Helicobacter pylori Cag type IV secretion apparatus. The FEBS journal, 2011. 278(8): p. 1203-1212.
[115] Suarez, G., et al., Genetic Manipulation of Helicobacter pylori Virulence Function by Host Carcinogenic PhenotypesH. pylori, Gastric Cancer, CagY. Cancer research, 2017. 77(9): p. 2401-2412.
[116] Kanada, R., et al., Genotyping of the cagA gene of Helicobacter pylori on immunohistochemistry with East Asian CagA‐specific antibody. Pathology International, 2008. 58(4): p. 218-225.
[117] Yamaoka, Y., et al., Molecular epidemiology of Helicobacter pylori: separation of H. pylori from East Asian and non-Asian countries. Epidemiology & Infection, 2000. 124(1): p. 91-96.
[118] Basso, D., et al., Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology, 2008. 135(1): p. 91-99.
[119] Queiroz, D.M., et al., Higher frequency of cagA EPIYA-C phosphorylation sites in H. pylori strains from first-degree relatives of gastric cancer patients. BMC gastroenterology, 2012. 12(1): p. 1-7.
[120] Higashi, H., et al., SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science, 2002. 295(5555): p. 683-686.
[121] Atherton, J., et al., Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology, 1997. 112(1): p. 92-99.
[122] Djekic, A. and A. Müller, The immunomodulator VacA promotes immune tolerance and persistent Helicobacter pylori infection through its activities on T-cells and antigen-presenting cells. Toxins, 2016. 8(6): p. 187.
[123] Boquet, P. and V. Ricci, Intoxication strategy of Helicobacter pylori VacA toxin. Trends in microbiology, 2012. 20(4): p. 165-174.
[124] Lu, H., et al., Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterology, 2005. 128(4): p. 833-848.
[125] Yamaoka, Y., Roles of the plasticity regions of Helicobacter pylori in gastroduodenal pathogenesis. Journal of medical microbiology, 2008. 57(Pt 5): p. 545.
[126] Queiroz, D.M., et al., dupA polymorphisms and risk of Helicobacter pylori-associated diseases. International Journal of Medical Microbiology, 2011. 301(3): p. 225-228.
[127] Yamaoka, Y., D.H. Kwon, and D.Y. Graham, AM r 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proceedings of the National Academy of Sciences, 2000. 97(13): p. 7533-7538.
[128] Sallas, M.L., et al., Status (on/off) of oipA gene: Their associations with gastritis and gastric cancer and geographic origins. Archives of microbiology, 2019. 201(1): p. 93-97.
[129] Franco, A.T., et al., Regulation of gastric carcinogenesis by Helicobacter pylori virulence factors. Cancer research, 2008. 68(2): p. 379-387.
[130] Kim, K.-M., et al., Helicobacter pylori γ-glutamyltranspeptidase induces cell cycle arrest at the G1-S phase transition. The Journal of Microbiology, 2010. 48(3): p. 372-377.
[131] Oertli, M., et al., Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance. Proceedings of the National Academy of Sciences, 2013. 110(8): p. 3047-3052.
[132] Gong, M., et al., Helicobacter pylori γ-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology, 2010. 139(2): p. 564-573.
[133] Crabtree, J., et al., Immune responses to Helicobacter pylori in children with recurrent abdominal pain. Journal of clinical pathology, 1991. 44(9): p. 768-771.
[134] Smith, S.M., Role of Toll-like receptors in Helicobacter pylori infection and immunity. World journal of gastrointestinal pathophysiology, 2014. 5(3): p. 133.
[135] Smith, M.F., et al., Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-κB activation and chemokine expression by epithelial cells. Journal of Biological Chemistry, 2003. 278(35): p. 32552-32560.
[136] Alandiyjany, M.N., et al., A role for the tfs3 ICE-encoded type IV secretion system in pro-inflammatory signalling by the Helicobacter pylori Ser/Thr kinase, CtkA. PLoS One, 2017. 12(7): p. e0182144.
[137] Wilson, K.T., et al., Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line. Gastroenterology, 1996. 111(6): p. 1524-1533.
[138] Lundgren, A., et al., Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infection and immunity, 2003. 71(4): p. 1755-1762.
[139] Crabtree, J., et al., Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis. Gut, 1991. 32(12): p. 1473-1477.
[140] De Melo, F.F., et al., A regulatory instead of an IL-17 T response predominates in Helicobacter pylori-associated gastritis in children. Microbes and Infection, 2012. 14(4): p. 341-347.
[141] Nurgalieva, Z.Z., et al., B-cell and T-cell immune responses to experimental Helicobacter pylori infection in humans. Infection and immunity, 2005. 73(5): p. 2999-3006.
[142] El-Serag, H.B., et al., Houston consensus conference on testing for Helicobacter pylori infection in the United States. Clinical Gastroenterology and Hepatology, 2018. 16(7): p. 992-1002. e6.
[143] Dore, M.P., et al., Dyspepsia: when and how to test for Helicobacter pylori infection. Gastroenterology research and practice, 2016. 2016.
[144] Wang, Y.-K., et al., Diagnosis of Helicobacter pylori infection: Current options and developments. World Journal of Gastroenterology: WJG, 2015. 21(40): p. 11221.
[145] Pichon, M., et al., Diagnostic accuracy of a noninvasive test for detection of Helicobacter pylori and resistance to clarithromycin in stool by the Amplidiag H. pylori+ ClariR real-time PCR assay. Journal of clinical microbiology, 2020. 58(4): p. e01787-19.
[146] Ferwana, M., et al., Accuracy of urea breath test in Helicobacter pylori infection: meta-analysis. World journal of gastroenterology: WJG, 2015. 21(4): p. 1305.
[147] Mezmale, L., et al., Epidemiology of Helicobacter pylori. Helicobacter, 2020. 25: p. e12734.
[148] Leal, Y.A., et al., 13C‐urea breath test for the diagnosis of Helicobacter pylori infection in children: a systematic review and meta‐analysis. Helicobacter, 2011. 16(4): p. 327-337.
[149] Peng, N.-J., et al., Clinical significance of oral urease in diagnosis of Helicobacter pylori infection by [13C] urea breath test. Digestive diseases and sciences, 2001. 46(8): p. 1772-1778.
[150] Ricci, C., J. Holton, and D. Vaira, Diagnosis of Helicobacter pylori: invasive and non-invasive tests. Best Practice & Research Clinical Gastroenterology, 2007. 21(2): p. 299-313.
[151] Bordin, D.S., et al., Current Helicobacter pylori diagnostics. Diagnostics, 2021. 11(8): p. 1458.
[152] Dore, M.P., et al., Characterization of a culture method to recover Helicobacter pylori from the feces of infected patients. Helicobacter, 2000. 5(3): p. 165-168.
[153] Gisbert, J.P., F. De La Morena, and V. Abraira, Accuracy of monoclonal stool antigen test for the diagnosis of H. pylori infection: a systematic review and meta-analysis. Official journal of the American College of Gastroenterology| ACG, 2006. 101(8): p. 1921-1930.
[154] Guarner, J., et al., Helicobacter pylori diagnostic tests in children: review of the literature from 1999 to 2009. European journal of pediatrics, 2010. 169(1): p. 15-25.
[155] Dore, M.P. and G.M. Pes, What is new in Helicobacter pylori diagnosis. An overview. Journal of Clinical Medicine, 2021. 10(10): p. 2091.
[156] Best, L.M., et al., Non‐invasive diagnostic tests for Helicobacter pylori infection. Cochrane Database of Systematic Reviews, 2018(3).
[157] Malfertheiner, P., et al., European helicobacter and microbiota study group and consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut, 2017. 66(1): p. 6-30.
[158] Okubo, M., et al., Changes in gastric mucosal patterns seen by magnifying NBI during H. pylori eradication. Journal of gastroenterology, 2011. 46(2): p. 175-182.
[159] Stefano, K., et al., Non-invasive tests for the diagnosis of helicobacter pylori: state of the art. Acta Bio Medica: Atenei Parmensis, 2018. 89(Suppl 8): p. 58.
[160] Tu, H., et al., Serum anti-Helicobacter pylori immunoglobulin G titer correlates with grade of histological gastritis, mucosal bacterial density, and levels of serum biomarkers. Scandinavian journal of gastroenterology, 2014. 49(3): p. 259-266.
[161] Dixon, M.F., et al., Classification and grading of gastritis: the updated Sydney system. The American journal of surgical pathology, 1996. 20(10): p. 1161-1181.
[162] Varbanova, M., et al., Impact of the angulus biopsy for the detection of gastric preneoplastic conditions and gastric cancer risk assessment. Journal of clinical pathology, 2016. 69(1): p. 19-25.
[163] Graham, D., et al., Early events in proton pump inhibitor‐associated exacerbation of corpus gastritis. Alimentary pharmacology & therapeutics, 2003. 17(2): p. 193-200.
[164] Glickman, J.N., et al., Helicobacter infections with rare bacteria or minimal gastritis: expecting the unexpected. Digestive and Liver Disease, 2015. 47(7): p. 549-555.
[165] Snead, D.R., et al., Validation of digital pathology imaging for primary histopathological diagnosis. Histopathology, 2016. 68(7): p. 1063-1072.
[166] Benoit, A., N. Hoyeau, and J.-F. Fléjou. Diagnosis of Helicobacter pylori infection on gastric biopsies: Standard stain, special stain or immunohistochemistry? in Annales de Pathologie. 2018.
[167] Godbole, G., F. Mégraud, and E. Bessède, Diagnosis of Helicobacter pylori infection. Helicobacter, 2020. 25: p. e12735.
[168] Seo, J.-H., et al., Limitations of urease test in diagnosis of pediatric Helicobacter pylori infection. World Journal of Clinical Pediatrics, 2015. 4(4): p. 143.
[169] Cho, J.-H., et al., Factors for improving the diagnostic efficiency of the rapid urease test from the gastric corpus. Scandinavian Journal of Gastroenterology, 2017. 52(12): p. 1320-1325.
[170] Parihar, V., et al., A combined antral and corpus rapid urease testing protocol can increase diagnostic accuracy despite a low prevalence of Helicobacter pylori infection in patients undergoing routine gastroscopy. United European Gastroenterology Journal, 2015. 3(5): p. 432-436.
[171] Dechant, F.-X., et al., Accuracy of different rapid urease tests in comparison with histopathology in patients with endoscopic signs of gastritis. Digestion, 2020. 101(2): p. 184-190.
[172] Kuhns, L.G., et al., Carbon fixation driven by molecular hydrogen results in chemolithoautotrophically enhanced growth of Helicobacter pylori. Journal of Bacteriology, 2016. 198(9): p. 1423-1428.
[173] Pohl, D., et al., Review of current diagnostic methods and advances in Helicobacter pylori diagnostics in the era of next generation sequencing. World journal of gastroenterology, 2019. 25(32): p. 4629.
[174] Omori, T., et al., Correlation between magnifying narrow band imaging and histopathology in gastric protruding/or polypoid lesions: a pilot feasibility trial. BMC gastroenterology, 2012. 12(1): p. 1-7.
[175] Shukla, R., et al., Endoscopic imaging: How far are we from real-time histology? World Journal of Gastrointestinal Endoscopy, 2011. 3(10): p. 183.
[176] Alaboudy, A.A., et al., Conventional narrow-band imaging has good correlation with histopathological severity of Helicobacter pylori gastritis. Digestive diseases and sciences, 2011. 56(4): p. 1127-1130.
[177] Kawamura, M., et al., Topographic differences in gastric micromucosal patterns observed by magnifying endoscopy with narrow band imaging. Journal of gastroenterology and hepatology, 2011. 26(3): p. 477-483.
[178] Ji, R., et al., Mucosal barrier defects in gastric intestinal metaplasia: in vivo evaluation by confocal endomicroscopy. Gastrointestinal endoscopy, 2012. 75(5): p. 980-987.
[179] Neumann, H., et al., in vivo imaging by endocytoscopy. Alimentary pharmacology & therapeutics, 2011. 33(11): p. 1183-1193.
[180] Zhang, J.-G. and H.-F. Liu, Functional imaging and endoscopy. World journal of gastroenterology: WJG, 2011. 17(38): p. 4277.
[181] Kalach, N., et al., Usefulness of gastric biopsy–based real-time polymerase chain reaction for the diagnosis of Helicobacter pylori infection in children. Journal of Pediatric Gastroenterology and Nutrition, 2015. 61(3): p. 307-312.
[182] Ogaya, Y., et al., Detection of Helicobacter pylori DNA in inflamed dental pulp specimens from Japanese children and adolescents. Journal of medical microbiology, 2015. 64(1): p. 117-123.
[183] Ismail, H., et al., A newly developed nested PCR assay for the detection of Helicobacter pylori in the oral cavity. Journal of clinical gastroenterology, 2016. 50(1): p. 17-22.
[184] Zhou, L., et al., A creative Helicobacter pylori diagnosis scheme based on multiple genetic analysis system: qualification and quantitation. Helicobacter, 2015. 20(5): p. 343-352.
[185] Rabelo-Goncalves, E., et al., Evaluation of five DNA extraction methods for detection of H. pylori in formalin-fixed paraffin-embedded (FFPE) liver tissue from patients with hepatocellular carcinoma. Pathology-Research and Practice, 2014. 210(3): p. 142-146.
[186] Kim, J., et al., An appropriate cutoff value for determining the colonization of Helicobacter pylori by the pyrosequencing method: comparison with conventional methods. Helicobacter, 2015. 20(5): p. 370-380.
[187] Matsui, H., et al., Development of New PCR Primers by Comparative Genomics for the Detection of H elicobacter suis in Gastric Biopsy Specimens. Helicobacter, 2014. 19(4): p. 260-271.
[188] Fowsantear, W., et al., Comparative proteomics of Helicobacter species: the discrimination of gastric and enterohepatic Helicobacter species. Journal of Proteomics, 2014. 97: p. 245-255.
[189] Trespalacios, A.A., et al., Improved allele-specific PCR assays for detection of clarithromycin and fluoroquinolone resistant of Helicobacter pylori in gastric biopsies: identification of N87I mutation in GyrA. Diagnostic microbiology and infectious disease, 2015. 81(4): p. 251-255.
[190] Lee, J.W., et al., GenoType HelicoDR test in the determination of antimicrobial resistance of Helicobacter pylori in Korea. Scandinavian journal of gastroenterology, 2014. 49(9): p. 1058-1067.
[191] Malfertheiner, P., et al., Management of Helicobacter pylori infection—the Maastricht V/Florence consensus report. Gut, 2017. 66(1): p. 6-30.
[192] Murakami, K., et al., Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut, 2016. 65(9): p. 1439-1446.
[193] Molina-Infante, J. and J.P. Gisbert, Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance. World Journal of Gastroenterology: WJG, 2014. 20(30): p. 10338.
[194] Wang, L., et al., Ten-day bismuth-containing quadruple therapy is effective as first-line therapy for Helicobacter pylori–related chronic gastritis: a prospective randomized study in China. Clinical Microbiology and Infection, 2017. 23(6): p. 391-395.
[195] Muller, N., et al., Rescue therapy with bismuth-containing quadruple therapy in patients infected with metronidazole-resistant Helicobacter pylori strains. Clinics and research in hepatology and gastroenterology, 2016. 40(4): p. 517-524.
[196] Nishizawa, T., et al., Clarithromycin versus metronidazole as first-line helicobacter pylori eradication. Journal of clinical gastroenterology, 2015. 49(6): p. 468-471.
[197] Zullo, A., et al., Prevalence of lesions detected at upper endoscopy: an Italian survey. European Journal of Internal Medicine, 2014. 25(8): p. 772-776.
[198] Gisbert, J., et al., Third‐line rescue therapy with levofloxacin is more effective than rifabutin rescue regimen after two Helicobacter pylori treatment failures. Alimentary pharmacology & therapeutics, 2006. 24(10): p. 1469-1474.
[199] Paoluzi, O.A., et al., Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy. World Journal of Gastroenterology: WJG, 2015. 21(21): p. 6698.
[200] Liou, J.-M., et al., Genotypic resistance in Helicobacter pylori strains correlates with susceptibility test and treatment outcomes after levofloxacin-and clarithromycin-based therapies. Antimicrobial Agents and Chemotherapy, 2011. 55(3): p. 1123-1129.
[201] Matsuzaki, J., et al., Efficacy of sitafloxacin-based rescue therapy for Helicobacter pylori after failures of first-and second-line therapies. Antimicrobial agents and chemotherapy, 2012. 56(3): p. 1643-1645.
[202] Mori, H., et al., Efficacy of 10‐day sitafloxacin‐containing third‐line rescue therapies for Helicobacter pylori strains containing the gyrA mutation. Helicobacter, 2016. 21(4): p. 286-294.
[203] Murakami, K., et al., Multi-center randomized controlled study to establish the standard third-line regimen for Helicobacter pylori eradication in Japan. Journal of Gastroenterology, 2013. 48(10): p. 1128-1135.
[204] Mori, H., et al., Acquisition of double mutation in gyrA caused high resistance to sitafloxacin in Helicobacter pylori after unsuccessful eradication with sitafloxacin-containing regimens. United European gastroenterology journal, 2018. 6(3): p. 391-397.
[205] Ciccaglione, A.F., et al., Rifabutin containing triple therapy and rifabutin with bismuth containing quadruple therapy for third‐line treatment of Helicobacter pylori infection: two pilot studies. Helicobacter, 2016. 21(5): p. 375-381.
[206] Gisbert, J. and X. Calvet, rifabutin in the treatment of refractory Helicobacter pylori infection. Alimentary pharmacology & therapeutics, 2012. 35(2): p. 209-221.
[207] Mori, H., et al., Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: a pilot study. United European gastroenterology journal, 2016. 4(3): p. 380-387.
[208] Lim, H.C., et al., Rifabutin‐based high‐dose proton‐pump inhibitor and amoxicillin triple regimen as the rescue treatment for Helicobacter pylori. Helicobacter, 2014. 19(6): p. 455-461.
[209] Nishizawa, T., et al., Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction. World Journal of Gastroenterology: WJG, 2012. 18(21): p. 2735.
[210] Miehlke, S., et al., Randomized trial of rifabutin‐based triple therapy and high‐dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Alimentary pharmacology & therapeutics, 2006. 24(2): p. 395-403.
[211] Okimoto, K., et al., Efficacy of levofloxacin based triple and high-dose PPI-amoxicillin dual eradication therapy for Helicobacter pylori after failures of first-and second-line therapies. International Scholarly Research Notices, 2014. 2014.
[212] Nishizawa, T., et al., Effects of patient age and choice of antisecretory agent on success of eradication therapy for Helicobacter pylori infection. Journal of Clinical Biochemistry and Nutrition, 2017. 60(3): p. 208-210.
[213] Sachs, G. and D.R. Scott, Helicobacter pylori: eradication or preservation. F1000 medicine reports, 2012. 4.
[214] Adachi, M., et al., Reinfection rate following effective therapy against Helicobacter pylori infection in Japan. Journal of gastroenterology and hepatology, 2002. 17(1): p. 27-31.
[215] Zendehdel, N., et al., Helicobacter pylori reinfection rate 3 years after successful eradication. Journal of gastroenterology and Hepatology, 2005. 20(3): p. 401-404.
[216] Ryu, K.H., et al., Reinfection rate and endoscopic changes after successful eradication of Helicobacter pylori. World journal of gastroenterology: WJG, 2010. 16(2): p. 251.
[217] Wheeldon, T.U., et al., Long‐term follow‐up of Helicobacter pylori eradication therapy in Vietnam: reinfection and clinical outcome. Alimentary pharmacology & therapeutics, 2005. 21(8): p. 1047-1053.
[218] Seo, M., et al., Recurrence of Helicobacter pylori infection and the long-term outcome of peptic ulcer after successful eradication in Japan. Journal of clinical gastroenterology, 2002. 34(2): p. 129-134.
[219] Matysiak-Budnik, T. and F. Megraud, Epidemiology of Helicobacter pylori infection with special reference to professional risk. Journal of physiology and pharmacology: an official journal of the Polish Physiological Society, 1997. 48: p. 3-17.
[220] Williams, C., Helicobacter pylori and endoscopy. Journal of Hospital Infection, 1999. 41(4): p. 263-268.